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. John Francisco Garcia

    Thank you Prof. Racaniello. It takes a big person to admit they made a mistake. I agree this debate is far from over! Clinical trials would be one way to settle this debate once and for all.

  2. Pingback: XMRV and CFS(ME) – It’s not the end « Rutts tankespinn og ME-nyheter

  3. Thank you for doing the right thing and retracting your initial comments. I wish more people showed such integrity and a desire to seek the truth.

  4. Thank you, Dr. Racaniello. I know I am not the only person in the patient community who looks to you for help in understanding this very complex and confusing “early science.”

    As for the question of how non-scientists fare in understanding and interpreting the results, I think we can easily see how widely and uncritically the Wellcome Trust’s press release was picked up and repeated in various news outlets, under headlines that stated the question was now settled and that contamination in past studies was “proven.” The wording of that press release was bald and unequivocal: “A virus previously thought to be associated with chronic fatigue syndrome is not the cause of the disease, a detailed study has shown.” Perhaps the ethical implications of researchers disseminating such unwarranted “conclusions” to the press would be an interesting topic for a future post.

    Patients, of course, want a cure, or at least better understanding and treatments than the non-understanding and non-treatments we currently receive. But those of us who are intellectually honest really want the truth above all else. What patients fear most is not that a promising line of research might not pan out; we fear that when the research gets difficult, the effort might be completely abandoned, as it was in the early 90s. We need MUCH more research funding, and the best scientists to be working on this problem night and day, without preconceptions on either side.

  5. As someone who has lived with ME/CFS for most of my adult life, all I want is good science. Thank you for taking the time to correct your initial post. It is much appreciated.

  6. Pingback: Tweets that mention XMRV and CFS – It’s not the end -- Topsy.com

  7. Thanks! Researchers such as yourself really helps in giving the very ill some hope to hang onto.
    Poorly written papers such as these, in Retovirology, really brings research progress to a halt. Unfortunately, the end result is the lose of precious lives. The research can eventually be fixed and continue to progress, but the lives lost are gone. All because of a few poorly written papers! What ashame!

  8. As someone that was extremely angered and upset by your quote in the Chicago Tribune I want to commend you for being Man enough to admit you were incorrect. Now how about an interview with Dr. Mikovits, Lo or Alter.:)

  9. Thank you very much. Is there any chance of getting Ms. Tsouderos and the Chicago Tribune to follow up with a correction?

  10. Thank you for your humble retraction, and your honesty. It would be wonderful if the Tribune would print this blog post in its entirety as a full article, and not just as a letter to the editor.

  11. Carlitos Gonzalez

    I am glad you make this rectification professor Racaniello, that makes you a wiser person, being able to stick to the truth, no matter if it means rectification of previous statements.
    Merry Christmas and thank you.
    Probably an idea would be to transmit this to Chicago Tribune as well…

  12. Dr. Racaniello,

    Your integrity is impressive but not surprising in someone who’s mission is to educate.

    There’s a lot more to learn here than ‘just’ virology.

  13. Yay Dr. R. Thanks for retracting your statement to the Tribune.

    However, the actions that occurred over the past few days with you , the 4 papers and the Trib should highlight to you the murky waters ME/CFS patients have been drowning in for years:

    No Science, Difficult to Understand Science, Purposefully Misleading Science, It’s All in Your Head Science….who knows?????? The only real science, we patients feel, we have had in decades is the WPI Science paper, Dr. Alter and Lo’s paper and Dr. Ila Singh’s research. Then 4 papers can come out in ONE day and nearly destroy the integrity of this science, even in the eyes of a professional virologist (that’s you).

    Hopefully you now can better understand the angst, trepidation, distrust and in some cases strong dislike (putting it nicely since it’s the Holiday Season : )) ME/CFS patients hold for certain, Dr’s, Scientists, Researchers and Government Agencies.

    Thank you for reviewing the papers again, realizing that your statements to the Trib were not accurate and retracting them.

