The Karolinska Institute in Stockholm has decided that surgeon Paolo Macchiarini is not guilty of scientific misconduct in his treatment of three patients with tissue-engineered tracheae. The decision, announced this morning by Vice-Chancellor Anders Hamsten, disagrees with the conclusion of a report by an independent investigator, released in May, which did find that Macchiarini had committed misconduct.
"I and my team are not guilty of anything. Not having falsified anything, not having embellished or withheld anything,” Macchiarini says. "The sense of innocence is prevailing.”
Macchiarini, a visiting professor at Karolinska, led teams that transplanted artificial tracheae into three patients at the institute’s hospitals. The patients had suffered damage to their tracheae because of cancer or side effects from another surgery.
The tracheae were made of a polymer scaffold that was seeded with the patients' own stem cells. The stem cells were supposed to grow into and over the scaffold to create a functional trachea. The first patient survived for 2 years after the operation. The second patient died a few months after receiving his transplant; the cause of his death was never made public. The third patient has been in intensive care at Karolinska since receiving her transplant in August 2012.
In August 2014, several doctors at Karolinska filed official complaints against Macchiarini, charging that the description of the patients’ condition in six scientific papers left out complications and that medical records did not substantiate the positive description of the graft’s development in the patients. They also challenged the results reported in one animal study of the technique. And they raised questions about whether Macchiarini had obtained proper ethical permits for the surgeries.
In response to the complaints, Karolinska commissioned an independent investigator, Bengt Gerdin, a professor emeritus of surgery at Uppsala University in Sweden, to examine the case. He concluded that there were significant discrepancies between the available medical records and the published results, and that the discrepancies constituted misconduct. He also said there were serious questions about the ethical permission for the surgeries, but left that to a separate investigation by Swedish medical authorities.
Hamsten’s decision takes into account Macchiarini’s rebuttal to the investigator’s report as well as additional testimony by doctors outside Sweden who had treated some of the patients. “The statements submitted by Macchiarini and many of his co-authors convincingly contest the essentials of the complainants’ criticisms and Gerdin’s assessment of the key issues that form the basis of his conclusion that scientific misconduct has been committed,” the decision says. “The main issues addressed … have been satisfactorily countered by Macchiarini and his co-authors, and so there is nothing to support the complainant's suspicions of scientific misconduct.” Hamsten told ScienceInsider that it was unfortunate that Macchiarini had not submitted the materials sooner. “From the university side, we are very impressed with the meticulousness and structure of Gerdin’s report. But he did not at that point in time have all the relevant information.”
Gerdin says he has not yet read the material submitted in response to his report. But he says the process was flawed, in that it allowed Macchiarini to pull “aces from his sleeve” after the external investigation was complete. That seriously undermined the impartiality of the investigation, he says. “It’s a meaningless process” to commission an independent external reviewer if the final decision is based on documents available only to Karolinska officials, he says.
Gerdin adds that he assumed that all of the records relevant to the papers would be available in Macchiarini’s department, because he was the lead author—not at doctors' offices abroad. Hamsten says that was a fair assumption. “Good research practice requires that all the documentation should be assembled in one place,” he says. (Karolinska has also posted Hamsten’s responses to frequently asked questions about the investigation at this link.)
The Karolinksa decision does find some fault with Macchiarini. “Certain circumstances that have arisen during the inquiry concerning Professor Macchiarini’s work show, however, that it does not meet the university’s high quality standards in every respect.” It says the vice-chancellor will meet with several heads of departments and Macchiarini to decide on further measures. Hamsten says that will include submitting errata on several of the papers in question. Macchiarini told ScienceInsider that he does not think any errata are necessary, but that the final decision will be up to editors of the journals involved.
Karolinska will also “review its procedures, rules and support structures for clinical studies, clinical therapies and clinical trials” to better coordinate between the institute and its university hospital, and it will also write new guidelines to govern the division between clinical application and research on experimental therapies. “It’s a very complicated area, and the regulations aren’t entirely clear,” Hamsten says.
A separate investigation of complaints brought against Macchiarini by trachea surgeon Pierre Delaere at UZ Leuven in Belgium was completed by Karolinska’s ethics council in April. It found that the complaints could be explained by a difference of scientific opinion between the two researchers and concluded there was no evidence of misconduct by Macchiarini. Local prosecutors are still investigating charges related to the case, based on referrals by the Swedish Medical Products Agency and the Health and Social Care Inspectorate.
Macchiarini says that a clinical trial he was conducting in Russia with engineered tracheae has been put on hold. “We are trying to improve the technology,” he says. “As soon as it is improved we will continue the trial."
*Update, 28 August, 1:36 p.m.: This item has been updated to include comments from sources involved in the investigation.