Macchiarini investigations outcome: the Karolinska Institutet

The second main investigation into lethal patient abuse by the thorax surgeon and regenerative medicine “pioneer” Paolo Macchiarini is now concluded in Stockholm. After the Karolinska University Hospital (Karolinska Universitetssjukhuset, KS) published their investigative report on August 31st (see my coverage here), the Karolinska Insitutet (KI) now followed suit on September 5^th.

This KI investigation was led by the former president of the Supreme Administrative Court of Sweden Sten Heckscher, who was assisted by the journalist Ingrid Carlberg and the Finnish biochemistry professor Carl Gahmberg. Interestingly, the very person who appointed Heckscher in February 2016 as external investigator, the Chairman of the KI University Board (Konsistoriet) Lars Leijonborg, surprisingly resigned just last Friday.

Given the professional specialisation of Heckscher as lawyer and policeman, his investigation focused on the administrative aspects, and not on science or medicine (which possibly was supposed to be covered by the KS investigation).

These are the results, according to the English-language summary and the translated Swedish full report.

Hardly surprising, the decision of the then-Vice-Cancalelor Anders Hamsten from August 2015 to trash the Bengt Gerdin investigation and to declare Macchiarini free of misconduct, was now seen as “poorly justified”. Otherwise: Macchiarini’s recruitment was inappropriate and done against all warnings (as already determined by the KS report), he was neither supervised nor evaluated and his research documentation disappeared after he left. Finally, the report suggests that KI bears no direct responsibility for the plastic trachea transplants which killed or maimed all of the 8 patients of the KI professor Macchiarini.

The others did it

Just as the KS report was pushing the bulk of the responsibility to the KI, now it is vice versa. According to the Heckscher report, which addressed the three plastic trachea transplant operation detailed by the KS counterpart, these were not clinical research, but health care, and thus it was the hospital which was primarily responsible:

“The operations took place at the hospital – where Macchiarini was also employed – and within the framework of health care. The decisions to perform the operations were taken at the hospital by hospital personnel, who also held all the pre-surgery discussions. According to the regulations pertaining to hospitals, responsibility for the decisions to carry out the operations – as well as how the operations were carried out – therefore unequivocally lies with the Karolinska University Hospital.

We believe, however, that KI also has a certain responsibility for the transplantations. There are many instances of KI employees being involved in the discussions preceding and following up surgery. KI has also, in several contexts, cited the transplantations as part of its own activities. For example, they have been quoted as research successes in KI’s evaluations of how research funding has been utilized”.

With that little responsibility for human experimenting just next door, it is rather unsurprising that the Heckscher report absolves KI of all responsibility on what their own professor did in Russia. There, the star surgeon and scientist transplanted several patients with plastic tracheas, all of whom are likely dead now (unless you trust Macchiarini and Russian official sources). The Heckscher team decrees:

“The only significant connection between Macchiarini’s activities at KI and the operations in Russia is Macchiarini himself. Our conclusion is therefore that KI cannot be held responsible for Macchiarini’s work in Krasnodar”.

Thus, KI is found not responsible for the death and suffering of all the eight patients whom their own star scientist transplanted with his “stem-cell regenerated” plastic tracheas, in Sweden and in Russia. KI is however criticised for not having properly scrutinised Macchiarini’s “extra-occupational activities” when they had a chance to do so, in 2012 and 2015.

Bad references

As already determined by the Karolinska Hospital counterpart-report, Macchiarini was recruited to KI despite negative references and warnings. The blame is assigned to the former Vice-Chancellor Hamsten (who resigned already in February 2016), while Macchiarini’s boss at the KI’s Department of Clinical Science, Intervention and Technology (CLINTEC), Li Felländer-Tsai, is absolved from guilt (just as by the KS report):

“Macchiarini was recruited to Karolinska Institutet and the Karolinska University Hospital in 2010 as visiting professor at KI (30 per cent) combined with an employment as consultant at the hospital (30 per cent). At KI, he was posted to the department of CLINTEC. His recruitment was initiated by then vice-chancellor of KI in the autumn of 2009. The vice-chancellor took an active part in and had personal contact with Macchiarini during the recruitment process in a way that constituted a breach of the delegation of authority and that created some confusion about who had responsibility for his recruitment. To the head of CLINTEC, it seemed like the decision was already taken and the recruitment process a mere formality”.

The earlier published report by the Karolinska Hospital mentions several instances of negative references provided by Macchiarini. Now, the Karolinska Institutet file names these sources:

“In August 2010, Professor Sven-Erik Dahlen, Head of Unit Experimental Asthma and Allergy Research at the Institute of Environmental Medicine, Karolinska Institutet, was contacted by an Italian colleague, professor of pulmonary medicine and asthma researcher Leo Fabbri, University of Modena and Reggio Emilia. Fabbri recited according to Dahlen “serious criticism of the PM’s research, clinical review and general character” and thought Dahlen would dissuade their colleagues at KI from recruiting Macchiarini. [..]

