n case there was any lingering doubt about the falsity of a 2014 claim that a Boston scientist and his colleagues had created embryonic stem cells by a near-magical technique, three studies published Wednesday slam the final nails into the coffin.
The technique did not prod adult cells to revert to an embryonic state. Instead, the cells were embryonic all along, according to two groups of scientists from five countries who carried out a painstaking forensic analysis of the cells.
Embryonic stem cells had somehow gotten mixed up with adult cells.
The 2014 papers reporting the technique had already been retracted, but “this is the smoking gun,” said stem-cell biologist Dr. George Daley of Boston Children’s Hospital and Harvard Medical School, the senior author of two of the debunking studies, published in Nature.
The original claim that adult cells had been transformed into embryonic stem cells made headlines worldwide because it promised a solution to one of the obstacles plaguing stem cell research: how to easily obtain the jack-of-all-trades cells, which scientists use to study the origins, mechanisms, and possible treatments of diseases including diabetes and Alzheimer’s.
Embryonic stem cells can come from days-old embryos, such as those created in fertility clinics. But opponents view that as unethical because the embryos are destroyed in the process. A 2007 discovery showed how to create them from adult cells, but the required genetic technique is difficult.
The 2014 claim, by scientists at Japan’s RIKEN center and tissue engineer Dr. Charles Vacanti of Brigham and Women’s Hospital in Boston, seemed to offer a third way. Bathing adult cells in acid acted like a time machine, they reported, turning them into cells very much like embryonic stem cells.
Called STAP cells, these acid-zapped cells reportedly had the key property of being “pluripotent,” or able to morph into any kind of cell, from muscles to neurons. (STAP stands for stimulus-triggered acquisition of pluripotency.)
Although the research used mouse cells, it seemed to offer a recipe for creating human embryonic stem cells, too.
Within days of the papers’ publication in Nature, however, scientists questioned whether the authors had truly done what they claimed.
Daley dispatched a colleague to Vacanti’s lab to try to replicate the results. “Very quickly he started finding problems,” Daley said.
Daley then enlisted seven labs to try to replicate the STAP claim.
They were quickly overtaken by events. The journal Nature retracted the papers in July 2014. Vacanti initially opposed the retraction but eventually agreed to it, though he continued to hold out hope that the results would be vindicated. An investigation by RIKEN concluded last year that some “errors” in the study, including manipulation of images, reflected misconduct by some of its scientists — and that there was little chance STAP cells had been created.
Daley’s group continued its work, however. The team used “forensic genomics” to determine the origins of the STAP cells — which turned out to be pre-existing embryonic cells, they report in the new paper. In his second paper, Daley and scientists from five countries detail how to use genomic analysis to determine the origins of any cells thought to be pluripotent, in hopes that an episode like STAP never happens again.
The third paper published Wednesday, based on the RIKEN study, echoes the others, describing how whole-genome sequencing revealed that all the STAP cells in the 2014 research “derived from previously established embryonic stem cell lines.”
Last September, Vacanti resigned as chair of anesthesiology at Brigham and Women’s and went on sabbatical. He said via e-mail on Wednesday that he was unable to comment. Before the stem-cell fiasco, Vacanti was perhaps best known for a 1997 experiment creating a lab mouse with human-ear tissue growing on its back.
In August 2014, a co-author of the retracted papers, Yoshiki Sasai, committed suicide. A lawyer for his family said he left behind a note citing “the responsibility he felt towards RIKEN and his laboratory.”