The Karolinska Institute in Stockholm today released its English translation of a report critical of surgeon Paolo Macchiarini, famous for transplanting tissue-engineered tracheae into more than a dozen people. The report concludes that Macchiarini committed scientific misconduct in publications describing the results of several of the transplants. Karolinska, where Macchiarini is a visiting professor, commissioned the external inquiry after allegations arose in August 2014.
The investigator, Bengt Gerdin, professor emeritus of surgery at Uppsala University, examined six papers about the patients and one on animal tests of the procedure and found multiple problems that he deemed serious enough to constitute misconduct, including inaccurate descriptions of the condition of patients at the time of publication and stating that ethical permission had been obtained for the work although there is none on record. The report, submitted to the Karolinska vice chancellor on 13 May, concludes that Macchiarini “bears the main responsibility for the publication of false or incomplete information in several papers, and is therefore guilty of scientific misconduct.”
Macchiarini has disputed the allegations, but he told ScienceInsider that he could not comment further until Karolinska Vice Chancellor Anders Hamsten issues his decision on the case. That is expected sometime in June.
Macchiarini and his colleagues attracted widespread attention by developing a technique intended to help patients whose tracheae were badly damaged by cancer, injury, or birth defects. They designed a polymer scaffold, which is seeded with the patient’s stem cells to construct a replacement trachea. The stem cells are supposed to grow over the scaffold and eventually develop into a living organ.
The allegations of misconduct came from four researchers at the Karolinska Institute and the affiliated Karolinska University Hospital, where three transplants took place. The four critics—who co-authored several of the controversial papers—say they became concerned in the fall of 2013 when they learned of serious complications in the first patient to receive an artificial trachea at Karolinska. (They say they were not involved in the care of that patient after the initial surgery in 2011. He was treated at a hospital at Karolinska’s Huddinge campus, 25 kilometers from the critics’ primary location in Solna.) When they looked into the case records of the patients operated on at Karolinska, they concluded that the papers failed to mention the serious complications the patients had suffered, and ultimately asked Karolinska to investigate.
In particular dispute is a paper published in December 2011 in The Lancet. It claims that, 5 months after surgery, the recipient, a 36-year-old graduate student, had no complications and the graft was showing early signs of tissue growth. However, there are no clinical records of the patient’s status 5 months after surgery, Gerdin points out; the available clinical data in the records were from August, 11 weeks after surgery. In November, several weeks after the paper was accepted but before it was published, the patient was readmitted to Karolinska with complications that ultimately required a stent to keep his airway open. The engineered trachea had significant problems, the critics say in their complaint, but Macchiarini did not notify The Lancet. Nor did he mention the complications in a Lancet review paper published 3 months later. That paper says that the graft was in good condition 8 months after surgery.
In his initial written response to the accusations, Macchiarini denied any misrepresentation. Philipp Jungebluth, an assistant professor at Karolinska who was recruited with Macchiarini as a postdoctoral researcher, also maintains that all the papers in question are accurate. Both he and Macchiarini say that the complications that arose after the paper was accepted were not relevant, because the article was intended to provide a clinical snapshot. Jungebluth says that despite the complications, the patient did well for at least a year after his initial surgery. He finished his studies and had a second child after the transplant, Jungebluth notes. All the patients who received artificial tracheae were complex medical cases who had no other options, he says, and post-transplant complications were to be expected.
The four physicians who reported concerns about Macchiarini also alleged that he did not get proper authorization from an ethics review board for the surgeries and failed to get informed consent from the patients. Such issues fall under Swedish health care law rather than scientific misconduct regulations, Gerdin says, so his report did not pass final judgment on those allegations. The Swedish Medical Products Agency referred the case to a prosecutor earlier this month.
A separate investigation by Karolinska’s ethics council into allegations of misconduct brought by Pierre Delaere, a surgeon at UZ Leuven in Belgium, was completed in April. Delaere, who has developed a different method for replacing a damaged trachea, has long criticized Macchiarini’s work, saying that his papers do not reflect the true condition of the trachea recipients. The ethics council report concluded that Delaere’s complaints were either due to a difference of opinion or were too vague to be substantiated. Gerdin says he does not disagree with that report. The allegations brought by the Karolinska researchers were more concrete, Gerdin says, and addressed specific discrepancies between patient records and published papers.
Gerdin’s report says Macchiarini bears the primary responsibility for the misconduct. However, he also faults the Karolinska Institute for failing to anticipate that Macchiarini’s surgeries would need clear ethical oversight and the co-authors for signing off on papers that were inaccurate.
Macchiarini and the researchers who brought the complaints have 2 weeks to comment on Gerdin’s findings. Vice Chancellor Hamsten will then decide what action to take, a Karolinska representative says.