Okaaaaaay…

*squint*

Let me preface this post by stating that I am not an MD. I dont care, particularly, about whether CFS is a ‘real’ disease or psychosomatic or a catch-all category for people MDs dont know how to treat. Sorry. So if you want to bitch about CFS, pro or con, dont do it in this post.

What I care about is retroviruses.

The behavior of this retrovirus in humans does not make sense as a causative agent for CF or prostate cancer.

It does not make sense.

Thus I think its an effect, not a cause.

Let me give you an example– Human Herpes Virus 8.

The seroprevalence of HHV8 in the general US population is meh, 3.5%.

The seroprevalence of HHV8 in AIDS patients in the US shoots up to ~25-35%.

OMG! 3.5% in normal population, 35% in AIDS… HHV8 causes AIDS!

Just like 3.7% of the normal population is XMRV DNA positive, 67% in Chronic Fatigue Syndrome… XMRV causes CF!

Just like 4.0% of normal prostates express XMRV proteins, 23% in prostate cancer patients… XMRV causes prostate cancer!

We know why “HHV8 causes AIDS!” is nonsense, because we know what really does cause AIDS– HIV-1. But that example demonstrates why the “%normal” “%sick” comparison can be a trap. If you have to make up new rules of virology (transmission, cell tropism), new rules of epidemiology (how is a philharmonic orchestra having a retroviral epidemic? Orgies? Theyre all sharing heroin needles?), new rules of cancer biology (why arent prostate cancers clonal masses of XMRV+ cells? why arent CF patients ravaged with cancer from insertional mutagenesis?), then the % connection is a lark. Its a side-effect distracting you from the real cause.

There is more to connecting a virus to a disease than simply comparing prevalence in diseased vs normal populations.

Once again, referring back to HHV8:
The seroprevalence of HHV8 in the general African population varies by country, but its anywhere from 25%-85%. Normal, healthy people. Not AIDS patients. Just people. Higher percentage than US HIV+ people.

This normally ‘harmless’ virus is more prevalent in certain areas of the world (Africa) than in others (US), and is ‘enriched’ in sick populations where its not normally so prevalent (US HIV).

Similarly, XMRV was not found in 589 prostate cancer biopsies in Germany. None. Zero. In 589 biopsies, as opposed to the 233 in the XMRV+ paper I wrote about earlier.

It could be that XMRV is a US bug, like HHV8 is an African bug. Bugs that just tag along for the ride, and take advantage of immunocompromised people when the opportunity presents itself.

Connecting a disease to a virus takes a lot more than what XMRV proponents have now.

While Im sure they realize that (*wink!*), I wish they were doing a better job of communicating that to the public, and not pimping XMRV test kits to patients and doctors.

Comments

  1. #1 gf1
    October 23, 2009

    I’ve not seen many (any?) people jumping to the conclusion the XMRV must be the cause of CFS, but if you’ve been stuck in bed for twenty years with an unknown illness, it’s not surprising you’d want to be tested for even the most unlikely of potential causes. What else are you going to do?

  2. #2 NewEnglandBob
    October 23, 2009

    Sadly to say I must unsubscribe to this blog because do not understand most details provided and will not spend the time to learn. No reflection on this blog, its just not my cup of (lay person’s) tea.

  3. #3 speedwell
    October 23, 2009

    Bob, I am an educated laywoman and I understand well enough. I was taught to ask questions and do research outside of class when I felt like I was in over my head, though. Sometimes I do need to look up the occasional thing. But posting comments saying you don’t understand something so your bowing out, given that the comment section is the number one best place to ask questions, is more than absurd. It’s cowardly and ignorant. Sorry to have to be so blunt.

  4. #4 speedwell
    October 23, 2009

    “…so your bowing out…” should, of course, be, “…so you’re bowing out….” I was originally thinking of constructing that sentence a bit differently…

  5. #5 Uncle Glenny
    October 23, 2009

    Sadly to say I must unsubscribe to this blog …

    You’ll miss the puppehs!

  6. #6 Chloë Moíra Smith, PhD.
    October 23, 2009

    What does not make sense is a person stating that they are “not a MD” then going on to say that a retrovirus being the cause of prostate cancer or CFS, “does not make sense!”

  7. #7 daedalus2u
    October 23, 2009

    A good and fair analysis of the XMRV-CFS possible connection.

  8. #8 Optimus Primate
    October 23, 2009

    NewEnglandBob, I encourage you to stick with it. For the longest time, Abbie’s non-Arnie posts left me slack-jawed and dead-eyed. But I found her passion and enthusiasm for the subject infectious, so I stuck with it.

    These days, I think I grok a good 25% of it. (You could probably bump that up to 30% or so if we could just get her to use the occasional apostrophe.)

    It’s opening this old biology geek up to a world he never even really considered. I really, really wish someone would write a book on the principles of virology for those of us who struggle with the jargon, but for now, I honestly know of no better resource on the subject for the interested layperson than this blog.

    It’s worth the effort.

  9. #9 Prometheus
    October 23, 2009

    1000 quatloos to Optimus Primate for bringing back the expression “Grok”.

    -10 quatloos to Englishbob whose comments are usually interesting because he is bowing out.

    I don’t get the reaction.

    The O.P. is not tying a gordian knot. Abbie seems to being doing just the opposite to wit digging into a bag of snakes and laying them out flat.

    She demonstrated with examples how “Correlation does not imply causation” a proposition which has been around and sound long enough that it is usually in Latin.

    Speedwell, “an educated laywoman” by day and crimefighter by night?? is prepared to call Ebob cowardly and ignorant but I am curious as to why this particular post puts such a hitch in his git along.

  10. #10 ERV
    October 23, 2009

    Chloë– I put that disclaimer there because I didnt want people thinking my post was saying that because I dont think XMRV–>CFS makes sense, I dont think CFS exists.

    Frankly, CFS patients, rightly or not, arent exactly pleasant commentors when they think they are being attacked.

    Im not attacking CFS.

    Im attacking a correlation between virus–>disease which doesnt make sense when observing the behavior of MLV (the ‘original’ XMRV) or other retroviruses.

    And again, frankly, most MDs are not in a position to discuss this topic. I doubt many MDs could name a retrovirus other than HIV-1, and they would probably call it ‘HIV’. Not that Im better/smarter/cooler than Average MDs, its just that I am a PhD student specifically studying retroviruses and cancer… and as much as I would like to believe these connections, I dont.

    They way XMRV has to be behaving in humans for these connections to work makes no sense.

    Im surprised you dont understand the differences between MDs and PhDs, considering you have a PhD…

  11. #11 brandon
    October 23, 2009

    Looks like your facts are from old news! After looking for antibodies of XMVR, a more sensitive test, they found that 95% of people with CF have/had XMVR. Some are claiming that it’s due to a weakened immune system, which it may be. BUT, 95% where it’s only in 4% of the sampled healthy population…that seems extremely significant. If it is a weak immune system, then why don’t they have a multitude of other viruses, why is this one so prevalent??

  12. #12 BAllanJ
    October 23, 2009

    I suppose that even if the virus doesn’t cause CFS, its presence could still be used a bit for diagnostic purposes. It may even help treatment, if the virus exacerbates any of the symptoms of CFS, so the patient would benefit from its removal.

  13. #13 brandon irwin
    October 23, 2009

    Oops…forgot. Google “xmvr antibodies 95%” for the news articles related to my previous post.

  14. #14 Jim Bob Cooter
    October 23, 2009

    Here you go brandon: http://tinyurl.com/ykgqr2s

    95% is a more convincing number than what they had before (though I’d like to see the apparently as-yet-unwritten paper), but the same principle still applies. All you can definitively say is that XMRV is strongly associated with CFS. It’s the old “correlation does not imply causation” deal. It could just as easily be that XMRV is particularly adept at taking advantage of whatever actually causes CFS or prostate cancer, which would also explain why serum levels of XMRV were high while others were presumably not.

    This research provides a route for looking into the actual causes of these diseases; for instance one can ask what makes XMRV different from other retroviruses and use that information to help you figure out where to look for the culprit, whether it is actually XMRV or not.
    The point is that all this is is a strong correlation, and saying at this point that XMRV causes these diseases is flat-out bad science.

