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?

Written testimony to CFSAC 10/13/10

Testimony to the
Chronic Fatigue Syndrome Advisory Committee of the
Department of Health and Human Services
October 2010

Mary M. Schweitzer, Ph.D.

Thank you for allowing me time to speak.

I have XMRV.

I was one of the subjects who tested positive for the retrovirus in the Lombardi et al study published in Science October 9, 2009.

I first fell ill in 1990 while living in Delaware. I was a tenured professor at Villanova University outside Philadelphia. I had giardia followed by Epstein-Barr during an outbreak at my university. In the four years that followed, I had bronchitis eight months out of the year; I lost my sense of balance; the slightest bit of alcohol made me sick; I had increasing trouble falling asleep; and I could not do my usual Nautilus circuit and aerobic exercise without my pulse skyrocketing. Yet I had periods of health; I skied every winter.

Then, on October 24, 1994, I had a blackout in my office. When I came to, I could not understand a word of the essays in the bluebooks in my lap. It took fifteen minutes to be able to stand. I do not know how I made it home. My chair put me on short-term leave, which eventually became long-term disability. Although I was “resting,” I got worse instead of better. After a blackout while driving close to home left me and my car on top of a stone fence (and no memory of how I got there), I gave up my car keys. At first I could walk across a room; eventually I could only move about the house by leaning on walls, furniture, and my golden retriever. When outside my house, I was in a wheelchair. Increasingly, however, I could not go outside because I could not sit up that long. This is a very isolating disease.

I continued to have a social life on internet, because nobody could tell how long an email or website took to complete – and other brainfoggy patients didn’t mind misspellings or wrong words inserted into a sentence. By fall 1998, however, even internet was too hard.

About a year into my illness I developed Hashimoto’s thyroiditis. I also was found to have NMH/POTS. My Washington specialist, Dr. Marsha Wallace, treated the sleep problems, the thyroid problems, and the disautonomia, but I continued to deteriorate. Eventually I spent most of my time curled up in bed, in the dark, listening to a favorite movie (because it was too painful to look at the tv); severe pain behind my eyes, in the back of my neck; migraine-level headaches; and general muscle aches everywhere.

In 1996 I heard Dr. Robert Suhadolnik of Temple present on his new discovery, 37kDa Rnase-L, and I was fascinated. Two years later, Dr. Wallace arranged for Dr. Dharam Ablashi to have my blood spun down into a PMBC pellet to be sent to Redlabs in Belgium for testing; at the same time, Dr.Ablashi tested me for HHV-6, Variant A, which he had co-discovered at NCI. I was positive for both.

I had read that abnormal Rnase-L was a good predictor of success with an experimental immune modulator, Ampligen, an asymmetrical double-stranded synthetic RNA. I had also read a study by Dr. Ablashi and Dr. Paul Levine that had shown Ampligen inhibited the growth of HHV-6 in vitro. With that evidence to work with, I made the decision to go on the experimental drug. I was too sick for the double-blind study then being set up, but that was just as well – I wanted to know I was getting the drug.

I responded extraordinarily well. My brain began behaving normally within four months; soon I was driving and reading again. Eventually I would return to research, but I have never regained normal stamina. The slightest illness would set me back for weeks. Nevertheless, I could go places again with my husband; travel and see things; walk – walk on a beach, walk on a trail far enough that I did not hear the sound of automobiles anymore. If you have ever been confined to a wheelchair, you will know what that meant, to be able to walk again. I had dreamed of walking. And now I could stride.

Ampligen was expensive. After 20 months I quit taking it. I experienced what we Ampligen patients sometimes refer to as the “Ampligen Honeymoon” – I felt so normal and was so happy. I even negotiated with Villanova to return to teaching.

And then, on October 6, 2001, at Cal Ripken’s last baseball game, I had a blackout. The usher, who knew us, got me to First Aid and found Bob (who was visiting friends). Bob got the car while a nurse took me out in a wheelchair. The Disease was back.

The next morning I forgot what had happened and went to get out of bed as usual – but I fell to the floor. Six weeks later Dr. Ablashi confirmed that HHV-6, Variant A, was back. I could not send blood to Belgium, but the HHV-6 results were enough. I knew I had to get back on Ampligen.

The physician who had provided Ampligen in 1999 was no longer doing so, but I learned that I could receive Ampligen infusions at Hahnemann Hospital in Philadelphia, where they had permission for double-blinds because of Phase II’s on rare blood diseases. It took seven months, but I finally was on Ampligen again. I had deteriorated terribly, however. It was as if I had never been better at all.

So I had to climb back out again. After that, I was afraid to go off the drug. I remained on it from May 2002 to February 2008. Dr. Wallace had retired, so in 2005 I began seeing Dr. Dan Peterson at Incline Village (joking that the price of a ticket on Southwest Airlines was cheaper than Amtrak to NYC, my other choice).

The money is a problem – but it is roughly the same as my after-tax disability pay, so I live on the largesse of my husband, who is a chaired professor in a business school and does a lot of moonlighting – everything from teaching banking in executive ed programs to college lacrosse officiating and odd jobs for Major League Baseball. We manage.

But so few of my friends could afford the testing I’ve had, let alone the treatment. Every test for which I am positive is on the CDC’s hit list – that paragraph that states the test is inappropriate for CFS. Consequently, insurance won’t pay for those tests. At roughly $500 apiece, the expense adds up. Nobody can get tested, nobody can say they have what I have, and if they could, they couldn’t get treatment anyway. Pretty neat deal. For the insurance companies.

I continued to do well on Ampligen and made great progress on a book. Then my worst nightmare came true. In January 2008, dear Dr. Brodsky, now in his 80s, passed away. In February I received a phone call: FDA had taken away the drug. Hahnemann applied twice to get it reinstated, and I am not sure where the bottleneck was, but they were denied. Which means I was denied.

All the places where it used to be possible to get Ampligen on the East Coast were no longer in the program. Now I began to panic. I knew I was a ticking time bomb – I hoped perhaps I could stay relatively well for more than a year because I had been on it for so long, and I was so much better. I was wrong.

Seven months after losing Ampligen, in September 2008, I had my third episode of sudden onset. Once again I descended into hell. I lost the ability to walk normally and we had to bring the wheelchair back up from the basement. I dropped things, and when I tried to load the dishwasher I crashed one glass against another. The exertion of five minutes of testimony at the October 2008 CFSAC meeting sent me to the floor; my friends helped me lie down softly as I had once been able to help them. It made no difference that now I knew the names of the various symptoms – ataxia, expressive aphasia, short-term memory loss, central auditory processing dysfunction, etc. My brain had disappeared. And there was the exhaustion. And the pain. Pain, pain, pain.

