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CFIDS: THE ITERATION OF X (A breakdown of the Dr. Singh's Study)

Cort

Phoenix Rising Founder
It is possible the WPI are better able to find XMRV/MRV in the blood than Dr. Singh.
The WPI have said more than one time, i think, that the blood is not a good place to look for MRV.

I would be very surprised if Dr. Singh was not, at least at this point, much better at finding XMRV than in the blood than the WPI was a year and a half ago. Virtually every researcher should be better at this point than the WPI was back then. Why? Because we know so much more about XMRV. All its proteins have been painstakingly isolated; they know which receptors it enters through, extensive genetic analyses have been done....specific antibody tests have been developed for it. More PCR tests have been developed and they are more sensitive than ever....they know which kind of fluids test best, whether storage conditions are a problem.....blah blah blah

Remember that the WPI put out a paper indicating that they had changed their testing procedures since the original study...

'The WPI used a gag and an env test and an antibody test that was not specific to XMRV. Dr. Singh used 9 tests including several from the original paper. She is working with one of the top speciality diagnostic labs in the country (ARUP_. Given her resources I would expect that she would able to come with a better test than the WPI, I would think. After all she's been studying XMRV longer than they have...
 

Cort

Phoenix Rising Founder
I strongly disagree. This is your opinion, but i don't think it's a good interpretation of the facts. The studies concluding that there is no association between XMRV and ME/CFS were 0/0 studies. While it's really very hard to explain why there have been so many studies with this result (i don't know why), those studies have little credibility, as long as the prostate cancer studies are not discredited. Because they are contradicted by those. So i don't think they are a strong argument against the positive studies. Even though it might be true that Lombardi et al. and Lo et al. were wrong, i don't deny this possibility.

I also don't like everything the WPI has done and i also expect answers. And results, even more.

But it's not only them, who have said that XMRV is probably hard or at times even impossible to find in the blood. The macaque study concluded the same. So does the latest Switzer study.

Please don't evade and comment on the question that seems to be the most important one:
How can the 0/0 studies be valid, if the positive prostate cancer studies are not seen as wrong?
I don't think it's possible. So before those are proven to have been wrong, i don't see how you could use the 0/0 studies as arguments.

Its easy to explain the difference between the prostate cancer studies and CFS; one is looking for XMRV in the tissues and one is looking for it in the blood. It may be present in the tissues and not in the blood. It could also be that its present in prostate cancer but not in CFS. But to suggest that the egative studies have little credibility because the some researchers have found it in the prostate - that doesn't really follow to me.

I think we can overinterpret the macaque studies. They were directly injected with an enormous of virus - far more than an animal or human would be directly exposed to in nature. (If it was HIV it apparently would have quickly killed them). Yes the virus was able to spread throughout their bodies but the immune system appeared to quickly get it under control and the animals suffered no apparent negative effects. So yes you can say - looking at that study - that yes, it infected the animals but also - they quickly controlled it.

The macaque studies were done in order to produce the antibody - not to determine the pathogencity of XMRV. That is why they, force fed, so to speak the primates with so much virus. If they had been exposed to 'normal' levels of the virus its possible they might have fought it off.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
Its easy to explain the difference between the prostate cancer studies and CFS; one is looking for XMRV in the tissues and one is looking for it in the blood. It may be present in the tissues and not in the blood. It could also be that its present in prostate cancer but not in CFS. But to suggest that the egative studies have little credibility because the some researchers have found it in the prostate - that doesn't really follow to me.

I think we can overinterpret the macaque studies. They were directly injected with an enormous of virus - far more than an animal or human would be directly exposed to in nature. (If it was HIV it apparently would have quickly killed them). Yes the virus was able to spread throughout their bodies but the immune system appeared to quickly get it under control and the animals suffered no apparent negative effects. So yes you can say - looking at that study - that yes, it infected the animals but also - they quickly controlled it.

The macaque studies were done in order to produce the antibody - not to determine the pathogencity of XMRV. That is why they, force fed, so to speak the primates with so much virus. If they had been exposed to 'normal' levels of the virus its possible they might have fought it off.

I think Eric was saying that if some prostate cancer studies found xmrv in controls (as well as in PC) then the fact that the 0/0 studies found no xmrv at all may indicate they just can't detect xmrv, not that it isn't in the samples. Weren't there some PC studies that used just blood (not tissues) and found xmrv in both controls and (in higher prevalence) PC blood.

It's possible that this was just contamination and the PC and ME samples in the positive studies tested positive for HGRVs with higher frequency because they may have been handled more/differently. But the fact that the percentage is always 2-4% (and once 7%) makes it seem that contamination is unlikely.