  15. #15 Prometheus
    October 23, 2009

    ERV @ #10

    “I’m surprised you dont understand the differences between MDs and PhDs, considering you have a PhD…”

    I was busy wondering how a couple of Northern Irish names acquire an umlaut and acute accent mark when I decided to back away slowly and not make any sudden moves.

  16. #16 Brian
    October 23, 2009

    In the case of Chloë, that’s not an umlaut but a dieresis, indicating that there are two syllables.

  17. #17 titmouse
    October 23, 2009

    daedelus2u, I bring you a present.

  18. #18 SC
    October 23, 2009

    I’m reserving judgment on the notion that 67% or (95% of CFS patients) are positive for XMRV and the question of correlation versus causation.

    A huge issue to resolve is the most basic question of diagnostic criteria. Sixty seven percent (or 95% or some other percentage) of the group meeting the Canadian diagnostic criteria for CFS seems to be a statistically stable difference (but what percentage of those meeting the CDC criteria?).

    Now lets hope those studying this get rid of as much of the noise inherent in a diagnosis of exclusion as they can. Only then will determination of a direct causal link be possible.

  19. #19 The Backpacker
    October 23, 2009

    Brandon- You missed the point just a bit. It would not matter if everyone with CFS had XMRV it would not show causation. If you want to say XMRV causes CFS then you need a mechanism otherwise you are just guessing.

  20. #20 ERV
    October 23, 2009

    brandon– Thats a whole nother kettle of fish.

    The XMRV–>CFS groups have been saying lots of things to the public that they have *not* published. Ive seen that 95% statistic. Ive also seen them saying that theyve seen ERV particles. Thats also how I found out their study subjects were not from a CFS cattle-call (norm for other studies– “Do you have migraines? Sign up for this study!”), they actively stacked the deck by only looking at specific ‘outbreaks’ of CFS… and they only got 50% (antibodies, different test from the 67% PCR positive). What did they do to get 95%? Who knows, they havent published.

    What theyre doing is unprofessional, which makes me question them even more.

    And again, even if 100% of CFS patients are XMRV positive through hook-or-crook, that still doesnt mean XMRV=CFS, and it doesnt make the virology make sense. How do you get a retroviral outbreak in a philharmonic? Acute infection and disease alllll at the same time, with a retrovirus, in a philharmonic. Uh uh.

    Off topic, but a non-XMRV/CFS example for how presence does not necessarily mean disease, see this post on ERV-W/MS.

  21. #21 gf1
    October 23, 2009

    If it really was 95+% of CFS patients with XMRV, but only 4% of the general population, would this make causation more likely? Could we assume that the likely modes of transmission for a retro virus would make it unlikely that such a difference would occur in a purely oportunistic manner?

    Even if XMRV wasn’t the primary cause of CFS, it could well make recovery more difficult, and offer a potential course of treatment.

  22. #22 Prometheus
    October 23, 2009

    Brian at #16

    Duhhh, like Chloë Agnew. Okay, my bad. I have been spending the week with Austrians so I have umlaut bias.

    I guess the acute accent makes sense too if she’s Welsh or something.

    I was picturing some weird Franco Prussian colony skulking around the outskirts of the village of Gob.

  23. #23 SC
    October 23, 2009

    ERV: I agree entirely that correlation is not and that causation and that claims to that end are premature. I also agree that the degree of caution and not overstating results speaks a great deal to one’s professionalism.

    I disagree with your concerns about the WPI folks stacking the deck. Until recently, the CFS deck has been an absolute mess and the noise has been deafening. If a more restrictive diagnostic criteria were to result in 20% of those presently diagnosed with CFS (by exclusion) being found to have some common pathological issue, then that 20% gets removed from the crowd and the ‘noise’ drops for everyone.

    ‘Stacking the deck’ is long over due and perhaps the CFS research would be far more productive if we stopped treating this group as homogeneous when it is so often constructed using such subjective criteria.

  24. #24 gf1
    October 23, 2009

    I wrote my post before I saw the last two comments, but my question still kind of stands (as far as I know). If XMRV could only be transmitted through blood and saliva, such a high difference in infection rates between CFS and the healthy population would indicate some sort of causal link, wouldn’t it?

    @ERV – I thought they’d been open about having targeted their study at CFS patients most likely to suffer from a viral infection. Given the difficulty of diagnosing CFS, and that they were examining a possible viral cause, that seems a perfectly sensible thing to do.

  25. #25 Heidi
    October 23, 2009

    I tend to agree with this premise, if only because my Fibro/CFS diagnosis was arrived at backwards. The first thing we discovered is that my immune system is completely shredded. Significant protions of my immune system simply do not ewxist.

    Then came the never ending battles with the insurance companies to allow me to take the tests that diagnose the various opportunistic infections (mycoplasma, MRSA. pneumonia, etc.) thst take advantage of my compromised condition.

    I don’t doubt the reality of XMRV, nor do I doubt the prevalence in CFS patients. But any theory that surmises that controlling the XMRV also controls CFS is incomplete, much as earlier theories involving mycoplasma.

  26. #26 Diana
    October 23, 2009

    First off, I’m glad you aren’t an MD because your lack of empathy about this illness (you don’t really care, don’t come here to bitch about being sick) is startling!

    Secondly, as a sufferer myself, I am not thinking automatically that XMRV is the smoking gun, although it may be to CFS what HIV-1 is to Aids. The most important thing about this research is the visibility it has suddenly given to CFS, which has been virtually ignored in this country. The fact that the country’s blood supply may be infected with an infectious retrovirus “linked to” prostate cancer and a serious immune disorder may get them to finally do some decent research themselves.

    And I don’t see how comparing Herpes viruses with a retrovirus of this caliber and rarity makes any sense at all. Patients with CFS have known for years that we carry chronic relapsing viruses like HPV, CMV, and EBV, but we’ve also known for years they are hitchhikers, allowed to relapse because of our damaged immune systems. We’re not as naive as you think.

    XMRV causes damage to the immune system. So you’re comparing apples and oranges with your HHV8/AIDS argument.

    There was a lot of anger towards AIDS patients in the early days. Looks like we are being spurned just as they were. Such rancor!

  27. #27 VOR
    October 23, 2009

    It seem that ERV is saying XMRV must not be causative becuase correlation in some CFS patients is not necessarily
    and indicatin of causation. Now THAT makes no sense. Seems to me that neither of those makes much sense. Why say ‘It does not make sense’ without a reason? In other words, wth would you lean in either direction? Of course correlation is not the same as causation, duh. But you are talking as if correlation just plain rules out causation, which, without futher explanation, sounds equally or more stupid. After all HIV1 DOES cause aids, and its a retrovirus. ERV, what do you base your opinion on besides the obvious fact that correlation does not necessarily indicate causation? Are you basing it on transmission limitations?

  28. #28 Eric Johnson
    October 23, 2009

    Of course no one has *concluded* that XMRV is causal. Not a single learned person has. Nor has anyone even said that anyone has; Abbie didn’t.

    > XMRV causes damage to the immune system.

    XMRV is not proven to do anything, including cause CFS, and the established immunological alterations in CFS are modest.

    > such a high difference in infection rates between CFS and the healthy population would indicate some sort of causal link, wouldn’t it?

    No, it wouldn’t prove it, it is merely suggestive. 67% vs 4% would be pretty suggestive and 95% vs 4% would be more suggestive.

  29. #29 Eric Johnson
    October 23, 2009

    Frankly, CFS patients, rightly or not, arent exactly pleasant commentors when they think they are being attacked.

    We actually don’t like you that much either. Just kidding – we aren’t totally wild about you, but you seem alright. To repeat myself, it’s perfectly true that we average crabbier than normal subjects, at least online (p < 0.01). If you don’t want people to carry on about the broader debate, people should respect that because it’s certainly your prerogative not to care about it as much as we do.

  30. #30 Eric Johnson
    October 23, 2009

    less than 0.01). If you don’t want people to carry on about the broader debate, people should respect it because it’s certainly your prerogative not to care about it as much as we do.

    (I shoulda hit “preview”! Watch out for that “less than” sign.)

