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Lawsuit sheds light on controversial heart stem cell papers

A lawsuit filed earlier this week by two researchers involved in an investigation into possible scientific misconduct offers the first indication of just what was amiss in two papers that have been called into question. The complaint filed in a federal district court acknowledges that there are fictitious data points in a now-retracted 2012 paper that appeared in the journal Circulation, and altered figures in a much-publicized 2011 paper in The Lancet that is now under scrutiny. But it blames those problems on a third researcher—raising questions about who bears final responsibility for possible misconduct.

The lawsuit was filed by cardiac stem cell scientist Piero Anversa of Brigham and Women's Hospital in Boston, an affiliate of Harvard Medical School, and Annarosa Leri, a Harvard associate professor in his lab. The pair is suing Harvard and Brigham, claiming that investigations launched by the institutions have wrongfully damaged their careers. In particular, they allege that news of the investigations, which came to light this past April, cost them millions of dollars by derailing a deal to sell their stem cell company, Autologous/Progenital, and took them out of the running for lucrative faculty positions. They are asking for unspecified compensation. The complaint alleges that Anversa and Leri were unaware of any misconduct and lays blame on Jan Kajstura, the first author on the retracted paper and a former member of a lab headed by Anversa.

In the case of the Circulation paper, which reported a surprisingly high turnover rate for muscle cells in the adult heart, Leri and Anversa say that Kajstura apparently altered, without their knowledge, data from mass spectrometry experiments performed at Lawrence Livermore National Laboratory (LLNL) in California. (A researcher at LLNL contacted Anversa’s lab after noticing there were 20 additional data points in the Circulation paper than he had sent in a spreadsheet, they say.)

They further argue that Kajstura and another unnamed scientist under his supervision were responsible for the now-questioned figures that ended up in the Lancet paper, which reported on the results of a phase I clinical trial involving a stem cell treatment for heart failure. The figures apparently don’t match other clinical trial paperwork characterizing the stem cells that were used. (Anversa and Leri say they are willing to correct that paper, but claim they are waiting for approval from the institutional review board that oversaw the study.) The complaint also notes that 15 other papers were later added to the investigation.

Kajstura could not be reached for comment. And it is not known whether he is implicated in the investigations under way at Harvard and Brigham, because the institutions have not released any findings so far and have declined to comment on the inquiries.

The lawsuit raises broader questions about who bears responsibility for misconduct in large biomedical research laboratories involving many researchers, who often work in relative independence. “In the abstract, I think everyone agrees that a principle investigator has to take responsibility for whatever goes on in his or her lab,” says Ferric Fang, a microbiologist at the University of Washington, Seattle, who has published several analyses of retractions, misconduct, and the scientific enterprise. But the community is often forgiving when misconduct slips past a principal investigator, he says. Several high-profile scientists have survived damage to their careers by being forthright about wrongdoing in their labs.

In this case, the retraction and investigation occurred even as other outside observers were raising questions about the science and integrity of both the lab and Anversa specifically, he notes, including recent criticism of the lab culture published on Retraction Watch by an anonymous former trainee. As a result, he says, damage to the researchers’ careers may not stem entirely from actions by the institutions. “Aside from the specifics of this particular case,” he says, “I think it would be a very dangerous precedent to hold institutions culpable for doing due diligence in investigating allegations of problematic data,” he says.

In the complaint, Anversa and Leri make specific and very strong accusations about the mishandling of the investigation and possible conflicts of interest. They are suing both Elizabeth Nabel, president of Brigham, and Gretchen Brodnicki, Harvard’s dean for faculty and research integrity, who launched the initial inquiry into the lab and called for the retraction of the two papers.

Nabel, who is also a scientific adviser at Moderna Therapeutics Inc., should have recused herself from the investigation, Anversa and Leri argue, because Moderna is developing a treatment that competes with therapies developed in their lab. They also say that she is a financial stakeholder at Moderna and that she inappropriately disclosed information about the investigation and personally maligned Anversa and Leri.

The claims of a confidentiality breach and conflict of interest, if they prove true, “are serious, and are not off-the-wall,” says Paul Rothstein, a professor of torts, evidence, and civil litigation at Georgetown University Law Center in Washington, D.C. They could “give a court some serious issues to deal with and think about.”

As for the damages over lost employment opportunities and the derailed business deal, Rothstein points out that courts require a high degree of proof that the defendants are directly responsible—and that the business deals would have been a certainty if not for the defendants’ actions. That is often hard to demonstrate, Rothstein says, suggesting Anversa and Leri may face obstacles in making their case.