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Retraction Watch

Tracking retractions as a window into the scientific process

Another XMRV shoe drops: PLoS Pathogens study linking prostate cancer to virus retracted

with 13 comments

Less than 24 hours after the publication of a study showing no link between XMRV, aka xenotropic murine leukemia-related virus, and chronic fatigue syndrome (CFS), the authors of a a study claiming a link between the virus and prostate cancer have has been retractedit. The move comes along with the publication of a new study showing that no such link exists.

Here’s the notice, from PLoS Pathogens:

Retraction: Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, et al. (2006) Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant. PLoS Pathog 2(3): e25. doi:10.1371/journal.ppat.0020025

In light of the findings from a recent study “In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer” and others in the field, the editors of PLOS Pathogens have issued a retraction of this study. The association of XMRV with prostate cancer has now been thoroughly refuted. Although the original finding of a novel gammaretrovirus, XMRV, with the use of a pan-viral detection microarray is valid, and sequencing and phylogenetic characterization of the virus still stands, the editors agree that it is clear that XMRV found in this study is laboratory-derived and there is no association of XMRV with prostate cancer. As a result the paper was retracted from PLOS Pathogens on September 18th, 2012.

The “recent study” to which the authors refer is quite recent, in fact: It was published yesterday, September 18, in PLoS ONE. It shares a number of authors with the now-retracted PLoS Pathogens paper, which has been cited 346 times, according to Thomson Scientific’s Web of Knowledge. One of the authors of both papers — the Cleveland Clinic’s Robert Silverman –  also co-authored the now-retracted Science paper linking XMRV to chronic fatigue syndrome.

In a blog post accompanying the study, a PLoS ONE editor, Gilda Tachedjian, explains why this is the “final chapter” in the story alleging a link between XMRV and prostate cancer:

Despite the controversies in the CFS field, at that time the XMRV prostate cancer story remained an open question.  Fast forward to early 2012 – and over a 100 publications later – XMRV was accepted by the majority of the scientific community to be a contaminant with no role in causing prostate cancer. This was due to several studies published in late 2010 and early 2011 demonstrating that XMRV was a laboratory-generated virus (Paprotka et al 2011) and that highly sensitive nucleic acid detection assays were not detecting a bone fide infection of XMRV or related viruses in humans, but instead contamination from a variety of sources including mouse DNA, XMRV plasmid DNA, and XMRV from infected cell lines (see reviews by Sfanos et al 2012 and Groom and Bishop 2012).

Why was the new PLoS ONE study important? Tachedjian continues:

In the context of these findings, this study in PLOS ONE by Lee and colleagues is significant because it has allowed the authors who originally reported the association of XMRV with prostate cancer to set the record straight.  Using careful molecular detective work, they found that the original archived prostate cancer tissue was negative for XMRV although the archival extracted RNA from the original study was positive for XMRV.  They also failed to demonstrate the presence of XMRV in new prostate cancer samples. In addition, they discovered that the source of XMRV contamination in the archival extracted RNA was from an XMRV-infected cell line used in the laboratory.  The inability to confirm their original findings published in PLOS Pathogens represents the final chapter that closes the book on XMRV and its role as a naturally acquired human infection associated with prostate cancer. The PLOS Pathogens paper is retracted today.

Update, 10:45 a.m. Eastern, 9/19/12: As a commenter notes, the notice refers only to the editors, not the authors. We’ve contacted the corresponding authors — many of whom, as we point out, are also authors of the PLoS ONE study overturning their findings — and the editor of PLOS Pathogens, to ask whether the authors agreed to this retraction, and will update with anything we find out.

Update, 4:30 p.m. Eastern, 9/19/12: This article has been updated to include information from a nice story by Martin Enserink at Science. It turns out the retraction caught the authors by surprise and was not at their request. Neither the authors nor the journal have responded to our request for comment.

Update, 5:45 pm Eastern, 9/19/12: Kasturi Haldar, the editor of PLoS Pathogens, tells us the journal acted after not hearing back from the authors:

PLOS Pathogens is a member of the Committee on Publication Ethics (COPE: http://publicationethics.org) and we follow their guidelines in reviewing any situation in which the literature may need to be corrected. The decision to retract the original 2006 paper was made in consultation with a large group of PLOS Pathogens’ senior editors. The authors were contacted by email on August 27th regarding our decision, and were asked to comment on the retraction text and suggest changes. We did not receive a reply, and decided to move forward with the retraction in conjunction with the PLOS ONE publication yesterday, September 18th.

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Written by ivanoransky

September 19, 2012 at 6:30 am

13 Responses

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  1. I commented earlier for the earlier PLoS One retractions. Not again PLoS Journals…there is a fundamental problem with the processing, I guess.

    Ressci Integrity

    September 19, 2012 at 7:47 am

    • No- it is more likely an effect of the PLoS journals becoming one of the largest publishing groups, mainly driven by the growth of PLoS ONE to become the biggest journal on the planet. If the retraction rate is similar to other journals, you would expect to see more retractions coming up for PLoS Journals.

      Ivan (not Oransky)

      September 19, 2012 at 1:09 pm

  2. This notice says “editors of PLOS Pathogens have issued a retraction”, not the authors. I don’t see any indication that the authors have retracted it, agreed to the retraction, or indeed that they were even notified of the retraction. It’s probably the way it was worded, but if in fact this paper was unilaterally retracted by the editors without consulting the authors, one day after a contradictory study was published, it seems problematic to me.

