Scientist Smackdown: Is a Virus Really the Cause of Chronic Fatigue Syndrome?

By Andrew Moseman | January 6, 2010 5:18 pm

chronic-fatigue-virusAn estimated three in 1,000 people suffers from the mysterious affliction chronic fatigue syndrome. Those people were probably enthusiastic in October when a team of U.S. medical researchers released a study arguing that not only is the syndrome real (some doctors dismissed it as purely psychological “yuppie flu”), but also that they’d connected it to a specific virus. DISCOVER covered the hubbub after the paper came out in the journal Science.

But now, in a study in PLoS One, a British research team has cast doubt on the American team’s findings, saying there’s no conclusive link between the virus and chronic fatigue syndrome, which is also known as myalgic encephalomyelitis.

The U.S. team’s findings sounded robust when they came out. They found the murine leukaemia virus-related virus (XMRV) in blood samples of 68 of 101 patients diagnosed with chronic fatigue syndrome. Just eight out of 101 healthy “controls” drawn at random from the same parts of the US also tested positive, suggesting that XMRV played a key role in triggering the condition [The Independent]. When the scientists from Imperial and Kings colleges in London attempted to replicate these findings, however, they found nothing of the sort. Of the 186 people with the syndrome that this team tested, not one showed signs of XMRV, or of any related virus.

Study coauthor Myra McClure of the Imperial College also criticized the U.S. team and the journal Science for rushing the findings into print in October. “When you’ve got such a stunning result you want to be absolutely clear that you are 1,000 per cent right and there are things in that [previous study] I would not have done. I would have waited. I would have stalled a little” [The Independent], she said.

As for the new study conducted in London, McClure declared: “We used very sensitive testing methods to look for the virus. If it had been there, we would have found it…. We are confident our results show there is no link between XMRV and CFS, at least in the UK” [The Guardian]. But the U.K. team says its contradictory findings could have resulted from differences in patients. According to the new study, the discrepancy “may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.”

Though McClure and her colleagues can’t say for sure how they and the Americans came to such different results, they wanted to put a stop to the rush of patients who started seeking antiretroviral treatments for chronic fatigue after the Science paper came out in October (XMRV is a retrovirus, like HIV). They say potent antiretroviral drugs should not be used to treat CFS because there is not enough evidence that this is necessary or helpful. The drugs may do more harm than good, they say [BBC News].

This might throw a wrench into the plans of Judy A. Mikovits, the lead author of the U.S. paper, to go ahead with antiretroviral testing. But the “avalanche of subsequent studies” that one medical researcher predicted to The New York Times after Mikovits’ paper is sure to continue.

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Image: Whittemore Peterson Institute

CATEGORIZED UNDER: Health & Medicine
  • Myrtie Johnson

    It’s odd that Dr. McClure criticizes the consortium of researchers who published in Science last October for rushing into print.

    The paper by those authors–from the Whittemore Peterson Institute, the Cleveland Clinic, and the National Cancer Institute–was reviewed for six months before publication. McClure and her colleagues, on the other hand, paid to have their paper appear online after only a few *days* of review.

    McClure’s failure to replicate the Science findings may stem from the fact that her sample was selected by psychiatrist Simon Wessely, who has long considered ME/CFS a psychiatric disorder. Rather than being true ME/CFS patients, those tested may have been fatigued for psychological reasons.

  • Myrtie Johnson

    Dr. Suzanne Vernon’s response to the Wessely/McClure paper may be viewed at http://www.cfids.org/cfidslink/2010/010603.asp.

  • blick

    Myrtie Johnson, you should have put quotes around your post, as the comment you wrote was cut and pasted from the WPI web site.

  • http://xmrv.blogspot.com carlos

    Official Press Release from WPI states clear that what this UK study has failed to do, is not only to detect XMRV in CFS patients, they have mainly failed to do a replication study published in Science last October, and therefore the UK study is meaningless scientifically speaking.

    http://www.wpinstitute.org/news/docs/WPI_Erlwein_010610.pdf

  • http://www.wpinstitute.org Whittemore Peterson Institute

    FOR IMMEDIATE RELEASE

    Frankie Vigil
    R&R Partners for
    Whittemore Peterson Institute
    775-336-4555
    frankie.vigil@rrpartners.com

    Official Statement from the Whittemore Peterson Institute Regarding UK Study

    The Whittemore Peterson Institute (WPI) has reviewed the paper entitled “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome.” This study did not duplicate the rigorous scientific techniques used by WPI, the National Cancer Institute and the Cleveland Clinic, therefore it cannot be considered a replication study nor can the results claim to be anything other than a failure not just to detect XMRV, but also a failure to suggest meaningful results.

