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Retraction Watch

Tracking retractions as a window into the scientific process

Chronic fatigue syndrome-XMRV paper retracted by Science, completely this time

with 39 comments

The editors of Science have fully retracted a study they published in 2009 alleging a link between chronic fatigue syndrome (CFS) and the virus XMRV.

The notice begins with a nod to the reasons that the paper has already been partially retracted:

Science is fully retracting the Report “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome” (1). Multiple laboratories, including those of the original authors (2), have failed to reliably detect xenotropic murine leukemia virus–related virus (XMRV) or other murine leukemia virus (MLV)–related viruses in chronic fatigue syndrome (CFS) patients. In addition, there is evidence of poor quality control in a number of specific experiments in the Report. Fig. 1, table S1, and fig. S2 have been retracted by the authors (3).

It also refers to evidence of image manipulation that was described by blogger Abbie Smith and then reported in the Chicago Tribune:

In response to concerns expressed about Fig. 2C [summarized in (4)], the authors acknowledged to Science that they omitted important information from the legend of this figure panel. Specifically, they failed to indicate that the CFS patient–derived peripheral blood mononuclear cells (PBMCs) shown in Fig. 2C had been treated with azacytidine as well as phytohemagglutinin and interleukin-2. This was in contrast to the CFS samples shown in Figs. 2A and 2B, which had not been treated with azacytidine.

The notice also makes it clear just how contentious a process it has been to sort all of this out:

Given all of these issues, Science has lost confidence in the Report and the validity of its conclusions. We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement. It is Science’s opinion that a retraction signed by all the authors is unlikely to be forthcoming. We are therefore editorially retracting the Report. We regret the time and resources that the scientific community has devoted to unsuccessful attempts to replicate these results.

Despite the retraction, you can be sure you haven’t heard the end of this story. For one, one of the authors, Judy Mikovits, is embroiled in a legal battle with her former employer, the Whittemore Peterson Institute in Reno, Nevada, over whether she has the right to lab notebooks and other materials. She recently spent five days in a Ventura, California jail as part of the case. And she is also part of an ongoing study by Columbia University’s Ian Lipkin of 150 blood samples from people with CFS, to figure out if anything — including XMRV — can be considered a cause of the disease.

Update, 5:30 p.m. Eastern, 12/22/11: ScienceInsider has details on how the retraction came to be.

Update, 11:15 a.m. Eastern, 12/23/11: Read Ivan’s take on how Science handled the release of news of the retraction.

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39 Responses

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  1. Thank goodness this house of cards has finally fallen. I can only imagine what people suffering from CFS go through every time some false hope like this appears.

    sfs

    December 22, 2011 at 11:31 am

    • I can only echo what you have said. Entirely.

      Jack

      December 22, 2011 at 12:07 pm

    • I think most people with CFS, like myself, really just wish XMRV would would go away at this point. The actions of the Mikovits, and the WPI unfortunately cast a negative image on the CFS patient population as a whole. I just cringe every-time I see a headline about XMRV; it was handled just about as poorly as possible by the WPI and Mikovits. It was really a time that they could have rallied the troops and brought scientists together to study CFS; instead they attacked everyone who disagreed with them.

      I am hopefully though that all in not lost and some scientists will stick with it, as hard as it can be given the perception of the disease and give it the research is desperately needs and deserves for all those suffering for decades with no answers.

      luke

      December 23, 2011 at 12:48 am

    • So you won’t mind if an ME patient breath’s on your family and friend or donates blood and tissue.

      Give me a break.

      They are all backing away because the implications could not be more severe. It is the most disgusting vile piece of propaganda.

      Hol

      December 26, 2011 at 4:33 pm

      • And “Hol”, where is your evidence for your claims? Any evidence? There is none. So this makes YOUR claims “the most disgusting vile piece propaganda”.

        And no, just because XMRV was bad science does not mean that ME/CFS isn’t caused by virus(es).

        And what do you gain by hanging on to bad science?

        Tony Mach

        December 27, 2011 at 1:49 pm

  2. This is such a sad outcome. I feel especially sorry for the patients that are so desperately searching for a cause for this condition. Once again, poor experimental controls, lack of understanding of the pitfalls of the experiments they are using, and personal ambitions have caused so much heartache.

    Science should and could have handled this better. The partial retraction was a joke and we all knew this would be the outcome.

    Dave

    December 22, 2011 at 1:39 pm

    • More than any errors in methodology or failures to adequately control, this whole farce seems to have been brought about by deliberate deception. And it seems increasingly clear that there was a single driving force behind it.

      I can’t understand the motivation though. You cannot possibly carry this level of deception off. So it actually seems almost as mad as it is bad and sad.

