May 05 2011
Chronic fatigue syndrome (CFS) is an enigmatic disorder. The primary symptom is debilitating fatigue that does not resolve with rest. Fatigue, however, is a very non-specific symptom, meaning that it can potentially result from many underlying causes. Anything that saps the energy our body uses to function will cause fatigue. In part CFS is a diagnosis of exclusion – it is based upon the presence of fatigue in the absence of any identifiable underlying cause. Therefore not everyone with chronic fatigue has CFS.
The non-specific nature of the clinical syndrome also frustrates our attempts to find the underlying cause or causes (it may, in fact, be many diseases all with a similar clinical presentation). So many things can potentially cause chronic fatigue – where do we begin. However, a chronic viral infection has long been suspected as a likely cause, at least in some cases.
Recent studies have found a potential association between CFS and a retrovirus called XMRV (xenotropic murine leukemia virus-related virus). This has led some desperate patients with CFS to take anti-retroviral drugs (used mostly to treat HIV – another retrovirus) off label in order to treat their CFS. But these studies, while intriguing, were considered preliminary.
Now a larger, more rigorous and comprehensive study has been published and has found no association at all between XMRV and CFS.
We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blinded manner using molecular, serological and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS. We did not find XMRV or related MLVs, either as viral sequences or infectious virus, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies.
This looks like a very thorough study – they looked for the virus, or pieces of the virus, or antibodies to the virus, in their new subjects plus in samples from a previous positive study. They further identified possible evidence of contamination that could have caused the prior study to be a false positive. This seems like a pretty solid nail in the coffin of the XMRV hypothesis.
This episode reveals many of the features of medical research that are worth pointing out. First – much preliminary evidence will turn out to be wrong. That is the nature of exploratory research. This is partly due to the fact that preliminary studies tend to be small and less than rigorous. This is not due necessarily to being sloppy – the point of preliminary studies is to see if there is any potential to more elaborate research. These studies are testing the waters, to see if further investment in money and effort is warranted.
Preliminary studies are also used to learn how to better study a question. The most useful data to come out of such studies is often how to conduct better studies. This partly flows from having the broader community criticize the preliminary studies, probe for weaknesses and potential error. Then all of that criticism can be taken into consideration when designing later confirmatory studies.
But as I have discussed often on this blog, we now live in the age of mass media and the internet. Preliminary exploratory studies are made available to the public at large, including patients and their families. The media often does not do a good job of putting such preliminary evidence into context, so every study is a “breakthrough” or “may lead to a cure.” More often than not the preliminary research does not pan out, as seems to be the case with XMRV and CFS.
It is human nature to focus on the potential for benefit. People who are sick see a potential cure, and may not appreciate the potential harm of an experimental treatment. I am not aware of any comprehensive studies, but there is at least the reasonable concern that all of the medical treatments based upon preliminary studies likely cause more harm than good. Patients are playing the lottery, and everyone thinks they will be a winner, when in fact most people lose (almost by definition).
There is some threshold of evidence beyond which benefit starts to outweigh harm. That line is not sharp, and honest and informed experts can disagree (and do) about where exactly the line should be placed – but there is a line. It is the responsibility of the medical community and of regulatory bodies to minimize and avoid practicing medicine below that line (causing more harm than good). While the purpose of research is to clarify where the line actually is.
There are numerous examples today of medicine being practice below the line – taking anti-retroviral therapy for CFS is just one example. Another prominent recent example is using the liberation procedure for alleged CCSVI as a cause of multiple sclerosis. Stem cell clinics for a host of neurological disorders are another example, although that also appears to be an example of fraud, not just premature treatment.
I would also argue that the vast majority of what passes for so-called complementary and alternative medicine (CAM) also exists below the line, and is causing more harm than good. This is the very definition of CAM – treatments that have not be adequately established to be safe and effective, and many of which are so implausible they are likely to never be.
The XMRV story is just another example of why we need good science to guide medical treatment, and why we need to be patient to let the process work itself out to an adequate degree before we jump on a new treatment.
17 Responses to “XMRV Not Associated with Chronic Fatigue Syndrome”
Leave a Reply
You must be logged in to post a comment.