    The scientific methods used by WPI are very exact and require specific techniques to ensure accuracy. Differences in techniques employed by Erlwein et al. not only explain their failure to replicate the WPI study, but also render the conclusions meaningless. These differences include, but are not limited to the following:

    1)blood sample volumes and processing;
    2)patient criteria/population differences;
    3)number and type of tests done to assure accurate results, including white blood cell culture;
    4)use of a molecular plasmid control in water versus a positive blood sample; and
    5)different primer sequences and amplification protocol used to find the virus, which were not validated by a clinical control.

    The WPI study was published after six months of rigorous review and three independent lab confirmations, proving that contamination had not taken place and that infectious XMRV was present in 67 percent of CFS patients diagnosed according to the Canadian and Fukuda criteria. In contrast, this latest study was published online after only three days of review. Significant and critical questions remain as to the status of patient samples used in the UK study as those samples may have been confused with fatigued psychiatric patients, since the UK has relegated “CFS” patients to psychiatric care and not traditional medical practices.

    “Little is known about the prevalence of XMRV world-wide, much less the incidence of XMRV in ME/CFS or prostate cancer” emphasizes Dr. Judy Mikovits. “WPI and its NCI collaborators are actively engaged with international research teams to investigate these important questions.”

    WPI does not recommend the use of anti-retroviral drugs that have yet to be proven to be effective in treating XMRV infection. However, several large pharmaceutical companies have expressed interest in developing anti-retroviral and immune modulating drugs that will effectively treat XMRV associated diseases.

    WPI looks forward to the results of other scientific groups around the world, serious about replicating its scientific results, by using the same techniques as WPI and its collaborators. The fact that XMRV was detected in 67 percent of the CFS samples in the U.S. study determined a significant association between XMRV and CFS, demanding a much more serious inquiry by responsible health agencies around the world as to the cause of this debilitating disease.

    -###-

    Whittemore Peterson Institute
    The Whittemore Peterson Institute for Neuro-Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of the immune system and the nervous system, often results in lifelong disease and disability. The WPI is the first institute in the world dedicated to X associated neuro-immune disease (XAND), and other X associated diseases, integrating patient treatment, basic and clinical research and medical education.

  • Anne

    Rushed into print?

    The WPI study was peer reviewed and only published after two independent labs had verified their findings.

    McClure needs to do her homework.

    It seems she can’t be happy simply to stand by her own findings and needs to criticise WPIs process to give her own study extra weight.

    McClure makes it sound as if the London study was published to prevent people rushing off to try antiretrovirals. That the motivation was to stop patients pursuing a certain type of treatment. Is that good science?

  • Another Anne

    What’s been sad about watching this unfold is how quickly the press seizes on this study as if it were equal to the WPI study. They didn’t use the same methodology or cohort, and the standards for publication in the two journals are much different.

    The cohort issue is huge–the Brits, because they think it’s psychological, exclude people with evidence of organic illness, including things that are hallmark signs of CFS. It’s possible that no one tested actually has CFS.

    The rushed into print thing is pretty hilarious given this journal gave this study three whole days.

  • Emily

    “(some doctors dismissed it as purely psychological “yuppie flu”)”

    Do you have a source for this?
    It was the media who coined the term “yuppie flu”. If you check your facts I think you will be hard pressed to find one doctor who would go on record as saying CFS is purely psychological.

  • Ed

    The WPI’s press release casts more doubt on the validity of their claims than ten contradictory studies possibly could. I’m not surprised though after all the hyperbole from WPI people on the talk-show circuit last fall.

    Seriously: the Brits got different results because they used a different blood collection tube? That was point 1. Yeah, they probably used different chairs for the patients to sit in and needles to poke them with and freezers to store the samples too, but it’s irrelevant. Point 2, WPI says patient and population differences could be responsible. Maybe if you assume CFS is so vague as to be diagnostically useless, or if this is the first virus ever that’s scared of air travel. Point 3. Number of samples? The new article studies almost twice as many patients. Point 4, WPI says the other people didn’t use a positive blood sample. Well, if there aren’t any positive blood samples you can’t use one now can you? Same thing for lack of a “clinical control” in WPI’s Point 5.

  • Emily

    If I understand correctly, the British team didn’t test any samples from healthy people (or didn’t report their findings). The WPI found XMRV in 3.7% of their healthy controls. This has implications beyond CFS, to the general population. Isn’t it important to know how many healthy people would test positive for XMRV in the London study? If they found no XMRV in any healthy controls either, how would the study prove or disprove anything about CFS?