  31. #31 kg
    October 23, 2009

    “Similarly, XMRV was not found in 589 prostate cancer biopsies in Germany. None. Zero. ”
    I apologise if someone has already mentioned this, but I should point out that a study published last November in the Journal of Clinical Virology, by German scientists based in Hamburg (Fischer et al), found XMRV infection in one prostate cancer case and one control. Clearly the incidence in Germany appears to be lower but it is not zero.
    Despite this oversight, this is an excellent blog!

  32. #32 Eric Johnson
    October 23, 2009

    > OMG! 3.5% in normal population, 35% in AIDS… HHV8 causes AIDS!

    OMG u have 1 example but u don’t have 2. I’ll be impressed if you can think of another one that isn’t really asterisky.

    AIDS is what, about ten to a billion times more immunosuppressive than other diseases? (I’m not counting SCID or other super-rare genetic defects, or falling-apart cancer patients 3 days before they die.) That’s why AIDS subjects have ten times the prevalence as normals for 999 different infections, from HHV8 to tuberculosis to parasitoid extraterrestrial larvae (if those existed).

    By asterisky, I mean stuff like the superinfection of leprosy sores by semi-commensal bacteria, bacterial superinfection of the lungs in flu, or promotion of HIV transmission by STD lesions – since all those things are probably caused primarily by the disruption of dermal/epithelial barrier function, at least as far as I know.

  33. #33 Eric Johnson
    October 23, 2009

    Oh hell, I thought of one myself! EBV prevalence is elevated in multiple sclerosis and as I recall, also in systemic lupus according to the large majority of studies. Since EBV prevalence is close to 100% in normals, it doesn’t make for a highly dramatic difference – still, that doesn’t make it’s unremarkable or easy to explain.

  34. #34 titmouse
    October 23, 2009

    I had a look a the company making those test kits. Here’s a brochure.

    Their web site is quite sciency. But I am not impressed.

    Mainstream medicine is just beginning to understand the connection between inflammation and disease. Our environment has changed to such an extent that our
    immune system is facing challenges that were never before understood. Throughout our day-to-day lives we are continually exposed to new chemicals and pathogens. This
    assault on our immune system may result in pathology that is difficult to diagnose and treat. Many factors may complicate the picture such as diet, genetics, lifestyle
    and stress.

    This company has no fidelity to science. Sectarianism (“mainstream medicine”) has no place in science.

    There exists an international network of shady MDs doing shady research using shady assays from shady labs, for the prescription of shady, unregulated supplements. The shady MDs are now at our top medical schools, getting multi-million dollar multi-year grants from private doners and supplement manufacturers. Soon it will be nearly impossible to sort real science from pseudocience within medicine. Five years, I’d say.

    Nevermind the thought that the next generation of doctors will be brain damaged by the nonsense they’ll be forced to swallow. Sciency-seeming medicine will destroy our economy.

    The Discovery Institute liars are amaturish, small-time losers in comparison to Bravewell.

  35. #35 titmouse
    October 23, 2009

    How to fix this Orwellian nightmare:
    1. Repeal DSHEA.
    2. Shut down NCCAM.
    3. 2 independent, controlled trials for any novel therapy or GTFO (like in the pre-DSHEA world).
    4. No marketing of lab tests to the public.
    5. No marketing of prescription meds to the public.
    6. Rape Herbalife and the like, hard. There must be a way.

  36. #36 Eric Johnson
    October 23, 2009

    > Soon it will be nearly impossible to sort real science from pseudocience within medicine. Five years, I’d say.

    Color me skeptical. Sketchy medicine has existed for ever. (For example, laetrile.) It was and is also practiced by uncontacted Yanomamo shamans deep in the jungles of Venuzuela. People were so tired of phony TB cures that they were almost acridly skeptical when the first results from streptomycin trials were publicized. I readily grant, that company’s palaver is not impressive. But that kind of stuff will never impress people with disciplined training. Science is robust in that way. What we should do is simply continue to promote evidence-based thinking – as an end in itself, not as an aegis under which to reign in every maverick MD.

    I wonder what evidence there is that government regulation of bunko medicine has actually cut down on bunko medicine all that much. It’s hard to compare across time periods, of course, because wealth has increased so dramatically since 1900, making people more willing to spend on silly things.

    Here’s a little kink in the Big Government dream. The more your prohibit harmless nonsense like homeopathy and dictate what people may do with the fruit of their labor, the less willing they are to respect the learned and be led by elites when it comes to things that really matter, some of which ordinary people can’t understand any more than I could do your quantum mechanics homework. Just look at the amount of bunko global warming skepticism, believed by hundreds of millions of Americans who have no idea what they are talking about. Think about the big picture. Elites were respected more, as part of the natural order of things, before they started regulating every little thing. Making everyone safe from everything makes it safe for everyone to be a big, stupid, bored blowhard. I’m not saying you have no arguments at all, but those are my arguments.

  37. #37 Eric Johnson
    October 23, 2009

    > 1900

    Scuse me, 1800.

  38. #38 titmouse
    October 23, 2009

    Eric Johnson,

    There has always been quackery. There will always be quackery. But since the 1910 Flexner report, the quacks were on their own, outside of academic medicine.

    Then in 1990s the “integrative medicine movement” started. And now over 40 of our top med schools have departments of integrative medicine. Quackademic medicine.

  39. #39 Sili
    October 23, 2009

    Iiiiiinteresting.

    Does anyone know the prevalence of XKCD in clinically depressed patients? Or some similar group of people who might have slightly compromised immune systems.

  40. #40 Ryan
    October 23, 2009

    I agree. I’m an epidemiologist, and after reviewing that paper it was a big WTF?

    The authors didn’t report how they picked their cohort, or any other characteristics. Considering that the cohort was “well-characterized”, you’d think we could have seen a scintilla of evidence that the two groups were comparable.

    I know Science has a deep distrust of all things epidemiology, but I was pretty disappointed…

  41. #41 Cheryl
    October 23, 2009

    I am not a doctor, not medical in any way, just a normal person… oh and I have had Fibromyalgia since 1981 and Chronic Fatigue Immune Dysfunction Syndrome since 1989 after a major bacterial pneumonia, or so they thought.

    Fact is that I study genetics… on my own, using every medical book and study available to me in hospital libraries and online.

    In my family there are 8 cases of FMS, 3 Cases of CFIDS, 1 mentally retarded, 1 Schizophrenia, 1 bipolar and 1 tourette, a number of ADHD and Alzheimer’s and one Polio survivor.

    I can prove that the root is genetic… absolutely prove it. BUT, I also totally agree with the original post.
    We are walking condominiums for anything that wants to live inside us. This includes several homosexual members of my extended family. One big, northern European ancestral condominium.

    However, to date there has not been any virus or bacteria found that has had such a high antibody count as 95% in us… or 67% if that were the published number originally.
    Therefore, while Epstein Barr and Parvo and Lyme tics might be living on floor 8 and 9…. it would be real nice to find what is living on the base…. perhaps XMRV is a major factor – a crucial factor.

    When you get a flu or 24 hour virus it goes away. Something that took us down, didn’t go away. We live sick ever day of our lives.

    I did read that Ampligen, which probably works with all of it, took a lady out of a wheelchair. All I had to do was move to the desert of Peru, get very hot and dry and went into remission for 5 years.

    Finally, we have some hope that a specific target might give us a chance at life. I lost mine a long time ago.

    I don’t believe its a cause… I know better. But it could be causing symtoms!

    Hope to have my book out in a year or so… I just need energy to finish it.

  42. #42 Eric Johnson
    October 23, 2009

    titmouse,
    I couldn’t agree with you more about those govt and academic institutionalizations of alternative medicine. Bad. Negative. Terrible. What nonsense. It’s fine to run high-quality trials on some of those treatment modalities. If they work, great – then they aren’t “alternative” anymore. There is no possible reason why they need their own department. Tons of doctors and researchers, even some of the smartest ones (Linus Pauling), have always been interested in endless different odd-and-probably-stupid ideas, and they always will be – no one needs to hire professors and researcher who are /particularly/ interested in weird stuff. If anyone arguably treads slightly too narrow a path it’s the NIH grantmeisters, not the professorial hordes that daily pray unto them. But that is not necessarily fixable.

    I mean, Linus Pauling is probably the most accomplished american ever, over the whole of the arts and sciences, and we all know about his wack attack regarding vitamin C. Plenty of oddballs out there.