I went to see Dr. Peterson at the end of September, and he put me through a series of tests. My MRI results were negative but I had an abnormal SPECT scan. My VO2 MAX stress test was below the level Social Security lists as an automatic disability for people far older than me. My Holter Monitor test was abnormal, and a 24-hour blood pressure and pulse test showed an NMH/POTS event when I was standing in line at the pharmacy – suddenly my systolic dropped 40 points while my pulse skyrocketed 40 points. (That was the first time I had ever seen a readout of it.)

I was active for Epstein-Barr (it goes dormant and reactivates over and over again if I am not on medication). I can now add a low natural killer cell count and a very low natural killer cell function (2%). More viruses had appeared – most seriously, HHV-7 and cytomegalovirus (CMV). I was also weakly positive for Coxsackie B2, B3, and B6. We did not find HHV-6 in my plasma, however.

During this period I went back to see Dr. Peterson every couple of months. I could do this only because of the kindness of the people who push wheelchairs for Southwest Airlines, the airport limo drivers and Tahoe taxi drivers, and the kind people who run a motel on the north shore of the lake, who have a family member with The Disease. When I was scheduled for a lot of testing, my daughter would fly up from Los Angeles to drive me around. Somehow we made it work. But I always came back home.

In the fall of 2008 Dr. Peterson tried Vistide, a drug that is approved for CMV. I had my first two doses a week apart while staying at Tahoe. He had then set up a dose at an infusion center connected to the only infectious disease practice in northern Delaware – but when I came for the infusion, they refused to give it to me. “I’m sorry,” the doctor said, “we can’t give you this. It’s a strong drug, and all you have is CFS.” But I have cytomegalovirus, and Vistide is approved for cytomegalovirus. “We know. And if you had something serious, like AIDS, or were on chemo from cancer, we would give it to you. But all you have is CFS.” But you told my specialist you would administer it to me. “Yes, but we hadn’t seen your files yet. We didn’t know you have CFS.”

I had to fly to Reno, spend the night, get my dose, and fly home.

But Vistide was not in the works for me. Ironically, while I seem to be the poster child for Ampligen, Vistide made my liver function tests go off the charts. My SGOT and SPGT counts were 500 times what they should ever be. They returned quickly to normal, so we tried a half dose of Vistide and then halved it again, but each time SGOT and SPGT spiked just as before. Vistide was out of the question.

In July 2009 I had a spinal tap - my daughter and her boyfriend came up from L.A. to help me again (Bob was just trying to earn money!). Aha – that’s where HHV-6 had been hiding out. So now I could say I ran the table – HHV-4, 5, 6 and 7.

At one point I remember saying to Dr. Peterson, it has to be my immune system. Something has to be really wrong with my immune system. Otherwise this does not make sense. He agreed, and then he said, “Oh, there are things I would like to tell you!”

Now, I will admit here that the very well-kept secret did not turn out to be what I was hoping for. I hoped desperately that Ampligen had by some miracle been approved. The finding that there was a retrovirus in 2/3 of a sample of 101 CFS patients completely bowled me over. That one I had not expected. And a few weeks later, by email, came the suggestion from a fellow patient that I ask WPI if I had been in the study. I assumed it was the Tahoe-Truckee cluster outbreak of 1984-85. Instead, they had deliberately picked zip codes from all over the place – so my Delaware zip code had bought me a free XMRV test. I was afraid to call and find out – not afraid to have it (I had plenty!) – afraid that I would not have it. Just as I had been afraid of the Rnase-L test 11 years earlier. The epithet of diagnosis-seeker only has meaning to someone who has never struggled to find treatment for a severe illness. XMRV means two things to me: an explanation for why I can’t go off Ampligen without getting sick, and the possibility of a substitute for Ampligen if FDA refuses to approve it. It means hope.

One more anecdote: During this period I fell, resulting in a slipped disk. (I fall a lot when sick.) I have a good neuro-spine surgeon at Penn, and he shaved a piece off quite neatly. But I was amazed at the response from the anesthesiologist, and later the nursing staff, to my warning that I had been diagnosed with a newly discovered retrovirus and they needed to take precautions. I was treated very differently than in the past – same symptoms, same litany of diseases and abnormalities, but now we had added a recognized disease (CMV) and a retrovirus (XMRV), and everything had changed. They were very happy to get me out of the hospital as fast as possible – so was I.

CMV and XMRV represent the first diagnoses I have ever had which turned heads among hospital staff. But as my daughter said when I told her about my new diagnoses, “you were sick long before anybody said what you had, Mom.” And she should know. She spent five years taking care of me.

Last year my husband, Dr. Peterson, and I decided that because I responded so well to Ampligen, I had to go back on it. That meant I was going to have to live in Incline Village, NV, until Ampligen became available at home again. It’s ironic – I live in the Northeast Corridor – 10 minutes from I-95, 5 minutes from a train station. I’m within driving and/or easy Amtrak distance from 40 percent of the nation’s population. But I had the choice of western North Carolina or a resort town on Lake Tahoe to be able to go back to the only medication that has ever worked for me. Since Dr. Peterson was my specialist, the choice was obvious. And I imagine I won’t get much sympathy for having to live at beautiful Lake Tahoe. But I have been married 35 years, and I miss my husband terribly. At our age, you feel like two heads of the same body. It’s awful. Thank heavens for unlimited long distance calling, MLB.com’s internet package, and Southwest Air.

I know that XMRV is “hot” right now, and dominates the discussion. But please remember that there are a number of immune biomarkers and viruses that we have that CDC also pretends don’t exist. They couldn’t find XMRV? I’m not surprised – they never could find HHV-6, natural killer cell dysfunction, mycoplasma, or NMH/POTS, either. It’s been the same thing for years: A quick study with a few patients chosen in a creative manner and then they can announce that X, Y, or Z is not “The Cause” of CFS. Why should it have been any different with XMRV?

But look at my history – and I am no different from many, many others with my disease who have also been able to get testing and treatment. I have some things others don’t have; others have things I don’t have. There’s a young man getting Ampligen with me who shares HHV-6 and the 37kDa Rnase-L (and XMRV) – but he also has parvo, which I don’t have, and myocarditis, which I hope I don’t have. There’s a pretty standard array of testing that works for us – that demonstrates a very serious set of biomedical abnormalities. What matters right now is not finding The Cause, but identifying patterns that can lead to treatment and improvement. That can turn around the downward spiral.

When you go to test whether XMRVs or PMRVs are related to the condition known as CFS (Fukuda 1994), please go back to everything else CDC has ruled out for the 25 years they have hidden this disease. This is important. Our lives are in your hands.

Thank you.

What do we have if we do not have CFS?

