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XMRV Buzz - Take a Deep Breath/the Big XMRV Meeting, Singh On XMRV, Sample prep?

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by Cort, Nov 5, 2010.

  1. Cort

    Cort Phoenix Rising Founder

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    Some people are missing the Buzz with the website down; here's what it would have said

    • Big Meeting in New York: Take a Deep Breath - XMRV's Time is Almost Here: [/B]- Amy Dockser Marcus reported that "W. Ian Lipkin, the Columbia University-based virus hunter tasked by the government with resolving some of the XMRV questions, is convening a meeting this week. Representatives from HHS and the academic and advocacy communities are in New York to develop a strategy for a study to determine whether XMRV is found at higher rates in CFS patients." Dr. Lipkin is to use the findings from the Blood Working Group to inform how he does his own study - but this is apparently bigger than a single study. Dr. LeGrice said about three weeks ago that the blood storage/contamination issues would be cleared up in three weeks. He was echoed by the NHLBI rep in her testimony at the same meeting. Now we have representatives from the government, research and advocacy organizations meeting sometime this week, which means, given that her blog was on Thursday, Thursday or Friday or it has already occurred.

    Dr. Singh on Detecting XMRV - the title of Dr. Singh's commentary in the Viruses journal went right to the heart of the matter. The problem right now is a simple one; "Detecting Retroviral Sequences in Chronic Fatigue Syndrome". That's the whole ballgame - that's all that anyone cares about right now - its ALL about detection - this was a timely article and it was nice to see someone tackle this publically. Dr. Weiss's Rumor Virus article gave a good historical overview of the sometimes extraordinary difficulties pathologists can face now given the immensely powerful technology available to them but Dr. Singhs article actually delved into the specific issues surrounding XMRV.

    • Splitter or a Lumper? Dr. LeGrice and others looked narrowly at the pMLV finding and stated that, until we know more, they should be treated as unrelated finding - which has its own logic. Dr. Singh took a broader view and stated the opposite; both have their own logic. For Dr Singh, considering that the pMLV's and XMRV share 95% sequence similarity sequences, the same receptor and, get this, are actually closer to each other than different variants HIV (85-95%), it appeared it was easy for Dr. her to place the pMLV findings by Alter/Lo firmly within the context of the Science papers XMRV finding. It's all about emphasis.
    • One Big 'Happy' Family? Is Dr. Singh implying these are all one family of of viruses that interact with each other like HIV does? Dr. Mikovits hinted, if I remember correctly, that more than one type of virus may be needed for them to survive in the body and Dr S. Ruscetti is reportedly looking at how these viruses combine with each other. There is also section of the pMLV's that we know can jump into other viruses...Are the pMLV's and mPMV's and XMRV's all one family????
    • Contamination - Dr. Singh felt contamination of the Lo/Alter samples was unlikely because the instruments used to search for it were 100 x's more powerful than those used to look for XMRV and the wide discrepancy in prevalence between the healthy controls and CFS patients. She noted, however, that with the exception of the 8 samples from present day patients that samples for most of the controls and patients were handled differently D) evidence of a replicating virus using antibody tests or actually finding the virus are critical E) (The same thing applies for the original Science study)
    • The 'Perfect' XMRV Study - But how to do a study that helps to clear up the confusion? That, according to Dr. Singh is certainly doable (and not easy) and definitely has not been done. That study needs to (A) collect blood from a large # of healthy controls and patients from the same area using the same techniques (B) the investigators must be blinded (a horrible fate but if it's necessary, it's necessary :) the Alter/Lo study researchers were not and the WPI study did not report it was in the Science paper) (C) negative controls on XMRV should be checked for contamination prior to amplifying the samples (D)detailing the limits of detection is important E) replicating one element of the positive study using blood from positive patients collected by a phlebotomy lab.
    • Note that Dr. Singh does not believe that it's necessary to replicate every procedure from the first paper - one is enough. We can guess that Dr. Singh's XMRV study probably :))) closely replicates her advice and we can get prepared for a very precise methodological section - probably the most comprehensive yet as she details exactly what she did and didn't do - which is what the National Cancer Institute, in fact, is asking XMRV researchers to do right now. Dr. Singhs autopsy study should be at the publishers now and her XMRV study is believed to be finished as well. Hopefully we will hear from her in another scientific journal soon.

