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Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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MacchiariniGate: The Fall from Grace of Stem Cell Healer, Paolo 

Macchiarini, and Clues and Concerns from the Early Literature that Cast 

Ethical Doubts 
 

Jaime A. Teixeira da Silva 

P. O. Box 7, Miki-cho post office, Ikenobe 3011-2, Kagawa-ken, 761-0799, Japan; jaimetex@yahoo.com 

 

Abstract: After a long and successful career in tracheal surgery and lung cancer, Paolo Macchiarini became 

very famous in 2008 with the transplantation of a trachea from a cadaver that then apparently used the 

patient’s own stem cells to supposedly regenerate new trachea, i.e., tissue-engineered tracheae. Among the 

nine patients that received this revolutionary treatment, using biological or artificial tracheae, under 

Macchiarini’s supervision, six have reportedly died. Although several critics had expressed concerns with the 

procedures, allegations of misconduct against Macchiarini first arose in August of 2014 by four Karolinska 

Institutet (KI) colleagues, and an independent investigation was called for by KI based on claims made in 

seven published papers. Among the claims were the fact that the procedure constituted a high risk, 

information on the patients was incomplete and that there was no or incomplete ethical approval, thus 

constituting misconduct. His CV was also shown to contain inaccuracies. By September 10, 2016, most of 

these claims have now proved to be true, and Macchiarini was found guilty of misconduct by KI. This paper 

looks primarily at earlier published papers by Macchiarini and his collaborators in a search for clues to better 

understand the evolution of altruism, or narcissism. An assessment of the controversial papers, and of letters 

written by critics and skeptics like Pierre R. Delaere, indicate that insufficient experimental evidence was 

presented for several case studies, and that claims made about the success of the procedures exceeded 

what was shown by the evidence. A domino effect of personal and professional tragedies ensued, in rapid 

succession, between 2014 and 2016. The effect on the field of stem cell research has been chilling, and the 

side-effects have taken their toll, with several high-profile resignations, primarily at KI, within the Swedish 

education system and in the Nobel Committee. This case has mesmerized the bioethics and biomedical 

communities for years. 

 

Key words: ethics in medicine; Karolinska Institutet; legend; science; stem cell; tracheae 

 

Paolo Macchiarini’s experience and rationale: 

clues from the early literature: To understand how 

it is that a famed thoracic surgeon, Paolo 

Macchiarini, born in Basil, Switzerland, in 1958, and 

the child of Italian parents1, has become the center 

of one of the world’s greatest stem cell research 

scandals, a look at the individual’s publishing history 

could reveal clues as to how ideas and objectives 

may have evolved over time. Most stories that have 

more recently grabbed headlines over the past four 

years, from 2014-2018, either in the mainstream 

media, or on blogs, tended to focus on a very 

specific set of papers that later became the subject 

of an ethics investigation and a complex series of 

events that would eventually lead to the current 

downfallen status of Macchiarini. Most of those 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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stories, however, do not appear to have examined 

the early Macchiarini literature in detail, in a search 

for clues that could allow the public and stem cell 

community to better understand how Macchiarini 

and colleagues could have reached this state of fall 

from grace. In this first section, I seek to find clues in 

earlier papers and the wider Macchiarini literature, 

in a bid to understand how things began to fall apart. 

 

It is important to maintain this scandal in mind, 

because it may afflict any stem cell scientist that is 

left with their guard down, who has been careless, 

who has cut corners in an attempt to gain fame or 

reputation using less than accepted methods, or 

who has dappled in misconduct. 

