Today the Swedish Karolinska Institutet (KI) will announce its decision about 6 papers of their former professor and surgeon, Paolo Macchiarini. This article will be updated accordingly. Update 14:00: a decision was published, all 6 papers are to be retracted, 7 scientists found guilty of misconduct.
The background: On 30 October 2017, Swedish Central Ethics Review Board (CEPN) requested that 6 publications by Macchiarini and co-authors, all authored while at KI, are to be retracted, in a press release and a statement I received, in English original. The decision was based on the expert review by Martin Björck, professor of surgery at University of Uppsala, and Detlev Ganten, professor emeritus of pharmacology and former CEO of the Charité university hospital in Berlin, Germany, their report is available here on my site. The two experts found Macchiarini and his former acolyte and right-hand man Philipp Jungebluth guilty of breaching the Nuremberg Code of 1947 and Helsinki declaration, which forbid unethical and dangerous medical research on humans. One of those papers set for retraction is Jungebluth et al Lancet 2011, where a patient from Iceland was tricked to subject himself to a deadly experiment with a never before tested plastic trachea (that issue lead to a major investigation in Iceland and now is even about to be addressed by the Icelandic parliament).
Judging from last week’s email by Jungebluth to KI which I quote below, a call for retraction is expected.
Those were the 6 Macchiarini papers scheduled for retraction, describing the 3 plastic trachea transplants performed at KI hospital:
- “Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study”, published in Lancet 2011 (Jungebluth P, Alici E, Baiguera S, Le Blanc K, Blomberg P, Bozóky B, Crowley C, Einarsson O, Grinnemo KH, Gudbjartsson T, Le Guyader S, Henriksson G, Hermanson O, Juto JE, Leidner B, Lilja T, Liska J, Luedde T, Lundin V, Moll G, Nilsson B, Roderburg C, Strömblad S, Sutlu T, Teixeira AI, Watz E, Seifalian A, Macchiarini P)
- “Engineered whole organs and complex tissues”, published in Lancet 2012 (Badylak SF, Weiss DJ, Caplan A, Macchiarini P)
- “Verification of cell viability in bioengineered tissues and organs before clinical
transplantation”, publicerad i Biomaterials 2013 (Jungebluth P, Haag JC, Lim ML, Lemon G, Sjöqvist S, Gustafsson Y, Ajalloueian F, Gilevich I, Simonson OE, Grinnemo KH, Corbascio M, Baiguera S, Del Gaudio C, Strömblad S, Macchiarini P)
- “Are synthetic scaffolds suitable for the development of clinical tissue-engineered tubular organs?”, published in the Journal of Biomedical Materials Research 2014 (Del Gaudio C, Baiguera S, Ajalloueian F, Bianco A, Macchiarini P)
- “Airway transplantation”, published in Thoracic Surgery Clinics 2014 (Jungebluth P, Macchiarini P)
- “Biomechanical and biocompability characteristics of electrospun polymeric tracheal scaffolds”, published in Biomaterials 2014 (Ajalloueian F, Lim ML, Lemon G, Haag JC, Gustafsson Y, Sjöqvist S, Beltrán-Rodrìguez A, Del Gaudio C, Baiguera S, Bianco A, Jungebluth P, Macchiarini P)
Macchiarini’s former acolyte and right-hand man Philipp Jungebluth wrote to KI’s legal counsel Mats Gustavsson on June 21st, which kind of indicated the expected verdict:
“Dear Mats Gustavsson,
Thank you for your notice. Of course, you just do your work but how many times more KI purpose to annoy everyone with its farce of investigation and subsequent announcements.
Since 2016 KI failed during the entire process to provide a fair and unbiased evaluation in this matter.
Just for the records and to remember: in 2015 we were entirely and officially cleared by KI from all accusations.
We already know the result of this “all show lawsuit” but this won’t help Karolinska Institutet to overcome their incompetence and incapability of handling internal conflicts (and that is all what it was and is!!) in its appropriate manner.
Jungebluth’s anger with KI and Sweden is understandable. That horrid country grabbed by his collar and sent him back to Germany, after finding out that he played doctor at KI hospital without a licence and pretended to having a PhD degree he didn’t have, to obtain research funding as assistant professor (read here, where I naively thought that facts, common sense and basic human rights would have any meaning in court).