  • Hip

    One of the co-authors of this study, Simon Wessely, has a vested interest in the outcome of such virus studies. Simon has staked his entire academic career on the laughable idea that neurological diseases like chronic fatigue syndrome are caused by purely psychological factors.

    Therefore Simon Wessely would be the last person you would want in a study like this: if he finds the virus in CFS patients, he shoots himself in the foot, and his career may never recover. So I wonder just how hard he looked for this XMRV virus.

  • cheap copays save the day

    CFS is an over diagnosed disease that lines the pockets of placating Dr.’s, while providing a cop out for the sheep that go bleating into their offices. We are the fattest, laziest, most decadent society ever. CFS diagnosis goes up at the same rate our waist lines do.

  • Gil

    @9: Those are all actually bigger deals than you might think, prima facie. Different blood collection tubes have different preservatives, and can effect what one can find in the sample. that’s one of the reasons they take multiple tubes for testing when you donate blood: the different tubes are for different tests. Using a positive control is also basic science, and your positive control does not come from your unknowns (the patients). Not using a positive control means that you haven’t proven your testing methodology would’ve detected the agent if it was present, which means negative results are meaningless.

  • Ed

    Gil is right, blood anti-coagulants like EDTA, heparin, citrate can affect common medical tests. They can also affect DNA isolation and PCR. There is no evidence they have sequence specific effects like commenters are saying, like the WPI group could amplify XMRV because they used heparin and the UK people couldn’t get this sequence because they used EDTA. Do your washes right and your DNA isolation right and include inhibition controls like the UK group did and it will not matter what anti-coagulant you use.

    Of course the UK people used a positive control. They even did a titration of their positive control down to 1 copy and their test was sensitive to one copy per sample. The UK people had six negative controls and one specificity control and two positive XMRV controls in every PCR run. The PCR technician did not know which samples were which unlike the WPI people. It is very difficult to believe the UK people would not have found any XMRV with all the positive and negative controls and proven sensitivity and specificity and experimental blinding and contamination precaution.

    It’s easy to contaminate a sample or a whole panel of samples or your entire lab. It’s not easy, no it’s currently impossible to take one specific DNA sequence out of a sample while leaving control DNA sequences unaffected.

  • John

    I can tell you with all certainty that CFS is not caused by psychological factors. In fact, it’s the other way around. Psychological and neurological aberrations are caused by CFS. This assumes that such a person actually has CFS and not some other issue. This is the purpose of the WPI effort. People will one day prove that our thoughts and feeling are more of a slave to our pathology/environment than our pathology is a slave to our psychological processes! Never put the cart before the horse.

  • John

    Also, don’t let your pride get in the way of finding the truth. Lastly, for all of you who think CFS is psychological, just one look at the so-called treatment ‘reverse-therapy’ will show that this way of thinking is utterly preposterous, non-scientific and sheer quackery. Here is a quote from a webpage (http://www.reverse-therapy.com/downloads/article.html) -
    “In this approach we reverse the (understandable) urge to get rid of the symptoms of CFS/ME/FMA straight away. Instead we focus on why the physical symptoms are still being produced, without resisting them. When we have listened to the message of the symptom, and the environmental problem it is based on, we can facilitate its release. The bodymind reverses the symptoms naturally because it is responsive to new learning and because emotions, thoughts and physical reactions are all aspects of the same mind-body learning state. For example, an individual with Irritable Bowel Syndrome might have had the perception, ‘this is upsetting me, making me angry and I can‘t cope’, when faced with emotional conflict in any given situation. This manifests itself initially through the Hypothalamus acting on the Endocrine and Autonomic Nervous systems to over-activate the smooth muscles and glands in the bowel. For example, the underlying message could be: ‘My symptoms of IBS are with me as I have not so far learnt to digest anger’. Once this message has been understood and acted upon the bowel symptoms (which are only the physiological expression of the bodymind learning state associated with conflict) can be reversed. The hypothalamus is able to release them because it is now acting on new messages from the thinking centres/emotional brain that tell it that the threat has been recognised and dealt with.” WTF is this bodymind BS? Don’t you think this is outrageous (I have not so far learnt to digest anger)?After reading this, WPI’s committments, efforts and purpose become so much more rational and real.

  • KAL

    A number of pertinent, accurate and scientific responses have been made. Inaccurate and/or unscientific opinions, while interesting perhaps, are less relevant.

