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Article: Dr. Mikovits and Dr. Racaniello on XMRV

Great article Cort, I feel reassured that XMRV is probably the cause of my illness, I do fit the CCC perfectly. I have a friend who could fit a lousy diagnosis of CFS and it's nowhere near like what I have, sure she gets fatigued more easily than most of people (since mono) and have frequent infections, but she can work, exercise, socialize and stuff.

So no doubt she would test negative on a lousy cohort selection despite her being fatigued. Guess they had a lot of person with this profile on the CDC study.
 
In case any scientists are reading. Here is a link from the WPI site about methods and I think more is available at Science and from WPI.
http://www.iacfsme.org/BULLETINSPRING2010/Spring2010MikovitsLetter/tabid/427/Default.aspx

I also think Dr. Racaniello is talking about the lack of CCC (Canadian Consensus Critieria) in the CDC paper not the WPI study.

This is amazing from Dr. M above: Prostate cancer in younger men is a totally different disease with inflammation and the tumor microenvironment playing a big role. We looked at a cohort of men from the NIH Clinical Center (these are the sickest young men and most aggressive tumors) and we found evidence of infection in >50%". And they have found XMRV in 99% of MECFS patients tested, and there is still no funding for XMRV research.

We need to ask Congress for Congressionally Mandated Research funds through the Dept. of Defense so this infectious retrovirus can get immediate attention.

Thanks Cort for trying to untangle the testing issues.
 
Thanks so much for this Cort. It's such a relief to get confirmation that some real validation studies are actually taking place.

Is it just my ME adled brain not computing what is actually being said, or is Dr R saying under "To PCR or Not To PCR?" that though PCR does NOT identify infectious virus it's the preferred method because it's cheap and everyone knows how to use it properly, therefore it's the method of choice? :confused: If so, I don't really follow that logic. It sounds to me like the same logic employed when buying something in a sale that you don't want, need or will ever use just because it's cheap. It's hard to see how gathering thousands of samples for a proper study versus using a method that isn't actually capable of finding infectious virus could "impede progress". Isn't the fact that they are using ineffective methods one of the things that's actually currently impeding progress?
 
Great article Cort, I feel reassured that XMRV is probably the cause of my illness, I do fit the CCC perfectly. I have a friend who could fit a lousy diagnosis of CFS and it's nowhere near like what I have, sure she gets fatigued more easily than most of people (since mono) and have frequent infections, but she can work, exercise, socialize and stuff.

So no doubt she would test negative on a lousy cohort selection despite her being fatigued. Guess they had a lot of person with this profile on the CDC study.

Hi gu3vara,

I don't think it is fair for you to judge your friend because she can work, exercise and socialize.

I believe I have a classic case of CFS fitting the CCC definition. After Mono in college I experienced the classic symptoms of enlarged lymph nodes, fever and fatigue. Two years later the Doctors at the University of Michigan thought I had Mono. Except that I already had had it in college, I went on to a rewarding career and very active socail life (albeit more tired than most). 13 years later, I finally crashed ultimately exhibiting all the PEM and cognitive problems.

Your friend could just be in the early stages.

Lynn
 
Great article Cort. I have a very minor criticism. A lot of very important points were made in the latter third of the article (which was quite long). Would it help to make a few short dot points at the very start of the article, just to bring home the important parts of the interview. Cheers Russell.
 
Dr Racaniello said
Not at all he said, PCR is the gold standard for diagnosing viral infections. When you think you have flu, your doc gives you a rapid test in the office. Those are antigen-based and are lousy. If the answer is negative, you go to PCR.
he missed the point.

Flu is actually a good example of the problems of PCR. It doesn't show up in blood, you have to look at respiratory secretions.

PCR works well if you know which probes and primers to use and if you actually have some of the virus in your sample, but that means you have to know which tissue to use and how to treat your sample to maximise your chance of getting a virus in it.

They have been trying to get PCR to work with some bugs for years.

It is not a "gold standard" for proving virus is there - photographing the virus, as Elaine De Freitas did, is the real proof and antibodies can be found even if the virus can't be isolated. What PCR does have is it is modern and "cool" as well as being automated (so cheaper). Diagnostic microbiologists are often mocked because their techniques have not changed much since the nineteenth century, they still grow bacteria on agar plates for instance. Virology, though, has come on in leaps and bounds and PCR is a chance to join in the biological revolution so it's advantages are often overstated.

