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TWiV 151 (CFIDS, CFI)

Discussion in 'General ME/CFS News' started by Waverunner, Oct 2, 2011.

  1. Firestormm

    Firestormm Guest

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    Yeah I know I read her blog. Science also carried a story entitled 'False Positive'. Don't know who got the idea first really. Did you see/read Jamie's comment on Racaniello's site by any chance? I don't think she was very happy - but I felt the 'burning cross' was over the top. Still Racaniello pulled the T-Shirt image didn't he? After receiving a more reasonable request.

    Anyway, what did you think of the above? Racaniello said something about another paper coming out in a few weeks - wonder what that is all about?
     
  2. Daffodil

    Daffodil Senior Member

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    racaniello is a very kind, caring man. long ago, when they thought XMRV was "it", he answered many of my desperate emails with compassion.
     
  3. Firestormm

    Firestormm Guest

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    Cool. I had only been following his stuff for a year or so I suppose. I am quite looking forward to his being involved more. A CFS episode of TWiV sounds a pretty good prospect to me and anyone who takes the time to help others understand gets a tick in my book.
     
  4. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    Alan Dove and Rich Condit add noise and nonsense when it comes to their discussions on "CFS" and "XMRV." Prof. R is better. I think he is generally a good person with his heart in the right place. I think he is open to bona fide science in ME. Sometimes he is a little closeminded, though i think. for example the emphasis on "the CFS people need to realize that XMRV is dead." Everyone realizes that, even Mikovits. She has been focusing things for a long time on the broader range of HGRVs. HGRVs are not dead, but he doesn't mention that.

    I commend him highly for giving up his time to be involved in ME. Unfortunately, he's doing it with CAA so I am worried that Kim McCleary and Vernon will be distorting things as usual to him. CAA also gets a bit of a bump up from being associated with a respected virologist and that's not good for pwME. It's a smart move for CAA to raise their profile off the coat-tails of WPIs hard work; i don't blame them.
     
  5. Firestormm

    Firestormm Guest

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    Was just checking the comments again for this episode and there seem to be far more - so perhaps word is spreading about the possibility of a CFS TWiV?

    Anyway, this question and reply from the Professor was I though also interesting:

    Trembo: 'When will the professor start talking about the human gammaretroviruses the Lombardi group discovered and not VP62/XMRV, which those viruses are not.'

    Professor: 'I will talk about human gammaretroviruses when there is evidence that they infect humans. As of this moment there is none. As the Lombardi et al. 2009 Science paper stands now, it contains no proof that HGRVs infect humans.'
     
  6. justinreilly

    justinreilly Stop the IoM & P2P! Adopt CCC!

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    What do the science-literate people think of this statement? Accurate?
     
  7. alex3619

    alex3619 Senior Member

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    Accurate? Hardly. Hyperbole, unsubstantiated and misleading perhaps. A correct statement along similar lines would be "The evidence for HGRVs in humans is contraversial and has not been conclusively proved. Given the problems with contamination we cannot be sure that it is not due to contamination or some other error. Further research to validate or invalidate the HGRV hypothesis needs to continue."

    I am not actually as negative as that in respect to HGRVs, but its a more concrete and accurate version than what the prof is quoted as saying.

    The argument that APOBEC3 and other defences stop all HGRVs infecting us is ABSURD. Its more accurately a claim that we are highly resistant, so the transmission rate will be very low. Low transmission rate? Isn't that what we see?

    Of course something else happens to increase transmission in epidemics if the HGRV hypothesis is correct. My guess is the immune system is already overwhelmed by another virus, or that only those with pre-existing HGRV infections get ME.

    We NEED the Lipkin study. There are no strong arguments for or against the HGRV hypothesis at the moment. Some people are looking at what might be true, and arguing that it IS true, for or against. The Lipkin study into association with CCC CFS will give us a number to attach to the probability of the hypothesis being correct. Hard data.

    Failing that the only other outcome is a breakthrough that validates the research very strongly. That could happen, but we wont see it coming, it will be a surprise - thats what happens in cutting edge science, surprise after surprise, if not disappointment after disappointment.

