Efforts to repeat controversial stem cell technique intensify

In an effort to bring clarity to one of the most controversial and confusing scientific findings in recent memory, three Japanese scientists have released a detailed protocol explaining step by step how to create stem cells with a simple acid bath. A leading stem cell scientist at Boston Children’s Hospital is working directly with the scientist who led the work to try and repeat the technique.

The surprising report in January by Boston and Japanese scientists that stem cells, with the ability to develop into any cell in the body, could be created with the seemingly straightforward technique sparked a raging and very public debate in the scientific community.

Within a month, a problem with images in one of the papers was revealed, which the scientists have said will be corrected. Other possible problems have been pointed out on online forums. An investigation by the Japanese scientists’ institution has been ongoing, spurred by questions raised by outside scientists.

What can be easy to forget is that it is not unusual for a new technique that upsets conventional knowledge to be carefully and critically vetted. That process is appropriate and part of how science works; it’s just usually hidden from public view. Only rarely are discoveries so unexpected and high-profile that they trigger this level of public skepticism. The ultimate test of the stem cell-creation technique, as with any other scientific discovery, will be whether it can be repeated by other scientists.

The doubts have gushed out over the last month. Laboratories across the world have been trying to replicate the result, and people have shared reports of initial failures, although many of those were using different types of cells than those the authors reported using in their paper.

It is also is not uncommon for an experiment to not work when it is first attempted, so reports of a failure don’t mean the technique is wrong or doesn’t work. The new protocol will provide scientists a careful recipe to follow -- allowing them to rule out that differences in their technique might be causing them to fail.

In Boston, there are several scientists who are working to repeat the technique. I asked Dr. George Q. Daley, a stem cell scientist at Children’s Hospital and the Harvard Stem Cell Institute, what his experience has been so far.

Daley said he is working directly with Dr. Charles Vacanti, the anesthesiologist at Brigham and Women’s Hospital who was the senior author on the paper describing the technique. Although many have been quick to air their doubts about whether the method is just too good to be true, Daley said he would like to feed the evidence base and not the rumor mill. Vacanti, he said, has been very helpful and cooperative.

“If the technique is robust and highly reproducible it will be replicated quickly. If there are subtleties and nuances of the technique, then it will take longer. Only time will tell, and this is how science works,” Daley wrote. “If there is some fatal flaw in the technique, then it will be revealed in time. I am concerned about the rush to use blogging and social media to report early experience with a complex biological experiment. Most scientific experiments take time and many replications to work confidently, and early reporting may reflect a negative bias.”

In an e-mail, Vacanti said that the reason he is not a coauthor on the protocol that has been posted by the Japanese RIKEN Institute where many of his coauthors work is because he was not asked to take part.

He said that he plans to post a protocol for creating the stem cells -- called STAP cells -- on his laboratory website in the next few days, and added that the methods posted by RIKEN and his three Japanese coauthors are slightly different than the way it is carried out locally.

“I am hoping that what we post will be applicable on a broader scale,” Vacanti wrote. “The technical details are such that what works well in one person’s hands may not work as well when done by another person. We hope to post a protocol that will be most likely to work well regardless of who is doing it, and be translatable to multiple cell types and sources.”

Paul Knoepfler, a stem cell scientist at the University of California, Davis, has been chronicling the controversy and collecting early reports of scientists’ efforts to repeat the experiment on his blog. In an interview Knoepfler posted recently, Teruhiko Wakayama, a highly respected cloning expert who was one of the authors of the work, asked that people wait at least a year for the technique to be replicated before prematurely dismissing it.

Knoepfler has posted his first reactions to the 10-page protocol. He raises a number of technical questions, but one of his early take-aways is that although the technique sounded quite simple, there may be nuances in the method and it may not work readily on many types of cells.

“To paraphrase, I’d say the gist is, ‘Caution: STAP cells are extremely difficult to make,’ ” Knoepfler wrote.