    We need scientists, researchers, doctors and governments looking for the bio-physical cause of this debilitating disease…we finally have a few….we hope and (some do pray) the momentum for more research and treatment keeps moving forward and not backward as it did on 12/20/10.

    Warmly, Lisa

  14. Thanks for the update. Is there any way we could get a more detailed post about the Hue paper and how (in your opinion) it affects the likelihood that XMRV is circulating as a human pathogen?

    As you say, it’s a complicated paper, and I think that a lot of us non-scientists are struggling to understand it, especially as the Wellfare trust press statement sounded so certain (particularly in regards to XMRV and CFS), while it seems most other scientists are rather less convinced by their work. What’s going on here?

  15. Thankyou as someone from the UK I admire you for quickly retracting you initial statements on the 4 contamination papers . Its a shame certain UK scientists ( i will name no names ) are not willing to also swallow humble pie and perhaps admit they have been hasty in their judgements of XMRV and its role in diseases such as me/cfs and prostate cancer . They have been offered help and on several occasions now , so that they would actually be able to find XMRV in the first place , however this has fallen on deaf ears or should that be overinflated egos .
    So thankyou once again for having the guts to admit you were wrong , what is it they say honesty is the best policy ? I hope the UK are now listening and taking note but then again pigs might fly !

  16. Ojos Estrellados

    Thank you very much for apologizing to us and looking further into this Prof. Racaniello. I just want researchers to find the truth regarding ME. You’ve renewed my hope that this might just happen for us.

  17. I join the ranks in applauding your integrity, and the strength of character it takes to admit and try to rectify an error. I am another person with ME/CFS who is looking for good science, wherever that may lead us. This post and your actions signal to me that you are one of the people looking for good science as well, and not acting from a personal agenda. Thank you.

  18. Thank You, Dr. Racaniello from a patient community that only asks that the public have the facts, we are grateful that you have corrected the record. It is a shame that others who incorrectly reported the story aren’t as stand up as you are. I look forward to future TWIV’s hopefully with Dr. Judy.

  19. Thank you, thank you, thank you for your retraction and clarification. Re: your letter to the editor of the Chicago Tribune; would you be willing to cc that to some of the major news outlets around the world, some which published articles even more misleading than the one in the Tribune? Thanks for your consideration.

  20. Professor,

    As others have said, you are a man of integrity and honor.

    We ME/CFS patients just want the scientific truth in the most expeditious manner possible. As you have noted contamination is indeed a very important consideration but not the end of XMRV in human pathology.

    One retrovirologist who is very cautious in her work is your colleague Dr. Singh. We expect multiple papers from her in the new year and if her patent application is any indication XMRV may hold more surprises in 2011.

    I wish you and yours a Merry Christmas and a healthy and happy 2011.

    Best regards,
    Otis

  21. In Hebrew we have a saying that’s translation is: “A person who admitts and let go shell be forgiven”.
    It’s good that you have written this post.
    However, I feel that your last sentence in this post is sarcastic, and if it is, it’s sad that it comes after apologizing. Reminds me of the chapter in seinfeld where George asks a former friend of him to apologize for insulting him – because the friend has to ask for forgiveness during one of the steps in Alcoholics Anonymous. Eventually the friend says: “I’m sorry George”, but when George asks for a sincere apology the friend goes on by sayinh: “I’m sorry that I had let you ruin my nice sweater with your melone head” (or something like that).
    Anyway, scientists can make mistakes, and ofcourse having a laboratory condition where the are no other elements, a scientist should have a much better chance to understand something scientific, that a non-scientist have. But also non-scientists understand that we are in no laboratory situation here, we are in life, and very very sadly, even when it comes to ill people, these life contains many politics. People usually believe what they want to believe (and that is correct to woth sides). In any case, like in politics (and because the scientific world sadly has politics inside of it [I mean that there are politicians in that world]), anyone should be able to choose who he trust – like people are able to choose their president. Now, given a fight between the person who got everyone to think wrongly that there are viruses, called “xenotropic”, which cannot infect mice (Coffin) + the person who attacks the WPI day and night, and also attacks patients – although she just couldn’t find anything (McClure) + the person that might be a very nice guy and a good virologist, but he hosts in his podcasts Alan Dove, who acted in a very cruel and disgusting way against patients – and on the contrary side I have a person who has a 30 year carreer in retrovirology (Dr. Mikovits) + A person who discovered Hepatitis C and HCV, and helped discovering HBV (Dr. Alter) + The persons that were there for their patients, and supported them with no conditions (Dr. Petereson and Dr. Bell) – I choose the latter option, because I have much more trust in those people.

