Sunday, November 15, 2009

Waiting in Limboland with XMRV

A subset of sick people round the globe are in an odd state just now.  We have this tantalizing bit of new information, that a newly-identified retrovirus is showing up in a high percentage of very sick people with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome).  But it is just one published study (Lombardi et al., "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome," Science [Sciencexpress, online], Oct. 8, 2009), and everybody knows scientific certainty and causal linkage require more than one study.  So we’re waiting.
I’ve calmed myself down partly through mental exhaustion.  I just have to.  And I’ve been lulling my mind with the thought of January.  I’ll expect something more by January.  More information by January.  January.  Don’t worry, Priscilla, January is coming.  I have no particular reason to expect anything in January; it’s just far enough away to be reasonable (as opposed to tomorrow) and close enough to be comforting (as opposed to 2020).  My mind can curl around the thought, settle down, and purr.  January, yes. 

And I gather things are moving fast.  I don’t think Judy Mikovits, director of research at the Whittemore Peterson Institute (which conducted the original study linking XMRV and ME/CFS), was waiting for the article in Science to come out before continuing her work.  So we might hear something more from her team, in the form of published findings, soon . . . say, by January.  In the meantime, I’ve been looking around for good criticism of their study.  If there are problems with it I want to know about them.  A false hope is of no use to me.  So far I haven’t found any telling critiques.  Among the people who are equipped to understand the science, there have been a few turf-defending weenies whose peevish remarks were easily answered, but I have not been able to find any substantive criticism.   Mostly there’s only the sound of shoes tapping on the linoleum, as scientists head back to their labs to see what they can find.  That’s what we need.  If it’s going to be refuted, it will be refuted from the laboratory stool, not the library armchair.

It has been interesting, though, to try to find some legitimate criticism.  One of the most common objections is, “We’ve been through this before with other microbes.”  I thought something similar when I first heard of the finding.  I thought I would file it away and wait and see what happened.  A related dismissal has issued from Dr. Jacob Teitelbaum, who wrote a useful book with an offensive title, From Fatigued to Fantastic (which my Larry calls From Fucked to Fucktastic).  He has immediately incorporated the news into the model of CFS he’s already using: there are many factors in CFS, including lots of viruses, treating infections is already part of my protocol, this is just another infection, it will be good to treat it too.  Like almost all the other critics I’ve read, Dr. Teitelbaum opinionates freely without addressing the specific research findings.  The technical term for this is “hand waving.”  The term for the work of Dr. Mikovitz and her colleagues is “science.” 

Science runs on numbers.  Scientists love numbers so much they even use numbers to talk about their numbers. 
The frequencies of CFS cases vs. healthy controls that were positive and negative for XMRV sequences were used to calculate a Pearson [chi-square] value of 154 (two-tailed P value of 8.1 × 10–35). These data yield an odds ratio of 54.1 (95% confidence interval of 23.8–122), suggesting a non-random association with XMRV and CFS patients.
Here’s an abbreviated version of the statistics tutorial that my Larry gave me.  (I hope any real statisticians who wander by have someone handy to catch them if they faint.)  Let’s just take the P value.  The P value is a statistical expression of the strength of the null hypothesis.  The null hypothesis says there isn’t actually any difference between whatever two things you’re trying to compare: null.  In this case, we’re comparing rates at which XMRV DNA is isolated from blood of CFS patients versus healthy controls.  The P value is a number between 0 and 1, 1 being absolute victory for the null hypothesis, 0 being absolute defeat.  The convention is to reject the null hypothesis if your P value is less than .05 or .01.  I guess there are slightly different conventions, but we’ll go with .01 because we like rigor. 

The P value for this comparison of infection rates in CFS patients and healthy controls is 8.1 × 10–35.  Powers of 10 are used in science to compactly express very large and very small numbers. In this case it’s a very small number.  That 10–35 means you take the decimal point in 8.1 and move it 35 times to the left, adding 34 leading zeros.  That’s a very small number.  It’s a whole lot smaller than .01.   The number “.01” is one one-hundredth; 8.1 × 10–35 is just a tiny bit bigger than a trillionth of a trillionth of a trillionth.  It suggests, it indeed suggests, “a non-random association between XMRV and the CFS patient population.” Larry said that statement was the driest humor he had ever read.

