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No Longer Naive in the Ways of The Beast
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Cleaning up after XMRV

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by Ecoclimber, May 18, 2012.

  1. Mark

    Mark Acting CEO

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    I'm watching it too - it got a little less boring since you posted. :)

    As far as the semantics go, I just looked up 'pathogen' to check, and as I thought, there's no requirement in the definition for it to be circulating in humans for it to be 'pathogenic', the only requirement is that it causes disease. It would be pathogenic in humans even if it weren't communicable from human to human. I would say it can be a human pathogen even if no humans are or ever have been infected by it. Smallpox is a human pathogen but it is not circulating in humans.

    That is fundamentally why saying "XMRV is not a human pathogen" and claiming that it is 'impossible' for it to be a human pathogen is overreaching the evidence enormously. You could say it is 'highly unlikely' that it is 'currently circulating in humans' and 'there is no evidence that it causes any human disease', and there would be much less to take issue with; there would be no fundamental logical flaw in statements like that. And I don't understand why scientists in this area are so prone to making definitive statements about what is 'absolutely impossible' when the rest of the time it's so hard to get them to say anything without a thousand qualifications, ifs, buts, maybes and "more-research-is-needed"s.

    Well, OK, although I say I don't understand, I think I have a good idea of why. The controversy has been difficult and embarrassing for a lot of people and there are many reasons why people want to stamp it out and put an end to the public discussion of the issue, so that makes them prone to over-stating their case. And specifically it is now especially important to assert that XMRV is not pathogenic to humans in order to allay fears that a human pathogen may have been created accidentally in the lab. It's similarly important - in quite a deep way, psychologically speaking, as well as politically - to emphasise that 'there is no evidence' that any similar lab-created retroviruses that replicate efficiently in human cells have ever infected real humans or caused disease in humans, and it's similarly important to persecute and ridicule anybody who suggests that they might have. That's especially important to do because we know that the processes which can create such novel viruses and retroviruses have been standard practice in labs for several decades, so the idea that any of these potential lab-created pathogens might actually be real live pathogens is profoundly, profoundly disturbing. And don't even dare to think about where such pathogens might have spread to from their lab environment...

    I could also take issue with 'if it was a circulating pathogen it would have been found by now' because there are too many assumptions in that statement as well; I would prefer a 'probably' in there as well and it's a massive assumption to think that widespread lab-created contaminants can't be at the same time be pathogenic and non-communicable. But I would rather leave it to others to get into those arguments really; I am sticking to my argument that comments like "XMRV is not a human pathogen" and "that hypothesis has been disproved by..." are going too far. If we accept that XMRV has never successfully infected a real live human being, then how can we say it definitely wouldn't be pathogenic if it did? And if it's "definitely not a pathogen" then what exactly are these "biosafety biohazards" that these papers are still warning about?
    currer likes this.
  2. Mark

    Mark Acting CEO

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    You're continuing to stand by "impossible" that XMRV is pathogenic then? You don't have to demand that it's "impossible" and then I probably wouldn't bother to argue the point, but so long as you are saying it's impossible when there's no proof of that, I'm going to continue to disagree.

    And if Dr Mikovits in those circumstances was claiming that it was "absolutely proven that XMRV is the cause of ME/CFS" then I have absolutely no doubt that such a definitive statement would be widely criticised, and I would agree with that criticism because I don't like scientists claiming certainty about matters that are unproven.

    Of course, despite all that, Lipkin's expensive study has continued, and Mikovits, it seems, still stands by the significance of her findings, so that too should say enough, for now. There were 4 parts to Lombardi et al, and the BWG only addressed one of them, it was never defined as the definitive test, there was always Lipkin still to come, so it should not be taken as definitive now. The antibody results, among other aspects, remain unexplained, and really it doesn't matter whether XMRV itself or other MLVs or MLVRs, endogenous or otherwise, play a role in ME/CFS, if there was something there in the different results between patients and controls in Lombardi et al and Lo/Alter then we should all want to know what that was - that's why a proper explanation of the difference in those results is so important, and "probably handled differently" is just not good enough.

