On 10/08/09, the NIH and Science through press releases announced the following remarkable information: Consortium of Researchers Discover Retroviral Link to Chronic Fatigue Syndrome (CFS). From Science on line:
Scientists have discovered a potential retroviral link to chronic fatigue syndrome, known as CFS, a debilitating disease that affects millions of people in the United States. Researchers from the Whittemore Peterson Institute (WPI), located at the University of Nevada, Reno, the National Cancer Institute (NCI), part of the National Institutes of Health, and the Cleveland Clinic, report this finding online Oct. 8, 2009, issue of Science.
“We now have evidence that a retrovirus named XMRV is frequently present in the blood of patients with CFS. This discovery could be a major step in the discovery of vital treatment options for millions of patients,” said Judy Mikovits, Ph.D., director of research for WPI and leader of the team that discovered this association. Researchers cautioned however, that this finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS.
I was as surprised as others on reading this release. A disorder followed for over a century, commonly believed to be an emotionally-based, mood disorder (somatization) is found to have a viral “association”? Although the release states “association,” many readers are likely to read “cause.” The vigor of the news releases and the enthusiasm of investigator comments sure lead one in that direction.
Surprised? Rather, shocked – reading simultaneous news releases from the journal Science (on-line version) and the NIH plus about association with the Cleveland Clinic. These are big time sponsors and investigators. The announcements are intended to be taken seriously. Yet I have doubts.
The announcements and releases are a bit trumpety. But aren’t most such releases the same? Yes, but then why the doubts here, which led to a skeptical blog like this. Well, I saw a few problem clues – I thought I’d “share.”
But first, here are the present principles we use in thinking about CFS. These principles compose a paradigm of the nature of CFS for which the new findings, if proved causal, would require a thorough re-structuring.
CFS has been recognized and described for over a century. It is commonly known by an array of different names, applied to the phenomenon’s syndromes, most of which have shared characteristics: chronic fatigue, fibromyalgia, da Costa syndrome/effort syndrome, neurasthenia (and even “pseudo-neurasthenia,”) myalgic encephalitis (M.E. – UK) chronic Lyme disease, multiple chemical sensitivities, Icelandic (Akureyrie) disease, subclinical hypothyroidism, hypometabolism, hypoglycemia, candidiasis, chronic mononucleosis/ Epstein-Barr disease. Sharing symptoms and presumed differing only in prior associations have been shell-shock (WWI,) battle fatigue (WW II),) post-traumatic stress disorder (Viet Nam and subsequently,) and Gulf War Syndrome. The current paradigm includes all these as variants of somatization, somatiform illness, somatic conversion – all expressions of the same problem through a similar mechanism.
Each of those syndromes differs from others in the focus or dominance of the major symptom and the perceived cause. According to medical historians, these functional disorders were described as early as the mid-19th century (Charcot), and defined or elaborated and popularized by Freud in the early 20th as hysterical (blindness, paralysis, etc.) illness or conversion hysteria.
Later 20th century manifestations were mostly vague physical symptoms, still expressive of somatization – a transfer of focus from emotional source to bodily functions and discomfort. The originating problem is thought to be too threatening to the person’s self image or identity to deal with consciously. Most physician observers detect signs of secondary gain in most patients.
A signal finding of CFS people is a solidified lack of insight, and resistance to introspection and to pursuing psychotherapy or psychological investigation. Psychotropic drugs are generally unable to produce relief or a sense of help. This characteristic has made a diagnosis of underlying depression uncertain, and psychological approaches unsuccessful. But the lack of insight and the surface hostility to medical approaches cause a standoff between the affected and the medical system. Affected people drift easily into aberrant sectarian systems and methods, often claiming dramatic, though temporary results from them. Although most psychological approaches meet with resistance, some success is reported with cognitive behavioral therapy, perceived as non-threatening.
CFS uniformly spontaneously resolves over time. According to CDC, almost all cases are resolved by three years, although there are many of longer record. If anyone has ever died with CFS, I’ve not heard of it. Nor have there been complications or sequelae. Coming close was a young man whose self-recorded history is on Phoenix Rising, one of the CFS web pages I came across. His is a lengthy story – not a typical CFS case – remarkable in its severity, duration, and disability and even to cachexia.
The major and signal symptoms have varied over the decades (centuries?) to conform to changes in medical heuristics and scientific explanations. Patient perceptions seem to accommodate to physician perceptions of what might be acceptable as physical illness. Despite this variation, in the early to mid 1980s, the Centers for Disease Control (CDC) synthesized a collection of major and minor criteria for following a population of CFSers for epidemiologic study. At the time, some experts estimated the affected US population at some 2 million.
