A significant chapter of the nearly six-month saga of the STAP stem cell controversy has come to an end, with Nature running retraction notices for the two papers involved. The journal has also published an editorial about the case that’s worth a read.
The retractions for “Bidirectional developmental potential in reprogrammed cells with acquired pluripotency” and “Stimulus-triggered fate conversion of somatic cells into pluripotency” both read:
Several critical errors have been found in our Article (http://dx.doi.org/10.1038/nature12968) and Letter, which led to an in-depth investigation by the RIKEN Institute. The RIKEN investigation committee has categorized some of the errors as misconduct (see Supplementary Data 1 and Supplementary Data 2). Additional errors identified by the authors that are not discussed in RIKEN’s report are listed below.
(1) Figure 1a and b in the Letter both show embryos generated from STAP cells, not a comparison of ES- and STAP-derived chimaeric embryos, as indicated in the legend.
(2) Extended Data Fig. 7d in the Article and Extended Data Fig. 1a in the Letter are different images of the same embryo and not, as indicated in the legends, a diploid chimaera embryo and tetraploid chimaera embryo.
(3) There is an erroneous description in Fig. 1a in the Letter. The right panel of Fig. 1a is not a ‘long exposure’ image at the camera level but a digitally enhanced one.
(4) In Fig. 4b of the Letter, STAP cell and ES cell are wrongly labelled in a reverse manner.
(5) In the Article, one group of STAP stem cells (STAP-SCs) was reported as being derived from STAP cells induced from spleens of F1 hybrids from the cross of mouse lines carrying identical cag-gfp insertions in chromosome 18 in the background of 129/Sv and B6, respectively, and that they were maintained in the Wakayama laboratory. However, further analysis of the eight STAP-SC lines indicates that, while sharing the same 129×B6 F1 genetic background, they have a different GFP insertion site. Furthermore, while the mice used for STAP cell induction are homozygous for the GFP transgene, the STAP-SCs are heterozygous. The GFP transgene insertion site matches that of the mice and ES cells kept in the Wakayama laboratory. Thus, there are inexplicable discrepancies in genetic background and transgene insertion sites between the donor mice and the reported STAP-SCs.
We apologize for the mistakes included in the Article and Letter. These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real. 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.
Austin Smith, the author of a News & Views article accompanying the original papers, has also retracted that:
In view of the fact that the authors of ‘Stimulus-triggered fate conversion of somatic cells into pluripotency’ (H. Obokata et al. Nature 505, 641–647; 2014) and ‘Bidirectional developmental potential in reprogrammed cells with acquired pluripotency’ (H. Obokata et al. Nature 505, 676–680; 2014) are retracting their reports (see page 112), I wish to retract the News & Views article, ‘Potency unchained’ (Nature 505, 622–623; 2014), which dealt with these studies and was based on the accuracy and reproducibility of their data.
Nature also published an editorial on the case. While the journal acknowledges that the saga has prompted a review of their processes for checking image manipulation, and admit to at least one mistake, they try to draw lines around what their peer reviewers could and couldn’t have caught, and which of the papers’ problems were “fatal” and which weren’t.
First, they characterize the issues readers found shortly after the papers were published:
As various media outlets including Nature’s independent news team reported, errors were found in the figures, parts of the methods descriptions were found to be plagiarized and early attempts to replicate the work failed.
The problems that initially emerged did not fundamentally undermine the papers’ conclusions. Moreover, replication of such work is not necessarily straightforward or quick, and the ability to use some techniques can be very sensitive to aspects of the experimental protocol.
The figure errors may lead to changes in how Nature checks images:
We at Nature have considered what lessons we can derive from these flaws. When figures often involve many panels, panels duplicated between figures may, in practice, be impossible for journals to police routinely without disproportionate editorial effort. By contrast, image manipulation is easier to detect. Our policies have always discouraged inappropriate manipulation. However, our approach to policing it was never to do more than to check a small proportion of accepted papers. We are now reviewing our practices to increase such checking greatly, and we will announce our policies when the review is completed.
The journal takes pains to say that the public post-publication peer review wasn’t what sank the paper for good; that took an institutional investigation:
But only since the RIKEN investigation has it become clear that data that were an essential part of the authors’ claims had been misrepresented. Figures that were described as representing different cells and different embryos were in fact describing the same cells and the same embryos.
Nature then makes an argument many journals have used when confronted with deception by authors: There’s no way for reviewers to catch those sorts of problems:
We at Nature have examined the reports about the two papers from our referees and our own editorial records. Before publishing, we had checked that the results had been independently replicated in the laboratories of the co-authors, and we regret that we did not capture the authors’ assurances in the author-contributions statements.
We have concluded that we and the referees could not have detected the problems that fatally undermined the papers. The referees’ rigorous reports quite rightly took on trust what was presented in the papers.
It’s always good to see journals note the limitations of peer review, but may we suggest that a group of editors get a list of peer review’s flaws together and publish them before the next scandal involving a hot field such as stem cells? (We also note that Cell, Science, and Nature rejected earlier versions of the STAP papers, according to Science.) Of course, that might undermine a major justification for journals’ attempts to prevent publicity about research before they’ve published it, aka the Ingelfinger Rule. But it would sure be honest.
Nature also highlights some important aspects of retraction policy:
The papers themselves have now been clearly watermarked to highlight their retracted status, but will remain hosted on Nature’s website, as is consistent with our retraction policy. (In our opinion, to take down retracted papers from journal websites amounts to an attempt to rewrite history, and makes life needlessly difficult for those wishing to learn from such episodes.)