TOKYO—An investigating committee has concluded that falsification and fabrication mar two recent Nature papers reporting a new, simple way to reprogram mature cells into stem cells. The committee concluded that these acts constitute research misconduct, but it stopped short of calling for the papers to be retracted and will leave the question of disciplinary action to a separate committee. RIKEN President Ryoji Noyori today said he favors one paper's retraction if the committee’s findings are upheld in an appeals process.
“I am filled with feelings of indignation and surprise,” said lead author Haruko Obokata, of the RIKEN Center for Developmental Biology (RIKEN CDB) in Kobe, Japan, in a statement. She wrote that she intends to appeal the judgment.
The committee's final report (in Japanese), released today, is the latest blow against a surprisingly simple method for creating stem cells, known as STAP (stimulus-triggered acquisition of pluripotency), published in a Nature article and an accompanying letter online on 29 January by Obokata and colleagues at RIKEN CDB, along with other institutions in Japan and at Harvard Medical School in Boston. Their method relied on briefly bathing blood cells from newborn mice in a mildly acidic solution and then tweaking culture conditions to produce stem cells. This method, if it proves viable, would be an alternative to far more complicated but established methods of deriving stem cells, which are prized for possible use in regenerative medicine.
Almost immediately after publication, bloggers in Japan and contributors to PubPeer, a website where scientists discuss published papers, started pointing out possibly manipulated images and apparently plagiarized text. A RIKEN researcher notified the institute's Auditing and Compliance Office of these doubts on 13 February. On 17 February, after a preliminary compliance office investigation, RIKEN assembled a six-person investigating committee chaired by Shunsuke Ishii, a RIKEN molecular geneticist, to investigate six specific allegations. The committee, which includes outside experts, released an interim report on 14 March that found problems but stopped short of calling them misconduct. Its final report, released today during a press conference, did identify two instances of research misconduct.
One of these involves splicing together parts of two photos of electrophoresis gels into figure 1i of the paper. The report calls this an "act of research misconduct corresponding to falsification." The other instance was reusing data apparently from Obokata's doctoral thesis in the paper, even though the doctoral experiments were significantly different and conducted under different conditions. The reused images appear in figures 2d and 2e of the paper and constituted "an act of research misconduct involving fabrication," the report states.
Regarding figure 1i, “[t]he idea was to present an easy-to-view photo,” Obokata wrote in her statement. The changes to the image “did not change the obtained results.” Problems with figures 2d and 2e were the result of a simple mix-up that the team had spotted on its own, she wrote, adding that they have submitted a correction to Nature.
The report found further problems that affect the credibility of the research. For example, part of a description of a method for karyotyping—examining the number and structure of chromosomes in a cell—was not only copied from a paper published by a separate group, but was also not consistent with the procedure actually followed by Obokata’s team. But the committee says Obokata had faithfully cited many other publications and couldn't recall where the text came from, so the committee found it impossible to call this misconduct.
The report also says that the experiments are so poorly documented "that it will be extremely difficult for anyone else to accurately trace or understand her experiments." In a stinging summary, the committee wrote: "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 was the only member of the team judged guilty of research misconduct. But the report notes that co-authors Teruhiko Wakayama, a former RIKEN researcher now at the University of Yamanashi in Kofu, and Yoshiki Sasai, of RIKEN CDB, who worked with Obokata to finalize the research, "allowed the papers to be submitted to Nature without verifying the accuracy of the data, and they bear heavy responsibility for the research misconduct that resulted from this failure on their part." The report does not mention the non-Japanese co-authors.
At a press conference today, Ishii emphasized that the panel focused solely on the six issues that were raised at the outset of the investigation. He said the committee did not try to assess the overall validity of the papers, whether they should be retracted, or if STAP cells can be created.
Wakayama, in a written statement, expressed remorse “for failing to look into the legitimacy and accuracy of data produced in my lab by someone under my supervision.” But Obokata remains confident in her finding. “At this stage, considering the STAP cell discovery itself to be fabricated is a misunderstanding; I cannot possibly accept this," she wrote.
At today’s press conference, RIKEN president and Nobel laureate Ryoji Noyori said that RIKEN researchers will attempt to replicate the disputed findings; the institute will also cooperate with outside groups trying to replicate the STAP method. Although many groups have apparently tried, there have been no reports of success. "I don’t really hear from almost anyone who fully believes in STAP cells anymore," wrote stem cell researcher Paul Knoepfler of the University of California, Davis, School of Medicine wrote in a 25 March blog post.
"I will, if the misconduct is confirmed following the proper appeals process, recommend that one of the papers in question be retracted,” Noyori said, reading a prepared statement. (Most of the problems identified by the committee pertain to the research article.) “Further, strict but fair disciplinary action will be taken on the basis of recommendations by a disciplinary committee set up for this purpose."
He also promised to set up a committee of external experts to appraise research procedures; its findings will guide changes in governance and policies at RIKEN to prevent a recurrence, Noyori said.