 

A search for Paolo Macchiarini on PubMed – the 

world’s leading medical science data-base – 

revealed, until 2016, 193 papers related primarily to 

thoracic surgery, lung cancer, and 

xenotransplantation, the latter which involves the 

transplantation of non-human cells, tissues or 

organs into humans. Macchiarini in 1998 described 

himself, in a three-person correspondence to Nature, 

while working at the Department of Thoracic and 

Vascular Surgery, Hôpital Marie-Lannelongue, 

Paris-Sud University in France, as “a clinician 

involved in clinical allotransplantation and 

experimental xenotransplantation (heart-lung and 

lung)”2. That 1998 letter to the editor, which was in 

fact a rebuttal to Butler et al., also published in the 

same year3, revealed some fundamental aspects of 

this thoracic surgeon that might later have led to his 

unravelling and consequent downfall. The Butler et 

al. paper in fact sounded an alarm on 

xenotransplantation, highlighting the risks involved, 

and claiming that there was insufficient scientific 

evidence to allay such fears, especially in the light of 

evolving regulation, particularly in the US where, at 

that time, the US Food and Drug Administration 

(FDA) had placed a moratorium on porcine 

transplants in the light of the fact that endogenous 

retroviruses found in pigs could infect human cells in 

vitro, a revelation made by Le Tissier et al. in 19974, 

researchers at British institutes, of the so-called 

“Trojan pig”. Butler et al. further injected fear into the 

unregulated use of xenotransplantation in surgeries 

in “xeno-havens”, where experimental surgeries 

using xenotransplants and stem cells could take 

place under a business model that was waiting to 

explode to deal with surgeries dying to find solutions. 

In 1998, Macchiarini countered these concerns and 

fears by stating, in a direct personal jab at Butler et 

al.1: “Although you have published quite a lot on this 

subject, as far as I know none of the authors has 

been at the bedside of a patient”, suggesting that 

the emotive and subjective perspective took 

precedence over objective, evidence-based science. 

Further widening the rift with the stance by Butler et 

al., by claiming to understand the pain and struggle 

of patients, Macchiarini stated: “They [referring to 

Butler et al.] cannot feel the frustration of patients 

who die while waiting for an organ nor the wonderful 

sensation of being able once more to breathe or to 

move without effort. What about the parents seeking 

a therapeutic solution for children with terminal 

diseases? As a clinician, is it really ethical for me to 

have no solution or should I be more concerned with 

infection and social arguments?” This fascinating 

emotive appeal to patients’ struggles – even if 

implicitly ignoring the scientific evidence or red flags 

– may have served as the apparently altruistic factor 

that would spur ensuing research into 

xenotransplantation and thoracic surgery by 

Macchiarini. In the same letter, Macchiarini 

describes the successful use of a “nude mouse to 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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host a human trachea derived from human 

embryonic cells.” Several months later, 10 cm3 of 

that human trachea was transplanted “into piglets to 

test whether the process might be used in human 

babies as an alternative to their death.” Claiming 

success with this procedure, Macchiarini then 

challenged Butler et al.: “Do I have the right to 

propose this technique to the parents? I think I do 

and we are in the process of asking for permission 

to do it.” With this seminal statement that challenged 

conservative protocol, Macchiarini positioned 

himself as being a surgeon with an altruistic 

objective aimed at aiding dying patients with 

life-saving remedies in the form of xenotransplants, 

even if these went against popular or cautionary 

rationale, or scientific evidence (e.g.4). Planting his 

exploratory flag into unchartered territory, 

Macchiarini ended his commentary by emphatically 

stating “The time has come for clinicians rather than 

basic researchers to give their opinions on clinical 

xenotransplantation”, projecting thus himself and his 

research group, as a key solution to dying patients. 

 

Why did Macchiarini make such bold and confident 

assertions when his own published findings of a 

pig-to-human xenograft, in which pig lungs were 

perfused with human blood, showed “an early and 

violent hyperacute rejection that results in 

irreversible pulmonary dysfunction and failure within 

approximately 150 minutes of reperfusion”5? Such 

failed xenografts, and other failed tracheal and 

tracheoesophageal allotransplantation experiments, 

which were made by The Paris-Sud University Lung 

Transplantation Group6,7, should have served as 

humbling experiences to indicate that the risks – 

both violent and fatal – supported the concerns and 

warnings made by Butler et al. and should have 

served as risk-limiting factors in the search for 

supernatural solutions to human medical 

deficiencies. Close examination of the 1997 

Macchiarini et al. paper5 reveals that other than 

broad statements related to animal care and 

informed patient consent to use blood, no other 

ethical guidelines or approvals were indicated. 

