1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Science to Patients: Talking ME, Exercise and the Mitochondria - with Dr Charles Shepherd
The latest video release from the Dutch group ME/cvs Vereniging, with Dr Charles Shepherd from the UK ME Association, and announcing a live chat session to be held Thursday, April 10, 2014...
Discuss the article on the Forums.

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

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    I agree that the focus on the blood seems unfortunate. We should have, though, Dr. Singhs autopsy study coming up which should show researchers were else in the body to look. The WPI study, though, did find XMRV in the blood in a high percentage of patients and I imagine that is going to have to be validated before they make a push elsewhere.
  2. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    My question is..if they had this meeting last week - why haven't we heard anything? I wonder if Amy Marcus was off a bit in her timing.
  3. Francelle

    Francelle Senior Member

    Messages:
    444
    Likes:
    15
    Victoria, Australia
    Is it usual to reveal findings only part way through a research trial to the public? I thought not. This is just the end of phase 2 of the BWG trial isn't it, with several stages yet to go?
  4. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC

    Yes, it would be if it was a research study but this is more a research effort by the federal govt to clear up confusion in this area - apparently a very different thing. They've said that they would reveal the results as quickly as they get them.
  5. George

    George waitin' fer rabbits

    Messages:
    846
    Likes:
    44
    South Texas
    Yes this is part two of four, however the BWG has promised to reveal each stage. If you remember they revealed phase I on which groups could detect XMRV and at what sensitivity earlier this year. (the little orange graph, remember that?) Phase II was promised by the first week of November by Dr. Glinnis (sp?) of the BWG at the CFSAC meeting. We should see results of Phase III no later than the first week of January. The final phase IV before the April NIH conference.

    I'm hoping and would bet a bone that the April conference will be followed by a public announcement and we'll be off to the races. Right now I just want my pooping Phase II results!!!!!!!!!!!!! (growl) Why is it so hard to get these people to do what they promise?
  6. Gemini

    Gemini Senior Member

    Messages:
    373
    Likes:
    187
    Good news! Links to BUZZ Website back up on 11/7.
  7. Sasha

    Sasha Fine, thank you

    Messages:
    7,437
    Likes:
    5,304
    UK
    Today! Excellent!
  8. SA2

    SA2

    Messages:
    20
    Likes:
    0
    I have several major problems with the idea of XMRV as contamination and not a human infection.

    1. What is the source of contamination? That is, what besides humans is infected with XMRV in enough abundance that it crops up in so many different labs and different procedures? If it's lab mice, which mice are they and how is it that primarily only samples from CFS patients seem to get contaminated? This simply does not add up.

    2. Why is it that other primates such as monkeys get infected (and remain infected) and in vitro human cells get infected by XMRV, but somehow humans and particularly CFS patients somehow cannot be infected by XMRV? And if humans can be infected by XMRV why is it not happening? This also does not add up.

    3. If its contamination, then how is it that the WPI Britain BLINDED study found it primarily in the CFS samples, yet again? If it's contamination, then a blinded study would show approximately the same amount of contamination across all samples, since even some difference in procedures would affect the samples randomly and roughly equally since the researcher has no idea which sample is which. This also does not add up, at all.

    4. Why is it that so many researchers (WPI, Alter-Lo, Spain, and others) are consistently finding XMRV in about 70% of the CFS patients and ~4-7% of healthy controls, if its just a contaminant? You would expect a contaminant to produce results all over the place, not 70% or 0%.

    Whether XMRV is the primary cause of CFS is certainly still up in the air, but explaining the above problems away as some sort of contamination due to sample preparation, research procedures, or whatever, seems well beyond believable.
  9. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    Good point. You'd think it would be one reagant or one something. On the other hand mouse DNA is apparently everywhere. On the other hand -everybody knows that and both the WPI and Alter searched their reagants (I believe) for it and didn't find it.
    Right, one question here which someone made me aware of is that in none of the positive studies were the patient and healthy control samples prepared the same way - when they were collected. Nevertheless! Contamination would presumably have come during the preparation phase for the PCR - and that should have effected both groups equally. Score another point for no contamination :)

    I think they do think humans can be infected - the question is which humans and where the infection is. The apes were infected, as I remember, by actually injecting them with it.