I have always despised the concept and name “chronic fatigue syndrome,” created in 1988 to describe a group of patients who had previously been thought to have “Chronic Epstein-Barr Virus.” “CFS” is not scientific. It is a social construct, a shape-shifter, something that gets redefined as those in a position of power, or society at large, wish to redefine it. But it had one advantage. It helped researchers study a group of patients who have been sick for decades with a mysterious, apparently contagious, disease. It helped researchers define subgroups of patients who exhibited similar patterns of biomarkers and pathogens. If CDC defines CFS so that those patients are no longer considered to have the disease, then what can we say they have? And what is left that can be called “CFS”? Why would we study CFS at all?

Defining CFS so that it no longer fits “CFS” patients

In the late 1990s, it had become clear that “chronic fatigue syndrome” had been polluted as a research term because there were so many different – often conflicting – definitions in use. How could you compare a study conducted using patients from Simon Wessely’s psychiatric practice at King’s College, London – where patients with confirmable physical ailments were turned away – with a study conducted using patients from Dr. Dan Peterson’s practice at Incline Village, NV, one of the most-studied sites of a cluster outbreak in the 1980s? Over time Dr. Peterson and others had found tests that distinguished the cluster-outbreak patients from those with simple “chronic fatigue” – low natural killer cell function; the 37kDa Rnase-L defect; SPECT scan abnormalities; extremely low VO2 Max stress test scores; viruses such as EBV, HHV-6, and cytomegalovirus. Other researchers have found mycoplasma infections, mitochondrial dysfunction, abnormal immune cell ratios, NMH/POTS; myocarditis. The list goes on. Formally, they were all using the CDC’s 1994 Fukuda definition in their research, but practically speaking, the patients came from practices where clinicians had seen chronic fatigue syndrome in cluster outbreaks.

The result is research that defines subgroups of patients with patterns of biomarkers and pathogens. In fact, this was how Dr. Fukuda had imagined research would proceed with CFS. In the 1994 article that introduced what is called the “Fukuda definition” to the world, he wrote that “additional subgrouping or stratification of study cases into more homogeneous groups is necessary for comparative studies.” An entire section of the short (6-page) article was devoted to “Subgrouping and Stratification of Major Classification Categories”:

"In formal studies, cases of the chronic fatigue syndrome and unexplained chronic fatigue should be subgrouped before analysis or stratified during analysis by the presence or absence of essential variables, which should be routinely established in all studies. Further subgrouping by optional parameters can be performed according to specific research interests."

But CDC has steadfastly ignored that mandate. Instead of studying evidence of subgroups, CDC would take each new biomarker or virus, run a small study that sometimes even didn’t even test for the right laboratory finding, and then announce to the public that X or Y or Z was not “the cause” of “Chronic Fatigue Syndrome.” The Fukuda article is referenced only for the research definition – not for the imperative to subgroup into homogeneous classes. Most patients, clinicians, and researchers are probably unaware that the article even mentioned – let alone emphasized – the need to define homogeneous subgroups.

Twenty-five years after CDC was first asked to examine cluster outbreaks of the disease they would later name “chronic fatigue syndrome,” the website states as the first obstacle to diagnosis:

“There's no diagnostic laboratory test or biomarker for CFS.”

That simple statement shows the extent to which CDC missed the point of the Fukuda article. Fukuda assumed there would be no such tests that would hold for everyone. The tests would define subgroups.

Today on CDC’s website you will find an entire paragraph devoted to the testing that has identified the subgroups Fukuda envisioned – but CDC’s approach could not be further from what he had described. Some are listed as exclusions; others as experimental. In the latter case, one wonders how long after peer-reviewed publication does information continue to be viewed as “experimental.” Much of this information was first published 15 years ago. Perhaps more to the point, denying patients access to this testing also results in denying them access to treatment that has been found successful for patients who have such biomarkers or pathogens.

CDC’s emphasis on one test-one result also denies the reality that most patients with “CFS” (according to the original definitions) have more than one thing wrong with them. But there is no way to tell that from the CDC website (See

http://www.cdc.gov/cfs/general/diagnosis/testing.html)

"A number of tests, some of which are offered commercially, have no demonstrated value for the diagnosis of CFS. These tests should not be performed unless required for diagnosis of a suspected exclusionary condition (e.g., MRI to rule out suspected multiple sclerosis) or unless they are part of a scientific study. In the latter case, written informed consent of the patient is required. No diagnostic tests for infectious agents, such as Epstein-Barr virus, enteroviruses, retroviruses, human herpesvirus 6, Candida albicans, and Mycoplasma incognita, are diagnostic for CFS and as such should not be used (except to identify an illness that would exclude a CFS diagnosis, such as mononucleosis). In addition, no immunologic tests, including cell profiling tests such as measurements of natural killer cell (NK) number or function, cytokine tests (e.g., interleukin-1, interleukin-6, or interferon), or cell marker tests (e.g., CD25 or CD16), have ever been shown to have value for diagnosing CFS. Other tests that must be regarded as experimental for making the diagnosis of CFS include the tilt table test for NMH, and imaging techniques such as MRI, PET-scan, or SPECT-scan. Reports of a pathway marker for CFS as well as a urine marker for CFS are undergoing further study; however, neither is considered useful for diagnosis at this time."

While these tests might not be useful in “diagnosing” a single entity called "CFS", they are very useful in understanding and treating CFS. I have three of the four pathogens mentioned. I also have cytomegalovirus (CMV), which I imagine CDC considers exclusionary for CFS. I am abnormal in testing for three of the four immune markers mentioned plus the 37kDa Rnase-L which is listed there as a “pathway marker for CFS,” I have NMH; and I have abnormal SPECT scans.

More to the point, there is a subgroup of patients within the larger CFS-diagnosed community whose testing turns out almost identical to mine. So researchers identify a subgroup, but instead of using that to benefit patients, CDC insists it is either unrelated to CFS, or exclusionary for CFS.

Furthermore, the pattern of biomarkers and viruses - not a single test – is critical for understanding various subgroups that could now be defined empirically, if CDC permitted it. And by listing everything as if each was a single test, and each test represented a different disease, CDC effectively misleads anyone who comes to their website seeking an understanding of “CFS.”

I fit quite neatly into a subgroup of CFS patients who were caught up in a cluster outbreak in the north Tahoe area of Nevada in the winter of 1984-85. The Holmes definition of 1988 and the Fukuda definition of 1994 were both explicitly intended to describe those patients. When Congress voted for research funding and an advisory committee (today's CFSAC) for “CFS” in the Department of Health and Human Services, they did not mean for these resources to go to just any old thing CDC wanted to call “CFS” – they wanted to find answers for the people who got sick in the 1980s, and later, with a disease that appeared similar among oubreaks.

We have reached a point where CDC explicitly defines CFS to exclude the very patients they were charged with helping.

If the patient representatives on the CFSAC do not have “CFS” according to CDC’s restrictive parameters; if the researchers on CFSAC do not study “CFS” according to CDC’s website; if clinicians on CFSAC do not treat “CFS” as defined by CDC – precisely what is CFSAC supposed to do?