      The worst part is that nobody really won anything. Mikovits is dead in terms of a mainstream career (watch this space for Wakefield-esque martyr career). Co-authors won’t feel too great. Science journal is tar

      Nucleotide Boy

      December 26, 2011 at 10:14 am

      • Sorry. Hit the wrong button and sent too early. But you get the gist! Nobody wins, though credit to those who fought to sort this mess out.

        Nucleotide Boy

        December 26, 2011 at 10:17 am

      • Rubbish, there is no evidence of poor control or contamination in either study.

        Too right no one is winning. Only more will become infected now. Great job scientists. You really have killed off the entire field.

        Hol

        December 26, 2011 at 4:34 pm

  3. A patient advocate, Khaly Castle, made this comment a few months ago, which aptly summarises what is so wrong about this whole affair. Science have just demonstrated how the ME community’s concerns, (and dismay) were, and remain, completely founded:

    “Patients are not pushing for a favorite pathogen. Patients are pushing for real science to occur and to take its course before the door gets slammed on ANY potential avenue of study. Patients are not stupid and are tired of being treated as such. Patients are particularly irked that they point out the discrepancies in scientists’and government’s claims, and said scientists and government continue to push the mistruths forward as if by saying it loud enough and long enough, it will be true.”

    Angela Kennedy

    December 22, 2011 at 2:33 pm

    • That comment seems to make no sense. Did you intend to post it somewhere else?

      autiemum

      December 22, 2011 at 3:33 pm

      • Why does that not make sense?

        Dave

        December 22, 2011 at 4:47 pm

      • I agree with autiemum. That comment by itself doesn’t clarify the discrepancies or what “mistruths” are being put forward. There is fundamentally bad science being done in this paper. That’s all this retraction is about. This doesn’t mean we are slamming the door on research into CFS. This just means this particular avenue of research has seen its research dollars wasted because of poorly done controls and experiments or worse, a deliberate misconduct.

        If you are promoting this research paper just based on your fear that this avenue of research will be abandoned, then you are not letting the real science to occur. This is the way science self corrects itself. Let scientists do their research. Letting a badly done research paper stand despite its failure to stand for itself in the face of close scrutiny does more immeasurable harm down the road.

        JKR

        December 23, 2011 at 11:25 am

      • JKR makes perfect sense.

        Jack

        December 23, 2011 at 11:31 am

    • I think the comment makes sense, but I’m not sure how it fits in the current context. I’ve read over a bunch of the articles on Abbie Smith’s blog (http://scienceblogs.com/erv/), and some of the CFS forums that are mentioned.

      First, my heart goes out to those suffering from CFS, but some of them really drank the kool-aid that Judy Mikovits was peddling. The comments section of Abbie Smith’s blog is just littered with vitriolic comments from the CFS community. It’s like they latched onto this new hope, and just couldn’t let go, despite the mounting evidence that the XMRV link was simple contamination.

      The issue here isn’t the discipline of science, but the complex interconnection between science, the news media, funding, and fame. And it seems like Mikovits rode this thing for as much fame and ego as she could.

      Don’t blame scientists for this one. Blame one scientist who, after two years of contrary evidence, continues to push XMRV, its now-dubious link with CFS, and its always-dubious link with autism.

      sfs

      December 22, 2011 at 9:02 pm

      • For those who see the off-base comments by some CFS patients please try and resist the urge to characterize a whole group of people from the actions of the few. There are millions of CFS patients world-wide and as in any very large group of people there will be a small sub-set with extreme and illogical viewpoints. I think this is just more prominent in the CFS community not because we are more mentally unstable than any other chronically ill patient population but instead because we have very few or no outlets. Like for example a doctor that understands what is going on and tries to help. There are only a few doctors in the US who even know what to do with us. I think the really outspoken off-base comments have come from patients who have let the anger all of CFS patients feel from time to time take control of them. I have gone from specialist to specialist and have been blown off or told I need to see a psychiatrist, that takes a tool on anyone no matter what your physical or mental state is.

        This is all really saddening to me; I wish the patients making the ridicules comments saw the damage it does to image of the patient population as a whole. I think patients are desperate for answers and they latch on any hypnosis that makes sense to them. If you do not understand the data and science it is easy to accept something using emotion instead of logic. That being said I do not believe XMRV is anything other than a lab contaminate and the vast majority of CFS feel the same way.

        luke

        December 23, 2011 at 1:17 am

      • Unfortunately, the vitriol wasn’t limited to patients. Many were responding to the name calling and nastiness initially dished out by Abbie herself and others responding to comments. A sad situation all around.

