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BWG Phase Two Results - Webinar

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by jspotila, Dec 11, 2010.

  1. SOC

    SOC Back to work (easy, part-time work)

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    True. On the other hand, after today's seminar I'm confident that a positive CULTURE test from VIPDX is not at all likely to be a false positive or an artifact.

    They were describing culture as done by WPI as the "gold standard". They were NOT denying that WPI was really finding XMRV by culture. This is good, right?
  2. Cort

    Cort Phoenix Rising Founder

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    On the other hand that's true!!!! ...they seemed to fully accept the culture findings.....:). That's a good point. Well, that should prod them to work even harder to figure out what's going with the straight PCR......if they accept the culture tests then it must be there - so find it!

    My guess is that this bug has them stumped.....Someone told me that culture is not done that much any more; its kind of considered 'old (but proven!) technology"; I can't imagine that anyone expected culture to trump ordinary PCR - and for the culturing to be done far longer than is traditionally done...

    I actually see how people could take either side because I flip flop all the time - you can make a case for both sides. The only thing I know for sure is that this needs alot more study!
  3. SOC

    SOC Back to work (easy, part-time work)

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    Clearly, finding XMRV in blood is much harder than finding a needle in a haystack. A needle in a hayfield, maybe.

    Dr Singh's comments about long-hanging fruit come to mind here. They're working at the very limits of their technology.

    I think (in the scientific world anyway) it's no longer a question of "Is it there?" but "How can we detect it?"
  4. Cort

    Cort Phoenix Rising Founder

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    I guess this is why Lipkin showed up. I was surprised that he did show up in the middle of the game but I imagine this is why...
  5. alex3619

    alex3619 Senior Member

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    Hi I would just like to add in case anyone missed it that the samples were all from Peterson's cohort according to the webinar. bye, Alex
  6. LJS

    LJS Insert Witty Comment Here

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    I feel this is a bit of a miss-characterization, their tests have to be extremely accurate and very fast. People should not get the idea they are going to test the blood supply with an inaccurate test. I am sure you have watched the presentation by Dr. Louis M. Katz where he said the final blood screening test has to be over 99% accurate and it is a great primer on all the complexities in testing the blood supply. There is no way they are going a approve a test until labs are getting extremely repeatable accurate results on the same samples.
    Dr. Louis M. Katz presentation: http://www.youtube.com/watch?v=ex6iS_2RqiY

    -----

    With regards to the comments that many people are making that the BWG is only concerned about the blood supply. I do not know how you could ask or expect more from them. Their job is the protect the blood supply and all there resources have to be focused on that, they do not have the resources to study CFS. They are relying on others like Lo/Alter to determine if XMRV causes disease while they are trying to work out how to test for in a high throughput manner. A one month culture would never be an acceptable test for blood supply screening and is impractical for everything outside of a research setting or expensive low volume test patients can buy out of pocket.

    I am disappointed that they are not further along, the mishaps in testing, and didn't use more samples but I did not find their presentations negative or have a issue with any of the presenters. They spent a lot of time creating and presenting this information to patients and they obviously care but are limited in what they can do for us, their focus in the blood supply tests and restricted by the resources they have.

    The big problem is not the presenters today or even the labs selected to do the testing the problem is not enough importance and resources has been put on the need for a XMRV blood supply test so they are doing things in a smaller scale then maybe the would if there were more concern. They will get to the bottom of it but I am sure it will take longer then any of us would like. Our focus should be keeping the pressure on the people who make decision for the funding of XMRV tests and research.
  7. Anika

    Anika Senior Member

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    "Pedigreed Positives" - Persons vs Blood Samples - Virus in and out of blood

    One question I had from my (interrupted) listening to the webinar seems to be answered by earlier posts. That is, that the "pedigreed positives" were persons whose blood samples at one point were confirmed as positive by multiple labs. The samples themselves were not "pedigreed".

    There was an implicit presumption that the persons whose blood had earlier been "pedigreed positive" would continue to have positive blood for purposes of later sampling.