    Bye
    Alex
     
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  8. joshualevy

    joshualevy

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    Yes. I don't have enough time to go into details, but this is a thumbnail of how it looks:

    I. Scientific Results
    A. 2 studies (1 partly retracted) found something. 20+ did not.
    B. Of the "second wave" studies, the bigger, higher quality, better design studies which learned from the mistakes of the early studies, there were 4. Of these, 3 found nothing (Knox/Levy, Singh, BWG), and 1 we are still waiting for (Lipkin).
    II. Scientific Progress (or Regression)
    A. Neither group that had positive results have published a follow on paper of any kinds with new positive results.
    B. The main paper has been partially retracted.
    C. At least one paper has been published showing contamination in each of the two "success" papers. And the main paper was partly retracted because of contamination.
    D. One of the groups with a successful paper, isn't even talking about their research, anymore.
    E. A paper has been published showing very clearly how the RV in question was created, and it doesn't mesh with the natural history of ME/CFS.
    F. At least one paper has been published showing that the body's immune system would immediately destroy XMRV, if it were present in a person.
    III. Scientific People
    A. Ask yourself this question: how many scientists though the XMRV-ME link was correct in Sept-Nov 2009? Quite a lot (Coffin and Singh, for example), but now, almost no one still believes it. Just the authors of the original paper, and not even all of them, and maybe half a dozen others.
    B. Another way to think of this is as follows. In the last 18 months, how many retrovirologists have changed their minds from not believing the XMRV-ME link, to believing it? I don't think even one. On the other hand, in the last 18 months, how many of them have switched from believing in the XMRV-ME link, to not believing it? Many. This is critical. For the last 18 months the scientific results have been very clear. The more we learn, the stronger the evidence. We get better over time, not worse.

    (You'll notice I haven't talked about sloppiness or scientific misconduct. Those are very damaging, too. But in a sense, they don't matter, because since there is no evidence that HGRV exists, the fact that the original paper left out critical information about the use of 5-AZA (scientific misconduct) doesn't really matter. The fact that the original researchers were so sloppy as to reuse a slide with different labels to illustrate a different point, that's just putting a stake into a body that is already dead.

    One comment on the 2 vs 20 number. A lot of people without scientific backgrounds (who's only science was in high school) are going to say things like "well those 20 studies didn't exactly reproduce the first two, so that doesn't matter. This kind of argument really shows off their lack of scientific experience. If something is really there, then there are many ways to see it. You don't need an exact repeat of another experiment. Quick analogy: someone tells you "I can hear some one in the next room". You look in the next room, and don't see anyone. You say there is no one there. The other person says you didn't reproduce the experiment exactly you should have listened. But the truth is , that if there was a person there, you would have seen and heard him. Arguing that the 20+ experiments failed to exactly reproduce the first one misses the point: if XMRV was there someone else would have detected it.

    Joshua (not Jay) Levy
     
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  9. jace

    jace Off the fence

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    Thank you for that, Alex. Here on the forum we have what appears to be a polarised discussion, but the fact is that the scientific investigation into HGRVs in neuro-immune disease groups needs to continue. Since days after the Science paper we have seen efforts to shut it down, sometimes appallingly rushed. Witness Erlwein 2010, and the slew of papers (with their misleading press release from the Wellcome trust) published in Retrovirology on 12/20/2010.

    HGRV research is the only area that creates such a vitriolic response. One has to ask why. The show must go on, and be allowed to play out to it's conclusion, whatever that is.
     
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  10. Firestormm

    Firestormm Guest

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    Hi Alex,

    Working through the thread here...

    He was talking though about the Lombardi paper, right? And even if you buy all that was in that paper - or all that remains in it now - it suggests an 'association' of XMRV and not that HGRVs infect humans. Or am I being a dumb-ass? :)
     
  11. Firestormm

    Firestormm Guest

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    Hi Joshua,

    I 'liked' your review btw. One point though, under III A I would suggest that other scientists were enthused by the original paper not that they thought it was 'correct'. Small point I know.

    I posted elsewhere a link to the F1000 Post-Publication Peer Review: http://f1000.com/1166366 (you can obtain a free trial and read it). Here is where Patrick Moore first raised concerns or rather was more concerned than the preceding reviewers I should say, and you can see the reaction from Judy Mikovits also.

    When it first came out Lombardi et al. excited (perhaps that is the better word?) a lot of people. The possibilities excited people and I think this was why it was published in Science. It appeared to be a (dare I say) 'breakthrough'. Certainly captured the headlines.

    Then of course the process of science began in earnest and I can't honestly believe that many scientists would say that this paper and its' implied 'association' of XMRV (an MLV) with CFS hadn't received due attention.

    The BWG was a good paper by all accounts and no author of Lombardi or the BWG papers have chosen to not endorse it completely.

    p.s. I like your analogies :cool:
     
  12. Firestormm

    Firestormm Guest

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    Morning Jace,

    Because the paper hasn't held up to scrutiny perhaps? If Mikovits and/or Ruscetti can publish another paper or indeed Lo (though the BWG featured samples from that too and found nothing), to support their theory that it wasn't 'XMRV' but something else entirely (or even related), then it would be terrific to see - of course it would.

    Vitriol? You mean personal attacks (of a verbal nature) at Mikovits? What has that got to do with the science? And what vitriol anyway? That only seems to stem from forums or blogs. I don't understand that bit.