Admittedly, at that time, it is likely that International 

Committee of Medical Journal Editors (ICMJE)-style 

requirements for animal-based tests or human trials 

– which have only in recent years become detailed 

and stringent for biomedical results to be published 

in biomedical journals – did not yet exist. 

 

Failed procedures were no stranger to Macchiarini, 

as was shown by a paper detailing a failed tracheal 

allograft replacement8, a product of his PhD thesis. 

However, the attention to scientific discovery as the 

guiding force to find medical solutions to treatment 

and surgery seemed to have predominated 

Macchiarini’s earlier work on lung cancer, for 

example in 19919, apparently driven by sound 

scientific principles and patient-related ethics. So, at 

what point did Macchiarini deviate off the ethical 

path, or was it a gradual progression in a passionate 

desire to find a cure for respiratory ailments, but 

brought down by an incredible growth in power and 

global fame, and a concomitant increase in funding 

by European and Russian agencies? 

 

Examination of Macchiarini’s CV 

(http://www.circare.org/info/pm/CV_eng.pdf) 

published by his (until recently) Swedish employer, 

the Karolinska Institutet (KI), in Sweden, indicates 

some facts worthy of pointing out, as a background 

to the evolution of research in xenotransplantation 

that will support this evolution in stances and 

practice by Macchiarini that eventually led to his 

downfall. This CV, which was used to guarantee 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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Macchiarini’s position at KI, specifically at the 

Karolinska University Hospital, was shown by KI on 

September 9, 2016 to carry inaccuracies. 

 

Statements made in 2004 by Macchiarini10 suggest 

Macchiarini’s frustration with the progress of science 

in finding innovative solutions to tracheal grafts or 

replacements, alluded to in the title as “déjà vu all 

over again”, noting that “an ideal graft must have 

some prerequisites: lateral rigidity and longitudinal 

flexibility, complete air tightness, biocompatibility, 

nonimmunogenicity, nontoxicity, resistance to 

bacterial colonization, freedom from the need for 

immunosuppression, permanent construction, ease 

of implantation, and the ability to provide a platform 

of ciliated respiratory epithelium resurfacing.” With 

this statement, the mental blue-print for how he 

would achieve his revolutionary xenotransplantation 

surgeries were set in stone. 

 

The rise of Paolo Macchiarini to legendary 

status: Macchiarini’s bold objectives appeared to 

thus have been set in stone by 2004, at which point 

he moved from Hannover Medical School in 

Germany (1999-2004) to the University of 

Barcelona in Spain (2005-2009). The work 

conducted in Germany with the Hannover 

Interdisciplinary Intrathoracic Tumor Task Force 

Group and in Spain, together with his collaborators, 

would ultimately propel Macchiarini to legendary 

status. Was an invitation to speak on “Surgical 

management of the subglottic airway” at the Royal 

Bristol Infirmary, University of Bristol, UK, in 

November 12, 2001, as documents his KI CV, the 

stepping stone and start of what would be a highly 

productive and fame-inducing collaboration with the 

Martin Birchall group at the Division of Surgery, 

Department of Clinical Medicine, University of 

Bristol? From 2009-2012, Macchiarini was an 

Honorary Professor of Surgery at University College 

London, suggesting that the Birchall alliance was 

rewarding. Independent of what the driving forces 

were that led to this powerful Germany-Spain-UK 

experience, by the time Macchiarini reached KI in 

Sweden, he had already clocked several dozen 

publications in some of the most respected and 

leading medical journals related primarily to 

xenotransplantation and surgery, including – but to 

name a few – the British Journal of Surgery11 of 

JIF2015 = 5.596, multiple papers in The Journal of 

Thoracic and Cardiovascular Surgery of JIF2015 = 

3.494, Annals of Thoracic Surgery of JIF2015 = 0.658, 

Biomaterials of JIF2015 = 8.387, New England 

Journal of Medicine of JIF2015 = 59.55812, and The 

Lancet of JIF2015 = 44.00213. In fact, Macchiarini was 

no stranger to publishing prowess, scoring a paper 

in The Lancet in 1992 from work with his Italian 

collaborators at the University of Pisa on 

neovascularisation and metastasis in lung cancer14. 

