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Fraud alleged in findings on stem cells

Accused scientist had connection to Brigham lab

RIKEN Institute’s investigative committee found Haruko Obokata guilty of research misconduct in two instances.

AP/File

RIKEN Institute’s investigative committee found Haruko Obokata guilty of research misconduct in two instances.

A dramatic advance in creating stem cells for research received a serious blow Tuesday when a Japanese scientist who led the work was accused of fraud by her own institute.

The RIKEN Institute announced that its scientist, Haruko Obokata, was guilty of two instances of scientific misconduct and that it planned to call for the retraction of two Nature papers based on her work, but would wait to allow Obokata to appeal the investigative committee’s findings.

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She disputed the conclusion that she fabricated data.

Several RIKEN coauthors failed to catch the data inaccuracies and problems with the “legitimacy of the conclusions of the papers,” said the institute’s president, Ryoji Noyori, a Nobel laureate. Calling the incident “extremely regrettable,” he apologized in a written statement for the RIKEN scientists’ actions.

Harvard researcher Dr. Charles A. Vacanti, head of the department of anesthesia at Brigham and Women’s Hospital in Boston, was the senior author of one of the papers but was not named in an English-language draft of the RIKEN report provided to the Globe.

Vacanti said he continues to stand behind the main findings of the research he did with Obokata, who worked in his Brigham lab for several years.

“While the investigation determined there were errors and poor judgment in the development of the manuscript, I do not believe that these errors affect the scientific content or the conclusions,” Vacanti said in an e-mailed statement. “It is imperative to correct the errors, but absent any compelling evidence that the overall scientific findings are incorrect, I do not believe that the manuscripts should be retracted.”

RIKEN Institute’s investigative committee found Haruko Obokata guilty of research misconduct in two instances.

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But other stem cell researchers said there was no choice but to retract the papers, now that fraud has been discovered.

“It’s embarrassing; it’s not good for the field,” said Rudolf Jaenisch, a stem cell scientist and biology professor at the Massachusetts Institute of Technology and the Whitehead Institute.

The publication of the two papers in January created huge excitement, because they revealed what appeared to be a fairly simple way to create stem cells, merely by dipping mature mouse cells into a mild acid bath. Like embryonic stem cells, the so-called STAP cells created in the experiments were reported to have the power to become any of the many cell types in the body.

Such stem cells are seen as potential treatments for conditions such as diabetes, Parkinson’s disease, and paralysis.

But doubts soon surfaced among scientists, after labs around the world said they were unable to validate the findings by replicating the work. Jaenisch said he was initially intrigued by the papers, because of the simplicity of the method and his respect for the senior Japanese researchers involved in the work. Researchers in Jaenisch’s lab immediately tried to create stem cells the same way, but they could not get the method to work. More recently, they tried a second technique that Vacanti had posted on the Internet after questions were raised about the papers. They could not get that to work either, Jaenisch said.

In his statement, Vacanti cited a blog post Tuesday reporting on work by a Hong Kong scientist and critic of the stem-cell findings. His initial result using Vacanti’s protocol “appears promising,” Vacanti said. The Hong Kong researcher could not be reached via e-mail.

But that work is still a long way from a confirmation of the Nature papers, said Paul Knoepfler, a stem cell specialist at the University of California Davis School of Medicine.

The inability of other scientists to reproduce the method “doesn’t mean that all the published STAP results are wrong,” Knoepfler said. “There still could be some kernels of truth in there somewhere, but I don’t believe that the key conclusion of the papers — that powerful stem cells can be made from ordinary nonstem cells in this purportedly simple, quick, and easy manner — is likely to prove accurate.”

RIKEN’s investigative committee — composed of three RIKEN scientists, two university researchers, and a lawyer — reviewed six concerns that had been raised about the papers. Four mistakes were dismissed as innocent. In the remaining two, the committee found Obokata guilty of research misconduct.

One problem related to an image that Obokata created by combining two others, which the investigators said was deliberately inaccurate and could lead to “misinterpretation of the data.” In the second, Obokata apparently reused a picture from her doctoral thesis over a different caption. The committee said her actions “completely undermined the credibility of the data.”

The investigators added, “Dr. Obokata’s actions and sloppy data management lead us to the conclusion that she sorely lacks, not only a sense of research ethics, but also integrity and humility as a scientific researcher.”

Obokata released a letter saying they were all simple mistakes that did not change the validity of her results, according to published reports. She has already sent Nature a correction for the errors and plans to appeal the findings.

RIKEN said it has established a scientific team that will try to make its own STAP cells.

Nature released a statement Tuesday saying it takes concerns raised about the papers “very seriously” and is carefully considering the institute’s findings. “We do expect to be able to provide a further comment in the near future,” it said.

Vacanti, working with his brother Martin, came up with the idea for the simpler method of making stem cells and then developed the initial experiments with another Brigham colleague and Obokata. He said in an e-mail last month that he “met regularly with her to develop, design, review, and discuss the results of many of the experiments reported in the first paper.”

The Brigham, in a statement, reiterated the hospital’s commitment to “the highest standards of biomedical research” and said any concerns regarding research there “are confidentially evaluated per the hospital’s policies and federal regulations.”

Harvard Medical School, where Vacanti is a professor of anesthesia, reiterated the school’s commitment to “upholding the highest standards of ethics and to rigorously maintaining the integrity of our research.”

The silver lining to the controversy is that it offers the public insights into how science operates, Dr. Jonathan Garlick, a stem-cell expert at the Tufts University School of Dental Medicine, said Tuesday.

“The scientific process of checks and balances actually works,” said Garlick, who has tried unsuccessfully to repeat the method described in the Nature papers. “The scientific community does not shoot from the hip.”

Karen Weintraub can be reached at weintraubkaren@ gmail.com.
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