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Switzer - Publishes new XMRV varieties, and challenges Coffin's recombination theory

Discussion in 'XMRV Research and Replication Studies' started by Bob, Jun 30, 2011.

  1. eric_s

    eric_s Senior Member

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    Ruth, does it really not make a difference wheter the control is a sample spiked with genetic material or an actual clinical sample of the same kind like the samples studied?
     
  2. Bob

    Bob

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    This is not the case if the patient samples have even lower copy numbers than the spiked positive controls.
    There may be other reasons why spiked positive controls are easier to detect than wild virus.

    Patient cohorts might be a significant issue. Judy Mikovits doesn't select ordinary CFS patients. She has further selection criteria.

    I haven't yet seen a peer reviewed analysis of the newest XMRV genbank sequences, so can we actually comment on them in an informed way?

    A lack of gene variability says nothing about whether someone is infected with a virus or not, for a couple of reasons that I am aware of.
    The apparent high frequency of lab culture contamination and xenograft contamination suggests a higher possibility that humans are exposed to these viruses via contamination.

    There might not be a wider conspiracy, but there is definately an attempt from some individuals in the scientific community to move the science community away from XMRV research, especially in relation to CFS. I don't know how deep and wide the influence of those individuals is.
     
  3. RedRuth

    RedRuth Senior Member

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    No, it really doesn't and anyway the Levy paper spiked the control DNA into a negative sample, this is to make sure that having genomic DNA in the sample or anything else in the sample doesn't inhibit the PCR reaction. DNA is DNA is DNA it's the binding of the primers to the target sequence that's important and getting the right conditions for the buffer, dNTPs, enzyme.
     
  4. RedRuth

    RedRuth Senior Member

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    But the positive controls are extremely low copy number which means the PCR is very sensitive why would the Mikovits' lab PCR be more sensitive than say the Levy lab's PCR? Not very likely especially as they did qPCR. The point about patient selection is valid but is muddied by the fact that they find positives in healthy controls.



    I was just repeating Cort's comment, I assume he keeps up with the current research. What new genbank sequences are you talking about?



    It comes down to method of replication. Generally retroviruses use their own reverse transcriptase for the first stage of infection of a host cell, this enzyme is error prone so sequences between patients and even from the same patient will vary considerably. If however the retrovirus has become endogenised into a Human cell line then replication will only be via the host error checking machinery. So high sequence variability is evidence of an infective, replicating virus. Low sequence variation is evidence of a contamination of lab reagents with the DNA from an endogenous retrovirus.
     
  5. eric_s

    eric_s Senior Member

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    I think Judy Mikovits said it does make a difference, but i have no background in these things, so i will just have to take your statement and hers and leave it open.

    I just find it very hard to believe that a number of labs would find XMRV/MRV in different kinds of samples with different types of methods, more often in cases than in controls, and not figure out it's caused by contamination for such a long time. At least some of the studies were blinded, which makes it even harder to explain, if there is not truly an infection.
     
  6. Jemal

    Jemal Senior Member

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    I am not sure what kind of state the US media are in... but over here (Netherlands) they are in a bad shape. They mostly recycle the content of the big press agencies, like Reuters or they lap up easy stories. This is not an easy story to cover. Far from it: many scientists are disagreeing with each other and I am sure the few journalists that might be interested (still talking about the Netherlands) think it's a hornet's nest. So that the media are not reporting on it, doesn't mean it's not a hot topic, or at least I think so.

    I fully agree with this.
     
  7. eric_s

    eric_s Senior Member

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    One more interesting thing, Ruth, is that basically all the labs i know of that could find these viruses or sequences first didn't find them and then got in contact with the WPI and after this they were able to find something. It happened like this with the Lo lab (FDA) too, if i remember correctly. I don't think this is beacuse they got contaminated material from the WPI, because they certainly checked for that. Now it would be interesting to know if these labs, prior to finding XMRV/MRV in clinical samples, were able to pick up the spiked positive controls. If they could find the DNA in these controls but not in clinical samples that would argue against that kind of controls, i think.
     
