XMRV and CFS – It’s not the end

22 December 2010

Yesterday the Chicago Tribune published my reaction to the four papers on the retrovirus XMRV published this week in the journal Retrovirology. I was quoted as saying ”These four papers are probably the beginning of the end of XMRV and CFS”. I wish to retract this statement and explain my reasons for doing so.

Early Monday a reporter for the Chicago Tribune, Trine Tsouderos, sent an email asking for my thoughts on four XMRV papers that had just been released (paper one, two, three, four). I read all four papers and decided that they raised serious concerns about the role of XMRV in human disease. Specifically, the four papers demonstrated different ways that assays for XMRV could be subject to contamination with murine viral sequences. I wrote an email to Ms. Tsouderos outlining my summary of the papers, and later that day her article was published. My statement was reproduced exactly from the email I had sent her, so I was not misquoted.

I then set out to write about the papers for my blog about viruses. I read the papers over again, and began checking XMRV sequences in Genbank. I also began an email correspondence with authors of three of the four papers, and spoke with my virology colleagues here at Columbia. As a consequence of this additional research I decided that my initial impression of the papers was incorrect, which is evident in my post entitled ‘Is XMRV a laboratory contaminant?‘. Almost immediately after publishing the piece readers began to ask why my comments to the Chicago Tribune had such a different tone. I concluded that a retraction and explanation were necessary.

Upon re-reading three of the four Retrovirology papers it became clear to me that they show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised by these findings. Clearly any new studies done on XMRV should keep in mind the potential for contamination from PCR kits and murine nucleic acids.

I was initially more troubled by the fourth paper by Hue and colleagues. There are four major findings in this paper (gag PCR primers are not specific for XMRV; the virus is present in 5 human tumor cell lines; two XMRV isolates are nearly identical to a virus from the human prostate cell line and also contain an insertion from the murine retrovirus MoMLV; and there is more nucleotide diversity in viral sequences from 22Rv1 cells than in all the patient XMRV sequences). The fact that two XMRV isolates seem to be laboratory contaminants – judged by the presence of MoMLV sequences – was initially unsettling until it became clear that other XMRV isolates do not have this insertion. That leaves the fourth finding – that XMRV from 22Rv1 cells appears ancestral to, and more diverse than, all the human XMRV sequences. I decided that this result was less troublesome than I had originally believed, in part because it is not clear that the differences among the 22Rv1 viruses did not arise during PCR amplification.

My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination.

In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others.

I would like to apologize to anyone who was offended, angered, or disappointed in any way by my statement to the Chicago Tribune. It is my goal to educate the public about virology, and clearly I did not do that very well.

There are at least two lessons that you can take away from this incident. First, that I make mistakes, and that I’m willing to admit it. Everyone does, including scientists. Second, if I had difficulties interpreting these papers, how would non-scientists fare?

  • Anonymous

    Having trouble posting this

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  • lancelot

    hell yeah, it’s not the end just the beginning for XMRV!

    What’s going to be the end is the UK’s rubbish studies.it’s junk for a junk government run healthcare.

  • Marymsch

    When fellow economist Joan Robinson once criticized John Maynard Keynes for being inconsistent over the breadth of his work, he famously answered, “When someone convinces me that I am wrong, I change my mind. What do you do?”

    Thank you.

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  • Justin Reilly, esq.

    Prof. R.,

    Thanks for the updates on XMRV! And thanks for your retraction of ‘the end of XMRV and CFS’. Unfortunately, usually what gets reported is the press release and then a few sound bites. I trust you now see that the ‘evildoers’, eg CDC, NIH (at least in the past) and the small cadre of UK psychiatrists and their cronies, take advantage of this and issue press releases packed with lies based on weak or invalid ‘studies’. This kind of talk all seems like kooky conspiracy theories until you actually witness it up close, huh? Now that you see how they just stack lie upon lie in the press in their war on ME science and patients, PLEASE speak up loudly to your colleagues, the media and HHS about how ME science is being railroaded! You would be doing a huge amount to advance science! Thank you for your consideration.

    Justin Reilly, esq.

  • Justin Reilly, esq.

    I agree. CDC, NIH and the small band of UK psychiatrists have been waging a well calculated war on ME science and patients for 25 years on behalf of insurers. This putting out a press release packed with bald faced lies is just a repeat of what they’ve done a thousand times before. If charlatans, accepted as authorities, lie over and over to the press, the media will just act as stenographers and then most lay people and even doctors and scientists will believe the lies and insurers can avoid making “chronic disbursements” (as a CDC “CFS” naming committee member wrote in an email) for decades.