  43. #43 judderwocky
    October 23, 2009

    It is infectious. They said in the statement that they had evidence it infected prostate cells and immune cells. They also might have had a faulty RNase L immune pathway though… it might only infect people that have a genetic predisposition to the virus, hence its presence in 3% of the healthy population. Or it could just have a period where people don’t present symptoms… like HIV which takes years to develop into AIDS.

    MORE TESTING REQUIRED is all we can currently conclude.

  44. #44 Mark London
    October 23, 2009

    Unfortunately, HHV-8 is not quite a “harmless” virus. It is well known that the cause of Kaposi’s sarcoma, a form of cancer. Quoting from the following article:

    http://www.ncbi.nlm.nih.gov/pubmed/19235482

    “In several African regions, epidemic KS is the most frequently diagnosed malignancy. In 2002, the estimated annual incidence of KS worldwide was approximately 65,000 cases, representing 1% of all diagnosed cancers. HHV-8 is also associated with primary effusion lymphoma, some cases of multicentric Castleman disease, and other rare lymphomas.”

    It is true that “all these tumors mainly affect immunodeficient patients.” But this is exactly the model that the XMRV-CFS connection is based on also, i.e. that the CFS immune system is deficient in a way that allows the normally harmless XMRV virus to infect the body.

    And whether XMRV leads to cancer is irrelvant. The types of immune dysfunctions that exist in people with CFS, might not be the type that allows XMRV to affect or cause cancer (assuming that it actual can do that). CFS immune systems might simply allow the virus to affect other areas of the body, i.e. damage to the nervous or immune system.

    Having a 95% association of a virus with a disease has to meant SOMETHING, even if it’s not the cause of the disease. This is especially true for a disease where the population is quite heterogeneous in nature, and the fact that blood samples were taken from a wide spread population, from different time periods. What that SOMETHING is obviously still needs to be discovered.

    What we really need is for studies to be done in other countries. I think the results of such studies will prove whether XMRV is really a strong factor or not. – Mark

  45. #45 titmouse
    October 23, 2009

    Meanwhile, judderwocky, while we’re waiting for the scientists to do more of that testing stuff…

    For the low, low price of only $895.00 you or any of your loved ones can be tested for CFS, using the Complete Chronic Fatigue (CFS) Diagnostic Panel from the VIP laboratory. This panel includes the RNAP, RNAA, Elastase, NKCP, and NOAS tests.

    Can you afford it? Can you afford not to do it?

    “Removing the doubt is part of the cure.”

    Please be sure to visit VIP’s affiliate, BioRay Inc, for all your liver flushing needs.

  46. #46 titmouse
    October 23, 2009

    Eric Johnson:

    I couldn’t agree with you more about those govt and academic institutionalizations of alternative medicine. Bad. Negative. Terrible. What nonsense.

    Good. That’s two of us here plus there are a dozen or so at SBM who feel the same way.

    Sadly, we might be f*cked. Have a look at the other team.

    God wishes he had this kind of money.

  47. #47 Eric Johnson
    October 24, 2009

    > you’d think we could have seen a scintilla of evidence that the two groups were comparable

    That’s a fair criticism. At the same time, with 100 patients and 200 controls showing an 18-fold difference in XMRV rates, I’d be gobsmacked if the finding were entirely spurious. If the true difference were 9-fold instead of 18 I’d be non-gobsmacked but still surprised. What kind of control matching do you want anyway? Just age, sex, and status? Race? Correcting for status or race might be misleading, anyway, since they might actually be risk factors for acquiring the virus. By Leonard Jason’s population-based work, CFS is about 1.7x more common in latins than in blacks or whites. It is also slightly more prevalent in non-professionals.

  48. #48 Eric Johnson
    October 24, 2009

    > Can you afford it? Can you afford not to do it?

    You have a point, but they also aren’t holding a gun on anyone. Did that customer bust ass making $895 so you could tell ‘em what entirely harmless products they may and may not buy? :)

  49. #49 Eric Johnson
    October 24, 2009

    To clarify, I’m all for you making fun of them all over the internet, I’m just leery about putting the ban on them.

  50. #50 titmouse
    October 24, 2009

    Harmless? That liver flush page has a “kids corner.”

    Yes, real MDs with academic affiliations are recommending parents flush their autistic kids’ livers.

    I’m not talking about banning quacks from the internet. That’s impossible. I merely want them out of Harvard, Yale, UCSF, etc.

  51. #51 Eric Johnson
    October 24, 2009

    I didn’t mean banning them from the internet – I meant that I am leery of making some kinds of medicine or “medicine” illegal. Of course, that already happens de facto, because extremely few MDs will risk dislicensure, and dislicensure can happen.

    One of the first things they taught me as I slowly turned into a Mencken-like paleoconservative neanderthal, was that the dastardly statists would always clamor “but the children!” Nevertheless, I can’t say I have a glib answer for political philosophy problems involving children. But somehow I doubt many livers have been fried, else those doing it would probably be facing licensure hearings.

    I would be OK with a dual system where the same or even a slightly narrower range of wacky treatments were allowed to be to given to children compared to what is allowed (de facto) today – but where even more & wackier treatments were permitted to adults, if have them they must.

  52. #52 rusty bucket
    October 24, 2009

    If you read more than a couple of headlines about this, you’d know that testing methodology has been a big issue, as has poor lab practice. The 95% figure comes from Europe where the science was able to break out of the gravitational pull of the insurance companies’ profits.

    Stay tuned. Fat lady ain’t sung yet. Not hardly warmed up, acsurely.

  53. #53 kim
    October 24, 2009

    Prometheus at #15, the diacritic over the i in Moíra (Chloë Moíra Smith) is called a fada. Can’t get more Irish than that.

  54. #54 MadScientist
    October 24, 2009

    Ah, but there are truckloads of money to be made from people who *do* suffer CFS if you push the correlation = cause trope just as there are tons of money to be made pushing “detox” programs and fad diets.

  55. #55 MadScientist
    October 24, 2009

    @titmouse #34:

    “Soon it will be nearly impossible to sort real science from pseudocience within medicine. Five years, I’d say.”

    I agree with Eric Johnson #36; there has always been woo-woo in medicine. If you only look back about 120 years, medicine as it was then barely has any resemblance to modern medicine. I remember as recent as 20 years ago some BIG pharmaceutical companies were still marketing quite a few cures which were really only placebo. I don’t know what pushed the companies to remove those products from the market, but these days selling vitamin and mineral supplements as “natural” cure-alls is surely a far larger business than pushing placebos for specific ailments.

  56. #56 kg
    October 24, 2009

    “..the MLV coat protein can disrupt red blood cells in mice, leading to low blood oxygen levels..”
    http://www.bioedonline.org/news/news.cfm?art=5704
    I’ve been looking for the paper containing the above data and it’s driving me nuts. Any virologists out there know the reference?

  57. #57 John
    October 24, 2009

    ERV, I commend you and completely agree. Well maybe not completely in the sense that there’s anything fishy with the research but totally agree that it seems highly likely that there’s more to it than just a retrovirus. Much much much much much more. Did a bunch of mice just drop dead in the water supply or something over a period of months/years? What about the sudden vs. gradual onset thing? Still, when the *(&^ing CDC itself has been on the fast track(for the past twenty-plus years) to claiming CFS patients are suffering from psychoneurosis, you’ll possibly understand why this XMRV study is such a supernova for CFS patients. I’m with you though, as I would imagine the study authors themselves are as well as the greater CFS patient and research populations, there’s lots more that still needs to be done.

    For instance, like you mention about the North Carolina Symphony Orchestra, CFS can occur during epidemics which have traditionally been associated with enteroviruses. There’s a long history of enteroviral association(if that’s the right word) with CFS from the first recorded outbreak that I’m aware of, the Los Angeles County Hospital outbreak in 1934 which Alexander ‘Sandy’ Gilliam, who went on to become the Surgeon General of the US, documented and referred to as ‘atypical’ or ‘abortive’ poliomyelitis due to the fact that it occured either during the middle or close to a regular polio outbreak and itself resembled a polio outbreak except people did not become paralyzed. Children have also been hit hard during epidemics.