In his home country Germany, Jungebluth was met despite everything a hero and became a rising star of German medicine, supported and protected by the society elites, in particular other clinicians. German medical ethics do not seem to cover actual patients, as I learned during a related investigation (where I was also sued, but saved by the presence of media in the court room), and definitely have meaning for patients abused abroad. That Nuremberg Code of 1947 is something certain German medical elites have little respect for, because a colleague’s career is simply more important than any patient’s life can ever be. The lengths which German doctors (and even judges) went to help Jungebluth prove it.
Jungebluth’s former senior colleague at his former workplace at the Thoraxklinik of University Heidelberg recently as Editor-in-Chief of the journal Respiration categorically refused KI’s request to retract one of Jungebluth’s and Macchiarini’s papers, denying KI the competence to decide on such matters. That paper was not about a trachea transplant, but about a terminally ill patient abused to satisfy his doctors’ curiosity until he died. From a different corner of Germany, another powerful peer played his magic to help a colleague in need: the president of Hannover Medical School (MHH) issued last year a decree forbidding his university to investigate the MD doctorate thesis of Jungebluth, which was supervised by MHH adjunct professor Macchiarini and which reports the first trachea transplant of 2008, all despite the known massive ethics and regulation breaches as well as gross misrepresentation of basic facts.
Even better: just last month, Jungebluth had me sentenced in a court in Berlin for libel, in two injunctions, with two hefty fines on top, for referencing his own written quotes. The verdict of the appeal court declared that the statements Jungebluth wrote and said did not mean what was written or said, and was a scientific communication in English language anyway, all of which I was accused of being maliciously and slanderously ignorant of. Unlike the judge, who literally explained that she also went to school and hence knows all about English language, international biomedical publishing and even surgery training. Prior to sentencing, the Berlin judge reminded me of two things: that I am an immigrant in Germany, and that Macchiarini, as all doctors, could not have done anything wrong or illegal, by definition. Jungebluth was instead advised by the judge to sue Swedish media for reporting about his being “kicked out” from KI.
Jungebluth now started a new medical career in his home town of Wolfenbüttel in northern Germany. After the Berlin court used me to create a lasting legal precedence to deter every journalist near and far, there will be no attempts at Macchiarini reporting in the country where the trachea transplant affair began, for the foreseeable future. Jungebluth’s medical career in Germany is now flowering, lucky patients of his indeed who will never know what an honour they have. And maybe even Macchiarini will eventually return to the neighbouring city of Hannover: he still only calls himself Professor Macchiarini only thanks to the ongoing title loan of MHH.
Sweden is still struggling with the aftermath of Macchiarini affair, which changed the country’s understanding of science and medicine and hopefully taught a long-lasting lesson. Though for now, Macchiarini and his colleagues somehow escaped the charges of manslaughter, despite 3 dead trachea transplant patients in Sweden alone, which leaves yours truly as the only person ever sentenced and punished for Macchiarini’s trachea transplants in a court of law.
The KI decision will appear here once it is announced, and updated with a full report I requested.
Update 14:00. The KI decision was published:
Seven researchers responsible for scientific misconduct in Macchiarini case
On 25 June, the President of Karolinska Institutet made the decision to find seven researchers responsible for scientific misconduct in research. The case concerns six articles published in the scientific journals The Lancet, Biomaterials, The Journal of Biomedical Materials Research, and Thoracic Surgery Clinics. Paolo Macchiarini is one of the main authors of the articles.
The research reported in the articles relates to the transplantation of synthetic tracheal prostheses and describes the clinical course of treatment of three patients who were transplanted at Karolinska University Hospital 2011–2013. According to the President’s decision, an additional 31 authors are blameworthy for their contributions to the articles, however not responsible for scientific misconduct. Another five authors are cleared of blame and of responsibility for scientific misconduct. Karolinska Institutet is requesting that the six articles be retracted without undue delay.
Today’s decision was made following a new investigation of the six articles, and overturns the decision made on 28 August 2015 by the President at the time. The case was reopened in February 2016.
The new investigation points to serious inaccuracies and misleading information in the reviewed articles. The articles contain fabricated and distorted descriptions of the patients’ conditions before and after the operations. Justification is lacking for treatment of the patients on the grounds of so-called vital indication (when a given treatment is the last resort for survival), and one misses reference to relevant animal experiments which must precede human studies that involve unproven methods. Furthermore, ethical approvals are lacking, as are appropriate informed consents.
