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Doctor in stem-cell probe sues Brigham, Harvard

Calls investigation flawed

A prominent and controversial heart stem-cell scientist at Brigham and Women’s Hospital and his collaborator have filed suit in federal court against the hospital and Harvard Medical School, saying the institutions are conducting “a procedurally and legally flawed investigation” into alleged scientific misconduct by the researchers.

The lawsuit, brought by Dr. Piero Anversa, a professor of anesthesia and star researcher who brought in $6.9 million in federal grants to the hospital last year, provides a rare public glimpse of internal investigations into potential scientific misconduct. The 29-page complaint, filed Tuesday in Boston, includes allegations of conflicts of interest during the investigation that involve some of the top people in biomedical research in the area, including naming Dr. Elizabeth Nabel, president of the Brigham, as a defendant.

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Anversa’s research has long been divisive, but questions about its integrity began this year, when one of his papers investigating the heart’s ability to regenerate itself was retracted after an internal probe revealed it had used compromised data. Another study overseen by Anversa that reported on an early clinical trial testing the use of heart stem cells in patients was flagged due to the ongoing probe.

The allegations of misconduct raised questions about one of the hottest and most contested areas of stem cell research: how and whether such cells could be used to treat heart disease. That work has received millions of dollars in federal research funding and has led to tests in patients, even as some of the underlying ideas have been questioned by outside scientists.

The suit, which seeks unspecified monetary damages, alleges that the lengthy investigation has inappropriately damaged the careers of Anversa and Dr. Annarosa Leri, an associate professor of medicine at Harvard, and that the alleged misconduct lies solely with a scientist named Jan Kajstura, who has since left the Brigham. For more than two decades, Kajstura and Anversa worked closely together on a daily basis, according to the lawsuit, and Kajstura is a co-author on some of their most prominent scientific findings.

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Efforts to reach Kajstura on Wednesday were unsuccessful.

The case offers a window into how the first instance of alleged misconduct came to light and shows how the investigation widened into other research.

According to the lawsuit, a researcher from the Lawrence Livermore National Laboratory in California alerted Kajstura, Leri, and Anversa in October 2012 to discrepancies between data the researcher had sent them and the results that were later published.

An internal inquiry was convened by Harvard and the Brigham in early 2013 to determine whether a full-scale investigation was needed. That panel suggested the retraction of two papers, a full investigation, and an “evaluation of whether the Brigham laboratory is an appropriate environment for trainees.”

The lawsuit reveals that over the course of the inquiry and subsequent investigation, additional work was found to have possible misconduct. An unpublished paper submitted to the journals The Lancet and Science in 2013 was found to have “apparent manipulation of confocal microscope images.” An additional 15 papers were also added to the allegations of misconduct over the course of the investigation.

“Any questions, concerns, or allegations regarding research conducted at BWH are confidentially assessed per hospital policy and federal regulations,” a spokeswoman wrote in an e-mail.

The lawsuit centers on the argument that the investigation is contrary to law, because it proceeded “on the theory that Dr. Anversa should be held responsible for arguably negligent failure to investigate Dr. Kajstura’s research misconduct.”

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It also alleges that the investigation has violated a federal law that requires such probes to be completed within 120 days. Susan Garfinkel, director of the Division of Investigative Oversight at the federal Office of Research Integrity, wrote in an e-mail that institutions almost always need to request extensions, and that in at least one case, such an investigation has taken up to four years.

The length of the investigation “depends on many factors, including the complexity of the case (more than one institution, more than one respondent, many allegations) and whether the respondent is cooperative or obstructive,” Garfinkel wrote.

Nicholas Steneck, director of the Research Ethics and Integrity Program of the Michigan Institute for Clinical and Health Research, said it is impossible to know the full story until Harvard responds.

“The most interesting question is whether the university is justified in doing a fuller investigation,” Steneck wrote in an e-mail. A broader investigation could be justified, he said, but it is also important to avoid “a fishing expedition.”

The lawsuit also alleges several conflicts of interest in the investigation process.

It accuses Nabel, the hospital’s president, of intervening in the investigation on two occasions. It also alleges a member of the investigative committee had a conflict of interest.

A hospital spokeswoman did not respond to specific accusations in the lawsuit.

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“The Brigham does not comment on issues relating to ongoing legal proceedings,” she said in a statement.

The plaintiffs say the investigation has caused financial losses. They said prospective buyers canceled a multimillion-dollar offer to purchase their company, Autologous/Progenital, after the news of the investigation became public. They also said that two outside institutions, University of Miami and Icahn School of Medicine at Mount Sinai in New York, were pursuing Anversa and Leri and put offers on hold during the investigation.

Related coverage:

Brigham researcher facing new questions after retraction

Data faulted, Brigham study on heart cells is withdrawn

Retracted stem cell papers get public, private scrutiny


Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.