The indestructible Swedish regenerative medicine researcher Suchitra Sumitran-Holgersson could have been stopped early on, and a patient of hers could have been alive still. The former professor at the Karolinska Institutet (KI) was caught faking data in 2009. A paper had to be retracted as consequence (Elsheikh et al, Blood, 2005) , but in 2011 the entire external investigation and its results was declared nil and void by the Swedish Research Council Vetenskapsrådet (VR) which had originally commissioned it. The reasons used back then were rather incomprehensible, it boiled down to the accusations against the two investigators themselves, of having found research misconduct where they were not supposed to find research misconduct (for details, see my earlier report). To top it off, all frozen funding of this cheater professor was reinstituted and the University of Gothenburg together with its Sahlgrenska University Hospital welcomed Sumitran-Holgersson as a “genius”. There, at the Department of Surgery at the Sahlgrenska Academy she established a hub of regenerative medicine, helped by her husband Jan Holgersson (whose company had been threatening his wife’s investigators, silently condoned by VR), and by the head surgeon Michael Olausson. Together, Sumitran-Holgersson and Olausson produced a string of regenerative medicine papers of which the University of Gothenburg and Sahlgrenska used to be very proud. Maybe less so these days, since a rich evidence of fresh data manipulations surfaced on PubPeer several months ago (see examples here). Meanwhile, part of Sumitran-Holgersson’s tremendous funding has been frozen, though VR still maintains their trust in her research. Apparently, also the Sahlgrenska Academy of Gothenburg.
The actions of Sumitran-Holgersson and Olausson were investigated by a committee chaired by Bengt Gerdin, the same investigator who uncovered Paolo Macchiarini’s misconduct in 2014/2015, only to see his report being trashed by the then-Rector of KI, Anders Hamsten. The Gerdin report for the Gothenburg University Hospital is now finalised, its main findings were published as press release. Strikingly, there are no criticisms on the scientific aspect of the technology applied by Sumitran-Holgersson and Olausson, only on their evasion of appropriate ethical approvals.
The investigation at Sahlgrenska started in early 2016, after the death of an elderly patient who received a trachea transplant, which was prepared with a method similar to that of Macchiarini. Sumitran-Holgersson and Olausson used a decellurised donor carcass and “regenerated” it using the patient’s own bone marrow cells, which according to these two scientists can generate any tissue or organ when told to do so. Also the similarly made experimental transplants of “regenerated” veins into three child patients became subject of the investigation (all three are in life-long medical care, one graft proved as failed, patient received a liver transplant; another child patient suffered severe complications even after another graft was implanted).
When the scandal of the lethal trachea transplant and data manipulations broke, it quickly turned out that the authors failed to obtain ethics approval for either of these interventions, while pretending to the opposite in their publications. Only the trachea-transplant paper (Berg et al, Tissue Eng Part A. 2014) has been retracted so far as the consequence, other journals like The Lancet seem to value ethical issues as secondary to exciting (even if potentially fake) results (see Olausson et al 2012). The Gerdin report according to press release, now found:
“There had been four critically ill patients who had major difficulties in their daily lives with lower quality of life as a result and the high risk of deterioration and at worst fatal.
Other forms of treatment were not obvious, and the three children had the option of liver transplant as an alternative treatment.
The transplants were in patients’ best interests, and the primary aim was to give patients the best possible treatment.
Prior consent of the patients and / or ethical considerations were made for the treatments but there are shortcomings in the documentation of these considerations.
Other documentation about the care, treatment and decision is flawed.
There had also been a contact with various authorities and ethical assessor, although these contacts are not documented in writing, but in several cases attested orally afterwards.
The report shows that the relevant legislation was changed meanwhile and that the introduction of new laws and regulations passed slowly. Although it criticizes the investigators for not having sought sought permission for the production of stem cell treated grafts and for administering to patient drugs which were not registered as medicines.
The investigators suggest that the current trend appears to have been made on a scientific basis and that, therefore, according to the Ethical Review Act is tantamount to research. Therefore, treatments have required the approval of the regional ethical review board”.