 

Of importance to the realization of Macchiarini’s 

altruistic dreams, and to finally solidify his proof of 

success, serving as a counter-argument to the 

disagreements with Butler et al.3 that surfaced a 

decade earlier, several of those papers projected 

the stem cell-based tissue-engineering theory into 

practice, including with human trials, such as in five 

papers13, 15, 16, 17, 18. 

 

The Macchiarini turning point, or was the only 

way up? Emboldened by increasingly challenging 

research, larger research groups, bigger funding 

and higher profile publications in leading medical 

journals, both as original research and reviews, 

Macchiarini was on track to global fame with 

tracheal transplants, until a rock was hit on the road 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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to fame, a classic case of a boom-to-bust career 

caused by uncontrollable public scandal18. That rock, 

which may now be considered as one of several 

fatal boulders, refers to the 2008 paper in The 

Lancet2. From that paper, a 2009 erratum emerged 

in which it was found that the affiliations of three of 

the authors were incorrect. In November 2008, while 

praising the experiment in the 2008 paper2, Sato 

and Nakamura19 also expressed reservations about 

the mechanism underlying its success, stating that 

“Macchiarini and colleagues did not use any specific 

measures to aid revascularisation in the graft. 

Nevertheless, they observed rapid recovery of blood 

flow and luminal mucosal appearance. The seeded 

epithelial cells and chondrocytes in the biological 

prosthesis before the implantation may have 

induced early revascularisation. However, as the 

investigators mention, it is unclear whether the 

seeded cells regenerated the tissue, including the 

cartilage and mucosa. Until the functions of the 

seeded cells are more clearly elucidated, some 

doubt remains about whether their results should be 

regarded as a fully tissue-engineered replacement 

or an allotransplantation of the trachea.” 

 

Despite this, almost mesmerized by the almost 

magical discovery, a reporter from a British 

newspaper, The Independent 

(http://www.independent.co.uk/us), Jeremy 

Laurance, wrote a commentary for The Lancet using 

hyperbolic praises, such as: “Every superlative in 

the book from an “astonishing milestone” to “the 

start of a new era in medicine” has been used to 

describe the first successful windpipe transplant”, 

“unquestionably a major development”, “On a 

scientific level, the procedure has proved that it is 

possible to grow organs using a patient’s own stem 

cells, eliminating the problems of rejection that have 

always plagued transplants. Stem-cell research, 

which has promised so much in the laboratory, has 

at last delivered a genuine clinical advance”20. The 

Macchiarini-Birchall alliance, which started in 1997, 

and everyone in between, had finally received 

dividends from its investments, a medical discovery 

almost too good to be true. The Lancet page 

indicates that, to date, that paper had been cited 

778 times on Scopus until the end of 2016. 

 

