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2 more studies that found, you guessed it, zero XMRV

Discussion in 'XMRV Research and Replication Studies' started by mojoey, Oct 12, 2010.

  1. Jemal

    Jemal Senior Member

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    Yeah, a lot of these studies come to some outrageous conclusions. It does make me wonder how scientific these studies were, so I agree with your point.
    I also agree with Cort though that there seem to be certain unusual requirements to detect this virus.
     
  2. urbantravels

    urbantravels disjecta membra

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    From your lips to God's ears, Cort!

    But...if Le Grice thinks it's all about to be straightened out soon...why was he singing such a long and repetitive song about contamination in his talk on Science Day??
     
  3. urbantravels

    urbantravels disjecta membra

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    Also - I guess we're not quite to the point yet where peer reviewers for scientific papers are going to send the authors of scientific publications back to the bench because they're clearly using inadequate methods for detection. At least the cat is out of the bag now that there's been SO much open discussion of assay methods, people can't pretend forever that the inadequate methods are somehow going to settle the question of whether the virus(es) are present.

    I hope, hope, hope the assay standardization happens SOON, so that we don't get more publications, using inadequate methods, to provide more fodder for those who are just all to eager to console the poor patients about having gotten their hopes up again....
     
  4. Esther12

    Esther12 Senior Member

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    'Sorted out' doesn't necessarily mean 'shown to be false'. He could think it's a quite likely possibility, and be in the midst of experiments which will settle the matter one way or the other.
     
  5. currer

    currer Senior Member

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    Hi. We already know that XMRV is not very infectious sexually. ME/CFS does not show up with great frequency between sexual partners. It seems to transmit in families via some other mechanism. We also know that gay men and drug abusers are not the usual ME/CFS patient. That patient is usually female. So I cannot see the point of the Barnes/Mclure study. Why study groups that are known not to be usually associated with ME/CFS? Why go to great lengths to show something that is already known? A number of these research studies reveal that the authors know little about the features of the illness and are not thinking deeply enough.
     
  6. Mark

    Mark Acting CEO

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    This is a cast-iron point. No scientist can be unaware of the issue of investigator bias. Any good science should be conducting their investigations of scientific questions with an open mind, and taking pains to ensure their objectivity. And yet there is abundant evidence regarding many of the negative studies that their authors did not believe the results would be positive. Even going so far, in Wessely's case to say "I don't think we're going to find it..." and then after the briefest of pauses..."nope, see, we didn't find it - told you so!".

    As to what is going on in their heads regarding their true motivations for not believing they will find anything...well, I hate to see people trying to look inside other people's heads, so it is much better not to speculate, and to simply observe the evidence that demonstrates those preconceptions and biases. Asleep has listed a few possibilities, there are many, and I don't know which ones apply to which individuals.

    But "My expectation is that we will not... [find it]" is a subtle phrase, if you look up "expectation" in a dictionary...
     
  7. Mark

    Mark Acting CEO

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    Sorry currer but that's not proven to my satisfaction. There are yet more possibilities which seem interesting to me...

    If XMRV rarely becomes a replicating infection, and does so only to a limited extent and under very specific conditions, then it's quite possible that when sexual or other transmission of XMRV occurs, only a tiny amount of XMRV is transmitted. That transmission could lead to a very, very slow build-up of latent XMRV infection, and perhaps disease symptoms only become evident when a critical threshold has been passed, or when some other factor like a separate infection enables active replication. So in a sense XMRV would not be 'very' infectious sexually, but it would be infectious and a slow, gradual build-up. This seems to fit anecdotal evidence of long-term partners showing signs of infection after many years.

    Those instances of familial transmission could equally be masked if only a small percentage of people are susceptible to disease as a result of infection, or again, if only certain circumstances allow the virus to replicate.

    I agree that it does now appear likely that infection can take place through more casual routes - I have (virtual) money on the sweat hypothesis for example - but I still think there's a very good chance it is regularly transmitted sexually.

    Whatever the explanation I think it's clear that there are some confounding factors involved in the pathology and disease progression that make most tentative partial conclusions seem contradictory to other evidence at first glance. But that's exactly what you would expect of a good "stealth virus"...

    ETA: Plus I'm not convinced there is any good evidence about familial transmission of ME/CFS to make the oft-repeated claim that it doesn't seem to be infectious. In terms of accepted biomarkers, at least, there isn't any rock-solid data on anything else, and there's never been a reliable way to measure ME/CFS other than patient reports of illness, and even regarding that the data hasn't been remotely well-collected, so I don't see how we can take it as a given that it doesn't tend to spread between partners.
     
  8. Jim

    Jim Senior Member

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    keep in mind le grice also said this: "We’re not far from a controlled clinical trial." sounds like a treatment trial to me, which obviously means he believes in xmrv or mlv's.
     
