Electrifying stem cell finding retracted
A bombshell stem cell discovery by Boston and Japanese scientists was withdrawn Wednesday from the journal that published the work — amid allegations of fraud and a tide of incredulity from outside scientists.
It is one of the highest-profile retractions of the last decade, and several stem-cell researchers said they are now convinced that the stunningly simple method for producing stem cells, reported in two papers in January, won’t work.
The journal Nature published a retraction notice Wednesday from the authors, including the Harvard and Brigham and Women’s Hospital scientist who originated the idea and oversaw part of the work. They cited the results of a Japanese investigation that found evidence of scientific misconduct and listed five additional errors they had identified, including misrepresented or mislabeled images and “inexplicable discrepancies” that raise questions about how the cells were created.
“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 retraction notice states.
The authors apologized for the mistakes in the articles, writing, “These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the . . . phenomenon is real.”
Rudolf Jaenisch, a stem cell biologist at the Massachusetts Institute of Technology who was not involved in the research, said experiments in his laboratory quickly convinced him the technique does not work. “It’s fine to have it finally settled,” he said. “Many people wasted their money and their time and their resources on repeating this.”
He added that Harvard should be more forthcoming as evidence mounts of errors, image misrepresentation, and possible fabrication. “I think the silence of the Brigham, of Harvard, was deafening,” Jaenisch said. “I find this just really not good and a bit problematic. . . . There are so many great stem cell biologists at Harvard, and I think they are embarrassed by it.”
In the January papers, the researchers claimed they had created powerful stem cells, capable of becoming any organ or tissue in the body, simply by dipping white blood cells from young mice in an acid bath. The result generated enormous excitement because it pointed to an easy and fast technique for creating stem cells, which are seen as potential therapies for diseases ranging from type 1 diabetes to heart failure.
But almost immediately, other scientists began questioning aspects of the work. Key authors of the papers publicly called for them to be withdrawn, especially after an investigation by the RIKEN Institute, a Japanese research center, found evidence of fraud by one of its scientists, Haruko Obokata, who led the work.
The official decision to withdraw the research depended on the agreement of all 14 of the scientists who contributed.
Dr. Charles Vacanti of the Brigham and Harvard Medical School, the senior author of one paper and a coauthor of the second, had not publicly said he agreed to withdraw the findings until now.
Vacanti, chairman of the Brigham anesthesiology department, said in a statement that he still believed the concept would be proven right, but felt that problems with the paper “impair the credibility of the manuscript as a whole.”
“In science, the integrity of data is the foundation for credible findings. I am deeply saddened by all that has transpired, and after thoughtful consideration of the errors presented in the RIKEN report and other concerns that have been raised, I have agreed to retract the papers,” Vacanti wrote.
Although much of the research was based in Japan, Vacanti and his brother, Martin, began working on the idea more than a decade ago at the University of Massachusetts Medical School. In an e-mail interview with the Globe earlier this year, Vacanti said he and another scientist in his laboratory worked closely with Obokata, when she was a researcher in his Brigham laboratory, “to develop, design, review, and discuss the results of many of the experiments” in one of the withdrawn papers. Vacanti has not been implicated in the fraud allegations made by the Japanese investigators.
It is not clear whether the Brigham or Harvard Medical School is investigating the research to assess whether any of the problems that have been found in Japan occurred while Obokata worked here. Both institutions have a policy to not confirm or deny the existence of such reviews.
In an editorial accompanying the retraction notice, Nature said the critical errors that undermined the evidence in the papers were found during the Japanese investigation.
“Figures that were described as representing different cells and different embryos were in fact describing the same cells and the same embryos,” Nature editors wrote. “All co-authors of both papers have finally concluded that they cannot stand behind the papers, and have decided to retract them.”
For many outside scientists, the retraction will bring closure to a high-profile drama that has played out in packed press conferences in Japan, anonymous attacks on blogs, and within laboratories where scientists have so far unsuccessfully tried to repeat the technique, called stimulus-triggered acquisition of pluripotency, or STAP.
For a scientific finding to be accepted as true, it must be repeated by other laboratories. That hasn’t happened yet, and the retraction means that the finding itself no longer exists.
Japanese media recently reported that RIKEN, where many of the authors work, planned to allow Obokata to repeat the experiment for five months — despite the institute’s finding that she committed scientific misconduct. Obokata will work under close supervision, including video surveillance.
“The suspicions surrounding the STAP cell papers have not been decisive (in denying the existence of STAP cells). We’d like to determine whether STAP cells really exist or not through experiments at the hands of Obokata herself,” Masatoshi Takeichi, director at the RIKEN Center for Developmental Biology, told the Japanese newspaper Mainichi Shimbun.
In his statement, Vacanti said he was heartened by news that efforts would be made to repeat the technique. Vacanti has also been trying to replicate the technique in his own laboratory, but an update on those efforts was not available.
A statement from the Brigham said Vacanti had found the last six months a frustrating ordeal.
“He firmly believes in the STAP cell phenomenon and is devastated by all that has transpired. At this time, he feels that it is not productive to rehash what has transpired and is instead focused on his research and his efforts to replicate the STAP cell findings,” the statement said.
One of Vacanti’s coauthors, however, said he now doubts that the method works.
“With the retraction of the papers, there is no longer any experimental basis to support the consistency of the STAP phenomenon, and considering the discrepancies that have been pointed out recently . . . it has become increasingly difficult to call the STAP phenomenon even a promising hypothesis,” Yoshiki Sasai, a scientist at the RIKEN Center for Developmental Biology, wrote in a statement.
Dr. Leonard Zon, a Harvard scientist and director of the stem cell biology program at Boston Children’s Hospital, said that the topic has dominated discussions in the field and the retraction should seal the fate of the finding.
“I don’t think there’s any shred of hope for these cells,” Zon said. “I really feel that there have been a lot of people trying different techniques, modified techniques, and I can’t find anybody who can reproduce it.”
The episode is already having an effect on stem cell research, Zon said. At the meeting of the International Society for Stem Cell Research last month, there was a mentoring session for junior scientists focused on scientific integrity and best practices for collecting and publishing evidence.