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What causes Chronic Fatigue Syndrome? Many patients tuned in to the National Institute of Health State of the Knowledge Conference on April 7-8, 2011. What did we learn?

John Coffin, Ph.D., has all but concluded that the retrovirus XMRV is not the cause of CFS. He believes he knows exactly where XMRV came from, a recombinant of two mouse retroviruses. Both of these retroviruses contaminated the Cleveland Clinic lab where they found XMRV in prostate cancer tissue. Then this retrovirus combo contaminated the Whittemore Peterson Lab were Dr. Judy Mikovits found XMRV in 95% of CFS patients and 3-4% of seemingly healthy people tested. A similar retrovirus contaminated the NIH lab used by Drs. Alter and Lo. How did these labs get so dirty? They used contaminated products or they had mice running around at night while humans were sleeping. Dr. Coffin even shared a picture of a mouse sitting on a block of cheese.

Coffin’s conclusion? XMRV is an endogenous retrovirus, a retrovirus that has integrated into human cells. XMRV has been around a long time and is found in lots of humans with no effect on their health. Strangely, Dr. Coffin didn’t find it in any of the samples he studied.

All of this makes perfect sense, right? WRONG. It makes no sense at all. Dr. Coffin is speculating to rationalize why he didn’t find XMRV, while others did. Either the labs finding XMRV are contaminated or the retrovirus other labs found in human cells is harmless. Neither theory fits reality.

There is no evidence that either Mikovits’ or Lo’s labs were contaminated. In fact they both stated they tested repeatedly to be sure there was no contamination. There is, in fact, a total negation of that theory since patients have produced antibodies in their blood to XMRV. This cannot possibly be explained by lab contamination of a blood sample. It also cannot be explained by assuming that XMRV is endogenous – a harmless retrovirus hanging out in human blood and tissues. We don’t produce antibodies against something harmless.

Furthermore, it cannot explain the extreme difference in the numbers of CFS patients versus the healthy people also carrying XMRV – a difference ranging from 97% to 4%. This extreme difference strongly supports the notion that XMRV makes you sick. Coffin’s second theory, that XMRV is a harmless endogenous retrovirus, does not explain why Coffin’s lab found none.

Why can’t Coffin find XMRV? Cort Johnson interviewed Dr. Brent Satterfield who owns Cooperative Diagnostics where they are developing rapid testing for various infections. Satterfield charged patients a lot of money to detect XMRV. Turns out Satterfield didn’t find one patient infected with XMRV. Not one. He, in fact, charged patients to allow him to look for XMRV when he had NEVER FOUND XMRV IN ANYONE. He made fun of Mikovits for needing a post doc working for her to look up how to run PCRs in some lab books, like she wasn’t smart enough to know how. Mikowits stated, Nested PCR of cultured samples provided the best results for XMRV detection, it amplifies single molecules within a large sample… You really have to optimize the magnesium and base everything on the annealing temperatures.

I have to wonder, if you increased magnesium and heated things up a bit would you miraculously produce a new retrovirus? The fellow running the lab in South Carolina invoked God and compassion. Can someone please invoke the use of the human brain to see the obvious? XMRV is real but quite a few labs have no idea how to find it.

I was going to write a detailed overview of the science discussed at the state of the knowledge conference, but I decided, since this is my writing blog, that a better use of my time would be to work on getting my new novel published. My novel is more true to life than some of the science presented at the NIH State of the Knowledge Conference.

Dr. John Coffin said, “…leave XMRV behind.” Dr. John Chia wants us to consider enterovirus in the gut as causal, because he found 85% of CFS patients have enterovirus in the gut. Some are still knocking on the door of Epstein Barr virus or chronic mono, yet Erik Johnson will tell you plainly he was in the original cohort of CFS patients at Lake Tahoe and has never had mono, ever. My personal pet infection used to be mycoplasmas. Other researchers suggest patients have various infections. A lot seem to have Lyme disease. So why not leave XMRV behind? Never mind that Mikovits has found 97% of patients testing positive. If those other 3% are negative XMRV must not cause CFS, right?

But here’s the problem: we don’t have a good test yet, and there are other strains – PMRV anyone? That’s P for polytropic, probably what Alter and Lo found. This is getting complicated. Let’s leave XMRV behind, PMRV too. My head hurts.

Katie, bar the door! Do not let XMRV escape. You researchers don’t get off so easy. Think about the theory – XMRV suppresses the immune system and feeds off of stress steroids such as cortisol. You get mono, or you get an enterovirus or Lyme. You miss some sleep. You are stressed. What you don’t realize is that there is a monster in the closet, in your immune cells, and it ain’t mono or an enterovirus in your gut. It’s a retrovirus that won’t let your immune system control these common infections. You can treat the secondary infections and maybe, just maybe, recover for a few years. But the next stressor or infection is bound to happen. It’s just a matter of time and stress before you relapse.

We have to spend the money, do the research on XMRV. Now is not the time to simply move on and let XMRV walk out the research door.