If any other studies of viral or bacterial infections in CFS patients have had this kind of statistical strength in their findings, I’d like to know about it.  But I don’t think they have.   All those other viruses and bacteria are common in the general population and easy candidates for opportunistic infection.  This one, so far as we know, is not. 

The results of this study, this new research, are uncertain, but they’re also unprecedented.


  1. P value is one of the only things I remember from my statistics classes. Hell, it was one of the only things I understood in my statistics classes at the time.

    Here's the way I explain it. You've found different results for your control group and experimental group (for instance, 3.7% of healthy controls test positive for XMRV, compared to 67% of people in the sick population). If your P value is less than .05, that means the odds are less than 5% that the difference is due to random chance.

    So is January just a guess, or is it based on comments from the WPI? January would sure be nice ...

  2. It's not just p-value, it's also the prevalence of a virus in the general population. Most other viruses are fairly widespread, to say the least- EBV is in like 85% of the population, HHV-6 maybe 90%, yada yada yada... So for 99 of 101 CFS patients(unpublished data mentioned in newspaper interviews + Dr. Peterson's CFSAC presentation) to have XMRV is like whoa.

    Also, I came across your page a while back and really liked it. I thought of contacting you to see if you would mind doing a calendar, mugs, etc. to donate to WPI, since you give your stuff away anyways, and then saw some people on the WPI Facebook site talking about calendars and stuff and linking to this page! Are you helping them?


  3. Here's my criticism or perhaps I should put it this way: here's the part I don't get that just does not add up to me, and that pertains the alleged mode of transmission via bodily fluids of breast milk, blood, or semen. The disease of CFS just does NOT seem that contagious, despite what they say, the researchers in this XMRV study among CFSers. It just does not seem sexually transmitted and why not if it is in fact contracted via something like semen. Wouldn't we know that already. So, in my case, I have FMS, so maybe I don't even have XMRV but if I do, I just don't see how I could have gottten it. Not from my mom's breast milk. She has NO signs of CFS or FMS. Maybe my dad did, because I do think there's genetics involved, but of course he didn't breast feed me. I can't think where I would have contracted this via blood. How about others out there? that leaves sexual transmission as the only plausible route that I can think of, but then that would make CFS/FMS a sexually transmitted disease. I don't think most people with this disease are worrying about giving it to mates. So, to me, this just doesn't add up. That's what makes me have doubts and reservations. yes, I know there are cases of CFS outbreaks but that is not necessarily the norm at all. So, why not? So, it just makes me wonder if there is some other common denominator, like an impaired immune system, that makes one highly susceptible to getting XMRV as well as other viruses. Just a thought.


  4. Cinderkeys: “January” doesn’t even rise to the level of a guess; it’s just a comforting mantra. Probably by mid-December I will be saying, “March, more information by March.”

    I think what you say about P-value is basically right, but I hesitate to use words like “odds” and “chances” when I think they have specific meanings in statistics that I’m not entirely sure of here.

    John: Yes, I will probably submit something for the calendar those folks are doing, though they are trying to move fast and I am very slow. I would probably also be happy to have my cartoons used in the other ways you mention to benefit the WPI. It doesn’t even have to be limited to XMRV cartoons. If you (or somebody else) want to do something else you can contact me at ms leaf at wildblue dot net.

    As I understand it, that difference between XMRV in the general population and CFSers is what makes the P-value so strong in favor of non-random association.

    Paula: I think you have a good question, but I don’t think there is necessarily a problem there. HPV causes most types of cervical cancer; however, most women infected with the virus will not develop cervical cancer. The situation with XMRV could be similar. So if you have the virus, and if it is making you sick, it is quite possible, maybe even likely, that the person you got it from would not be sick.