    If you search through the literature there is a constant nagging association with enteroviruses but nothing has been definitively nailed down. Chia just reported last year that 81% of CFS cases had enteroviral infection of the stomach compared to 20% of controls and has been researching that angle for a while now. He just reported a case study of three individuals with acute enteroviral infection which went on to develop CFS. Stephen Tracy at the Univ. Nebraska just showed that contrary to popular belief, it was possible for enteroviruses to persist long-term in the body as opposed to the popular notion that all enteroviral infections were short lived by nature. So it could be a one-two with a pre-existing XMRV infection followed by an enteroviral infection that sets off CFS.

    Then you get into the matter of subtypes- it has been documented that CFS happens in both sudden and gradual onset types since the above mentioned 1934 LA County Hospital epidemic, with many researchers thinking that CFS might actually be several or perhaps even numerous distinct clinical entities that merely presented similarly. How does everyone being infected with XMRV explain that? Sudden onset patients generally complain of sore throat, swollen lymph nodes and neurological sequelae while I’m not sure if gradual onset cases report these, I’m gradual onset and I don’t.

    So I think you’re asking all the right questions, and hopefully we can get to the bottome of it by the NIH and CDC spending more than $3-5 million a year on CFS(now XMRV) research and quit thinking it’s no more than psychoneurosis, respectively.

    And post#40, I think by ‘well-characterized’ they might mean ‘not neurotic’. It’s fairly common practice by psychiatrists/psychologists in the UK and the Netherlands to use a watered down definition of CFS, the Oxford definition, to include patients with depression, anxiety disorders, PTSD, etc. in their ‘CFS’ studies which is a whole another ball of wax.

    But as for the German prostate study, that raises a big red flag to me when researchers report zero prevalence in their studies. Both the CFS and prostate studies on XMRV in the US reported similar prevalence rates in the general population, around 4%, so it seems like the Germans should have found something. For them to find zero kind of makes me think their methodologies might have been off, which is what was suggested by Silverman, the lead author of the first study to find XMRV in prostate cancer patients. There was also a study done on enteroviruses in CFS by Evengard a while back that showed zero prevalence of enterovirus in patients and controls when just by chance alone it seems like they should have found a couple. That study put the kibosh on enterovirus research in CFS for a pretty long while until Chia just re-lit the fire recently. Just something to think about.

    Links-
    ME-CFS epidemics
    http://fm-cfs.ca/ME_epidemic.html

    Chia presentation on enteroviral research in CFS-
    http://www.scivee.tv/node/6991
    Chia papers on enteroviral association with CFS-
    ‘Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach’
    http://www.ncbi.nlm.nih.gov/pubmed/17872383
    ‘Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence’
    http://www.ncbi.nlm.nih.gov/pubmed/19828908

  58. #58 titmouse
    October 24, 2009

    Doctors can’t spot the quacks any longer. That’s the problem. Look here’s one at Man’s Greatest Hospital.

    I just want the boundary between medicine and pseudomedicine back as it was in the 1980s. I can’t share patients with anti-vax DAN! doctors –it’s just too painful for all concerned.

    Licensure laws have recently been changed in most states now so that “integrative medicine” is not actionable.

  59. #59 Ian H Spedding FCD
    October 24, 2009

    I’m just an occasional visitor here because I’m a hardline anti-antapostrophist but I want to say that, as a layperson, I find ERV dumbs down the explanations of these very complex topics just right for me.

    The HHV8 story is a really neat illustration of the old point that correlation is not the same as causation.

    Loved the orange kitteh video, BTW.

    And am I the only one who gets an image of the character of Abby from NCIS whenever I read the ERV posts?

  60. #60 Neuroskeptic
    October 24, 2009

    “What does not make sense is a person stating that they are “not a MD” then going on to say that a retrovirus being the cause of prostate cancer or CFS, “does not make sense!”"

    Most MDs don’t know anything about retroviruses other than that HIV is one. If they went to med school in the last couple of decades they’d probably have learned more than that at some point, but unless they’re a virologist they’ll have forgotten it again.

    In my experience when it comes to theoretical questions, and this is one, a scientist specialising in the field will know more than 99% of MDs, even clinicians in that field.

  61. #61 kg
    October 24, 2009

    XMRV WAS ALREADY DOCUMENTED IN GERMANY. HELLO??
    Can I repeat my previous post as it obviously hasn’t been seen by several people. This will save anyone else embarrassing themselves by claiming the latest German research has thrown the CFS work into question. It hasn’t. More people should read the comparatively small literature on XMRV before making comments.
    My previous post :
    “”Similarly, XMRV was not found in 589 prostate cancer biopsies in Germany. None. Zero. ”
    I apologise if someone has already mentioned this, but I should point out that a study published last November in the Journal of Clinical Virology, by German scientists based in Hamburg (Fischer et al), found XMRV infection in one prostate cancer case and one control. Clearly the incidence in Germany appears to be lower but it is not zero.”

  62. #62 cynical1
    October 24, 2009

    “There is more to connecting a virus to a disease than simply comparing prevalence in diseased vs normal populations.”

    ERV – Oh, you are so right on that point. And isn’t it easy to reference your virus of study, HIV? Yeah, it’s well known about the association of HIV, HHV-8 and Kaposi’s Sarcoma. It’s equally well known that CMV causes retinitis in HIV patients but not in others (most of us) that carry the virus. (BFD). And HIV patients are more at risk for EBV-linked lymphomas. Yeah, that would be ~90% of us who carry that one as well. Big deal – HIV is the most studied virus in the history of the world and I’m glad that you have an arsenal of data to draw on for your conclusions.

    However, you are a complete fool when you pretend to understand viral links to autoimmunity. And I think there is a fair amount of data to suggest that CFS has an autoimmune etiology (and I’m not an expert in that area). Epidemiology goes out the window when you start looking for autoimmune responses to pervasive viruses. In reality, the discrepancy between CFS patients and controls is staggering when examining XMRV (assuming subsequent substantiation). And, after all, CFS is a differential diagnosis which muddies the waters quite a bit.

    Before you judge, perhaps you should look at mechanisms such as bystander activation, hit-and-run and molecular mimicry as mechanisms for viral involvement in autoimmune diseases.

    Alternatively, you should look at the research of James and Harley at U. or Oklahoma regarding EBV in Lupus patients – particularly the pediatric ones. Why are all pediatric SLE patients EBV+? Or perhaps you should look at the work of Ascherio, from Harvard, on EBV in MS patients. Pretty interesting to watch their antibody levels go up over a decade prior to diagnosis. Yeah, 90% of us have that virus. But 100% of MS and SLE patients have it. Riddle me that? (And the odds ratios are as strong as cigarettes and lung cancer.)

    In reality, the viral association with EBV and MS and SLE is so profound at this point that one has only to try to understand the immunological mechanisms now, not whether they play a causal role in the disease. I know – I ran a research collaboration with three professors who worked on that virus. By the end of our collaboration, none of them doubted (and some of them were actively working on it).

    So before you make a judgement on XMRV and CFS, please keep an open mind. The virus might play a role in initiating the disease or it might be a prerequisite for another virus. Remember, some viruses allow other viruses to infect cells that would not otherwise have tropism for that cell type.

    As a medicinal chemist, research like this makes our jobs exciting. I know it may be proven wrong. But we can fight a virus. I know. I fought HIV successfully (even to phase III) for a living.

    (BTW – I really like spaghetti westerns as well………..)

  63. #63 jeremy
    October 25, 2009

    Re the earlier comment on difficulty of reading this blog – it *is* a difficult blog to read, I agree. I think it’s important to push yourself with this kind of stuff though (I end up understanding about half of what is written from a technical perspective). Even looking for simple themes that give an insight into the importance of approaches to scientific thinking can be quite rewarding. If I’m reading correctly, this is as much about “a causes b” as opposed to “a occurs at the same time as b”. Also, Abbie is way funny to read and quite pretty.

  64. #64 Rrr
    October 25, 2009

    Also, Abbie is way funny to read and quite pretty.

    Nah, I think shes a dog. Oh — that was HER dog? Never mind. Sry. What you said. :-)

  65. #65 Richard Wolford
    October 26, 2009

    Frankly, CFS patients, rightly or not, arent exactly pleasant commentors when they think they are being attacked.