    Good point! Score another for no contamination :)
    Agreed!
    I don't think its unbelievable because respected researchers are suggesting it. Even Coffin is leaving that door open - but it does seem very difficult for everything that needs to line up to line up - for contamination to be the cause. On the other hand, if it isn't contamination I think they can't figure why so many groups can't find it either. We should know soon.
  10. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    Here's the latest from the Buzz by the way (its not up)..I'm beginning to wonder if there was a big meeting and if there was one, why?

  11. Otis

    Otis Señor Mumbler

    Messages:
    1,116
    Likes:
    115
    USA
    And if those respected researchers wish to stay respected they should put forth a cogent theory or shut the hell up. I find it unbelievable but that's just me.

    Coffin has been very standoffish at least since the 1st International XMRV conference. He seems to want to "say above the fray". From my perspective he has abdicated leadership in working towards getting to the bottom of this and has opted rather to loll in his swimming pool, which quite frankly isn't a mental image that's easy on the eyes. Coffin should have come down from the mountain with talking points long before Dr. Singh's recent effort or turn over the mantle of 'grandpa retrovirus' over to someone else, preferably Frank Ruscetti.

    Anyone leveling a contamination charge should answer the critics just as those researchers with positive results must first ensure they don't have a contamination, then convince the peer reviewers (and apparently the publisher's lawn service) there is no contamination and then fend open ended accusations ad nauseum. But if you want to put out out a quick and dirty PCR-only 0/0 study no equivalent set of hurdles are presented and you are welcomed with open arms into the 'It's Contamination' club with a dozen rotten eggs to throw.

    The double standard really pisses me off and the lack of equivalent scrutiny across the papers does not speak well to the "scientific process" when in fact it's neither scientific nor a process in this case.
  12. akrasia

    akrasia Senior Member

    Messages:
    156
    Likes:
    179
    Hi Otis,

    You have to wonder what other conversation about a serious illness would tolerate Le Grice's invoking John Coffin's swimming pool. Call it the argument from ubiquity; contamination is everywhere, pity the poor scientist.

    All the opponents of XMRV in M.E. have to do is invoke the possibility while claiming that their PCR method is "state of the art", shielded from the corruption afflicting all the other positive results, and research should come to an end. Curious isn't it, that the only labs that escape the demon contamination are those that can't/don't find XMRV/MLVs at all. And all the very sound, logical criticism, some of which was just recounted in another thread, is never engaged.

    It's like the "Godfather":I am convinced that you need "protection" by other scientists who have both individual and institutional cachet if you are going to launch a major new scientific truth into the world. Without the Ruscettis, Bob Silverman, Alter/Lo and their powerful institutional affiliations, XMRV in the PBMC of people with M.E. would have a very difficult time surviving.

    Why is Ian Lipkin being made the arbiter of anything? That is completely inimical to the scientific process, The good news is that whatever he comes up with will not be allowed to stand uncontested by very prominent voices. And Singh's autopsy study, if it demonstrates that like what was shown in the macaques, that xmrv is present in many places in the body, will challenge the supremacy of the blood as the major reservoir of disease, pointing towards the necessity of evolving a more global view of the pathogenesis of the illness. I remember someone saying that Mikovits told her when she came up negative on the culture and antibody tests not to worry that she very well might have the illness but it's gone deep into tissue.

    We've privileged the blood as a means of discovery for too long and the elusiveness of MLV bears witness to this. It seems truly stupid to limit investigation to convenience and economics. Anyway, in spite of the dismaying, unappetizing spectacle we've been treated to, I'm still with Frank Ruscetti and his prediction that this intellectual crapfest will be over by the new year.


    Otis wrote

    The double standard really pisses me off and the lack of equivalent scrutiny across the papers does not speak well to the "scientific process" when in fact it's neither scientific nor a process in this case.[/QUOTE]
  13. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    I imagine that they do have a cogent theory for all of this - they are just not communicating to us about it - they've left us out, which is bad, because they really are engaged in this topic and they know that. I wish to God I had asked LeGrice about the antibodies and the ability to grow the virus at the CFSAC meeting - I just spaced it out.