The email mentioned to Dahlen two points in Macchiarinis public CV which Fabbri claimed were incorrect. According to Fabbri, Macchiarini was not like he declared a professor of surgery at the University of Barcelona. Nor had he been Professor of Surgery at Hannover Medical School. In Barcelona Macchiarini had according to Fabbri only a temporary appointment at the hospital and had to quit “when he neglected the duties”.

Other sources of references were the larynx surgeon Martin Birchall in London (who now has his own line of regenerated trachea experiments in humans), Alvar Agusti and Manuel Bernal, two professors of medicine at the University of Barcelona, as well as Tobias Welte, professor of pulmonary medicine at the Hannover University School of Medicine (MHH).Welte was also one of the examiners at Philip Jungebluth’s medical doctorate defence (more about Jungebluth and his dissertation here). This was what Dahlen summarised in his email to the director of CLINTEC’s Ear-Nose-Throat division Lars Olaf-Cardell:

“Altogether, we have a positive reference from London (Martin Anthony Birchall), a negative from Florence (Leo Fabbri) and two negative from Barcelona (Alvar Agusti and Manuel Bernal). We will receive a copy of the critical letters which Tobias Welte in Hanover wrote to colleagues in Barcelona before Macchiarini’s employment there (this, however, Barcelona chose to ignore when he was hired). All referees agree that he  is a technically dazzling surgeon. From Florence and Barcelona came forward consistent evidence that he has a distinct personality that makes him difficult to accept both adversity and
opinions regarding the surgery that does not coincide with his own. […] From Southern Europe: sweeping, yet consistent allegations of negligence in terms of dealing with the truth, lack of collegiality, poorly consideration for patients and families as well disrespect for the rules (both actual and moral). The accuracy of his long and impressive resume has been questioned by Florence and we therefore requested Thursday additions in the form of certificates on three key points concerning the hand of service. These have not yet been received”.

Welte then described Macchiarini as “a brilliant surgeon, very innovative”, “a real academic researcher with good and relevant research proposals”. His key concern was that this star clinician was “very difficult to negotiate and cooperate with”. The information about the negative references was however never forwarded to the Recruitment Committee at Karolinska:

“The reason for this, according to the prefect Felländer-Tsai, have been that it was not needed because the Recruitment Committee shall only make a scientific assessment of the applicant”.

Also the certificates of Macchiarini’s professorships which Felländer-Tsai requested on the account of the negative reference outcomes seemed not to have been closely examined. Instead, she and Cardell wrote  to the regional president of Tuscany for a “better” letter of reference. Which they promptly received, the entire communication is available exclusively here.

Nobody checking anything

After the outrageously biased recruitment, Macchiarini’s employment as KI-professor was extended twice in 2013 and 2015, without any evaluation:

“Our inquiry shows that KI initiated no real evaluation and assessment of Macchiarini’s work at KI, neither ahead the contract extension in 2013, nor ahead the contract extension in 2015. For the 2013 extension there were countless circumstances that should have warranted such an evaluation. This includes the uncertainty surrounding the reason for the legal action taken against Macchiarini in Italy in the autumn of 2012, and the objections to Macchiarini’s activities raised by the Karolinska University Hospital in 2013 that made the hospital decide to stop further transplantations and terminate its part of Macchiarini’s contract”.

Back in 2013, Karolinska hospital banned Macchiarini from operating, but made sure his medical licence in Sweden was extended. His professorship and research into regenerative medicine at KI continued, and the experimental bit, involving human research subjects: that was apparently “outsourced” to Russia. An authoritarian state, known for its corrupt medicine, bureaucracy and its even more corrupt, actually farcical, justice system.

The Heckscher report apparently did not address the scientific side of the Macchiarini scandal, (though one of the Committee’s members, Gahmberg, is a biomedical scientist). It would have been very informative nevertheless, given that two KI’s own internationally recognised stem cell researchers ( Urban Lendahl and Ernest Arenas) recommended Macchiarini’s employment in the notorious 2010 letter to the  KI rector Harriet Wallberg-Henriksson (which I publish here). Wallberg then played a key role in Macchiarini’r recruitment and claimed to have been unaware of his dishonest CV or bad references. In 2012, Wallberg-Henriksson wrote to Macchiarini an email, with Lendahl and the Dean of Research in cc:

“Dear Paolo, I am writing to inquire whether you are available for a meeting in August. Based on your extremely successful time at Karolinska Institutet I would like to meet with you and discuss (together with the Dean of Research, professor Martin Ingvar) the possibility of a more permanent position for you”.

The fact that Macchiarini had to retract a paper for plagiarism (Gonfiotti et al 2012) was only seen as problematic because it could affect his big funding and professorship. So a supportive verdict was reached in early 2013 by the corrupt Ethics Council of KI (meanwhile dismissed), under pressure from Wallberg-Henriksson and CLINTEC boss Felländer-Tsai, later on approved by the new rector Hamsten.

In fact, the former university head Wallberg-Henriksson had a unusually close relationship to her guest-professor Macchiarini:

“The guest professor accrued his private relationships with KI’s top management, hospital management, and donors, in a way that does not occur frequently. He and the rector had their own meetings without the knowledge or presence of the people who are in the line between the principal and the guest professor. Guest professor also gives the impression of having worked relatively informally, contracts and written agreements were missing in several cases where the internal audit perceive that such ought to be”.

