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XMRV Webinair - Results of BWG - Q&A Video and Slides

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by Firestormm, Oct 16, 2011.

  1. Firestormm

    Firestormm Guest

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    14 October 2011: http://www.research1st.com/2011/10/14/xmrv-updates/

    I can't believe this hasn't been posted elsewhere (maybe it has?) anyway, I have been without the internet for a few days, but this was very interesting:

    'The CFIDS Association of America hosted a webinar on Oct. 14, 2011 to provide information about the Phase III results of the multicenter study of XMRV known as the Blood XMRV Scientific Research Working Group (SRWG) study. The results were published on Sept. 22, 2011 in Science. The webinar extended a Sept. 23, 2011 presentation given at the IACFS/ME Biennial Research Conference in Ottawa. Here are details about links to the webinar materials:

    Title: Results of the Blood XMRV Scientific Research Working Group Study
    Speakers:
    Graham Simmons, PhD of Blood Systems Research Institute
    Michael Busch, MD, PhD of Blood Systems Research Institute
    Steven Kleinman, BSc, MD of University of British Columbia

    Link to slides: http://www.cfids.org/xmrv/srwg-webinar-oct2011.pdf

    Link to webinar recording: http://www.youtube.com/watch?v=ayUUIT85KZQ&feature=channel_video_title


    During the webinar, Dr. Simmons addressed 10 common criticisms of the SRWG study that have been posted in several online discussion groups. They are listed below.

    The speakers addressed other questions submitted by registrants and during the presentation. They also presented a sequence analysis of the three positive PCR results obtained by the Whittemore Peterson Institute (WPI) lab that shows the sequences to be consistent with contamination with 22Rv1.

    From the webinar:

    Answers to 10 Common Criticisms of the SRWG study by Graham Simmons, PhD

    1. All of the controls were not screened by all of the labs.

    Response: Controls were screened by at least five labs: WPI, National Cancer Insitute/NCI-Ruscetti, Food and Drug Administration/FDA-Lo, Centers for Disease Control & Prevention (CDC) and NCI/Drug Resistance Program (DRP).

    2. Control peripheral blood mononuclear cells (PBMCs) were not screened prior to blinding, so could not have been ruled as negative.

    Response: Three out of the 15 did have their PBMCs extensively screened prior to blinding, yet two of these were still called positive in various assays by the WPI and NCI/Ruscetti in the study.

    3. No cryopreservative was used for the storage of the PBMCs, which would prevent the WPIs assay from working. No Trizol was used.

    Response: Due to the short-term nature of the study it was not felt that preservatives were required for PBMC cryopreservation. The Lo/Alter study detected sequences in PBMCs stored for 15 years in the absence of preservatives. Trizol is for the extraction of nucleic acid and laboratories were given the option of choosing their own extraction methods

    4. The length of time allotted for the serology and culture assays was massively reduced, so that the WPI or NCI/Ruscetti assays were not performed as desired.

    Response: All the laboratories were allowed as much time as required to perform their desired assays. The culture and serological assays were performed by WPI and NCI/Ruscetti to their own specifications.

    5. The WPI was not given the opportunity to complete virus culture assays.

    Response: The WPI encountered mycoplasma contamination of their target cell population, and used the plasma samples without results. This was very unfortunate. There were no further stocks left to perform repeat cultures with. It was deemed by both the WPI and the working group that performing the studies on freeze/thawed material would be invalid.

    6. Samples and collection tubes were handled in the same laboratory as 22Rv1 cells used to spike the analytical controls.

    Response: As stated in the paper, 22Rv1 cells were handled in a separate facility to where all other activities were performed. The fact that only one laboratory detected PCR and virus culture in clinical samples supports the fact that 22Rv1 contamination did not occur at the central laboratory.

    7. Patients were on additional therapies that would produce false negatives.

    Response: Lo/Alter patients were not on any additional treatments. It is unclear what additional treatments patients were on at the time of Lombardi et al. There is no published evidence that additional treatments would have positive or negative effects.

    8. FDA/Lo used the wrong assay from Lo et al. and instead used the one that could not detect positives.?

    Response: Lo et al. used their own criteria to decide on which assay(s) to use, but it is clear that both primer sets in their paper are equally capable of amplifying diverse polytropic murine leukemia viruses (MLVs), so it is not obvious that one would be better that the other at detecting positives.

    9. The NCI did no PCR and could not use their clinically validated serology and culture assays.

    Response: NCI felt that they were not sufficiently experienced at PCR to participate in the study. They did perform their serology and culture assays just as performed in Lombardi et al.

    10. All the SRWG labs optimized their assays to VP62. VP62 does not exist in nature and Lombardi et al. is now known to have discovered HGRVs. Does your study include HGRVs? Or how do HGRVs relate to XMRV?