It seems to me that Singh did an excellent study, though I am a layperson and not conversant in 'science'. You agree that it's possible hgrvs were present in the patients' tissues, but not blood. Do you think, then, as I do, that it is overreaching to say flatly that "xmrv is not associated with CFS." This is the 'take away' message anyone reading the news on this gets.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
You can not prove a negative. It is like trying to prove the loch ness monster does not exist, it can not be done. So scientist are doing what they can do, try everything they can think of to find XMRV with basically no positive repeatable results. Only a few of the prostate studies found XMRV just like a few blood studies but serious questions have be raised about some of that data. I can go and look it up but it was published and discussed here earlier that some of the techniques used to find XMRV in prostate cancer are highly susceptible to contamination.
Where am i asking to prove a negative? Prove the positive... find the reason why the prostate cancer studies were wrong. Find the contamination there. Or prove the assay from this latest study is able to find XMRV by using it on the positive subjects from Schlaberg et al.
You have not answered my question. Before those thwo results are in concordance, you can't rule out the association between XMRV and ME/CFS
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
I would be very surprised if Dr. Singh was not, at least at this point, much better at finding XMRV than in the blood than the WPI was a year and a half ago. Virtually every researcher should be better at this point than the WPI was back then. Why? Because we know so much more about XMRV. All its proteins have been painstakingly isolated; they know which receptors it enters through, extensive genetic analyses have been done....specific antibody tests have been developed for it. More PCR tests have been developed and they are more sensitive than ever....they know which kind of fluids test best, whether storage conditions are a problem.....blah blah blah

Remember that the WPI put out a paper indicating that they had changed their testing procedures since the original study...

'The WPI used a gag and an env test and an antibody test that was not specific to XMRV. Dr. Singh used 9 tests including several from the original paper. She is working with one of the top speciality diagnostic labs in the country (ARUP_. Given her resources I would expect that she would able to come with a better test than the WPI, I would think. After all she's been studying XMRV longer than they have...
All of this doesn't matter. She has now two studies out that have conclusions that logically can't both be true, given the data.

As long as this is not resolved, you can't draw a conclusion regarding ME/CFS and XMRV based on this work.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Its easy to explain the difference between the prostate cancer studies and CFS; one is looking for XMRV in the tissues and one is looking for it in the blood. It may be present in the tissues and not in the blood.
Yes, exactly. And given this possibility should we now move on from XMRV? I'd think not. And you, as having a ME/CFS charity, should fight for this question to be answered (wheter it's there in tissues or not), i guess.
It could also be that its present in prostate cancer but not in CFS.
The two studies by Ila Singh don't allow that conclusion, as one has found XMRV in healthy controls and the other one hasn't. If the prostate cancer study was correct, XMRV is in 4% of healthy controls. The ME/CFS study found it in 0% of healthy controls. So if the prostate cancer study was correct, the ME/CFS study would have to be wrong. Unless XMRV only appears regionally (which Ila Singh in her video has said she doesn't believe).
But to suggest that the egative studies have little credibility because the some researchers have found it in the prostate - that doesn't really follow to me.
I've said why it's like that in the paragraph above. It's a sound logical conclusion. Tell me why not.
The point is that they have found it in healthy controls. You can't find it in healty controls in one study and not in the other one and say both are correct, if the number of healthy controls is large enough, and it was. The chance for this to happen (no XMRV+ in 200 samples, given a chance for XMRV to be present of 0.04, according to Schlaberg et al.) is extremely small.
Unless XMRV was a regional phenomenon and the studies were designed in such a way that this could lead to conclusions that can't be generalised to the entire population. Which would be a bad design anyway, i'd think.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
CAA has gone way too far once again

CAA's attitude of "XMRV is not related to ME, case closed" is absolutely unacceptable. CAA needs to dissolve; it is acting against bona fide science and patients far too often to be considered a non-profit and thus is operating unlawfully, in my opinion.
 

LJS

Luke
Messages
213
Location
East Coast, USA
CAA's attitude of "XMRV is not related to ME, case closed" is absolutely unacceptable. CAA needs to dissolve; it is acting against bona fide science and patients far too often to be considered a non-profit and thus is operating unlawfully, in my opinion.

Huh? If you look at the bona fide science it is hard to come to any other conclusion: the WPI is not in fact finding XMRV in blood but something else. That is why the overwhelming percentage of scientist think that XMRV is not present in CFS. It is still possible the WPI is the only one able to find XMRV but highly unlikely considering the extent to which other have tried and come up empty handed at this point. The CAA follows the science closely and reports what the current state of science is which currently is that XMRV most likley has nothing to do with CFS. I think the CAA is great, they are calm cool and collect. I have no idea why you think they are operating unlawfully, that is pretty off base.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
It is still possible the WPI is the only one able to find XMRV but highly unlikely considering the extent to which other have tried and come up empty handed at this point.

NCI, CC and Cornell have found xmrv in ME. FDA and NIH found four other closely related strains. I think Singh said she looked for related HGRVs in this study and couldn't find them either (so that's contrary to the FDA and NIH study). And Singh and everyone else who has found xmrv in controls has found it in higher percentages in whatever else they were looking at (Prostate Cancer or ME) except I guess Switzer in his last study which found it in 2% of PC (and i assume the same percentage in controls since the title of the paper was that "xmrv isn't associated with PC", but in his ME study didn't find it at all, even in controls).

So it is very clear that the science does not support the what CAA and Singh are saying.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
Someone emailed me to ask where CAA said "XMRV is not related to ME, case closed" as I put it. They didn't literally say that in 'the iteration of X' (whatever that's supposed to mean). It was just my summarizing of the tone I felt they were strongly trying to put across.

It seems to me they are deliberately not saying those words, so they can't be accused of saying that, while saying lots of "wrapping it all up and moving on" type talk to give the feeling that it's all done and we need to move on now. like someone got fired (WPI and XMRV) and the boss is saying "well they failed, but we learned a lot from their mistakes and we wish them well in their leaving to pursue other opportunities."

That may seem like reading too much into it to some, but I really feel that way, so I'm saying it.