February 7th, 2012

Chronic Fatigue: Is There Hope After XMRV?

I’ve been following the chronic fatigue/XMRV story from the start, which was compelling for several reasons, including:

  1. A potential cause was identified of a very debilitating, mysterious illness.
  2. Lots of very smart ID people (including some of my colleagues) studied it.
  3. Media coverage, notably from the Wall Street Journal and the New York Times, was particularly skillful.

In that last vein, the Times today has a fascinating summary of the current situation for this once promising link.

In a word, the link is kaput

After numerous investigators were unable to duplicate the original results, Science issued an “Expression of Concern” about the paper they had published in 2009. Then in late December, that paper was fully retracted by the Editor of the journal, as was a key supporting paper — really the only supporting paper — that had been published in the Proceedings of the National Academy of Sciences. 

Could things get any worse? Of course. Here’s what’s come of the lead investigator in the original Science paper:

Dr. Mikovits left her position as research director at the [Whittemore Peterson Institute] in a dispute over management practices and control over research materials. The institute sued her, accusing her of stealing notebooks and other proprietary items. Dr. Mikovits was arrested in Southern California, where she lives, and jailed for several days, charged with being a fugitive from justice.


But even with all these clouds, there’s an  important silver lining to all this news nicely articulated by a noted virologist:

“The disease had languished in the background at N.I.H. and C.D.C., and other scientists had not been paying much attention to it,” said John Coffin, a professor of molecular biology at Tufts University. “This has brought it back into attention.”

I couldn’t agree more. And with that greater attention, perhaps we’ll see some discoveries that really help people.

7 Responses to “Chronic Fatigue: Is There Hope After XMRV?”

  1. Kate XMRV Positive UK says:

    Research continues. Professor Ian lipkin, Dr Judy mikovits, Frank Ruscetti, CDC, NIH and FDA all continue to look into XMRV and Mouse retroviruses.
    Tests used on ME/CFS patients blood were picking up new human retroviruses.

  2. Jon says:

    Paul, great post! I think that characterizing her recent arrest as “a dispute over management practices and control over research materials” by the NYT is letting her off way too lightly. I had originally thought that her results were due to contamination alone, but after reading this, outright fraud is not out of the question:


  3. Julia says:

    Diseases with a high incidence in one country and a low one in another always make me wonder. Chronic fatigue, fibromyalgia and ADHD requiring stimulant treatment are on this list. In my country of origin, their incidence is so much lower than here that I’ve always wondered what pressures people are under here to make these diseases a necessity.

    Maybe the 6 weeks vacation and 38 hour work week that people have in my country of origin result in less chronic fatigue. Or is it the fact that people call in sick (and get full pay) when they are just feeling really lousy for a day? Maybe getting little breaks helps against these diseases whose main characteristic seems to be the body’s rebellion against unjustly exhausting demands.

    • Paul Sax says:

      Hi Julia,
      Not sure where you are from, but it certainly sounds nice! And you are right that being run ragged by work is something we Americans sometimes take a perverse pride in — and why?

  4. Julia says:

    Going off on a tangent that comes to mind – why is it that “adolescent fatigue syndrome” – tiredness, body aches, malaise, the need to miss weeks of school – attributed by helpless pediatricians to EBV or Lyme disease and sent to ID clinic – seems by my anecdotal impression to occur predominantly in upper middle class families?

    Could it be that this is the demographic among whom young people have to be “the best” in everything they undertake? In my country of origin, you can get a decently respected and fine-paying job by completing an apprenticeship. You don’t have to go to college. If your talents lie more towards work with your hands, it’s acceptable, even if your father is a doctor.

    Since it is very painful to begin to recognize that one will not be “the best” at everything or even at anything, if one’s value as a person is predicated on that by those around us, I suspect many of these young people are just despairing at the idea of 40 more years of this kind of pressure ahead of them.

    Not an issue that is resolved with a course of antibiotics – as many families hope to do.

  5. Cre says:

    “In a word, the link is kaput.”

    Not in any scientific sense is it kaput.

    There has been no replication study of the proven methods. There has been no negative study that used clinically validated assays.

    There is no evidence of mouse contamination and no evidence of VP62 plasmid contamination. Only Silverman’s error was the link to VP62. The sequences detected are polytropic as were those found by Lo and Alter, who also did not ask or agree with the retraction of their paper.

    Furthermore the paper Paprotka et al. that claimed to have found the origin of VP62, which was a lab artefact created in 2006, has been left in tatters since it was revealed that an assay is missing and tests were used selectively, that the tests were not very sensitive and that they likely had human contamination of the mice they tested. Also, PreXMRV-2 is missing to have created XMRV.

    Are you aware that Mikovits could not have been a fugitive as there was no restriction on her going home to California prior to leaving Nevada? That she denies having the notebooks. Also, the western blots in Lombardi et al. were not her work.

    Anyway the prostate viruses are represented by VP42, the viruses in ME patients are polyropic. Lots of trouble ahead for virologists who attempt to ignore this.

  6. KAL says:

    @Julia – You don’t seem very familiar with either the epidemiology or the diagnostic criteria for myalgic encephalomyelitis – sometimes called chronic fatigue syndrome. The World Health Organization classifies it as a neurological disease by the way not “tiredness”.

    The key symptom according to clinicians and researchers is post exertional exhaustion lasting 24-hours or longer unrelieved by rest and upon minimal exertion such as doing the dishes or walking the dog. Vacations and shorter work weeks are irrelevant in other words.

    It is also far more than the solitary symptom of pathological fatigue however, this PEME is part of a distinctive pattern that includes objectively proven deficits in memory and concentration for example. (Carruthers et al 2011; Jason et al 2011)

    Epidemiology in any disease is directly tied to specificity and severity in the diagnostic criteria/definition used. It can also tied to how comprehensive the health system is in the country in question. Many patients are misdiagnosed or under-diagnosed whereas other definitions may mix in people who do not have a disease with patients who do thus confounding the scientific literature. For example in the early 1990s the disease was given the misnomer “yuppie disease” because the study only looked at upper class women and the pattern of reports from doctors. Subsequent epi studies showed this to be inaccurate because not all variables such as race, age and socioeconomic demographics were accounted for.

    As for adolescents with ME or CFS you might want to read the longitudinal work being done by Ben Katz and Renee Taylor for some accurate information. There is no antibody test for privilege, but there are tests which proven pathogen involvement in subsets of patients.

    Factual information is publicly available – you just have to inform yourself.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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