    Response: As demonstrated in an earlier slide, although this study was initiated after Lombardi et al. as a study of XMRV, as soon as Lo et al. was published the mission of the study was broadened to include all MLV-like viruses. Thus, almost all of the assays were designed to perform against MLVs in general and were optimized and tested as such. As our study has demonstrated there is no such thing as an independently validated clinically positive sample against which to test. Currently there is no such thing as human gammaretroviruses (HGRV). No published virus has been isolated, cloned or sequenced from a human.
     
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  2. Boule de feu

    Boule de feu Senior Member

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    I'm so glad you posted this. I had register for the Webinar but woke up to late to attend. I was pretty upset! I can't wait to hear what they had to say.
     
  3. Nielk

    Nielk

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    Yes, Firestorm. This was very informative. Thank you for posting.
     
  4. jace

    jace Off the fence

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    It is still not clear still whether all controls were screened by all labs

    But PBMCs from 12 of the 15 were not screened before blinding

    Not possible to order more LNCaP cells? Sold out all over the US??

    Contamination may have come from another source than 22rv1. Apart from that, did the same personnel work in both places? Was the tube inspection done all at once, or in batches at the CDC? Were the WPI and NCI sample batches handled differently in any way at any time from prep to point of distribution?

    Since which virus is being looked for is not agreed, and since nothing works anyway for CFS according to established thinking, it is not surprising that the question of what treatments donors were on is dismissed out of hand. However, some of us may beg to differ.

    The paper states, with modifications

    So the primers would have picked up any MLV-like virus?

    The BWG did not use clinical positive samples, but rather samples from people who had previously tested positive.

    Really poorly right now, but I could not let this pass. I may not be back to respond to responses.
     
  5. Firestormm

    Firestormm Guest

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    Afraid my internet went down on Friday so I wasn't able to listen in live or ask some questions but they seem to have posted answers to much of what qualified as 'criticisms'. Am listening to it now actually, and will try and transcribe something from it later maybe.

    Fascinated to discover (though it was mentioned in the paper) that WPI/Lo were not able to come up with the originally promised 25 'positive' samples. This seems to be why only 15 'positives' comprised the study.

    Amazing when you think that so many 'positives' had been advertised previously - must be some reason for them not being able to produce even 25 I guess.

    Anyway, back to the broadcast. Oh you can leave comments on the CFIDS site - Research 1st - through that very first link (in bold).
     
  6. SpecialK82

    SpecialK82 Senior Member

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    thanks Firestorm, I wasn't able to watch either.
     
  7. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    More overreaching from the anti-HGRV virologists. They phrase this to convey the impression that they are sure that no HGRVs exist, not that they haven't been proven to exist their satisfaction. This kind of sloppiness (or obfuscation) is unacceptable.
     
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  8. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I'm afraid the whole things reads like a PR response carefully worded to mask over cracks. Still as long as they are trying so hard to say one thing, it can only mean the opposite.
     
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  9. Firestormm

    Firestormm Guest

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    When such a thing is discovered no doubt the whole scientific community will be fascinated. As it stands, and as was said above quite clearly (though obviously not clearly enough for some to suggest otherwise), suggestions that HGRVs exist or that they have some association with 'CFS' are theories at best.

    How hard can it possibly be for someone to prove they exist? I mean after all this time we have heard and seen nothing from Mikovits or any of the others supporting this theory, and yet now that 'XMRV' is dead, we are suddenly being told 'it' was really something else? Bring on the evidence and people will sit up and take notice.

    The BWG was begun within months of that Lombardi paper. Those who contributed and signed off on the results had nearly TWO YEARS to provide samples and carry out testing as they saw fit. And the results were NOT supportive at all of the association claimed in Lombardi et al.

    I believe Mikovits herself was quoted as saying 'We got it wrong' or words to that effect?* Will try to dig out the quote if you like although a statement to that effect might have meant more to those who had bought all the scare stories resulting from that paper.

    Anyway, back to the broadcast - I am listening for a second time today and will make some notes/transcribe if I am able :cool:

    Edit:

    *'The next day, Mikovits presented the results of the latest study negating her research at a CFS conference in Ottawa, Canada, where she shared the podium with retrovirologist John Coffin of Tufts University in Boston, an opponent of her hypotheses. As a Science news article reported, Mikovits did not make a case for XMRV, admitting she may have been wrong about it. Instead, she proposed that CFS patients were infected with an XMRV-like virus from the gammaretrovirus family. Few at the meeting swallowed this alternative theory. As Swedish retrovirologist Jonas Blomberg told Science: Its like the argument follows the availability of the data.

    http://blogs.nature.com/nm/spoonful/2011/10/theres_no_tiring_of_controvers.html

    Will have to find that Science article now for the actual quote I guess!
     
  10. Lee

    Lee

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    justinreilly:

    "They phrase this to convey the impression that they are sure that no HGRVs exist, not that they haven't been proven to exist their satisfaction. This kind of sloppiness (or obfuscation) is unacceptable."

    I guess you could say it that way, if you are wiling to interpret the fact that there is no repeatable evidence for HGRV's in humans to mean "they haven't been proven to exist their satisfaction."
     