The issue is about to come to a head.

CDC insists that XMRV is not “the cause” of CFS. According to a reporter from the New York Times a month after the Science study had revealed the discovery that 2/3 of a sample of CFS patients had tested positive for the new retrovirus:

"Among those expected to try to replicate the XMRV findings is the Centers for Disease Control and Prevention. But Dr. William C. Reeves, who directs the agency’s research on the syndrome, has said that he does not expect to find the virus in blood samples from patients. He said that no other studies had ever proved a virus to be the cause, and that stress and a history of sexual and emotional abuse were more likely to play a role in many cases."

True to his prediction, when Reeves did publish a study on XMRV, he did not find any of the virus at all (despite consistent findings in earlier prostate cancer studies that 2-4% of controls had the retrovirus).

It now appears clear that if the scientific community accepts XMRV as the third known human retrovirus, CDC will simply define CFS so that it is not related to XMRV – they will simply add XMRV to that paragraph that lists all of the testing that is “inappropriate” for CFS. Thus Reeves will always be right when he declares XMRV to be unrelated to CFS - because CDC will redefine CFS such that XMRV by definition will be unrelated to it.

I was in the Science study and I was positive for XMRV. So I’m out of the CFS club, it appears. But I was already kicked out by virtue of testing positive for so many viruses and biomarkers. More to the point – if CDC defines CFS in such a way that the very patients it was created to describe no longer fit the description, what is the point of having a disease category called CFS in the first place? What is the point of a division of CDC devoted to CFS studies? What is the point of an advisory committee at DHHS to coordinate agency activities regarding CFS?

From the beginning, “chronic fatigue syndrome” was a disastrous name chosen to replace “Chronic Epstein-Barr Virus” back in 1988. It could not have been more dismissive if it had been chosen by a focus group. “Chronic” as in “chronic complainer” and “chronic whiner;” “fatigue” as in “yeah, I’ve been tired lately myself;” and “syndrome” as in “syndrome of the month.” In the first decade of the name, comedians had a field day with it. As recently as this year, a popular comedy show in England mocked the name and the disease.

Researchers familiar with the disease known as Myalgic Encephalomyelitis (M.E.) in England and old Commonwealth nations, and Epidemic Neuromyesthenia in the U.S., expressed the opinion at the Holmes meeting in 1988 that the disease was most likely M.E. (Epidemic Neuromyesthenia was no longer being diagnosed). But that information was not even included in a footnote.

M.E. would not be linked to the mysterious illness of the late 1980s as a possible biomedical explanation except in reverse. British psychiatrists eagerly grabbed the name “chronic fatigue syndrome” to portray M.E. as a psychogenic illness, “neurasthenia” (formerly known as “the vapors”). According to the British psychiatrists (Simon Wessely, Peter White, Michael Sharpe, Trudy Chalder, among others), patients with CFS had allowed themselves to become deconditioned because of “inappropriate illness beliefs.” A course of “cognitive behaviour therapy” (CBT), to teach the patient she wasn’t really sick at all, followed by “graded exercise therapy” (GET), to get her back into shape and on the job, was all that was needed.

British psychiatrists used a definition that omitted the sickest patients, excluded anyone with a physically diagnosable condition, and included patients with depression and anxiety disorders. Nothing could be further from the Fukuda definition – yet even today, because they say it is “CFS,” the media and many medical experts assume it is the same thing.

For years CDC used the Fukuda definition. Today, however, they use what can only be called the “Reeves” definition, after William Reeves at CDC, who created a set of questionnaires that he claimed “operationalize” Fukuda, but do nothing of the sort. The questionnaires – explicitly modeled after those used by British psychiatrists – define a population that is not severely ill, and contains patients who suffer mainly from depression or anxiety disorders. In short, CDC has moved to join the British psychiatrists in portraying the disease as psychogenic in origin – CDC uses the term “stress” instead of “neurasthenia” (because neurasthenia is not an accepted diagnosis by U.S. psychiatrists – it was omitted from DSM-IV, along with “hysteria,” because of the strong gender bias associated with the diagnosis). As Reeves told the reporter, CDC expresses the view that “a history of sexual and emotional abuse were more likely to play a role [than viruses or biomarkers] in many cases.”

Cognitive Behavior Therapy and Graded Exercise Therapy (CBT/GET) are now prominently displayed on CDC’s website as treatment for the disease. For a patient such as myself, who had viruses and immune defects, CBT is not going to bring about a cure. And for those of us who score abysmally low on the VO2 MAX stress test, GET is downright dangerous. But we are supposed to have been weeded out. Who is left?

How convenient to have a moving target, the social construct “chronic fatigue syndrome,” so that as research reveals the biomedical roots of the disease, CDC can maintain that it’s really caused by stress – having portrayed all the results of biomedical research as either inappropriate or useless. What good are thousands of refereed journal articles into biomedical causation (according to Harvard professor Anthony Komaroff) if CDC redefines the disease each time to exclude the new discoveries?

What the future will bring

As CDC’s pattern (and Reeves’ confession) make clear, patients with XMRV are going to be defined out of the CFS population. Will they have their own division at CDC? Will they have their own advisory committee at DHHS?

As researchers begin to study patients with XMRV formerly diagnosed with CFS, they will discover the patterns that CDC has heretofore hidden from public view – patients such as myself, with multiple immune defects, opportunistic viruses, and the resulting damage to the central nervous system, the brain, and multiple systems of the body.

What about those who do not test positive for XMRV? Will they be left behind, defined as having psychogenic CFS?

Or will the medical community come to its senses and realize that the real disease is in the patterns? Will they finally understand that the subsets of this disease were diagnosable with biomedical markers a long time ago?

If we do not have chronic fatigue syndrome, what do we have?

Testimony to CFSAC May 2010

Testimony to the CFSAC of the
U.S. Department of Health and Human Services
May 10, 2010
Mary M. Schweitzer, Ph.D.

Thank you for allowing me the opportunity to present testimony. My testimony today addresses four issues, but they are all tied to one that is most basic: Accountability.

1. Accountability.

There is a stunning disconnect between what we supposedly know from this committee, and what the public knows (including medical professionals).

I have attended all save one or two of the meetings of the CFSCC and the CFSAC. Everything I know about my disease has been presented to this committee at one time or another. Dr. Suhadolnik spoke about the Rnase-L defect. Dr. Ablashi spoke about HHV-6. Dr. Rowe spoke about NMH/POTS. In the course of fifteen years there have been many more scientific presentations – and the presentations were tied to peer-reviewed journal articles.

Yet these researchers could have been shouting into the wind for all the good it has done. At its worst, the CDC and NIH have produced quick little studies enabling them to say “there is no known relationship between CFS and [pick a virus or biomarker].”[1] At its best, the CDC has simply ignored the information.