    Recalling the original macaque study, I think the virus couldn't be detected in the blood (vs tissues) at some point after infection was introduced. I don't recall if evidence of reactivation with virus in the blood later was shown in macaques. But I think that those "pedigreed positive" macaques couldn't always be relied upon to produce detectably virus-ridden blood.

    This seems consistent with what Mikovits and team have said, about multiple samples being needed to confirm whether a person had an XMRV infection.

    In light of Mikovits and now the blood group work, what is amazing is that Lo/Alter were able to get a positive test for MRV with fresh samples from 7 of 8 of the persons whose old samples had tested positive years earlier.

    The research is that much harder when you can't count on getting (detectably) MRV-infected blood from MRV-infected patients.
  8. pictureofhealth

    pictureofhealth XMRV - L'Agent du Jour

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    Another clue to discrepant results.

    Its great for the long term treatment prospects for us, if this was the case.

    BUT I don't think it was clever to select someone who was taking ARV's, or to have allowed them to continue in the trial under the circumstances.

    I'm mystified, surely scientists know basic abc on how to select candidates for trials? Selecting someone who is not being treated at the outset of a trial, and then is being treated during a trial, is a c*** up and an avoidable one.
  9. VillageLife

    VillageLife Senior Member

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    yep remember how everyone was saying culture just isn't used anymore, everyone was saying you should be able to do a quick PCR and find it.

    and yesterday the scientist on the webinar said.....Culture is the gold standard at the moment.
  10. eric_s

    eric_s Senior Member

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    I don't think we should be unhappy about the fact that the goal of the BWG's work is mainly to protect the blood supply. After all, we've complained many times why they're not doing more in that regard (banning blood donations, etc.).
    In the end this will lead to where we want it to, i think, if they are successful in finding XMRV. Because if it turns out that XMRV is in the blood supply and maybe even transmissible, they will have to find out what it does in the body. And this is what we want. A potential finding that it is in the blood supply and in the general population would certainly speed things up a lot and help us.

    And there is the Lipkin study to determine the role of XMRV in ME/CFS, so it's not like they don't care about that at all. Also the fact that the first meeting of the BWG was in december of last year, very soon after publication of Lombardi et al. in Science, shows that they took this serious right from the start.

    The only problem i have is that it might easily take another 4 months for phase III to complete :eek:. It's very frustrating and hard to bear how slow everything is moving.
    I have also noticed on the timeline presented during the webinar that in most cases the WPI was the last lab to return results. So we can't really blame the government, apart from not providing more funds to the WPI. Of course the WPI is doing a lot of other work, so that's not necessarily a bad thing for us. They are probably confidnet enough about their own testing and don't need the BWG to learn how to do it. But they would profit from being vindicated through the BWG results, i guess. This might lead to journals publishing their papers.
  11. garcia

    garcia Aristocrat Extraordinaire

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    This is the main issue. WPI lack funds, and since they are a key part of this whole thing, everything is proceeding much slower than it otherwise could. This in turn is leading to the delay in publishing papers (journals are reluctant to publish), which in turn is leading to the lack of funds. It's a real catch-22.

    Note to ME/CFS patients: The only way to speed things up is to fund the WPI, and to advocate vigorously for the WPI to be funded from government agencies.
  12. jspotila

    jspotila Senior Member

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    This is an unanswered question from the webinar - who was in charge of designing the study and selecting the samples?

    Another unanswered question is the amount of funding being provided for the BWG studies. The work IS being funded by REDS-II, so WPI and other labs are not having to pull money from other projects to run the BWG samples, but what is the level of funding? Is that why there were only 4 subjects and 1 control in Phase II?

    ETA: I will check on the final numbers for registered/attended, and report back once I have those.
  13. Otis

    Otis Señor Mumbler

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    Yes! Great post!

    My big lesson is that the BWG is busting their humps to get testing done and to provide us information.

    We need to turn up the heat on the decision makers to get funding for this work and for additional ME/XMRV testing.

    I also want to see a more balanced presentation of the facts. It shouldn't take a Dr. Alter smackdown to shut up the Contamination Accusation. If this is what is being said in public, what's being said privately to the higher-ups when they WANT to hear there is not a real problem? In my mind John and the Coffins (Stoye, Le Grice, etc) are a major source of disproportionate negative feedback that must be counteracted. Scientific skepticism is one thing, this nonsense is quite another.
  14. free at last

    free at last Senior Member

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    If the goverment now regognizes the WPI as a allie for a fuller understanding and assements of this risk to the populations,just like Alter and Lipkin, considering the WPI are already setup to help.

