Field of Science

Chronic fatigue syndrome hypothesis collapses further


Two years ago, a team of scientists announced with great fanfare that they'd found the cause of chronic fatigue syndrome: a mouse retrovirus called XMRV. There were many media reports and much excitement, and at least a dozen studies were launched to look for this virus in more patients. Unfortunately for patients, the findings turned out to be seriously flawed.

New results published this week seem to be the final nail in the coffin for the XMRV hypothesis. The editors at Science have taken the unusual step of publicly asking the authors of the 2009 study to retract their findings. As reported in the Wall St. Journal, Science sent a letter to the authors stating:
"At this juncture, Science feels that it would be in the best interest of the scientific community'' for the co-authors to retract the paper."
In addition, the editors published an "expression of concern" this week, which is their way of warning everyone that the results are wrong. Judy Mikovits, the leader of the study, steadfastly insists that she is right and all the others are wrong.

Despite Mikovits' claims, the evidence is very clear that she is wrong. Study after study has found no trace of the virus in CFS patients. Where Mikovits' original study found 67% of the patients had XMRV, followup studies found 0%. A set of three papers in the journal Retrovirology, published in December, showed conclusively that the finding was due to laboratory contamination. The XMRV virus turned up as a contaminant in cancer cell lines that are widely used in laboratory research. As I wrote in January:
"It turns out that a common tumor cell line called 22Rv1 is infected with MLV-X. It also turns out that all the XMRV sequences from human patients are far more similar to the exact same strain of MLV-X that is in the mouse cell line. The tumor cell line was in the lab doing the experiments: ergo, it's contamination. Elementary, my dear Watson."
Two new papers in Science this week found the same thing. One of them, titled "No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected" looked at patients who had tested positive for the XMRV virus, and found that they didn't have it all. The second study provides new detail on how the XMRV virus got into the cancer cell lines.

So why does Mikovits cling so fiercely to her claims? (She posted a long letter defending herself at the Whittemore Peterson Institute, where she works.) What she doesn't say is that she has gone far beyond her original findings: she and her institute are actively promoting the use of anti-retroviral therapies for CFS patients. As Nature News reported in March,
"The WPI owns a company that charges patients up to $549 to be tested for XMRV, and Mikovits believes that patients who test positive should consult their doctors about getting antiretroviral drugs normally prescribed to those with HIV."
This is a blatant conflict of interest, and it perhaps explains some of Mikovits' stubbornness.

It gets worse. As Trine Tsouderos reported last summer in the Chicago Tribune, Mikovits claimed at the Autism One conference that XMRV also causes autism. She has no evidence to support this startling claim. Mikovits stated to the Tribune that "unless we do something now this (XMRV) could be the worst epidemic in U.S. history."

Mikovits also believes there is a conspiracy against her. In March, she told Nature "I had no idea there was that much bias against this disease." Nonsense. The collapse of the evidence about XMRV and chronic fatigue syndrome is just science doing what it is supposed to do: when a study cannot be replicated, then the hypothesis is abandoned and we move on.

This is a classic tale of a scientist gone bad. Unfortunately for CFS patients, Mikovits is distracting attention from efforts to find the real cause. By speaking at the Autism One conference, she has joined the ranks of pseudoscientists and anti-vaccinationists. It's pretty clear now that she will never retract her findings, despite the pressure from the editors at Science. I can only hope that CFS patients, who are understandably desperate for a treatment, won't be fooled into taking ineffective and possibly harmful therapies based on the failed XMRV hypothesis.

9 comments:

  1. Steve, this will seem a bit obvious, but Dr. Mikovits is a human being not a disease. She clearly states that the bias is against CFS, not XMRV or herself. Nor does the quote you used say anything about a conspiracy.

    Your point about science being science is a good one, but accuracy is just as important in writing as it is science.

    It took ten years for scientists bucking the mainstream thinking to prove h pylori caused ulcers not stress. And until technology improved MS was mistakenly referred to as hysterical paralysis. Was there bias toward one hypothesis over another? Did it hinder the most effective treatments for patients? Probably, but it is a stretch to say that because there were clearly opposing ideas that that made it a conspiracy.

    Bias and conspiracy are not synonyms.

