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A primer for XMRV, XAND, M.E. - and CFS
By Mary Schweitzer, Ph.D.A primer for XMRV, XAND, M.E. - and CFS
On October 9, 2009, an article was published by Judy Mikovits et al in the highly prestigious research journal Science announcing the findings that a newly discovered retrovirus, called XMRV, had been found in 67 percent of a sample of patients diagnosed with CFS over a period of 25 years. There are only 3 known human retroviruses: HTLV, HIV (which leads to AIDS), and now XMRV. The importance of this finding cannot be overstated. The Cleveland Clinic had already found XMRV in roughly 10 percent of prostate cancer patients, but the more startling news had been that it was present in 3.4 percent of controls. That was too high. So they began to look for other possible roles this virus played.
The new , or WPI, combined resources with the Cleveland Clinic and the National Cancer Institute (one of the National Institutes of Health, or NIH) to arrive at this startling conclusion. Mikovits is Research Director of the WPI, a private research institute created four years ago in association with the University of Nevada at Reno.
Here is a quick primer for those who have been diagnosed with CFS or M.E., and the many who have XMRV but have yet to be diagnosed. I am a social scientist, not a hard scientist, so keep in mind my viewpoint is that of the lay public. I will add more information and sources over time, but right now this basic primer should be of help.
- XMRV is not CFS
- XMRV is a retrovirus
- XAND is to HMRV as AIDS is to HIV
- What is XAND?
- Where does Myalgic Encephalomyelitis fit?
- What is the U.S. government doing about XMRV?
XMRV is not CFS
XMRV cannot be CFS because CFS is what is called a "socially constructed concept," not a scientific one. It means too many different things in the realms of medicine, research, and popular culture, and even has contradictory research definitions.For example:
According to British psychiatrist Peter White, CFS is a condition of unexplained symptoms that results from "inappropriate illness beliefs." It is best treated with Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET). And this is pretty much the version of CFS that has been adopted by Britains National Health Services and their "NICE" medical guidelines.Patients diagnosed by White and other British psychiatrists as having CFS cannot have any physical explanations for their symptoms. Therefore they cannot have XMRV.
Another way of putting that is: the moment a patient diagnosed in the UK with CFS is diagnosed with XMRV, he or she is suddenly free of the interim diagnosis of CFS. By the British medical establishments own rules. That means that any statement by CFS experts in Britain such as Peter White, Trudy Chalder, Michael Sharpe, or Simon Wessely, with regard to XMRV, is out of their field of expertise they are all psychiatrists.
The official Holmes (1988) and Fukuda (1994) definitions fpr CFS at CDC had no restrictions that could preclude XMRV as either correlated or causal. The Canadian Consensus definition for ME/CFS (2003) rests even more greatly on physical symptoms that could be associated with viruses, and hence associated with a retrovirus. However, many of the patients diagnosed using the CDC's questionnaires created in 2005 do not have any physically verifiable symptoms. Independent research comparing patients diagnosed with the Fukuda definition and those diagnosed using the CDC "empiric" questionnaires found that the latter method left out thirty percent of the Fukuda-defined patients - the ones with the worst symptoms - but added in many more patients with symptoms associated with melancholic depression. Using the Fukuda definition, DePaul researcher Leonard Jason found that one million adult Americans probably have "CFS"; using his questionnaires, CDC researcher Willliam Reeves came up with an estimate of 4-7 million. The significance of the differences between the groups should be obvious.
Thus, whereas the Science article found that 60 percent of a sample of "CFS" patients had XMRV, those patients were diagnosed using more restrictive criteria than is now used by CDC. If CDC tested their Georgia cohort for XMRV, it would be surprising to find more than 15 percent of those patients had XMRV. And this would be true of any attempt by CDC to "replicate" the research using their own questionnaires rather than the Fukuda and Canadian definitions that were used in the Science study.
It is no wonder that the head of the CDCs program on CFS for the past twenty years, Dr. William Reeves, immediately responded that none of the CFS patients in his new Atlanta-area study would have the virus. "Dr. William C. Reeves, who directs the agencys 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." (See ).
I agree. Few of Dr. Reeves' patients will turn out to have XMRV. That is because for twenty years he has been studying fatiguing illnesses not anything to do with the immune defects and viruses that caused cluster outbreaks of disease all over the United States.