    Fire x
     
  13. jace

    jace Off the fence

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    Vitriol, from forums and blogs. Oh yes. ERV is perhaps the worst example, and has been insultingly potty-mouthed about both ME/CFS patients in general, and Mikovits in particular since the off. Even Raciniello can be less than polite. Stoye and other researchers test themselves regularly for HGRVs and yet do not "believe" the investigations into the association with human diseases should continue??? (ref. CROI this early spring).

    Did you see my demolition of the screen-scraped slur on Mikovits? It didn't take long to work out.

    The Science paper stands, barring the retraction on Silverman's sequencing of what turns out to be a contaminant from his own lab, VP62. Yet from the off, it has been subject to increasingly sophisticated attacks. We start with the McClure paper, Erlwein 2010, rushed through in a few weeks, and only four days in peer review for a pay to publish paper. Humm.

    For months now, eminent scientists like Coffin and Stoye (but not we notice Alter) have been asking us to move on from HGRV research, saying the case is closed. Nothing to see. All a con. Heck, that's even argued here, on a patient forum. Yet, they test themselves for HGRV infection? Yet, there are papers being published every week into the finer details of the human/HGRV connection. Yet, Dr Snyderman's biomarkers are improving on ARVS. Then there is a loud cry from the denialists that we should not treat ourselves thus (what do they think we are? Stupid? Children? Some of us are so sick, without any hope, that ARVs are an alternative to suicide - might as well give it a shot, right?)(But only under the supervision of a doctor versed in treating HIV)(and plenty of money).

    How many times does one have to say Please Please Please let the scientific process play out. Give sufficient resources to both sides. All we are asking is for the science to be played fairly, equitably and with humanity.
     
  14. Overstressed

    Overstressed Senior Member

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    I agree with Jamie, because Racaniello pulled the T-shirt image AFTER he received a mail to remove the image. You would expect from a person who holds a Professor title to show some empathy, but instead he might have some IQ(unless he bought his academical title on the internet) but NO, ZERO EQ.

    In German there's a nice word for such people: "FACHIDIOT".

    What I say might be rude, and disrespectful, but his action caused me a crash because it made me angry and distressed at the same time. He lost all the credits he had, no matter how often he apologizes. Simply, because somebody made him realize what he did was plain WRONG!

    OS.
     
  15. Overstressed

    Overstressed Senior Member

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    I don't know whether I understand your post correctly, but if the 'vitriolic response' relates to the scientist trying to shutdown the research into HGRV's and not to the discussions here on the forum, I also ask myself the same questions....

    If humans would be infected by mouse viruses, then I would think that scientists work all the time with mice. Maybe we must try to imagine what would happen when this proves to be true ? Would mice be abandoned from labs ? That would have a huge impact on the scientific world, no ?

    OS.
     
  16. currer

    currer Senior Member

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    Can anyone clarify a point for me? Does Silverman still stand by his finding of MLVs in prostate cancer?
    Because if he does, the main problem still exists, and HGRVs infect humans

    The real question, and one that is carefully not asked, is how did these mouse retroviruses cross into humans. It was admitted in the Urisman paper that in the modern world, casual contact with mice is hardly likely to be the answer.

    We know that these retroviruses are endemic in laboratories, and readily infect cell lines, even transmitting themselves by the formation of aerosols
    Frequent detection of Infectious Xenotropic Murine Leukemia Virus in Human Cultures Established from Mouse Xenografts.
    Zhang et al.
    http://www.landesbioscience.com/journals/5/article/15955/

    At the CROI conference virologists were horrified at the thought that they had been exposed to an infectious MLV.

    So is it only that HGRVs do not exist in ME, but can quietly go on existing in leukemia, prostate cancer etc?
    If so how did the population get exposed to these new retroviruses?

    Or will no-one ask that question of familiar diseases and is it only ME that is the smoking gun?
     
  17. currer

    currer Senior Member

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    There is another problem with the HGRV finding.

    That is that gene therapy vectors using MLVs cannot go ahead if these HGRVs exist in the wild, ie in humans.

    It doesnt matter if they are disputed in ME.
    Even if HGRVs are found to cause prostate cancer or leukemia it will never be safe to release MLV gene vectors because of the danger of recombination between an engineered replication incompetent vector and an infectious wild HGRV.

    This is a disaster for the bioengineering industry because millions have been spent developing these agents.

    The profit motive must not be allowed to supress the real issues here that need to be resolved before new agents can be passed as safe.

    So what will be done? Will this technology quietly be withdrawn, much like the withdrawal of plans for xenotransplantation of pig organs?

    We need to know for certain whether HGRVs are in the population or not, and singling out Judy Mikovits and Frank Ruscetti for criticism will not help resolve this problem.

