Biologists delete paper from literature after realizing they’d deleted too many genes

Researchers deleted more genes than they bargained for in a Drosophila strain, a mistake that resulted in a retraction of a paper from 2007.

Ron Wides, a biologist specializing in pattern development at Bar-Ilan University, Israel, and colleagues have retracted a paper published in Mechanisms of Development after his lab found that their technique to delete the Ten-a gene ended up deleting other nearby genes, too.

It was deletions of other genes, and not Ten-a, that killed the fruit flies, Wides concluded. His group had also concluded, erroneously, that Ten-a is what’s known as a “pair-rule” gene. Fruit fly embryos develop in stacked segments, like tubes of Pringles; pair-rule genes guide the development of alternating segments. Those other loci, and not Ten-a, caused lethality and caused the flies to develop improperly early,  Wides concluded.

The retraction reads in full:

This article has been retracted at the request of the author, for the following reason.

A recently produced deletion mutation of the Drosophila melanogaster gene Ten-a removes the entire gene, yet does not lead to lethality. Thus the lethality and the pair-rule gene roles reported for Ten-a in Mech. Dev., 124 (2007) 911–924 cannot be attributed to this gene, but to second site loci in mutants studied. Given the centrality of the pair-rule claim for this paper, it has been retracted. The other findings of the paper remain as reported, particularly molecular and biochemical characterizations of the Ten-a gene, its alleles and its transcripts.

This seems like a worthy attempt to correct the literature, the kind we generally applaud. There doesn’t seem to have been any misconduct involved.

So we were puzzled when we didn’t hear back from Wides, and when David Wilkinson, the journal’s editor-in-chief, referred our questions to a spokesperson for the journal’s publisher, Elsevier — who in turn declined to comment. That lack of willingness to answer questions always makes us wonder what’s really behind a notice, of course, and we’ll update with anything else we learn.

So in the meantime, we looked into what effects the retraction might have on the field. The paper has been cited eight times, according to Thomson Scientific’s Web of Knowledge, most recently by two papers in Nature in April that appeared here and here.

We contacted Tim Mosca, a co-author of the two Nature papers, to ask what effect the withdrawal might have on the field. In those papers, Mosca and his colleagues found a completely different function for Ten-a than the Wides group originally did. Ten-a and another similar protein Ten-m act together to help information flow from neuron to neuron across what’s known as a synapse — the miniscule gap between neurons — the Stanford group concluded.

Mosca — which means, we feel obligated to note, “fly” in Spanish — said their work did not lead to the Wides retraction. He tells Retraction Watch:

As far as I know (since I am not the person in the lab who made the Ten-a mutant), we made the mutant some time ago just because we identified Ten-a in a nervous system screen and needed a mutant.

For the Stanford group, lethality — aka viability — wouldn’t have become an issue since the researchers deleted the Ten-a gene’s activity from single neurons, and not from the entire fly.

For many of our studies involving mosaic cell analysis, it doesn’t matter if the mutant is non-viable (so that doesn’t factor in for us) since we can remove function specifically in single neurons. That way, we can bypass any organismal need for a specific gene in viability. Fortunately for us, the viability of a fly doesn’t typically hinge on a single olfactory projection or receptor neuron!

12 thoughts on “Biologists delete paper from literature after realizing they’d deleted too many genes”

  1. “The miniscule gap between…” You know, that definition applies to a lot of things. It’s all a matter of scale.
    It’s nice to see a retraction that actually adds to the knowledge base and doesn’t involve western blots.

    1. You know I’m going to mention western blots in every comment from now on, just like Mitt Romney putting his dog on the roof of his station wagon for a twelve hour trip to Canada.

  2. I agree that it was a retraction that adds to what we know by removing confusion.
    Cases like this one belong in a “journal of negative results that mean something”.
    They thought they had hit the spot, but later they realized (from other work)
    that they had hit other things too, and that something else was responsible for what they
    did observe. Admitting this does not leave the readers with the wrong impression, and is the right thing to do.

    Contrast the corrective action taken by the Ron Wides group with the “business as usual” approach of other groups when their conclusions are challenged by some quite thorough data.

    The challenge to the idea that Runx3 acts as a tumour suppressor gene: it is not in the cells that get the cancer.
    EMBO Mol Med 3, 593–604. Absence of Runx3 expression in normal gastrointestinal epithelium calls into
    question its tumour suppressor function. Ditsa Levanon et al. 2011.