Institutional review board and ethics 

permissions: Yet, statements made by Birchall in 

the Laurance piece may have proved to be the 

fateful blow and the beginning of the end to 

Macchiarini’s rise to fame: “Ethical permission was 

obtained — which would not have been possible in 

the time in the UK, according to Birchall — and the 

team got the go-ahead. A donor trachea was 

obtained and stripped of its living cells using a 

process developed at the University of Padua. Stem 

cells from Castillo’s bone marrow and airway were 

taken to the Faculty of Clinical Medicine and 

Dentistry, University of Bristol, and grown following 

a protocol developed by Anthony Hollander. There 

was even a moment when the project teetered on 

the verge of disaster as easyJet refused to allow the 

cells on board its flight. Then a medical student 

remembered a German physician with a plane who 

agreed to fly the cells to Barcelona, where they were 

placed with the trachea in a bioreactor developed in 

Milan and, 4 days later, the seeded trachea was 

transplanted.” This paragraph, even to non-medical 

scientists, reeks of questionable ethics: if it was 

impossible to obtain ethical permission for such a 

procedure in the UK at the time, then how was it 

possible to complete the procedure at the University 

of Bristol in the UK? Clues to this question later 

emerged in a 2012 paper by Lowdell et al.21, as 



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described later. Why did EasyJet refuse to carry 

these cells? Who was this elusive German 

physician who transported the cells? And most 

importantly, was there proof at all, from any of the 

researchers’ research institutes, of ethical approval 

for this procedure? Ironically, Birchall stated to 

Laurance: “We, Paolo and I, took the biggest 

personal risk. We could have been in serious 

trouble if things had gone wrong—fingers would 

have been pointed.” These issues remain 

unclarified, and an investigation into Birchall’s 

decisions and level of responsibility in the 

Macchiarini-Birchall alliance have yet to be explored 

and resolved. 

 

Global criticism of the Macchiarini et al. (2008) 

paper: Coincidentally, or not, three letters to The 

Lancet were published in February 2009, by Wu et 

al., of the School of Stomatology, Fourth Military 

Medical University, Xi’an, in China, by Delaere and 

Hermans, of the Department of Otolaryngology 

Head & Neck Surgery and the Department of 

Radiology, respectively of the University Hospital, 

Catholic University of Leuven, Belgium, and by 

Zhang et al., collectively from the Department of 

Orthopaedics, Second Affiliated Hospital of Zhejiang 

University School of Medicine, in Hangzhou, China, 

and the Tissue Engineering Centre, Shanghai 9th 

People’s Hospital, Shanghai Jiaotong University 

School of Medicine, in Shanghai, China. The most 

pertinent criticisms made of the 2008 Macchiarini et 

al. paper, and whose process is described by Wu et 

al.22 as “Macchiarini and colleagues then used this 

tubular matrix [referring to “a nature-derived 

tracheal matrix from donor tracheal tissues”] as a 

scaffold on which to engineer native tracheal tissues 

by seeding autologous epithelial cells and 

mesenchymal stem cells.”, by these three groups 

were: 

“Macchiarini and colleagues do not indicate whether 

this tracheal matrix would eventually be replaced by 

newly formed cartilage tissues. Such a 

decellularised matrix would degrade completely in 

vivo, and would lose its original supporting role, 

which would lead to the collapse of the airway. We 

suggest detailed follow-up of morphological 

changes to the patient’s trachea”22. 

 

“Macchiarini and colleagues seeded cells with a 

density of 1.0×106/mL onto the surface of the 

scaffold. For cartilage tissue engineering, the 

preferred cell density is 5.0×107/mL, because of 

chondrocytes’ limited proliferate and migrating 

ability in vivo. In this study, how many cells could 

penetrate into the pores of the scaffold, and could 

the above cell density provide sufficient cells for 

further tissue formation? Perhaps such data could 

be presented in in-vitro specimens” 22. 

 

“Although revascularisation has been noticed in the 

inner surface of the graft, we think it will be difficult 

for the seeded epithelial cells to survive and form 

mucosal tissue at this site, because of the length of 

time full revascularisation will take and of the very 

limited nutritional perfusion from surrounding tissues. 

We suggest that Macchiarini and colleagues could 

collect the patient’s sputum postoperatively and 

analyse the cells in it so that we can ascertain 

whether the seeded epithelial cells have been 

chipped out and discharged” 22. 

 

“The main drawback of the proposed reconstruction 

is the lack of an intrinsic blood supply”23. 