    I agree that the onus is now on the WPI - and there is little public discussion of the other possibilities - which is rough. Hopefully all the other possibilities are being explored behind the scenes. I imagine we would know from Judy if they weren't be being explored. So hopefully this is just a difficult time in which they have to grin and bear it and it will work out in the end.

    Coffin is definitely staying above the fray - I think he must either be unclear about XMRV or he is one of those guys that wants to stay above the fray.

    I imagine they are discussing the difficulties ad nauseam. I looked at LeGrices presentation as a warning - not a statement -he did ask researchers to provide every detail of their protocols to them. I agree that his presentation was weighted towards contamination - but they are pursuing other possibilities as well.

    There is no easy answer for any of this - sample preparation? The WPI found XMRV in samples prepared by some blood bank........the prostate clone? Not everyone used it and several studies failed to find conserved sequences for pMLV's as well - they looked for both. They should have at least been able to pick up conserved sequences that are variable that are found across all MLV's - but they didn't. And of course the contamination has a boatload of problems.

    For me this is nothing more than a mystery.

    Coffin lolling about in his swimming pool is not a pretty image :)
  14. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    428
    Raleigh, NC
    It's only when you actually find something that contamination becomes a possibility

    I agree that no one has publically countered the logic.

    Absolutely. Although I think that's true with any major discovery and I would say 'validation' or the credibility given by them. We've seen again and again that that is the way of science - like many other fields. If you are not well known then you need the credibility provided to you by well known and respected members of the field to make a big difference like this.

    I don't know why (or even if he is, according to Amy he is) but isn't this just how it works? The top names in any field lead the major efforts. They have earned others respect and they listen to them. According to Susan Vernon Ian Lipkin does by the way believe a pathogen is causing CFS and he is currently engaged in two studies on CFS. Dr. Montoya, a huge friend of CFS, was recently quoted as saying that Ian Lipkin would get to the bottom of the discrepancies. He's a huge name in pathogen detection - who else would rather want?

    That is a good point! It'll be interesting to see if XMRV presentation coincides with disease; ie does XMRV infection in X organ lead to organ damage or death?
    The WPI found it in the blood -that was what started the whole year on XMRV - I think the research community feels they have to duplicate their results.

    I agree and I think Chia's work bears this out - except that he can find enteroviruses in the blood as well. But how do you access tissues - you have to take biopsies - maybe that's what it takes, doing biopsy after biopsy.

    Looking forward to Frank Ruscetti being proved right.
  15. Sean

    Sean Senior Member

    Messages:
    1,155
    Likes:
    1,693
    Agree with that.
  16. pictureofhealth

    pictureofhealth XMRV - L'Agent du Jour

    Messages:
    534
    Likes:
    1
    Europe
    I think the Blood Working Group need to be able to have a workable blood test - to know if its in the blood supply. That at least makes sense to my mind - no point in going for a tissue sample there.

    As far as the rest of us go though (those of us patients who are already ill and the general population that need to be tested), totally agree that tissue sampling is the best way forward. Is it really necessary to have an painful operation or invasive biopsy to access body tissues though? How about just scraping cells from the nasal sinuses with a swab, or testing semen samples from men and menstrual fluid samples in women (which comes from the inner/tissue lining of the womb) or cervical smear tests for XMRV? How about scraping the tongue for cells, or testing saliva, or tears (from the eyes, which are natural extensions of the brain)?

    There are so many other creative ways we could try and find XMRV tissue samples - and I guess/hope that once Dr Singh's monkey autopsy studies are published, we will have a much better idea of where to look first.
  17. Sasha

    Sasha Fine, thank you

    Messages:
    7,437
    Likes:
    5,304
    UK
    Argh! :eek:

    Phew! :Retro redface:
  18. Mark

    Mark Acting CEO

    Messages:
    4,462
    Likes:
    1,846
    Sofa, UK
    Regarding the blood test issue in general, I agree with the point you're making here Cort, it does make sense to try to detect XMRV in blood given that's what the WPI claimed. And it also makes sense to pursue blood tests because they're cheaper and easier; that's not an irrelevant argument. It's just that the point about tissue reservoirs is valid as well and researchers should rather explore those possibilities than just dismiss the whole thing.

