Letter from America



Recently several establishment organisations, media outlets and some individuals have been casting doubt over the recent research by the Whittemore-Peterson Institute/National cancer Institute/Cleveland Clinic. Amongst these have been the British Medical Journal which has been quick to publish comment designed to criticise the XMRV research published in Science magazine in October 2009 [1].

Dr Mary Schweitzer has provided this commentary on the XMRV research.

XMRV - The Story is Just Beginning

by Dr. Mary Schweitzer Ph.D.

Dr. Mary Schweitzer from Delaware, USA, was a tenured professor of history before becoming ill with ME in 1994. Mary has been an active and very passionate advocate for people with ME for several years writing articles and taking part in the CFSAC (Chronic Fatigue Syndrome Advisory Committee) meetings to allow the patient's voice being heard.

  March 2010


The point that seems to be missing here is that the question, "Is XMRV the cause of CFS or M.E.?" is NOT primarily what scientists were interested in with the "Science" study.

They want to know what XMRV does, and that's a different question entirely.

When you ask if something was wrong with the research, the answer lies in the lab, and specifically, whether the finding was a result of contamination. (Answer: No contamination - "Science" made them run specific tests to confirm that).

Beyond that, collecting so many specimens that were positive is going to be very helpful in figuring out what this disease does - but while, for us, the pressing issue is "Does XMRV cause CFS or M.E.?" - for scientists, the pressing questions are "What does XMRV do to subjects who have it," and "How do we deal with it?"

In the end, there is going to be a subset of patients who are really XMRV patients.
What percentage? Too early to tell.

We knew what AIDS was before HIV was discovered. What is the equivalent for XMRV? It will help greatly in answering that question to have a ready-made data set. CFS - or, rather, a major subset of CFS - appears from the "Science" study to be that short-cut.

Are any scientists seriously questioning the existence of XMRV? None of whom I am aware.

The German study presented a conundrum, because they did not find any XMRV at all - not in the research subjects (men with prostate cancer), nor in the control group.

They should have found some.

Every prostate cancer study - except the one in Germany - has found a consistent level of XMRV in controls: 3-4% in the U.S., 1-2% in Japan.

The argument has been made that perhaps there are geographic differences in the prevalence of the disease. But I find it hard to believe that a disease that presumably has been around for 25 years has not found it's way from the US to GB, the Netherlands, or Germany.

So why the different results? In two cases there were glaring differences in the sample characteristics plus they did not use the same method; In the third study (Kerr), it's hard to say.

But absence of confirmation is not confirmation of absence - particularly in this case. Scientists had already moved on beyond "is there a newly discovered gamma retrovirus?"
The question now is "what does it mean?".

What did we learn from the studies that couldn't find XMRV anywhere, including the controls? Not much. The most we can do is ask what was different about the studies. Since they were not replications, there's a lot of potential reasons why the results were different.

If I want to learn what XMRV does, I need to find people who are positive and look at their characteristics. The Science study was helpful in that regard.

The four European studies, not so helpful. You can try to figure out what was different between the positive and negative studies - but it might be more fruitful to just move on from the Science study.

Every time the question has been, "Does virus A cause CFS?" a negative study has ended the conversation. [Even if it turns out that Virus A identifies a subset of CFS patients.]

We're all used to that. We're so used to it that some of us haven't noticed that THIS time it's different. It's different because it isn't about US.

So McClure-Wessely publish a quick and dirty study, and there's a pause ...

Must mean CFS doesn't have anything to do with XMRV, guess XMRV is going away.

[Note: the press is also off the mark here, for the same reason - they are used to CFS studies; they think they know this drill.]

But XMRV is not about CFS, and it most definitely is not going away.

We are not in sync with the scientific community, because the question we're real interested in is "Does XMRV cause CFS or M.E.?".

But the doubts raised by the European studies all come down to:
"Here's a group of CFS patients. If they don't have XMRV, then XMRV has nothing to do with CFS."

That leads us into the fuzzy world of "What is CFS?".