When the Science study by researchers from the Whittemore-Peterson Institute, Cleveland Clinic, and National Cancer Institute first surfaced, Dr. Reeves of CDC responded as he always has: the CDC will end up invalidating the findings. Because that is what he has been doing for twenty years; it is what Stephen Straus did for fifteen years.

It does not matter what testimony scientists have presented to this body; it matters even less the testimony that patients have struggled to bring to the attention of the agencies. There has never been any mechanism by which any of the agencies had to do anything at all relative to the information that came out of these meetings.

Every time CDC addresses the public about this disease, they begin with some version of the following: “Chronic fatigue syndrome (CFS) is an important public health problem. The causes of CFS are unknown and effective prevention strategies remain elusive.” [From the CDC's information for patients and caregivers] [2]

The same can be found in the “Toolkit for Professionals”:

“Diagnosing chronic fatigue syndrome (CFS) can be complicated by a number of factors: 1) there's no diagnostic laboratory test or biomarker for CFS…”[3]

And also from CDC’s “Toolkit for professionals:”

"Theoretical and Experimental Tests: A number of tests, some of which are offered commercially, have no demonstrated value for the diagnosis of CFS. These tests should not be performed unless required for diagnosis of a suspected exclusionary condition (e.g., MRI to rule out suspected multiple sclerosis) or unless they are part of a scientific study. In the latter case, written informed consent of the patient is required. No diagnostic tests for infectious agents, such as Epstein-Barr virus, enteroviruses, retroviruses, human herpesvirus 6, Candida albicans, and Mycoplasma incognita, are diagnostic for CFS and as such should not be used (except to identify an illness that would exclude a CFS diagnosis, such as mononucleosis). In addition, no immunologic tests, including cell profiling tests such as measurements of natural killer cell (NK) number or function, cytokine tests (e.g., interleukin-1, interleukin-6, or interferon), or cell marker tests (e.g., CD25 or CD16), have ever been shown to have value for diagnosing CFS. Other tests that must be regarded as experimental for making the diagnosis of CFS include the tilt table test for NMH, and imaging techniques such as MRI, PET-scan, or SPECT-scan. Reports of a pathway marker for CFS as well as a urine marker for CFS are undergoing further study; however, neither is considered useful for diagnosis at this time."[4]

What is the purpose of having researchers present information to the CFSAC if the CDC is going to deny it has any relationship to CFS? Along with many other patients, I have been diagnosed using many of the tests that the CDC continues to label “experimental,” and I have been treated as successfully as possible on the basis of those tests. We are well past the point where these should be still considered “experimental.”

Let’s contrast the CDC’s current position with the article by Fukuda et al establishing the current working research definition for CFS: “In formal studies, cases of the chronic fatigue syndrome and idiopathic chronic fatigue should be subgrouped before analysis or stratified during analysis by the presence or absence of essential variables, which should be routinely established in all studies.”[5] An entire section of the Fukuda article was devoted to the importance of establishing subgroups. That was sixteen years ago. Where are the subgroups?

Despite Fukuda’s urging, CDC has continued with a “one size fits all” approach to the disease. Either everybody has it, or it doesn’t matter. The possibility that there might be patients out there who were positive for any of the above viruses and biomarkers – let alone that there might be patients who were positive for several of them – is not admitted by CDC. Fukuda’s mandate to find diagnosable subgroups was completely ignored by CDC – and remains so to this day.

That stands in stark contrast to the numerous presentations and discussions I have heard while attending the CFSCC and CFSAC.

It also stands in contrast to what I know from my own experience. I am one of a subset of CFS patients who has both immune markers and numerous active viruses. I have abnormal Rnase-L; my natural killer cell function is 2%; I have recurring EBV and active HHV-6, HHV-7, cytomegalovirus – and XMRV. We’ve known about most of this for twelve years, and as a consequence, I have benefitted from treatment with the experimental immune modulator Ampligen. During these 12 years, why has not the CDC investigated the subset to which I clearly belong? Why haven’t other patients had the opportunity to be tested and treated?

So this is my first and primary question:

Where is the accountability from the federal agencies that report to the CFSAC?


2. Next I need to point out that there is a serious issue that the CFSAC must address, and address soon. That is the creation of a new psychiatric category for DSM-5 called CSSD, or Chronic Somatic Symptom Disorder.[6] The head of the committee that created CSSD is Michael Sharpe, a psychiatrist who is part of the Wessely school – a small group of professionals who assert that what appears to be a physical illness in CFS is actually “deconditioning,” which has been caused by “inappropriate illness beliefs.” The “cure” is for the patient to undergo Cognitive Behavior Therapy (CBT), during which the patient learns she is not physically ill at all, in conjunction with “graded exercise therapy” (GET) to get her back in shape. On the King’s College, London, website, one of the examples they give of their success with CBT/GET is a patient who is brought to the clinic in a wheelchair. She must be separated from friends, family, and medics who confirm her “inappropriate illness beliefs.” Then, and only then, she can rise out of that chair and walk.

Make no mistake about it, CSSD is designed for Michael Sharpe’s own specialty: CBT for CFS.[7] The APA received numerous letters protesting the category during an open comment period that ended April 20. They sent the protests back to the same committee, with the same person presiding. There will be another opportunity for open comments this summer. The CFSAC must formally address this effort to create a psychiatric category for chronic fatigue syndrome. At the least, before diagnosing a patient with CSSD, a doctor should be required to check for the symptoms of CFS. If the patient has CFS, then the patient cannot have CSSD.

3. Dr. Reeves may have left the CDC’s section on CFS, but his questionnaires remain. The Reeves questionnaires have created a different definition for CFS. While the CDC insists that the “Fukuda definition” has been used in all recent research, that statement is simply untrue. The Reeves questionnaires do not create a data set that conforms with the Fukuda definition. Therefore CDC must either acknowledge that we have a new definition, the “Reeves definition,” or it needs to disavow those questionnaires entirely.

4. Direct changes to the charter

We have been asked to comment on changes to the charter for the CFSAC when it is renewed in the fall.

(1) The first and most important of these must be some way to hold the agencies accountable for their speech and actions regarding CFS. It is as if the CDC had continued to refer to GRID long after everyone else had agreed to use AIDS. They seem stuck in the period before any biomedical research had been conducted on what was a mysterious illness in the mid-1980s, but is not such a mysterious illness today. I do not know what the answer is – but there must be some way to require that the agencies take seriously what goes on in these meetings – or why are we bothering at all? I suggest that the CFSAC not only report to Secretary Sebelius, but also to Senator Tom Harkin, Chair of the Senate Committee on Health, Education, Labor, and Pensions.