  • Justin Reilly

    I have no evidence that Prof. Wessely is getting rich off of persecuting patients. He could be getting bribed by insurers (though again i have no direct evidence of this). I think it’s more likely that as a quid pro quo he is backed and supported by insurers (including the British govt). By backed and supported, I mean that they use their influence to make sure Wessely gets and retains prestigious tenured posts and can publish his papers in top journals. This sort of prestige and security is probably part of his reward. Also, I assume he takes a sadistic pleasure in persecuting the most vulnerable. I can think of no other reasonable conclusion.
    His father was incarcerated in a concentration camp. Perhaps he sees a duality in the world that if one is not a abuser, then one is a victim, so he tries to be the abuser.

    I must also agree with Suze B. Mikovits, the Whittemores and Dr. Peterson are not getting rich off of WPI! The road to hell is paved with cow-patties like Wessely.

  • Justin Reilly

    I agree. I am not science oriented, but I have had to basically study medicine for years while extremely sick, in severe pain and unable to think straight in order to find out what is wrong with me because Medicine is not willing to. That I and so many millions of others have to go through this (or else struggle just to live) because Medicine will not help us is an absolute disgrace. I don’t mean to be rude, but after reading the news articles, reviewing the papers, WPI’s statement and a few patients’ forum posts, I came to the conclusion that this was just more lies from our persecutors. If I and so many other patient lay people can quickly come to the right conclusion, why didn’t you? My point is that everyone including clinicians, researchers and HHS administrators MUST GIVE PATIENT- EXPERTS (AND WE ARE INNUMERABLE) THE RESPECT AND DEFERENCE TRUE EXPERTS DESERVE!! I’m sure that if you had just emailed a couple of patient-doctors/scientists/professors/PhD’s that crowd the forums they would have straightened you right out and your initial statement to the Chicago Tribune would have been accurate! Why is it that the patients have to do and fund all the work and then we are not listened to? Again, disgraceful.

  • Justin Reilly

    They certainly are not sweeping the contamination issue under the rug. That’s ludicrous. There is very serious prejudice in the major journals against publishing studies showing viral (especially retroviral) associations with ME. So the fact that they satisfied the Science reviewers specifically on the issue of contamination (prior to publication) speaks volumes to me.

    Also, these papers were saying sloppy PCR can pick up contamination. We already know that. That’s the very reason why the Science paper’s authors tested with multiple methods.

    What do you say to WPI’s assertion that (1) it’s impossible for a person to mount an antibody response to a contaminant and that (2) the positive cultures also show it was not contamination, inter alia?

    BTW, if you are in favor of WPI doing more research including sequencing, please donate to them; we patients are already tapped out financing decades of research on our own and NIH certainly isn’t going to give them any money if they can get away with it; so who else is going to pay for these studies if you aren’t willing to?

  • Justin Reilly

    Agreed. I want to echo everyone here who’s said that we’re not wedded to XMRV, we’re wedded to the truth whatever that turns out to be. We just want to get better asap and get on with our lives and the only way to get better is to find out as much of the truth about this disease as we can. We understand XMRV may not be the/a cause, but it’s a promising line of research we’d like to see get scientifically resolved asap without charlatans throwing monkey wrenches into the works.

  • Justin Reilly

    Yup. Apparently her sister is a scientist who collaborated with CDC in publishing on autism. She has a vested interest and it shows. Please Prof., don’t just be diplomatic, call it as you see it or these charlatans will keep on persecuting us if not enough people stand up for us!!

  • Justinreilly

    Perfectly said, Gob987.

    a.scientist: we patients may seem irrational in our denial of psychogenesis of ME because we are so adamant about it. But we are only adamant about it because (1) we experience it every day so know it well and (2) have generally researched it to death so do know the truth behind the psychiatric lobby’s press releases and journal papers which are really the same thing- all propaganda and contrary to virtually all the science. Please, read up on the disease, you will be shocked by what you read, eg, redefining ME as ‘CFS’ then in the UK redefining ‘CFS’ as idiopathic chronic fatigue (1991 Oxford definition and CDC “Reeves definition”) and then doing studies on ‘CFS’ using these patently invalid definitions and using the conclusions to say that ME/CFS is merely idiopathic chronic fatigue, much of which is psychiatric in origin!! You probably don’t believe that they are this bald about their deceptions, but believe me they are. Please look into it and decide for yourself, we need as many educated, smart people such as yourself to become informed about ME! Thank you.

  • Harry P.

    Justin,

    It takes much more than a small cadre of UK psychiatrists to fool their entire government and all its agencies beyond its healthcare system. It goes much higher up in their government and involves many more people than you realize .

    Psychiatrists are nothing but peons( and future scapegoats) in a much larger government cover up and conspiracy. When you’ve used lies for so many decades to cover up incompetence, patient mistreatment, and patient deaths, it has become more important to avoid a national scandal than the lives of 250,000 PWME.

