Despite being found guilty of scientific misconduct, Paolo Macchiarini has published a new stem cell paper that is not far removed from his past work.

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Disgraced surgeon is still publishing on stem cell therapies

Paolo Macchiarini, an Italian surgeon, has been fired from two institutions and faces the retraction of many of his papers after findings of scientific misconduct and ethical lapses in his research—yet this hasn’t prevented him from publishing again in a peer-reviewed journal. Despite his circumstances, Macchiarini appears as senior author on a paper published last month investigating the viability of artificial esophagi “seeded” with stem cells, work that appears strikingly similar to the plastic trachea transplants that ultimately left most of his patients dead. The journal’s editor says he was unaware of Macchiarini’s history before publishing the study.

“I’m really surprised,” says cardiothoracic surgeon Karl-Henrik Grinnemo, one of the whistle-blowers who exposed Macchiarini’s misconduct at the Karolinska Institute (KI) in Stockholm. “I can’t understand how a serious editorial board can accept manuscripts from this guy.”

Macchiarini was once heralded as a pioneer of regenerative medicine because of his experimental transplants of artificial tracheas that supposedly developed into functional organs when seeded with a patient’s stem cells. But his career came crashing down after the Swedish documentary Experimenten showed the poor outcomes of his patients, all but one of whom have now died. (The lone survivor was able to have his implant removed.) Macchiarini was subsequently fired from KI, both the university and a national ethics board found him guilty of scientific misconduct in several papers, and Swedish authorities are now considering whether to reopen a criminal case against him.

In the new study, published online in the Journal of Biomedical Materials Research Part B: Applied Biomaterials, Macchiarini has turned his attention to the esophagus, creating polymer scaffolds designed to mimic the structure of esophagi taken from baboons. He and his co-authors report seeding these scaffolds with stem cells taken from human fat tissue and bone marrow, and finding that a portion of these cells survived and adhered to the scaffold. They write that these scaffolds could be a promising tool in tissue engineering. But Grinnemo says that this method will never produce a working organ because unlike the biological matrix that makes up a real esophagus, synthetic material cannot send the right signals to cells to form a functional unit. He also points out that the authors were unable to get endothelial cells to stick to the scaffold; these are necessary for providing a blood supply, without which any tissue will not survive. Grinnemo says the new paper’s problems have “very clear similarities” to the issues he and others raised regarding Macchiarini’s past studies on artificial tracheas at KI, half a dozen of which should be retracted according to Sweden’s Central Ethical Review Board. 

Macchiarini conducted the research while he was employed at Kazan Federal University (KFU) in Russia, and was supported by a grant from the Russian Science Foundation (RSF). In March 2017, RSF decided not to renew Macchiarini’s funding, and a month later the university fired him. Yet the paper notes a KFU affiliation and email address for Macchiarini, even though it was submitted several months after the university terminated his position. Neither KFU, Macchiarini, nor the first author of the new paper responded to requests for comment.

This is not the first time Macchiarini has attempted to create a bioengineered esophagus. In a study conducted at KI, he transplanted rat esophagi that had been stripped of their cells and then reseeded with stem cells. But in March 2017, a related paper was retracted by Nature Communications following a review by the Swedish Central Ethical Review Board. The review found that the authors could not provide the board with complete data, had violated their animal ethics permit, and had provided a “misleading presentation, interpretation and description of the results,” Although Macchiarini and the other authors on the new paper do not include a formal citation of this retracted study, they appear to refer to it as an example of their past work. 

The editor of the Journal of Biomedical Materials Research Part B: Applied Biomaterials, Jeremy Gilbert, a bioengineer at Clemson University in South Carolina, says he was unaware of Macchiarini’s history before being contacted by Science, and that no one involved in the review process indicated any knowledge of his circumstances. “The peer review of this manuscript was rigorous,” he says. “It included evaluations from a significant number of reviewers. These reviews were extensive and thorough and focused on the science presented.” Still, Gilbert adds, “It is unfortunate that such circumstances arise in the field of scientific inquiry and it would have been helpful to have better understood the circumstances surrounding this author prior to his submission of the manuscript to my journal.”

In a paper published this month in Research Policy, Solmaz Filiz Karabag of Linköping University in Sweden, who studies organization theory, examined how Macchiarini’s misconduct at KI was sustained by individuals and institutions, including journals. She says part of the problem is a lack of accountability in academia. “We need some kind of overarching international institute which will actually have control over journals,” she says. Karabag writes that academia could learn from the sporting world, which “has built international institutions to detect and penalize … advanced forms of misconduct.” Another of the KI whistleblowers, cardiac surgeon Matthias Corbascio, agrees. “Unless there’s … [a] system to maintain some sort of vigilance, then these individuals will keep doing what they’re doing,” he says. “It’s an unregulated industry.”

For now, it appears possible that Macchiarini could publish more in the future. According to RSF’s website, his team gave 10 baboons artificial esophagi in August 2016. In a December 2017 interview with Icelandic broadcaster RÚV, Macchiarini said that he was conducting a 1.5-year follow-up on the animals “so that we have sufficient data to … make an analysis and move forward,” though he avoids mentioning which research institutes he is working with. Grinnemo says that given Macchiarini’s systematic misconduct, no journal should accept his papers: “A person with these ethics should not be able to publish anything these days.”