    ReplyDelete
  2. It's true that she said the bias was against the disease, but that quote is part of a pattern of behavior where she claims the scientific community is against her. In the Chicago Tribune last summer, she was quoted thusly: "I know that presenting unpublished data will hurt me but the political attacks on the WPI and the lack of government response to a Science paper showing a new human retrovirus detected in a huge proportion of CFS patients told me that unless we do something now this could be the worst epidemic in U.S. history. Our continent will be like HIV Africa only worse!"
    Claiming that the attacks on the WPI (her institute) are political is another way of saying that scientists are criticizing her for reasons other than her science. (And don't get me started on her wild hyperbole in claiming that XMRV will turn out to be like HIV.)
    You comment about H. pylori is an example of "The Galileo gambit", in which a scientist who is criticized claims (or his/her supporters claim) that he is just like Galileo (or other famous scientists) who were criticized for their new ideas, and who were later vindicated. I know Barry Marshall personally (he's the scientist who made the H. pylori discovery, for which he won the Nobel Prize), and he is nothing like Judy Mikovits. And he didn't claim that all the critics were wrong, he just stuck to his science and produced more evidence. And in his case, the replication experiments proved him correct - which makes all the difference.

    ReplyDelete
  3. I'm afraid I didn't compare Dr. Marshall to Dr. Mikovits and since I don't know either of them I really can't say nor did I compare their situations - why did you think I did?

    You have now explained why you ad libbed in the word conspiracy, but without that explanation my comment about both Dr. Marshall and MS related to your statement implying that bias meant a conspiracy.

    One more time. Her sentence was regarding bias against a disease. You added in the word conspiracy without any supporting data. My response merely pointed out that bias and conspiracy are not the same thing. Based on what you wrote you seemed confused so I used two other situations to illustrate why controversy may generate bias but not necessarily be a conspiracy.

    Got it?

    ReplyDelete
  4. You wrote " It took ten years for scientists bucking the mainstream thinking to prove h pylori caused ulcers not stress." Perhaps you didn't know that Barry Marshall was the scientist who discovered that H. pylori causes ulcers, but it was he. As for conspiracy vs bias - perhaps the real culprit is Mikovits colleague at WPI, Jamie Deckoff-Jones, who is using her blog "to allege a cover-up by researchers seeking to discredit the XMRV link." She is quoted in the Chicago Tribune in March, http://www.chicagotribune.com/health/ct-met-chronic-fatigue-xmrv-20110317,0,6116823.story?page=1.

    ReplyDelete
  5. My understanding of the controversy involving the chronic fatigue syndrome (CFS) comes partly from what I've read; however, before the community comes to the conclusion that the virus is simply a contaminant and unrelated to the syndrome, it's probably worth examining the research closer.
    CFS may in some respects look like a stubborn low level infection that doesn't resolve. If the possible infective agent in CFS, like in AIDS, infects blood cells (for example) and, in a sense, goads the immune system into targeting and destroying a population of red cells, and this leads to a low level anemia or systemic symptoms like lethargy, it may not be inconsistent with what we know of the syndrome.
    Perhaps this type of mechanism of disease follows what may have occurred in the Spanish influenza epidemic back in the early part of the 20th century. In that situation there was an anomalous result in that young people died at a relatively high rate. This is the opposite of what one might normally expect in influenza or any respiratory disease. One might expect that older people would be the population suffering highest mortality (eg because of weakened immune systems or troubled breathing capacity). However, young people died at a tragically high rate, and this may have been because of their strong immune system attacking the domain of infection of the influenza pathogen (ie lung or associated tissue). So what may have occurred is that there was a pathogen that unfortunately infected lung tissue, which then triggered a robust immune response, and this immune response naturally went after infected lung tissue. However, just as if a criminal barricades himself in your home, and the police go after him and target your home, and then have a shootout, your home likely will suffer damage.
    So in addition to possibly triggering a cytokine storm, Spanish influenza may have goaded younger adults' strong immune systems into attacking lung tissue. And strangely, those with a weaker immune system may have survived the infection better than those with a strong one.
    There may be eerie confirmation of this model of pathogenic lethality in other diseases like AIDS or rabies or malaria. In AIDS, what may be going on is that a virus has a particularly dangerous domain of infection, namely the T4 cell. The immune system may then target the T4 cell which means paradoxically, the more effective the body is at wiping out infected T4 cells, the more damaged the immune system becomes. And even worse, the body may begin to indiscriminately attack T4 cells even if they are uninfected. Again cytokinemia could result or irreparable destruction of the immune system could result or both. And sadly, subsequent infection by other pathogens that might normally have been fought off with ease, may now be fatal, because the immune system has been attacking itself. (This possible disease mechanism may also explain why a vaccine has been so difficult to create. A vaccine that succeeds in creating a robust immune response may inadvertently prime the body to react even more dangerously to its own infected T4 cells should they subsequently become infected by HIV well after vaccination.) (end of Part I of comment; part II follows) --Jacob Frumer (LEWRITER@EARTHLINK.NET)

