On 4 March 2019, The Lancet published a piece of Correspondence, authored by Laureano Molins, head of thoracic surgery at Hospital Clinic Barcelona in Spain. This short letter, hardly noticed by anyone, opened a new chapter in the trachea transplant scandal of the thoracic surgeon Paolo Macchiarini. The issue here is the seminal paper Macchiarini et al 2008, which described the first ever trachea transplant using a bioengineered decellularised cadaveric graft. To this day it is being paraded as an example of a success story, even after the scandal of Macchiarini’s deadly plastic tracheas made worldwide news and eventually led to two retractions in Lancet, in particular Jungebluth et al, Lancet 2011. The journal was very reluctant to retract that 2011 paper, and has been fighting tooth and nail to protect Macchiarini et al 2008. Lancet Editor-in-Chief Richard Horton is convinced that he is a victim of a harassment campaign, and that Macchiarini is a perfectly trustworthy medical colleague who just happens to be vilified. The Committee on Publication Ethics (COPE), which Horton co-founded, apparently shares this view.
But others don’t, first and foremost the Liverpool-based regenerative medicine researcher Patricia Murray, and the cardiologist Peter Wilmshurst, legendary whistleblower who once saved countless patient lives by taking on Big Pharma and Harvard elites, and even won in court when sued for libel. Murray and Wilmshurst both have been alerting UK authorities and Parliament to the trachea transplant scandal, Wilmshurst took it upon himself to try and convince The Lancet. He failed, but then television came to the rescue, and now the journal started to show signs of surrender:
If the Macchiarini et al 2008 paper does get retracted, its 5-year follow-up study in same journal Gonfiotti et al 2014 must logically follow, also because it is even more fabricated. Both works still serve as a template for new human experiments with trachea transplants, in UK, Russia and probably also elsewhere. Since that first ever transplant in 2008 on patient Claudia Castillo, at least 12 more patients received such cadaveric trachea transplant, from Macchiarini or his collaborators. All but one boy are dead, and Claudia survived because hers was not a trachea replacement, but a bronchus graft. She merely lost a lung where others lost their lives. The boy, Ciaran Lynch, survived due to permanent intensive care and constant stenting of his airways, yet also his case and the relevant Lancet paper Elliott et al, 2013, serve as justification in UK to keep applying this deadly technology to patients.
Because of Wilmshurst’s and Murray’s incessant advocacy, the case of the cadaveric trachea is being reopened, and I will tell you what has been happening behind the curtains. Lancet does not look good there at all, certainly not as a medical journal with patients’ interests in mind.
The Trachea Transplanters of 2008
That 2008 Macchiarini paper in The Lancet kick-started four different careers:
- Macchiarini himself, who went on to trachea transplant spree with cadaveric and plastic grafts which left almost everyone dead, in Spain, Italy, Sweden, Russia and USA. Macchiarini lost all his academic affiliations, but he is still adjunct professor at Hannover Medical School (MHH), the German university was involved into 2008 transplant, and has even today only the highest opinion of that Lancet paper.
- Martin Birchall, UCL professor and regenerative medicine enthusiast, who regenerated Claudia’s graft in his former veterinary lab in Bristol without telling the authorities. Birchall presently tries to restart his own airway transplant clinical trials after they got suspended or terminated following Murray’s notifications to authorities. Birchall and his partners are responsible for a deadly trachea transplant of their own, on the child patient Shauna Davison in 2012, and they performed another one as compassionate use in 2017, outcome secret.
- Philipp Jungebluth, Macchiarini’s student, who prepared the graft and whose award-winning medical dissertation from 2010 at MHH was based on this Lancet paper. In the 2008 publication, Jungebluth pretended to hold a medical doctorate (MD), while in reality he hasn’t even finished his university studies when the paper was published. Such title pretense is criminal in Germany, but Jungebluth is well-supported by German academics and clinicians, and presently continues his career as surgeon. He recently had me sentenced in Berlin court, where the judge educated me that neither Doktor Jungebluth nor Professor Macchiarini ever did anything wrong, certainly not in Spain.