  • Anonymous

    Members of the house of Lords are certainly involved.

  • Harry P.

    Yes they are. the house of lords have actually given Simon Wessely official praise and a medal for his psychological work in ME. They have all agreed to continue treating ME as a psychological disease and to block all national and international efforts to uncover ME/CFS’s physical cause and pathology. An entire nation would be charged with genocide when the truth comes out.

  • a.scientist

    Actually, I have also done [1] and [2] and came to very different conclusions. And I think you are incorrect about the “deception”: the reason that ME is not used as a diagnosis any more is because the etiology of ME was incorrect (and if you do some research you’ll find that the person who coined the term ME knew this at the time).

    The main problem with CFS is that some people just don’t like a psychiatric explanation, either due to a prejudice or a lack of knowledge (not knowing that psychiatric illness can and does cause physical symptoms).

  • Anonymous

    Denying the existence of thousands of papers on the known underlying biology of ME is ridiculous. ME is still used as a diagnosis. The CDC still state to this day that ME is not CFS, i.e. fatigue. Yet no diagnostic criteria is provided to give an ME diagnosis, so they end up with the non-existent disease described by the empiric CFS criteria. The UK may have broken with the rules of the WHO, to which they have signed up to, and put these two different diseases together, but that clearly does not change the classification of ME. The Government and the Department of Health state that ME is neurological.

    “…I want first to put on the record that we accept the World Health Organisation’s classification of ME as a neurological condition of unknown cause.”
    Gillian Merron, Minister of State, Department of Health, House of Commons (Hansard, Column 276, 23 February 2010) http://www.publications.parliament.uk/pa/cm200910/cmhansrd/cm100223/debtext/100223-0022.htm

    You are very much in denial of the facts, and have NOT been bothered to find out.

    When you state that, “…some people just don’t like a psychiatric explanation”, it is an excuse to deflect attention away from the facts of the case. It has nothing to do with the prejudice you obviously have for anyone who has a mental health disorder, and those with ME already experience prejudice and bigotry on a far greater scale than even some mental health disorders. It is that the scientific evidence does not support, and has never supported, that conclusion.

  • Anonymous

    Top ten biomedical research findings in ME/CFS summarised in 2008 by Anthony Komaroff, Professor of Medicine at Harvard and author of more than 230 research papers on ME/CFS

    (1) many patients with ME/CFS have no diagnosable psychiatric disorder and ME/CFS is not a form of depression
    (2) there is a state of chronic, low-grade immune activation, with evidence of activated T cells and evidence of genes reflecting immune activation, as well as evidence of increased levels of cytokines
    (3) there is substantial evidence of poorly-functioning NK cells (white blood cells that are important in fighting viral infections)
    (4) there are white and grey matter abnormalities in the brain
    (5) there are abnormalities in brain metabolism (and evidence of dysfunction of energy metabolism in the mitochondria)
    (6) there are abnormalities in the neuroendocrine system, particularly in the HPA axis but also in the hypothalamic-prolactin axis and in the hypothalamic-growth hormone axis
    (7) there are cognitive difficulties, especially with information processing, memory and/or attention
    ( there are abnormalities in the autonomic nervous system (including a failure to maintain blood pressure, abnormal responses of the heart rate, and unusual pooling of blood in the legs, as well as low levels of blood volume)
    (9) there is disordered gene expression, especially in those genes that are important in energy metabolism and in genes connected to HPA axis activity, to the sympathetic nervous system and to the immune system
    (10) there is frequent infection with viruses, especially herpesvirus and enteroviruses.

  • a.scientist

    Just to respond to a few of those: patients with depression also have abnormal SPECT/MRI scans. People with PTSD have significant physical changes in brain structure which are reversed after recovery. I’m not suggesting that CFS = depression or PTSD, just giving examples. Also the immune system and HPA axis are part of the stress system, so will be significantly influenced by stress. Also, regarding gene expression: even just 30 mins of physical exercise in a healthy person significantly alters the gene expression of immune and stress related genes in the blood!

    As for patients not having a diagnosed psychiatric disorder: that’s a circular argument. As CFS isn’t defined as psychiatric, patients obviously won’t have a psychiatric diagnosis. Most research, however, shows that CFS patients have a higher chance of lifetime psychiatric diagnoses.

    Oh, and you are incorrect in your assumption that I am prejudiced against psychiatric illness or CFS – quite the opposite in fact. You are also incorrect in your assumption that I am either in denial or haven’t bothered to find out the facts.

    I think you need to look at all the research with an open mind, not just the studies that appear to prove your pre-conceived notion of the illness.

