Researchers worldwide once hailed his research as revolutionary, promising the seemingly impossible: a way to grow new heart cells to replace those lost in heart attacks and heart failure, leading killers in the United States.
But Harvard Medical School and Brigham and Women’s Hospital in Boston, his former employers, this month accused Anversa and his laboratory of massive scientific malpractice. More than 30 research studies produced over more than a decade contain falsified or fabricated data, officials concluded, and should be retracted. In 2017, the hospital paid a $10 million settlement to the federal government after the Department of Justice alleged that Anversa and two members of his team were responsible for fraudulently obtaining research funding from the National Institutes of Health.
“The number of papers is extraordinary,” said Dr. Jeffrey Flier, until 2016 the dean of Harvard Medical School. “I can’t recall another case like this.”
Anversa’s story has laid bare some of the hazards of modern medical research: the temptation to embrace a promising new theory, the reluctance to heed contrary evidence and the institutional barriers to promptly stopping malfeasance. Even after three independent researchers were unable to reproduce his findings in 2004, Harvard hired him in 2007 and his lab continued to churn out studies upholding his theory.
“Science at this level is like a battleship, and it’s really hard to turn it around,” said Dr. Jonathan Moreno, a professor of bioethics at the University of Pennsylvania. “People get emotionally invested, financially invested, professionally invested.”
Anversa, 80, insists he did nothing wrong, that his stunning results are real, and that he was betrayed by a rogue colleague who altered data in paper after paper. On a recent afternoon, he sat on the sofa, pecking on his laptop with two fingers, calling up emails from people who had supported him.
His is a particularly acrid cautionary tale of scientific hubris.
At a meeting of the American Heart Association in 2000, Anversa, then a professor at New York Medical College in Valhalla, strode to the podium and delivered a dramatic announcement: In mice, bone marrow contained stem cells that could be used to regenerate heart muscle.
He was suggesting that a basic tenet of cardiology — that the human heart cannot be regenerated — was wrong. If he was correct, he had discovered hope for millions of heart patients.
The presentation was replete with colorful slides of small and underdeveloped cells — new heart muscle cells maturing, he said.
“It was like he grew the heart back,” recalled Dr. Charles Murry, director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington Medicine in Seattle.
From the very beginning, there were scientists who doubted Anversa’s claims. He had not been the first to wonder if stem cells from bone marrow could be transformed into heart cells. Murry and Loren Field, a professor of medicine at Indiana University School of Medicine, had tried the experiment in the late 1990s. They saw no new heart cells and moved on, never publishing those data.
They sat together in the audience when Anversa presented his findings in 2000. Murry turned to Field and asked, “How the hell did we miss this?” They returned to their labs to redo the experiment. But again, they could not make the process yield new heart cells.
Their paper was published in the journal Nature in 2004, along with another study by Irving Weissman, director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University. He, too, failed to replicate Anversa’s results. That same year, Dr. Bernd Fleischmann, a professor of physiology at the University of Bonn, reported in Nature Medicine that he had been unable to replicate Anversa’s results. The Times covered the questioning of Anversa’s findings in a 2005 article, “Tracking the Uncertain Science of Growing Heart Cells.”
Other labs reported seeing a few heart cells generated, but nothing close to what Anversa reported.
“Those incremental results kept hope alive,” Field said.
As Anversa’s fame grew, along with grants, he earned perhaps the greatest of scientific plaudits in 2007: a professorship at Harvard Medical School and a position at its teaching hospital, Brigham and Women’s, as director of its Center for Regenerative Medicine.
In 2012 a new controversy emerged.
A key member of Anversa’s team, Dr. Jan Kajstura, was the first author on a paper in Circulation that seemed to offer final proof that the heart can regenerate. He worked with a scientist at Lawrence Livermore National Laboratory, Bruce Buchholz, who measured carbon isotope levels in 36 hearts from people ages 2-78. Because of nuclear testing done in the 1950s, older people were exposed to more radioactive isotopes than younger people.
If the body cannot produce new heart cells, the amounts of radioactive carbon should have been higher in the heart cells of older people. But in that paper, Kajstura and his colleagues reported, older hearts did not have more radioactive carbon. Heart cells are constantly being replaced, they concluded.
When Buchholz read the paper, he was stunned. He had provided data on radioactivity levels to Kajstura, but the data published in the study had been altered to make the old hearts look the same as the young ones. Buchholz said in an interview that science depends on trust among collaborators, that he had implicitly trusted Anversa’s group with his data. Now that trust was broken.
“I learned an unpleasant lesson,” he said.
He called Anversa and demanded that the paper be retracted. If data were changed, Anversa recalled telling him, it was not with his knowledge. “I said, ‘Bruce, you are saying Jan is a fraud,'” Anversa said.
Anversa said he confronted Kajstura, who did the analysis again. Anversa said he was reassured by the revised work and believed the findings in the paper were still correct. But the hospital retracted the paper in 2014.
Kajstura left the laboratory in 2013, Anversa said. In a statement, lawyers for Anversa and his colleague, Dr. Annarosa Leri, blamed Kajstura for digitally manipulating images published in scientific journals.
In 2015, Anversa was forced out at Harvard. He moved to research posts in Switzerland and Italy, but was fired from both, he said, as the controversy followed him overseas.
This month, Anversa got Harvard’s conclusive findings on his life’s work. In an Oct. 3 letter that Anversa provided to The Times, officials at Harvard and its teaching hospital told him he had “committed research misconduct” in eight papers, some published and others submitted for publication, as well as in a grant application. Although he was the lead author on many of the other papers that Harvard said must be retracted, the university said the evidence did not support his being responsible for the malfeasance in those cases. Harvard did not name the culprit or culprits in its letter to Anversa.
But the university said 31 scientific papers produced by Anversa’s laboratories, going back to 2001, should be retracted. University and hospital officials notified each journal of their conclusions as well as the Office of Research Integrity at the Department of Health and Human Services, which can recommend that the federal government ban researchers from receiving federal funds. Anyone associated with Harvard or the hospital who gives Anversa a reference must also describe his misconduct.
Source: indiatimes.com
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