    I count 7 ways that the work in EMBO Mol Med 3, 593–604 (2011) showed that Runx3 is not expressed in the gastrointestinal epithelium, yet there are still claims by the Ito group championing Runx3 as a tumour suppressor gene, here:

    Gastroenterology. 2011 May;140(5):1536-46.e8. Epub 2011 Jan 27.
    Loss of Runx3 is a key event in inducing precancerous state of the stomach.
    Ito K, Chuang LS, Ito T, Chang TL, Fukamachi H, Salto-Tellez M, Ito Y.

    Most famously in:

    Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY,
    Nomura S, Lee CW, Han SB, et al (2002) Causal relationship
    between the loss of RUNX3 expression and gastric cancer. Cell 109: 113-124

    I am confused.

  3. From your article: “…..So we were puzzled when we didn’t hear back from Wides, and when David Wilkinson, the journal’s editor-in-chief, referred our questions to a spokesperson for the journal’s publisher, Elsevier — who in turn declined to comment. That lack of willingness to answer questions always makes us wonder what’s really behind a notice…..”

    I think you guys need to remember that scientists have no obligation to speak to ‘retraction watch’. Your blog is useful, but please don’t get too self important – just because scientists who retract don’t want to speak to you, it doesn’t mean you should start to “wonder whats really behind a notice”

    1. Point taken about scientists not having any obligation to speak to us, but researchers and editors who aren’t willing to answer questions aren’t exactly a model of scientific transparency, are they? And trust is built on transparency.

      1. I guess I’m just arguing that “retraction watch” shouldn’t be considered as the ultimate forum for answering questions – In this case the retraction and explanation from Dr. Wides was very clear and transparent (as you acknowledge)

        1. We don’t claim to be the “ultimate forum,” in fact we’re quite happy when others pick up stories we’ve covered and advance them. We just think answering questions is an important part of transparency and trust. So do a lot of other people, including Ben Goldacre:

          If scientists want to limit the amount of trust people have in them, that’s their business, but we’re not going to stop asking questions. Neither is Carl Zimmer, who got the “we will only respond to questions in a peer-reviewed scientific forum” from arsenic life researcher Felisa Wolfe-Simon:

          Perhaps you feel differently and can shed some light on the ways that failing to answer questions builds trust. Or perhaps you know something about this case that you’d be willing to share.

    2. Excellent point. From what follows below, it is clear that these guys are self-important. Ron Wides has clearly behaved correctly. He saw a mistake in his work (HE saw it, not Retraction Watch or other researchers), so he retracted the paper. He owes no reply whatsoever to Retraction Watch or Mr. Ivan Oransky.

      1. I’m glad you agree Asher.

        I’ll state again that I think this website offers a very useful service to alert us to retractions. But the implicit suggestion is that if you aren’t willing to answer questions to Retraction Watch then you aren’t being transparent or trustworthy

  4. @placemat. ““retraction watch” shouldn’t be considered as the ultimate forum”.
    The problem as I see it is that there is no suitable forum – at least until recently. RW has stepped up to the plate, gained national and international recognition, and, IMHO, provides a valuable service to the scientific community. So while perhaps not the ultimate forum (should there be one?), it is a major forum. Prior to RW, it seemed like no one was asking questions – especially to the publishers.

    1. As a disclaimer: I don’t know anything specific about this particular case nor am I connected in any way to the researchers; I’ve just read the paper and the retraction.

      Its clear that the original mutant line that Dr. Wides was studying does in fact have a second mutation that probably accounts for the original phenotypes. Hence, he quite rightly points this out and retracts the paper. It is not uncommon for mutant Drosophila lines to have unknown ‘second hits’ that can confuse and obscure their analyses – all Drosophila researchers will appreciate this and will fully understand the basis for the retraction.

      What I felt compelled to write about was the suggestion that because Dr Wides didn’t answer your questions that this represented a lack of transparency and trust. Far from it – the retraction is very transparent and the reasons for the retraction are also transparent.

      1. The transparency of the notice is separate from being willing to answer follow-up questions. That’s why we discussed both in the post. We’ll have to agree to disagree about whether failing to answer follow-up questions — and we were referring not only to Wides but to the editor and publisher of the journal — reflects transparency. We obviously think it doesn’t. Thanks for your feedback and input, which we always appreciate.

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