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Confusion as institute releases report on controversial acid-bath stem-cell papers

Posted on behalf of David Cyranoski.

Beleaguered Japanese researchers are wavering over whether to retract two stunning but controversial papers that detailed a simple acid-bath method of reprogramming mature cells to an embryonic state.

At a marathon press conference held in Tokyo today, officials from RIKEN, Japan’s largest research institute and home to several of the papers’ authors, announced the findings of an interim investigation into alleged inconsistencies in the studies. But despite apologizing for errors in the papers, they gave ambiguous signals about whether retractions will occur and about the veracity of the method.

The investigation followed the publication of the papers in Nature on 30 January. The acid-bath technique described in them by Haruko Obokata and colleagues, which they called stimulus-triggered acquisition of pluripotency (STAP), gained headlines around the world because cells reprogrammed into this state are ideal for studying the development of disease or the effectiveness of drugs, and could also be transplanted to regenerate failing organs. But within weeks of publication, the papers were assailed for using duplicated images and problems with reproducibility, prompting RIKEN to investigate.

The press conference offered a glimpse of just how the papers and the furore over them have mesmerized Japan. A handful of television trucks with satellite dishes lined the street in front of the building in downtown Tokyo. Some 200 journalists packed the meeting room and were flanked by two dozen video cameras and crew at the front. There, Nobel laureate chemist Ryoji Noyori, director of RIKEN, who made a last-minute decision to participate, sat with four other RIKEN staff, including Masatoshi Takeichi, the director of the RIKEN Center for Developmental Biology (CDB) in Kobe. Several dozen more journalists watched the televised broadcast from there.

For almost four hours, reporters peppered the officials with questions about conflicts of interest, compliance, RIKEN’s scientific fraud policy, and the emotional state of Obokata, whose scientific work, from her dissertation to the STAP papers, has been alleged to contain a variety of problems. Noyori and his staff alternated between disappointment, frustration, bemusement and apparent fatigue, and were often at a loss to explain the errors that had been found in the papers.

Most of the errors detailed by the head of the investigative committee, Shunsuke Ishii, were already known to those who have been following the story. Two image duplications were dismissed as regrettable mistakes. Four more serious problems, including the uncited use of long passages from another paper, were still under investigation. Ishii’s committee is looking for signs of deliberate manipulation of data, and said he has so far found none.

At the conference, Takeichi told reporters that after advising the three leading RIKEN CDB co-authors on the papers — Obokata, Yoshiki Sasai and Hitoshi Niwa — to retract, they agreed. But a 14 March statement written by the trio, who were not present, said only that, because of the public uproar over the errors and the questions over reliability of the data, they “were contacting the other co-authors to discuss the possibility of a retraction”.

Takeichi was asked multiple times to expand on the possibility of a retraction, including one reporter trying to pin down the exact wording they used in agreeing to his advice. Takeichi said he could advise but not force the researchers to retract. Asked whether, in the absence of any binding agreement to do so, they might change their minds, he said: “That is up to them.”

Takeichi had previously resisted the need for a retraction until more was known about the papers, but one error — the use of an apparently identical photo in both Obokata’s doctoral thesis and one of the Nature papers — pushed him to call for a retraction of the papers. Obokata has continued to call the problems simple errors that do not affect the findings. Another co-author, Yamanashi University’s Teruhiko Wakayama has also publicly announced his desire that the papers be retracted.

Charles Vacanti, of Harvard University in Cambridge, Massachusetts, who is the senior corresponding author on the more crucial of the two papers, has made clear that he does not plan to retract. He told Nature News: “I believe the questions and concerns raised do not affect the findings or conclusions in our article.”

If the RIKEN researchers do request a retraction, Nature‘s journal editors will have to step in. The journal tries to get all authors to agree before retracting a paper. According to a spokesperson for Nature: “In cases where not all of the authors agree on a retraction, Nature evaluates whether the evidence available supports the main conclusions of the paper. We may decide to retract in cases where the authors cannot provide evidence to support the main conclusions of the paper. In such cases, if some authors still disagree with the retraction, we note the dissenting authors in the retraction notice.”

The investigation has been taking its toll on Obokata, Ishii said. She “coolly” sailed through the first hearing, but she started to seem nervous in the second. For the third, she had been asked to prepare large amounts of data and she seemed more tired and anxious, he added. The investigation will continue, and the committee hopes to report back “soon.”

Nature News is editorially independent of the research publications section of Nature.


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    Gaia Shamis said:

    This is a great and comprehensive review of this ongoing situation. As it says in the post, we want to believe and can’t wait to see how the story unfolds.

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    Seiichi MYOGA said:

    What interests me here is the use of “may” in “(1) We may decide to retract in cases where the authors cannot provide evidence to support the main conclusions of the paper.” It seems to me to be objective epistemic.
    On an everyday, subjective epistemic reading, (2) may mean “For all the speaker knows, it is possible that Alfred is unmarried (because the speaker doesn’t know that Alfred is not unmarried).
    (2) Alfred may be unmarried.
    On this reading, we can add, for instance, “or may not” as in “Alfred may or may not be unmarried,” meaning “Alfred may be unmarried and Alfred may not be unmarried.”
    But for (1), the clause beginning with “in cases” (that is, the authors’ failure to provide the required evidence) virtually represents a necessary condition for Nature’s decision to retract, so unlike (2), it seems imossible to insert “or may not.” So what do you mean by “may”? My main interest lies in linguistic aspects, but part of the reason I’m asking is that there seems to be some misunderstanding of the procedure of retration here in Japan.

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