“This decision has been made after careful investigations in a case that has had major impact on Karolinska Institutet, on the scientific community at large, and on public confidence in medical research. In particular, the case has had tragic consequences for patients and their relatives, for which I am deeply sorry. Karolinska Institutet will now continue to implement the measures that are necessary to prevent something like this from happening again,” says Ole Petter Ottersen, President of Karolinska Institutet.
One of the authors that was found responsible for misconduct was among those who blew the whistle on Macchiarini in 2014.
“The investigation points to inaccuracies for which Paolo Macchiarini is ultimately responsible but for which several of the co-authors also bear responsibility. The four whistle blowers are to be commended for their action in this case that has contributed to the investigation. However, it is KI:s firm opinion that a whistle blower who has participated in a scientific study and also as author of a scientific article, despite reporting, cannot be freed from blame or absolved from responsibility”, says Ole Petter Ottersen.
- According to Chapter 1, § 16 of the Higher Education Ordinance, a university that becomes aware of suspected scientific misconduct at said institution is obliged to investigate. In the course of an ongoing investigation, the higher education institution may solicit the opinion of the Expert group for misconduct in research at the Central Ethical Review Board, CEPN. According to KI procedure, suspected scientific misconduct is to be reported to the president of the university, and the president shall initiate an investigation and make a decision in the case.
- The university where the research was conducted has an obligation to investigate suspected scientific misconduct even if all the involved researchers are not employed at or affiliated to that university.
- Today’s decision differs from the report of the Expert group for misconduct in research at the Central Ethical Review Board, CEPN, who considers all authors responsible for scientific misconduct. Karolinska Institutet’s investigation has examined the responsibility of each individual author (a total of 43 researchers).
- Only a few of the authors are currently employed at or affiliated to Karolinska Institutet.
Update 16:00. I now received the full report, in Swedish. An English language one will follow. This is the central message:
“Responsible for scientific misconduct
Paolo Macchiarini, Philipp Jungebluth, Karl Henrik Grinnemo, Jan Erik Juto, Alexander Seifalian, Tomas Gudbjartsson and Katarina Le Blanc are responsible for research misconduct.
Evren Alici, Tolga Sutlu, Silvia Baiguera, Guido Moll, Pontus Blomberg, Béla Bozóky, Sylvie Le Guyader, Staffan Strömblad, Oskar Einarsson, Jan Liska, Ola Hennanson, Tobias Lilja, Gert Henriksson, Bertil Leidner, Tom Luedde, Christoph Roderburg, Ana Isabel Teixeira, Vanessa Lundin, Emma Watz, Bo Nilsson, Johannes C Hague, Mei Ling Lim, Sebastian Sj, Ylva Gustafsson, Fatemeh Ajalloueian, Irina Gilevich, Oscar Simonson, Matthias Corbascio, Constantino Del Gaudio, Alessandra Bianco and Antonio Beltrán Rodríguez is worth mentioning, but not to the extent that they are
considered guilty of research misconduct.
Not responsible for scientific misconduct and not blameworthy
Clarie Crowley, Stephan F Badylak, Daniel J Weiss, Arthur Caplan and Greg Lemon are through their involvement not guilty of research misconduct.
Notification to journals
Journals The Lancet, Biomaterials, Journal of Biomedical Material Research and
Thoracic Surgery Clinics will be notified with a request for the items to be immediately withdrawn”.
Update 18:15. Karolinska fingered one of the whistleblowers Karl-Henrik Grinnemo (now at University of Uppsala) as one of the 7 scientists guilty of misconduct (two others, Corbascio and Simonson were found “blameworthy”. This is a bizarre decision, because KI refuses to apologise to the 4 whistleblowers of Macchiarini’s fraud and patient abuse for having threatened and harassed them when Macchiarini was initially absolved in 2015. KI apparently cannot forgive them for engaging the journalists, without whom in turn there would have been no Macchiarini affair. Grinnemo now sent me this comment:
“Being judged by KI is like a soccer game where the other team’s coach is the referee. KI has during all these years neglected to act against Paolo Macchiarini and we whistleblowers have been very hard on them and pushed a thorough investigation. The price we are now paying is to be judged by the same corrupt team. After such decision no one will ever react against research misconduct in the future. I hope the research society understand the irony behind this decision and see what it is- namely a continuation of 5 years harassment”.