When Dr. Mikovits found that 95% of CFS patients from a large selection of practices in the U.S. had XMRV, it was a result that will not be replicated by the U.S. CDC using its own data sets of CFS patients. Because all over the world, CFS has been redefined as a disease of fatigue, and patients so diagnosed have nothing to do with the original cluster outbreak patients for which the name was created. We patients and our doctors have known this for a long time.
At the first CDC-sponsored conference to come up with a name for the new disease, several experts present suggested that these were outbreaks of Myalgic Encephalomyelitis, a neurological disease that has been diagnosed for over half a century in the UK, and has been coded under neurology by the World Health Organization for forty years. The disease is characterized by significant central nervous system (CNS) dysfunction, brain dysfunction, and muscle pain (myalgia). But the CDC rejected that name, too, because there was no evidence of inflammation, they said. They did not include a reference not even a footnote to the possibility that CFS was actually M.E. in the 1988 Holmes article. The link was not made until British psychiatrists, acting in concert with Dr. Straus of NIH, used it backwards: M.E. was really CFS, and CFS was really neurasthenia a neurosis.
For years the CDC and NIH have brushed off all evidence that subgroups of the total set of people with a CFS diagnosis have very specific immune defects and active viruses, because it wasnt true for all of them. Well, now that doesnt matter, does it?
Finally, XMRV cannot be the same thing as CFS because it was first discovered among victims of prostate cancer apparently at least 10 percent have XMRV. Unless prostate cancer is considered a form of CFS (to my knowledge it is not), then XMRV cannot be CFS.
XMRV is not CFS.
XMRV is a Retrovirus
Viruses fall into classifications. Polio is an enterovirus. Epstein-Barr is a herpes virus. XMRV is a retrovirus. And there are categories within categories. Human Herpesvirus 1 (HHV-1), or herpes simplex virus, causes cold sores. And thats about it. But HHV-8 causes Karposis sarcoma in AIDS patients and kills them. None of the viruses just mentioned have anything to do with what we know as the cold. And even H1N1, the new virus that popped out this year, already has variations.What makes this discovery so profound is there are only three retroviruses known to be active in humans: HTLV, HIV and now XMRV.
The second reason this discovery is so profound is that retroviruses cause problems by creating an environment for other viruses to flourish and even transform themselves into something new.
Lets look at HIV, then.
HIV is important because it either causes, or is so close to the cause as to be indistinguishable for practical purposes, AIDS. In fact, the name was chosen to refer to AIDS Human Immunodeficiency Virus HIV.
AIDS itself means Acquired Immune Dysfunction Syndrome. Ironically, when the CFS outbreak first occurred in the middle of the AIDS outbreak many patients on both Coasts called the disease HIV-negative AIDS. Quite a comedown in how you perceive the disease from HIV-negative AIDS to chronic fatigue syndrome, isnt it? Many patients still refer to the disease as CFIDS Chronic Fatigue and Immune Dysfunction Syndrome. But from the first article and definition (Holmes, 1988) from CDC, the agency has insisted that they were studying Epstein-Barr negative mononucleosis best described as being tired all the time for no good reason. Chronic Fatigue Syndrome. As theyve branched out into the study of all Fatiguing Illnesses, its no wonder that Dr. Reeves does not think any of his patients will have XMRV. Many perhaps most - wont. But they were the wrong patients to be studying in the first place, werent they?
Patients diagnosed with HIV arent sick yet. They are quite normal (which has made it easier for them to advocate for action to be taken against the disease we dont know were sick until were really sick).
The CDC and WHO both consider a patient to have AIDS when he has both HIV and an enumerated AIDS illness such as Karposis sarcoma (a type of skin cancer that was relatively benign and limited to elderly Mediterannean men) or pneumocystic pnsumonia, once an extremely rare opportunistic disease.
HIV alone does not equal AIDS.
HIV + Karposis Sarcoma = AIDS
HIV + pneumocystic pneumonia = AIDSJust as there are perfectly healthy people walking around with HIV, there are perfectly healthy people walking around with XMRV. My husband could be one of them. (Yet another set of people due for early testing - healthy family members of patients who are sick and have XMRV.) Bob has been perfectly healthy the entire time I have had the disease, and this is true of a lot of ME/CFS spouses. Perhaps he is a carrier.