    Surely a cheaper very knowledgable allie for them, is right by there side, just needing some of that funding to help be a force in the long term.

    It makes no sense to deny funding to a group already setup, that obviously should be central to the whole goverment effort.I dont get the logic ?

    And as for the publishing embargo on wpi studys, thats because this confusion is really not being cleared up quickly enough,all those negative studys doing damage,which is why they should now be shouting loud and clear, yes Alter Lo are now finding xmrv in their samples,not just a variant. Nothing at the BWG meeting ?

    Someone in goverment needs to make a statement of support on their behalf (not just Alter] stateing that XMRV IS REAL AND NOT CONTAMINATION and the wpi are fnding it, and other goverment departments are confirming yes that is the case, its real, its not contamination,it is infecting humans, and likely causing disease. Im sorry, its time to simply just do it all
  15. anciendaze

    anciendaze Senior Member

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    There had to be reasons that nobody had stumbled across this in the past, even those who weren't concerned with CFS. Accidentally finding a new retrovirus in humans should have been a major discovery long ago. (Yes, I'm well aware of DeFreitas' work. She thought she was chasing a delta retrovirus. Had she been supported well enough to resolve the confusion she might have found this. Here I'm talking about others.)

    One clarification here, "straight" or "direct" PCR is a conversational term for something different from "nested" PCR, and this distinction is central to the dispute. The first stage of nested PCR amplifies a lot of junk. The second stage carefully picks out specific sequences. Varying the primers and conditions has enormous effect on sensitivity and selectivity. Used carelessly nested PCR can produce bizarre results.

    One discovery during the last year, (which has yet to influence these trials,) was that, at least in some cells, enzymes called APOBEC3 'hypermutate' inserted provirus. This is a natural defense against retroviruses; other mechanisms may remain undiscovered. Essential human genes are either not mutated by this, or are repaired by other cell mechanisms. The virus takes advantage of redundancy in the genetic code to use codons which will be converted to synonyms by these mutations. The result is that the vast majority of sequences inserted by the virus are not letter-for-letter copies of the reference viral sequence, which PCR typically requires.

    Because mutated sequences with substitutions leading to synonyms will produce the same sequence of amino acids in polypeptides, and the same proteins, these different sequences will produce the same virus. APOBEC3 mutates inserted DNA sequences, not the RNA sequences the virus uses for its genes. Some resulting virions will likely be competent to reproduce, and may be identical to the unmutated virus.

    This makes a stage of culturing virus essential to detection. Culturing has been specifically left out of these trials. How WPI was ever able to detect virus without it puzzled me. My tentative answer is that they chose patients with active infections, where immune cells infected by the virus were naturally activated and already reproducing to combat it. This fits the peculiar finding that the strongest evidence of virus often comes from people who are asymptomatic. If their immune system shows a healthy response to infection, something equivalent to culturing is going on. Newly inserted provirus has yet to be hypermutated. (This may also be relevant to the discussion about delayed processing.)

    Comments about any small number of false positives have to consider the wildly improbable things that happen when people are rushed and the situation is confusing. (We have plenty of reason to believe there has been confusion.) Some cases come down to such absurdities as applying a label for the wrong sample, or mixing up the box with guaranteed-clean sample containers with those still untested. If the sample is contaminated near the source it may say nothing about the lab. If you use large numbers of samples, the probability some will be false positives goes up. If you stick with small numbers, the effect of a single error with be exaggerated.

    (I can testify to similar mix ups in a completely different context where expenses are very high and development speed is important. In trying to trace the cause of failures in new electronics for important projects, one report I saw revealed the integrated circuit inside a package was an entirely different device from the one labeled on the outside. Avoiding these blunders is one aspect of the problem which raised the cost of generic ICs from 40 cents to $100 in some high-reliability applications. This seems absurdly excessive, unless you learn that those components control nuclear weapons. "All in favor of economy measures raise your hands." Eliminating these was neither cheap nor easy.)