    ReplyDelete
  6. Similar disease processes may occur with ALS (body possibly attacking stubborn infection in muscle or nervous tissue), MS (body possibly attacking infected myelin), rabies (body possibly attacking infected brain and/or nervous tissue), and malaria (body possibly attacking infected blood cells).
    Interestingly, there may be a number of people whose immune systems adapt to or can deal with the infection. Perhaps this is what is occurring with elite controllers in AIDS, or maybe we see a temporary glimpse of this in partial remission in MS patients. (Also, incidentally, quinine which was effectively used for treatment of malaria may have an immune dampening effect. There's also some old literature indicating that quinine had success in treatment of at least one case of clinical rabies which is normally almost 100 % fatal. Also, in the recent Wisconsin case of successful clinical rabies treatment, vaccination against the virus was not given; this may have helped prevent an overblown immune response.)
    The touchstone in some diseases may be: what is the body's reaction to infection. If it is too powerful, sadly the very nature of the reaction may be the ultimate mechanism of fatality.
    I would be in favor of additional examination and investigation of the CFS findings before reaching a final conclusion. (end of Part II of comment) --Jacob Frumer (LEWRITER@EARTHLINK.NET)

    ReplyDelete
  7. My understanding of the controversy involving the chronic fatigue syndrome (CFS) comes partly from what I've read; however, before the community comes to the conclusion that the virus is simply a contaminant and unrelated to the syndrome, it's probably worth examining the research closer.
    CFS may in some respects look like a stubborn low level infection that doesn't resolve. If the possible infective agent in CFS, like in AIDS, infects blood cells (for example) and, in a sense, goads the immune system into targeting and destroying a population of red cells, and this leads to a low level anemia or systemic symptoms like lethargy, it may not be inconsistent with what we know of the syndrome.
    Perhaps this type of mechanism of disease follows what may have occurred in the Spanish influenza epidemic back in the early part of the 20th century. In that situation there was an anomalous result in that young people died at a relatively high rate. This is the opposite of what one might normally expect in influenza or any respiratory disease. One might expect that older people would be the population suffering highest mortality (eg because of weakened immune systems or troubled breathing capacity). However, young people died at a tragically high rate, and this may have been because of their strong immune system attacking the domain of infection of the influenza pathogen (ie lung or associated tissue). So what may have occurred is that there was a pathogen that unfortunately infected lung tissue, which then triggered a robust immune response, and this immune response naturally went after infected lung tissue. However, just as if a criminal barricades himself in your home, and the police go after him and target your home, and then have a shootout, your home likely will suffer damage.
    So in addition to possibly triggering a cytokine storm, Spanish influenza may have goaded younger adults' strong immune systems into attacking lung tissue. And strangely, those with a weaker immune system may have survived the infection better than those with a strong one.
    There may be eerie confirmation of this model of pathogenic lethality in other diseases like AIDS or rabies or malaria. In AIDS, what may be going on is that a virus has a particularly dangerous domain of infection, namely the T4 cell. The immune system may then target the T4 cell which means paradoxically, the more effective the body is at wiping out infected T4 cells, the more damaged the immune system becomes. And even worse, the body may begin to indiscriminately attack T4 cells even if they are uninfected. Again cytokinemia could result or irreparable destruction of the immune system could result or both. And sadly, subsequent infection by other pathogens that might normally have been fought off with ease, may now be fatal, because the immune system has been attacking itself. (This possible disease mechanism may also explain why a vaccine has been so difficult to create. A vaccine that succeeds in creating a robust immune response may inadvertently prime the body to react even more dangerously to its own infected T4 cells should they subsequently become infected by HIV well after vaccination.) (end of Part I of comment) --Jacob Frumer (LEWRITER@EARTHLINK.NET)

    ReplyDelete
  8. Similar disease processes may occur with ALS (body possibly attacking stubborn infection in muscle or nervous tissue), MS (body possibly attacking infected myelin), rabies (body possibly attacking infected brain and/or nervous tissue), and malaria (body possibly attacking infected blood cells).
    Interestingly, there may be a number of people whose immune systems adapt to or can deal with the infection. Perhaps this is what is occurring with elite controllers in AIDS, or maybe we see a temporary glimpse of this in partial remission in MS patients. (Also, incidentally, quinine which was effectively used for treatment of malaria may have an immune dampening effect. There's also some old literature indicating that quinine had success in treatment of at least one case of clinical rabies which is normally almost 100 % fatal. Also, in the recent Wisconsin case of successful clinical rabies treatment, vaccination against the virus was not given; this may have helped prevent an overblown immune response.)
    The touchstone in some diseases may be: what is the body's reaction to infection. If it is too powerful, sadly the very nature of the reaction may be the ultimate mechanism of fatality.
    I would be in favor of additional examination and investigation of the CFS findings before reaching a final conclusion. (end of Part II of comment) --Jacob Frumer (LEWRITER@EARTHLINK.NET)

    ReplyDelete
  9. I don't know why part II of my comment got posted before part I. --Jacob Frumer (LEWRITER@EARTHLINK.NET)

    ReplyDelete

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