David S Bell, MD | Lyndonville News

Information and Support for the ME/CFS/FM Community
David S. Bell MD, FAAP, Editor

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On January 6, 2010, the first paper to refute the Lombardi et al.(1) paper in Science was published in the journal PLoS ONE: Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue syndrome.(2) It was bound to happen. Then came papers two and three, again polymerase chain reaction studies on stored blood(3, 4). Nothing in ME/CFS is easy, but this is the way it works in science. There are two possible scenarios:

Scenario one is that several quick papers can't find it. The first paper was two months from idea to lab tests to writing to review to publication - that’s quick. The Science paper was two years in the making and the review process itself took six months! So, we may have a rush to judgement here. In this scenario the scientists will get discouraged and accept the inevitable - this is just another of many, many dead ends. The Science study will be quickly buried and forgotten. It has happened before.

Scenario two is how science should work. Someone publishes a paper showing a virus called XMRV is found in persons with ME/CFS. Somebody else says it cannot be detected. And reading the fine print it turns out that one study uses heparinized tubes, the other ACD tubes. Then they collaborate and share data and work out some of the differences. And there are many, many differences. I remember that in 1990 I asked the Fedex driver to hold the samples in his lap because the back of the truck was frozen with Upstate New York January air. At that time I didn't know if freezing was going to alter the results.

With each study we should learn something. A study may show different numbers and a slightly different sequence. We learn something. A scientist pokes holes in a colleagues paper. That colleague goes home, thinks about it and learns something. He or she comes back into the lab and does another experiment. It is a marvelous process. And I remain confident that we will arrive at the truth, whatever that is.

And the papers published so far have not "failed to replicate," as none of them have tried to replicate. And, as Hilary Johnson has pointed out, there was an enormous rush to pin AIDS on HIV when it had been found in a couple of people. XMRV has been isolated from seventy five individuals.

Dr. Nancy Klimas said in her lecture, "And if you see some negative papers coming out, don’t be discouraged. It’s going to happen. There are going to be some negative papers. People really jump to do this. And the method is not that easy, and getting the right bits and pieces you need together, it’s not: read the paper and then go do it."

"and I would like to be around when all those snarks have to swallow their vastly irritating lumps of hubris." I am not quite sure what it means but it was referring to the negative papers.

I have heard third hand that someone at the CFSAC meeting did not like the letter I wrote asking persons to contribute $10 each to the WPI. I agree, it is not the way science works. It is absurd to think that a few $10 bills will change anything. It is also a little embarrassing. Oh well.

There have been over 5,000 scientific papers written on ME/CFS. Huge amounts of money have been spent on psychological studies, behavioral therapy studies. Even trying to define the illness has been impossible, but the money goes there as well. It may be time to put some research effort into good virology. But here is the letter I wrote. And I have sent in my $10 check.

            I would like to put out a personal appeal for funds to be sent to the Whittemore-Peterson Institute (WPI) in order to speed up the progress of the current research. Here is my reading of a very complex situation.
            Medical authorities, educational institutions, governmental agencies, and most practicing physicians have disrespected and minimized CFS in just about every way possible, from creating an insulting name for the illness to advising extreme caution in treatment, except cognitive behavioral treatments.
            It is easy to dismiss my remarks to follow by saying that I am biased. And it is true, I am very biased and for twenty five years I have quietly sat on the sidelines believing that science will win out and true progress will be made. I am beginning to think this has been a great mistake. The profession I love has failed miserably.
            In 1985 an outbreak of CFS hit Lyndonville NY and affected 210 persons, 60 of whom were children. The official response from the CDC and the New York Health Department was that this was mass hysteria. No one talked with a single patient. In 1990 I worked with Dr. Elaine DeFreitas and Dr. Paul Cheney and a retrovirus was found and the material published (DeFreitas E, Hilliard B, Cheney P, Bell D, Kiggundu E, Sankey D, et al. Retroviral sequences related to T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci. 1991;88:2922-6). A second paper had been accepted by PNAS and contained a photograph of C-type retroviral particles from a tissue culture of spinal fluid of one of the children in the Lyndonville outbreak. This paper was suddenly pulled and not published after a couple of flawed negative papers. A complete description of these troubled times is in Osler's Web by Hilary Johnson. The funding for our studies was pulled and all work on this abruptly stopped.
            I think the same tactics are being employed to hamper the current work on XMRV by the WPI. The WPI is a private organization and, as I understand it, no federal grants or funding has been forthcoming. There have been three negative PCR-only studies which have established only that CFS can not to be superficially studied. At this time no study that has attempted to replicate the WPI study has been heard from. Many CFS research organizations have declared publically that "XMRV is a dead issue."
            Nothing is farther from the truth. I cannot predict the future, but my fear is that the current political and scientific organizations who do not want to see retroviral involvement will attempt to stifle studies on XMRV in CFS. Huge amounts of money are spent on studies on cognitive therapy, and studies proving that CFS is heterogeneous (you can argue that polio is heterogenous).
            We have not heard from the CDC, other than the inappropriate comment that this was not likely to turn out to be anything, made right after the Science paper publication in October 2009. We are now eight months later and not a peep. Maybe they are finding XMRV and want to be very careful. Maybe they haven’t looked and are assuming that this heretical idea will blow away. Eight months? And the Band Played On.
            It is possible that thirty other labs are finding XMRV in CFS or that no one else in the world is even looking for it. Science requires that labs do not disclose their findings prior to publication and I agree with this rule. But is the WPI going to be isolated by the scientific community and wither away because of lack of funding? Is XMRV going to become more of the compost of CFS research?
            But there is an alternative. We cannot wait ten years for science to grind out its conclusions. Every person in the world who believes that CFS is important should send $10 to the WPI. I plan to send $10 today. It may not be much, but it is a start. There may be 10 million persons in the world with CFS. Lets see, that’s…I need a calculator. May 12 is our day. Let’s do this.
            After 25 years of work in this field I do not have much. But I have my integrity. I feel that WPI has made an important discovery and I feel they are an ethical organization, they are not padding their pockets. But I also have my fears. And the greatest fear of all is that their discovery may not be appropriately followed up.
            For the 9,999,999 other people out there who think CFS is both real and important, send $10 to: Whittemore Peterson Institute, 6600 N. Wingfield Parkway, Sparks, NV 89436. Thank you.

