Nature STAP stem cell studies retracted after more errors found

Following months of controversy, editors at the scientific journal Nature have retracted two high-profile studies that purported to demonstrate a quick and simple way of making flexible stem cells without destroying embryos or tinkering with DNA.

“Several critical errors have been found in our Article and Letter,” Nature wrote in a retraction statement issued Wednesday. “We apologize for the mistakes.”

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FOR THE RECORD:
Stem cells: An article in the July 3 Section A about two controversial stem cell studies that were retracted had stated that the decision was made by editors at the journal Nature. The retraction decision was made by the authors of the studies. Additionally, the comments in the retraction statement should have been attributed to the authors of the studies, not to the journal editors. —
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The two reports described a new way of reprogramming blood cells so that they would revert to a developmentally primitive state and be capable of growing into any type of cell. Researchers from Japan and the United States said they accomplished this feat by soaking the cells in an acid bath for 30 minutes and then spinning them in a centrifuge for 5 minutes.

The resulting stem cells – dubbed stimulus triggered acquisition of pluripotency, or STAP – had the hallmarks of embryonic stem cells. When the researchers injected them into developing mice, the STAP stem cells grew into heart, bone and brain cells, among others, the research team reported in January.

Scientists in the field of regenerative medicine were giddy at the prospect of using the cells to grow new insulin-producing cells for people with Type 1 diabetes or central nervous system cells for people with spinal cord injuries, to name a few examples. Since these replacement tissues would be generated from a patient’s own cells, researchers believed they would not prompt the immune system to attack, eliminating the need for patients to take immune-suppressing drugs.

But it didn’t take long for some researchers to suspect that STAP stem cells were too good to be true. Critiques posted online gained more currency when labs began reporting that they weren’t able to replicate the experiments. Then one of the senior researchers who worked on both of the studies called for the papers to be withdrawn until the results could be independently verified.

In April, the Japanese research institute where most of the work was conducted accused study leader Haruko Obokata of intentional misconduct.

Investigators at RIKEN said Obokata had manipulated two images of DNA fragments to make the results of her experiments look better than they really were. They also found that data were handled inappropriately and that two of the images in the study were duplicates.

Investigators at Nature cited five additional errors that were not included in the RIKEN investigation. Figures and images in the studies were improperly labeled, and one of the images was digitally enhanced, according to the retraction statement. They also identified “inexplicable discrepancies” in the cells of mice that were injected with STAP stem cells.

“These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real,” Nature wrote in its retraction. “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.”

All of the researchers who contributed to both papers have agreed with Nature’s decision to retract them, according to an editorial published by the journal.

Obokata, who shot to fame in Japan after the studies were published, has not commented on the retraction. In April, she held a tearful news conference apologizing for what she described as careless mistakes. But she also struck a defiant tone, insisting that STAP stem cells were real and that she had created them “more than 200 times.”

Two of her colleagues at RIKEN have issued apologies for their roles in the troubled studies.

“As a researcher, I am deeply ashamed of the fact that two papers of which I was an author were found to contain multiple errors,” Yoshiki Sasai, a deputy director at the RIKEN Center for Developmental Biology, said in a statement. “I apologize wholeheartedly for the confusion and disappointment that this situation has caused.”

RIKEN said it had removed articles on its own website promoting the results of the STAP stem cell studies.

Dr. Charles Vacanti, a senior author of one of the studies and co-author on another, said he agreed that the papers should be retracted because the errors they contain undermine their credibility.

But Vacanti, a tissue engineering researcher at Brigham and Women’s Hospital in Boston who came up with the idea behind STAP stem cells with his brother, Dr. Martin Vacanti, held out hope that the studies would be verified by other research groups.

“There has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself,” he said in a statement.

Sasai did not share that optimism, saying “there is no longer any experimental basis” to back up the idea that cells can be reprogrammed by exposing them to acid and other environmental stresses.

“It has become increasingly difficult to call the STAP phenomenon even a promising hypothesis,” Sasai said.

Paul Knoepfler, a stem cell scientist at UC Davis who was among the first to question the legitimacy of the STAP studies, said it was time for researchers to “move on from this mess,” as he put it in a blog post. He credited social media for enabling stem cell experts to get to the bottom of the controversy so quickly, thus expediting Nature’s retraction by more than a year.

“Why does this matter?” Knoepfler wrote. “Millions of dollars in scarce research funds would have been wasted along with potential damage to many young scientists’ careers who might have been directed to work on STAP in labs around the world potentially for years.”

Nature, too, used the occasion to reflect on the peer-review process that scientists have long used to vet and share scientific findings. In particular, the journal wondered whether it should should have caught the mistakes that skeptics flagged shortly after the studies were published.

In their editorial, the Nature editors exonerated the independent scientists who assessed the studies when they were submitted for publication. The editors also noted that they had checked to make sure that the STAP results “had been independently replicated” by the scientists who collaborated on the papers.

“We have concluded that we and the referees could not have detected the problems that fatally undermined the papers,” the editorial said. “The referees’ rigorous reports quite rightly took on trust what was presented in the paper.”

More generally, the problems with duplicated figures and images may be “impossible for journals to police routinely without disproportionate editorial effort,” the editorial said. Though it’s easier to spot manipulated images, “our approach to policing it was never to do more than to check a small proportion of accepted papers. We are now reviewing our practices to increase such checking greatly.”

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