    Similarly, as Wessely has asserted, we'll "probably never know" what caused Gulf War Illness. I wasn't happy about that admission of defeat either. It's not merely of academic interest as to what the difference between patients and controls was in all those studies, it's of clear practical interest whether scientists are missing some fundamental problem, whether the studies were fraudulent, or whether there was some medically significant reason for the difference which just wasn't exactly what the researchers assumed. Apart from which, the controversy and the conspiracy theories will continue forever, unless and until those different results between samples from patients and control samples, in multiple studies, are adequately explained, and the same thing will happen again the next time somebody makes a similar methodological mistake - if, indeed, it was a series of mistakes that explain those results.
    currer likes this.
  3. FancyMyBlood

    FancyMyBlood Senior Member

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    Thanks, I was under the assumption that a 'pathogen' must cause disease before it can be called a 'pathogen'.Obviously, to establish this it must be circulating in humans (human pathogenic) first. My main point was that it' not circulating in humans, so it's not a human pathogen. However, I agree with you that it might be a possible human pathogen if it escapes from the lab. I think the authors of the bioharzard paper are refering to this too:)

    I believe most of our argument boils down to the question when it's justified to make complete statements. I respect your assertion that you want to have complete assurance. Unfortunately that's impossible, we should screen the whole human population and even if we did there are many other 'improbable possibilities' (there it is again!:p)

    My personal opinion is that given a very high probability it's justified to make these statements. The probablity of other 'improbable possibilities' is so incredibly low it would be futil to acknowledge them.( I used a 500 word analogy here but I deleted it because I think that's too much off-topic).
  4. Esther12

    Esther12 Senior Member

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    I'm afraid that I've not been able to keep up with this thread but re this:

    My impression is that it's just a different use of language that's the problem here.

    Some people will happily say "it's impossible for Wigan to win next years Premiership", using the term 'impossible' in a loose conversational sense to mean 'extremely unlikely'. People can do the same with words like 'proven' too. It will only stand out to people who are used to using those terms more precisely. As I've learnt more about the exact meaning of certain medical and scientific terms, I notice how often they are misused in everyday speech (and I'm sure I do it too), and scientists can do the same with more philosophical and abstract terms (as can we all). Almost nothing is truly impossible, or genuinely proven, so most of us use these terms somewhat inexactly to indicate differing levels of probability, depending upon context, the manner in which we're communicating and with whom, etc. The use of the word 'proven' in relation to an argument which didn't seem very strong to me did strike me as odd... but there you go. It was only a blog post, so was probably written casually.

    That's my little contribution anyway.
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  5. FancyMyBlood

    FancyMyBlood Senior Member

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    Thank Esther, you summed it up nicely. It basically boils down to the issue when it's justified to make a certain statement. It's obvious Mark and I disagree about this, but I believe we're not too far off regarding our views on XMRV.

    I must say this, the whole XMRV saga has frustrated me immensely and I really hope the Likpin study will be published soon and the results will be satisfactory for everyone.
  6. Mark

    Mark Acting CEO

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    Well yes, it must be known to do so before we can say that it is - but it may be pathogenic even if we don't know yet that it is, or even if it hasn't caused a disease yet. It's just that we don't know it's a pathogen, not that it isn't one.

    I've tried to question "circulating" because that seems to be an article of faith in the whole argument, and one that is unjustified - it ignores more possibilities that are taboo to consider or discuss, and given the epidemiology of ME it seems strange to ignore those possibilities in this context. For example, a pathogen that could not establish an infection that was communicable would not exactly be circulating in humans, but you would consider it pathogenic if it was injected into you and it caused disease and could be inherited by your children.

    Good: then it seems we are at last agreed that it is not impossible for it to be a human pathogen.

    So it's impossible to rule out the possibility that XMRV is a human pathogen. My head is spinning a bit over the impossibility of saying something is impossible, in general I'm uncomfortable with that 'impossible' too, but in practice I can't think of a way to prove that it's not pathogenic, so yes, basically that's what I'm saying and I agree with that.

    And here again is exactly where we differ. You think it's justified to say that something is "impossible" because it is very improbable. I just don't understand what the need or justification is to use words like "proven", "disproved" and "impossible" to describe probabilities. I think most people understand what those words mean, it's not just mathematicians who think "impossible" means "not possible" and take it as a definitive statement, and I don't think it helps anyone to use such inaccurate terminology to communicate about science. Why not just be accurate and say that it is "extremely unlikely"?

    I mean...where will it end? If scientists think it's OK to go around telling the public that something has been proven or disproven and that something is "impossible", before you know it that absolute certainty will become devalued, and they'll feel they have to go even further and claim things are "1000% certain" after one experiment...and who's going to trust people who say things like that?
    currer likes this.
  7. Mark

    Mark Acting CEO

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    Yes, but having an interest in football I would say that there is more precision in the way that sort of language is used about football then I've seen from the scientific community in discussions about XMRV!

    As the discussion has honed in on the 'impossible' point, and I've been trying to emphasise that definitive statements aren't helpful to understanding, that point about the 'proven' conclusion from a relatively weak argument may have rather been lost. But that was my starting point really, and I do think that argument is way too weak to be called 'proof' - even for scientists.
    currer likes this.
  8. Esther12

    Esther12 Senior Member

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    I don't follow football closely... but I've got a lot of respect for Wigan. They're a tiny club who are pretty consistently mid-table. They could get lucky!

