This information is reproduced with kind permission from the October 2009 issue of Dr. Bell’s free Lyndonville News e-newsletter. It was published shortly after research linking the “XMRV” retrovirus and ME/CFS went live in the journal Science on October 8.
Holy smokes! Just when I want to retire this comes along. How am I going to get any peace and quiet?
Here is the Lyndonville News coming out within a week of a paper being published, and already what I have to say is old news. Probably everyone reading this newsletter has been on the edge of their seats listening to NPR, CBS, Reuters, and so on. The CDC has already said that it isn't going to pan out. It is my guess that the media coverage will intensify because this is really big news.
First of all, congratulations…
To Drs. Judy Mikovits, Vincent Lombardi, Robert Silverman, Dan Peterson and the rest of the authors. And a special congratulations to the Whittemore Family Foundation, and the Whittemore-Peterson Institute for putting this together. For many years ME/CFS has been limping along on complex science that points to mechanisms of illness that most physicians have ignored. Limped along with skeptical specialists, medical establishments, government agencies. Limped along despite attacks by disability companies. Now we can get down to business.
In this issue of Lyndonville News I will briefly repeat what has been reported in the Science paper and the press releases.
But most of all I want to predict where this is going.
I am using the "force" here. I have no special or inside information from the Whittemore-Peterson Institute. They have to be cautious and circumspect. I don't. I am an old man sitting on my porch rocking chair, desperately trying to retire; I will say what I think is true.
By the way, people are already asking me if this is related to the retroviral sequences we published in 1991. Please don't ask me, history will sort this stuff out; the focus and attention now needs to be upon the current work, mechanics of symptom generation, epidemiology, and treatment implications.
The focus needs to be upon the Whittemore-Peterson Institute, and other scientists who will become involved in replicating the material and moving on from there. When I was on the CFS Advisory Committee we recommended that ME/CFS centers be established. That advice fell on deaf ears.
But now, before the Whittemore-Peterson Institute has even opened its doors, we get privately-funded science that will end up changing the world.
Literature Review: XMRV in Science
Dr. Judy Mikovits of the Whittemore Peterson Institute in Nevada and colleagues at the National Cancer Institute and the Cleveland Clinic have published a paper in the prestigious journal Science, an article entitled "Detection of an infectious retrovirus XMRV, in blood cells of patients with chronic fatigue syndrome" – Online 8 October 2009; DOI: 10.1126/science.1179052. [To read the full text article, go to the WPI website and click on "View Reprint."]
• The virus, an infectious gammaretrovirus, XMRV (for Xenotropic Murine RetroVirus), was found in the blood of 68 out of 101 chronic fatigue syndrome patients, by looking for DNA.
• The same virus was present in only 8 of 218 healthy people.
• This virus is known to be "oncogenic," meaning that it can cause cancer. At this point only a link has been established between XMRV and CFS.
XMRV was first linked to human disease by Robert H Silverman, PhD, at the Cleveland Clinic, in patients with prostate cancer who also had a defect in the RNAse L antiviral pathway. As this pathway has been known to be abnormal in CFS(1,2), it was reasonable to search for the virus in CFS. In their first paper on XMRV, it was linked with this RNAse L defect, but this has since been revised(3).
The XMRV DNA is present in 67% of cases, and few controls. (More data show greater than 95% of the more than 200 ME/CFS, Fibromyalgia, and "Atypical MS" patients tested positive for XMRV antibodies, as per their website – www.wpinstitute.org). High levels of XMRV proteins were expressed, and they were able to produce infectious particles in culture.
In the paper, the authors are cautious, stating that the finding only shows a link between the virus and CFS, and does not prove that the pathogen causes the disorder.
Personal Comment: XMRV as "The Puppet-master Virus"
Is CFS a single illness or a heterogeneous collection of fatigue-causing illnesses? This question has been important for 25 years and needs to be addressed at the beginning of the XMRV era.
In some senses all illnesses are "heterogeneous." There is the viral agent and there is the host. No two hosts are identical, and even identical twins have "epigenetic" differences. Therefore it is inevitable that phenotypes (the way an illness appears in a person) may vary. Poliovirus is a good example. One agent causes a mild flu-like infection in one person and paralysis in another. But polio should not be thought of as a heterogeneous illness.