“Histological analysis of the full thickness of the 

cartilaginous and membranous tracheal construct at 



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the time of implantation would have allowed for a 

comparison of the transplant histology with that of 

the normal tracheal wall. The paper’s illustrations 

show only isolated and non-organised clusters of 

epithelial and cartilage cells, and do not allow for 

histological comparisons”23. “The volume-rendered 

CT images and virtual bronchoscopic images … 

provide no clear information about the 

reconstructive value of the tissue-engineered 

tracheal transplant.” 23 “The reconstructive value of 

the avascular tissue-engineered transplant remains 

unclear in the absence of information about 

preimplantation histology and postreconstruction 

morphology”23. 

 

“One point was not discussed”; “what would 

Macchiarini and colleagues have done if, having 

prepared the tissue-engineered graft, the patient’s 

condition was found to be unsuitable for 

transplantation at that time?”; “although Macchiarini 

and colleagues’ result is very exciting, perfection of 

graft preservation might ultimately do more to 

further the clinical application of tissue-engineered 

products”24. 

 

Almost ironically, what had given the appearance of 

a magical, perfect treatment to treat 

trachea-bronchial problems, suddenly appeared to 

have a series of defects and insufficient proof to 

support the stated claims. In their 2009 response, 

Macchiarini et al.25 rebutted all three sets of readers’ 

concerns, while stating: “Although there are many 

important scientific questions to be addressed, 

including those raised by our correspondents, we 

argue that clinical outcomes are far more important 

in assessing the value of the technique than pre 

implantation histology.” What was curious about the 

authors’ response was that it was co-authored by 

only five of the 15 original authors. Were the 

remaining 10 co-authors consulted, and had they 

approved this response on their behalf? No public 

explanation exists for this discrepancy in authorship. 

 

Refutation of criticism by Macchiarini and 

colleagues: The patient in the 2008 paper13 is still 

alive, a fact that Macchiarini et al. could use to 

argue the fact that their experiment was a success. 

In 2011, Jungebluth et al.26, with Macchiarini as the 

last, senior author, and who was already associated 

with KI in Sweden at that time, a new case was 

presented as part of this collaboration between 

Sweden, Iceland, Germany and the UK. The 

authors reported, in a 36-year-old male patient, a 

“clinical transplantation of the tracheobronchial 

airway in a patient with recurrent primary trachea 

cancer, with use of a tailor-made artificial scaffold 

reseeded ex vivo with mononuclear cells (MNCs) 

and a growth factor-induced endogenous stem cells 

mobilisation.” The deviation of the technique from 

the 2008 paper was rationalized and explained as 

follows: “In 2008, we reported the first fully 

tissue-engineered tracheal transplantation with a 

non-immunogenic decellularised human donor 

trachea reseeded with bone-marrow-derived 

mesenchymal stem cells (MSCs) and respiratory 

cells. However, this approach is limited by the 

shortage of donor organs of an appropriate size and 

has other disadvantages ... As a result, an 

alternative, tailor-made synthetic tracheal scaffold is 

an urgent clinical need.” Soon after, a study 

published in The Lancet by Birchall in a 

UK-exclusive collaborative effort, and excluding 

Macchiarini, reported on the “replacement of an 

adult airway using stem cells on a biological 

scaffold”, i.e., a stem-cell-based organ transplant, in 

a 12-year-old boy27. The study concluded by stating: 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

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“At 2 years follow-up, he had a functional airway and 

had returned to school.” At first sight, three 

successful studies, with three The Lancet 

publications and a massive spike in research 

funding would spell apparent glorious success. Yet, 

this was not to be. 