    No probs. It did seem like much of the disagreement stemmed from the way in which ideas were being presented... I'd deleted an earlier post in this thread because I realised how difficult it would be to express myself clearly.
  9. Mark

    Mark Acting CEO

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    There's a simple explanation for their success despite having such low attendance figures.

    $$$$$$$$$$

    Such clubs are likely to struggle to maintain their place when the Financial Fair Play rules kick in.
  10. Esther12

    Esther12 Senior Member

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    That makes it less respectable. I thought it was clever management and plucky players!
  11. Mark

    Mark Acting CEO

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    Sadly, no - the modern premier league is more like the end stages of a game of Monopoly these days.

    ETA: Although of course the management are still clever and the players still plucky, no disrespect to that, it's just that they expect to be very, very well paid for it.
  12. barbc56

    barbc56 Senior Member

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    I think the above statment might be a leap of logic. My interpretation It's not that scientist think XMRV is harmless because it was created in a laboratory but because the data is showing XMRV is harmless.

    I wonder if the statement about the biohazard was included as the scientis are basically covering their behinds. :aghhh: My opinion here. It's also important to consider that if laboratory workers are infected by XMRV, that would increase the chances of contamination. In any experiment.

    It also my understanding that only the positive cultures were cultured. If this is true then they were handled more than the controls.. I could be wrong about this.

    In the paper, Absence of XMRV and other MLV-related viruses in patients with Chronic by Singh et. al., they assert the following may account for the discrepancies in patients and controls in the original study.
    • Too small control populations
    • Patient and control samples collected at different times
    • Investigators generally not blinded to sample identity
    • PCR assays that rely on conservation of viral sequence mainly used
    • Limits of detection, reproducibility, and precision of assays unknown
    • Controls for each step that would identify analysis not done
    • Insufficient numbers of negative controls included
    • No study included positive samples from the original 2009 patient cohort of Lombardi et al.
    http://jvi.asm.org/content/early/2011/05/04/JVI.00693-11.abstract


    I don't think the authors of the original study can be completely faulted when it comes to the contamination issue, as we know a lot more now than we did almost three years ago. Even Ila Singh admits that she didn['t think her lab was contaminated, she looked for contamination over and over and eventually found that one of the instruments was contaminated with XMRV.

    Contamination is hard to control and in the example of this study, even sometimes to find.

    Barb C.:>)
  13. barbc56

    barbc56 Senior Member

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    Here is a copy of the post I put on the other thread. I include it here as it contains some points I didn't put above. and this thread is specifically talking about Virology Blog. Some points are repeated. Sorry about that. I am exhausted after writing the above. I may come back and delete the repeated sections at a later time.

    VOC thank you for posting these studies.

    Vincent Racaniello wrote about them in his blog today:

     

    http://www.virology.ws/


    However, just because something is possible does not necessarily make it probable and IMHO the reality is that the most likely explanation is contamination. I will write another post on why I think this as this getting rather long and I am having trouble with my computer. I can't emphasize enough that I had high hopes for XMRV so it was disappointing to get all the negative studies. I guess it's better to find out now rather than later.



    While I think there is some merit in further studies I would rather see the money spent on studies that look for other causes such as another RV, viruses and the possibility that are immune systems make us susceptible to viruses others to not catch.

    Barb C.:>)

    ETA Please excuse any typos, etc.as I am having a great deal of difficulty posting this and don't know if it is my computer or not. If I have to edit again, I am going to start screaming.:eek:
  14. Mark

    Mark Acting CEO

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    Those points are about problems with the negative studies.
  15. Mark

    Mark Acting CEO

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    I'm fairly sure that the culturing you're referring to came after the original PCR detection so it can't explain the differential between the results. I'm also fairly sure that in the culture test proper (not the subsequent analysis you're referring to), the patient and control samples were treated equally. Incidentally, although blinding and coding was not referred to in the paper, my recollection is that Mikovits has asserted that all samples were coded for the Lombardi experiments, and she didn't know which samples came from where until they were decoded some months after publication - although I'm not sure I'd say that the exact details of that entire process were ever made entirely clear.

    I agree, and I'd go further: I think it's very important to point out that there was not just one study here; there was work in Germany, Spain and Japan, and if you include the prostate cancer studies there were lots of studies that found different percentages in patients vs controls. So I don't think it's at all fair to place all the blame on Dr Mikovits: there are many others who could be 'faulted' for making this 'error', and the nature of this widespread worldwide contamination of lab materials with a lab-created retrovirus that infects human cells was not known before this research began.
  16. Mark

    Mark Acting CEO

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    I do understand the concern that money might be wasted on fruitless research into XMRV that would be better spent on other ME research, but unfortunately that concern is groundless because there is no choice being offered between the alternatives you cite: the money that was spent on XMRV research never was ME/CFS money. They never have bothered to spend such serious money on ME/CFS research, and there's still no sign of any government agency spending anything significant on it.