    Funding for crash programs researching questions pertinent to national survival runs into the billions, with much wasted in retrospect. This question has not been funded that way. Many avoidable mistakes will be obvious in later analysis.

    Research on anything new is constantly chasing a moving target. Not only are many labs having to play catch-up out of the starting gate, they are competing with greyhounds who have nearly caught the hare. Expecting quick resolution in these circumstances is a recipe for disappointment.
  16. urbantravels

    urbantravels disjecta membra

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    Do we actually know whether the WPI has been "denied funding" and in what way? Does this mean they have applied to NIH grants and not received them? Which ones? The existence of NIH grants is public information.

    It is my impression that most applications for CFS research to the NIH get turned down, regardless of the investigator(s) who are applying. Do we have actual information that the WPI is being discriminated against more than any other lab?

    How well-funded is the WPI at this point? Has anyone looked at their financials?

    Before everyone jumps down my throat about being anti-WPI, I'm just saying that a lot of people are repeating things they've overheard about the WPI being "denied funding" and "denied publication" and all of this seems to be based on remarks Judy Mikovitz has made in talks. On the other hand...I've seen Andrea Whittemore herself correcting people on Facebook when they seem to be claiming that the XMRV breakthrough research was made via "one private insitution" (WPI); she pointed out that the research was a collaboration between WPI, the NCI, and the Cleveland Clinic. And the WPI's new building was funded through a combination of Federal money (research grant overhead), state funding, and private WPI money.

    I'm all for funding the WPI, but I am equally in favor of funding being made available to a diversity of investigators at different institutions, especially since the WPI is controversial in nature. There is a much larger, systematic problem about CFS research not being funded and not being published, and that needs to be addressed in a way that's not solely about what one single institution is getting.
  17. free at last

    free at last Senior Member

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    Agreed, but if a instuition as central to the xmrv problem cant get EXTRA funding.Then worrying about other institutions getting any seems a little mute to me.

    There was a appeal for funds recently for the wpi, and yes i guessed they was being straight.I didnt research if it was true or not, maybe i just trust those more, who seem to be wanting to actually help a group who have done so much for us. Infact thats a understatement. But agree CFS/ME is underfunded across the board
  18. OverTheHills

    OverTheHills

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    I know its hearsay as confirmation but I went to one of Nancy Klimas' talks for medics on XMRV & CFS a couple of weeks ago and she said something about the WPI had managed to get funding for this swanky new building but not for ongoing work. Can't remember her exact words (I'm doing well to remember anything at all, given my memory).

    PS I would like to echo Otis' thought that congratulations are due to the BWG for giving us the full facts, confusing as they are. Given the low level of trust from the patient community (very well-merited) and the confusing/unfortunate situation with the research, this is the only way to go. We patients need to consider our interpretation of the facts.
    I am cheered by the fact that the BWG are proceeding honestly. More money could be applied and experimental design improved I'm sure but this is no designed to be negative trial. And ALL the panel members voted for a ban (with 9 - 4 for a question). And Harvey Alter is very definitely on our side. A big name and an effective political force with his lovely speech.
  19. eric_s

    eric_s Senior Member

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    That's why i think it's better to fund research through a CFS org (if there is a good one) than as individuals. An organization can have much more control about what the funds are used for, can demand more insight, etc. I have no idea about the budget and financial situation of the WPI or other institutions, what it costs them to do what they are doing, and so on. Such things would be interesting to know, to see where the money is needed most. We (the people with CFS) should have more control, try to take matters into our own hands more.
  20. urbantravels

    urbantravels disjecta membra

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    The WPI occupies only part of the new Center for Molecular Medicine building; my impression is that the Federal overhead funding portion of the costs were covered by grants to other occupants of the building (multiple research groups from the University's medical school), not WPI. I don't know what percentage of the square footage of the building is actually occupied by WPI.

    The WPI is sending out fundraising appeals, but that in itself indicates nothing - every nonprofit sends out funding appeals at the end of the year. It's a crucial time for donations because many donors make last-minute decisions at the end of the tax year.

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