  9. Hope123

    Hope123 Senior Member

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    This is what I understand:

    1. Very few studies on ME/CFS transmission. Back in Incline Village and other related outbreaks, they did early studies which showed that spouses were not at higher risk than the general population but there were several family clusters (including Nevada and upstate NY). Also several other outbreaks (high school, professional symphony group, etc.) argues against just sexual transmission as the only or even main route although as others have said, it's possible if this is a virus, in certain states, might be able to be more sexually transmitted than at other times.

    2. This is the 3rd study by my count using PCR showing no XMRV in HIV patients. Haven't read this one but the other two had a fair number of untreated HIV subjects.
     
  10. lansbergen

    lansbergen Senior Member

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    Methods. Two cohorts of HIV-1infected individuals were
    tested for XMRV, 1 for patients with acute and 1 for those with
    chronic HIV-1 infection (Table 1). The cohort of patients with
    chronic infection included Swiss participants from the Swiss-
    Spanish Intermittent Therapy Trial, described elsewhere [11].
    All patients were not receiving therapy at the time of sampling
    and had received a median duration of 26 months (range, 8.5
    44.5 months) of highly active antiretroviral therapy at study
    entry. The median time not receiving therapy for the cohort
    was 14 months (range, 319 months). The second HIV-1
    infected group of patients were recruited from a study of acute
    HIV-1 infection at St. Marys Hospital, London [12]. Plasma
    samples were obtained from these individuals prior to receipt
    of antiretrovirals. For both cohorts, plasma samples andPBMCs
    were stored in 80C freezers and liquid nitrogen, respectively,
    for up to 6 years.
     
  11. acer2000

    acer2000 Senior Member

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    I wanted to post this language which comes from the other study to be released at the same time as the two mentioned at the top of this thread.

    http://www.journals.uchicago.edu/doi/abs/10.1086/656146

    The study found the following - A) That XMRV showed up in 22% of prostate cancer patients that they tested B) it was not correlated with the RNASE mutation as was originally hypothesized (ie people with normal RNASE QQ genese had it as well) C) it infected not just malignant cells in the people who carried it, and D) infection with XMRV didn't seem to correlated with severity of prostate cancer.

    In the discussion section they state:

    Of note is the comment:

    Basically what I take from that statement is that the sequences that they have to amplify to find XMRV are different if they aren't going to culture it in the LNCaP lines. So the same assay wouldn't work with both types of samples and this might account for why some assays have failed to find the virus.
     
  12. Cort

    Cort Phoenix Rising Founder

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    I think this points out how much they are still learning. I think we should rely on the opinions of the people who have the most expertise in this virus; that would Dr. Singh and Sandra (and therefore) Frank Ruscetti. Dr. Singh has been studying this type of virus for 10 years - when I talked to her she said she was not at all surprised at how much difficulty researchers were having. (She also said she didn't contamination was an issue).

    Its amazing how messy science really is. Weiss's commentary, which I didn't think was particularly powerful actually, was obviously persuasive to some researchers but this is Dr. Singh's mileu; it's not LeGrice's focus and its certainly not Dr. Houghton's focus - so I, for one, am going to stand on Dr. Singhs opinion like it's a rock. Her study should be finishing up pretty soon and hopefully it won't take too long before we know the results.

    Her study, the Blood Working Group, the Lipkin study and the CAA/GSK studies all sound like they are going to be more comprehensive than any coming before them and the Singh and CAA/GSK study will more closely follow the WPI's techniques. I imagine this set of studies will be definitive. Let's wait on them.
     
  13. Cort

    Cort Phoenix Rising Founder

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    I had always heard that CFS was not infectious but the PR forum poll on family members with this disorder or similar is intriguing. I just met somebody who has ADHD and autism and CFS in her family and we did see all that overlap in the Cheney report at the Workshop. I think there's still alot of ground to cover in that area.

    With the patient data repository/Treatment Review program we will be picking all that up.
     
  14. Mark

    Mark Acting CEO

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    Thinking this through...

    If CFS were partially or wholly caused by any environmental factor, then in at least some proportion of cases, that environmental factor must be expected to be shared by some proportion of groups of people who live together.

    If CFS were partially or wholly explained by some genetic factor, then there would be a family association.

    If CFS were partially or wholly explained by a virus, then again there would be a detectable association with family members.

    Heck, even if it were all down to purely psychological factors, you'd expect it to cluster in families to some extent.

    Whatever it is, you have to be at increased risk if a family member has it.

    But there's no evidence of family association. So what?

    The received wisdom that there's no such association just leads me to question where that received wisdom comes from - sure ain't from comprehensive study of us!

    Personally, I have always assumed that my own condition may very well be contagious, to such an extent that, even in the absence of any direct evidence, I have always been very worried that I might infect my friends. Two family members, one related by adoption, acquired rare and ideopathic chronic illnesses at roughly the same time as me. And I have long suspected that I infected one friend who came down with what sound like very similar symptoms to my own after we shared a hotel room in Amsterdam for a few days...which points towards my theory of potential transfer through sweat, on towels, at a time of high infectivity on one side and lowered immune capability on the other...

    All anecdotal, so scientists may discount this evidence if they choose...

