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!]