XAND is to XMRV as AIDS is to HIV
XAND means XMRV Associated Neuroimmune Disorder, and XAND is to XMRV as AIDS is to HIV.As the many of the diseases and immune defects that caused the AIDS epidemic had already become known by the time HIV was discovered, so too many diseases and immune defects associated with XMRV are already being studied in the context of original CFS patients or CFIDS patients or M.E./CFS patients (a compromise name recognizing the placement of CFS in the M.E. code under neurological diseases in WHOs ICD-10 but the U.S. is still on ICD-9 and does not recognize the connection). ME/CFS has the best diagnostic guidelines, the Canadian Consensus Document - and patients so diagnosed have already tested positive for XMRV.
So that is our AIDS. The disease that popped out in the 1980s that the CDC did not deign to actually study, choosing instead to create a "new" disease entity that they described as the result of upper middle class women trying to have it all. It is not the disease that, today, they define mainly as an inability to handle stress because of childhood emotional injuries.
Our AIDS is the disease behind an outbreak of geographic clusters of serious diseases throughout the United States in the 1980s, often (but not always) tied to Epstein-Barr Virus; often described as a bout of the flu that refused to go away. Our AIDS is the disease that the CDC refused to study at all. And our AIDS has been permitted to spread as a result.
There is one intriguing difference between HIV and XMRV. HIV apparently causes AIDS by permitting the AIDS abnormalities and diseases to flourish in an infected body. XMRV may actually cause neurological symptoms by itself.
For now, we could easily - immediately - begin to turn to our "AIDS" - to the cluster of conditions we already know are associated with CFS. Over the past 25 years, using homogeneous population groups that fit either the Holmes or Fukuda definition, or both, clinicians and researchers have come up with a number of immune defects and viruses associated with their CFS samples. (Again, not the CDCs CFS samples. The CDC would be the first to tell you that.)
It begins with M.E., which has been associated with coxsackie B for years.
Patients from the cluster outbreaks were prone to immune defects such as T-cell inversions, natural killer cell dysfunction, and a defective form of Rnase-L. They were far more likely than the normal population to have HHV-6 (particularly Variant A), Cytomegalovirus (CMV), mycoplasma, a particular enterovirus that caused severe IBS symptoms, and parvovirus B19. Conditions such as parathesias, photophobia, chronic hypothyroidism, chronically low adrenal levels (never formalized into a disease name), and the autonomic nervous system dysfunction known as NMH/POTS (neurally mediated hypotension/postural orthostatic tachycardia syndrome) were brusquely dismissed with a sample of, say, 35 patients. The press release would say, for example, HHV-6 has no statistical relationship to CFS. And that would be the end of that.
Each time researchers discovered a biomarker or virus connected to a cluster of patients who fit the Holmes or Fukuda research definitions of CFS, the CDC or NIH brushed it aside because the finding was never a perfect marker for CFS.
That meant that we are starting out with a list of possible cofactors with which to connect the retrovirus XMRV to the disease XAND.
What is XAND?
Note:XAND is a proposed name already in use, but it will take years for it to become official. Since XMRV is a newly discovered disease, we believe that the use of the new name XAND from the beginning will avoid confusion resulting from existing definitions for associated diseases.XAND (pronounced "Zand") stands for XMRV Associated Neuroimmune Disorder.
To understand it, lets go back to the AIDS model again.
HIV by itself is not AIDS. You have to have one of many defining diseases to be diagnosed with AIDS.
HIV + Karposi's sarcoma = AIDS
HIV + pneumocystic pneumonia = AIDSSo what is XAND?
XMRV + natural killer cell dysfunction = XAND
XMRV + active HHV-6 = XAND
XMRV + active CMV = XAND
XMRV + T-cell abnormalies = XAND
XMRV + Coxsackie B = XANDThe disease that XMRV has now made it possible to diagnose is XAND.
Myalgic Encephalomyelitis
Where does XMRV fit in with M.E., or Myalgic Encephalomyelitis?Perhaps M.E. is a cofactor: XMRV + M.E. = XAND.
Perhaps we can divide M.E. into ME-XMRV and ME-Ramsay (just as there are cases of prostate cancer that have nothing to do with XMRV).
