A Japanese team announced Friday in Tokyo that it has been unable to reproduce a new, astoundingly simple way of generating pluripotent stem cells, despite working directly with the lead author on the Nature papers reporting the breakthrough method. That researcher, Haruko Obokata, also today resigned from the RIKEN Center for Developmental Biology (CDB) in Kobe, home of most of the team conducting the research.
Despite an 8-month effort, "We could not verify the STAP cell phenomenon," said Shinichi Aizawa, a CDB developmental biologist who led the verification team, at a press conference, referring to the so-called stimulus-triggered acquisition of pluripotency (STAP) method. He added that RIKEN was halting efforts to verify the STAP approach.
"I remain very puzzled by these results," Obokata wrote in a statement released to the press. She admitted being unable to reproduce satisfactory results, though she complained about the conditions under which she had to try. (Documents from the press conference are available in Japanese here.)
The announcement was not a surprise. The STAP team, which included researchers at other institutions in Japan and at Brigham and Women's Hospital (BWH) in Boston, an affiliate of Harvard Medical School, grabbed headlines with its claim that briefly bathing adult cells in an acidic solution could produce stem cells capable of developing into all of the cell types in a mammalian body. Previous methods of creating stem cells involve complex and challenging laboratory techniques. The method was described in an article and a letter published online in Nature on 29 January.
Within weeks, scientific bloggers identified problematic images. Soon, researchers around the world reported being unable to reproduce the results. RIKEN launched an investigation and by April concluded that Obokata was guilty of research misconduct. Nature retracted the papers in July. Despite numerous problems in the papers, Obokata and co-author Charles Vacanti, a BWH tissue engineer, staunchly maintained that the STAP phenomenon was real and kept releasing tweaks to their published protocols. RIKEN officials decided to settle the issue by methodically redoing the experiments described in the papers. In an interim report released in August, the verification team reported not being able to produce STAP cells. At that time, the team invited Obokata to participate in their efforts to see if there were subtleties in her experimental techniques not defined in her published protocols.
At today's press conference, Aizawa suggested that Obokata may have interpreted the glow from a marker gene inserted into tissue indicating pluripotency when a much stronger signal is required. The verification team also succeeded in creating cells that fluoresced, but not at the levels typically expected to indicate pluripotency. The team failed in its efforts to produce further, more convincing evidence of pluripotency.
Aizawa said he could not say whether Obokata still believed in the STAP phenomenon, and her statement is vague on that point. Obokata, now just 31, blamed her "immaturity at the time of the publication and retraction of the papers" for the trouble caused to those at RIKEN and to many others. "I don’t have the words to apologize," she wrote. A BWH representative told ScienceInsider: "At this time, Dr. Vacanti does not intend to speak with media."
The scandal has already had a wide-ranging impact, tarnishing the reputations of several highly respected co-authors as well as of RIKEN, Japan's national network of laboratories. One co-author, Yoshiki Sasai, took his own life in August. RIKEN radically reorganized CDB, cutting staff from more than 500 to 250. The Japanese name was changed but the English name was retained.
The incident leaves a number of lingering questions. Her Japanese co-authors had previously admitted that none of them had tried to reproduce the results of what was supposed to be a phenomenally simple way of making stem cells, though it is not clear why. Another puzzle is why the papers were accepted by Nature. Science had rejected an earlier version of the papers. Nature's reviewers pointed out numerous problems and recommended rejection. Nature later accepted what apparently were slightly revised versions. Nature previously declined to reveal what led to the decision to accept the revised papers or if they were sent back to reviewers before acceptance.