 

In an interview with David Holmes1 regarding the 

Jungebluth et al. study26, which Holmes described 

as “the world's first transplant of a trachea made 

entirely from a synthetic nano-composite scaffold, 

seeded with the recipient's own stem cells”, 

Macchiarini stated “I'm like a wild animal that does 

not need to be in a cage, I need to express my 

convictions that I can help a patient with innovative 

things.” He also stated that “only those who risk 

going too far can possibly find out how far one can 

go.” In the same interview with Holmes, Philipp 

Jungebluth, who at that time already had an 11-year 

relationship with Macchiarini, noted: “Crossing 

frontiers is the only way to develop medicine and 

research further. Paolo crossed them already and 

changed medicine, and he will keep on going.” This 

was also a fateful prediction. Teaming up with a 

team of heavy hitters in the world of medicine in the 

US, Macchiarini indicate that “biological scaffolds 

made of allogeneic or xenogeneic extracellular 

matrix derived from nonautologous sources. These 

scaffolds can act as an inductive template for 

functional tissue and organ reconstruction after 

recellularisation with autologous stem cells or 

differentiated cells.” and that, when “guided by 

appropriate scientific and ethical oversight, could 

serve as a platform for the engineering of whole 

organs and other tissues”28. In a personal email to 

the author in September 2016, Badylak would come 

to distance himself from Macchiarini. 

 

In a 2013 paper29 that includes an interview with 

Macchiarini and Birchall, as well as the opinions of 

critics such as Delaere, Vogel stated that in addition 

to the 2008 case, another 14 patients had received 

bioengineered tracheas, by either the Macchiarini or 

the Birchall group. Raising great concerns in that 

piece, Vogel stated that “The researchers have 

mentioned other patients in passing in several 

papers, but no formal reports have been published 

about their health, and Science has not been able to 

independently verify the current status of all the 

patients.” In the Vogel paper, it became evident that 

at least two of the patients had died, but a 2016 

report indicated that 6 out of 9 patients had 

deceased30 while the reporting by a science 

watchdog31, Leonid Schneider, indicates that many 

more patients exist, although their deceased status 

is unclear32. It is unclear if there are other patients. 

Birchall claimed that one of the children died of the 

cancer while Macchiarini indicated that “another 

adult patient also died of the cancer that had 

damaged the trachea.” Consistent with other 

criticisms of the Macchiarini and Birchall findings, 

Delaere affirmed that “If they claim something 

miraculous, they have to show corresponding data. 

They don’t do that.” Almost coincidentally, Gonfiotti 

et al.33 showed how the 2008 patient, despite 

requiring repeated endoluminal stenting, was able 

to sustain a relatively normal social and working 

lifestyle, five years after the original transplant. 

 

In 2013, Birchall et al.34, excluding Macchiarini, 

offered a rebuttal, indicating that all three projects 

were different, independent, but “congruent”, and as 

an “evolution in thought”. Stressing that clinical trials 

are need to support their one-off case reports, 

Birchall et al. further defended their studies by 

indicating that the treatments differed for different 



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patients, but that all were “treated under 

compassionate use-licences”, referring to the use of 

a highly controversial approach in which “Advanced 

therapy medicinal products (ATMPs) are 

substantially modified human or animal cells or 

cell-device combinations” used to treat patients 

outside of a clinical trial21. Birchall et al. close their 

rebuttal by stating that “There will probably always 

be a need for the compassionate use of evolving 

techniques. Such uses provide not only hope for an 

individual, but useful clues to inform the necessary 

laboratory science.” In essence, the Macchiarini et 

al.25 and Birchall et al.34 rebuttals failed to offer 

concrete responses to scientific concerns, preferring 

instead to offer broad excuses, the “evolving” and 

“compassionate” arguments, and little substance to 

explain the observed medical shortcomings. 

 

Until mid-2014, it would have felt that Macchiarini 

and colleagues were still on track to increased fame, 

until tragedy after tragedy struck. The saga as 

continues to unfold from 2014-2018, is summarized 

by Kremer30, Retraction Watch35, with alternative 

perspectives by Schneider36, who is being sued by 

Macchiarini. A formal report issued to KI on 

September 23, 201637, sheds new light on possible 

ethical figure-related issues with Macchiarini-related 

papers. This will surely not be the last we hear of 

MacchiariniGate. 

