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The STAP cell controversy: post factum

7 July 2014
Appeared in BioNews 761

Two papers published back-to-back in Nature took our breath away (1,2) earlier this year. A young Japanese scientist had found a way of inducing pluripotency in differentiated cells by exposing them to a physical stress. The technology behind stimulus-triggered acquisition of pluripotency (STAP) was magnificent in its simplicity. The very same day, scientists around the globe began rushing to the lab, giving their cells an acidic bath and hoping for a miracle.

But a miracle did not happen, the research community became sceptical and the published work was subjected to unprecedented scrutiny. Tampered images were found. Some of them could have been an honest mistake, but others were less likely. Apologies were offered and series of hearings followed unrelenting, brutal media coverage. The Salem witch trials had begun. The investigators themselves became the target of investigation. Tampered images were found in their published work too. Now, after several months of agony, Nature has finally withdrawn the papers.

The RIKEN Center for Developmental Biology in Kobe is one of the most venerable institutions in Japan. Nature is the most prestigious scientific journal in the world. How is it possible that something like this could happen? It is easy to moralise and point fingers afterwards, but I will let others do that. I found it fascinating that such a young and inexperienced scientist could even come up with the idea of building a grandiose deception of these proportions and have the courage to submit it for publication in Nature, no less.

The work described in these two papers cannot be done in a month or two; it had to be done over the course of several years. There were, for sure, occasions when she was presenting her data to other investigators in her department or institution. She would have had to be extremely cunning (and not to mention extremely bright, too) to be able to conceive all of that and fool all of them. Obokata is now trying to (or being forced to) redeem herself. She is doing the experiments to verify the findings of her research. Transparency is secured by video-recording her experiments and through other means. Whether she will be able to or not, time will show.

Replicating published experiments is not as simple as one may think. Anyone who has spent even part of their career in a laboratory knows how difficult and time-consuming it can be to introduce a new technique. When we tried to reprogram human fibroblasts into induced pluripotent stem cells using synthetic modified mRNA (3), it took six months to generate reagents and another six to tweak the protocol in such a way that it would work in our hands (4): and it did not even seem to be difficult at first glance.

Or, in another example, when we were attempting to reproduce the derivation of human embryonic stem cells from a single blastomere (5), a written detailed protocol was not sufficient (6). A member of the team that had originally performed the experiment, with hands-on experience, had to fly to out and guide us, step by step. Only then could we reproduce the technique (7). Once we had done it, repeating it later was easy. With all this in mind, I was not troubled by the fact that the scientists, including my team, could not reproduce Obokata's experiment. My doubts arose when it was found that she used images from unrelated experiments, though the data were peripheral and I ascribed it to time pressure and her immaturity.

But the final straw for me was when it was proven that Obokata's STAP cells did not match the mouse strains supposedly used in the research. This suggested that if Obokata created STAP cells, she did so on a different mouse strain than reported. Although this may seem also peripheral, because it does not disprove that STAP cells could be generated, it does not make sense to be untruthful here, let alone to make an honest error of such magnitude. If you work with mice, you know very well which strain they are and how important that could be for outcome of the experiments. If you do not, then you do not have a place in such a line of work.

Regardless of whether or not Obokata will be able to prove that STAP cells are real, the whole affair should serve as a reminder to all wannabe scientists and moralists that in exact sciences the truth has and always will prevail, no matter what.

1) Obokata H, Wakayama T, Sasai Y et al. Stimulus-triggered fate conversion of somatic cells into pluripotency.
Nature |  29 January 2014
2) Obokata H, Sasai Y, Niwa H et al. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency.
Nature |  29 January 2014
3) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA
Cell Stem Cell |  2010
4) Petrova A, Celli A, Jacquet L et al. 3D In Vitro Model of a Functional Epidermal Permeability Barrier from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.
Stem Cell Reports |  2014
5) Klimanskaya I, Chung Y, Becker S et al. Human embryonic stem cell lines derived from single blastomeres.
Nature |  2006
6) Klimanskaya I, Chung Y, Becker S et al. Derivation of human embryonic stem cells from single blastomeres.
Nature Protocols |  1963
7) Chung Y, Klimanskaya I, Becker S et al. Human embryonic stem cell lines generated without embryo destruction.
Cell Stem Cell |  2008
11 August 2014 - by Antony Starza-Allen 
A leading Japanese scientist who was embroiled in the STAP cell controversy has been found dead in an apparent suicide....
16 June 2014 - by Dr Greg Ball 
The controversy surrounding the creation of so-called STAP cells continues with a report recommending the closure of the RIKEN Centre for Developmental Biology, the institute where the research was carried out...
9 June 2014 - by Dr Rachael Panizzo 
The lead author of a controversial study describing a new type of stem cell - stimulus-triggered acquisition pluripotency (STAP) cells - has agreed to retract two research papers published in the journal Nature in January 2014...
12 May 2014 - by Purvi Shah 
Japan's RIKEN Center has announced that an appeal by stem-cell scientist, Dr Haruko Obokata, found guilty of research misconduct in relation to her claims of converting blood cells to stem cells using an 'acid bath', has been rejected...
14 April 2014 - by Dr Greg Ball 
Dr Haruko Obokata, the lead author of two controversial stem cell papers that reported discovery of so-called STAP cells, has apologised for errors in her work...
7 April 2014 - by Dr Greg Ball 
An investigation has found that the lead author of the widely reported 'breakthrough' stem cell papers is guilty of misconduct...
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