    Would be nice to hear from the authors.

    Ian

    September 19, 2012 at 8:47 am

    • Good point, we’ve added an update and have contacted the authors.

      ivanoransky

      September 19, 2012 at 10:46 am

      • Yeah, wow. Based on the Enserink story, that’s really not OK. This is not a slam-dunk retraction; the editors should not have made that decision unilaterally.

        The authors say they didn’t hear anything. The editors say they didn’t hear from the authors after one set of emails sent Aug 27. DId they send them to the emails listed in 2006? Did they try to phone, or mail, or send a registered letter? Even assuming the emails were sent correctly, and not lost as spam, that’s about three weeks, including a major US holiday (Labor Day), just 10 business days if I’m counting right.

        Retractions should be a big deal. Retractions should be considered and thought about, if it’s not blatant theft or fabrication — which this paper was not, of course. Even if the retraction was justified — again, debatable — the editors need to take it seriously. Here, they seem to have been lazy, cavalier, and sloppy.

        Really not acceptable behavior from the journal. I hope the editors retract their retraction and apologize to the authors.

        Ian

        September 20, 2012 at 6:57 am

  3. Ivan–Martin has a nice backstory on this retraction. See http://news.sciencemag.org/sciencenow/2012/09/retraction-of-first-paper-on-xmr.html?ref=hp

    John Travis

    September 19, 2012 at 4:23 pm

    • Thanks John, updated with link.

      ivanoransky

      September 19, 2012 at 4:37 pm

  4. In that article in Science it says: “Several other journals with a higher impact factor than PLoS ONE had agreed to publish the paper, but on the condition that the authors retract the 2006 study—which the team refused unanimously, says Chiu, who wasn’t involved in that study himself. ”

    and later: “It was a bit ridiculous,” he says. “The reviewers all said, ‘Great, this needs to be published.’ But the editors said what prevented them from publishing was that the authors refused to retract the original paper.”

    That seems a little too much like journal one-up-manship to me.

    ” Chiu declined to name those journals” – come on, name and shame!

    I’d also agree with Kim McCleary who says the researchers deserve a medal. Particularly Judy Mikovits’ name has been dragged through the mud so I was glad to see her pursuing this and being second author on the new CFS paper (of course, there is still that issue with a gel that seems to have ‘mislabelled’ samples!)

    Booker

    September 19, 2012 at 6:07 pm

  5. 1. Dr Mikovits appears to have been “rehabilitated” in view of her second authorship on the new paper. As avid readers of this blog well know, she was busted last year for theft on the information of her boss, the nouveau riche couple with a daughter who has CFS/ME… even though the research was supposed to be helping the daugher, they couldn’t resist marketing(?) a blood test for the presence of XMRV that was developed in their lab, charging as much as $2400 a pop even though the virus wasn’t confirmed to cause any known disease or risk… makes a person think the source of their wealth should be evaluated with a jaundiced eye. Just saying. But Dr Mikovits’ good karma has served her well.

    (Sad to say that the CFS/ME crowd has a lot of individuals who are well to do but suffering from an incurable disease–or have a close relative with the disease. These people have a tendency to develop both desperation and single-mindedness, a bad combination when good judgement.is called for. Thus the particular dismay I feel when observing the treatment/exploitation of these patients by the institute Judy used to work for.)

    2. XMRV has got to be good for something.

    3. The group refused to retract their 2006 paper because… there was nothing wrong with the science?

    What a country! You even have the right to vote!

    puzzled monkey

    September 19, 2012 at 7:30 pm

  6. What’s up with the timing? Why’d both papers come out, in different journals, on different but related topics, on the same day [September 18]? Did PLoS rush to get theirs up after the mBio one was published? Just a coincidence?

    Amos Zeeberg

    September 19, 2012 at 8:15 pm

    • Perhaps the retraction was rushed out to coincide with the publication of the new paper; that would explain why they only waited three weeks after emailing the authors and didn’t try any alternate means to reach them for a discussion as to whether the paper should be retracted (Whatever happened to snail mail? Three weeks would be a good wait time for a certified letter, which they should have sent.) Perhaps they guessed that the authors would refuse to retract and there would be a long drawn out discussion– so they short-cut the discussion when they heard the new paper was coming out. Sounds like a good conspiracy theory to me.

  7. I wonder why this was a retraction and not an erratum. Seems like even if the prostate link want valid, the “this virus could be a major confound in studies” info should still be out there?

    drgunn

    September 22, 2012 at 5:02 pm

  8. I appreciate the comment oif Dr. Gunn- it would be useful to have a caution at the end of the citation in database that says “see journal page year” which indicates this information has been contradicted by more recent work. This would be useful in cases where one believes a piece of work to have been faked and can show from later published work that the results and conclusion are incorrect e.g.a finding that E. coli has 2 genes coding for a certain gene whereas the chromosome of E. coli when sequenced has only one. This has the advantage of not having to raise the issue of fraud and at the same time, avoiding continuing misinformation.
    Elaine Newman

    Elaine Newman

    September 25, 2012 at 7:19 pm


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