Over the past twenty five years I have had the opportunity to see lots of things through CFS colored glasses. For example there are all these case definitions and diagnostic criteria. Yet as the years pass I see patients who go from one set of criteria to another. Presently I am writing the twenty-five year follow-up paper. And some remarkable things have emerged. They are so remarkable, non-clinicians will not believe them. Here is an example.

Mary got sick in 1985 with a typical mono-like illness and missed two years of school. She experienced the usual discrimination and physician abuse, except (I hope) in my office. She was for real. Strong, gutsy kid who kept up her studies despite not going to class. Her SAT scores were good and she went to college, part time at first, then almost full time and graduated. Fell in love, got married, had kids, had a job. She did great.

In 1995 we published a "Thirteen year follow-up" and she was one of the recovered patients. 80% of the kids followed up at 13 years were doing well, and it is one of the reasons there has been the general perception that kids are more likely to recover. I had made a mistake and did not realize what I know now. So we do the 25 year follow up questionnaire.

The first question on the SF-36 is "how do you rate your health?" excellent/very good/good/fair/poor are the response choices. Mary put down Very good. Then we look at her daily symptoms. Severe headaches. Moderate muscle and joint pain, doctors don't know what it is. Irritable bowel syndrome. Sleep is terrible. Memory and concentration is poor. Severe fatigue. When you look at all the questionnaire scores she is as bad as she was twenty five years ago. Except for one questionnaire.

Her activity is 16 hours a day. She can function a whole day, so she can work and raise a family. At the beginning of her illness her activity was only three hours a day - that was why she could not attend school. The only thing that has improved is the orthostatic intolerance - the ability to function in the upright position. And that is why she feels that she has recovered. The daily somatic symptoms are an annoyance which she copes with very well; ignores in fact. It is ironic that her fatigue is severe, but without orthostatic intolerance, so she considers herself to be "recovered."

But she has not recovered. She is still ill with all the symptoms of CFS except orthostatic intolerance. So when people say whether or not they are better, usually they refer only to that one central symptom that determines if you can function like a normal person. The degree of recovery is, in fact, merely the improvement of this one central symptom.

As we are testing some persons for XMRV, it turns out that people who say they are well, may not be fully recovered. One person, a regular blood donor, considered herself pretty well after "recovering" from CFS. She was positive for XMRV. Do you call them a positive control or a positive XANDer who is doing pretty well? The studies to take place in the next few years are not for the faint of heart.

Question:

In the Dubbo study, a percentage of persons developed CFS after Epstein-Barr virus, Ross River virus or Q fever. They must have saved blood from those who came down with CFS and those who did not. Test the blood for XMRV. If this virus is present in the subjects who came down with CFS, but not present in the blood of those people who had regular illnesses and quickly recovered, we would have the answer as to whether XMRV "causes" CFS.

Excellent question. I would hope that the CDC and the Australian government are doing exactly this.

1. Lombardi V, Ruscetti F, Gupta J, Pfost M, Hagen K, Peterson D, et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. . Science. 2009;326(5952):595-89.
2.   Erlwein O, Kaye S, McClure M, Weber J, Wills G, Collier D, et al. Failure to detect the novel XMRV in chronic fatigue syndrome. PLoS ONE. 2010;5: e8519. doi:10.1371/journal.pone.0008519.
3.   Groom H, Boucherit V, Makinson K, Randal E, Baptista S, Hagen S, et al. Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology. 2010;7(10 [Epub ahead of print]).
4.   Kuppeveld F, de Jong A, Lanke K, Verhaegh G, Melchers W, Swanink C, et al. Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort. BMJ 2010;340(doi:10.1136/bmj.c1018).
5.   DeFreitas E, Hilliard B, Cheney P, Bell D, Kiggundu E, Sankey D, et al. Retroviral sequences related to T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci. 1991;88:2922-6

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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.