Karolinska in denial, by Johan Thyberg

This is a guest post by Johan Thyberg, a 1947-born Swedish biologist and a well-known activist against science fraud. His 2009 published book “Scientific Fraud or Legal Scandal?” meticulously narrates several fraud scandals in Swedish science, one of which I referred to when introducing a guest post of another concerned Swedish academic. Until his academic retirement, Thyberg used to be professor for cell and molecular biology at Karolinska Institutet (KI) in Stockholm, the showplace of probably the biggest medicine scandal of recent times, that of the trachea transplant surgeon Paolo Macchiarini.

Below, Thyberg exposes Karolinska’s plans to shift the entire blame onto Macchiarini and wash themselves of the bulk of responsibility. In fact, every single academic institution where Macchiarini ever performed his tracheal transplant operations (British UCL, Spanish Hospital Clinic Barcelona, Italian University Hospital Careggi, German Medical University Hannover) is keen to beat distance to his person, but strangely, not to his human experiments as such. In fact, even Macchiarini’s former Russian host and Megagrant recipient, the Kuban State Medical University in Krasnodar quietly separated from him, while previously defending all those four disastrous human experiments with plastic trachea which they performed together. The star surgeon is now based many miles away at the Federal University of Kazan in Russia, as a local Russian newspaper reported. There, Macchiarini goes under the title of “professor Open Lab Institute of bioengineering and regenerative medicine” and is busy experimenting (or torturing) monkeys with oesophageal transplants. His contract seems to run until the end of 2017. The Russian state also provided him with a fresh research grant (see Nr 14-45-00018 here), to test a tissue engineered oesophagus on primates.

The preliminary results were recently presented by Macchiarini at a November 2016 regenerative medicine conference in St. Petersburg, section  “Bioengineering esophagus in non-human primates” (see abstract book, page 68). Also his acolyte Philipp Jungebluth was listed with a talk, and their common recent collaborator, the German nanotechnology professor Wolfgang Parak. Is Macchiarini moving into nanoparticle-assisted stem cell technology with his oesophageal transplants, after the outcomes of initial attempt in rats had to be rigged to be published in a Nature Communications paper? Just now, on December 12^th Macchiarini taught students at a “conference-school” in Kazan about “Tissue engineering-New approaches”, which he organised following his rector’s order (sic!). He was assisted there by his faithful followers Jungebluth, Silvia Baiguera, Costantino Del Gaudio and Parak’s guest-postdoc Neus Feliu Torres (whom Macchiarini worked with already back at KI, where she did PhD). The latter guest from the University of Marburg spoke about the “Development of nanoparticles for tissue engineering”. Update 26.03.2017: I received reliable first-hand evidence that Feliu was not present at that conference.

It is the person of Macchiarini which his former and current collaborators and employers tell us to see as the sole and exclusive problem, not his scientific and clinical technology. Three of a total of nine plastic trachea transplants were performed by Macchiarini in Stockholm, another transplant in Krasnodar was approved by Karolinska doctors over a video conference. This is something KI is strongly refusing to admit, and what Thyberg now exposes, among other things.

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Johan Thyberg on the Paolo Macchiarini investigation at Karolinska

In the so called Macchiarini affair at Karolinska Institutet (KI) and the Karolinska University Hospital (KS), some concern has been paid to the question of what KI/KS actually knew about the collaboration Paolo Macchiarini had with the Kuban State Medical University in Krasnodar, Russia. The former vice-chancellor of KI, Anders Hamsten, claimed that KI lacked knowledge about these activities and the transplantations made there. In this context, considerable attention has been paid to a video conference held in February 2012 with participants from Karolinska University Hospital (Stockholm), Kuban State Medical University (Krasnodar), Russian Academy of Medical Sciences (Moscow), University Hospital Careggi (Florence), and MD Anderson Cancer Center (Houston/Texas).

Conference to test the equipment?

In the external reports examining the responsibilities of KI (Heckscher et al) and KS (Asplund et al) in the affair, this conference is taken up. In the Heckscher report, it is concluded that the conference was of no real value and basically could be seen as an unsuccessful attempt to test communication equipment. The Asplund commission gives a more detailed description of the conference and the work of Macchiarini in Krasnodar. Information about the video conference in February 2012 is available as a slide show and as summaries prepared in Krasnodar and Moscow, respectively (see enclosed document – Video-conference).

It is very difficult to see this as the Heckscher commission did, i.e. as an “unsuccessful attempt to test communication equipment”. The persons who participated from KI was in addition to Paolo Macchiarini (director ACTREM – a unit at the KI department CLINTEC) and his close collaborator Philipp Jungebluth (executive director ACTREM), Lars-Olaf Cardell (head of the ENT division at CLINTEC to which ACTREM belonged) as well as two high representatives of the ENT clinic at KS/Huddinge, Richard Kuylenstierna and Mats Holmström.

