XMRV and CFS – It’s not the end

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?

191 thoughts on “XMRV and CFS – It’s not the end”

  1. Thank you very much Dr. Racaniello.

    I appreciate you honest excuses. The internet facilitates the patients to react fast when disturbing and dishonest news is published in the media. I don’t want to think about me being ill for ten years now without internet, without the patients advocating. What would have happened then?

  2. Monique Martens1

    Thank you Dr. Racaniello, It takes courage to admit a mistake. I deeply appreciate this.

  3. Thank you, Dr. Racaniello! My only hope is that research will continue and a conclusive answer, whatever it will be, will be found for the cause of CFS.

  4. Thank you Dr Racaniello for listening to us and for retracting your original statements. I very much appreciate your committment to getting to the truth of the scientific issues surrounding ME/CFS. We desperately need scientists with integrity on our side!

  5. Thank you for your retraction. I wonder if you would consider ensuring that the British media – especially the BBC, The Guardian, and The Independent – publish your revised views? Thank you.

  6. Your willingness to admit an error is commendable. This is never an easy thing to do. Admitting a public statement was made in haste before a thorough reading of the material reinforces your role as a trustworthy educator and scientist.

    Having a public platform is a sticky wicket, as you’ve discovered. Journalists’ motivations are by nature different from those of scientists and educators. Their goal is to sell papers and retain advertisers, or whatever the modern media corollary of that may be.

    We who suffer from an illness that for decades has been dismissed, and proclaimed as imagined and non-existent by the medical, scientific, insurance and governmental communities and therefore by our families and friends as well, are justifiably alarmed, but not particularly surprised, when the press immediately pounces on and sensationalizes as scientific truth anything and everything that reinforces the long held, wholly unscientific, unproven hypothesis that there is nothing worth investigating in this illness.

  7. Professor.
    Nice of you to take the blame but Ms Tsouderos previous article if I remember correctly was not very kind to ME/CFS patients or XMRV research. I think she chose to find what she was looking for in your quote. If you had said these studies should be ignored orid not discredit the connection between these retroviruses and ME/CFS I truly believed she would have used a quote from someone else that echoed your now retracted quote. She has been leading up to this story I believe. Please read your previous articles in chronological order and make your own decision if Iam correct on this.

    Thanks again for retracting Keith
    Family of 4 with ME/CFS for 24 years.
    Two sons both with high functioning autism

  8. That is correct.

    It is the Wellcome Trust and Greg Towers who have stated in a press release that their findings negate previous work. Yes, they must retracted their statements immediately.

  9. I’m so grateful for you taking a closer reading. I have learned, six years into this illness and three years in of being bedridden (this week!), to take any universal pronouncement, positive or negative, with a major grain of salt. That’s what I did with yesterday’s stories. The trouble here, of course, is that a big, splashy discrediting nets major interest – the nuanced reading that follows, and letters to the editor, which are often where the truth of the matter lies, never do. I know that this will make you more careful in the future.

  10. Thank you. I doubt that the newspapers reporting on this will bother to print your new conclusions, but you can bet that going forward, we’ll be copy-pasting the highlights on every story that gets it wrong.

  11. Professor Racaniello, you’re a big man to admit a change of heart like that.

    Could you explain a bit more about how differences in n 22Rv1 viruses could appear during PCR amplification and how likely that is – since this addresses what seems to be the key finding in the Retroviology papers? Thanks

    “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.”

  12. Greatly appreciate your honesty and integrity, and also the promptness of your public correction. A few of your medical colleagues could learn from your example.

  13. Hi Prof R, I just wanted to make an observation on your blog…

    In the last 2 days and 2 posts you have had over 150 comments compared to 1 or 2 for the previous blogposts or podcast.

    While many patients with ME/CFS have a base of science, one cannot deny the interest for GOOD science and the search for the truth, without political ties attached. Patients, whether beddridden or housebound, have time to take a look at science and trying to understand what is going on in their bodies, likely because not many have bothered doing it for our disease. Thus the interest to your virology blog.

    I appreciate going out of your way to open your mind and consider all options when it comes to XMRV.

  14. Dr. Racaniello, I am humbled to read this gracious post. In our competitive universities today, there is too little of this thoughtful reflection on one’s errors and willingness to apologise publically for one’s mistakes, especially when they affect the lives of others. Your courtesy and integrity are a model for other academics, in the sciences and beyond. Would that they follow your strong example.

