Nature paper retracted following multiple failures to reproduce results

nature 2-27-14An international team of researchers from the NIH, Harvard, the University of Michigan, and two Chinese universities — Fourth Military Medical University and China Medical University — has retracted their 2012 paper in Nature after they — and a number of other groups — were unable to reproduce the key results.

The original abstract for “The NAD-dependent deacetylase SIRT2 is required for programmed necrosis” said that the findings

implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction.

But here’s the notice, by corresponding author Toren Finkel and colleagues:

We retract this Article because some of the data, specifically the data reported in Fig. 2 demonstrating an in vitro requirement for Sirt2 in TNF-α-mediated necroptosis, appears to be irreproducible. We and others have confirmed that Sirt2 and RIP3 interact, and we continue to believe that the absence of Sirt2 protects against ischaemic myocardial damage. Nonetheless, our inability to reproduce the data in Fig. 2 involving TNF-α-mediated necroptosis undermines our confidence in the scientific conclusions reported and the proposed mechanism. Although the matter is currently under further review, we wish to retract the Article in its entirety, and regret any adverse consequences that may have resulted from the paper’s publication.

The paper has been cited 21 times, according to Thomson Scientific’s Web of Knowledge.

The retraction is accompanied by a Brief Communication Arising from what looks like eight groups around the world, explaining what happened when they all tried to reproduce the results. The abstract:

Sirtuins can promote deacetylation of a wide range of substrates in diverse cellular compartments to regulate many cellular processes1, 2; recently, Narayan et al.3 reported that SIRT2 was required for necroptosis on the basis of their findings that SIRT2 inhibition, knockdown or knockout prevented necroptosis. We sought to confirm and explore the role of SIRT2 in necroptosis and tested four different sources of the SIRT2 inhibitor AGK2, three independent short interfering RNAs (siRNAs) against Sirt2, and cells from two independently generated Sirt2−/− mouse strains; however, we were unable to show that inhibiting or depleting SIRT2 protected cells from necroptosis. Furthermore, Sirt2−/− mice succumbed to tumour-necrosis factor (TNF)-induced systemic inflammatory response syndrome (SIRS) more rapidly than wild-type mice, whereas Ripk3−/− mice were resistant. Our results therefore question the importance of SIRT2 in the necroptosis cell death pathway.

7 thoughts on “Nature paper retracted following multiple failures to reproduce results”

  1. I barely imagine the number of labs/people wasting time, reagents and money trying to reproduce the results, which is very strange to be irreproducible since its just the paper main finding and should be had a lot of care to report. This certainly prejudice a lot of people. The authors will refund another researchers now?

    1. Nature should be congratulated both for publishing the comment, and for retracting the paper. I hope this ushers in a new era where Nature promotes research integrity, and helps correct the literature by retracting papers.

      Suggestions for the next three papers (all of which have been featured on Retraction Watch) that they might reconsider are:


      In Figure 4b the MyHC loading controls for 2 different dogs (Varus and Vampire) are the same.


      An investigation by McGill University found that Figure 4c had been “intentionally contrived and falsified.”


      In the correction, animals are shown with tumors that are more than 5 cm3 in size. That Nature believes such animal cruelty is acceptable is unconscionable.

      1. A heads up. A story about Haruko Obokata and a Nature paper is getting alot of attention in the past week in national (Japanese) and international media. It is also getting attention since Obokata is often referred to as the most beautiful scientist in Japan, implying also that most, if not all, others, are not. Apparently at least three issues related to image manipulation, which the authors confirm, and if lead to a retraction, would very well be the first black mark on Riken’s publishing profile. Riken is as major as research institutes go (, so if this occurs, this would serve as a premise for a wide-scale examination of Riken-published papers in a post-publication peer review. This has massive repurcussions for Japan, where we have been seeing an increase in reported misconduct. Some background reading here:

        1. They should also correct Fig. 1C in the Brief Communication Arising of the very same Nature paper.

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