The Incline Village epidemic
The current CFS wave started in about 1985 with a small population of patients in a small medical practice of two physicians in Incline Village Nevada, a resort collection of homes and condos on Lake Tahoe. The two physicians claimed that the symptoms of fatigue and poor mental functioning had affected the town in unusual numbers. They suspected the condition acted like a viral disease traveling through their community. Thus began a search for a viral etiology – Epstein-Barr, followed by HHV-6, then mycoplasma, and other organisms. The affair led eventually to a national search and a sudden appearance of other clusters as well as widespread isolated cases.
Among multiple news stories in print and television, was a Newsweek cover story, identifying the phenomenon as an epidemic of mysterious origin, and ignoring the century-long identified history of mood disorder.
Another vogue concept in the mid-1990s was some ill defined adreno-pituitary-hypothalamic axis “imbalance” as seen by yet another array of mild abnormalities on various measurements including stress testing, hormonal assays, and blood pressure measurements, especially to tilt-table positioning. These have led to other theories of vascular and pressure instability or electrolyte imbalance. Some of these studies bore the name of the future Director of the National Center for Complementary and Alternative Medicine, Steven E. Straus.
The problem has been that no laboratory or physical test abnormality had been found consistently in different groups or by different investigators. There are over 4 600 references in Medline, and Google Scholar records over 400,000 references. One would think there would be little left to discover. And, there is already a credible explanation for most cases of CFS – somatiform illness.
When the CDC completed its initial investigation, it found no evidence of a viral etiology, or even of an identifiable physical disease. To many of us, the sudden epidemic-like spread acted as much like a mass psychogenic illness as it did an infectious disease. At least two self-help, patient-organized CFS societies formed for patient education and advocacy, lobbying the CDC for research, and Congress for funds.
CFS, lacking consistent definable characteristics, was somewhat arbitrarily defined by epidemiologists at the CDC in order to select a study population. Simply put, the symptoms are common to almost everyone at some time or other – fatigue, myalgia, specific tender “trigger points,” sleep disturbance, sore throat, mental fog, and inability to concentrate, all lasting a minimum of six months. The physical findings are also minimal – limited to perhaps a mild fever and/or mildly enlarged lymph nodes without pathology, tender muscle areas, but no specific objective finding, no radiographic finding, and no consistent blood or other lab test abnormality.
The virus found by the current investigators was described as a xenotropic murine leukemia related retrovirus – like RNA virus previously found in men with aggressive prostate cancer. I know nothing about this virus or why they suspected it or how they happened upon it. The article’s full text was still unavailable at the time of this writing. If I had read it, I still might need a virologist to interpret the lab methods and findings.
The report’s abstract:
Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines following exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
Note the description of a debilitating disease of unknown etiology… with no mention of current theory – none of the reports so far has mentioned the current opinion on the nature of CFS and its other forms – somatization. All news reports contain only comments on theories of infection and the mysteries of CFS. Nevertheless, the researchers found the virus in blood and immune cells of 67 percent of CFS people as compared with 3.7 percent in normal people. That is impressive. Determining what the XMRV is doing there is guesswork at this point.
Then two names on the news releases and the report caught my eye. The major research organization publicizing the discovery was the Whittemore-Peterson Institute for Molecular Biology. Reno is not far from Incline Village and the name D. Peterson – that turned out to be Daniel Peterson, the second physician in the original Incline report, along with Paul Cheney. Over twenty years of searching for a cause of a phenomenon (an infectious epidemic) determined not to have occurred – and the search continues? I could not help but take notice. And who is Whittemore? He is a real estate developer in Reno who supplied the first $1.4 million for the new research institute to be at the University of Nevada Reno’s medical school, to be devoted to investigating neuro-humoral systems. I suspected some family connection to CFS so looked through the releases and found a note that his daughter, 26, is…a sufferer from CFS. None of this detracts directly from the weight of the experimental findings, but it’s just unsettling.
I do not know what will result from this work. Certainly, the work of 13 authors from four different research institutes must mean something. They could not all be deceived? Eight authors from four countries were deceived in the original Benveniste homeopathy report. Then, tens to hundreds of investigators at NIH may have drunk of the NCCAM Kool-Aid by this time, believing at some point that there might be something worthwhile in CAM methods. Funny things happen. I’m betting that either the work will not be replicated, or that some other innocent explanation such as an artifact of lab technique accounting for viral presence will be found. I estimate the odds at 80:20 (4 to 1.)
If the association is confirmed, the finding will have near-revolutionary implications for our understanding disease – particularly infectious disease. If there is a confirmed model for such a vague set of symptoms signifying some occult infection limited to immune cells, which produces no repeatable cellular or antibody abnormality, no susceptibility to other infections (such as with HIV) and in which the sites of infection (immune cells) bear no relation to the sites of symptoms and produce no physical abnormality, I haven’t known of it. Interesting times.