- Anthony Hollander, whose fantasy technology of turning bone marrow cells into cartilage served as the rationale for this first ever in-vivo experiment on Claudia and a boon to his company Azellon. Hollander is now Pro-Vice-Chancellor for Research at the University of Liverpool, where Murray works.
The Correspondence piece in The Lancet by Molins from 4 March 2019 went like this:
“In 2008, Macchiarini and colleagues1 described the first patient to be treated with a tissue-engineered airway transplantation, and a 5-year follow-up was communicated by Gonfiotti and colleagues2 in 2014. This patient has since had a left pneumonectomy. Colleagues and I have been monitoring the patient’s progress in the past few years, and at the invitation of the Editors, I here describe the events leading up to the need for surgical treatment and the patient’s current clinical situation.
In June, 2008, the patient received a left main bronchus transplant at the Thoracic Surgery Hospital Clínic, Barcelona University. The patient was followed up in the Department of Thoracic Surgery until March, 2009. 3 weeks after the transplantation, it was necessary to stent the transplanted bronchus because of a homograft collapse. 9 months after transplantation, the patient initiated follow-up in a new institution, and, consequently, we had no further news from her.
In February, 2014, the patient was admitted to the Department of Thoracic Surgery again with acute respiratory failure and total atelectasis of the left lung. Bronchoscopy showed an 80% bronchial collapse. The patient referred that during the previous 5 years, she had been treated with multiple bronchial stents, most of which were bio-absorbable. In this clinical setting, we placed a silicone stent, after which lung re-expansion was achieved.
Since then, however, the patient’s quality of life has not been good; she has needed multiple fibre-optic and interventional rigid bronchoscopies (18 procedures in total) to maintain a relatively open bronchus. The left lung has a very poor function (20% of that expected), and the patient has had repeated bronchial obstructions, with multiple lung infections that required several interventional bronchoscopies, so a more expeditious surgical procedure was indicated. In July, 2016, a transternal left pneumonectomy was done. The postoperative course was uneventful, and the patient was discharged on the eighth postoperative day.
30 months after pneumonectomy, the patient is fully recovered and has not had any other medical events.”
Lancet under siege
That Correspondence is merely a small tip of a huge iceberg. The Lancet has been fighting off critics and even the Hospital Clinic Barcelona for at least 2 years, because the truth would have spoiled its reputation as the publisher of the beautiful seminal trachea transplant paper of 2008. Claudia’s lung test results presented in the paper were simply made up, the graft failed already after 3 weeks the operation, yet Macchiarini and his coauthors wrote in the paper’s abstract:
“The graft immediately provided the recipient with a functional airway, improved her quality of life, and had a normal appearance and mechanical properties at 4 months”.
Antoni Castells, medical director of Hospital Clinic Barcelona, wrote to me on 4 March 2017, exactly 2 years before the Molins letter appeared in The Lancet:
“A research letter explaining clinical evolution of the patient from transplant to year 2016 was submitted to a medical journal but, unfortunately, rejected.”
Castells neither confirmed nor denied if the medical journal might have been The Lancet, but it is the only one which would make sense here. What is known for sure, he contacted The Lancet again in May 2018, as Castells himself wrote to Murray:
“We emailed to The Lancet in middle May; they confirmed its reception but we have not received Editor’s response yet. Our letter included both problems with the pulmonary function tests and patient’s follow-up. With respect to the latter, we specified that “three weeks after the airway transplantation procedure, it was necessary to stent the transplanted bronchus, due to an homograft collapse”.
With respect to where the trachea was regenerated, I honestly can’t ensure it. To the best of our knowledge, we understood it was regenerated mainly in Bristol, but we can not confirm it.
On the other hand, permission to perform the airway transplantation (“trachea homograft treated by bio-molecular engineering”) was granted by Catalan authorities in April 17th, 2008.”
On 28 July 2018, Wilmshurst sent a letter to The Lancet’s editor-in-chief Horton, outlining the case for retraction of Macchiarini et al 2008 paper (and by extension, of the 5-year follow up Gonfiotti et al 2013) which described the trachea transplant on Claudia. The letter is available here, it contained followed attachments:
- Appendix 1, a FOIA reply from the University of Bristol where they declare to have been informed the operation served “to save the life” of Claudia, something Macchiarini never said. Who postulated that false claim then? Either Birchall, or a bird sang it in a tree. Bristol University also admits to have received patient’s tissue on 1.04.2008, i.e. before an official approval to perform the transplantation was obtained in Spain.