(2) Return to the format of the CFSCC in the 1990s, when the public was permitted a short question-and-answer period after each ex officio presentation. When the CFSAC first met in 2003, we were told that only the representatives of the public on the committee had any right to address the ex officio members. I had the unpleasant experience, while testifying, of having to ask Dr. Reeves for a clarification of some of his research (the question had actually been asked of me by a public member on the CFSAC.) Dr. Reeves responded, “I don’t have to answer to you” and turned his back to me! I do not know what language was in the CFSCC that gave me the right to ask a question and have it answered, but I think we deserve to have that right back again. There needs to be a microphone in the middle of the aisle, and at some point people in the audience who wish to ask questions should be allowed to line up at the microphone. It is a simple courtesy.

(3) Require that patients be permitted at least 5 minutes of oral testimony each.

(4) Make available the records of past CFSAC and CFSCC meetings. The minutes were edited heavily during both the Clinton and Bush administrations, but an unedited aural tape was made of all the meetings, and I was assured it was being preserved. The public should have access to both the printed minutes and the unedited aural tapes.

(5) Return to the format of meeting four times a year. There is already too much to be done to be able to accomplish what is needed in only two meetings a year.

(6) For over a decade, the Committee as a whole as known that at least 800,000 adult Americans have this condition and do not have a diagnosis. At what point are we going to do something about that?

(7) Research by Leonard Jason and others has suggested that teenagers fall ill with this disease at a rate about half that of adults. But the age range for adults is much longer than it is for teenagers. That would suggest that while the incidence in adolescence is half of what it is in adults, the prevalence may be much higher. The CDC has no program for children and adolescents. These are the most vulnerable of all patients. The IACFS/ME has a clinical definition for children and adolescents, but CDC has refused to admit its existence. Because of the enormous ignorance about the disease in the public arena – yet anther disconnect - schoolchildren who have a diagnosis have been taken from their parents and placed in foster care. And what happens to schoolchildren who are every bit as sick, but have no diagnosis? Again I ask, at what point are we going to do something about this? The charter must include language directing the agencies to address the needs of children and adolescents with this disease.

(8) The CFSAC should hold at least one state-of-the-science meeting a year. This would require funding, but since CDC apparently believes that we do not know anything about how to diagnose or treat a disease that impacts at least one million Americans, it’s about time we made a start.

(9) NIH spending on CFS must be comparable to the estimate of at least one million adults with the disease, and the agency must be accountable for where the funds are spent. It is a good sign that the NCI has been involved in research on XMRV, but in the meantime, the dollars spent on researching CFS and its subgroups have been miniscule. At most, NIH has spent $6 per patient per year – and most of that money has gone to projects (such as pain clinics) that have little or nothing to do with CFS at all. The Congressionally mandated CFS study group for allocating research funds at NIH is a sham; the majority of the members know nothing about the disease,[8] and therefore research projects directly addressing CFS are seldom approved.

I wish to thank the Committee again for the opportunity to offer testimony.

Mary M. Schweitzer, Ph.D.

--------------------------
Endnotes:

1. As a recent example, see the effort to discredit research on NMH/POTS in Jones JF, Nicholson A, Nisenbaum R, Papanicolaou DA, Solomon L, Boneva R, Heim C, Reeves WC. "Orthostatic instability in a population-based study of chronic fatigue syndrome." American Journal of Medicine 118:1415.e19-1415.e28, 2005.

2. This particular quote came from “Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study,” Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC. Archives of General Psychiatry 63:1258-1266, 2006.

3. http://www.cdc.gov/cfs/cfsdiagnosis.htm- accessed 26 April 2010.

4. http://www.cdc.gov/cfs/cfsdiagnosisHCP.htm - accessed 26 April 2010.

5. Fukuda et al, “The Chronic Fatigue Syndrome: A Comprehensive Approach to its Definition and Study.” Annals of Internal Medicine, Vol. 121, December 15, 1994, pp. 953-959.

6. See my essay on CSSD on this blogsite: Slightly Alive: Letter to the APA on CSSD as well as the APA’s website on the proposed category: http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=368

7. Psychiatrist Michael Sharpe was an early proponent (and continues to be) for cognitive behaviour therapy (CBT) and graded exercise therapy (GET) as cures for CFS. “Chronic fatigue syndromes are not new. Victorian physicians diagnosed them as neurasthenia … Cognitive behaviour therapy … emphasises consistency in activity management and the gradual attainment of behavioural targets. Taken together this evidence suggests that it is important to differentiate between the needs of the patient with acute fatigue and the patient with a chronic fatigue state; rest may be indicated for the former, but a gradual increase in activity should be at the heart of the treatment plans for the latter.” Michael Sharpe and Simon Wessely, “Editorial: Putting the rest cure to rest – again: Rest has no place in treating chronic fatigue.” British Medical Journal 316 (14 March 1998) 796-800. It would be disingenuous to suggest that Sharpe’s interest in creating the category of CSSD is unrelated to his professional commitment to the psycholization of CFS and its treatment. For other samples of Sharpe’s view of CFS, see M Sharpe, KE Hawton, S Simkin, C Surawy, A Hackmann, I Klimes, T Peto, D Warrell, V Seagroatt. “Cognitive behaviour therapy for the chronic fatigue syndrome: a randomised controlled trial.” British Medical Journal 312 (1996) 22–26. S Wessely, C Nimnuan, M Sharpe. “Functional somatic syndromes: one or many” Lancet 1999:354:936 939; P Davison, M Sharpe, D Wade, C Bass. “’Wheelchair’ Patients with Nonorganic Disease: A Psychological Inquiry.” Journal of Psychosomatic Research 47 (1999) 1:99-103.

8. According to the research subcommittee of the CFSAC, during the Bush administration only 17% of the members of the Congressionally mandated CFS study group that is supposed to examine potential research projects for NIH funding has ever published or presented a paper on CFS.

Can we choose "all of the above"?

The critiques are beginning to come in about the discovery of a new retrovirus in patients with an agressive form of prostate cancer - and in patients with the diagnosis "chronic fatigue syndrome." [Lombardi et al, "Detection of Infectious Retrovirus, XMRV, in the Blood Cells of CFS Patients,” Science (9 Oct 2009).]

Everyone familiar with what passes for government-approved "research" regarding "chronic fatigue syndrome" knew that it would not take long for there to be a response denying the validity of the article on the retrovirus XMRV that was published in Science in October. We also knew that there would be no respect shown for the professionalism of the team that produced that research: the Whittemore-Peterson Institute, the Cleveland Clinic, and the National Cancer Institute of NIH.

Those of us who are saddled with the pathetically inept diagnosis of CFS are particularly vulnerable to the public dismissal of any and all research because of the success of various interest groups in creating an inchoate, ever-shifting social concept, "Chronic Fatigue Syndrome," in the guise of a disease. CFS may have been created to refer to a speciifc group of patients - but a quarter-century later, it has so many multiple meanings as to be absolutely useless for purposes of sound research.