Margaret Williams has suggested a natural relationship because of decades of evidence that M.E. is related to coxackie B. (See )
Unlike CFS, M.E. is a disease, a disease that has been diagnosed for half a century and coded under neurological diseases in ICD-10, the World Health Organization's current International Classification of Diseases (G93.3) - and it has been there for FORTY YEARS.
The whole CFS problem might not have gotten away from us had the authorities followed the advice of specialists who strongly suggested, in 1987, that the 1980s outbreaks were due to M.E.
And M.E. would be a well-known disease today, as M.S. is, had it not been for a cult of British psychiatrists who claimed to follow the theories of "biopsychosocial" medicine (and whose answers fit well the needs of insurance companies and national health agencies to save money after the unexpected jolt of AIDS).
How silly it will look to have attributed the results of a retrovirus to "inappropriate illness beliefs."
What is the U.S. federal government doing about XMRV?
To their credit, the highly respected National Cancer Institute (NCI), part of the enormous NIH system, is taking this very seriously. NCI scientists assisted in the Science article. Now NCI and the Whittemore-Peterson Institute are working to create a test that will take three hours or less, and that can be performed by commercial labs around the nation. NCI is particularly worried about XMRV getting into the blood supply, but it seems to me that horse left the barn 25 years ago. They hope, nevertheless, to be able to screen the current blood supply (and let's all hope that it hasn't already been mixed into all the combination blood products out there these days), and then to prevent future donations of blood from XMRV-positive patients to enter the nation's blood supply.
Once that test is completed, then NCI and CDC can go public with the news of the disease. They do not want to say that there is a new retrovirus out there that has contaminated the blood supply, and they don't know how to get it out. But that certainly is an improvement in the way The Disease was treated for 25 years. (And I don't want it in the blood supply either! But then, I haven't given blood in fifteen years.)
I think there is a very good chance that patients diagnosed with XMRV will get serious research programs (finally!). The programs, of necessity, should involve the XAND conditions and diseases - all those biomarkers and viruses that CDC has shoved aside for twenty years. If XMRV is taken seriously, it won't be long before HHV-6 is taken seriously, along with its two variants A and B. Coxsackie B is another disease associated with this condition that should get new respect. The Rnase-L defect, ignored by NIH and CDC for almost fifteen years, is going to get serious attention because of its role in connecting the prostate cancer victims with XMRV to the CFS patients with XMRV. Natural Killer cell dysfunction should get new attention.
As a result, even those patients who do not now test positive for XMRV - but have XAND conditions and diseases - should get new-found respect.
Pay me now or pay me later. Every year the authorities refused to face this disease head-on, they saved money in the short run by leaving patients out in the cold. But they also increased costs in the long run by ensuring the disease would spread from the tens of thousands to millions - and now, without an end in sight.
Had everyone involved dealt with the CFS outbreaks as outbreaks of M.E. at the time, we would not have anywhere near so many people sick today. Perhaps they did not have M.E., but we would have learned a lot about what they did have. And patients with M.E. would not have been sacrificed to the effort to bury CFS.
Hard as I find it to believe, the same shysters who for years ran quick and dirty studies to "disprove" the biomarkers and viruses that we were discovering in patients with The Disease, are back again. The first three studies published in Europe have claimed to have disproved the NCI/WPI/CC discovery - but they did not use the same methods, and in two of the three cases, they used patient groups wildly divergent from those in the Science study.
What is needed now are replication studies - studies that use the same standards for the data set, and use the same methods to test for the disease. The WPI has offered to cooperate with everyone. And those studies are under way - it just will take some time.
I think the deniers - particularly the British psychiatrists - believe they can make XMRV disappear using the same tactics they used for everything from NMH/POTS to HHV-6 to the Rnase-L defect - cooking the data set, sticking to very small samples (which by nature are not going to show statistically significant responses), and violating a standard rule of statistics: claiming to have disproved something simply by failing to find it.
The old strategies are not going to work this time. XMRV is not going to disappear.
My one fear is that those paients who test negative for XMRV will remain in the limbo of pseudo-psychiatry. Anybody who has this disease is sick; they are just misdiagnosed. Ideally, CDC and NIH could recommend diagnoses based upon a patient's actual symptoms (not on "fatigue," which is common to all serious diseases). Hence, some would get a preliminary diagnosis of "endocrine dysfunction, cause unknown;" others a diagnosis of "cardiac dysfunction, cause unknown." "Cause unknown" should not be a free pass for any nutty theory that some interest group wants to espouse; it should not be a ticket to a psychiatrist's office, a British mental hospital, or an American foster home; and it should not leave patients at the mercy of insurance companies trying to get out of their contractual obligations.