Update 27.06: I now received the English version of the KI report. Those are excerpts from statement on individual author responsibilities for Jungebluth et al Lancet 2011:
“As one of the principal authors Philipp Jungebluth bears considerable responsibility for the established misconduct. He was one of the drivers of the project and had detailed knowledge of the research and he is the one who subsequently received, stored and sent tissue samples for analysis, one of which indicated almost normal conditions.[..] Philipp Jungebluth is responsible for scientistic misconduct. […]
Claire Crowley [who manufactured and then personally delivered the plastic trachea to KI in private luggage, read here -LS] joined the author group in the ﬁnal month as a student. Granted, she too should have reacted to the patently erroneous ﬁve month status reported in the paper, but in that she became involved at such a late stage and was a student, KI ﬁnds that she is not responsible for scientiﬁc misconduct and not blameworthy.[…]
Alexander Seifalian necessarily deserves criticism for non compliance with the
Medicinal Products Act’s quality GMP criteria in, and the lack of Medical Products
Agency permit for its manufacture [all which was actually approved by UCL Business office UCLB, read here -LS]. He was also a member of the first author group and should have demanded that steps be taken to address the views of the reviewers. Alexander Seifalian is therefore responsible for scientistic misconduct. […]
Oskar Einarsson and Tomas Gudbjartsson participated in the clinical care of the patient, mainly on Iceland; Tomas Gudbjartsson also participated in the operation performed at Karolinska University Hospital. [..] Tomas Gudbjartsson was a member of the first author group and should have demanded that steps be taken to address the views of the reviewers. He is therefore responsible for scientistic misconduct. Oskar Einarsson was a member of the author group recruited after the NEJM rejection. He did not react to the patently erroneous ﬁve month status reported in the paper. Oskar Einarsson is blameworthy but not to an extent that would constitute scientistic misconduct. […]
Ola Hermanson and Tobias Lilja were responsible for the epigenetic studies. There is nothing to suggest that these studies are in themselves to be judged as dishonest in either execution or outcome. Ola Hermanson [who used to defend Macchiarini, attack whistleblowers and openly accused the 2015 Bengt Gerdin investigation into that same trachea transplant of being biased, acting on behalf of Grinnemo, of “serious flaws and formal errors”, who claimed all ethics approval were in place and that “accusations of scientific misconduct are thus completely unwarranted” (read here and here , LS] was a member of the first author group and should have demanded that steps be taken to address the views of the reviewers.[…]
Bo Nilsson and Katarina Le Blanc participated in various analyses. Katarina Le Blanc also undertook the bone marrow isolation to obtain stem cells with which to coat the synthetic trachea. Neither of them reacted to the patently erroneous ﬁve month status reported in the paper. Katarina Le Blanc had in this regard greater responsibility by virtue of her seniority and her responsibility for the production of the stem cells that made the project possible. […] Katarina Le Blanc is responsible for scientistic misconduct. Bo Nilsson had a subordinate role and was only recruited as a co author ahead of submission to the Lancet. B0 Nilsson is blameworthy but not to an extent that would constitute scientistic misconduct. […]
Karl Henrik Grinnemo was one of the surgeons who participated in the transplantation and who wrote the biopsy referrals during the work reported in the paper. He has confirmed that the clinical status he sent to Paolo Macchiarini was based on an epicrisis written by the patient’s doctor in early August 2011. This clinical summary, which was completed on 29 August, then accompanied the different versions of the paper over the ensuing months. Karl Henrik Grinnemo reasons that since he was working at the thoracic surgery clinic and that during this time the patient belonged to the ear, nose and throat clinic, he was unable to access the patient’s clinical development. The source data show that the last clinical bronchoscopy and biopsy examination was done on day 76, roughly eleven weeks after the operation. Karl Henrik Grinnemo thus had every opportunity to understand that even before the paper was submitted to NEJM at the end of August it did not describe the patient’s actual condition, since these biopsies taken by the hospital and on Iceland did not provide any underlying data for the cell status at seven days and two months as reported in the paper. He claims that he knew nothing about the patient’s clinical development since after his operation he was cared for at another clinic. This raises questions about how he could accept his co authorship. Since it was such an unusual operation, it is unlikely that he did not even make private contact with the relevant clinics to find out how things went for the patient. Karl Henrik Grim1emo is one of the authors who had direct knowledge that the patient’s status as described in the paper cannot have reflected the actual situation at five months. Karl Henrik Grinnemo was a member of the first author group and should have demanded that steps be taken to address the views of the NEJM reviewers. The evidence found no evidence that he tried to update his clinical description in the prefinal manuscript to the Lancet in early November, that he actively tried to block publication at this time, that he tried to withdraw his authorship or that he tried to update the description of the patient’s status in the paper during the interval between publication online on 24 November and its printing on 10 December, by which time the patient had already (in November) been re admitted to Karolinska University Hospital.