- Appendix 2, an official letter from Castells and his Hospital Clinic to Murray, dated 4 May 2018. Castells speaks again of falsified lung function tests and declares that Macchiarini never mentioned any “life threatening risk”. The Hospital Clinic director also states that internal approval for trachea transplant was issued by the hospital’s ethics committee on 2 April 2019 and external approval from Catalan Transplant Organization on 19 April 2008. Which means, the patient was subjected to invasive and painful bone marrow retrieval days or even weeks before an ethics approval was in place.
- Appendix 3, translation from a relevant section in the Russian book Megagrant (a Macchiarini biography the man himself dictated his Megagrant manager, Elena Kokurina) where it is narrated how Macchiarini meddled into Claudia’s child custody legal procedure in order to make her agree to a transplant.
- Appendix 4, another translated excerpt from the book Megagrant where it is clearly stated that the trachea regeneration process took place in Bristol, something the university found itself unable to confirm after they declared all documentation to be unavailable.
In October 2018, Wilmshurst received a reply from Horton. It contained an attachment, a summary of the recommendations Horton received from COPE on the Macchiarini affair. Horton specifically pointed Wilmshurst to the first sentence in this letter:
The journal should resist being stampeded into a quick decision and should not be pressured to action by threats. Just because an author’s work has been found to be ethically compromised, that does not necessarily mean that every paper from that period is compromised. It also does not mean that earlier work was necessarily compromised.
That may, or may not, be the case. The journal needs to ensure that the concerns are valid and substantiated for these papers as well. The only course of action is due process, where all the information is given to competent third parties to assess, and that takes time. Does the journal know if the institution investigated the other papers as well? Did the institution disagree with the statement from the clinic?
According to the COPE Whistleblower flowchart (https://publicationethics.org/files/RespondingToWhistleblowers_ConcernsRaisedDirectly.pdf), the journal would clarify in detail the specific evidence to support the claims. Are the two papers in question directly related to the retracted papers and the previous reason for retraction (for example, same flawed study, same patient, same dataset, same study that did not have approval, undeclared conflict of interest, no consent?) or is this a new complaints, such as image manipulation? Just having authors in common is not enough, so the specific reason/s for suspicion would need to be documented and relayed to the institution/employer (the university not the hospital), following the Suspected Ethical Problem flowchart (https://publicationethics.org/files/Ethical%20problem.pdf although the flowchart refers to submission step only rather than post publication). It is possible the new cases are directly related to other retractions from other journals, so the whistleblower would need to clarify if that is the case. If the corresponding author was fired, the institution can deal with contacting that person or a coauthor.
According to the Suspected Ethical Problem flowchart, if the response from the institution is unsatisfactory, the next step would be to refer the case to other authorities.
The journal could retract the articles even without a finding by the institution in Spain if they are satisfied they have done due diligence as described above. The journal would have to be very transparent with their retraction notice.
Nobody threatened Horton, but apparently this Elsevier snowflake, accustomed to have his bum constantly pampered, felt that a polite but determined letter from Wilmshurst constituted a threat, and so felt Horton’s protective colleagues at COPE. Mind you, one very rarely sees anyone openly side with Macchiarini (though some German editors at Karger recently did), but here you have COPE advising against thinking bad of that great Italian surgeon and pioneer of regenerative medicine.
Wilmshurst is COPE member since 1997 and on 31 October 2018, two days after including COPE in one of his emails to Horton, he decided to raise this issue at the upcoming COPE online meeting scheduled on 5 November 2018. When trying to log in, Wilmshurst received this message:
“Your registration for the COPE Forum on Monday 5 November, 4pm, was denied. We thank you for your interest in COPE but the Forum is available to members only.”
Wilmshurst wrote to COPE administrator Natalie Ridgeway, explaining:
“Your records should show that I have been a member of COPE since it was founded in 1997, that I wrote the first drafts of some of its guidelines, that I chaired and lectured at some meetings and I have continued to receive emails and news from COPE until now. I registered for the webinar on 5th November after an email from COPE on 30th October invited me to register.”