    The reason is simple: They do not care about the suffering of ME/CFS patients, what they cared about here was (a) the possibility that a retrovirus might be at large and might infect lots of other people, and (b) the public health scare and scandal of this news story and the possible catastrophic implications for many vested interests if it were true (the insurance industry would have been down by over a trillion dollars and that's just the start of it). That was enough to get lots of scientists around the world spending money on research, and relatively little of it was even spent on ME/CFS research, it was spent on researching possible connections between XMRV and other diseases. 17 million chronically ill people is unfortunately not sufficient reason to provoke significant interest in itself, and none of the research investigated any other details of ME/CFS patients, such as whether they had any other evidence of any other retroviral activity.

    So ME/CFS research has lost nothing from the money spent on XMRV: that has all come out of the other colossal pots of money spent into research into all kinds of other diseases, and it's a drop in the ocean in that context, which only demonstrates once again that there is plenty of money available to fund ME/CFS research, but there's no will to do so and indeed there seems to be a continuing determination not to properly fund research into this particular chronic illness - a determination which only fuels the sense of hopelessness and distrust of the patient community.
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  17. ukxmrv

    ukxmrv Senior Member

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    Can someone please correct me if I am wrong.

    Not one of the retrovirologists who worked to tell us that XMRV could not be the cause of CFS ever tested patients for reverse transcriptise or tested patients to see if there could be a related retrovirus or any other retrovirus in this group.
  18. currer

    currer Senior Member

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    Well said Mark, in all your posts. I agree absolutely with everything you have said. I too am infuriated by the sloppy reasoning that purports to "prove" XMRV or related MLVs cannot be human infections.
    Mikovits has been saying for a year that it is a HGRV.
    All these negative papers killing XMRV loudly and publicly over and over and over raise nasty suspicions of a coverup in my mind. Why dont they look for the related MRVs that Mikovits ( who has so conveniently been silenced now) has been attempting to publicise? What about Dr Snyderman's blood results, which clearly point to a retroviral infection of some sort? Or are we supposed to have no interest in WHY someone who ought to be dead by now is still alive?

    Retroviral infections can only be transmitted blood to blood because the envelope protein is fragile, and so human intervention is necessary to account for why animal retroviruses haveopassed into humans This is a dangerous area for any researcher - few will be brave enough now to look into it.
  19. currer

    currer Senior Member

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    I am having problems editing my previous post so I will add here instead the further point that this whole debate has been artificially narrowed into "disproving" the xmrv sequence. Yet the scientific question of whether traditional methods of producing vaccines over the 20th century could have transferrred animal DNA into the human population , and what effects this could have is a perfectly valid concern. Why is it not properly investigated?

    I have found at home, an old penguin book written in the early sixties about cancer. Now the author is just on the verge of realising that some murine nucleic acids are cancer causing if transferred into other mice. He does not know why DNA, which he thinks of as a stable transmitter of genetic information, could do this, and is clearly dubious about these findings. He knows nothing yet about retroviruses incorporated in what he thinks of as a fixed and stable substance, the DNA.
    And yet animal experiments transferring parts of tissue from one animal to another were well advanced, and xenotransplantation in the form of vaccine production was done all the time. They knew nothing about the dangers of retroviral infection from these procedures.

    They also did not fully accept that viruses could cause cancer at that time. The author is very dubious about this as they did not have a model for how the virus could damage the cell sufficiently to create cancer in that cell. I suppose they did not know that retroviruses could insert into DNA, not knowing about the existence of retroviruses then.
    this makes me think that we could indeed have transferred many agents unwittingly into the human population via vaccines or by other experiments involving the transfer of animal tissues from one animal to another long before the dangers could be known.
    This book was published in 1962. It is a revelation to read.
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  20. lansbergen

    lansbergen Senior Member

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    http://en.wikipedia.org/wiki/Feline_leukemia_virus

    Feline leukemia virus (FeLV) is a retrovirus that infects cats. FeLV can be transmitted between infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal’s immune system, the virus can be lethal.

    http://www.vet.cornell.edu/fhc/brochures/felv.html

    How is FeLV spread?
    Cats persistently infected with FeLV serve as sources of infection. Virus is shed in very high quantities in saliva and nasal secretions, but also in urine, feces, and milk from infected cats. Cat-to-cat transfer of virus may occur from a bite wound, during mutual grooming, and (though rarely) through the shared use of litter boxes and feeding dishes. Transmission can also take place from an infected mother cat to her kittens, either before they are born or while they are nursing. FeLV doesn't survive long outside a cat's body—probably less than a few hours under normal household conditions.

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