And (frankly) the young scientists interested in XMRV internationally really don't care what CFS is. They're trying to figure out what XMRV is.

So a study that finds XMRV in a clear subset of CFS is useful to the scientist working on XMRV - but a study that doesn't find it isn't all that useful, unless we try to focus on why there were different.


Whatever you think of the answer to that question, understand that this study was not conducted by the Whittemore-Peterson Clinic acting alone.

It was the result of a COLLABORATION among the WPI, the NCI, and the Cleveland Clinic.

So be sure to include the National Cancer Institute in your critique. As someone who knows the researchers at WPI, I take exception to the accusation that there's something unethical or incompetent going on there..

Extend your assumptions to the National Cancer Institute - if you think that's appropriate.

The existence of XMRV is not being questioned by biologists - they are all eager to play with the third known HUMAN retrovirus. But again, let me remind you how many years it took to really nail HIV - and a vaccine continues to elude us.

For a long time HTLV was the stepchild of retrovirus studies - what did it do? - but now we know it's connected to certain leukaemias.

Again - the REAL question is what does XMRV do?

We know it correlates with a virulent form of prostate cancer. Since the other two human retroviruses are associated with cancers, that makes some sense.

But in matching XMRV to a data set that already has known pathologies, we suddenly have learned a lot more.

I think I was probably a fairly typical subject in the study - I am positive for some odd immune markers and have a trail of viruses that won't behave, but there is no good explanation of how that came to be.

What do we know, if I am a typical patient in that study? WE KNOW NOTHING, except it can be present in people who, biologically, can't get prostate cancer.

But we can surmise.
We can suggest.
We can get a direction to move in.

I have the Rnase-L defect (similar to, but apparently not a perfect match for, the Rnase-L defect in that group of prostate cancer patients - mine weighs 37kDa, theirs weighs a little more, I think). I also have a natural killer cell function of 2%.

We already knew that I had recurring EBV, plus active HHV-6 (Variant A), HHV-7, and cytomegalovirus (CMV). In the course of this disease I have battled thrush, do not seem to be digesting proteins, have had polio-like paralysis of my left leg with a dropped foot, significant myofascial pain; can't pass a simple Romberg test; score abysmally on just one day of VO2 MAX stress tests (we've done more than one since I lost Ampligen), suffered blackouts, and been so confused I once poured an entire pot of coffee into a silverware drawer, absolutely convinced it was a cup.

Did XMRV cause these things?
Did XMRV cause the immune defects which caused the viruses which caused these


So let's go back over how we got here:

1. The researchers working on the relationship between XMRV and a particularly virulent strain of prostate cancer noticed that every time they did a study, the prevalence of XMRV among the study controls was higher than the prevalence of prostate cancer - it was consistently in the range of 3-4%.
2. The prostate cancer/XMRV researchers began to present papers suggesting there must be a link between XMRV and some other condition. They also noted that their XMRV patients tested positive for a strange defect in the 2'5'A synthetate antiviral pathway, producing Rnase-L that was basically half-sized.

3. A number of studies in the 1990s had found a similar link between defective Rnase-L and CFS (Fukuda) - specifically, the Rnase-L weighed 37kDa, roughly half the size of normal 80kDa Rnase-L. (I had one of the first commercial tests for LMW Rnase-L and I was positive for the abnormal protein).
NOTE: When Reeves or Wessely says there were promising biomarkers that turned out to be immaterial, ONE of them was the Rnase-L defect.
Looks like it was useful after all.
4. Judy Mikovits of the WPI approached the Cleveland Clinic about trying to see if CFS patients had XMRV, since so many had the defective Rnase-L.
The Cleveland Clinic and the WPI were joined in this effort by the National Cancer Institute, the latter being alarmed by the implications of a retrovirus in 3-4% of the population.
5. The research took almost four years. Patients in the study were tested using a number of different methods. THE JOURNAL "SCIENCE" MADE THEM CHECK AND DOUBLE-CHECK THAT THE SAMPLES WERE NOT CONTAMINATED.
6. After a rigorous process of ensuring the study met very strict scientific standards, an article suggesting a link between CFS and XMRV was published in "Science." Science is about as "A" list a research pub as it gets, because it encompasses ALL the sciences. (It outranks BMJ, Lancet, JAMA, and the NEJM, for example.)
7. NIH, WPI, and groups in several other countries are really busy trying to find a relatively quick test for XMRV that is accurate and can be performed by lots of commercial labs.

