William Switzer - CDC looking for XMRV and MLV in lab workers!

[Dreambirdie]

Okay, desperation aside... I am getting the feeling it's time for an emotional intermission on this thread.

Gotta love the Marx brothers!

[video=youtube;9IrCgCKrv8U]http://www.youtube.com/watch?v=9IrCgCKrv8U&feature=related[/video]

 

[Jemal]

Okay, desperation aside... I am getting the feeling it's time for an emotional intermission on this thread.

Gotta love the Marx brothers!

LOL... this thread is hot, hot, hot.

 

[Esther12]

Why are there so many conspiracy theorists amongst us? Is that another symptom of CFS?

CFS has been badly treated. I'm not surprised that it undermines the faith many have in society/authority. It's easy to move from that to a more conspiratorial view of life.

 

[Cort]

Yes, a relatively quick look given the potential consequences and no, they haven't been interested in the same cohort nor in replicating the original methodology or that of Lo/Alter.

Actually that's not true either. If they didn't replicate the PCR and antibody tests in the first study they did in the second and they added their own improved one (as the techniques improved) and they used a similar cohort with the Cooperative Diagnostics study. They have not done culture. I think they did look for MLV's in their first study I believe.

Here's what I got out of the first paper:

Antibody Results - First the CDC personnel crunched up cells that were infected with polytropic murine leukemia retroviruses (MuLv’s) (PMLV) and then developed Western Blot antibody tests that reacted against antigens found in the env and pol regions of these viruses. Two of the tests had been used successfully in studies before to find the virus; Lombardi used the SFFV test to detected XMRV in 19/30 patients in the Science paper. Dr. Singh used another test to prove that XMRV was present in prostate cancer.

PCR tests - a PCR assay on the gag section of the virus that was used by both Dr. Singh and Dr. Lombardi (in the Science paper) to find XMRV in prostate cancer and CFS patients and they looked for a ‘highly conserved’ pol sequence present in both XMRV and MulV. (The pol sequence changes little over time and thus is a check against genetically varied samples) They used samples provided by Dr. Silverman at the Cleveland clinic to ensure that they were able to find the virus. They reported the assays they used were four to five times more powerful than any of the assays used in the previous studies which meant they should have been able to find very small amounts of the virus.

 

[toddm1960]

Bush said that they (The Blood Systems Research Institute) have been getting occasional positives in "pedigreed negatives, some times lab workers" AND UNTIL NOW THEY'VE IGNORED THEM (assuming that they must have been false positives)! And now he's getting worried.


I remember the "pedigreed negatives" being questioned when the BWG first reported. What a coup d'etat it would be if these turn up to be infected lab workers and WPI was the only lab to find them.

 

[August59]

Cort, be careful not to give more weight to short-term trends over long-term research (recency effect might be kicking in for you).

Much more research has to be done, and is currently being done, to determine the importance/existence of XMRV. Until such research is conclusive either way (which it is not currently), look for studies to continue to be published arguing both for and against.

It is entirely too soon to say one way or the other how this is going to play.

Christopher - Do you know what the process is for getting a study published? Does the researcher author pay to have it published? Does the journal buy it? Does a federally funded study automatically get published somewhere?

I have no idea how this "publishing" works. All I can say is that there appears to be several studies\papers that are on the "for" XMRV side, but they cannot get them published due to journals do not think a "for" XMRV study will help sales for their journal. However, the "not for" studies are making it into just about any journal the prefer.

I just get the impression that "good science" and "capitalism" is not giving us the truth.

I really want to find out how the publishing process works

Thanks

 

[Dr. Yes]

Originally Posted by CBS Yes, a relatively quick look given the potential consequences and no, they haven't been interested in the same cohort nor in replicating the original methodology or that of Lo/Alter.

Actually that's not true either. If they didn't replicate the PCR and antibody tests in the first study they did in the second and they added their own improved one (as the techniques improved) and they used a similar cohort with the Cooperative Diagnostics study. They have not done culture. I think they did look for MLV's in their first study I believe.

Actually Cort, CBS is correct. The CDC has never replicated the WPI's methodology for PCR and serology assays. They used different methodologies in both cases. In order to be so certain that your assay can detect something that failure to detect it would imply absence of that 'something', you really should test that assay on a clinical positive sample. Now it's possible that there is nothing to detect in there, but if others can detect stuff there and you can't (using the same primers in the case of PCR), that suggests the possibility that your assay doesn't work. Using the assays from its published studies, the CDC could not find a single positive in over twenty sent by the WPI. (Using two different PCR assays as part of the BWG, however, they COULD find positives in WPI samples.) So the smart thing to do, the scientific thing to do, would have been to attempt to replicate the WPI's methods and compare the results on the same samples to the ones they got with their own assay. They of course did not do this.