Mr. President: Please appoint a private commission of retroviral, XMRV, and originalCFS and M.E. experts to organize the funding, testing, and treatment of patients with XMRV and XAND. Please do so as soon as possible because we have already lost 25 years, and this is a contagious disease.
And please see to it that those who do not test positive for XMRV get a correct diagnosis, too.
The good news is that the answers are only a blood test away. It is a matter of organization, care, and funding. This time, let's get it done right.
Let's insist that the correct terminology for diseases in the context of a retrovirus be used. The CDC always said that when there was a scientific reason to drop CFS, we would drop CFS. WE MUST INSIST UPON IT THIS TIME.
XMRV is not CFS.
XMRV is to XAND as HIV is to AIDS.
After 25 years, time to study the right disease. Let's conquer XAND.Oh - Yes, I have XMRV. Explains a lot.
Mary M. Schweitzer, Ph.D.
Postscript
Scientists have a lot to keep them busy. Hundreds of thousands of patients diagnosed with "CFS" are going to want to take the test, which is currently being offered in the $500-$600 range at in Reno. Eventually the testing process will have to be more formalized, but at least they have made the test available so patients do not have to wait. Profits from the XMRV test will go to further research at the Whittemore-Peterson Institute. But if you want to support the WPI, write them a check. Then wait for the new test to emerge from the collaboration between WPI and the National Cancer Institute. We've waited decades; we can wait another year.Among the questions to be answered: How is the virus transmitted or activated? Is XMRV by itself a symptom-causing disease, in addition to the peculiar role it plays in conjunction with other diseases (as do all retroviruses)? What diseases are activated by XMRV? What treatments are already available, and how long will it take to get new treatments to patients? What does it mean that roughly 3.5% of apparently healthy people are positive for XMRV?
For a good summary of the issues involved, by a clinician in the center of the battlefield for 25 years, read . There are good British summaries, one by and another by the .
For a clear and professional seminar on XMRV, watch the presentations by Dr. Dan Peterson and Dr. Coffin on the videotape of the October 29, 2009, CFSAC meeting at DHHS in Washington. Go to the main CFSAC website at . Click on "Day 1 videotape" in the box to the right of the page. You need to have RealPlayer to view it (it can easily be downloaded for free at if you do not already have it.) Dr. Peterson's presentation begins at roughly one hour and 23 minutes into the video for Day 1; Dr. Coffin's presentation follows.
I have had the disease derisively called "CFS" for two decades; I have been unable to work for 15 years. My natural killer cell function is 2%; I have the abnormal Rnase-L. I suffer from recurring bouts of Epstein-Barr, and I have chronically active cytomegalovirus (CMV), HHV-6 (Variant A), and HHV-7. I responded well to the immune modulator Ampligen but the FDA has so restricted it I cannot get it any more on the East Coast, so right now I am very ill. I am hoping to be able to get Ampligen at a site very far from home. It will mean leaving my husband of 35 years, but we do what we must. (If I do get Ampligen I will change this essay to reflect that.)
And now I know that I also have XMRV. It makes sense. But it also lends a sense of urgency to my need to get back on Ampligen. Ampligen is an immune modulator; it probably worked by controlling XMRV. Seven months after I lost it, I began to relapse. Two years after losing it, I'm very sick. How long can I go with this disease untreated before I develop something that Ampligen can't reverse?
Finally - The private needs your help to continue this work. It is a nonprofit institution founded by the parents of a courageous young woman who has had the disease for over 20 years - since she was 12. A donation as low as $5 will help speed up the time it takes to get people tested, identify cofactors, start treatment with existing remedies, and continue research on the nature of the disease and new treatments to offer.
Here is the website for donations to the Whittemore-Peterson Institute; they take credit cards and Paypal: .
Other similar nonprofit patient-run institutions created to support research include in the UK, and the .
Our world is about to change.
Mary M. Schweitzer
This website is owned by Mary Schweitzer. You may reach me by going to , where my blog is.
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