    None of my friends have ever been at all worried about getting infected. I guess if they secretly doubt I'm really sick, it would be less of a concern. But I reckon that psychology of the population at large is the real reason why we have always heard that CFS is not infectious...

    Studying this question by survey would have been so easy and so cheap. Large population of CFS sufferers: how many people do you know personally who have CFS/developed CFS while you knew them/ have ideopathic conditions/etc? Compare with general population. Design survey carefully. Cheap and easy.

    Of course, you would have to find us first. And you would have to give a damn...
     
  15. jace

    jace Off the fence

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    Back to negative studies, briefly. I posted this on another forum - short and sweet. I can't see anything wrong with the logic:


    I think I'm right in saying that all the high-profile negative studies find no XMRV at all anywhere. None in controls, none in study cohort.

    This alone should be enough to discredit their methods (and it has to be method, as G says, and not cohort, or they would have found the background infection of 4 - 7%) unless it is believed that XMRV does not exist anywhere. No-one is saying that, are they? No one is disputing the truth of the budding XMRV virus, taken by electron microscope, no one is saying there is no XMRV in prostate cancer.

    IMHO if a study finds zero XMRV it is ipso facto discredited.
     
  16. Mark

    Mark Acting CEO

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    I agree Jace, with the exception that if such a study describes its blood-collection and storage methodology and its testing methodology thoroughly, attempts to test a 'known positive' sample from somebody who can find XMRV, and simply states as its conclusion something along the lines of "we were unable to find XMRV in any samples using this methodology" rather than overreaching wildly and irresponsibly, then they have the potential to add to scientific knowledge by clarifying what does not work for the detection of XMRV. The majority of the negative studies have drawn conclusions that their results do not support, and some have even gone to efforts to speculate beyond those findings in the press. That's what discredits them.
     
  17. Cort

    Cort Phoenix Rising Founder

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    No study is validated until independent labs verify it - that's why they go through this process. If it didn't have to be verified we wouldn't see all these people spending all this money trying to find it so I disagree - only when they figure out what is causing the disparities will they be to say whose results are right and whose are wrong. I still think that most groups feel they are doing everything right - that they are using methods they believe can find the virus - and it is eluding them.

    I don't know how the 'we don't think XMRV is there group' can explain away the budding virus - I assume they have some way to do that or they wouldn't be making their statements.

    But I think we should all hold our horses until the big studies come out; the Blood Working Group should be making an announcement in the next month or so about the contamination and I would assume the blood storage issues. The Singh and CAA/GSK studies have been underway for awhile. The NIH knows about all the controversy and the disparate findings and yet they put together an expensive study with a top researcher to work things out. That indicates to me that they think this issue is hardly resolved (they wouldn't do that if they really thought it was contamination) - that's a big positive for me. The lack of positive results is disappointing but no one know how this will turn out.

    I would note that the latest study used the clone Dr. Mikovits warned about.
     
  18. currer

    currer Senior Member

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    Thanks for posting the Houston study, Acer2000. It looks like thoughtful and careful research and shows how tricky finding XMRV is. I thought their discussion very revealing. I remember Dr Singh saying on TWIV that the low hanging fruit had already been picked where virus detection was concerned. I cannot usually download the complete papers to read but what seems wrong to me about the negative studies is the reliance on one simple approach. I dont think a virus in CFS/ME would be EASY to detect or it would have been detected years ago. The researchers have to expect a difficult search.
    In Britain CFS/ME is considered to have some genetic association. A recent study (I cant remember which one) did find a higher incidence in family members - not necessarily close family, cousins uncles that sort of thing, which suggested a genetic susceptibility. Among my friends with CFS/ME there is a definate association between CFS and autistic spectrum disorders in families. This is a newly discovered association and a worrying one. I also have friends with CFS/ME who think they have infected their partner.
    I suppose a micrograph of a budding virus could be any virus budding out of a cell. Can it be conclusively proven that THIS virus is XMRV?
     
  19. Hope123

    Hope123 Senior Member

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    The older "rumor viruses" article by Voisset? that Kurt posted a long time ago talks about this and how it could be an artifact of the techniques or budding endogenous retroviruses (which can happen) rather than a true exogenous virus about to lyse. One method it suggested resolving something like this is to get the photo at the same time using antibodies specific for the exogenous virus of interest. In that case, you get both the "budding virus" and some confirmation that this is an exogenous virus. Of course, there are probably steps in the technique I am not aware of that could still cause artifact.
     
  20. currer

    currer Senior Member

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    Hi. A friend has just pointed out to me why the Weiss paper (which was not well argued) is so persuasive. IT REMINDS RESEARCHERS HOW DAMAGING MISTAKES ARE TO THEIR CAREERS. It is much safer to publicly declare that you are not convinced by new work. You can change your mind without loss of reputation when it becomes clearer what the general consensus is. Weiss has reminded researchers how he nearly made a BAD mistake. They do not want to be next. Judy Mikovits has been very brave in standing by her findings.
     

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