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11 Mar 2014 15:48

Riken considers withdrawal of breakthrough STAP cell reports

March 11, 2014

THE ASAHI SHIMBUN

The Riken national research institute is considering withdrawing two scientific reports that were acclaimed as a major breakthrough in stem cell research over discrepancies that surfaced after they were published in the prestigious Nature magazine in January.

Riken has been investigating allegations by experts and Internet bloggers that the papers contain suspected irregularities in parts of their imagery and text. The research institute released a statement on March 11 that it is "eyeing the possibility of withdrawing the two reports from the standpoint of their credibility and research ethics."

It will hold a news conference on March 14 to update progress on its inquiry.

University of Yamanashi professor Teruhiko Wakayama, a co-author in both papers, said March 10 that he had called on his co-authors at Riken to withdraw the articles.

"Three (senior) Riken officials contacted all of us authors by e-mail and phone around noon today to suggest a withdrawal of the papers," Wakayama told reporters at his workplace in Kofu, Yamanashi Prefecture. "That pushed me to make up my mind to call for a withdrawal."

Haruko Obokata, 30, the lead author in the pair of articles on a mechanism called "stimulus-triggered acquisition of pluripotency" (STAP), became an instant rising star of Japan's scientific circles when the publications appeared on Jan. 29.

Obokata, who leads a research unit at the Riken Center for Developmental Biology in Kobe, along with her colleagues at Harvard University and elsewhere, said in those reports that strong external stresses, such as a weak acid bath, could reprogram lymphocyte cells from young mice into pluripotent cells, which can develop into different body organs and tissue.

The discovery was touted as a rewrite of accepted theories of life sciences and raised hopes worldwide for possible applications in regenerative medicine.

CO-AUTHOR 'NO LONGER SURE'

The possibility of withdrawing the groundbreaking papers arose after an Internet blogger, specializing in uncovering irregularities in scientific research, called the very pluripotency of STAP cells into question on March 9.

The blogger said four images in one of the Nature articles, which were supposed to show how STAP cells grew into muscle and bowel tissues, looked strikingly similar to photos used in Obokata's 2011 Ph.D. thesis, which had nothing to do with STAP cells. The photos in the doctoral dissertation were supposed to show the growth of pluripotent cells that inherently exist in bone marrow.

"Those photos demonstrated that the cells can develop into different forms," said Wakayama, an authority in mouse cloning. "But we now have no evidence that they developed into different cells. That undermines the core part of our study. I can no longer say with certainty what I did in my experiments."

Wakayama participated in the studies that led to Obokata's pair of articles, in which he was in charge of experiments for providing irrefutable evidence that STAP cells are pluripotent. He said March 10 he planned to provide the STAP cells to a third-party research institution and ask for an analysis.

While pluripotency is considered a key attribute of STAP cells, another characteristic, deemed no less important, has also been called into question. Skeptics now doubt that STAP cells can actually be engineered from regular somatic cells.

The Nature articles said that STAP cells were engineered from lymphocyte cells in the blood and were found with gene mutations that showed they were artificially derived. But when Riken released detailed technical instructions on the manufacture of STAP cells on March 5, the document said STAP stem cells, or a modified form of STAP cells, were not found with those gene mutations.

Earlier allegations said that two images used in different contexts in one of the Nature papers looked extremely similar, and that parts of the text in the other paper are almost identical to passages in publications written by other researchers.

But those earlier suspicions were not believed to affect the authors' central claims that they have engineered STAP cells. Wakayama, too, continued defending Obokata.

"I want to believe in our research results," Wakayama said. "So I hope we can withdraw our papers, redo our research and republish articles that nobody can find fault with."

While the authors initially said STAP cells can be engineered fairly easily, a number of researchers complained that they have attempted but have not been able to successfully replicate the results.

RIKEN SLOW TO RESPOND

Riken's response has been slow in addressing the developing controversy.

The national research institute has cited "ongoing investigations" in declining to make in-depth comments on the successive allegations. It has maintained that the core part of the research has not been compromised.

Obokata, the leading author, has not consented to media interviews over the allegations. She last attended a news conference along with Wakayama when they announced the publication of the Nature papers on Jan. 28.

A representative of the Riken Center for Developmental Biology on March 10 said that Obokata is "taking the various comments seriously."

The representative also said any decision on withdrawal would require the approval of all the authors. A total of 14 authors were involved in publishing the two papers.

THE ASAHI SHIMBUN
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Teruhiko Wakayama, a University of Yamanashi professor, speaks to reporters at the university in Kofu on March 10. (Ryo Suganuma)

Teruhiko Wakayama, a University of Yamanashi professor, speaks to reporters at the university in Kofu on March 10. (Ryo Suganuma)

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  • Teruhiko Wakayama, a University of Yamanashi professor, speaks to reporters at the university in Kofu on March 10. (Ryo Suganuma)
  • University of Yamanashi professor Teruhiko Wakayama, right, and Haruko Obokata of the Riken Center for Developmental Biology give a briefing on STAP cells during a news conference in Kobe on Jan. 28. (Asahi Shimbun file photo)
  • STAP cells (Provided by Riken)

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