COPE administrator Linda Gough educated Wilmshurst then:
“The COPE Forum is for COPE members only. According to our records, you are not a member of COPE”
On 3 November 2018, Wilmshurst explained to Gough that he is very much COPE member, in fact one of the founding ones, author of the first COPE guidelines and co-chair of a COPE meeting on whistleblowing. On 5 November Wilmshurst was informed by Ridgeway:
“We are aware of your previous involvement and the important contributions you made to COPE when COPE first began and during its subsequent years. However, in 2015 COPE underwent a major change in its governance structure, which was approved by its members at that year’s AGM, and one part of that change saw the removal of the honorary membership role. Hence I’m afraid you are not an official member of COPE […]
We strongly refute any implication that the timing of this response is any way connected to your email to Richard Horton, which we have in fact not seen.”
Ridgeway however eventually confirmed to Wilmshurst that COPE did advise The Lancet on the Macchiarini issue, confidentially, and therefore refused to share the full communication:
“The Lancet asked COPE for advice on 7 September. The case as presented to us was circulated to Council for their comments on 10 September and advice was sent to The Lancet on 14 September.”
Non peer-reviewed blogs
On 13 November 2018, The Lancet Editor-in-Chief Horton wrote to Wilmshurst:
“Dear Peter – We have now received replies from Spain and COPE, and we have assessed what actions we should take. We do not find any sound reason to retract the 2008 paper. Disappointingly, most of your reference sources are from non peer-reviewed blogs, books, and letters. As with research papers, we try to base our decisions on peer-reviewed publications and institutional reviews. Regarding the 2014 follow-up paper, there are several issues about which we are seeking further clarification. When we have the answers to these questions, we will be in touch again.”
The Gonfiotti et al 2014 follow-up paper might actually remain standing even if Macchiarini et al 2008 original gets retracted, if Horton insists on a green light from the responsible institution, which in this case is in Italy. After the adventurous surgeon was kicked out of Hospital Clinic in 2009 (one reason might be his continues secret and illegal experiments with trachea transplants on patients), he went to Careggi University Hospital in Florence. Between 2010 and 2013, Claudia had to regularly travel from Barcelona to Florence (it seems Macchiarini paid the trips privately, don’t ask) for examinations. At least 5 patients received a trachea transplant form Macchiarini at Careggi, all are dead. However, the last thing that hospital wishes to do, is to speak about that. One reason might be that the governor of Tuscany, Enrico Rossi, is a big fan of Macchiarini’s, even now. The new head of thoracic surgery at Careggi, Luca Voltolini said this In August 2017 about Macchiarini’s local partners in Claudia’s case and the 5 trachea transplants, Massimo Jaus and Alessandro Gonfiotti:
“It is not for me to judge these cases, but I am extremely convinced that it must be made light. As for the two doctors you mentioned, the first one moved from Careggi to Rome before I got there. The second, from the time I am hare, was professionally impeccable.”
Five dead, one mutilated, doctors professionally impeccable. No wonder Macchiarini and the impeccable Gonfiotti later served as expert witnesses in Jungebluth’s court trial against me in Berlin. The judge highly valued their opinion, all my evidence was dismissed as fake or irrelevant. In any case, you now see that Careggi closed ranks behind Gonfiotti and even Macchiarini. The Lancet can rely on Careggi not to say a single critical word about the carnage Macchiarini caused there, or that outrageous Gonfiotti et al 2014 paper which paraded Claudia as completely cured and rehabilitated while she was constantly suffering and almost died because of that failed bronchus transplant. Dead patients mean nothing to medical elites concerned about their “reputation” and money streams. Which is exactly why The Lancet constantly takes sides with its authors against the patients.
