Science in Mind

Japanese investigation of stem cell research finds errors but no fraud so far

Nobel Prize-winning chemist and President of Japanese research institute Riken, Ryoji Noyori (left, C) and other Riken executives attend a news conference in Tokyo March 14, 2014. Japanese research center Riken apologised for what it calls 'grave mistakes' in their stem-cell study published in Nature magazine. REUTERS/Toru Hanai (JAPAN - Tags: HEALTH SOCIETY SCIENCE TECHNOLOGY)
Riken executives attend a news conference in Tokyo March 14, 2014. Japanese research center Riken apologised for what it calls 'grave mistakes' in their stem-cell study published in Nature magazine. REUTERS/Toru Hanai

At a lengthy, four-hour press conference in Japan Friday afternoon, officials from the prestigious RIKEN research institute disclosed the interim results of its investigation into controversial stem cell papers, acknowledging serious problems with the research but no evidence so far of outright fraud.

Three RIKEN scientists who contributed to the research have now agreed to consider a retraction, in addition to a prominent Japanese scientist and senior author of one of the two papers published in the journal Nature, who earlier this week called for the papers to be withdrawn.

“It is extremely regrettable that significant discrepancies have been found to have been generated in the process of preparing the Nature articles for publication,” Ryoji Noyori, the president of RIKEN and a Nobel laureate, said in a statement. “We are investigating these discrepancies, with the understanding that it may become necessary to demand the withdrawal of the articles.”

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The research, coauthored by Boston and Japanese scientists, electrified the scientific world because they reported a shockingly simple way to make stem cells from mature mouse blood cells, by bathing them in a weak acid. If the work is verified by other scientists and reproduced in humans, it could make it easier for scientists to produce stem cells, which have the capacity to become any of the numerous cell types in the body and are seen as providing potential therapies for a range of conditions from diabetes to heart failure to paralysis.

But since the papers were published in January, numerous allegations have emerged in online forums about possible problems with images and plagiarism. A spokeswoman for RIKEN said that three scientists have agreed to consider a retraction—Yoshiki Sasai, Hitoshi Niwa, and Haruko Obokata, who was the lead resesarcher. But, the spokeswoman added, the papers won’t be retracted unless all co-authors agree.

The Boston scientist who was the senior author of one of the paper, Dr. Charles Vacanti of Brigham and Women’s Hospital, has stood by the core findings and said in a prepared statement that while he awaits the outcome of the complete RIKEN investigation and plans to speak with all of his co-authors, he still believes the results are sound.

“I continue to feel that the findings presented in these papers are too significant to disregard based on relatively minor errors or external pressures. In the absence of compelling evidence that the data presented is incorrect, I do not believe that the manuscripts should be retracted,” Vacanti said. “I firmly believe that the most appropriate course of action at this time is to clarify, in a very specific manner, all of the subtleties associated with the creation of STAP cells by posting specific details of our most effective protocol on our laboratory web site.”

STAP cells are the name given the type of stem cells created in the experiments—which the authors reported behave similarly to embryonic stem cells.

According to a Wall Street Journal live blog of the press conference, Vacanti’s main contribution to the research was developing the idea for how to create these stem cells—and he did not play a role in reviewing RIKEN’s data.

RIKEN scientists said they were unaware that any independent scientists had succeeded in replicating the experiments and producing stem cells with the acid-bath technique, according to the blog. A Hong Kong scientist Thursday posted a report of his failed efforts to repeat the experiment on a website called ResearchGate, but such failures can be difficult to interpret because initial difficulty repeating a new technique is not uncommon.

In an e-mail to the Globe, Teruhiko Wakayama, a co-author and professor at Yamanashi University who earlier this week called for the papers to be withdrawn, said he had not changed his mind and still believed the papers should be retracted.

“However, I do not know [if] my decision is correct or not. Therefore, I need discuss with all author[s],” Wakayama wrote.

RIKEN officials gave a detailed list of the issues that have been brought up with the papers—a total of six separate potential problems. The institution has concluded its investigation of two items—an image of colored cell parts that had an “unnatural appearance” and two images that appeared strikingly similar.

The colored cell image was not found to be research misconduct. The possibly duplicated figure was not referred to in the captions or in the text, “but there was nothing to contradict the explanation that one of the figures had inadvertently been left undeleted during the process of manuscript creation,” the RIKEN report said.

The four remaining issues include possible image manipulation, possible plagiarism of part of the methods section from a different paper, a description that is different from the procedure used, and an image that resembles images from the lead author’s doctoral thesis.

According to the Wall Street Journal, RIKEN officials acknowledged that an initial proclamation the institution had made in February that the possible problems didn’t affect the overall conclusions may have been “too optimistic.” The newspaper also reported that Masatoshi Takeichi, director of the RIKEN Center for Developmental Biology where the lead author works, believes that the papers should be withdrawn because of the apparent duplication of an image from her thesis. Another co-author, Hitoshi Niwa, said he will try to replicate the findings.

Allegations have also arisen about other work by the lead author of both papers, Haruko Obokata, who did some of the research for her doctoral work in Boston. A website posted what it claimed was Obokata’s thesis, of which 20 pages were strikingly similar to a US National Institutes of Health website explaining background information on stem cells.

“About the scanned images posted on the internet, we do not know whether they are true copies of Ms. Obokata’s dissertation,” a spokesman for Waseda University said in an e-mail, adding that there are only two known copies of her dissertation and one is in use for the investigation. “The University is aware of many questions about Ms Obokata’s dissertation. They are currently under investigation. Actions, including possible revoking of the awarded degree, will be determined when the investigation is concluded.”

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