    Yes, Ed, exact protocols do matter in science regardless of the subject- for example if one study is on yellow paint and another study uses red paint, the red paint study is not a replicative study just because both studies used paint. It is far more complicated than that. Ask any reputable scientist.

    Rigorous testing is part of the scientific process and science has always been a contentious process – once again regardless of the subject. Dr. Robert Silverman MD, who is an expert on XMRV and the RNase L immune abnormality found in conjunction with subsets of CFS and prostate cancer patients, states people should be wary of any hastily performed and presented studies. As he has correctly pointed out previously, it takes more time than that to do a proper study, as frustrating as that might be for all involved.

    This is actually just the beginning. Many well known, highly regarded and serious virologists are in the process of rigorous and soon to be standardized studies regarding XMRV in CFS and other diseases worldwide.

    Regarding this specific study, as someone else noted, it is unusual to have three psychiatrists, well known for their adamant opinion that CFS is a psychosomatic disorder because they do not agree with the medical evidence, to be authors of viral research in CFS. While not a conflict of interest, common sense tells us it does suggest a potential bias. (CFS is by the way is officially listed as a neurological, not psychiatric, disease by the World Health Organization under ICD-10 G93.3 which specifically precludes it from being listed as a psychiatric disorder. Most biomedical experts in the field refer to it as a neuroimmune disease.)

    Perhaps it is best to use Dr. Wessely’s own words. Regarding viral involvement in CFS he states:

    “…the search for infective causes and triggers for psychiatric disorders has never ceased …”

    “…it is clear that the drive to find a somatic biomarker for chronic fatigue syndrome is driven not so much by a dispassionate thirst for knowledge but more by an overwhelming desire to get rid of the psychiatrists.”

    Wessely S (2009). Surgery for the treatment of mental illness: the need to test untested theories. James Lind Library.

    It is rather curious that a psychiatrist who holds the above views would be a part of viral study looking into a somatic explanation for CFS.

    Time and much more rigorous research will tell. Regardless of the findings such studies will hopefully expand the knowledge base and provide a basis for further study in many areas.

    Note to Anne: The WPI, Cleveland Clinic and National Cancer Institute study published in the highly regarded Science journal last October actual verified the study in three not two independent labs.

  • KAL

    comments loaded twice

  • Mary

    @emily “If you check your facts I think you will be hard pressed to find one doctor who would go on record as saying CFS is purely psychological.”

    You may not find many doctors willing to go on record to the media with such a statement, but if you have CFS, you will find PLENTY of them practicing that belief.

  • Anne

    KAL. Thank you for correcting me on that.

  • Emily

    Mary, I don’t doubt that at all. I’m just tired of seeing bloggers cite the archaic “yuppie flu” bias without scientific support. Who are the “some doctors” cited in the first paragraph? If the writer is not willing to quote from their published scientific articles, why would he give them this credit in his own article?

  • Myrtie Johnson

    The results of the WPI study, which found XMRV, were confirmed by both Dr. Robert Silverman, who discovered XMRV, and Dr. Francis Ruscetti, who co-discovered HTLV (in Gallo’s lab). Their names are on the paper as co-authors. In other words, the study had independent replication built in.

    The results of Wessely’s study, which didn’t find XMRV, were confirmed by…no one.

  • Ed

    True but if samples are contaminated every lab testing them should get a positive result. Cleveland tested 11 samples and NCI tested 20. How long have these samples been banked, and where? The WPI paper says their cohorts were described by DeFreitas, PNAS, 1992. The DeFreitas paper just has 30 patients. So are WPI samples 101 samples from 30 patients? In DeFreitas 19 are children from family clusters. Are the positive samples for WPI also related? Are the DeFreitas patients with positive HTLV Westerns the same samples with positive XMRV Westerns in WPI? How did WPI pick which samples for which figures? Did they do Western for all samples? Was the selection random? Were the samples related?

    Actually who cares about these samples, what is important is do the results apply to other people with CFS. So do people who are not using WPI samples and reagents get a positive result?

  • Alan

    Someone should look into the specifics of Simon Wessely’s financial ties with UNUM (and possibly other insurance companies), who stand to lose billions if ME/CFS is found to be of organic (rather than psychiatric) origins. And look into it SOON, before documentation can be shredded.