Wilmshurst wrote back to Horton 2 days later explaining his un-peer-reviewed references to my blog and other sources:
“You state “most of (my) reference sources are from non-peer reviewed blogs, books and letters”. It is true that 6 of the 33 references cited were blogs and one was a book. The blogger is molecular cell biologist who has worked for 13 years in stem cell and cancer research. He is multilingual and has read the documents that are less accessible to those of us that rely on English and he has communicated directly with some of those involved in the tracheal transplantation research. None of the 33 references was a letter, although there was a letter in the four appendices (see below). The remaining 26 references were not blogs, books or letters. They included two reports of institutional investigations, two sets of evidence to the UK Parliament, 8 articles in peer review journals, one grant application, one report on research to the funder, one PhD thesis, four on-line lectures by those involved in this research (at Innovation in Healthcare, the RSM, University of Oxford and Sacramento State University), one reference to the UCL website and two reports on Pubpeer. I would not consider any of those to be low quality evidence for a journal. The remaining 4 references were news reports. You may have a low opinion of the evidential value of news reports, but it was news reports by Brian Deer that exposed the fact that Andrew Wakefield had hoodwinked the Lancet and its peer reviewers over MMR vaccine and autism.
Of the four appendices, two were extracts from a book that is not in English and you were supplied with translations for your convenience. One of the remaining two appendices was a letter from Dr Castells, which clearly is relevant, because he is the Director of the Hospital Clinic Barcelona where the airway transplantation took place. The other was the response to a Freedom of Information request from the University of Bristol, where the transplanted trachea was prepared for the patient described in the 2008 paper. […]
The summary of the 2008 paper reports findings in two sentences. The first says “The graft immediately provided the recipient with a functioning airway, improved her quality of life, and had a normal appearance and mechanical properties at 4 months.” Dr Castells sent an email to Prof Murray (Liverpool University) in which he said that in his May 2018 email to the Lancet he had specifically informed you that it was clear after a review of the case notes that there was a problem with the reporting of both lung function tests and patient follow up in the 2008 paper. He says that with respect to the latter he specified that “three weeks after the airway transplantation procedure, it was necessary to stent the transplanted bronchus, due to an homograft collapse.” So how could it have had normal appearance and mechanical properties at 4 months. This means that the first of the two sentences in the findings in the abstract is also false.”
Parliament vs Lancet
The experienced whistleblower Wilmshurst then brought the matter to the attention of the UK Parliament, Science and Technology Committee. On 15 January 2018, the Committee chairs asked The Lancet to address Wilmshurst’s concern, via an official letter. Here it should be pointed out that not only are journal’s editorial offices based in London, it is also tightly intertwined with UCL, a public university. For example, Lancet and UCL have a joint commission on stem cells and regenerative medicine, and Birchall is a board member there, together with another UCL trachea transplanter, Paolo De Coppi. Because of earlier parliamentary Committee’s investigations into UCL trachea transplants (prompted by Murray), the Chairpersons wanted to know what The Lancet was up to.
On 25 January 2019, Horton sent this reply to the Science and Technology Committee:
“Many thanks for your inquiry. As you know, The Lancet is a member of the International Committee of Medical Journal Editors and we take our ethical responsibilities concerning research very seriously indeed. That commitment includes our responsibilities to authors, as well as our responsibilities to readers and the public.
You may also know that we have already retracted two of Paulo Macchiarini’s papers.
On the issue of the papers cited by Peter Wilmshurst, the advice we have received from the Committee on Publication Ethics recommends that we must not assume that evidence of past misconduct always indicates misconduct in other cases. Each case, and in this instance each paper, must be subject to its own consideration and investigation.
Regarding the papers Dr Wilmshurst refers to we are, of course, unable to access the patient records ourselves. As is usual practice in such situations, we asked the host institution to investigate the allegations. They have reported back to us that all ethical requirements for the clinical aspects of the work have been appropriately fulfilled. Dr Wilmshurst has been informed of the conclusion from this report.
Based on the evidence we have received so far, we believe that there is insufficient grounds to retract these papers.”
It is ironic that there is another Lancet paper on the topic of regenerative medicine, and in that case, the journal was informed by the University of Gothenburg that the ethics approval was fake, the authors lied about having obtained it. That study also contains manipulated data, and the authors Suchitra Sumitran-Holgersson and Michael Olausson, were found guilty of research misconduct. by the University of Gothenburg. Nothing happened to that Olausson et al 2012 paper or ever will. Incidentally, the authors are former Macchiarini collaborators and performed their own trachea transplant, patient died right after.