 

Conclusions and take-home message: The last 

few years has seen first large praise towards the 

Macchiarini (and to a less extent Birchall) successes 

with transplantations. Those studies were 

astonishing at the time, in a positive way, because 

they offered the hope and promise of real solutions 

to near-dying patients. Yet, it took so many years for 

specialists and scientists to notice the warning signs, 

many of which had even been fairly clear in 

published papers and editorials. Apart from a 

handful or less of outspoken critics, undoubtedly 

Delaere being the most vocal, the astonishing 

aspect of MacchiariniGate is how many elite 

journals, their editor boards, including 

editors-in-chief, and hundreds of scientists who 

cited these papers, failed to notice any irregularities. 

There was clearly a culture of suppressed opinion at 

KI, as several co-authors of a 2011 Jungebluth et al. 

paper38 only requested to be removed as co-authors 

in March and April 2016 after several ethical 

investigations had been initiated, two ethical reports 

had been issued and several negatively revealing 

documentaries were aired on Swedish television. 

MacchiariniGate shows that hyperbolic claims of 

magnificent and almost miraculous results should 

always be assessed with great caution and 

additional scrutiny. There is no doubt that the desire 

to publish a revolutionary medical finding may have 

also prompted insufficient scrutiny by The Lancet 

and other top level leading medical journals, as they 

sought the top publishing prize for bringing these 

“revolutionary” results to the medical and stem cell 

research communities. Although it is still unclear if 

Macchiarini himself is in charge of all of the ethical 

mishaps underlying these cases, two salient points 

remain: a) regarding the published papers, all 

authors assume collective responsibility when 

something is published, so they receive glory when 

the papers were lauded, but they must also assume 

collective responsibility should those papers be 

felled due to ethical oversight or misconduct; b) 

amidst the multiple co-authors, many young 

surgeons, medical practitioners and researchers will 

undoubtedly be – where in fact misconduct has 

taken place – be the innocent victims of another 

person’s lack of respect of research and publishing 



Bangladesh Journal of Bioethics 2018; 9(1):1-12 

 

 

10 
 

protocol and ethics. This case must therefore serve 

to fortify current checks and balances in research 

laboratories, with oversight by research institutional 

ethics committees, or even national independent 

ethical boards, greater scrutiny and a desire to slow 

down the publishing process to ensure more quality 

control and checks. As shown by the Obokata STAP 

stem cell scandal and now MacchiariniGate, there 

are risks to one’s career, and even to human life, as 

one seeks for research objectives with grand 

solutions. These aspects, together with six core 

ethical issues (1. ethical guidelines and laws for 

high-risk ethical procedures, transplantation and 

clinical trials; 2. the value and weight of “ethical 

guidelines”; 3. plagiarism, self-plagiarism and 

professional victimization; 4. ethical inconsistencies 

by the editor-in-chief of Elsevier’s The Lancet’s 

Richard Horton; 5. the need to show ethical consent 

forms as part of the open data debate; 6. The ethics 

of a factually inaccurate and outdated CV) 

discussed elsewhere39 merit greater open 

discussion by the biomedical community. Six 

Macchiarini papers are destined for retraction 

following an investigation by the Central Ethics 

Review Board40. Finally, the issue of brand 

protection in the Macchiarini case41, despite 

wide-spread evidence over many years, is a new 

issue worthy of debate in biomedical ethics. 

 

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Author contribution statement: The author 

researched, wrote, and edited all versions of the 

manuscript. 

 

Conflicts of interest and disclaimer: The author 

declares no conflicts of interest, financial or other. 

This research was conducted in the absence of any 

financial funding. The author has been in contact 

with Prof. Macchiarini and his co-authors, the 

journal editors and the Swedish authorities (KI and 

other), as well as media representatives, primarily 

between September 12 and 23, 2016, to deliver the 

reports indicated in 201637. None of these contacts 

has influenced the content or outcome of the 

perspectives outlined in this commentary, which 

was submitted prior to the first contacts. 

 