XMRV may "cause" CFS because it allows other agents (EBV, Lyme, enteroviruses, etc.) to be expressed differently. After all, XMRV is a retrovirus, and look at the variations in phenotype in other known human retroviruses.
The lymphocytes expressing XMRV were "activated," implying that this agent was not just quietly lurking in cells, as some agents do.
The "Two Hit" Theory has been circulating for 20 years.
• One hit is an immune altering silent hit,
• And the second is a herpes virus or some other agent.
Actually herpes viruses can carry retroviruses along, so here is more work for the Whittemore-Peterson Institute to do. John Coffin wrote "One New Virus – How many Old Diseases?"(4)
I would think of XMRV as the "puppet-master":
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• It is known to be linked to prostate cancer;
• It lurks in the shadows and pulls certain strings causing cells to become malignant.
• Perhaps it pulls another string to cause EBV to be more active, or Lyme, or enterovirus?
• Another string to alter RNAse L?
Many, many questions open up. But we already know several things.
• First, ME/CFS is not like your average infection, pneumonia for example. This is a really complicated disease. But AIDS was complicated and now is pretty well figured out.
• Secondly, we know the clinical aspects of ME/CFS, putting aside the arguments over what definition you use. And the good news: After following patients for 20 years, not many are getting cancer. But there is bad news; cancer takes a long time to get going.
But the really good news is that if XMRV is the puppet-master of ME/CFS, it conceivably could be very treatable. Theoretically, more treatable than HIV. Lots of work to do.
The politics of ME/CFS are daunting. But now may be the time to forge ahead and get something done. Congratulations again to the authors and the Whittemores. It is time for the CDC and the NIH to be constructive and do some science.
Lyndonville Research Group:
Let’s revive the Lyndonville research group again (gasp). I would like to test the original Lyndonville kids for XMRV, and if any of you reading this became ill in the Lyndonville, New York area around 1985, were 18 or under at the time, and want to be evaluated, please write to me at firstname.lastname@example.org. Even if you are feeling great now.
1. I feel like I am drowning, and what I ask is if you can recommend a good doctor that actually takes…Medicare. I…do not understand why average doctors seem to know so little about this…I am on disability; My resources are limited. I would have to do this all out of pocket.
Response: How can I answer these questions that I have now seen for 25 years? I would say that I feel badly for you, or shut my eyes and move silently on. I have been accused of being too optimistic in the past, and certainly those criticisms were correct.
But now things are different. Now I am not going to be too optimistic – I think XMRV is going to turn out to be the "cause" of ME/CFS, and I think treatments will be available from every family physician in America who accepts Medicare.
The question is whether this occurs next year or 20 years from now.
2. As a teacher-turned-programmer, due to CFS, cognitive functioning is particularly important for me… I now can barely skim through your not-too-difficult articles … Anyhow, you said, "I may consider testing some persons with… PCR for HHV-6, but this can be expensive and not covered by insurance." I would like to know about how much money this can be (the potential cognitive benefits could be well, well worth it for me)…
Response: There are two issues here. The first is cognitive. Historically I have always been struck by the similarities between the cognitive decline in ME/CFS and HIV infection. This is one reason that I have long felt that a retrovirus would be an excellent candidate to be the puppet-master. Secondly, as far as the finances are concerned, it is possible that things will change.
Federal approval of diagnostic testing needs to be put on a fast track. Now.
1. Suhadolnik R, Peterson D, Reichenbach N, et al. “Clinical and biochemical characteristics differentiating chronic fatigue syndrome from major depression and healthy populations: Relation to dysfunction of RNase L pathway.” Journal of Chronic Fatigue Syndrome, 2004;12:5-36.
2. Nijs J, De Meirleir K. “Impairments of the 2-5A Synthetase/RNaseL pathway in chronic fatigue syndrome.” Anticancer Research 2005;25:1013-22.
3. Schlaberg R, Choe D, Brown K, Thaker H, Singh I. “XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors.” PNAS 2009.
4. Coffin J, Stoye J. “Perspective – a new virus for old disease?” Science Express, online Oct 8, 2009.
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Disclaimer: Any medical advice that is presented in the Lyndonville News is generic and for general informational purposes only. ME/CFS/FM is an extremely complex illness and specific advice may not be appropriate for an individual with this illness. Therefore, should you be interested or wish to pursue any of the ideas presented here, please discuss them with your personal physician. © 2009 David S. Bell