        KAL

        December 23, 2011 at 12:47 pm

      • @luke: You’re right. It wasn’t my intention to use a wide brush when characterizing a subpopulation of CFS patients.

        @KAL:
        I’m more sympathetic to Abbie Smith and her readers. Her blog has long had a snarky tone to it; among other things, she’s been a (semi-?)public face in arguments against intelligent design, which may require a bit of snark-infused armor. IIRC, the vitriol was returned when a subset of the CFS patients began to question the integrity of the scientists unable to validate Mikovits’ result, and then Abbie’s own integrity.

        That said, it is a sad situation. My heart goes out to the patients, but I’m deeply upset by the “blame-the-messenger” vitriol and paranoia that a few of them show. Statements like “What Science gives, Science takes away” show a deep misunderstanding of the nature of science, and the purpose of journals like Science.

        sfs

        December 23, 2011 at 1:44 pm

      • @Luke – well said.

        Lance

        December 27, 2011 at 6:12 am

  4. This is a very interesting story. I’d like to read both links – to the Chicago Tribune and to Abbie Smith’s blog, but both links take me to Abbie Smith. I think you might need to fix it. Thanks.

    faye flam

    December 22, 2011 at 6:34 pm

    • Fixed — thanks.

      ivanoransky

      December 22, 2011 at 7:09 pm

  5. “the authors acknowledged to Science that they omitted important information from the legend of this figure panel. Specifically, they failed to indicate that the CFS patient–derived peripheral blood mononuclear cells (PBMCs) shown in Fig. 2C had been treated with azacytidine as well as phytohemagglutinin and interleukin-2. This was in contrast to the CFS samples shown in Figs. 2A and 2B, which had not been treated with azacytidine.”

    This isn’t a full answer to “Figure-2C-gate” though… In the paper, lanes 1 2 4 5 and 7 from Figure 2C were labelled as normal, but in the powerpoint presentation, 2 and 5 were labelled as patient samples.

    Not mentioning the azacytidine may have been a mistake in the paper, but in that case the powerpoint is still wrong (and very misleading).

    A more worrying scenario would be if the powerpoint was correct…

    Neuroskeptic

    December 23, 2011 at 4:20 am

  6. Why did Journal retract this study?

    Is the other possible cause contamination of the laboratory samples?

    Greetings

    Murat

    December 23, 2011 at 7:02 am

  7. Dr. Ian Lipkin is actually coordinating two studies on pathogens in ME/CFS. Dr. Mikovits is only involved in the study requested by Dr. Frances Collins which is XMRV only.

    Dr. Lipkin is also separately coordinating a very large metagenomics study of 200 well characterized ME/CFS patients using cutting edge next generation sequencing. This study is funded by the Hutchins Family Foundation. Dr. Mikovits is not involved with this study.

    And “something” always causes disease whether scientists know the specifics or not. Although far better researched scientists still don’t know what causes Alzheimer’s, MS, or Parkinson’s either.

    KAL

    December 23, 2011 at 10:11 am

    • If you mean the pathophysiology of the diseases, they are well characterized, and molecular basis of each of their pathophysiology are equally well studied. We even know some genetic basis for the diseases or have strong candidates.

      JKR

      December 23, 2011 at 11:15 am

  8. This whole debacle is making me sick to my stomach. CFS patients are not doing themselves any good by behaving the way they are on a few forums and blogs I have read this evening for two hours. Some even seem to be even attacking fellow patients who aren’t quite sold on XMRV-CFS link, and there is history on these forums that goes back ages that I don’t have the energy or the concern to even reply and rebut some of the ludicrous arguments being made.

    JKR

    December 23, 2011 at 11:06 am

    • What a mess. And all because the traditional medical model simply does not work for CFS and similar problems.

      Jon Beckmann

      December 24, 2011 at 7:20 am

      • Oh, it would work if those at the helm would tackle their own biases and let traditional medicine do proper biomedical research – like the excellent work people like Alan Light do.

        Tony Mach

        December 27, 2011 at 2:44 pm

  9. What Abbie Smith showed is not the only problem with the manuscript. Even a person like myself, with rudimentary computer skills and photoshp can see that some of the WB bands are made up. If you look closer, at high magnification with slight adjustment of brightness and contrast you’ll be abel to see that bands do not blend into the background, rather they have different pattern, we were scanned at different resolution.
    Maybe a smarter person with better skills and softwares can look and verify this

    Schmuck

    December 23, 2011 at 11:13 am

  10. It is indeed tragic for patients, but the editor of Science, Dr Alberts, did the right thing in retracting this paper. He has been very fair and impartial – other editors would have retracted even earlier.
    As for the lead researcher, Dr. Judy Mikovits, her conduct (if these allegations are correct) is utterly disgraceful and unworthy of a scientist. It is one thing to make an honest mistake and self-retract, entirely another thing to fabricate results and brazenly continue to defend them. Shame.

    mathguy

    December 24, 2011 at 9:42 am

  11. The medical establishment will have you believe that Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is some sort of ‘mysterious illness,’ but it’s no mystery to me; CFS/ME leads to HIV-Negative AIDS, idiopathic CD lympocytopena (ICL), a clinical diagnosis that I possess.