    In fact for the safety of us all, it would be a good idea to let the science proceed unhindered.

    In this context, the supression of the Lombardi paper could give the bioengineering community a false and dangerous sense of security.

    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003144
     
  18. alex3619

    alex3619 Senior Member

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    Hi Firestormm, I will presume that HGRVs are found in humans (not proven yet) for the first part of this argument. It is highly unlikely they don't in my view, but the prevalence is in great contention - it could be rare. In addition we don't know if its pathogenic or not. However it might still trigger ME even if its not pathogenic. I have presented this argument before in various forms but let me try an evolutionary perspective.

    I am looking at human evolution here, not viral evolution. Viruses evolve much faster, so it complicates issues, but looking at human evolution we have been infected with similar viruses before. We have strong defenses against them - which tells us they are dangerous or evolution would not drive such defenses because there would be no selective pressure. The human evolution of defenses would have been over large numbers of generations, perhaps starting in early mammalian evolution.

    I have a question, a possible way to look at this: what if we get ME because its an evolutionary advantage to the species that we stay sick unless we can resolve the virus? How bad would past epidemics have to have been to drive such an evolutionary change? I am not saying this is the case, its an open question not an answer. In less enlightened times most of us would have been ostracized or died. The risk of passing on the virus would be reduced. That is no longer the case with blood transfusions, cell cultures used in vaccine manufacture and social support (however pathetic it is) for the sick. However in this model the virus can be benign, but the effects still catastrophic. Its not just about the virus, its about virus-human interaction.

    So to go back to your question, could it be associated and not infecting humans (was this what you were asking?) the answer is no, unless its a lab artifact in which case its associated by accident only. However, low level virus infections may be nonpathogenic. Pathogenesis is an entirely separate question, and there has been little research on this because the association question has proved to be so problematic. If the Lipkin study shows association the pathogenesis studies will become much more important.

    Based on analogy with what MLLVs do in other species, and our strong evolved defenses, my best guess is that these viruses have low transmissibility in humans but high pathogenicity. Its a hard to transmit but very slow viral infection that can either result in death or severe disability. So a rare slowly transmitted virus is possible, which fits with the HGRV association hypothesis. We will know more when the Lipkin study announces results.

    Bye
    Alex
     
  19. markmc20001

    markmc20001 Guest

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    How about the 20 other studies? Those certainly aren't flawless, but don't seem to be getting the same kind of attention and critigue. What are the problems with those?

    I don't have much retrovirology experience, but have worked on worked extensively troubleshooting various precision equipment. If I were going to attack a problem and try to prove or disprove it, the first place I would start is to duplicate the same experiment. That is common sense.

    The idea with scientific problems is controlling all the variables.Change one at a time, and identify what changes as each variable changes. This way one knows what is causing the problem. If one is worried about contamination, they could go to a lab that is certified being clean, and run the experiment in question. If nothing is found, maybe it was a fluke. Repeat, and try and eliminate the other variables.

    So just by changing labs, and changing people doing the experiment, you already have introduced at least two new variables. If you change the whole testing process, who knows how many other variables one has introduced. I suspect even temperature could affect experiemnts like these. I know I would be frustrated if somebody told me my new design wasn't working, but they changed the temperature and turned all the knobs on the flowmeters, and changed all kinds of other parameters(using different adheasives, primers, didn't passivate the parts, etc,etc). More often than not, when problems have occurred with a process I have worked on (that was working fine for weeks until somebody else worked on it) is because somebody went ahead and changed the variables!

    The fact that the experiments were not duplicated/replicated exactly, tells me it is obvious there could be many other variables introduced in to whatever new study you guys were doing. This certainly isn't duplicating or replicating the original experiment that claimed to have found XMRV, and turns out is probably HGRV's)

    Common sense, and logical troubleshooting techniques that hold up across all types of science. Don't arbitrarily add in extra variables, and then claim the hypothesis didn't hold up. Your admitting you never tried the exact Lombardi et al procedure.

    The only thing the negative studies shows, is that HGRV's can not be found with the protocols used in the negative studies. That's it. If the Lombardi study is being debated, then follow the Lombari et al methods and then debate them, but don't change all the parameters and them come back and claim the protocol is not valid, because nobody has replicated it!
     
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  20. barbc56

    barbc56 Senior Member

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    I disagree. Does it really make sense to say, well it turned out the paper wasn't proven so that means it's okay if they left out information. The public as well as the scientific community need to know it's not kosher to do this. Continued discussion is needed, especially with the authors not being forthcoming. It doesn't necessarily mean people are being rude or putting people down.

    Reality is 90% perception.

    Did you mean something else?

    Thanks you for that nice summary. Love your analogies. BTW, I have a fire breathing dragon in my garage, LOL!!
     

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