Now, the KI chancellor Wallberg-Henriksson was sacked from her post by the cabinet minister for research and education, as soon as today’s report was published.

With science left largely aside, Heckscher’s investigation focused on the administrative side of the scandal:

“We criticize KI for its nonchalant attitude towards regulations – sometimes enshrined in the constitution – governing how public authorities are to manage their business. Not only are many public documents, such as external e-mails, not registered”.

This calls to memory another misconduct case at Karolinska Institutet. An investigative dossier about the data manipulations by the former KI scientist Suchitra Sumitran-Holgersson, addressed to the above mentioned Dean of Research Ingvar and submitted by hand to the KI registrar, disappeared into thin air, in fact it was also never registered as well (see my detailed report here).

Macchiarini was previously accused of data manipulation and research misconduct by the four KI whistle-blowers. The Heckscher commission found out that KI was not really eager to investigate those accusations:

“The six cases of alleged scientific misconduct concerning Macchiarini were administrated and examined in different ways. Sometimes no action at all was taken, sometimes the case was referred to KI’s internal Ethics Committee, and sometimes an external investigator was engaged. […] In none of the reported cases did KI turn to the Central Ethical Review Board as directed in the Higher Education Ordinance. […]It also appears as if KI did not ensure that the external investigator [Gerdin, -LS] received all the information he requested”.

Friends at CLINTEC

Proving whether or not and what data exactly Macchiarini has faked at KI will be difficult now, since his research documentation disappeared. He simply either destroyed it or took it with him when he left, while none of his superiors sought it as important to make sure any backup copies stayed at KI. Macchiarini’s ex-boss Felländer-Tsai apparently saw this as perfectly normal procedure, as the Heckscher report suggests:

“CLINTEC, the department where Macchiarini was based, is unable to provide complete information about the documentation of the visiting professor’s research at KI. The reason given is that Macchiarini and the rest of the group has left the department. It is unacceptable that a disbanding of a research group has such far-reaching consequences that documentation concerning completed research at KI can no longer be traced”.

In  fact, it it is not just that Macchiarini’s research notes disappeared. It is likely some animal experiments were either done on humans first, or not at all. Once again, humans (patients Beyene and Lyles) went under Macchiarini’s knife first, to test the water for rats:

 “In May 2012, he received permission to conduct animal experiments related to the trachea. Then it was concerned about attempts by both decellularized cadaver body as synthetic – artificial – frame. It may be noted that patients 1 and 2 by that time had already undergone surgery at Karolinska University Hospital. […]

Our investigation shows that the so-called bioreactor is not mentioned in any meeting minutes from Macchiarini and Sylvén [Christer Sylvén, boss of one of Macchiarini-whisteblowers, -LS], research took place only from March 2012 on. However, there is evidence that one of Macchiarinis employees may have worked “with non-sterile plastic tubes and cells with the so-called bioreactor “already. The timing is however uncertain”

The research documentation was gone together with Macchiarini anyway, just as in the next critical case. Macchiarini and his international collaborators published a report in a highly respected journal about successful artificial oesophagus transplantation in rats.  This is what the Heckscher commission found out in this regard:

“no animals have been ordered under the Animal Ethics statutes 6-11, 8-11 and 160-1137 despite at least permit No. 160-11 appears to be the basis of the scientific article Sjöqvist et al, Nature Communications 2014. Inquiry asked in this regard the prefect [Felländer-Tsai, LS] and head of the unit at CLINTEC (either  Cardell or Göran Gynther, head of division, -LS], but got the answer that because the research team leader not longer at KI department, they can not comment further in the matter”.

Why didn’t the CLINTEC head Felländer-Tsai backup Macchiarini’s research data? Well, as I found out, they used to be close friends. Felländer-Tsai was invited to Macchiarini’s fraud-wedding with the duped journalist Benita Alexander (see this Vanity Fair story for details), which was supposed to be ordained by the Pope himself. Unlike Vladimir Putin and Barack Obama, Felländer-Tsai was invited as a real and not as an imaginary guest, and so was her colleague Cardell. The former informed the groom-to-be that she wouldn’t be able to attend due to family engagements, but sent a present. Other real guests scheduled were, aside of Macchiarini’s lab members like Jungebluth, the families of the very patients who died after being transplanted with plastic trachea by the miracle doctor: those of Christopher Lyles (mentioned among other Macchiarini patients in my special report) and Hannah Warren. The sister of this two-year old victim of human experimenting was supposed to be the flower girl at Macchiarini’s lie of a wedding.

These two friendly clinician colleagues, Felländer-Tsai and Cardell, are still in their positions at Karolinska, while everyone around them has been (voluntarily or not) taking their hats for months.

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Note: this article has been updated twice since it first appeared, on 5.09, 6.09 and 7.09, to include information from the translated full version. For some reason, KI decided to publish their full Swedish-language report in a format unsuitable for machine translation. Elizabeth Woeckner found a way around it, here are the Google-translated chapters 6,7,8, 10, 11 and 12, highlight are hers. Macchiarini’s funding and ethics permits available separately  here. Many thanks to Liz.