    How can the AIDS establishment continue on with a stale “it’s caused by HIV” mantra when there are HIV-Negative AIDS (ICL) cases cited in medical journals dating back to 1992?

    While millions of ailing immunodeficient CFS/ME patients get purposefully belittled and neglected, perfectly healthy HIV+ people are allocated billions of dollars in taxpayer money. How can that make any sense to anyone?

    It’s so easy to see that the medical establishment simply has these paradigms (CFS, HIV) inverted. AIDS patients are simply more CFS patients, who happen to harbor a seemingly harmless virus, HIV. AIDS patients are just the tip of the CFS iceberg, and it’s already well-documented that HIV is not the cause of CFS/ME.

    AIDS + CFS + ME = one catastrophic epidemic (not caused by HIV)

    See how easy?

    Now that the ‘mystery’ has been solved, could we please stop wasting time and re-allocate all the HIV funding into CFS research?

    cfsboston

    December 25, 2011 at 10:47 pm

  12. And just for the record, some of the problems of the Lombardi et al 2009 Science paper:

    - Failure to state if samples were tested in a blinded fashion
    - Failure to state the reason why not all tests were done on all samples
    - Failure to sufficiently describe each employed test method
    - Mislabeling of at least one slide
    - Omission of the usage of 5AZA
    - Failure to publish viral gene-sequences
    - Failure to do phylogenetic analysis of viral gene-sequences
    - Failure to show integration into the human genome

    Notice how science choose only one subset of these problems as cause for their retraction? And didn’t mentioned the problems they could have caught in peer-review? If they would have done a proper review?

    Tony Mach

    December 27, 2011 at 2:34 pm

  13. To those ‘confused’ by my quickly submitted comment, go over to the entry on this blog about the retraction of the Lo/Alter paper. Some of you here are already exhibiting the usual problems I’ve alluded to in my posts over there- attacking patients and their supporters as irrational, ignorant, hostile recalcitrants. This is a common feature of the discourse on this whole subject (ME/CFS, possible retroviral involvement etc. etc.) and these threads invariably degenerate so that the facts/arguments of the matter get lost. To those of you GENUINELY interested in the scientific process and how ‘retractions’ are constructed within social and political contexts – an important part of science as anyone who understands Thomas Kuhn’s discussions at least will understand – please note how quickly ME/CFS sufferers and their supporters are constructed in such prejudicial ways. Meanwhile, there are major discrepancies in the ‘scientific process’ pertaining to the response to both the Lombardi and Lo papers which has made a mockery of science. Those of you reading retraction watch who are genuinely interested in ‘retraction’ as a ‘window into the scientific process’ – as opposed to those merely pursuing an agenda to kill further research into a possible retroviral link with ME/CFS and/or promote psychogenic explanations for ME/CFS – please note how relevant Khaly Castle’s concerns are, as demonstrated even by certain responses here for a start.

    Angela Kennedy

    December 28, 2011 at 3:37 am

  14. @ Tony Mach – are you REALLY suggesting ‘Science’ didn’t peer review the Lombardi Paper? Or are you just giving your opinion that the peer review wasn’t adequate, in your opinion? That is not a problem for me. As I believe you know, I have made formal complaints to the Lancet about the PACE trial on the basis of the many examples of profoundly flawed methodology that has made the conclusions of that trial not only scientifically unsafe, but quite literally unsafe for ME/CFS patients. I have asked for the trial methodology, and my own and others’ concerns about the discrepancies in this, to be scrutinised by independent reviewers. My opinion is that the peer review process for PACE was inadequate, based on all the evidence available so far, so I might sympathise (though not necessarily agree) with your belief that Lombardi et al might have problems with peer review: though the Lo retraction throws further problems on that issue, bearing in mind the tranparently STRICT peer review THAT paper underwent. Retractions do highlight issues with peer review, of course.

    Angela Kennedy

    December 28, 2011 at 3:46 am

  15. I have a question if I may. I know this thread is rather old now, but my question relates to XMRV and those studies that appeared to support the presence of this retrovirus in human samples, as well as those studies relating to XMRV and prostate cancer I suppose.