It is also not a "gold standard " for diagnosing viral infections. The older methods of detection, even growing samples on eggs, showed that a virus was there. You might not know what was killing the tissue culture but you knew something was. Now you could diagnose the patient as having a viral infection. Exactly what virus it was needed more thought, but you knew they were ill. Hepatitis non A non B led on to the discovery of the Hepatitis C virus but that can't happen using PCR as even when it works wonderfully it can only find what you already know all about and have a test for. Combine this with the modern tendency to assume psychological illness if a simple set of tests are negative and our horrendous situation can only spread.

XMRV is not the only retrovirus which is hard to find. Many papers describe the problems of detecting animal ones using PCR. Amplification gives the best chance of finding anything. The WPI did this after using simple PCR and when the CDC came up negative they should have taken this simple step. It is the sort of thing a Phd student would be expected to do, never mind a major research organisation.

Mithriel
 
Excellent post Cort!

I'm agreeing with Mithriel here. Only if nested PCR works it really is a "gold standard", because the sequence must contain a lot of information, and pass stringent tests. When it fails, you are left wondering why. It doesn't give you much help with near misses. You have to start looking for fragments, then slowly piece these together. This must have taken place in the prehistory of work leading to the Lombardi paper, but has not been done by groups with negative results.

The observation of hypermutation in T-cell lines is very revealing. For one thing, it shows this bug does not behave like HIV, which negates considerable "expert knowledge". For another, both the mechanism by which APOBEC3 editing enzymes inhibit replication, and the means by which the virus uses sequences with synonyms to evade this imply this is a highly-evolved interaction, not likely to appear with a totally novel pathogen.

I would say XMRV is likely to be the first member of a new class of human retroviruses. These have likely been in human populations for ages, with only variants causing new outbreaks standing out from the background. Even things "everyone knows" about a number of illnesses without clear etiology will need to be reexamined.

Research is definitely moving.
 
Great article Cort. I have a very minor criticism. A lot of very important points were made in the latter third of the article (which was quite long). Would it help to make a few short dot points at the very start of the article, just to bring home the important parts of the interview. Cheers Russell.

Good idea Russell, I put some bullet-points in there.
 
Thanks, Cort for a superb piece. Finally someone (you) collected the information, the major players, and results to date and put it into a very cogent article. Dare we hope again? I think we may.
 
Very interesting article that really filled in a lot of the science behind what's going on. All that information about the editing especially was really fascinating.

I didn't understand this comment from Racaniello when asked about detecting XMRV with PCR; he seems to contradict himself, and to contradict what Mikovits is saying later about being trained before PCR, etc. [emph. added]:

No. The best way would be to find infectious virus. PCR doesn't detect infectious virus; nor do serological methods. But not everyone knows how to do virus culture. Nearly anyone can do PCR. To validate the role of XMRV in CFS requires examining many patient samples (thousands) and to do this by virus culture would impede progress. PCR will do the job.

If XMRV is infectious, and PCR doesn't detect infectious virus, then how would PCR do the job? Obviously I'm missing something, but I'm unclear on what he's really saying there.

It's also heartening to see that respected scientists like Dr. Racaniello are seeing the flaws in the CDC study. Hopefully when the two new studies JM mentioned are out, the CDC study can fall by the wayside as the flawed joke that it is.
 
Well, well, well... you are reading all these replies. I'm impressed. Article is a bit sharper and harder. Well done.

Rusty,

I've been here for a while (not as long as some) and I can tell you that Cort reads an amazing amount of what gets posted here and he does it along with doing all of the work required to keep this site working, the interviews with key players in CFS, etc., etc., etc. What I can't tell you is how he does it.

Based upon my limited time here, it is my opinion that this site is the manifestation of an unwavering commitment to the CFS community and Cort's dedication and amazingly receptive and balanced approach to all things CFS.

Phoenix Rising and all that it represents (and like anything else, it isn't perfect) is an amazingly powerful resource that informs and unites a lot of people that would otherwise be very isolated with their illness. PR gives us all the opportunity to be heard as a united and educated voice (or more likely, voices). I don't know that we could ever thank Cort enough for what he has given to the CFS community. I'm sure that he's played a some significant part in the change being seen in the CFS world over the last year.

Cort - Thank you!
 
cort,

thanks so much for this article!

can we find out WHEN the 2 replication studies are due out and WHO is doing them?

rrrr

I believe one is taking place in the UK using an independent lab; I think this is the Invest in ME (?) study. They seemed to start working on it pretty quickly...not sure who the other one is. It could be the CAA/Glaxo Smith Kline study but I don't know.

Thanks for the nice comments -Its nice to be able to focus on something that really grabs my attention. I can thank my MCS, which really knocked me out of the workforce, for that. :rolleyes:
 
hmmmm too bad on swedish guy; free associating here but after reading some of stieg larsson's stuff and what he implied about that country and then he turned up dead....my imagination can wander