The bone marrow cell regeneration technology by Sumitran-Holgersson is presented as perfectly scientific, even retrospectively. No recommendations for the retractions of ethically flawed papers have been issued. The numerous instances of data manipulations in her publications were explicitly not taken into account, this was in fact how the investigation was designed from the beginning on. In March 2016, Gerdin wrote to me:
“What is done in Gothenburg is not an investigation due to suspicion of research misconduct, as was the case at KI, but an internal investigation based on a joint initiative between health care and university with the intention to assess in very detail what was done with respect to the transplanted trachea and the actual vein grafts, and secondly to analyze what to learn from that. In the end, the goal is to develop procedures for work in the boundary between clinical research and medical care. Professor Olle Lindvall, who is to lead the process to assess similar issues under the Royal Academy of Sciences, and professor Kjell Asplund, who is to lead the investigation on the parts of the Macchiarini affair that took place at the Karolinska Hospital [see here my coverage of the Asplund report on Macchiarini, -LS], are loosely associated in order to validate the process”.
Just days before the publication of the results of his investigative report, Gerdin stated that:
“this inquiry involves an assessment of the intellectual process and the depth of decisions before the surgeries. It aims to shape a basis for a future routine that fulfils ethical requirements and the law. It does not cover the content of the subsequent papers”.
The task to investigate the numerous data manipulation concerns therefore lies with the University of Gothenburg. From there, I was informed by the spokesperson Ulrika Lundin, that
“The Council for investigation of suspected misconduct in research at the University of Gothenburg is investigating the matter. The council does not comment on the matter during the investigation. When the investigation is done, a report will be presented to the vice-chancellor and the report will be made public”.
I also managed to obtain internal case numbers (D 2016/42 and D 2016/74) as well as the constituency of this Council: Björn Rydevik (chairman), Malin Celander (vice chairman), Yvonne Leffler, Philip Hwang, Lars Rönnbäck, Anders Carlsson, Leif Eriksson and Kerstin Landin-Wilhemsen.
Let us now wait what the Gothenburg University investigation will find out.
Summary of the Gerdin investigation, full version available in SwedishSwedish and Google-translated:
“A detailed examination has been made of the measures and assessments prior to and in connection with the four surgical procedures carried out in Gothenburg care years 2011 and 2012.
Intervention consisted partly of transplantation of autologous decellularized and then recellulariserad trachea, and partly by the establishment of the socalled mesoRex bypass in three children with of decellularized and then autologous recellulariserad donor vein. The actions were carried out during a period of major changes in the European and National legislation on the handling of tissues and cells for use in healthcare. The implementation of the new legislation in health care was at this time deficient.
The measures were performed on critically ill patients without the immediate threat of death. Isolated similar treatments with recellulariserad trachea had been carried out in the world and recognized in literature. In contrast, no similar meso Rex-operation was ever implemented. Both decellularized as recellularised tissue structures, however, had been used in other contexts as part of clinical research with the aim to improve the properties of various vascular grafts.
The Medical Products Agency had been contacted in writing. At these conversations, the official representative have expressed that some patients could have been treated under the current tissue regulations. A conference had also been held with local ethics boards, which ensured that the ethical aspects were included in the preamble before planned action. This was documented, but not in real time.
You can not retrospectively assess in detail whether there were any other realistic surgical options for the current four patients than those which were selected. Interventions were not carried out in an environment with very large clinical experience with the current conditions and with frequent international contacts which should have ensured that it had been aware of the opportunities and options at that time tried by other specialists in similar situations. It lacked, however, the production permit from the Medical Products Agency for grafts used in the interventions. Similarly lacking authorization to a patient intratracheal administration of three substances which were not registered as medicines.
Several factors suggest that intervention moved for development on a scientific basis, something that the Ethical Review Act equates with research and require the approval of the regional Ethics Board. Central considerations facing the performed interventions, including ethics problems, the medical work situation, the quality control of the grafts, and the decisionmaking process are missing in the available records. This makes it difficult to subsequently and unequivocally get a grip over the various steps in the pre-operative assessment.
Seen from an overall ethical and medical perspective, however, the impression that treatments were carried out with the patient’s best interests in mind and, as far as could be ascertained, with patients’ and relatives’ informed consent.
The patients have been followed continuously by clinical treatments and the results seen in the patient records.
This opinion can not form the basis of such an investigation of misconduct in research as stipulated in the Higher Education Chapter 1, Section 16”.