10 thoughts on “What Causes Chronic Fatigue Syndrome?

  1. Thanks, Paula. Nice overview of main players and shenanigans. Because of memory problems with this illness it can be hard to assemble the picture.

    Sad day today with release of the Singh study – as I understand, another non-replicating study using a different assay not validated with positive controls. No, it is not “time to leave XMRV behind.” Time to get up from this recent hit and continue to support the WPI.

    • Maureen, thanks so much for your thoughts. It took me 3 days just to write this summary. My brain isn’t so strong anymore with this disease. Yes, the Singh study looks to be another flub-up. When is this fiasco going to end for us patients?

      Paula

  2. Thank you for these thoughts, Paula. I think the release of the two negative XMRV papers today, the Singh paper and the Switzer Prostate Cancer paper, was orchestrated especially to discourage people who are supporting HGRV/XMRV research. It won’t work. We know that this research is our hope, and we will continue to support it.

    I agree with Maureen. This Singh paper is just another in the series of negative papers which did not use WPI methods. Singh used only her own new assays, none of which have been proven to work. She did not use use known positive samples. “She took fresh samples from patients who had previously tested positive, which isn’t the same thing. This is a very significant difference given the fact that WPI study subjects do not always consistently test positive. … ” (borrowed from Dr. Yes on mecfsforums).

    I agree with you, Paula. “Now is not the time to simply move on and let XMRV walk out the research door.” Now is the time to get serious and really do an actual replication of the Lombardi study. It’s time–it’s past time.

    Patricia Carter

  3. Hi Paula,

    You wrote: “Coffin’s conclusion? XMRV is an endogenous retrovirus, a retrovirus that has integrated into human cells. XMRV has been around a long time and is found in lots of humans with no effect on their health.”

    Actually Coffin isn’t even saying that. He is saying that XMRV was a lab accident made up of mouse endogenous retroviruses that contaminated the XMRV integration study at the Cleveland Clinic.. in other words he is saying it is NOT found in any humans, and the C.C.’s finding that it was integrated into human prostate tissue was actually a mistake due to contamination.

    Of course, this is his interpretation of data that has not been published, and would need to be validated/ confirmed/ replicated.

    • It was tough to write an article that made sense of Coffin’s statements since he contradicted himself. Of course, it can’t be endogenous and a lab accident. But he did suggest it was endogenous. Hum…

      Paula in la la land

    • That is Coffin’s new belief, but he also then suggested at the State of Knowledge conference that it must be the heperain tubes. He really can’t make his mind up, as he has no evidence for either. What a desperately sad bunch they all are leaving a sick community to rot while they mess about in labs not bothering to follow up of the science.

  4. Just to emphasize the reference to Erik Johnson and his comment about “mono”. Is he saying that while he has never had mono he does test positive for EBV. If so, then I can personally support that as have never had mono, but have significantly elevated EBV levels (HHV-6 as well).

    It really puzzles me as to why, even if it is very small study, that another lab would not gladly invite Dr. Mikovits to come into their lab and demonstrate (and replicate) the VIP Dx process for consistently finding the XMRV virus. If I was in charge of a lab I would be ecstatic to have another researcher reveal to me their method of delivering an anticipated results. I might not agree with it or I might find a blatant flaw in the process, but if I concur with the results as claimed then I’m now the second one to know the correct way to find it.

    Instead of working together it is if they are all working against each other. They will not share information until it can be published and if it doesn’t get published then they shelve it. This is not a football game! It is peoples lives and these lives are being lost to satisfy some type of competitive arrogance between these researchers.

    • Erik does not test positive for Epstein Barr. He is, in fact, the rare person who has never had it, yet he was in the original cohort who has CFS. He stays pretty healthy by avoiding toxic mold. It will be interesting to see if he tests positive for XMRV.

      Yes, it is confounding as to why the scientists don’t cooperate. I can’t read minds.

  5. Paula Carnes: hello, I am “AnonymousNonRetrovirologist” who posts sporadically on Dr. Deckoff-Jones’ blog. I did not notice your questions to me in your November 18, 2011@4:43PM post, as they were buried in all the bedlam after Dr. Mikovits’ arrest. I thought it best to respond on your WordPress blog directly instead of having it lost in the “fog of blog” battles going on elsewhere.

    To recap, you left this on Dr. Deckoff-Jones’ blog (http://treatingxmrv.blogspot.com):

    “Paula Carnes @November 18, 2011 4:43 PM said…
    “AnonymousNonRetroviruologist: Let’s forget for a minute about whether the PCRs were the same. And let’s overlook whether there was contamination.
    What about the cultures that grew? What about Dr. Lo finding a related retrovirus that doesn’t match with contamination? I wish he would speak up” ”

    My responses:

    1) Paula Carnes stated: “let’s overlook whether there was contamination”–OK, but it’s not “whether” anymore, there WAS contamination: Silverman, Das Gupta et al. (Partial Retraction of 22 September 2011 / Page 1/ 10.1126/science.1212182)– they plainly and honestly and properly admit of contamination by vp62 in the samples from Lombardi et al. (How and exactly when it got there is open to ongoing speculation.)