  15. This is an example of what real science should be about in my opinion. Always ready to re-evaluate, always critical. Towards others AND towards yourself. Thank you Mister Racaniello for setting this example.

  16. Trine is a shoddy journalist. She had the opportunity to research the story and analyse the arguments, but failed to adequately do either. This is in stark contrast to the Wall Street Journal’s Amy Dockser Marcus. This is harsh, but Trine is not capable of covering this story. Her lack of experience, talent and intelligence preclude such a possibility.

  17. Thank you Dr Racaniello for having integrity! Much appreciation. Why isn’t antibody activity a bigger part of the picture? I will continue to follow all of this drama with hopes of a good outcome. For myself and all of us suffering. Sincerely, Dr. Tracy Waechter

  18. Thank you for your honesty and integrity.

    I agree with comments above. If you look at Trine’s work you will know she is not a friend to those impacted by autism, lyme or ME/CFS. She has chosen to write about diseases that are not completely understood and is making a career out of “debunking” new research in these areas. It has only served to hurt these patient groups.

  19. Dr. Racaniello,

    I was most concerned that your blog yesterday might reflect the “hallway scuttlebutt” going around at Columbia, and worried that attitudes there are similar to the CDC’s (e.g., the mock letter from a “chronic fatigue” patient that engendered such hilarity at the CDC described in Osler’s Web).

    Like other patients and carers, I want to know what the best science can tell us about this disease. I’m therefore concerned that your colleague, Dr. Lipkin, and his associates are as scientifically excellent and objective as the NY Times portrays them, while they conduct the “definitive” studies on detection, prevalence and a possible causal link.

    I greatly appreciate your efforts to explain virology to laypersons and especially your clarification today.

    But now I’m concerned you may choose to stay away from translating the science for us!

    Thank you.

  20. I too wish to thank you for your retraction. Furthermore I would request that you make your comments available to the UK press, namely; British Broadcasting Corporation (BBC), The Guardian, and The Independent Newspapers so that they may share with the UK public your recent findings. Kindest Regards, Julie Jobson UK

  21. Trine Tsouderos found what she was looking for and she printed it. It is likely that, at some point, she encountered criticism of the contamination studies and chose not to print that.

    If you want to learn more about this entertainment-cum-science reporter, I suggest you read Hillary Johnson’s blog post, “Chicago Tribune Quack-Buster Making the World Safe for the Federal Disease Agencies’ Propaganda”.

    http://www.oslersweb.com/blog.htm?post=710020

  22. Having had no health issues my entire life except a few sore throats and hence very little direct contact with the medical profession until the onset of ME/CFS I’ve been taken back by the deification of self within the profession. Being diagnosed in 2004 after 5 years of symptoms I’ve had more Doctors than I can count make remarks to me that would not be tolerated in any other field I know of except maybe a police officer to a criminal. It seems the entire profession minus a few, feel they can insult, condescend and make disparaging remarks at will….it really is an psychological disorder known as superiority complex and needs to be treated. I yearn for some who have a little humility…enough to say I’m not sure….or I don’t know. Funny thing is often I get four or five different opinions of the same issue delivered with the same overpowering certainty and when I suggest what the others have said they resort to insults towards me and or the others doctors etc. I do have two doctors out of all those I’ve seen (probably around 100)over the last 11+ years who do display their humanity with humility, one even takes out medical books in front of me when its an area he doesn’t deal with all the time….love and respect this man….although neither are directly involved with this disease. You were just added to this list….thank you for being human!

  23. Professor Racaniello,

    I’d like to add my thanks for your retraction, commitment to the truth and to furthering ME/CFS research. It is greatly appreciated. As a housebound sufferer of over a decade and who lives in the UK I know the battle is far from over but am heartened to know credible and robust scientists like yourself are on the case. Much gratitude to you, we need all the help we can to counter the misleading press coverage in the UK which has left people believing the retroviral link to ME/CFS is now dead.

    I also wonder if you would consider ensuring that the British media – especially the BBC, The Guardian, and The Independent – publish your revised views?

    Thank you

  24. Thank you, Vince. I hope you did indeed learn something. I’m not as forgiving as everyone else, but I do appreciate it when a man is willing to admit he made a mistake. I’ll forgive you later, I’m sure.

  25. Thanks for demonstrating the your commitment to the truth is your most precious commitment Dr. It would be great to know how to clear up these mysteries?

