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Evidence Mounts Against Reprogrammed Stem Cell Papers

RIKEN President Ryoji Noyori (center) apologized for "grave errors" in two recent papers by RIKEN researchers.

Sorry. RIKEN President Ryoji Noyori (center) apologized for "grave errors" in two recent papers by RIKEN researchers.

Dennis Normile

TOKYO—Amid mounting allegations of problematic images and plagiarism, the lead author and two co-authors are considering retracting two controversial papers describing a simple method for creating stem cells known as STAP (stimulus-triggered acquisition of pluripotency). Their written statement was released during a press conference here today at which an investigating committee confirmed finding problems in the papers but stopped short of rendering a judgment on research misconduct.

“I apologize for the great trouble and concerns caused to so many in society by the STAP papers published in Nature by RIKEN researchers,” RIKEN President Ryoji Noyori said with a deep bow. RIKEN, with its headquarters near Tokyo, oversees a network of nationally supported research centers, including the institute at which three of the key authors work. Meanwhile, no one has reported reproducing the team’s method of creating STAP cells.   

Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe and colleagues at other institutions in Japan and at Harvard Medical School in Boston, reported a surprisingly simple way of creating stem cells in an article and a letter published online on 29 January in Nature. Their method relied on briefly bathing blood cells from newborn mice in a mildly acidic solution and then tweaking culture conditions.

Just days after the papers appeared, bloggers and contributors to the PubPeer website started raising questions about images in the two papers. Stem cell researcher Paul Knoepfler of the University of California, Davis, School of Medicine's Sacramento campus created a page on his blog where scientists who attempted to reproduce the technique could report their results. No one has reported success.

RIKEN launched an investigation on 13 February. But new allegations of problems with these and previous Obokata publications kept emerging.

Today, RIKEN’s investigating committee, chaired by Shunsuke Ishii, a RIKEN molecular geneticist, unveiled what it has determined thus far. The interim report focuses on six specific allegations, and the conclusions are mixed. One problematic image is figure 1f in the research article, which appears unnaturally distorted to some critics. The panel concluded this was an artifact of image compression. “It was concluded this was not falsification or improper conduct,” the interim report says.

But some claims against the papers are on target. Obokata and one of her co-authors told the committee that figures 2e and 2d in the article were used by mistake, though they did not mention that the images had appeared in Obokata’s doctoral thesis as has been alleged. Ishii emphasized that the committee so far has just determined the facts; judgments about misconduct will come after further investigation and deliberation.

As for whether STAP cells exist, Ishii said that question would be left up to the scientific community to determine. Noyori said he had instructed the authors to cooperate fully with researchers at outside institutions in their efforts to replicate the STAP cell results. On 5 March, RIKEN did release technical tips for STAP cell conversion. “We tried the new protocol but so far we haven’t had success,” says Hongkui Deng, a stem cell researcher at Peking University in Beijing. But he says he is willing to keep trying, especially if further details about the method are released as promised.

In their written statement, Obokata and two co-authors, Hitoshi Niwa and Yoshiki Sasai, apologized for the confusion resulting from the uncertainties and inaccuracies in the papers. “We are contacting other co-authors regarding the possibility of retracting these papers,” the trio wrote.

Teruhiko Wakayama of the University of Yamanashi in Kofu, a stem cell biologist and co-author of both papers, earlier this week called for at least a temporary retraction pending an investigation. A public relations spokesperson at the university told Science that Wakayama had no comment in reaction to today’s press conference.

“Should the investigative committee conclude that there was research misconduct, we will take strict disciplinary action as stipulated by our own regulations,” Noyori said in a prepared statement. Maki Kawai, director of research at RIKEN, said that the whole institute would review and strengthen its research ethics training.

The story goes beyond RIKEN as allegations surfaced this week that virtually an entire chapter of Obokata’s dissertation appears to have been lifted from a National Institutes of Health website and that footnotes to another chapter have no connection to that chapter’s text. "The doctoral dissertation that is currently making the rounds in the media is not the version that has passed (the university's) screening, but a rough draft," Obokata told The Wall Street Journal in an e-mail. A public relations spokesperson for Waseda University said an investigation is under way.

The STAP cells controversy also goes beyond the stem cell community. “[T]his mess impacts public trust and support for every field of science in Japan,” wrote Robert Geller, a University of Tokyo seismologist, in a guest post on Knoepfler’s blog. He called for Waseda to investigate how the problems with Obokata’s thesis escaped notice by reviewers. He also asked Nature to make public all the editorial correspondence (redacted to protect privacy) and every version of the papers so outsiders could judge if publishing the papers was appropriate.

A Nature spokesperson told ScienceInsider by e-mail that the journal’s investigation “is still in progress.” Not all the authors would necessarily have to agree to a retraction, the spokesperson wrote. “In cases where a coauthor disagrees on a retraction, the dissent is noted in the text of the published retraction.”

With reporting by Gretchen Vogel.