    I promise to be pleasant, and promise not to derail this thread, but there is a reason: when you’ve been told for 10+ years that your symptoms are just in your head, that there’s nothing wrong with you, it begins to wear you down pretty harsh. For over a decade I was told that there was nothing wrong with me at all, that my fatigue, and even my joint pain, was in my head. Years later I was diagnosed with ankylosing spondylitis, which also presents with CFS. Nobody seems to understand that CFS is very, very real and not pleasant to live with. My meds have actually helped, although my pain meds can cause insomnia which means I end up even more tired since I don’t get much sleep. Of course the chronic pain also keeps me up, so again it gets compounded.

    So the CFS folks here probably get irritated because they’re simply used to being told that they don’t really have anything wrong with them when they do, I know I do. I like this blog, I really do, and I intend on reading on a regular basis as I’ve done for quite a while, but you just have to understand where people like me are coming from. Being told you’re a hypochondriac for years makes you a bit bitter :)

    And I don’t find this blog hard to read at all, I always learn something.

    Anyway, sorry if I vented too much, just wanted to provide perspective.

  66. #66 LYSA
    October 26, 2009

    I think most of the people arguing the causation vs correlation point are missing the entire relavance of this research. It doesn’t matter if the virus CAUSES CFS. There has now been shown a biological effect in people claiming to have CFS. This is huge for their community because previous to this all CFS treatment was predicated on the idea that it was all psychological and they basically needed to find a way to get over it.

  67. #67 A;ex Barton
    October 27, 2009

    I agree with the author. People recover from CFS in the same way they recover from any illness, essentially by improving their diets and dealing with stresses and thereby strengthening their immune systems. The book “RECOVERY FROM CFS – 50 Personal Stories” available from Amazon shows 50 people who have recovered from CFS all using different methods, but the relief of physical and emotional stress is prevalent throughout the stories. If you want free stories from the book go to my website http://www.alexbarton.co.uk and a free recovery story will be sent to you weekly by email.

  68. #68 judderwocky
    October 28, 2009

    The cause is suggested for several reasons… 98% of CFS patients are being found to test positive for the virus (up from the initial report). This is a very high correlation that one would not expect if the virus were merely along for the ride. The retrovirus explains the over expression of other (upregulation of )genes in the cell, explains why the virus seems to flourish after activity (it replicates more intensely when cells divide), and explains why only certain populations become susceptible to it (some people carry a genetic defect that allows XMRV subside more easily in the body).

    just because there are some that it does not cause a problem for is irrelevant… there are some people that have been exposed to HIV but are genetically immune to it. Some people test positive for HIV in Africa, yet have no virus present in their body.

    It isn’t proven yet. But to claim in the face of so much evidence that there is no cause for a link is just ridiculous. This is the problem with a population that doesn’t understand statistics. They misinterpret studies and make curious statements about causality.

  69. #69 Dr Charles Shepherd
    October 28, 2009

    Those of you who are interested in how a patient support charity for people with ME/CFS in the UK is cautiously responding to these XMRV findings should read our letter to Sir Liam Donaldson, Chief Medical Officer at the Department of Health >>

    http://www.meassociation.org.uk/content/view/1059/161/

    My understanding is that the potential risk of viral infection in the blood of people with ME/CFS in relation to blood donation is being taken far more seriously here in the UK than elsewhere.

    Charles Shepherd

  70. #70 Alice B
    October 28, 2009

    HIV wasn’t found by checking all gay men who were feeling poorly. Some had other causes for their symptoms.

    They looked for the virus in particular groups and then had a name and a cause for the disease.

    Then the name defined the group and the disease.

    why should CFS be any different? Just because the diagnostic criteria is poor (and that is something the patients have been saying for years)

    So how do we set the cause of a disease? (bearing in mind that there are many resources on this and people have been re-reading them recently)

    ERV, do you argue that HIV is not the cause of AIDS

    What is your reasoning

  71. #71 cooler
    October 28, 2009

    Haven’t you guys heard of Koch’s Postulates? This CFS virus, like all other retroviruses fails all 3 of the postulates. Its was not found in abundance in the tissues with the electron microscope, and low doses were not injected into animals causing disease. I hope they don’t create a 10-50 year latent period like they did with all other retroviruses to save their hypothesis! That would be funny!

  72. #72 Eric Johnson
    October 28, 2009

    Cooler, you’re a donkey, a hyena, a chimp, a weasel, and a seal. But I’d probably like you more than most people, if I met you in real life. Koch’s postulates are not used anymore except as an epistemological ideal that can guide the far less ideal experiments that are usually used to deduce etiologicity in actual practice. There are four postulates, not three, you fine scholar. No virus satisfies the third postulate as written. The majority of pathological infectious agents do not satisfy the first postulate. Not even HIV! – since some tiny fraction of those infected do not get AIDS even after a long time.

  73. #73 cooler
    October 28, 2009

    No, they are three postulates you moron, one was added much later read “Causation and Disease: The Henle-Koch Postulates Revisited Alfred S. Evans”

    Yeah using the criteria your implying any microbe can be said to cause disease, you don’t need to find it in abundance with the microscope like Koch did with Anthrax, have an animal model, you can just stretch the latent period to 10 -30 years to explain away all the “infected” healthy people (as in the case with hepatitis c and HIV) with your money making microbe!

    It’s pretty sad you guys have such low standards for proving microbe causation considering the millions people make off terrorizing the public and being forced to take chemotherapies like AZT. Pretty low standards when any expert like Dr. Lynn Margulis knows most bacteria and viruses are harmless.

    Keep the cash flowing discovering money making microbes like HIV, htlv-1 htlv-2 FIV and hepatitis c! When are you guys gonna discover a new microbe that has a 150 year latent period?

  74. #74 Jean
    October 28, 2009

    One clue that XMRV could be a cause is that Ampligen has helped not just a few patients. Yes there is a lot to be discovered yet. As you all should know by now the % CFS patients with XMRV is 95%. I’m certainly going to get tested for this retrovirus, and treated if positive. Just as I got treated for HHV6 which is another virus with cancer associations.

    I do suggest looking up Koch’s postulates on Wikipedia. Understand it’s not the greatest source but it does explain that even during Koch’s time the postulates were seen to be flawed. And they have held back the field of virology – they were developed before viruses were recognized..

    It could be that XMRV is benign in people with strong immune systems. Those of us with very weak immune systems are easy victims. Whether or not Pasteur said “the terrain is everything” whoever said it had an excellent point.

  75. #75 Alice B
    October 28, 2009

    People with CFS have been reading Koch’s Postulates and Hill’s Criteria of Causation with added interest since the XMRV news.

    Having a new retrovirus is frightening. We want to know how it is implicated in CFS and what it means.

    It’s however, not as frightening as being chronically ill every day for decades. It doesn’t mean that our brains go out the window.

    We would like to get better to even have our symptoms controlled (like AIDS).

  76. #76 cooler
    October 28, 2009

    Alice, people are barking up the wrong tree, this whole retrovirus frenzy trend was started by a small group of crooked scientists in the 70′s. Gallo kept trying to pin retroviruses as the cause of cancer with no evidence, first he had HTLV-1, then HTLV-2 than came HTLV-3 that was later renamed HIV. Gallo found HTLV in like 4% of Leukemia patients and the idiot to this day still thinks its the cause, inventing 50 year latent periods to explain away healthy people “infected.”

    According to Gallo, Leukemia is contagious, cause him and his pals like Essex think it is caused by HTLV. Now ask any cancer expert if leukemia is contagious and they will laugh at you.

    Sadly, Gallo et all were able to convince some crooked public health officials Like Margret Heckler, and billions of dollars have being spent investigating retroviruses, and nothing else.

    Many scientists believe that other factors play roles in these diseases like extensive stress, chemotherapies like AZT, the enormous amount of Drug use in the gay fasttrack lifestyle and some like Montagnier and Lo et al blame mycoplasma incognitus. If you do a google scholar search on that microbe, you’ll find some real evidence. Overall, many prominent scientists have stated that just focusing on retroviruses like HIV, HTLV and nothng else has been a huge blunder.

  77. #77 cooler
    October 28, 2009

    “No virus satisfies the third postulate as written.” says Eric Johnson. LOL have you heard of the polio virus and Popper’s animal model?

  78. #78 Eric Johnson
    October 28, 2009

    My fault, I meant second postulate not third. A lot of people back in the day ran around trying to grow viruses on agar and such, with no host cells for them to infect. Because they didn’t know what viruses were.