    2) Paula Carnes asks: “What about the cultures that grew?” I am not an expert on virus culture. I’ve spent quite a bit of my thirty years in R&D doing DNA and RNA assay development (PCR, real-time PCR, Southern blots, Northern blots, cloning, sequencing etc.) I have a few years’ cell culture experience and I have never run a Western blot. But unlike other online personae (e.g. “Gerwyn” and “V99″), I will NOT claim any false expertise nor try to bluff my way through methods and techniques not understood nor performed. So with all that in mind, until the revelation of the 5-AZA debacle by the blogger ERV I was willing to give my remaining benefit of doubts to Lombardi et al. and accept the culture and Western blot data as genuine (at least until demonstrated by other experts otherwise). After the 5-AZA controversy, however, I am no longer sure. It could be that the “non-germane” use of 5-AZA went beyond the blot at issue, and it could have been used in other experiments, perhaps routinely, to resurrect “fossilized/Jurassic-Park” HERVs and perhaps other “silenced” ancient genomic artifacts/elements in order to fashion data bolstering XMRV’s association with CFS. As to culturing methods, and emphasizing again that this is not an expert’s opinion, I recall (cannot find the reference) that the WPI’s culture times seemed very long (25-30 days?)–wouldn’t this have created ample opportunities for contamination during maintenance of the cultures (which have to be opened periodically and old media removed and new media added)? And MLV contamination is quite common in labs handling prostate cancer cell lines (some of which, unbeknownst to the researchers, were shedding replication-competent virions undetected, possibly for years–see Sfanos KS et al. (2011) Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines. PLoS ONE 6(6): e20874. doi:10.1371/journal.pone.0020874). And other labs and follow-up studies (such as the BWG) have not been able to replicate, among other things, WPI’s culture results. And during the BWG they had a chance to convincingly shut up their detractors and deliver culture data, but could not (due to mycoplasma contamination–an unfortunate lapse during a most critical time.) And was WPI able to isolate, sequence and characterize any of these supposedly novel hitherto-undiscovered viruses successfully, routinely and abudantly grown in culture? (Isn’t that just classical virology–growing it up, isolating it, then characterizing it? So did they do this and what did they find?) So to me, a decidely non-expert outsider, the methods do not seem to be very robust nor reliable nor are they reproducible by expert workers outside of the WPI. (If there was something out there, it would be detectable by others using similar–not necessarily identical– methods once they were alerted to its prescence.) And finally, as a sociological aside, there seems there was an overabundance of infighting between Mikovits’ research arm and Lombardi’s ViPDx faction–sounds like a real fun place to work! Mikovits’ people within WPI intercepting packages addressed to Lombardi and then informing on him? What kind of petty Stalinist regime did they have going on in there? The term “civil war within a leper colony” does come readily to mind…

    3) Paula Carnes asks: “What about Dr. Lo finding a related retrovirus that doesn’t match with contamination?” I am puzzled by the Lo lab’s radio silence after the PNAS paper. Perhaps they are working away sequencing the flanking human genomic sequences at the proviral insertion points, thus demonstrating conclusively that they do indeed have bonafide human endogenous retroviruses? But no news in this case may not be particularly good news, especially since it’s been two years since PNAS publication and following the null results in the BWG. Perhaps more stringent controls against contamination and improvements in technique in the interval between the PNAS paper and the BWG study have eliminated low-level murine/MLV contamination, and with it, the “positives” seen in the original paper. Also they had to do ~80 cycles of 2-round nested PCR to detect! (We haven’t done any nested PCR since the 1990s; and we never go over 35-40 cycles in our runs.) And that many amplification cycles just increases the probability of bringing up all manner of spurious artifacts. And low-level murine sequence contamination has been noted in commercially available off-the-shelf reagent kits and columns. And nested PCR was just begging for contamination problems, as the tubes from the first amplification round have to be carefully opened and amplicon-laden aliquots removed and then tediously transferred to the second-round tubes–no thanks. (And how come no real-time quantitative PCR? Not only do you get specificity during amplification, but also increased sensitivity and better specificity in detection, plus higher throughput, less manipulation, and less chance of contamination as the instruments are designed for in-tube/in-plate detection.) And perhaps Lo and Alter (and/or their employers) are now having second thoughts about continuing any research into XMRV/CFS after the very public implosion and fiasco at the WPI and subsequent finger-pointing, alleged persecution and now, actual prosecution, between the University of Nevada, the WPI and Dr. Mikovits.

    Research into XMRV/CSF/ME/etc. in the U.S. has just been turned into the biomedical equivalent of Cold Fusion or “Area 51/Alien Autopsy/UFO-abduction-by-aliens-with-anal-probes-ology”. Contrast this with the no-fuss/no-drama rituximab results from Norway. Which route seems more efficient and productive?

    .

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