  8. Bob

    Bob

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    Well, this is the essential issue. We just don't know why Judy Mikovits can detect XMRV, and others can't. That's why many of us want to see the XMRV research continue, until we have definite answers.

    But with a novel virus, and copy numbers at the limits of detection, it doesn't seem beyond possibility that the small changes in methodologies and techniques in each study might make all the difference between detecting and not detecting the virus. The number of variables are enormous.

    Judy Mikovits has been refining her techniques for years now, and she is reportedly still detecting XMRV in CFS patients and healthy controls at different rates, which seems pretty significant to me.

    The WPI published some new sequences about 3 or 4 months ago. I haven't seen a peer reviewed analysis carried out on them yet. I don't know what information Cort is basing his comments on.

    There are two other reasons why the sequence variation might be low in a human infection:
    1. XMRV may be like HTLV, which has very low variation.
    2. The route of infection may not be from person to person, but it may be from contaminated lab product to human, such as in vaccines.
     
  9. jace

    jace Off the fence

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  10. currer

    currer Senior Member

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    Quote from Judy Mikovits reply to Science (the EEC)

    ...but good science is difficult and takes time...
     
  11. RedRuth

    RedRuth Senior Member

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    True, but Lo et al evidently did do some kind of qPCR in their PNAS paper,( it's in the supplementary) to test the sensitivity of their detection (threshold: 100 copies in 30 ng Human DNA). It's at least an order of magnitude less sensitive than Levy's method (threshold: 10 copies in 100ng Human DNA) It really is a shame that the Mikovits lab haven't determined how sensitive their method is.


    1. It's true that HTLV1 infects cells that then expand clonally (T cells I think) but there's no evidence that XMRV infects these cells but the real problem is with the phylogenetics. The sequences don't seem to fall into a nested hierarchy that would explain a slow evolving virus like HTLV (this is the conclusion of the Coffin paper that's the subject of another thread)

    2. This is a possibility though it seems far fetched. I'm no epidemiologist but is there any link between vaccination and ME?
     
  12. Bob

    Bob

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    Yes, there is a link, at least anecdotally. But I don't know if there has been any solid research on this.
    Hep B vaccines have been associated with ME, and people have reported becoming ill on return from holidays, for which they received vaccinations beforehand.
    Also, health workers are at high risk of getting ME, and they receive more vaccines than average.
    Again, I don't know how much research has been carried out here.

    Also, it could be possible that people carry XMRV for years before becomming ill with ME, in which case any link with vaccines would not be obvious.
     
  13. Mark

    Mark Acting CEO

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    I would say there is quite a lot of very circumstantial evidence to be found pointing in this direction when you look into the history, politics, pathophysiology and epidemiology from a generalist perspective. Pointers that I can think of...and yes I realise these are very circumstantial...the point is that this overall picture seems (to me) consistent, in the round, and explains many mysteries...

    - Perhaps the most suspicious evidence: Best known/seminal outbreaks: 1934 Los Angeles, 1955 Royal Free Hospital, almost exclusively affecting health workers and not patients (were those health workers heavily or experimentally vaccinated???). Experimental polio vaccines were being trialled in those areas at those times. The disease profiles in those outbreaks were initially characterised as somewhat atypical forms of polio.

    - I've come across several anecdotal patient accounts of their illness being provoked or seriously worsened soon after vaccination, though I certainly don't think there's any good evidence either way on this subject - a detailed survey would be very interesting.

    - Parallels/connections with autism: Some commentators go so far as to claim - on the basis of pathophysiology (eg immune/IBS/cognitive impairment aspects) - that autism and ME are fundamentally the same condition, with autism striking the same neurological aspects at a different stage of development; and there are many accounts of parents with ME who have children with autism. Suspicion of autism/vaccination connection remains despite the alleged disproof of this theory; considerable overlap between the political opponents of these theories.