  11. barbc56

    barbc56 Senior Member

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    The results of the BWG are very definitive.

    The 10 questions really answered a lot of questions that many have been asking.

    I think it's time that we move the focus of research in a different direction.

    While I don't think the last two years have been completely wasteful , the questions about xmrv/hgrvs could have been answered much sooner.

    Thanks firestorm.
     
  12. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    Just to be clear, I am not saying that HGRVs have been proven or that they will be proven to exist. I am saying that many of these scientists who oppose HGRVs make clearly overreaching and unsupported absolutist conclusions they send out in press releases and quote to media such as "XMRV is not a human pathogen", "XMRV does not cause 'CFS'" (back when it was not clear at all if it was or wasn't) and now "there is no such thing as HGRVs, currently." They are scientists so they are exquisitely aware of how to phrase things so as not to overstep the evidence. All these type of statements clearly overstepped the evidence available at the time they were made; they know that they're overstepping. This bias is not cool. again, i am not arguing for the existence of HGRVs (we need more evidence) i am saying all this bias is not at all acceptable.
     
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  13. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    It is my impression that Mikovits oversteps the evidence sometimes herself. This is not acceptable either.

    She has, though, been saying for quite a while that the focus should be on HGRVs, not really XMRV per se. Blomberg is upset that she is changing her theories to conform to current evidence. If he thinks this is unscientific, I think he's in the wrong business.

    I do understand the uneasiness of some scientists who wish there were more published evidence from Mikovits to support her presentations. She says she is having difficulty with funding and publishing because of the bias against bona fide ME science. Well, we all know the former (funding bias) is true, the latter (publishing bias) we all know is entirely consistent with the long history of ME science, though we can't say for sure without more information. Maybe she should spend more time in the lab rather than speaking on unpublished evidence; that sounds reasonable to me. I feel the level of invective against her is unwarranted though. I would like there to be a level and fair playing field for everyone.
     
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  14. Lee

    Lee

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    The idea that Mikovits could not publish because of 'publishing bias' is... well, I'll back off and be polite and say not well founded.'

    She got her original paper in Science. labs all over carved time out of their operations, and did follow up work, and got published. All those negative result papers. Alter and Lo got published. She sparked a bandwagon that led to, what is it, a couple dozen papers so far in the 2 years since Lombardi 2009?

    She had a head start - she was already doing the work. Where is the actual evidence for ANYTHING she has done since then. Not the claims - the evidence?

    Publishable work gets published. There are dozens of relevant journals that she could choose from. if she wants to be sure it gets published, she can drop a tier or two in journal prestige, to be sure it gets in - if it is publishable quality. Where's the work?
     
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  15. barbc56

    barbc56 Senior Member

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    To Lee, anyone who understands the science better than I do.

    If I remember my study design terminology correctly, wouldn't this be a case of a priori, which determines whether something is plausible to study? Given the number of studies published, the science knowledge we've gleamed from these studies, wouldn't that mean that the likelihood of finding hgrvs in future studies be low if almost nonexistent?

    Thanks.
     
  16. Firestormm

    Firestormm Guest

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    Obviously I am not going to begin to try and answer that one - though I get the gist of what you are saying.

    Me? I am still struggling with all the definitions HGRVs XMLVs XMRVs etc etc etc I have to look the darn things up every time I read a paper and especially before I even think about posting anything Lol

    I swear this condition is NOT conducive to reading science papers [period]. :D
     
  17. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    i wouldn't be so quick to condemn. it took komaroff 5 years after he wrote his landmark study up to get it published finally in 1992. the bias against bona fide ME science is huge. it seems like a judgment call, but yes, if it were me i would try to get it published in a lesser journal just to get it out.
     
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  18. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Are you and your three pals (persistently loyal aren't they) the only people on this forum who still believe in the impartiality of publishers? (rhetorical, don't bother answering. There have been enough studies on publisher and study bias to disqualify your comment completely).

    It was Mikovits herself that said she could not get published . So, despite your claims of being polite, you have just accused her of lying.
     
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  19. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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  20. currer

    currer Senior Member

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    I seem to remember the Ashford 50 study was an abstract, too at the first international XMRV conference last year.
    http://regist2.virology-education.com/abstractbook/2010_8.pdf

    Also Bob wrote a blog in which he collects together all the studies we had heard of since this began...published and unpublished
    http://forums.phoenixrising.me/entr...XMRV-studies-published-and-unpublished-papers

    And there is this (a favourite of mine)
    Development of XMRV producing B cell lines from lymphomas from patients with Chronic fatigue syndrome
    http://www.retrovirology.com/content/8/S1/A230

    And this, which was done with Dr Mikovits
    http://trialx.com/curetalk/2011/10/...-positive-judy-makovits-anti-retrovirals-cfs/
    http://www.scribd.com/doc/39288353/Ppt-CLL-and-XMRV-Houston-2010-1#
     
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