I gotta go. But I do hope we can all agree to check our facts before posting distorted interpretations of scientific information.


ETA - Hey Dee Bee! Thanks for the Marx Bros.. here's one from Groucho that reminds me of scientific discussions...

"Who are you going to believe, me or your own eyes?"
​

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[CBS]

Originally Posted by Jemal
Why are there so many conspiracy theorists amongst us? Is that another symptom of CFS?

CFS has been badly treated. I'm not surprised that it undermines the faith many have in society/authority. It's easy to move from that to a more conspiratorial view of life.

No conspiracy theories necessary. All it takes are a bunch of bureaucrats with no real skin in the game. CFS did not inform my lack of faith in governmental agencies. Working directly with governmental agencies more than convinced me that far too many "public servants" go that route for the security (aka "not rocking the boat of the established/predominant belief system") with little real passion for what they are doing. And if they entered the field with some passion, the bureaucracy most likely killed it in fairly short order.

When you listen to Marc Conant talk about the AIDS crisis, he cautions us to remember that the government is not our friend and that only scientific proof will force them to action. For the most part, it is the private interests that are irritating the govt agencies into action. There are people like Alter who manage to retain their integrity as they get higher on the chain of command. Too many of the others rise to positions of power because of their willingness to kiss some supervisors backside. I have great respect for the exceptions to this "rule" but make no mistake, they are the exception.

 

[Cort]

I don't know if that's correct; even Miller in his comment to Retrovirology about Paprotka et al states that he'd like to see evidence to support that assertion. In any case, and I repeat, Paprotka et al findings only apply to two of the fourteen integration sites identified in prostate cancer. They could not explain the other 12 as contamination.

From Racaniello - I do see that he said it 'is often ubiquitous' so I will pull back a bit on that http://www.virology.ws/. I thought he said it was always true.

These observations do not directly impugn the veracity of the other 12 XMRV integration sites identified in prostate tumor DNA. However, when DNA contamination occurs it is often ubiquitous. Hence the authors write:

Whilst it is conceivable that the other 12 integration sites apparently derived from prostatic tumor tissues are genuine patient-derived sequences, we suspect that some or all of them may also be the result of contamination with DNA from experimentally infected DU145 cells.

Dr. Yes - I know quite a bit about population genetics, as it happens! :Retro wink: Enough to have seen that Hue et al used a tiny sampling of extremely closely related human XMRV samples.. remember, until recently very specific primers have been used and only small amounts of the genetic diversity that's out there had been detected. Also, the claim that XMRV came from 22Rv1 kind of clashes with the other contamination argument that it came from DU145, doesn't it?

Hue used what he had. http://www.retrovirology.com/content/7/1/111/figure/F2 He had about 15-20 different clones from 22RV1, prostate cancer and the two full length clones from the WPI from CFS patients - so yes, he did not have many CFS patient clones....Then again what are the odds that both CFS strains would be so identical to each other and 22RV1?They are almost identical.

Plus, as I noted the WPI reported that the gag and env sequences of all the positive samples in the WPI study are 99% identical to each other (and to the reference strain (VP62)). Is it likely that hey remained stable and the rest of the genome changed? That just doesn't seem likely. The most likely conclusion it seems to me is that that all the original samples at the WPI are probably much like the two fully sequenced strains.

Which means they are very similar to VP62 and 22RV1 - which means the XMRV infection hypothesis for CFS is trouble. (That is unless XMRV just doesn't change when its in the human body). Yes, the evidence is ALL circumstantial..... and it's hard to explain away as well.

Dr. Yes - Not exactly - those three labs that found that their samples were contaminated did not find the wide difference in positivity rates between test subjects and controls that the WPI and others have. Similar results between test subjects and controls suggest contamination. Major differences suggest no contamination (and disease association).

Are you sure of that? Actually there were big differences -but one was in the wrong direction.agree that the differences in the WPI's test subjects and controls is an important point....some questions about that have been discussed. As I noted the BWG test will tell all - I think we can agree on that?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022687/?tool=pubmed

Surprisingly, a high proportion of DNA samples from the healthy volunteers (19/36), but only 2/112 of the CFS patients, yielded PCR products of the correct size, as tested on an agarose gel.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019155/?tool=pubmed

Twenty-one samples were positive for XMRV using the gag leader primers, and of these, 17 were from cancerous tissue and 4 from benign tissue.

Dr. Yes - Again, the CDC HAS detected XMRV in the Blood Working Group before, using samples from WPI pedigreed positive patients. But that was using different PCR assays that they have since abandoned...