    The overwhelming evidence and now the firmly established belief is that XMRV contaminated those human samples prior to them being tested or during testing. The main paper proposing the link with human infection has been retracted. So what happens to the previous papers purportedly showing ‘positive’ associations either in respect of CFS patients or prostate cancer?

    Are those authors obliged now to re-examine their studies and identify the contamination? I know some have but none have resulted in retractions – so what would warrant a retraction when the main paper has been effectively debunked?

    Or is it a case of the science has moved on now and so all those papers should be disregarded? I mean how does one know unless they are marked in some way?

    Apologies if this is a little outside your remit but it keeps coming up. The whole – ‘Well when are they going to retract the other papers then?’ and ‘What about those prostate cancer studies?’ and I don’t know enough about how the publication process (assuming there is one and that it applies).

    Thanks

    Jack

    January 16, 2012 at 10:42 pm

    • Hi Jack, thanks for the question.

      I assume you’ve seen that the PNAS XMRV-CFS study was also retracted: http://retractionwatch.wordpress.com/2011/12/26/another-shoe-drops-as-authors-retract-pnas-chronic-fatigue-syndrome-virus-paper/

      I haven’t heard anything about the prostate cancer-XMRV studies.

      I’m not sure scientists feel “obligated” to make notes on their papers, or even re-examine them, although they obviously should at least do the latter. This works better when scientists use tools such as “email me when this paper is cited,” since a retraction will count as a citation and trigger an email. But most don’t, as far as I can tell.

      I’m not sure if that answers your question; there aren’t any rules, really, and I can only describe the behavior I’ve seen, mostly anecdotally.

      ivanoransky

      January 17, 2012 at 9:08 pm

      • Thanks Ivan.

        That XMRV is a novel retrovirus is not in doubt. The doubt comes from the lack of evidence that it has infected/replicated in humans. And I suppose then that any papers that had stuck to the non-human infection angle i.e. simply studied XMRV in cell lines and primates etc. – don’t really need to consider retraction. This might apply more to the prostate cancer studies.
        However, those XMRV/CFS studies in particular that alleged a positive finding in human blood would be the ones in need of a review and/or citation.
        I notice that of the latest XMRV papers i.e. the pigtail macaque study from Del Prete, Coffin and Pathak, they do now review previous papers and talk about the lack of evidence for human infection etc. and provide references as perhaps one might expect from ‘better’ papers.
        So in a way I suppose the science has moved on: looking at forcing XMRV into animals to study and learning more about it and seeing how it cannot survive in blood etc.
        It would take another paper positing an association with human infection for the research to move in that direction again – I hope though that lessons have been learned from all of this which is kind of why I asked my original question. If they don’t review/retract/cite these former studies that supported the link with human infection – how will people know they were ‘spurious’?
        Anyway, thanks again for the reply.

        Jack

        January 18, 2012 at 4:07 am

  16. This was a very sad outcome given the number of people who suffer from chronic fatigue syndrome who had a momentary glimmer of hope.

    Jane's Addiction

    February 5, 2012 at 4:25 pm

  17. In the U.S. last year, the NIH spent $3.1 billion ‘researching’ (i.e., drugging)perfectly healthy HIV+ people. Sick, ailing immunodeficienct (some of us dying) CFS/ME patients received a meager $6 million.

    How can it make sense to you? Source: http://report.nih.gov/rcdc/categories/

    I demand a revolution!

    7 Step Plan to resolving our World’s catastrophic public health disaster:

    1. Demand research funding parity for CFS with AIDS.
    2. Suggest that CFS & AIDS be researched together by scientists rather than as separate entities.
    3. Urge the CDC to move their AIDS division under the CFS umbrella so they research all the infections that AIDS and CFS have in common.
    4. Urge that AIDS organizations (like AmfAR) include CFS under their umbrellas so that CFS advocates don’t have to reinvent the wheel.
    5. Demand that the White House, Fauci and the Director of NIH make a public statement that (just from what we know today) in terms of the immune dysfunction and human suffering, CFS is just as serious a public health problem as AIDS.
    6. Request that an annual international joint CFS & AIDS conference be held by the World Health Organization.
    7. Suggest that next December 1st be declared the first “World CFS/AIDS Day.”

    I stopped fighting for myself a long, long time ago.

    I fight for humanity.

    To learn more about HIV-Negative AIDS, and to see the *new* face of CFS/AIDS:

    http://www.cfsstraighttalk.blogspot.com

    Could I be you?

    CFSBoston

    February 5, 2012 at 5:10 pm


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