Another example of the importance of video conferences in the work of Paolo Macchiarini is found in the letter Ola Hermanson – a co-author of the Jungebluth et al, Lancet 2011 article and a strong defender of Macchiarini – wrote to the then vice-chancellor of KI Anders Hamsten as part of the misconduct investigation (enclosed). The letter is dated June 26, 2015 and in the second paragraph on page 2 the following is stated:

“May 27th (2011) I received an email from Jungebluth who then tells me that there has been a major multidisciplinary video conference with all involved “heads” of the clinical departments, including anesthesia, intensive care, thorax surgery, ear-nose-throat etc, and that the surgery of the 1st patient to receive a bioartificial trachea is planned for June 9^th”.

This again emphasizes how well informed all the clinical “heads” were. And no one stopped the use of humans as test objects for a method that had never before been tested even in laboratory animals and totally lacked a firm theoretical basis (as for example pointed out by the Belgian airway surgery specialist Pierre Delaere – Delaere & Van Raemdonck, 2014). Moreover, the transplantation Hermanson writes about in his letter lacked all permissions required by law and included treatment with a factor – TGFbeta – that according to the manufacturer is even forbidden to use on animals because of the medical risks involved. Ten microgram of this factor (a huge amount in biological terms) for the price of more than SEK 90,000 (~€9000) had been bought by the ENT clinic in Huddinge just before the operation in question (see enclosed invoice – R&D-invoice).

Who of all the “heads” Hermanson talks about had approved the ordering and the use of TGFbeta? Notably, it was in this clinic the first transplantation of an artificial trachea seeded with bone marrow cells was made in June 2011, described in the Jungebluth et al, Lancet 2011. This article is at present one of several that is examined by the Central Ethical Review Board in Sweden for suspicion of scientific misconduct. In addition, the operation described in the article is under invesigation by Police and Prosecutor for suspicion of serious manslaughter (sic).

It is clear from the enclosed document (Video-conference) that detailed discussions about a number of patients took place during the conference, including plans for tracheal transplantations. These discussions included the examination of, among others, X-ray and bronchoscopic pictures. At least one Swedish case was discussed, a young boy (it is even possible to see his name and personal identity number on several of the pictures).

Professor never at work, university doesn’t mind

It is also interesting to note that Paolo Macchiarini – the leader of the conference – at this time was not only employed in Stockholm (30% KI and 30% KS) but also in Krasnodar where he was “to be physically present at the University for not less than a total of 4 months in 2012 and not less than a total of 4 months in 2013” (see enclosed contract – PM-Russia § 2.4.3). In addition, he was employed in the Careggi University Hospital in Florence from March 1, 2012 with a working time of not less than three days weekly for 46 weeks per year (see enclosed contract – PM-Careggi – § 5.2, page 5). Before that he had another employment contract in Careggi with 38 working hours per week.

Still another matter of interest is that the Russian Ministry of Education and Science for the period 2011-2013 assigned a grant of 150 million Roubles (~SEK 23 million or ~€2.3 million) to the Kuban State Medical University “for a scientific research project in the field of molecular and cell biology, biotechnology, regenerative medicine to be implemented under the supervision of the Leading Scientist”. A little earlier in the agreement the following can be read: Kuban State Medical University … Paolo Macchiarini, citizen of Italy, passport No. AA5205147, hereinafter referred to as “Leading Scientist” (see enclosed document – PM-Russia pp 1 & 2).

As part of his activities within the framework of this project, Paolo Macchiarini made several transplantations of an artificial trachea in Krasnodar. One case that has become well known via TV documentaries is that of Julia Tuulik who was operated in the summer of 2012, i.e. shortly after the video conference discussed above. A person who was present during this transplantation was David Green, at that time CEO of the American company HART (Harvard Apparatus Regenerative Technology, now Biostage) that already from the beginning had cooperated closely with Macchiarini and owned the patent that was submitted in connection with the June 2011 tracheal transplantation in Stockholm (see patent). The whole business of HART was centred on Macchiarini and his ideas.

Slightly more than a year after the operation on Julia Tuulik, who was now in a bad state, a clinical study named “laryngo-tracheal tissue-engineered clinical transplantation” was registered at ClinicalTrials.gov (a federal US data base for clinical studies). The study was to be carried out at the Clinical Regional Hospital #1 in Krasnodar with Kuban State Medical University as sponsor/collaborator and Paolo Macchiarini from Karolinska Institutet in Stockholm as principal investigator (see enclosed document – ClinicalTrials-Gov).

Of course KI/KS knew about all these things and accepted that Paolo Macchiarini hardly ever appeared at his places of work in these two institutions (with no reduction in salary and big problems for the physicians that had to take care of the complications of his patients). Moreover, when he occasionally appeared there for one or a few days, KI paid for him to fly to Stockholm and then back to Barcelona (where he officially lived) or some other destination.

How the head of the CLINTEC department at KI, the head of the ENT clinic at KS/Huddinge and, ultimately, the vice-chancellor of KI and the director general of KS could allow all this to go on is a mystery.