    But the part I have to disagree with is the idea that "the research community feels they have to duplicate their results". Given that, a year after the Science study, nobody has even attempted anything that could fairly be described as a "replication study", it seems to me that nobody has even tried to duplicate their methods! The impression I get is that the research community feels a need to debunk and bury this whole business as quickly as possible, based on their assumptions that (a) all new virus discoveries are likely to be "rumour viruses" caused by contamination, (b) ME/CFS isn't really a biological/immune disease anyway, (c) whatever ME/CFS is, it's not a consistent single phenomenon so it's unlikely to have a single virus at the heart of it. It seems really clear to me that these 3 assumptions (all of them likely to be false) have coloured a lot of the thinking, in the UK at least.

    Finally, since we are discussing "contamination" yet again (yawn), it seems relevant to mention that the WPI fully sequenced 2.5 of the XMRV samples they isolated. These sequences were not mouse DNA, nor human DNA, and since they were sequenced I don't really see how there can be much dispute about that: whatever it was that WPI detected in the Lombardi/Science study, it was not mouse DNA contamination. It was XMRV: they sequenced it.

    So (along the lines of some posts above in this thread) if there were a contamination issue, it really has to be contamination by XMRV itself, surely? In which case, if this XMRV contamination is so widespread, one has to wonder whether the contamination-theorists think this XMRV that's floating around in labs and/or reagents has the potential to infect humans? I can't really understand how one can accept XMRV is an infectious retrovirus that can infect human cells in vitro and establishes an efficient spreading infection in monkeys, say that XMRV is a widespread contaminant in laboratories, and then dismiss the idea that XMRV is present in CFS patients on the basis of negative studies that can't find any XMRV anywhere.

    As has been noted many times above, the contamination-theorists do need grilling on what their actual theory is. But sadly, as has also been noted above, those contamination-theorists simply don't engage with any of the good counter-arguments, and resort to innuendo and smears instead. It's that kind of behaviour that makes me so comfortable with disregarding their findings and comments as untrustworthy and unreliable.
  19. Otis

    Otis Señor Mumbler

    Messages:
    1,116
    Likes:
    115
    USA
    Rumor Contamination: Put Up or Shut Up

    Boy I sure wished you would have asked Le Grice about that too. Perhaps I would feel better about Le Grice and his personal and scientific motives. As for the conversations to which we are not privy, I would say, "If you want to engender trust in this process then speak openly and in a detailed manner”. With patients in the room, on the video conference and watching it later, Le Grice's warnings took up a great deal of air-time without saying anything specific. Put up or shut up, my life is riding on your professional behavior. Posturing without substance, whatever the reason, is morally wrong. Don’t hide behind “scientific skepticism” with thin arguments about (rumor) contamination.

    I’m leaving open the possibility of XMRV just being there by happenstance but want to see this science nailed down openly and honestly and while I still might actually benefit from a treatment. Too many just seem to just want it to go away.

    People have gone to the trouble of putting rebuttals (some rather poor ones) to both the Lombardi et. al and Lo/Alter papers in the journals in which they were published. That's the bright light under the big top where the brave people stuck their neck out originally and did amazing work in the face of strong opposition. Go put forth the theory there rather than some half-baked notion in the halls of a conference. Put up or shut up, my life is riding on your professional behavior.

    As we know, there are obvious reasons to slow down research such as keeping panic in the public at bay, being able to say the blood supply is protected, all those disability/health insurance costs, SSDI costs, and George’s favorite – to have a cure before acknowledging the virus. I hope we don’t have to wait that long.

    Mark covers the attitudes and the desire to make this go away quite well.

