The relationship of XMRV to CFS and M.E.

I know that the “hot” topic of the moment is whether XMRV or the gamma retroviruses in general can be transmitted by way of blood donation, but I would like to back off for a minute and survey the problem.

I happened to be watching “And the Band Played On” last night, and I noticed that they were looking at material from lymph nodes, not from blood draws, when they discovered HIV. That’s very interesting for those of us who suffer from M.E. (given the hopelessly dismissive name “chronic fatigue syndrome” by the U.S. CDC in 1988), because, at least for those of us in the U.S., tender lymph nodes are a major characteristic of the disease. Dr. David Bell once pointed out that patients with this disease can point to lymph nodes other people don’t even know they have.

Why are we not looking at lymph nodes instead of just blood serum?

It seems to me that the primary issue is whether or not up to a million Americans, sick with a disease that has been given a stupid name and garbage diagnosis by the CDC, actually are carrying a retrovirus or family of retroviruses. CDC has been “studying” this disease for 25 years, yet freely admits that 85% of patients – at least 850,000 people – have the disease but no diagnosis.

Research in France suggested that the disease pools in the lungs of patients – boy would THAT be bad news! Why are we not looking for it in sputum, then?

Understand that a retrovirus – ANY retrovirus – is going to be transmissible through blood and body tissue because it becomes part of your DNA, and eventually finds its way all over your body. A better question, perhaps, is whether the mechanisms that have been used to keep from transmitting HIV and HTLV will work with a different family of viruses, the gamma retroviruses, where XMRV fits.

We do not know much about how gamma retroviruses in humans. XMRV was the first one found, almost five years ago, in patients with a particularly virulent form of prostate cancer). However, there is a lot of research into gamma retrovirus behavior in the animal world. So that part of it should not be that difficult.

In contrast, finding consistent and homogeneous data sets of patients with M.E. among those diagnosed with CFS the way recommended by CDC (by first starting with people who are fatigued, and then eliminating any possible physical cause), cannot be done without acknowledge the failure of the CDC approach.

Now I come to Exhibit A – me, moi-meme, I.

I was in the Lombardi et al study in “Science” (October 9, 2009), and I was positive for XMRV. Hmm, I thought, that’s interesting.

Interesting but not, for me, earth-shattering, because I already had plenty of abnormal test results and viruses! I have been the patient of two excellent specialists on this disease – Dr. Marsha Wallace of Washington, DC (who no longer practices), and Dr. Dan Peterson of Incline Village, NV, who has been treating patients with this disease and participating in research studies about it, since a major cluster outbreak occurred in the Tahoe-Truckee area, or North Lake Tahoe, where Incline Village is situated, in 1984-85. They knew I had what the cluster outbreak patients had, and every biomarker, every chronically activated virus, was another step in understanding what has caused these outbreaks.

I personally believe I was caught up in an outbreak centered on Cherry Hill, NJ, an area that contributed a large share of the students at Villanova University outside Philadelphia, where there was an outbreak of Epstein-Barr in 1990 that swept up not only students, but faculty as well, including two other members of my department besides me. My full collapse did not occur until later; I have often wondered if the information that was censored or dismissed in the late 1980s and early 1990s might have spared my transition into the hellish state of progressive M.E. on October 24, 1994.

More to the point, however, is that if anybody has what the CDC calls CFS, I do. (For the record, I do not have what the British psychiatrists call "CFS.") Let’s go back over some of what I test positive for besides CFS, shall we? (This is testing done most recently in 2008 and 2009, when I was in relapse off the experimental immune modulator Ampligen. I have been back on Ampligen for ten months, and many of these tests have better results now.)

1. Immune biomarkers: 37kDa Rnase-L, a natural killer cell function of 3%, and abnormal cytokine counts.

2. Active viruses (some even active in my spinal fluid): recurring EBV (comes and goes – the rest are active all the time off medication); HHV-6 Variant A; HHV-7; cytomegalovirus; and three strains of Coxsackie B.

3. Abnormal SPECT scan and very abnormal VO2 MAX scores.

4. Abnormal Holter Monitor test and abnormal 24-hour BP/pulse test; diagnosed NMH/POTS

5. Hashimoto’s thyroiditis; hypothyroidism apparently caused by an inability to convert T4 to T3 (I take supplemental thyroid medication to keep my T7 panel normal).

6. Major symptoms: Severe pain behind my eyes and in the back of my neck 24/7, plus frequently occurring severe headaches. Photophobia, sensitivity to loud noises, tinnitus, parathesias, severe muscle weakness (to the point of collapsing to the floor), ataxia, blackouts, expressive dysphasia, central auditory processing (CAP) difficulties, dyslexia, dysgraphia, loss of volition (what I would call "the pause," as if someone had punched the pause button on my control panel), and profound confusion.