  5. P.S. Cervical cancer also doesn't "seem contagious," but, as it turns out, the cause of most forms of it actually is—it's sexually transmitted.

  6. Dr. Teitelbaum is like all the other doctors out there involved in CFIDS: Make money off us sick. Ok, NOT ALL doctors that treat us CFIDS sick. My internist has paid a very dear price to take care of us CFIDS people in terms of time, energy and money. He's a saint and a rare example of a true physician trying to help. Teitelbaum - not so much I fear.
    Point fingers at the CDC/CFS and wonderful Dr. William Reeves, his idiot associates and thieving contractors (ABT Associates and Emory University MIND-BODY Program) for wasting over $100 MILLION DOLLARS during the last 25 years or so. And with NOTHING to show for it except that we CFIDS sick can't tolerate stress. Thanks for THAT information. Meanwhile, the two year old Whittemore-Peterson Institute with about $1million in private funding has discovered something of import to the CFIDS sick. Oh, and also to those studying cancers and many other diseases - the XMRV Virus.
    It is past time to clean house at the CDC and remove Reeves and either put him in jail OR give him a pint of our CFIDS blood. I'd go with jail if I were you Bill...

  7. The XMRV research study was published in THE most critical, picky and prestigious medical journal, Science. It has already been peer-reviewed there. I agree that more research is needed to study causality, prevalence etc etc. but it's pretty hard to find fault with the original study and its conclusions. :)

    It is unfortunate that Teitelbaum doesn't seem to recognize the difference between viruses and retro-viruses. I'm no expert either, but I'm pretty sure they require different approaches to treat, different drugs.

    In response to Paula's comment, I'd like to say that I've recently come across the idea that there are certain conditions that occur only in the presence of 2 viral agents, such as EBV and XMRV. Unfortunately I don't have that reference handly, but there are illnesses that fall into this category already, and so there is a chance that CFS/ME is one also.

    As far as transmission goes, you have to remember that you don't get HIV any old time you have sex with an HIV positive person. It is also harder to get HIV from women. In order for transmission to happen, the virus needs access to the blood, for example through a cut or sore.

    If you look at these two things together, it would explain why partners of people with ME/CFS don't get sick very often. The majority of people with ME/CFS are women. Even if their partners have XMRV, without a trigger, susceptibility or second virus, they would not have CFS (just like not every person with HIV would have AIDS).

    Blood-born viruses can also be passed through blood transfusion, and other contact with infected blood. I guess it is possible to call XMRV a 'Sexually Transmitted Disease' if that is what label we use with HIV. But as HIV is not AIDS, XMRV would not be ME/CFS.

  8. I THINK Dr. Mikovits or Ms. Whittemore (the mother of the daughter with CFS) said CFS is not sexually transmitted, that we know this. But I could be wrong in my recollection, so I'll have to look out for that. If they did say that, then it doesn't make sense to me why not. But maybe they never said that. Anyway, people offer good/interesting possibilities as to how this might be sexually transmitted without our having been made aware but i still find myself skeptical. I too heard the idea of needing two viruses activated for CFS/FMS to occur "a one two punch". I think Jonathan Bell and Paul Cheney may've spoken to this, but not sure. Anway, maybe that does explain it. Thanks to those who put thought into this question. ---Paula

  9. "XMRV is thought to be transmitted through body fluids such as blood, semen, and mother’s breast milk but is not transmitted through the air. It is not known whether XMRV is more easily transmitted than other human retroviruses." -from the Whittemore Peterson Institute website

    Paula: I don't think anybody has said that CFS is sexually transmitted. But XMRV is thought to be (as well as by other means). I think it will help if you make this distinction.

  10. Now I'm waiting for January too :-)

  11. I'm waiting too. I don't have the energy to write much but seeing as you're on a pretty scientific theme today with your scientists and labs and powers of 10 I thought you might like this Prascilla:

    Not to do with XMRV but still the chorus cheers me up and makes me think of getting well again...and it is sciency.

  12. Anonymous: Loved the video; hilarious.


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