The urgent question in the scientific community is NOT whether XMRV is the cause or consequence of CFS and M.E.

The urgent question is how to get it out of the blood supply and how to keep it out of the blood supply. As usual, our story is, frankly, tangential to what the scientists are REALLY worried about - is 3.5% in the normal population already so high that it is too late to prevent the disease from becoming endemic?

Finding it among patients in practices in the U.S. that already test for a number of biomarkers and viruses (and I do NOT know if this is the case; I'm operating on the assumption that they really did use the Canadian definition) - was helpful in suggesting what happens to patients with XMRV.

If we can use CFS patients as kind of a jumping off place for the epidemiology, in the context that, as it now stands, the method used in the Science study was very time and labour intensive -

We can get a rough picture of the syndrome that would correspond to the disease.

For example, we already know that defective Rnase-L correlates with XMRV. What, then, about natural killer cell dysfunction? HHV-4, -5, -6, and -7? Coxsackie B? NMH/POTS? Hashimoto's? Hypocortisolism?

What about the CD4/CD8 ratio?

What about the "CFS" cancers? (Stem cell, Burkett's, other lymphomas and leukaemias) - plus prostate cancer?

The questions on the minds of scientists have to do with how quickly this virus binds with DNA; what would keep it from replicating; characteristics (appears to be carcinogenic and damaging to the immune system all by itself); the envelope discovery by the French; what drugs impact it (people are talking about taking AZT but we don't know how it would respond to AZT); why is there a correlation with defective Rnase-L?

We are just at the bare bones beginning.

But I do want to point out that many of the biomarkers and viruses that were supposedly disproved are now commonly diagnosed in CFS if you have a cutting edge doctor. I have immune defects and viruses galore, but the only thing I have that is recognized by CDC is cytomegalovirus (which was discovered before AIDS, which should give you a hint as to why the other ones remain buried).

We are going to have to ask is M.E. really different from "cluster-outbreak" CFS (Tahoe-Truckee, Lyndonville NY, Rockville MD, and many, many more) - because obviously XMRV was not around in the 1950s; were there XMRV clusters in the UK in the 1980s? Is XMRV-CFS different from Ramsay-M.E.?

So - ultimately -

1. This is NOT about the Whittemore-Peterson Institute. They have been in the forefront of the news, but this was conducted in conjunction with the Cleveland Clinic and the National Cancer Institute, the part of NIH that co-discovered HIV all those years ago (and also where Ablashi was working when he discovered HHV-6 and its two variants). If you're going to make accusations of shoddy scientific method, include all three groups.

2. We are, quite naturally, obsessed with whether XMRV causes or even correlates with CFS-Fukuda and M.E. But the scientific community as a whole is not.

3. Personally, I wonder why we've found so many retroviruses in other mammals, but only 3 in humans - and they all showed up in the same decade. Weird.

4. Keep in mind that retroviruses do not behave like other viruses - they become part of your DNA - so figuring out how to attack this thing is not going to
happen overnight.

5. In testing CFS patients for XMRV, scientists were not unlike the drunk looking for his car keys under the street light. To the extent we can find links, that helps scientists draw a picture of what XMRV can do.

But to scientists, the question is precisely that:

"What does XMRV cause in patients?"


"Is XMRV the cause of CFS?"

Try to keep that in mind - this story is just beginning.

Mary Schweitzer

Last Updated: 21/03/2010


[1] Link to fuller description of WPI research

Further References:

Invest in ME Comment - Look to the End

Invest in ME Funding WPI research - click here