Back in late January, two papers were published in the prestigious journal Nature showing a completely novel and shockingly simply way to make stem cells – the approach used an acid bath. Since then, there’s been huge controversy surrounding the creation of these mouse stem cells, called STAP cells (for stimulus-triggered aquisition of pluripotency). This is because other researchers have had difficulty independently making STAP cells and there are accusations of misconduct — specifically falsification and fabrication of data. But just this Wednesday, lead author Haruko Obokata, a researcher at the RIKEN Center for Developmental Biology in Japan, publicly spoke at a press conference to adamantly defend the validity of her results and the existence of the STAP cells.
By mid to late February, researchers who tried to independently create STAP cells had not had any success yet using the theoretically simple and quick method. But since it was still early, this was not very surprising. However, in mid March, one of the authors, Teruhiko Wakayama, asked that Nature retract the papers – he had also had difficulty reproducing the results. By this point, there were also accusations that parts of figures had been duplicated within the paper. But if a paper is to be retracted, Nature generally wants all authors to agree to retracting it — since the other authors didn’t, the papers weren’t retracted.
While the other authors refused to retract the papers, RIKEN’s own internal investigation commenced and other researchers tried to independently create STAP cells. By late March, two out of more than six labs said they’d made STAP cells using the relatively simple approach. At the same time, one of the STAP papers’ authors posted another version of the protocol that they hoped would help people successfully reproduce their results. But this hasn’t seemed to help so far.
One particularly vocal researcher has been Kenneth Lee at the Chinese University of Hong Kong. In late March, he attempted to publish his failed STAP results with Nature, but Nature rejected the publication. Using the new version of the protocol, Lee then posted somewhat successful results on April 1, but surprisingly found that the best results were with cells that were treated according to the protocol but without adding acid. However, there were clearly some problems with Lee’s data and/or interpretations (likely autoflourescence-related) — just a few days later, on April 4, Lee announced that “I don’t think STAP cells exist” and that he’d no longer focus on reproducing the results (or at least not post them live on his blog). Lee’s results likely need further analysis, but they don’t seem encouraging.
Then, last Wednesday, on April 2, the six-person committee at RIKEN that had been investigating the case reported finding evidence of misconduct, which RIKEN defines as a malicious act, such as knowingly falsifying data. (Previously, in mid-March, the committee had reported that figures and data had been “inappropriately handled,” but did not find any actual misconduct.) Specifically, two items were identified as acts of misconduct — one was the splicing of gel lanes together in a figure, and the other was reusing images that appeared in Obokata’s doctoral dissertation (for different experiments). Obokata argued that she had spliced the gel lane images to “present an easy-to-view photo” of the results, and that ultimately this didn’t affect the paper’s results. (The committee also found evidence of plagiarism, but didn’t consider this to be “misconduct” since it wasn’t done with malice.)
As for copying images from her dissertation — Obakata addressed this in a two-hour press conference just yesterday, Wednesday, April 9. Obakata, who had not released comments since January (which she claimed was due to pressure from RIKEN), continued to stand by her claim that the STAP cells are real and that she made them “more than 200 times.” The 30-year-old Obakata explained that the manuscript mistakes had been due to her being careless, sloppy, and inexperienced, but the errors were not malicious. For example, the image from her doctoral dissertation that was in the recent papers had been used in a slide in presentations repeatedly, and Obakata claims that its origins had become obscured to her. She’s filed an appeal with RIKEN to re-examine the case, which could take about 50 days. Additionally, RIKEN will be working to independently replicate her results, but the process could take about a year.
All of this drama has taken its toll on Obakata, who was hospitalized Monday from mental and physical stress, and is said to have returned to the hospital after two hours of answering questions at the press conference on Wednesday.
Obakata’s take-home message is essentially that while her STAP publications had mistakes, the end result — the creation of stem cells using a novel, relatively simple methd — is still the same, and STAP cells do exist. RIKEN and other researchers are working to independently confirm this — it could be that the published protocols will need additional tweaking to be most successful.
While trying to reproduce somebody’s scientific results using a procedure they made can be difficult and challenging, it’s always important to evaluate whether it’s the procedure itself that doesn’t work (or needs tweaking to be more robust), or if the person doing the experiment is unintentionally doing something a little different than what the procedure calls for. It is often likely a combination of both, but in the STAP case the former situation seems more likely.
For further reading:
- Tracy Vence’s article “Stress-Induced Stem Cell Method Questioned”
- Tracy Vence’s article “Call for STAP Retractions”
- Charles A. Vacanti’s “Protocol for Generating STAP Cells from Mature Somatic Cells”
- Tomoko Otake’s article “Obokata says STAP cell discovery not fabrication, claims Riken dissuaded her from giving her side of story earlier”
- Teisha J. Rowland’s blog post “How to Make Stem Cells… Using Acid!”
- Teisha J. Rowland’s book Biology Bytes: Digestible Essays on Stem Cells and Modern Medicine