7. Other diagnosed related symptoms: inexplicable difficulty falling and staying asleep, myofascial pain syndrome, dropped left foot (that clears up on medication – I have no idea why), inability to pass a Romberg test.

See? XMRV was, well, okay, something new. And I find the research on both XMRV and the gammaretroviruses convincing, but then, I am not a scientist (although I can read statistics – and know how to put together a data set and how to evaluate one put together by someone else).

It is extremely important that while the light is shining on retroviruses, we not forget these other problems represented in one case – me – and that I share these viruses and biomarkers with a large number of my fellow patients (those who have had the money to get the tests, because by and large you have to pay cash for them, as I also have to pay cash for the treatment – the CDC is doing a tremendous job for the insurance industry). I have friends with infections I don’t have as yet – parvovirus, Lyme, mycoplasma, clamydia pneumonae. That we know of. And I have some things my friends don’t have.

We also have lost people to myocarditis (infection of the heart muscle), rare cancers such as stem cell cancer, and sometimes, just too many things wrong at the same time.

By and large this is a disease of immune defects, multiple infectious assaults, and resulting damage to the neurological, endocrine, cardiac, and biomechanic mechanisms.

The disease bears a resemblance to MS not only in symptoms, but also in having different flavors. I know patients who were sick in late adolescence, recovered completely, then relapsed again in their late 30s or 40s. I know patients who thought they had recovered until they started training for a marathon (one was a navy SEAL), which then threw them into a total bedridden state. I know patients who got very sick, got a bit better, and plateaued – have remained at that level, not well but not as sick as they originally were.

And then there are the people that call themselves “25-percenters” in the UK, because the best guesstimate would be that 25% of patients with M.E. have this disease in a progressive form that just keeps getting worse, and worse, and worse, leading eventually to a premature death. I believe I was a 25-percenter myself, saved from a lifetime in a one-person horror show by access to Ampligen. (I do not mean this to be an advertisement for Ampligen; I happen to respond unusually well to the drug. However, that should say something about both the drug and the patient, should it not?)

I have gone off Ampligen twice – the first time, after being on it 20 months and paying roughly $40,000 for the privilege (my parents helped my husband out with other bills), I thought I was cured. I had a wonderful year, which some of us call the “Ampligen honeymoon.” And then, at Cal Ripken’s last baseball game, October 6, 2001, I blacked out. When I came to, I was back in M.E.-land again, full throttle. The next day I had forgotten, and when I sleepily tried to get out of bed, I crumpled to the ground. Oh. That again. I could not get tested for the Rnase-L defect, but HHV-6 was back in spades.

It took seven months to get back into an Ampligen program, this time at Hahnemann Hospital in Philadelphia, about an hour from my home and accessible by train if I did not feel like driving. Once back on it, I swore I would not go off. The costs (including co-pays and testing not covered by insurance) was now down to about $20,000 a year, precisely my after-tax disability income. Our children were grown. We lived on Bob’s income.

But in January 2008, the head of my practice in Philadelphia died. Though he was not my doctor, he was technically the principle investigator on my “study.” In February I was informed that I could no longer receive Ampligen at Hahnemann. To my knowledge, no other Phase III patients (most of whom were patients with severe cancers) were cut off. They reapplied twice, but were denied.

In September 2008, I relapsed. And in the ensuing months, we did the testing that I listed earlier in this (increasingly long!) missive.

So there you have it. I have been back on Ampligen now for ten months. I can read again, I can drive a car, I can walk along Lake Tahoe, and all the symptoms I associate with encephalitis and meningitis – that is, encephalomyelitis – are gone. But I still suffer from pain, and stamina is still a major problem. My VO2 MAX scores remain abysmal. Unfortunately, since this drug is delivered by twice-weekly infusions, I am forcibly separated from my husband of 35 years, which to me is a terrible hardship. But then I see so many others with my disease who have suffered more, and I think I should not say much about being so homesick, about missing my dearest husband so much. After all, Lake Tahoe is not such a bad place to be marooned.

I’m just one case. Okay. But I will close with something an economist once said:

Anecdote is the singular of data.

I’m just one case, among many. When will we study the other aspects of my disease, of our disease? What else do we already know about M.E. (or “CFS”)? How many desperately ill people are out there, undiagnosed, untreated and confused? When I walked to Hahnemann on cold days, I would pass homeless persons huddled over heating ducts, and I would wonder how many of them had my disease.

There are one million people with some aspect of my disease, and 850,000 have no diagnosis. Of those who are diagnosed, only a handful are getting treatment. Where are the rest?

Where are the rest?

Myra McClure and NIH's SEP

[Note: Dr. McClure has withdrawn from the CFS SEP since the publication of this post - and many others.]