    Sample preparation - Really? - the emphasis now is on 'sample preparation' with Dr. Mikovits reportedly stating that may be the major issue. Consider this, though; Dr. Peterson was able to dig up an XMRV positive sample in a sample that had been stored in his freezer for decades. The 'Peterson' samples collected over the years in his practice were considered too suspect to use in the WPI's Biobank - which started anew with new samples. Dr. Lo was able to find XMRV in samples that had been frozen for over a decade. Plus, the WPI was able to find XMRV in samples from some sort of blood bank, whose sample collection procedures are apparently unknown - at least in the detail at which the Blood Working Group is looking at. The upshot is that XMRV has been found several times in samples which appear to have been collected differently and certainly not with the kind of care that the BWG is looking at. Can sample collection really be the whole answer?
  2. Sasha

    Sasha Fine, thank you

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    Thanks for posting this on the forums, Cort - I've really been missing XMRV Buzz!
  3. Otis

    Otis SeƱor Mumbler

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    Seems like Le Grice went out of his way to be a splitter. He didn't win my trust that he just wants to follow the science in a balanced fashion. I'm a lumper, especially after Dr. Singh's rebuttal.

    Sample prep could be critical. A combination of how quickly samples are tested or frozen and with what types of blood tubes, etc., could make a difference. Low copy numbers would appear to make the samples pretty fragile new or old.

    Method still plays a role and perhaps pointing to sample prep is an attempt to divert hostilities over methods and "contamination" discussions.
  4. Jemal

    Jemal Senior Member

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    Yeah, thanks for posting.
    I have the feeling we can expect some big news this year. I can almost feel the air crackling with excitement.
  5. George

    George waitin' fer rabbits

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    I don't know if any of you ever watched the show ReGenesis but there is this great scene where the head retroviroligist finds a cell line is contaminated with retrovirus and sends out the information for other people including her assays. She get's a ton of replies back that she's nuts and cell line is fine. So she goes back over her stuff again and again and again. Finally this microbiologist comes into watch her check her findings, once again, and points out that while she created her own solution most of the other teams use assay kits now. The kits don't add the magnesium solution because it's considered an unnecessary amplifier. So she sends out the information to mix up the assay with the prescribe magnesium solution and voila she's not a nutter any more. (grins)

    That scene has really stuck with me through the craziness of the last year since Lombardi et al used their own solutions for their assays which they got from Dr. Silverman and refined from Dr. Sandra Ruscetti. I just keep thinking that it will turn out to be something just that simple and then we can all get on with the important stuff.

    I'm on pins and needles right now waiting for someone to leak the Phase II info, they promised to make it available as soon as they had it and I'm about to loose a tooth gnawing on computer waiting. Phase II is really for all the marbles, it's either gonna be "we're right and you're wrong" or it's "pack it up and go home". Please, please, please may I get the right to gloat, I promise not to do it for long. (paws together)
  6. Jemal

    Jemal Senior Member

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    I think we all want to gloat...

    If this was a bet for money, I would put my money on XMRV. I think it's going to turn into something big. It's already big.
  7. Esther12

    Esther12 Senior Member

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    If sample preparation is the key, surely that points to contamination as the WPI were finding XMRV in samples provided by the Zero Swedish (somewhere like that) study. [edit - was forgetting the preparation could include things to amplify the bugs... but surely something like that should have been detailed in the initial paper?]

    But.... if the BWG have found the problem is only with contamination, why would they be planning to set up more big studies?

    If my fatigue was anxiety related, it should have gotten a hell of a lot worse over the last year!
  8. alex3619

    alex3619 Senior Member

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    Hi, I really think the lumper/splitter argument is a yin/yang argument: every study needs to be both lumped and split until we know what is happening. That way nothing will be missed. My personal bias is with the lumpers: Singh has made a very powerful argument; but science shouldn't be based on personal bias, and we need to cover both bases.

    Bye
    Alex
  9. Cort

    Cort Phoenix Rising Founder

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    I agree - the suggestion that they are setting up further studies is a hopeful one. The only caveat I can think is that they could be simply being very careful; that is if they did find a contaminant then its possible they will show how to avoid it and then will test CFS patients all over again. On the other hand they may have found another problem (sample preparation) and will do the same thing. Whatever happens it appears that the testing will be redone or expanded now that they feel they are on solid ground. that's my guess.
  10. beesknees

    beesknees Senior Member

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    Thanks for posting. A couple days without the Buzz page is more than I can take. :)
  11. Sean

    Sean Senior Member

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    Bam! Right between the eyes.