The winner in the "get rid of the evidence" sweepstakes was what is now called the "McClure article" because the first author listed is named McClure - but buried in the list of authors are the three who put together the data set: Simon Wessely and two other colleagues from King's College, London (KCL). [See
McClure et al, "CFS patients in UK show no signs of suspect virus."]

It beggars the imagination to suggest there is anything in common with the way Simon Wessely and Dan Peterson diagnose patients. KCL was very touchy on that subject, insisting that they followed the Fukuda definition precisely, but if you have any doubts about the views of KCL researchers on CFS, take a good look at the KCL website on CFS for professionals:

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

The authors even make the claim that talking therapy healed a "CFS" patient who had allowed well-meaning friends and physicians to confine her to a wheelchair. Imagine telling physicians that a patient confined to a wheelchair is just there because she thinks she shoul be - if the patient had Multiple Scerosis, or Muscular Dystrophy, or ALS. Imagine physicians looking at a CFS patient in a wheelchair and thinking all that has to be done is convince the patient she can walk. To me, it harkens back to the shysters of the old circus tent evangelicals in the U.S., who would claim to be able to heal people with a touch of the hand. There's something seriously wrong when a professional medical website reads more like Elmer Gantry than Gray's Anatomy [the textbook, not the show]. It gives new meaning to the old saying "the inmates are running the asylum."

Until scientists require as much rigor in the data selection process as they claim in modeling and statistics (and medical science leaves much to be desired on those points as well), opinion is elevated to the level of fact, and ideological dogma parroted by a lazy (or hamstrung) popular media.

For the last decade, CDC's program on CFS has been collaborating with Emory University's department of psychiatry, section on somaticizing. As a result, we have to be concerned that the CDC's work is now also dependent on data sets that conflate depression with chronic fatigue. The old promise that the name "Chronic Fatigue Syndrome" would be viewed as a discrete illness, and never be confused with "chronic fatigue," has been completely abandoned by CDC. With both CDC's and the UK's preoccupation with a female patient who thinks she's sick but is not, I am not only appalled by the absence of intelligent scholarship at both institutions, but also offended to find myself, as a female patient, the target of their biases.

There is, however, a greater problem:

Nobody asks the simple question: what might this new finding mean in and of itself?

Instead, the value of the finding is determined by its ability to fit old paradigms when, in fact, the discovery actually blows the paradigm apart.

It has been my unfortunate luck to be able to check "all of the above" on the lists of causation (except I had a great childhood). But the CDC wants no part of multivariate modeling, claiming Occam's Razor requires absurd reduction to the lowest common denominator - a perversion of that dictum in model-making just as destructive as their use of statistics in a manner that must make Popper whirl in his grave. [The laws of statistics prohibit claiming to "prove" that CFS is not associated with Factor A, B, or C, simply by noting you could not find a statistically significant difference between a sample of patients and a sample of healthy citizens, particularly when small sample sizes are used, as was the case in the Wichita two-day hospital stay.]

English professors and historians receive grants from the National Endowment for the Humanities [NEH]; physicists and chemists from the National Science Foundation [NSF]. Nobody at either institute has the right to claim a theory and deny funding to all who oppose it. I was astounded to find the opposite true of both NIH and CDC. How did the bureaucrats at those institutions become so all-powerful?

And if they are right, why are they still in charge of the disease?

If "CFS" is really a psychological disorder - a type of somaticizing [KCL] or a type of post-traumatic stress disorder [CDC] - why does it not fall under the purview of NIMH (National Institue for Mental Health)? If not, why are psychiatrists given such an important role as paid consultants by CDC with reference to "CFS" - and why are supposed specialists in viruses and infectious diseases allowed to play amateur psychiatrist?

How can you look at the McClure paper and not question the data set? For that matter, shouldn't at least 3-4% of the people in the data set, diagnosed with "CFS" or not, have tested positive for XMRV?

XMRV cannot be "CFS" - can't even be a marker for it - because CFS exists only in the eyes of the beholder.

CDC's response was predictable. According to the New York Times (12 Oct 2009), Dr. William Reeves, who has run the CDC's program on CFS for two decades, neatly dismissed the finding offhand. "'We and others are looking at our own specimens and trying to confirm it,' he said, adding, 'If we validate it, great. My expectation is that we will not.' He noted that there had been false starts before, including a study in the 1990s linking the syndrome to another retrovirus, which could not be confirmed by later research."

I am amused that in his insistence no role for XMRV will be found for "CFS," Reeves mentioned the previous "false starts" - not by name, but I assume that would include EBV, NMH/POTS, 37kDa Rnase-L, natural killer cell dysfunction, and HHV-6 (specifically Variant A, which CDC apparently chooses not to "believe" exists, either). I am amused because I have all of them. There are other markers for which I am not positive - no cancer yet, thank heavens.

Most of us with one "CFS" biomarker have others. Shouldn't that mean something?

For years I testified to the CFSCC, and then the CFSAC, about the evidence of immune and viral damage connected to this disease, only to have Reeves mutter something into the microphone after my testimony, when I was not allowed to respond. Sometimes he would say, "it can't be replicated [Rnase-L defect];" sometimes he said "it's ubiquitous [HHV-6]"). Each time, the biomarker or microbe was presented to the public as either The Cause for CFS, or a worthless finding altogether.

Setting aside the question of just what "CFS:" could possibly be that, after 25 years of so many multiple meanings, could be defined by anything scientific,

Is there a case to be made for "all of the above"?

Is there a case to be made for simply studying the patients who test positive for XMRV and describing their health characteristics? What else do they have (besides, in some cases, prostate cancer)?

In the 12 years since I first brought up the subject of a biomarker in my testimony at CFSCC, only to have it summarily shot down by Reeves or, in the case of HHV-6, Straus (who had been sitting in the back of the room), surely we could have learned something. The skimpy articles defining CFS by Holmes (1988) and Fukuda (1994) were so modernistically sterile as to be misleading about the true nature of The Disease.

Yes, some very good research has been conducted by those of serious intent, using only Holmes or Fukuda.

But let's face it - the best research was not conducted by looking at the Holmes or Fukuda definition through naive eyes, but in collaboration with a clinician who knew how to diagnose what I call The Disease for lack of a better name.

Researchers who have come into the field searching for "Fatigue" writ large have in general produced such brilliant correlations as "the experience of pain correlates with fear of pain" - and then concluded "catastrophizing causes pain." I wouldn't have passed an undergraduate who tried that line of reasoning in a term paper - yet that article was eventually published.

Both Holmes and Fukuda pass the test of modernist simplicity - but how useless compared to the old-fashioned type of epidemiology observable in Gilliam's brilliant, 100-page description in public health's 1938 bulletin on the 1934 outbreak of "atypical polio" at L.A. County General Hospital, or Ramsay's description of M.E. in his 1988 textbook. [The Canadian definition made an effort at complexity, but it, too, is denigrated as a "clinical" definition.]