    I’m not really sure what you’re driving at here. I don’t think the onus is on the WPI for anything right now in the context. Please clarify as I don’t believe until such time as a plausible, thorough and written contamination accusation is made it’s all Rumor Contamination. Again, put up or shut up.

    I would say it’s the latter and I’ve lost a measure of respect for the man who is one of the few people who could have gotten all the kids together and said “Shut up and color” but he instead has chosen to be aloof. It’s not hard to come to the conclusion that HE considers NOT being “neutral” to be a tenuous position. Neutral in this case means allowing unsubstantiated rumor contamination accusations to proceed unchecked.

    And who but Coffin might have selected Stoye to keep out “discussions of ‘policy’”. His mentee would have appeared to have served his master well.

    They are covering the topics at a high-level ad nauseam. The depth, more precisely the lack thereof, is what greatly concerns me.

    We are in agreement Le Grice served up a warning. A statement would have been more acceptable. The effect appeared to be extremely polarizing which was unnecessary. He picked the single bullet point on many slides to cherry pick his argument and apparently used the fact that pre-publication data was unavailable and thereby used only negative information to harvest his negative talking points. Not to mention it’s possible one of Dr. Mikovits’ “rejected” papers may very well have been presented at the conference. I don’t like the picture this forms of what is going on. I’m not simply going to assume it’s all OK and that believe privately things are more collegial than what we see.

    In order to do work in this controversial world you need top-cover (aka Godfather protection). Le Grice doesn’t appear to be neutral (I’m being kind) and Coffin has backed away. So who’s providing top-cover right now? Without Coffin and anyone with an accent - a la Stoye and Le Grice who does that leave really – Ruscetti? It seems his top-cover is tenuous. Is he being frozen out of publication too? His remark at the Q&A about moving from detection to pathophysiology was very interesting. I think he was essential saying to the entire group, “If you people want to squabble over what we already know with a high degree of confidence, I’m moving on. I’m done trying to convince the stubborn”. But is HE being frozen out too? He was pretty clear discretionary funding would dry up soon.

    There is the report from Judy Mokovits’ NJ CFS Conference that the NCI “has been told by someone high up in the government to pursue whether XMRV is involved in prostrate cancer but should distance themselves from CFS."

    Well, observable NCI behavior would back that up at the moment. Ruscetti notwithstanding and he pushed off retirement to pursue this therefore he’s not really worried about keeping his job or future grants so he’s definitely not going to be pressured and may be staying in the game in part to help Mikovits.

    My angel Ila Singh is able to proceed because she is so well established. If another outsider like the WPI somes along their chances of being able to publish are slim if Dr. Mikovits is stuffing papers in a drawer.

    Alter is able to ride on his reputation, mostly. I do wonder if he hadn’t confirmed the leak of his impending publication and results if it might have disappeared. I may be in the minority in that view. One way or another he had to run a gauntlet that fairly unreasonable, at best.

    My memory is poor. What studies looked for pMLVs?

    Well McClure seemed to have found it in a negative study and is relentlessly pounding the Rumor Contamination drum.

    I’ll let you know after the study is done. :Retro smile: If he collaborates well (off to a good start it would appear) this very positive and I have some optimism here. But there are concerns like Lipkn’s publication Microbe Hunting where he states he’s against using “known positive” samples Note: I don’t have access to the publication (wish I did) and am quoting a quote but I have a high degree of confidence in the accuracy of the following.

    I hope Singh and/or others convince him otherwise. They can use her recommended method of direct phlebotomy draws to all participating labs, which I believe Amy Dockser Marcus has indicated he’s doing anyway so why not go after positives in this manner. Hopefully there are positive patients in the geographic regions used for the study. Does anyone know those locations?
  20. illsince1977

    illsince1977 A shadow of my former self

    Messages:
    356
    Likes:
    21
    Cort-
    Don't beat yourself up about not asking LeGrice those questions. You do such a great job of standing up for us, sharing with us and helping us make sense of it all while dealing with the difficulties of this illness yourself! :D :thumbsup:It just won't do for you to second guess yourself in this manner.

See more popular forum discussions.

Share This Page