On 5.03.2019, Lancet‘s Senior Executive Editor (and former COPE Vice-Chair) Sabine Kleinert wrote to Wilmshurst:
“Just to clarify, in his response Richard referred to the summary conclusion by Antoni Castells to Professor Murray (in your Appendix 2):
“Upon reviewing all information and after verification of the original documents and records supporting the study, we concluded that there is not enough ground to ask The Lancet for retraction of the article”. We have further verified this statement with Dr Castells.
However, as part of our continuing investigation we have asked the UK- based authors of the original paper to respond to the Newsnight report from last week and the concerns that you had raised with us in July. We had also invited the most-up-to date information on the patient, which was published in a corresponding letter yesterday (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736
The UK-based authors are obviously primarily Birchall and Hollander. Birchall and his UCL will sure oppose any action on that paper, given how much money they made and also plan to earn with airway transplants. Hollander’s stance is not clear (btw, he once openly admitted that the 2008 trachea transplant was performed without any animal testing whatsoever).
“Your response does not give me any confidence that this issue is being handled appropriately, or with sufficient urgency. More broadly it underlines the Science and Technology Committee’s recommendation that a new national committee on research integrity is needed to improve public confidence in this area.
The risk for human health of mis-reported patient outcomes surely means that there is a need for the Lancet to be proactive on this issue. While it may be tempting to pass all responsibility back to the host institution, I would have thought that you owe a duty to the readers of the Lancet to ensure that problems such as this are actively pursued.
The Lancet has faced criticism in the past about failure to retract unreliable research in a timely manner. Lives are genuinely at risk if inaccurate research is allowed to persist in the published record without at least a ‘statement of concern’ from the publisher”.
On 13 March 2019, Kleinert, Horton, the Science & Technology Committee Chairs and COPE received a letter from Wilmshurst, quote:
“I believe that the Lancet has acted and continues to act in a totally unethical manner and has been prepared to put the lives of patients at risk in an attempt to preserve the reputations of the journal and its employees and associates. I am also concerned that the Lancet has attempted to deceive Parliament as well as doctors and their patients.
Thank you for sending the link to the letter by Dr Molins. Dr Molins confirms that the transplanted airway in Claudia Castillo, the patient described in the 2008 Lancet report by Macchiarini et al (Lancet 2008;372:2023-30), collapsed 3 weeks after the operation and needed to have a stent implanted. The Lancet has known this for 9 months, but delayed making it public until forced to do so when, two weeks ago, Newsnight and Norman Lamb MP exposed your inaction. Now the Lancet seems to be trying to get away with making a partial correction rather than retracting the fraud by asking Dr Molins to submit a letter for publication. […]
Concealment in the 2008 Lancet article that Claudia Castillo’s transplanted airway required a stent when it collapsed 3 weeks after the operation was a disaster for other patients that had transplanted airways without a stent and who died when the transplants they received collapsed (e.g.15 years old Shauna Davison, who suffocated
2 weeks after her tracheal transplantation at Great Ormond Street Hospital).
The letter by Dr Molins does not correct all the errors in the 2008 paper known to the Lancet. For example, the letter does not mention the fact that Claudia Castillo’s lung function did not improve after the airway transplantation. […]
In conclusion, a known research fraudster wrote the 2008 Lancet paper. You have clear evidence of serious errors in the paper that put patients at risk and which are so major that it is impossible to believe that those errors were the result of honest mistakes. The Lancet should not have attempted to save face by inviting submission and publication of a letter from Dr Molins correcting one of the errors, when you know that there are other errors. I cannot help wondering whether the reason that the Lancet is so unwilling to concede that research fraud occurred is that some of the members of the Lancet commission on stem cells and regenerative medicine were co-workers with Macchiarini on his airway transplant research. If, as it appears to me, Dr Horton’s letter was an attempt to mislead Parliament he should consider his position at the Lancet.”
Indeed, what if the Macchiarini affair becomes the final straw for Horton as The Lancet‘s gatekeeping Editor-in-Chief? What else on non-peer-reviewed information must come out before academic and medical colleagues distance themselves from Macchiarini, Birchall, Jungebluth and other trachea transplanters? At which point will human lives matter more than doctors’ careers?
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