In what can only be seen as a most unfortunate move, the NIH has added Dr. Myra McClure of the UK to the CFS SEP (Special Emphasis Panel) requested by Congress to evaluate proposals for grant money from NIH concerning CFS.

Thanks to the work of patient advocate Pat Fero, we have profiles of the members of this SEP - few of whom even claim expertise on CFS. These are mainly people who study pain, and more than one who studies psychological factors affecting the sensation of pain.

Then there is Jim Jones at CDC.  Jones started out working with a cluster outbreak in the Denver area, writing a companion article to Straus's at the end of 1984 suggesting CEBV (chronic Epstein-Barr Virus) was the culprit.  When Straus dropped CEBV and renamed it CFS, Jones quickly adopted a model of somaticizing.  It was particularly cruel because he worked with a lot of children and adolescents.  He has a kind of a CBT/GET/SSRI model at CDC, where he was hired to conduct physician education a few years ago.  I suspect he is the driving force behind that "new and improved" web site that praises the UK's NICE Guidelines [which attribute The Disease to "inappropriate illness beliefs" and recommend 10 weeks of CBT (Cognitive Behavior Therapy) plus 10 weeks of GET (Graded Exercise Therapy), known colloquially as CBT/GET, as a cure].

Now we come to Mrya McClure - co-author on a British study in PLoS One published just three months after the WPI/NCI/Cleveland Clinic study came out in "Science". **

Someone must have said they needed a retroviral expert on the panel.  Who better than someone who couldn't find a gamma retrovirus if they slapped her face with a cat suffering from feline leukemia?  As an observer commented at the time, did she take the lens cap off the camera?

Worse (in my opinion) for a person charged with evaluating grant proposals for CFS, McClure found nothing in any way peculiar about deriving her entire data set from patients in a purely psychiatric practice - Simon Wessely's and Anthony Cleare's at KCL (King's College, London).  Wessely once told me that because I had been diagnosed with Hashimoto's and NMH, I would have been sent to a different clinic at KCL and he would never have seen me.  So the patients chosen by McClure had NOTHING that could be diagnosed using biomedical markers.

If you harbor any doubts, this is taken from the abstract of the McClure's article failing to find XMRV.  How did they define their patient cohort?

"Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS." **

One might question what they mean by the "CDC criteria."   If you start out with a group of patients who are mainly depressed (as Michael Sharpe enthusiastically described the cohort defined by the Oxford definition in answer to a question at the 1998 AACFS conference - he agreed to my suggestion that up to 90% of his patients mainly had minor depression ...) you can squeeze through the Fukuda (1994) definition - fatigue, sleep problems, difficulty concentrating, headaches, muscle aches ... The critical point being that anyone with an organic explanation for any of this would already have been excluded from the group.  

It is a stretch to claim they meet Fukuda, but they would easily have met Reeves' definition (the questionnaires).  Lenny Jason found that the Reeves adjustment to Fukuda (those questionnaires) fail to diagnose the sickest 30% who would previously have met Fukuda, and then fold in a lot of patients with primary depression or anxiety .... So a data set consisting of patients from a psychiatric clinic could easily meet the Reeves criteria.

And, what a coincidence, Reeves referenced Simon Wessely and Trudy Chalder (British expert on "factitious illnesses" and "factitious illness by proxy") in the article that described his questionnaires, and Reeves sudden announcement in 2006 that 4-7 million people in the U.S. have CFS, is exactly what you would have gotten at the time using the Oxford definition (Wessely's).

If you want to see a website that will make your hair stand on end, take a gander at the KCL website on CFS (and you thought CDC's website was bad ...) - the emphasis is on getting rid of "enablers," such as doctors who do not spout Wesselyite dogma, helpful friends and neighbors, and wheelchairs.

http://www.kcl.ac.uk/projects/cfs/health/

Or you could skip to my two favorite sections, on "fear" and "letting go of support."

http://www.kcl.ac.uk/projects/cfs/health/#Fear

These were the folks who provided patients for McClure's study of XMRV.  

So they not only have added an "XMRV expert" who can't find XMRV ... But also someone who thought the KCL depiction of "CFS/ME" was accurate.

Slap in the face - but really more of a slap in the face to Lo and Alter and NIH's Natl. Cancer Institute (the latter had co-authors on the "Science" study) than WPI.  Their own institution kicked them down the stairs.

** "Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome"
Otto Erlwein, Steve Kaye, Myra O. McClure, Jonathan Weber, Gillian Wills, David Collier, Simon Wessely, and Anthony Cleare
PLoS One. 2010; 5(1): e8519. Published online 2010 January 6. doi: 10.1371/journal.pone.0008519.
PMCID: PMC2795199
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795199/

Mary Schweitzer, Ph.D. [Actually published in 2011, but changing the date was the only way to push it further down in the archives.]