    Again, probably most pathogens do not satisfy the first postulate. Including tuberculosis, but Koch didn’t know that – at least not early on.

  79. #79 Science_Shifts
    October 28, 2009

    First of all, I am skeptical that CFS is caused by XMRV, and I have CFS. I also agree with the poster that CFS does not appear to have the same epidemiological profile of HIV. However, I found a few problems with the blog post:

    1. Foremost, the blogger overstates the claims of the researchers, then attempts to disprove those “alleged” overstatements.
    Where is the evidence that the researchers are claiming to have found the de-facto cause of CFS? If you read the science article, they raise more questions than they provide such declarative statements — phrases such as “association” and “possible” were used.

    2. There have been few, if any, grants provided for viral or immune research into CFS since the late 1990′s. The NIH has leaned toward a “misperception of symptoms” theory and the CDC a “stress and sexual abuse” theory. Both agencies feel gender and the brain, not microbiology, is a prime role-player.

    Because of the federal funding climate, the researchers at WPI operate under a different set of political and financial rules than an HIV researcher. While the poster seems to have a solid grasp on HIV research, I think he is trying to extrapolate the AIDS research experience to CFS research. There really is no comparison.

    3. The correct position on the transmissibility of XMRV is that we don’t know how it is transmitted. We won’t know until wide epidemiological studies are done. In fact, the researchers involved know they are seeing some children infected with this virus, they are not able to ascertain why. At this point, they care to see the issue investigated. I disagree with the blogger’s claim that we know how XMRV is transmitted. Both the researchers at WPI, and even the “mad and beaten down as hell” CFS community are wanting more investigation.

    I, too, and skeptical that XMRV is the cold-hit for CFS, I have had this illness for 22 years. I DO KNOW that science will find the answer. There is a situation with CFS that will provide some researchers a HUGE payoff. Sometimes, the harder the political and public climate, the bigger the payoff.

    Answers will need to come from researchers who understand the need to move beyond the broader definitions of “fatigue syndrome” and look at a clinically distinct group of patients. These researchers understand the political landscape of CFS research, whether they found a causal agent or not. They are connected with clinical expertise that the federal agencies just don’t have, at this point.

    The blogger, while correct on the point that this study did not prove a causal link, overstated the claims of the researchers involved. Then, he attempted to prove those alleged ovestatments wrong. This thread is, as William Shakespeare would say, an argument that is “much ado about nothing”.

  80. #80 rene
    October 29, 2009

    “There is no symptom of CFS that cannot be explained by understanding
    the biology of this retrovirus. We will very soon have enough data to
    say X satisfies the same correlates of disease association as HIV and
    AIDS.”

    “The p value for association of CFS with X is 10 -35; Virtually impossible to have CFS without XMRV.”

    “We still cannot say cause…in fact one cannot say cause for HIV AIDS but everyone knows what that means.”

    “Science is conservative so we cannot say cause but have accumulated
    significant data that will within the year allow us to satisfy Hill’s
    criteria of causality the main point of which is every case of the
    disease contains the pathogen.” —– See the second link for Hill’s
    Criteria.

    “Since the submission of the manuscript on May 6th, we have developed a
    sensitive and specific seroconversion assay. We can detect antibodies
    to the XMRV envelope in>95% of the>250 patients we have tested
    from around the world. We have failed to call a case wrong either way.”

    “We see great promise of combination therapeutic strategies very
    quickly If an individual gets the immune system modulated to control
    and silence the virus then one can be well.”

    “John coffin is a member of the US National academy of Sciences. No
    greater authority on these viruses exists. 3 members of the US NAS
    reviewed this work and all are convinced of the science but need to be
    conservative so as not to scare the general public.”

    “They are convinced of the infection and the public health risk and our
    data suggest. 10 million Americans are infected with XMRV and at a risk
    for CFS and cancer. For me it is crystal clear and all of the
    scientists who have seen these data have the same response: Absolute
    amazement. The best in the world are all over it. They may not
    understand CFS bug they understand an entirely new human disease entity
    ten fold the incidence of HIV!”

    Judy Mikovits

  81. #81 KAL
    October 29, 2009

    If you want a good explainer on retroviruses and CFS you might want to check out the Oct 15 post on Columbia University microbiology professor Vince Racaniello’s blog.

    http://www.virology.ws/2009/10/15/xmrv-and-chronic-fatigue-syndrome/#comments

    Like many others I believe it is premature to speculate either way on the meaning of the correlation between XMRV and the neuroimmune disease ME/CFS. Scientists don’t know enough. Just as one study by the WPI is not definitive, one study in Germany is not definitive either. Causality may have to wait on biomarkers for a tie in.

    The WPI for Neuroimmune disease has a NIH R01 grant to further the study of this connection. A number of people have commented that how the population is defined is key to such studies.

    For example the CDC has openly said they won’t be able to replicate the study. That is to be expected since they don’t use the same research definition. You have to compare like to like or you cannot make a definitive statement regarding replication.

    To paraphrase: The devil is in the variable.

  82. #82 Rene
    October 29, 2009

    yes they have to compare like with like . how can Bill Reeves state openly before they have even tried to replicate the study that they will not be able to. Like wessely in ENGLAND saying it probably will not apply to MOST OF those in England with Me/CFS.. why because they know they have lost a genuine diagnosable illness to dusbin bin diagnosis for who anybody who has chronic fatigue and sure in advance they would would not be able to repeat the findings of WPi

    If the XMRV virus is found around around the world using the same research diagnostic criteria and the same sensitive and specific seroconversion assay test then even if just a small % of people who’s lives have been blighted by this illness will be out of the pshyciatric dusbin and may look forward to at least some genuine medical help.

    Rene

  83. #83 Eric Johnson
    October 29, 2009

    If you want to be taken seriously, saying “well, I am virtually sure I will get X result” before you have done a single thing is not a good idea.

  84. #84 Science Shifts
    October 29, 2009

    From the WPI:

    “Our initial research showed that 67% of the ME/CFS patient samples tested positive for XMRV. Further work has found that 95% tested positive. Work continues to understand how this virus works within neuro-immune diseases, but this discovery proves a SIGNIFICANT CORRELATION between this serious retrovirus and these diseases. Our work SUGGESTS, BUT DOES NOT PROVE that XMRV may be the underlying cause of ME/CFS. Much additional work needs to be done to understand how XMRV causes disease and what types of diseases it is linked to it.”
    “This looks like a very, very interesting start. It’s not impossible that this could cause a disease with neurological and immunological consequences, but WE DON”T KNOW FOR SURE.”

    And, from the actual set of “SCIENCE” articles, which you do not quote:

    “Another notable feature of XMRV is that the frequency of infection in nondiseased controls is remarkably high—about 4% in both normal individuals from the same geographicregion as infected patients with chronic fatigue syndrome, and in nonmalignant prostates. If these figures are borne out in larger studies, it would mean that perhaps 10 million people in the United Sates and hundreds of millions worldwide are infected with a virus whose PATHOGENIC POTENTIAL FOR HUMANS IS STILL UNKNOWN”.

    From the conclusions in the “Science” article:
    “In summary, we have discovered a HIGHLY SIGNIFICANT ASSOCIATION between the XMRV retrovirus and CFS. This observation raises several important questions. Is XMRV infection a causal factor in the pathogenesis of CFS or a passenger virus in the immunosuppressed CFS patient population? What is the relationship between XMRV infection status and the presence or absence of other viruses that are often associated with CFS (e.g., herpesviruses)? Conceivably these viruses COULD BE COFACTORS in pathogenesis, as is the case for HIV-mediated disease, where co-infecting pathogens play an important role (20).”

    “Finally, it is worth noting that 3.7% of the healthy donors in our study tested positive for XMRV sequences. Thissuggests that several million Americans may be infected with a retrovirus of as yet UNKNOWN PATHOGENIC POTENTIAL.”

    “Mikovits’ team said further research must now determine whether XMRV directly causes CFS, is just a passenger virus in the suppressed immune systems of sufferers or a pathogen that acts in concert with other viruses that have been implicated in the disorder by previous research.”