    - Recent Scandinavian 'narcolepsy' outbreak following H1N1 vaccination: children in at least 10 countries developed a novel neurological disease following H1N1 vaccination, which appears to only affect specific genetic groups; big pharma is now 'investigating' with big studies in the areas that weren't affected...this incident demonstrates that rare and new neurological conditions can be induced by vaccination, in localised outbreaks - possibly due to MLV-like contamination?

    - Nature of ME/CFS: Impaired neurological and immune function; often relapsing/remitting but I have never encountered a credible account of a complete cure, the condition is considered by most of those who have 'recovered' somewhat to be lifelong - as a risk of relapse, at least - all of which seems consistent with a persistent low-level retroviral infection (especially the peculiar immune impairment).

    I realise that's all pretty sketchy, but in all of these areas, sadly it's the only evidence we have got - none of these questions have ever been properly investigated. To me, the contaminated vaccine theory, combined with the recent discoveries around MLV creation/contamination, and XMRV, presents a very credible narrative with the ability to answer a wide range of mysterious questions which are otherwise very hard to explain. The whole thing is a very complex picture, but the more you look into the details, the more the dots seem to join up and it makes sense. Doesn't mean it's right of course...but I find it quite compelling...I'm really not wedded to vaccine mediated infection as a theory, but it seems like one of the strongest hypotheses going...
     
  14. Bob

    Bob

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    You make very good points here ukxmrv...
    Phylogenetic trees are helpful but cannot be used in isolation.
    And if lab products are contaminated with XMRV, then surely this is a threat to the human population.
    Surely it must be easy for vaccines to become contaminated if no one has been testing cultures, cell lines and xenografts for XMRV contamination up to now.
     
  15. Bob

    Bob

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    Interesting post Mark.
    And a nice summary of the possibilities, thanku.
     
  16. RedRuth

    RedRuth Senior Member

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    I'd have to disagree with that. Alot of money has been wasted on studies involving hundreds of thousands of children to show that there's no link between vaccines and autism, all started by a discredited piece of research. The money could have been spent better on finding the real cause of autism and possible treatments.
     
  17. leela

    leela Slow But Hopeful

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    "Discredited" is a word often used by the media when there is stirred-up controversy like this. Just watch "Under Our Skin" and the Burzynski movie, and you will see how and why skewed studies and smear campaigns that discredit doctors and theories are put together. (It's a horror show of negative propaganda and outright lying.)
    Seeing those films, one can begin to see how this kind of organized harassment is not conspiracy theory it's bald-faced fact. There is a lot of in-fighting not just for protection, but for profit, which really began in earnest in 1980 when it was, against all logic, suddenly permissible to patent organisms.
    This has skewed medical and scientific motivation in unimaginably nefarious ways. Though the films I mention are not about vaccines, I was very much enlightened by them regarding the process by which information is suppressed, skewed, and manipulated for interests other than public health, by the very agencies that are allegedly there to protect it. It really pisses me off!
     
  18. Bob

    Bob

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    Whatever the cause of autism, vaccines can cause neurological disorders in children, and the children have been compensated by the US government.
    The US authorities have also started a new investigation into the link between autism and vaccines. (Sorry, I can't remember the details.)
    Also, there seems to be a link between Gulf War Illness, and vaccines.
     
  19. markmc20001

    markmc20001 Guest

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    I totally agree money has been wasted on vaccine research RedRuth. I also agree that alot of money has has been wasted on all the CFS research by William Reeves, Simon Wessley, the pace trial, etc... :D
     
  20. RedRuth

    RedRuth Senior Member

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    No medical procedures are without risk, that said I think you're referring to the Hannah Polling case. The child had a mitochondrial disorder (a point mutation in the gene for the 16S ribosomal RNA (T2387C)), a subset of which cause autism like symptoms. Children with these disorders often regress when they get encephalopathy from any kind of stress or fever. In this case the US government accepted the fever may have been caused by vaccine ( a common side effect), it could just as easily have been any common childhood infection. I don't know if you have children but fevers aren't exactly uncommon in young children. At worst vaccination can trigger an extremely rare underlying mitochondrial disorder but then again so could any childhood illness.

    Anyway, that's the last thing I have to say about vaccinations.
     

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