    How will the scientific community determine if XMRV comes from man or mouse or a cell line tarnished with an endogenous retrovirus?

    Can the BWG or WPI simply sequence the XMRV they have to find if they have the MoMLV ( or do we already know that they do not?

    How to determine if the genetic variability of the 22RV1 cell line was produced during PCR amplification?

    If another research lab was to isolate XMRV – would that solve the contamination questions? Is it necessary to prove integration into the DNA and, if so, would that put the questions to rest?

    If the antibody results are validated by the BWG would that put the questions to rest.

    Finally, if you were to take a guess -how long before you think these questions will be put to rest?

  26. I am really looking forward to the Dr. Singh study. Hopefully it will be published soon add some much needed clues to the puzzle.

  27. hopefully, the Singh, BWG, and Lipkin studies will all be in consensus so we can put this controversial debate to rest! Enough with the Egos and media sword fighting! The patients need a government approved blood test and effective meds already! ME/CFS = TORTURE

  28. LOL that the above got through. Thanks, Cort, for trying to summarize the patients’ questions on the science.

    We patients/carers still don’t know the results from the BWG tests of whole blood. What conclusions can we draw from any PCR tests unless they culture their results up to 45 days? I’m not seeing any published studies where anyone is doing that, except WPI.

    It appears to be “sexy” to demonstrate results from high-throughput technologies. Surely we need high through-put assays! But it looks like, from a lay perspective, that we haven’t decided yet on what we’re actually looking for.

    Could you comment on that?

  29. It takes true strength of character to say that you were wrong.

    Well done Prof. Racaniello, you put others to shame.

    Thankyou.

  30. Perhaps you will start a trend that will become very fashionable in the new year – retracting statements and apologising for an error or miscalculation? I wonder why it is we teach our kids to be brave and to say sorry when they have made a mistake and yet as adults we rarely practice what we preach?

    Good on you.

  31. Ms. Tsoderos is clearly wrong about a correction. The best way for the Chicago Tribune/Ms. Tsouderos to follow up would be to follow your admirable lead. If they are really interested in journalistic integrity, they could run a headline and article of equal size and placement that says, “Oops, we were wrong. Articles only show contamination must be addressed, not that the XMRV is a dead-end.” Thank you, however, for doing what is in your power to do.

  32. Murky waters indeed! When investigating fraud the quickest way to the truth is to follow the money – and it is very clear that one of the main funders of the Wessely school of psychiatrists is none other than the Wellcome trust – the very organisation from which this latest press release emanates.

    Information for Clinicians and Lawyers. M Hooper et al, December 2000, p15: ‘Since 1988, psychiatrists of the “Wessely School” have been funded not only by the MRC, but by Wellcome Training Fellowships in Clinical Epidemiology, by a Wellcome Research Fellowship in Epidemiology; by the Wellcome Trust.

    Please read the following publication –

    A CONSIDERATION OF THE ROLE OF PROFESSOR SIMON WESSELY AND OTHER MEMBERS OF THE “WESSELY SCHOOL” IN THE PERCEPTION OF MYALGIC ENCEPHALOMYELITIS (ME) IN THE UK

    Perhaps Dr Mikovits is incorrect, perhaps XMRV is not real. However it is one thing to honestly believe in something and ask others to use your methods to confirm it and quite another to try ardently to disprove something using invalid methods, invalid patient criteria and then swamp the press with false conclusions that get repeated and reprinted over the entire world. One is the actions of a scientist, the other are the actions of propaganda and deception and have no place in science! Greg Towers, Bridget Huber, Simon Wessely, and Myra McClure have no place in the scientific community and it is time that any articles they publish are regarded from the starting point of fraud and deception.

  33. When one “follows the money” with XMRV, it leads straight to the door of the WPI and Judy Mikovits. Why are they exempt from scrutiny?

  34. The evidence shows it comes from man. The WPI and others have not found a contaminant. There is no evidence for that. Cort your questions are dull, and not the right questions.

  35. There is no high throughput test that works. It is not about being sexy, they need to be able to screen thousand of samples quickly in order to protect the blood supply. They know what they are looking for, they don’t know how diverse it is.

  36. Professor, I applaud your honesty and willingness to reconsider your position.

    In science one cannot jump to conclusions wholly unsupported by the evidence.
    However, it seems that there are other parties which have put all their eggs into the XMRV basket in a rather precipitous fashion, and who seem (judging from the WPI press release) to be very reluctant to entertain the possibility they may have been a little premature in pronouncing on their own findings. They certainly seem to wish to brush the possible contamination issue under the carpet and to carry on regardless. Surely that is poor science?