    BTW, has anyone else noticed that the ‘subscribe to all comments by email’ isn’t working?

  • a.scientist

    Actually, Wessely has done more biomedical research into CFS than almost anyone else – just do a search on pubmed and you’ll see. He has also said something like ‘the immune system is almost certainly involved’ in one of his reviews of CFS.

  • Anonymous

    Denying the existence of thousands of papers on the known underlying biology of ME is ridiculous. ME is still used as a diagnosis. The CDC still state to this day that ME is not CFS, i.e. fatigue. Yet no diagnostic criteria is provided by the CDC to give an ME diagnosis, so they end up with the non-existent disease described by the empiric CFS criteria. The UK may have broken with the rules of the WHO, to which they have signed up to, and put these two different diseases together, but that clearly does not change the classification of ME. The Government and the Department of Health state that ME is neurological.

    “…I want first to put on the record that we accept the World Health Organisation’s classification of ME as a neurological condition of unknown cause.”
    Gillian Merron, Minister of State, Department of Health, House of Commons (Hansard, Column 276, 23 February 2010) http://www.publications.parlia

    You are very much in denial of the facts, and have NOT been bothered to find out.

    When you state that, “…some people just don’t like a psychiatric explanation”, it is an excuse to deflect attention away from the facts of the case. It has nothing to do with the prejudice you obviously have for anyone who has a mental health disorder, and those with ME already experience prejudice and bigotry on a far greater scale than even some mental health disorders. It is that the scientific evidence does not support, and has never supported, that conclusion.

  • Harry P.

    it was a BLIND study! how would you know which are the patient samples so that you can get your mouse infected weasel hands all over them?

  • Harry P.

    you’re not a.scientist, but a.dumbass. Suck it weasel! your time is almost up!

  • Anonymous

    ab

  • a.scientist

    um, moderation anyone?

  • a.scientist

    Having trouble posting this. I guess there isn’t really much point continuing this, considering that you are just going to dish out abuse rather than discussing this rationally. I would just recommend that you read Acheson’s 1959 paper and you will see that he actually says that they didn’t know the cause of the illness, and that the etiology was presumed. Even at the time he acknowledged serious problems with the name, but he thought it was the best choice.

  • PBM

    Actually, if you read Judy Mikovits’ comments you will see that the patient samples and controls were collected differently: the patient samples were taken from 2006-2009 and stored in WPI’s repository, while the controls were sampled at doctors offices between 2006 and 2008.

  • Rob

    Here is a survey showing what patients believe caused their illness:

    http://www.curetogether.com/chronic-fatigue-syndrome/causes/

    and here is a study in a peer-reviewed journal:

    http://www.ncbi.nlm.nih.gov/pubmed/9201648

    Stress is the most common factor in both.

  • Anonymous

    Exactly, and you avoided the issue.

  • Anonymous

    Stress is not the most common factor, infection is. And the first link you posted is what? Not even a reliable charity.

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  • Jcstarke

    It’s not the end of XMRV and CFS/ME! Its true and well said. The WPI continue their good research. Please support them.
    http://www.wpinstitute.org/

  • http://www.facebook.com/people/Tina-Marie-Miller-Tidmore/738499772 Tina Marie Miller Tidmore

    Yes, good lessons indeed.

    Other human frailty l

    Thank you for your courage in admitting your mistake publicly and not blaming others.

  • Rob

    The second link is the only study that I am aware of that has looked into this, and as you can see it did in fact find that stress was the most common factor. The first link is just an informal survey of patients, in case you argued that most patients themselves believe that stress isn’t a significant factor…

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  • Anonymous

    And who contributed to that survey, patients with the neuro-immune disease ME/CFS or chronic fatigue? It makes a big difference.

    Lots of studies have looked at the most common factor to trigger ME/CFS, you are again talking about chronic fatigue. That paper used the Holmes (1988) definition.

    How about this study:
    “The key risk factor for post-infective fatigue syndrome is the severity of the acute illness and not age, sex, or psychological factors” (Post-infective and chronic fatigue syndromes precipitated
    by viral and non-viral pathogens: prospective cohort study, 2006)

    or
    “Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.”
    (Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies, 2007)

    or
    “These data suggest that a combination of host and environmental factors, including an infectious agent or agents, are involved in the etiology of CFS.”
    (Risk Factors Associated with Chronic Fatigue Syndrome in a Cluster of paediatric cases, 1991)

    or
    “Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month. ” (Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever, 1998)

    As you can see it is a mess, and all Health authorities have been avoiding a proper study on risk factors using a strict criteria, like the Canadian. But without a reliable MRV test the risk won’t be known either.

  • Nila

    Great Man who can admit his mistakes. I put you high in the human race!! Nila.. suffer with CFIDS

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