RIKEN President Ryoji Noyori announced plans to restructure the institute at the center of a stem cell controversy.

Dennis Normile/Science

RIKEN President Ryoji Noyori announced plans to restructure the institute at the center of a stem cell controversy.

In Japan, official effort to replicate STAP stem cells comes up empty

TOKYO—A team of researchers at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, reported today that they have been unable to reproduce a simple method of creating stem cells that was reported in two Nature papers by CDB scientists earlier this year. "But these are just interim results, not a final conclusion,” said Shinichi Aizawa, a RIKEN developmental biologist, at a press conference.

RIKEN, which operates a network of nationally funded research institutes, also announced today that CDB will be downsized, renamed, and relaunched in November under new management. 

In two papers, published online in Nature on 29 January, CDB's Haruko Obokata and others reported that simply subjecting mature mouse cells to a mild acid bath could produce stem cells, which are capable of developing into all the cell types in a body. Stem cells are likely to be at the heart of a wide range of future medical treatments. The stimulus-triggered acquisition of pluripotency (STAP) method, as the researchers named it, was far simpler than all other known methods of creating stem cells. Co-authors of the paper include researchers at CDB, at other institutions in Japan, and at Brigham and Women's Hospital in Boston, an affiliate of Harvard Medical School.

But the claims started unraveling within days as bloggers and contributors to the PubPeer website started noting problematic images and plagiarized text. Researchers around the world started reporting that they couldn’t replicate the results. A RIKEN investigating committee on 1 April announced finding Obokata guilty of research misconduct for several instances of falsification and fabrication in the papers. The committee cleared other co-authors of misconduct but said that senior scientists involved bore heavy responsibility for lax oversight of the then–30-year-old Obokata.

That month, RIKEN also set up a team to try to replicate the STAP phenomenon. An outside committee reviewing the case on 12 June recommended that CDB be dismantled. The authors retracted the papers on 2 July, though Obokata has continued to claim that the STAP phenomenon is real. In a tragic turn, Yoshiki Sasai, a highly respected stem cell scientist who was a co-author of the papers and CDB deputy director, committed suicide on 5 August. Reportedly one of the notes he left behind blamed the stress of the media attention.

The team attempting to replicate the STAP results is led by Aizawa and Hitoshi Niwa, another respected stem cell researcher who was also a co-author of the papers. In repeated experiments using different types of stress and cells from different tissues, they neither saw the fluorescent signal characteristic of stem cells generated from mice carrying a gene for green fluorescent protein, nor were they able to produce a cell mass as reported in the Obokata papers. Niwa noted that they used a common laboratory mouse strain known as C57 black 6. (A report in Japanese is here.) To be thorough, they intend to repeat the experiments with other mouse strains. They are also giving Obokata herself a chance to reproduce her results. They expect to complete their work by next March.

As for the fate of CDB, RIKEN President Ryoji Noyori said they will rebuild the institute around 250 researchers with the remaining staff moved to other RIKEN institutes. (A Japanese report is here.) CDB had a staff of 541 in 2013, according to the institute's annual report that year. A new director will be appointed for the institute, which RIKEN has tentatively named the "Multicellular System Formation Research Center."

Noyori also announced a multifaceted action plan to strengthen governance, establish a new research compliance office, improve awareness of research ethics, and provide guidance in properly recording and managing research data all to prevent a recurrence of misconduct and to regain the trust of the Japanese public.

*Update, 27 August, 8:16 a.m.: This story was updated with more information.

Posted in Asia/Pacific, Biology, People & Events Stem Cell Controversy