    In your view, what should the WPI, Lombardi et al and Lo et al all do now?
    Any decent scientist interested in the truth would surely pull out all of the samples and have them intimately sequenced and analysed to ensure their results were free of possible contamination.

    Should they and will they now do this?

  37. They aren’t exempt from scrutiny, the Science paper was subject to 6 months of rigorous scrutiny. Furthermore that paper was blinded in conjunction with the NCI and the Cleveland Clinic. In addition Harvey Alter and Lo have essentially supported the finding of the Lombardi group. I welcome fair scrutiny, as should everyone, it is the scientific process.

    However, I repeat again, it is one thing for a scientist to report their findings and subject them to the scrutiny of the world. And it is quite another for a group of people that have long held ME in contempt to published unfounded conclusions using the power of the Science Media Group and prestigious organisations such as UCL, while simultaneously refusing to follow accepted scientific protocol, which is to replicate the methods of the original scientists. That is deception and fraud. It is an attempt to steam roller their views in the absence of any actual conclusive backing.

    When one follows the money I guarantee you it does not flow to the WPI. They are being kept going by the dedicated work of the founders and donations of the public. Consider the money the the Wessely School psychiatrists have made from their faulty disease models and abuse of ME patients over decades and you will see that the WPI is but a drop in the ocean of that wealth. Not forgetting that Simon Wessely’s career, as of his supporters such as Tim Peto and Peter White, would essentially be over should XMRV be proven. What roll do psychiatrists have in a retroviral disease…. none! These are massive institutions, such as Kings and Barts colleges, the Wellcome trust, that have called ME a biosocial illness.

  38. Prof. Racaniello,

    Could the cell line 22Rv1 (or other laboratory cell lines harboring XMRVs) actually be the source of a human infectious XMRV? In other words, maybe XMRV is indeed an omnipresent contaminant, but some variations of it are capable of infecting humans? Wouldn’t this unify all the findings while at the same time point to the infection’s origin?

  39. Dr. Judy has always wanted to sequence the XMRV from each positive sample. At one point she was trying to raise money to do this. I don’t know if this work has been completed, but she has been unable to publish research on the grounds that her results are due to contamination. There is a lot of research going on at WPI that patients are not aware of. There would be a lot more still, it they could get more money. I know this from speaking to Dr. Judy at a conference and several other patients were listening in.

  40. As others have said, it takes courage and humility to admit mistakes and I honor that. What I’m interested in is the way you framed this research as the “beginning of the end” of the relationship of XMRV to CFS.

    Would you have spoken in such sweeping terms if the UCL and Wellcome Press releases weren’t trumpeting this conclusion? I don’t think this was deliberate but it’s important to be aware of how the debate is being framed, and to what policy ends.

    How do you know that Greg Towers also wished he didn’t make the statement he did? Have you spoken to him? What motivated his turning to the press with such certainty, particularly since the matter of XMRV/PMLVs as a cause of M.E. has never been asserted, though the association is a powerful one.

    And one last comment about the abysmal quality of Science journalism. We are all responsible for what we say and write, and if Ms. Tsouderos was out of her depth and could only unthinkingly parrot what you and others said, she shouldn’t have been assigned the task. Amy Dockser Marcus was able to present the differing views of this matter in a balanced way. This is not an unreasonable standard of practice. And as a corollary to this, must we have immediate feedback on complex and subtle research? Wouldn’t it have been better for you to get back to her, after a bit of consideration? Serious matters, as a rule, should be highly resistant to the written equivalent of the sound byte.

  41. I have been wondering the same thing….and perhaps there are genetic susceptibilities that allow some people to get sick, but not others.

  42. Thank you for your retraction.

    You help restore a bit of my faith in integrity and honestywhere medicine is involved.

    Since being diagnosed with ME/CFS and later finding it was Lyme Disease and on long term antibiotics recovering from being housebound to virtually 100% treatment that should have been denied me according to HPA/IDSA, I am staggered at the lengths doctors and scientists go to discredit others research based on opinion but not always science. I have seen this much in the controversy over chronic lyme and shocked to find similar with ME/CFS.
    Thank goodness there are some pioneering doctors prepared to go to great lengths to get at the truth and find treatments that work for us, we need many more to follow their example.

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