  22. thank you, dr. racaniello! YOU are an honorable man (a rarity…and the highest complement i can bestow, is to tell you that!)

    You have made my birthday (today) a happy one!

    (ME/cfs patient=SIXTY YEARS!, acyclovir – 5 yrs/ soon to start epivir)

  23. As always, you are an upstanding scientist and citizen. I’m not a patient with ME/CFS, but think you do a great job of promoting science, and what a scientist should be. This episode really displays how science works; you read the papers and made an opinion, then changed your opinion based on further exploration. No doubt opinions will change multiple times as this is studied further, and hopefully a picture will become clearer and not any murkier. Your last sentence is spot on too, it really applies to all areas of science. Thanks for being a great example of what scientists should be and do, hopefully our up and coming scientists will take note!
    -Amy

  24. I appreciated learning of the reasoning behind your first statement, and that you challenged your conclusions and were willing to retract them. We all want good science, and today’s blog has just given me more confidence in your explanations. Thankyou

  25. Richard Sherbird

    Thank you Professor Racaniello for your last statement.Welcome to the unethical world of ME/CFS.
    I think you would do us a great service if you make one of your progems about the WPI. Go visit them
    i think it would be a very interesting program.

  26. It must be quite easy, under the pressures of hectic everyday work, to skim through some papers when asked to comment on them, and them come to the wrong conclusions. In hindsight you realised that the papers were not all they were supposed to be, so you very honestly and graciously announced a public retraction. Good for you, really.
    But what of the AUTHORS of these misleading papers? They have the same knowledge of the subject as you. They have good working brains and access to all the articles, which of necessity they will have read assiduously. In my books, that makes them all dishonest, as they know the facts about the lack of contamination in the original Lombardi study, and about all the precautions, and about the problems of PCR (called DNA testing in their works) being a magnet for contamination. To me, they have all thrown away their integrity and henceforth deserve no respect from anyone.
    If they want to retract, fine. If you can do it so can they. I bet they won’t.

  27. Thank you very much Professor Racaniello – this is very honest of you to admit you jumped to a too quick conclusion.As the worldwide severely Neuro immune ill patients are waiting for believe & proper treatment & symptom control & better medical understanding a severe virus would explain the severity & the awful amount of symptoms & systems involved in this illness.To have all this amount of studies printed on the same day was no doubt done for maximum impact and very opinionated to say that the link to XMRV is now over is not good science when all the same methods of testing where not done.You are a very honest medical person only wish alot more were like this.Mother of 11 yrs old severe ME & virtually bed& house bound for over 2 yrs

  28. Laurence, the authors of the four papers have not claimed that their
    findings negate previous work – at least not within the published
    work. There is nothing wrong with the majority of the work in the
    papers, in that they simply show how contamination could be a problem;
    and advise that future studies must consider this. The science is
    fine; there is nothing to retract. However, the author on one of the
    papers has made very strong comments to the press, and this is what
    has been greatly publicized. I am certain that he also wishes he could
    retract his statements.

  29. Don’t blame Ms. Tsouderos – her experts all told her what she printed.
    Since she isn’t a scientist, she has to listen to them. I take the
    blame for the tone of that article.

  30. Pingback: XMRV and CFS: Were Mistakes Made? | Alan Dove, Ph.D.

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