  • InvestigativeRp

    Simon Wessely doesn’t have anything to do with it. Someone should look into Dick Cheney’s and Mahmoud Ahmedinejad’s ties to the International Brotherhood of Psychiatric Conspiracy. No doubt Cheney and Ahmadinejad have conspired to hide the real truth about CFS: it is caused by a reptile virus and can be cured by a common extract from the blood of the Loch Ness Monster. The Nessie cover-up itself is of course why Dick Cheney installed his buddies Tony Blaire and Margaret Thatcher in power. From what I hear, Ahmadinejad and B. Netanyahu sent a joint MOIS/MOSSAD task force to excise all copies of XMRV from Simon Wessely’s blood samples. CBT is an old KGB technique to get us all to forget what we know about this.

  • Hip

    VESTED INTERESTS OF SIMON WESSELY

    One of the co-authors of this study, Simon Wessely, has a vested interest in the outcome of such virus studies. Simon has staked his entire academic career on the idea that neurological diseases like chronic fatigue syndrome are caused by purely psychological factors.

    Therefore Simon Wessely would be the last person you would want in a study like this: if he finds the virus in CFS patients, he shoots himself in the foot, and his career may never recover. So I wonder just how hard he looked for this XMRV virus.

    For more info on this vested interest, Google: “Wessely School”

    The odd thing is, the authors declared in this study that they have no competing interests: not true! It is very much in the interest of Simon Wessely to not find this XMRV virus.

  • keith

    They didn’t do this study to stop people from tasking antiviral drugs with potential side effects. That’s such a deceptive statement. In the UK the medical insurance is state run so the government wasn’t giving people antivirals based on one american study. Wessely just wants to keep CFS psychatric for the health insurance companies and government.

  • Dr. Roger Mazlen

    Dr. Irwin Gelman and I found and published data on CFS patients and controls
    in which we demonstrated that a significant percentage of CFS patients had
    positive assays for reverse transciptase due to the presence of endogenous
    retroviruses, some with more than one type. There were some positives among the
    controls as well. Many CFS patients tested positive for P15 E which has
    immunosuppressive properties.

  • http://www.earthclinic.com parhatsathid

    It might not have been other virus. At the very least I was cured of CFS with just clove oil. A friend of mine had that, and magnesium and malic acid being the main components, with vitamin Bs as supporting one was also cured. The typical medicine used is Venlafaxine which a form of amphetamine. The CFS don’t however work using the typical antiviral as most virus produces low grade fever, or if along the spinal column, as in Lou Gehrigs or Polio,are similar too in symptoms, although Lou Gehrig’s don’t cause inflammation, they respond well to antiviral supplements (e.g. lysine, glycine, threonine) with possible blood brain barrier except for the threonine. In any event, these cause weakness of the muscle as in MS, but they don’t cause tiredness, which is more in line with brain metabolism rather than motor/neuron control in typical virus infected individuals. They maybe other forms of virus, but they are really hard to detect as they get destroyed easily and hence do not get detected. The Americans should repeat a study using different patients from different country however, since they did the initial studies. If they can repeat that, at the very least they can pinpoint whether the British study was correct or not. For example, get some patients from the British and see if you get the same results from there. That might possibly resolve some of the issue.

  • http://www.earthclinic.com parhatsathid

    On personal side, CFS seems to work with certain antiviral supplements such as magnesium, threonine, clove oil, are some. So it might not be XMRV or it might be other viruses.

  • ShowalterdontlikeME

    Simon Wessely talking about Rudolf Hess in 2006.

    “You have to remember that this is a guy who believes in astrology, numerology, homeopathy, and so on. This is a guy who takes all sorts of herbal, and alternative and natural medicines. So he believes that his food and environment is causing his symptoms, and I’ve got lots and lots of patients like that. It’s not in itself unusual, but then when these patients come under stress, it’s quite easy to slip into paranoid states”

    I think this might give an insight to what Wessely thinks about CFS patients.

  • http://none John

    KAL said on 7 January “CFS is by the way is officially listed as a neurological, not psychiatric, disease by the World Health Organization under ICD-10 G93.3

    UNTRUE, CFS is NOT ICD-10 G93.3. ME is. There is no such illness as ME/CFS. Only ME as defined by Ramsay is listed as neurological in ICD

    “CFS and M.E. should not be considered the same illness.”
    -Dr. Byron Hyde-
    http://www.name-us.org/DefintionsPages/DefHyde.htm

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    My brother suggested I might like this web site. He was once totally right. This submit truly made my day. You cann’t consider simply how much time I had spent for this information! Thank you!

  • Matt

    IMHO the Imperial College was only doing it’s part in downplaying XMRV because this would cause wide spread paranoia that we have yet another threat to our blood supply that no one has a clue in how to fix it. Kind of like the financial mess the USA and Europe are facing.

  • Shelby Kayat

    I like all their sounds this lady which means perfect they say no one is ideal and yet she is

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