Nature retracts controversial stem cell papers

Questions have dogged the STAP technique—which the researchers claimed could make all the cell types in a mouse fetus—from the start.

Questions have dogged the STAP technique—which the researchers claimed could make all the cell types in a mouse fetus—from the start.

Haruko Obokata

TOKYO—Nature today published a retraction of two controversial papers that had reported a new, astoundingly simple way of generating pluripotent stem cells. The retraction notice—for an article and a letter written by Haruko Obokata of the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, and colleagues there, at other institutions in Japan, and at Brigham and Women's Hospital in Boston, an affiliate of Harvard Medical School—had been expected for some time.

The two papers reporting the stimulus-triggered acquisition of pluripotency (STAP) phenomenon appeared online on 29 January. Questions about the papers arose almost immediately, leading to an investigation by RIKEN, the headquarters of the network of the nationally funded laboratories that is based in Wako near Tokyo. Investigators documented several instances of fabrication and falsification in the papers and concluded that some of these constituted research misconduct on the part of Obokata.

Japanese media recently reported that authors had agreed to retract the papers but were discussing the wording of the notice. In the note that appeared today, the authors point to errors previously identified by RIKEN investigations in supplementary documents. They also identify additional errors in both papers, including mix-ups in images, mislabeling, faulty descriptions, and "inexplicable discrepancies in genetic background and transgene insertion sites between the donor mice and the reported" STAP cells.

"These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the [STAP stem cell] phenomenon is real. Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers," the authors write.

Co-author Charles Vacanti, a tissue engineer at Brigham and Women’s Hospital and one of the staunchest defenders of the work, has agreed to the retraction as well. “Although there has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself, I am concerned that the multiple errors that have been identified impair the credibility of the manuscript as a whole,” Vacanti wrote on his lab’s website. He added that he still trusts that the STAP cell concept “will be verified.”  So far, no one has reported reproducing the results; several groups tried and failed.

Austin Smith, a stem cell researcher at University of Cambridge in the United Kingdom, has retracted a News & Views article in Nature that accompanied the STAP cell reports and discussed the results.

"We have concluded that we and the referees could not have detected the problems that fatally undermined the papers. The referees’ rigorous reports quite rightly took on trust what was presented in the papers," Nature writes in an accompanying editorial.

The editorial explains that Nature's policy had been "to check a small proportion of accepted papers" for image manipulation. In this case, as the authors explain in the retraction notice, images were duplicated across panels and in several panels, and images were mislabeled—problems more difficult to catch. "We are now reviewing our practices to increase such checking greatly, and we will announce our policies when the review is completed," the editorial notes.

Separately, RIKEN CDB announced today that Obokata will return to the lab to try to reproduce her results as part of efforts to redo every step of the STAP experiments. The institute already has a team led by Hitoshi Niwa, a respected stem cell scientist and co-author of the papers, working on the issue. Obokata will be set up in a separate building in a lab with 24-hour monitoring intended to strictly limit who enters. Precautions will be taken to prevent the introduction of extraneous strains of mice or cellular material.

If neither team can reproduce the first stage of the work, which involves demonstrating the appearance of a genetic marker for pluripotency in cells generated from adult cells, by November, the efforts could be halted, said Shinichi Aizawa, a RIKEN CDB group leader who is overseeing the project, at press conference in Kobe today. Aizawa explained that Obokata was invited to participate to find out if there are subtleties in her experimental technique not captured in her published protocols. "I know some are of the opinion that this is a waste of time, but we want to scientifically proceed to determine whether the STAP phenomenon and STAP cells exist or not," said Aizawa, who added that he remains neutral on that question himself.

At least one of RIKEN CDB's star researchers has had enough, however. "I can't stand RIKEN's ethics anymore," Masayo Takahashi tweeted yesterday as news leaked about the pending invitation to Obokata. Takahashi, a RIKEN CDB ophthalmologist, is producing replacement retinal cells for patients with macular degeneration and is leading the world's first clinical trials in which induced pluripotent stem cells are genetically matched to individual patients. She wrote that she would consider abandoning the procedure for patients who haven't yet started, and even stopping the treatment for those want to opt out midway. "I don’t think the circumstances [at RIKEN CDB] fit clinical studies,” Takahashi wrote. She did not immediately respond to an e-mail asking how the STAP cell problems affect her research.

A reform committee on 12 June called for RIKEN CDB to be dismantled or at least thoroughly overhauled, because of management shortcomings exposed by the incident, though many in the scientific community think that would be an extreme response.

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