Who Are Those Guys? Gazing at the distant cloud of dust raised by his dogged but mysterious pursuers Butch Cassidy turned to the Sundance Kid and with some awe muttered “Who are those guys?” Despite all their tricks that posse had stuck on their trail like glue. Has the Whittemore Peterson Institute’s posse caught one of the slippiest preys in all medicine? Or will a significant subset of ME/CFS patients slither through their hands?
A good part of that answer may depend on the answer to “Who are those guys?” Specifically when WPI researchers called the subjects of their study chronic fatigue syndrome (ME/CFS) patients just who were they talking about? And who will end up having this virus? Answering that question will determine if the WPI posse can corral the whole disease or just a portion of it.
Lets take a close look at just who was in the little study that shook the ME/CFS world.
Putting Your Best Foot Forward – The WPI did not choose your garden-variety chronic fatigue syndrome patients for their first study. They chose the kind of patients that they had the most confidence in with regards this virus. There’s nothing wrong with this; its standard procedure in the research world. In their first study researchers usually include patients they think will best make their case. Those patients still fit the definition of the disease but they’ll often have less than subtle differences. (Given the vague definition of this disease make that very large differences. This is presumably one reason the CDC went to a random sampling scheme.)
An immune researcher would probably try to include pathogen loaded, cytokine upregulated, fluey patients. A endocrine researcher might fit in patients with hormonal problems. Perhaps not surprisingly that first study usually works out pretty well but the second one by an independent researcher who didn’t try and gild the lily, so to speak, often doesn’t.
When scientists want to find a virus, we look for it in the sickest individuals because often this is where there is likely to be the highest levels of a virus, if present. Dr. Suzanne Vernon
A Special Group of Patients – In this case Whittemore Peterson Institute was refreshingly direct in how they ‘stacked their deck’. They stated the study participants had ‘severe disability’, low natural killer cell functioning, increased pro-inflammatory cytokine levels (primarily IL-6, IL-8), ‘extremely low’ VO2 max during exercise testing and RNase L dysfunction. During a radio interview we learned that 20% of the patients had lymphoma. Without knowing their functional status it sounds like they are housebound and many very well may have been bedridden.
Outbreaks! (Outbreaks?) – They also came from areas where ‘outbreaks’ had occurred. The WPI took a page from the distant past when they included outbreaks in the parameters. No one to my knowledge has officially reported an ‘outbreak’ in several decades. Why therefore specifically go back to where ‘outbreaks’ had begun (and therefore not include ‘non-outbreak’ areas)?
Was this to highlight the possibly infectious nature of this pathogen or to draw attention to an important but mostly forgotten era of ME/CFS thinking? Or was it central to their case? Was limiting the participants of the study to known infectious events one way the WPI gilded their lily? (Will ‘non-outbreak’ patients fit the WPI’s scenario? My guess is that they will but….).
Whatever the answer to that question its clear that these do not appear to be your ‘normal’ chronic fatigue syndrome patients. A recent Pacific Fatigue Lab study, for instance, found low VO2 max levels in about half their participants. A considerable number of those participants came from Dr. Montoya’s and Dr. Peterson’s pathogen studded patients. Given that these participants had very low VO2 it’s possible that a significant number of even pathogen ridden patients might not have gotten into this study.
This first paper clearly referred to a certain subset of patients. Again this is pretty much expected in the first paper but it does make it difficult to interpolate the results to other patients.
The Big Question – Do I have an XMRV infection? Taking a very conservative view of this question and going strictly off this paper you’d have a good chance of testing positive for it if you had the following characteristics; an infectious onset, extremely low VO2 max levels, low natural killer cell functioning, RNase L. problems and increased inflammatory cytokines. (If you have all of those plus lymphoma you’re almost certainly in – but in a very bad way). Even in these very poorly off patients only two thirds of them tested positive for the virus but that is apparently more a function of a not completely accurate test than a lack of virus – the WPI is working on a more accurate test right now.
Room For Hope – If you go strictly by the study it’s beginning to sound like it might not apply to the ‘average’ ME/CFS patient. There is considerable room for hope, however, that it will. Dr. Mikovits reported that 95% of a larger set of patients (n=330) tested positive to an antibody tests. The antibody test did not measure active infection but it did indicate that these patients have been exposed to the pathogen. Dr. Mikovits also stated that she expects most ‘ME/CFS’ patients will test positive for the virus. Dr. Cheney, our only independent guide to the prevalence question right now, contributed 14 patients to the study and reported that his results were similar to the group as a whole. That’s encouraging.
It’s also encouraging that the patients came from me areas across the US. The virus has also been found in some FM patients, autism patients and atypical MS patients which suggests that the number of people with this virus will broaden not diminish.
Thankfully the number of healthy controls testing positive has remained very low throughout; this pathogen – in contrast to all the others associated with ME/CFS – appears to to be quite rare in the general population – an important finding.
Plus the WPI recently stated that not all the people in the study had abnormal RNase L/NK cell results thus it doesn’t appear that you need to have these immune dysfunctions in order for the virus to be present. More and more it’s looking like the broad group of ME/CFS patients may have this virus. Still the only thing that will seal that deal are studies showing that moderately ill patients are infected.
Professional Recomendations – It wasn’t surprising that the first recommendation from the ME Association was for the WPI to begin
Carrying out further and larger studies using different populations of people with ME/CFS, including people at different stages of the illness (to see if the virus is present in the same percentages in both early and late cases) and in all degrees of severity.
Dr. Vernon echoed this when she stated that
“Independent replication studies should also include patients with mild and moderate CFS, at least one chronic disease control group (e.g., multiple sclerosis, lupus) and sex and age-matched healthy controls.”
Who Are Those Guys? So we don’t really know who ‘those guys’ – the ones with the virus – will turn out to be. Sure we have some tantalizing hints that the virus is found in more types of patients than the Science paper can show but before most patients pop the bubbly they should wait to see studies that contain patients that look like them. The good news is that those studies should already be underway.
Beachhead Established – the Jungle Awaits – This is not to criticize the Whittemore Peterson Institute. It’s about being wary in the face of a complex issue. Given how research happens these problems are inevitable. The WPI’s first job was to establish a beachhead and they’ve established the most biggest beachhead yet in this disease. Their next job is even more difficult – to try and work their way deeper into the jungle that has been ME/CFS. Hopefully they’ll be able to.
**Addendum – some good news has cropped up regarding the possible spread of XMRV in chronic fatigue syndrome patients. It turns out that one of the criteria the WPI used to select their patients in this study – RNase L dysfunction – is not a factor in who carries the infection. People with or without RNase L dysfunction can test positive for XMRN.
How ironic this is since it was the RNase L connection that led Dr. Mikovits to XMRV in the first place. As they say sometimes it’s better be lucky than right. In this case it looks like we were actually lucky.