This played out during the summer and autumn of 2011. His and the three other
complaints’ report was made in August 2014, i.e. three years later. The complainants
have said that they did not realise how the patient had fared until they were later brought in to take care of patient 3, when they realised the scale of the clinical problem. This is, however, of less relevance to the judgement of Karl Henrik Grinnemo’s responsibility since according to KI he appears to be the author who knew most about how the clinical report for patient 1 was prepared and who had authorial responsibility to make sure that it was reproduced correctly in the paper.
As KI has already made clear, a researcher may not evade investigation or be cleared of any guilt of suspected scientistic misconduct concerning research in which he or she has participated simply because he or she is a whistle blower. All credit must go, however, to the four whistle blowers for submitting a very thoroughly grounded complaint and thus triggering this investigation. As regards Karl Henrik GI‘l1′]Il61’l’10, he was a key clinician with insight into the clinical data, and was one of the principal authors of the paper. He did nothing to ensure that his and other people’s contributions to the scientistic description of the patient reflected the actual situation. He is responsible for scientistic misconduct.
The leading principal investigator was Paolo Macchiarini. The concept of principal
investigator includes taking responsibility for financing and initiating research, having overall control, taking responsibility for all data and bearing overall responsibility for the final scientistic paper. He is identified in the project description as the leading researcher, the leading author, the one who described how the synthetic trachea was to be designed, the leading surgeon, the one responsible for the pre and postoperative care, and the one who led the review of the paper that was required on different occasions. The investigation found that Paolo Macchiarini had taken the initiative already during the introductory phase to deceive on the matter of the patient’s status when he persuaded Tomas Gudbjartsson to change the referral text so that the patient would appear more sick than he actually was. Paolo Macchiarini thus acted in a deliberately deceitful manner from the very start without concern for the patient’s situation. As the senior investigator he must have been aware of the national and international regulations in effect at this time regarding research and development surrounding medical technology, for research with stem cells and comparable drugs, and that translational research requires preceding preclinical data and the establishment of high quality manufacturing processes. With this in mind, conducting research despite being aware of the methodological and administrative shortcomings appears almost amateurish or possibly fraudulent. Further there is a decision from the clinical manager at Karolinska University Hospital, Richard Kuylenstiema, that the work constituted healthcare but that a permit had to be applied for when it shifted to research. In light of this, an ethical permit and other relevant permits should have been obtained back at the time the paper was being planned. Paolo Macchiarini claims that he was aware that the clinical report on the patient’s status was written in August and that it was impossible to foresee that the patient’s clinical status would change during the postoperative phase. Since he was part of an experimental and preclinical unit, he was, by his own account, unable to check the patient’s status himself in the hospital’s medical records. He therefore assumed that the patient’s status was unchanged since he had heard nothing from the responsible clinicians. KI ﬁnds that there was nothing to stop him, as the leading author, asking the clinicians or co authors about the patient’s current status before the final manuscript to the Lancet. It is KI’s view that Paolo Macchiarini is responsible for scientistic misconduct”.
Update 6.07.2018. The Lancet retracted both papers as requested by KI (but not their above mentioned 2015 editorial). In a accompanying editorial of today, Lancet suggested that the whistleblower Grinnemo was just as guilty as Macchiarini and Jungebluth.
KI meanwhile issued another press release, explaining what the findings of misconduct and blameworthiness mean:
“Of the seven persons found responsible for research misconduct only one is an employee at Karolinska Institutet [Katarina Le Blanc, -LS]. Given the fact that it has been seven years since the current publication, the researcher was affected by other significant consequences, and that person was not even covered by the inquiry conducted in 2015 when Paolo Macchiarini was acquitted, the Karolinska Institutet will not issue to this researcher a reprimand for research misconduct.
The people employed at Karolinska Institutet and designated “blameworthy” in the decision are considered by the Karolinska Institute as not guilty of research misconduct. Therefore, no labour law measures are to be taken.
A number of people covered by the investigation have only a nominal connection with the Karolinska Institute and are employed by another employer. The labour law measures from Karolinska Institutet side are not applicable to these people”.
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