    I promise not to gloat. Well, not much. ;) :D

    But I do claim the right to hold certain people properly accountable. Which is how it should be. Anybody who wants to exercise power over others must be accountable.


    The fact that they are doing further studies doesn't tell me much either way. If they decide it is contamination then they should be doing further studies to confirm it. It is too important to leave any possibility untested.
  12. MarxyGrouch

    MarxyGrouch *****

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    1. Why do you give so much importance to sample processing, when XMRV has been found in samples frozen for over 10 years (Dr. Peterson samples) and Alter-Lo found HMRVs in 15 year frozen samples? Clearly MANY other problems are influencing the results of negative studies. Methodologies that rely on PCR using a synthetic clone of XMRV that had NEVER been found in blood are very very suspect to say the least.

    2. Why do you say that the Alter-Lo handled patient and control samples differently when they have clearly said they did not, and when Dr. Singh said nothing of the sort in her paper that I can see?
  13. George

    George waitin' fer rabbits

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    " We" as in members of the forum are not saying either of those things. The accusations have been made by members of the scientific community. "We" the members of the forum are waiting, very impatiently, for the release of the phase II two BWG study to resolve, put to bed, reveal the truth to the nay sayers.

    Welcome onboard (grins)
  14. Berthe

    Berthe Senior Member

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  15. omerbasket

    omerbasket Senior Member

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    Correct me if I'm wrong - but as far as I know, "preperation" doesn't necceserily means "storage". Perhaps it's related to the centrifuges? or to something else? Besides - even "storage" might be the same in one aspect of samples from different times (for examples - the material in the tubes, besides the blood ofcourse) and different from other samples (that might have different material in the tubes, if we go by that example".
  16. Gemini

    Gemini Senior Member

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    Thanks, Cort, for posting this great summary as always!
  17. Cort

    Cort Phoenix Rising Founder

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    I think you're right. From the way Dr. LeGrice was talking it could mean almost everything -basically, every step in the process.....which is why, I believe, the NCI is asking for very detailed descriptions of protocols. I think its wide open.
  18. free at last

    free at last Senior Member

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    So true Cort, and it means those that have had a positive result and firmly belive they now have there answer could be devastated by all this, exciting times, but very worrying too.What a emotional roller coaster this year is for everyone. One thing that i do struggle to understand is Judy is now ( i assume always has been ) using labs that are Virgin from mice. Also shes looking for evidence of mouse DNA to rule out contamination. And so far none has been found. could this really slip through her detection of mouse DNA all this time ? seems unlikely to me. but of course i dont know enough of how these things work. But for those that do. wonder what there thoughts on this are ? Make or break time isnt it
  19. ixchelkali

    ixchelkali Senior Member

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    I hope Ian Lipkin takes Dr Singh's advice to heart. I'd like to see a few studies like that done.

    Interesting question about the relationship between XMRV and pMLVs and how they might interact. It would be interesting to find out if there's a difference between the pMLV profile of XMRV-positive ME/CFS patients and XMRV-positive healthy controls, in case that makes a difference in disease genesis. Not to mention prostate cancer patients. But I'm still betting on an interplay between some form of XMRV-like virus and other viruses (EBV, Ross River, parvovirus, HHV, et al). Like XMRV compromises the immune system in some way so that when you get any one of a number of different viruses, the immune system turns on and never turns off. Or something.

    I also wish they wouldn't look exclusively at blood as the virus reservoir. Sure, a blood test is simple, not very intrusive, and relatively inexpensive, so it would be ideal. But if blood isn't the main hang-out of the virus, I don't want them saying "It's not in the blood, so it's not in the patients."

    Waiting, waiting, waiting...
  20. Cort

    Cort Phoenix Rising Founder

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    I think researchers are stuck between a rock and a hard place; the WPI study and the Alter studies were good ones and the WPI study had lots of confirmatory evidence. Yet, I think they are really puzzled by the negative studies as well - so they are looking at areas they don't usually look at. Dr. LeGrice said contamination could come from anywhere - a reagant that picked it somewhere or a test tube or ?????. On the other hand Dr. Mikovits said and Dr. Alter reported searching for contaminants and not finding any. My guess is that isn't going to an easy or obvious answer for this...its going to be something that's unusual....a unusual sensitivity of XMRV to some sort of sample preparation or something that slipped in somewhere.

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