    Most knowledgeable spectators believe the next ball that will drop is that the CDC will fail to replicate the study in their Wichita and GA cohorts. This will not end investigations elsewhere, as it did with Rnase L. There is too much interest in retroviruses outside of the federal programs that manage and implement CFS policy.

    Though Reeves is drawing a lot of fire for his comments that the CDC will not be able to replicate the WPI study, his comments make sense. He — and the CDC — holds to a very different clinical and conceptual picture of the illness.

    The CDC has found no evidence of immune irregularities, Rnase L, or abnormal viral loads in their samples — none. They are not finding many abnormalities in their unwellness phone samples. The WPI is.

    Sample selection means a great deal. And at this point, it tends to reflect a different conceptualization of CFS. And with any group of patients who have an illness whose pathogenesis is not well-understood, a variety of factors can influence clinical concepts: gender, race (for instance, Africans with HHV-8), and working environment. Since the CDC conceptualizes CFS as a possibly product of an abusive environment or lifetime stress, it makes sense they would not have virally active samples, at this point. No one who has a savvy understanding of CFS research is expecting them to correlate this finding.

    Like many people with CFS, I ran tests for Rnase L and various viral loads. Running these tests does not mean I believed those tests demonstrate any kind of clear a causative pathogenesis. Lupus and RA tests work in similar fashion. The tests did help prove disability and provided a better framework for how to manage the illness. When you have an illness that is not accepted as a serious problem by many in the scientific, medical, or research community, those tests – though not a panacea or even a suitable band-aid — are all you can do.

  85. #85 Alice B
    October 29, 2009

    Thanks Cooler for the reply.

    Before retroviral drugs were used, I lost several gay friends. Since the drugs have been used I have lost none.

    I’d like to me as high functioning as my HIV+ friends.

  86. #86 G Lyon
    October 29, 2009

    You’re right that correlation does not show causation. I think the Whittemore Peterson Institute have been careful to point that out; unfortunately, many of the news articles have not. In fact, Dr. Peterson said today that he doesn’t think that XMRV will turn out to be the cause of CFS…at least not by itself. The point is, that we need more research to find out what it means and why there’s such a strong correlation. I think it’s unfair to accuse them of simply “pimping” an XMRV test.

  87. #87 Yvonne
    October 31, 2009

    Thought you might be interested in seeing Dr Peterson’s presentation to the CFS Advisory Committee meeting on 29 Oct.
    This is the first part of his presentation and you can access the rest in the same way on YouTube, you could also wait for the archive to be put up on the government site.
    http://www.youtube.com/user/luminescentfeeling#p/u/10/80yKflt0tcA

  88. #88 InLabOnSunday
    November 1, 2009

    Did anyone else read the New York Times Op-ed by Hillary Johnson? In addition to a little science illiteracy, she reveals an interesting factoid the Science authors didn’t put in their M&M section:

    “…she (Mikovits) was also impressed that the doctor, Dan Peterson, had built an extraordinary repository of more than 8,000 chronic fatigue syndrome tissue samples going back as far as 1984. “My hypothesis was, ‘This is a retrovirus,’ and I was going to use that repository to find it,” Dr. Mikovits told me. What she found was live, or replicating, XMRV in both frozen and fresh blood and plasma, as well as saliva. She has found the virus in samples going back to 1984 and in nearly all the patients who developed cancer. She expects the positivity rate will be close to 100 percent in the disease.”

    That is, Johnson’s description is consistent with all of the samples in this study having been collected, stored, and maintained, in some cases for up to 25 years, by one person. You can control for PCR contamination all you want, but what if the source of contamination is your sample itself?

  89. #89 InLabOnSunday
    November 1, 2009

    I meant all of the CFS samples. Where did the control samples come from? Were they also collected by Dan Peterson and kept in his freezer for up to 25 years?

  90. #90 E. Johnson (geeking out at home on sunday)
    November 1, 2009

    The supplement says this much, which I admit is not as complete as what you mentioned from the H. Johnson:

    “Patients’ peripheral blood and plasma samples were from
    frozen banked samples”

    What is the physis of drawn blood, o knowledge seeker? How long do the leucocytes keep flappin’? I don’t know, myself. While PCR could easily be contaminated, the protein expression assays (which were controlled against healthy normals) could only be contaminated if XMRV can ingress, uncoat, and start expressing protein in withdrawn cells.

    What can’t really be messed up by this kind of contamination is the serology. Which was also controlled against healthy normals. There’s no way withdrawn blood that then gets contaminated can seroconvert. For that assay to be contaminated, the people themselves would have to get contaminated some weeks before being samples.

  91. #91 John
    November 4, 2009

    #88 and #89, some different facts are getting mixed up. Dr. Peterson has a personal repository, but samples used in this study did not come from that repository.

    From the WPI website-

    “Dr. Daniel Peterson understood the promise that a historical bio bank could bring to scientific understanding thus he began collecting and storing patient samples in the early 1980′s. However, it is important to note that no samples from this historical bio bank were used in the Institute’s XMRV studies.”

    and

    “Q- Where did the samples come from for the XMRV study?

    A- The WPI repository samples came from patients who live in many different locations around the US. Physicians who contributed patient samples include: Dr. David Bell, Dr. Paul Cheney, Dr. Daniel Peterson, and Dr. Eric Gordon. Other individual patient samples came from individuals who became ill while living in California, Wisconsin, South Dakota, etc.”

    -

    “Q- What about Dr. Peterson’s private repository?

    A- Dr. Peterson has a repository of samples from the original out break in Incline Village, Nevada which also includes longitudinal samples taken from patients from the 1980′s through 2005. None of these samples were used in the XMRV study.”

    http://wpinstitute.org/research/research_biobank.html

  92. #92 SC
    November 10, 2009

    It looks like we all might be getting a few answers (or at least some guidance in asking the right questions) sooner rather than later: Top scientists to meet at Cleveland Clinic on trail of XMRV, a suspect in prostate cancer (http://www.cleveland.com/healthfit/index.ssf/2009/11/top_scientists_to_meet_at_clev.htm).

    As for the WPI study, big claims come with commensurate scrutiny. This seems like some serious attention. It should be interesting.

  93. #93 SL
    November 12, 2009

    Well, ain’t it cool that you guys are talking about CFIDS? Wow. And that grant money is coming out now after all these years. Glad I was diagnosed with immunological dysfunction by a Director of HIV/AIDS Clinical Trials at one of our country’s main major med centers (hell, what do you put down for the code when you get heterophile positive mono over and over and then it seroconverts in between times? And you get C.Diff in the absence of taking antibiotics—over and over and over again—trying having that alone. And you have cardiac dysfunction that shows on echo? Jeez, could go on, but know I’ve bored you enough. Anyway, objective evidence and bingo—it ain’t what Reeves has been studying at the CDC! The CDC wouldn’t touch a subject like me. They might have to reveal what they might already know. Shrug. What’s the significance of XMRV? No idea whatsoever, but hey, it’s got you guys talking and money for research flowing. Finally.I never ever thought it would take this long.

  94. #94 Mary
    December 8, 2009

    I am a Fibro/Cfs/ME sufferer. I am not offended. Thank you for putting into words what I, (a layperson) have been trying to articulate about the information Whittmore-Peterson and the other XMRV popular articles have been putting out thus far. Thank you for making me laugh while you did it-I didn’t think it was possible the way I feel, and about a subject that is so serious. I only wish there was more scientists like you speaking out when scientists get ahead of themselves. I’m a psychology student at university so I know why they get ahead of themselves-usually for quite noble reasons. I know you are not laughing at suffering people. I wish the others could see you are actually trying to protect us! Keep up the good work!

  95. #95 Jim S
    December 14, 2009

    I am a layman who has had prostate cancer and may be in process of biochemical failure, depending on whose definition you choose. I am also in the process of being checked out (if that is possible) for chronic fatigue. I am persistently anemic (macrocytic with normal b12 and folate) with a low neutrophil count if that means anything. So, I’m more than a little interested in any proposition that the 2 may have an association. I’m no virologist, biochemist or M.D, just a humble B.S. But, I have to think that even the 67% number pleads an association much less 95%, if that holds water. I know the passions of true believers in every sphere and that the more allegiance you have to your area of discipline the more dogmatic you can become. In this case open minds are in order. Being pooped is one thing, dying from it is another.

    Thank You,
    Jim