By Dov Michaeli
This post may strike you as “inside the beltway”, some scientists arguing about arcane experimental results that have nothing to do with your life. I don’t think so. This post will show you how science works, and it will tell you why this is important.
In a February 11, 2011 post on this blog site we discussed CFS (Chronic Fatigue Syndrome) and the vexing diagnostic and therapeutic problems associated with it. We have absolutely no idea what causes this syndrome, and without an identified cause it is exceedingly difficult to devise rational therapy; you are basically shooting in the dark.
A momentary ray hope shone when a virus called XMRV was identified in over 60% of patients who were tested. Finally, a “real” cause, a tangible target. The enthusiasm quickly faded when science did what it’s supposed to do –try to replicate and confirm the results. Here is an extended quote from the February 11 post:
XMRV is a mouse virus that causes leukemia in mice. XMRV was first identified in 2006 in patients with prostate cancer. A study published by Lombardi and colleagues (Science, 2009;326:585) reported finding evidence of XMRV DNA and antibodies in about two-thirds of CFS patients and nearly 4% of healthy persons. Hopes were high that finally, at long last a “real” causative agent for this ill-defined disease was found. Not so fast; a bunch of other papers found no trace of the virus DNA either in patients’ or control blood. So what is the source of the discrepancy? It turns out that it was a simple case of contamination. DNA assay, called PCR, used kits that were contaminated with mouse DNA. Also, the most popular animal in biological laboratories is the mouse, and its DNA is literally everywhere. Consequently, incredible measures need to be taken to ensure lack of contamination. But, we are only human and sometimes we screw up.
The Lombardi paper in Science reports also on anti XMRV antibodies in the patients’ sera, and this assay does not depend on DNA, but on protein. However, a report published by CDC investigators and colleagues in July 2010 found no evidence of antibodies. I cannot think of an easy explanation for this discrepancy.
End of story? Not quite. In the May4, 2011 of the Journal of Virology, Singh and her colleagues published yet another study that refuted the findings that had led to the XMRV theory. They obviously were focused on eliminating any possible post hoc argument that their method of analysis was different from the original paper. They used the PCR technique, which is the most sensitive available for detection of viruses. They worked closely with the team that had carried out the original tests to make sure there were no discrepancies in the execution of the assays. They tested 100 HIV sera, including 14 of the original samples that tested positive in the Science paper. To remove any doubt, these sera were selected by Judy Mikovits, the lead author of the Science paper.
The results? (drum roll):
None of the sera showed any trace of XMRV. As Singh stated to Science: “I’d urge people to move on rather than to keep their hopes hanging on the link between XMRV and CFS,”
I agree. Singh and her colleagues went out of their way to ensure that there was no rational way to question their results. Yet, Mikovits stated to Science “”These people are infected. This study says nothing. We have complete confidence in every bit of the results in the Science paper. We don’t think any of it is wrong.” A surprising attitude from a scientist who is supposed to look unflinchingly at the data, personal bias notwithstanding. In any event, yet two additional studies examining all the original sera by independent groups as well as by Mikovits’ original group should be published in a matter of months. Will this nail it, once and for all?
Why is it important?
This is the way science works. You constantly check and re-check assumptions, theories, methodologies, results, analyses. I was surprised to read a couple of weeks ago that the journal Physical Letters published an experiment that verified, yet again, Einstein’s Theory of Relativity, at a cost of a few hundred million dollars. One may think that it is a bit excessive (as I think is the case with the endless studies refuting the XMRV hypothesis), but it is necessary.
People tend to cling to theories and faux-information that they want to believe in, regardless of the evidence. When it comes to ‘birthers’ and ‘deathers’ (people who don’t believe in Bin Laden’s death), I don’t think we need to waste time and money to persuade them. But when it comes to public health, it is more serious. Mothers who wanted to believe in the theory that vaccination causes autism put their children’s lives at risk. It is imperative that we disabuse them of the idea. Some people with CFS who believe in the virus theory take retroviral medication, used in HIV therapy. This is worse than useless –it is dangerous.
Despite CFS activists’ suspicions of anything that smacks of psychological therapy, there is an excellent study showing that psychotherapy coupled with graded exercise is the most effective of all the therapeutic modalities in clinical use. There is nothing denigrating about it. CFS is not “in your head”, just as rheumatoid arthritis isn’t. Yet, graded exercises coupled with psychological support works wonders for RA patients. Why not for CFS?