What we need first out of science is thick description of what it is we are looking at. But in a professional culture where modeling is supreme and basic description denigrated as "applied," even medicine, the most applied of applied sciences, only gains respect when pretending to be "pure." Even if that "purity" is outright fabrication [such as the references to Beard, American Nervousness, 1869, as a way to claim a scientific basis for "neurasthenia"].

Had we followed Gilliam's lead, we would now know so much more - had anyone in government shown concern for the long-run outcome of these conditions for the nation's health, instead of the short-run goal of keeping health care costs down, we would have made much greater progress in understanding The Disease, and whatever else gets dragged into that wastebasket diagnosis.

I actually do believe there is A Disease, and then a lot of misdiagnoses. To repeat: Those of us who test positive for one of the biomarkers tend to test positive for others. There is an identifiable complex disorder out there, and a lot of us have it.

We came to an understanding of AIDS symptom-first because we had to - the patients died off quickly, in the prime of life, from diseases they should not have had, before anybody had a clue as to a model or ultimate cause. The ramifications of HIV were shoved in everyone's faces. That those of us with this Disease die off two decades too soon isn't urgent enough to attract that kind of attention. So no one is interested in simply compiling a list of what goes together with what. Who would publish it? Who would care? That would be (shudder) clinical.

In addition to living a diminished life for years, unable to earn a living or enjoy the activities we used to, we do die early. We die an average of two decades too soon, of heart disease or rare cancers (leukemias and lymphomas). Ironically, after years and years of wishing CFS was not in our diagnosis, they finally take it out at the moment it should be there - when we die. There is no record of patients who have died of heart disease because of CFS, or leukemia because of CFS, or stem cell cancer because of CFS. The records say they died of heart failure, leukemia, or stem cell cancer. Period. We just know about it because they were our friends.

The XMRV discovery is a new opportunity for learning something, if we want to - and if we ask our governments on both sides of the Atlantic to show just a modicum of responsibility. And if we demand responsibility in the media and our professional publications.

Will we use this opportunity to actually study something before drawing vast conclusions?

This is the question I want answered:

*What do the patients diagnosed with XMRV have in common?"

Not "Is XMRV the answer to CFS?"

I want to see the CDC actually consider a multivariate model. I want the psychiatrists either out of the game, or an open admission that they're in - and if they are in, an explanation as to why research on The Disease isn't being managed by NIMH.

Otherwise, the discourse will dissolve again into competition for The One True Cause before we even know what it is we are studying. And, once again, the patients will be the losers.

Mary M. Schweitzer, Ph.D.

"Science" and the rush to judgment

Here we go again. We barely get a chance to think about a new finding in CFS, and the door is slammed shut. I see nothing wrong with Jay Levy writing an article stating that XMRV is a contaminant - but I think it is most unseemly for "Science" to call for a voluntary retraction by WPI (and, ahem, that should be WPI + the Cleveland Clinic + the National Cancer Institute) of the 2009 Lombardi et al study. It is amazing that anyone would call for a halt to work on the retroviruses before the NIH study being conducted by Ian Lipkin has a chance to show results.

Okay, so at least they gave us eighteen months. Usually we don't get that long.

There were problems. I tested positive in that original 2009 study - they found XMRV by serum and antibodies. But when Dr. Peterson sent a sample to VIP labs early in 2010, it came back negative. That happened to a bunch of patients. My own take was that I was positive - I learned having HHV-6, Variant A, that commercial labs can't go to all the trouble that a researcher does - Dr. Ablashi did all my early testing. That is one of the main problems we have - the methods used in studies are far too labor-intensive for labs. It took two years after HIV was discovered – with everybody and their uncle trying – to get a viable commercial test for HIV.

While I understand why they did it, it was naive of the Whittemores to buy a lab (Redlabs, which they turned into VIP labs) to do XMRV testing – and even more naive of all concerned to charge people for testing before they knew the testing was going to work! (They quit testing for a while, then started it up again, then quit again. I was not surprised for that, just frustrated that no one seemed to know how expensive this was for patients, or how bad it looked. It raised suspicions among those who could have been allies.

[Added after comments: I am sorry if I left the impression that, on the whole, there is anything wrong with either WPI or VIP labs. That was just an early mistake. I still use VIP labs for a lot of different testing, and WPI has been nothing but professional with me. In particular, I want to show my support for Dr. Judy Mikovits, who is a scholar of stature and is working hard to uncover the roots of this Disease, and has shown particular kindness to my family. At the same time, I have nothing but respect and affection for Dr. Peterson, who has been the rock for so many of us with this disease, and has himself been responsible for developing a program of diagnosing through biomarkers and treating with valid, published treatment programs, or in formal studies. I'm just asking that we keep this professional, for the sakes of those professionals who are doing so much for our community.]

What really impressed me was the Lo-Alter study. It wasn't a replication, but it was confirmation that the gamma retroviruses (of which XMRV is one) were involved. Then the Barcelona study – followed by the sudden withdrawal of funds to the Barcelona group, which is a great loss because they were working on other biomarkers. It was a message: find the retrovirus, lose your funding. Hmmmm.

While we're in the subject, I think we should keep mum publicly about any positive studies we know about that haven’t been published yet – for now.

And I’ll be honest about something: I don’t want a retrovirus – and I really don’t want my daughter, who hasn’t had children yet, to have a retrovirus.

Personally, I think HHV-6 Variant A is a scarier disease than XMRV. HHV-3 has a name – vericella zoster, or chicken pox and shingles. HHV-4 has a name – Epstein-Barr or mono. HHV-5 has a name – cytomegalovirus. But then there are no names. And when you tell a doctor you have HHV-6 variant A, which causes encephalitis and CNS damage and can cause myocarditis, they say, “what does HHV stand for?”. When you answer “human herpesvirus,” they say, “Oh! Herpes!” Oh great. They think we’re talking about cold sores (HHV-1) or STD herpes (HHV-2).

The press doesn’t know about HHV-6A and its role in our disease, thanks to the CDC and NIH. I’ve tried to get reporters who are hot on the trail of XMRV interested in the OTHER biomarkers and viruses we KNOW we get, but they are not interested. Yawn. I have both HHV-6 Variant A and cytomegalovirus in my spinal fluid for heaven’s sake. Yawn.

It seems in the press the choice is either XMRV or the PACE study – either we have a scary old retrovirus or we are nuts. It may be the editors, not the reporters, but the end result is the same. Either we have a scary retrovirus or we're nuts.

Is ANYBODY going to write about the severity of our disease just based on the severity of our disease? Guess not. Very dispiriting. [Actually first published in 2011 but changing the date was the only way to move it to the back of my files!]