Tuesday, January 12, 2010

XMRV, Chronic Fatigue, and Controversy

I've been following the XMRV research in detail. Researchers at the Whittemore-Peterson Institute affiliated with the University of Nevada have identified a strong link between CFS and XMRV. Some scientists have speculated (and have clearly identified it as a speculation) that it is the cause of CFS. All scientists who have made such speculations have stressed that we are in the early stages of research and that further research is needed.

Recently they were challenged by a paper from the UK by Simon Wessly et al published in PLOSOne. PLOSOne is a CROCK. PLOSOne is a pay-to-publish site with minimal peer review. With $1365 you too can publish your science there. I went and looked up their submission guidelines and policies myself. If the authors really did good science, why didn't they publish it in a normal medical or scientific journal with rigorous standards and a robust peer review process?

That paper, which purports to find no XMRV in 186 'CFS' patients has numerous screaming flaws; the biggest one of which is that the do NOT use the same definition of 'CFS' as the WPI research. Further, there's no healthy controls in the research and they didn't search for the same DNA sequence as the WPI. In other words, it looks like science, but it isn't. If I report apples, and you search for oranges and don't find them, it's meaningless. All it really proves is that apples aren't oranges.

WPI explicitly uses the Canadian Clinical Consensus, which is the gold standard in medical description of CFS. Here's a page with links to the Canadian Consensus: http://www.cfids-cab.org/MESA/ccpc.html -- If you have Chronic Fatigue Syndrome, think you might, or know somebody that does, the Canadian Clinical Consensus will be very helpful.

The UK paper does not use the Canadian consensus; they use the Oxford/CDC definition, which explicitly excludes anyone with a physical contribution to their fatigue. In other words, the WPI patients, which meet the Canadian consensus, all have demonstrable physical aspects to their illness, and therefore would not and could not be diagnosed with CFS in the UK.

The UK cohort consists of fatigued psychiatric patients, although it does excludes some psychiatric conditions as per the Fukuda definition. Note that their paper does not claim to follow the Fukuda definition, it merely claims to exclude the same exclusions that Fukuda does. Some people have said that both WPI and UK use Fukuda standards --no, the UK study does not.

Further more, the UK patients are all in routine treatment through the chronic fatigue center at Kings College. In other words, these are people who are willing to go along with a psychiatric diagnosis and treatment. People who don't benefit from psychiatric treatment or who believe their condition is physical, not mental, are not going to be members of this clinic!

Above and beyond that, the UK research did not follow the exact same procedures as the WPI research, which is essential in an replication study. The UK study also did NOT include healthy controls. Ergo, they have foregone one of the essential elements of sound scientific testing. They assert that their patients are typical of the UK -- they're not.

There's a lot of people in the UK, including scientists, who believe in a physical explanation and have produced research and documentation in support of their view. We cannot generalize from one clinic that specializes in somatoform CFS to the rest of the UK.

Not yet published is information about UK patients participating in testing who have gone through their medical doctors rather than psychiatric services. These Individuals participated in a group that sent their blood samples to the WPI to be tested. Some individuals have received their lab reports and posted their results online; they are XRMV+. This is a small number of people, so we don't know how many UK patients participated or what the over all result it, but clearly, XMRV does occur in some patients in the UK. Thus, the Wessly et al conclusion that XMRV is not in the UK is wishful thinking at best.

XMRV is known to cause disease in animals: nasty ones, such as immune and endocrine disorders, and cancer, such as lymphoma. While it is not known exactly what it does to humans, we can expect that it will do similar things to us as to other mammals. CFS patients have already been shown to have a higher risk of cancer, especially lymphoma. The symptoms of CFS (Canadian Consensus) are definitely like the symptoms of XMRV in animals. Ergo, it is plausible to suspect that it causes CFS. It remains to be be proven, but it's a promising line of research and more scientists around the world are after it.

'CFS' has been applied to a sloppy variety of conditions by many writers who choose to ignore and cherry pick the scientific evidence; but that doesn't mean that it isn't real or that XMRV is irrelevant.

The WPI researchers have proposed the name XAND for X-associated neuroimmune disorder for the Canadian consensus disease if the XRMV connection holds out. If Wessly and the other advocates of 'erroneous illness beliefs' want to hang onto CFS, let them. I'll get tested for XMRV and treated by medical doctors for XAND.

The UK paper does do one great good thing. It makes clear that two very different patient cohorts are being lumped together under the label 'CFS'. The authors appear to be unaware of that result; but once you've studied all the evidence in this and many other pieces of research, it is very clear that there are at least two different syndromes lumped together.

Of course, we already knew that. A study done in the UK by Dr. Kerr compared patients with Q fever, CFS, depression, and healthy controls. They fell into two clusters: Q fever and CFS shared many genetic anomalies (84-88), while depression and normals had very few to none (0-5).

However, nobody paid very much attention to any of the research about CFS until now. The only reason, I'm sorry to say, why this matters, is that the WPI study found that 3.7% of healthy controls were XMRV+. This finding has profound implications for the blood supply and public health. That's what made the medical establishment and government agencies sit up and take note at last. Oddly enough, they had previously ignored Japanese research that found XMRV in 2.7% of healthy controls. (This little tidbit is actually in the Wessly et al paper mentioned above!)

They're not terribly concerned about the CFS people, but they do care very much about the idea that the people who vote them into office might, say, be getting infectious cancers from the blood supply and passing them onto to others through saliva or blood... That's a nightmare scenario that must make you break out in a cold sweat if you were supposed to be a public health agency and you haven't done squat about CFS for the last 25 years...

Of course, we don't really know if that's possible, but it's not far-fetched. XMRV has been detected in saliva and blood, and is capable of transmitting infection via blood in the laboratory. Dr. Peterson in his comments at the CFSAC meeting told about a patient of his that got XMRV via blood transfusion--he has before and after blood samples.

XMRV causes cancer in animals and was discovered in connection with prostate cancer. Intimates of people with CFS are somewhat more likely than the general public to have CFS. One study of Gulf War Syndrome found that in a subset of parents with CFS, their children were much more likely to have autism.

On the other hand, German and Irish researchers have not found XMRV in prostate cancer. They have used much larger samples than the US research. Why? Some speculate that their methods are not capable of detecting it, which they vigorously deny. They prefer to speculate that XMRV is regional, and thus is found in the US but not Europe. That doesn't make much sense, either, given that viruses travel very well. Although viruses are more common in some areas than others, they still exist everywhere. On the other hand, that XMRV has been detected in Japanese and American populations does suggest another possibility: genetic susceptibility.

Japanese and Native Americans are descended from a common ancestor somewhere between 10,000 - 25,000 years ago. If XMRV or a genetic susceptibility entered the Asian genome before the population of America, people with Asian and Native American ancestry would be more likely to have XMRV than Europeans. This is not unusual; Africans are much more likely to get sickle cell anemia, for example. Still, no information has been provided about the ethnic makeup of the people who are XRMV+, so this is pure speculation. It also points out that race and ethnicity should not be ignored when conducting scientific research.

More research is under way, and more papers will be appearing over the course of the next year. It's an interesting topic with significant implications for the health of all of us.

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