Yes, but they also didn't find XMRV as often or more than they did find it....so it was clearly not a reliable test. It had at least 50% blow it rate did it not? It was definitely not ready for prime time. This is a pretty darn weak hook to lay your hat on.

Dr. Yes - It is not necessary to show integration to prove infection. Integration was not the yardstick for determining whether an agent was infectious or not for the vast majority of viruses that are accepted to cause human disease. A principal way to demonstrate that a virus is infectious is to look for an immune response to it. That is precisely what the WPI and NCI have done, and they have already reported these results at conferences (take their UK study, for instance, as reported at the BPAC and XMRV Workshop). Of course those results haven't been published yet, nor have the ones about cytokine profiles specific to XMRV positive patients, but we have seen the abstracts discussing these results.

No, no, no Dr. Yes. That kind of immune response will not do. Think about it.....That kind of response is not necessarily specific to XMRV and they want something specific to XMRV do they not?

Thankfully, there is an immune test that will do that and that is the antibody test results.....Those are the key - Dr. Mikovits has said that from the beginning. Right now - they apparently are pretty poor (based on the BWG report)> Hopefully by the next BWG report they will be better.

 

[alphahusky]

And Stoye appears to have tested himself more than once ("at least I was negative the last time I was tested". I wonder if he's tested himself multiple times in the recent past. He might be concerned about subsequent exposure or he may be serving as a "pedigreed negative" Still, it makes me wonder how much he believes in his own test.

If it's so innocuous, why bother getting tested? That's what I'm wondering.

 

[Dr. Yes]

Hue used what he had. http://www.retrovirology.com/content/7/1/111/figure/F2 He had about 15-20 different clones from 22RV1, prostate cancer and the two full length clones from the WPI from CFS patients - so yes, he did not have many CFS patient clones....Then again what are the odds that both CFS strains would be so identical to each other and 22RV1? Plus that the gag and env sequences of all the positive samples in the study would be 99% identical to each other (and to the reference strain) while the other parts of the genome changed radically. That just doesn't seem likely. The most likely conclusion it seems to me is that they were probably much like the two fully sequenced strains.

My understanding is that the gag and env fragments were bulk-sequenced in Lombardi et al, which means that some genetic diversity would be missed, such as the P-type viruses. The other point about Hue et al is that they ignored the possibility that the original source of the virus was the prostate tumor, not the mice. Garson et al tried to discount this possibility for DU145, but unconvincingly in my opinion.. I'm not sure about Coffin's latest as we have yet to see the full paper.

That kind of immune response will not do! Think about it Dr. Yes.... That is not necessarily specific to XMRV and they want something specific to XMRV do they not?

I am thinking about it Cort, you just misunderstood what I was saying. I was talking about the same thing you are - the immune response demonstrated, for example, in the UK study and by the NCI, using antibody tests.

I'm not sure how specific those tests are to XMRV, but they definitely provide evidence of infection with an MLV. Let us assume that they are not specific to XMRV: if you have a patient who is producing MLV-specific antibodies and he also happens to have XMRV (or PMRV) nucleic acid in his blood, how likely is it that those antibodies are being produced to something other than the MRV?

The cytokine profile stuff is additional evidence to support the serological evidence.

And now I will stop LYING to myself and actually lie down.

 

[Cort]

If it's so innocuous, why bother getting tested? That's what I'm wondering.

I think their actions suggest that its not necessarily innocuous - and how could they know? Its a new virus - it can infect human cells - its a retrovirus - the potential is clearly there for trouble.

 

[Cort]

My understanding is that the gag and env fragments were bulk-sequenced in Lombardi et al, which means that some genetic diversity would be missed, such as the P-type viruses. The other point about Hue et al is that they ignored the possibility that the original source of the virus was the prostate tumor, not the mice. Paprotka et al tried to discount this possibility for DU145, but unconvincingly in my opinion.. I'm not sure about Coffin's latest as we have yet to see the full paper.

I am thinking about it Cort, you just misunderstood what I was saying. I was talking about the same thing you are - the immune response demonstrated, for example, in the UK study and by the NCI, using antibody tests.

I'm not sure how specific those tests are to XMRV, but they definitely provide evidence of infection with an MLV. Let us assume that they are not specific to XMRV: if you have a patient who is producing MLV-specific antibodies and he also happens to have XMRV (or PMRV) nucleic acid in his blood, how likely is it that those antibodies are being produced to something other than the MRV?

The cytokine profile stuff is additional evidence to support the serological evidence.

And now I will stop LYING to myself and actually lie down.

I see that you were referring to the UK antibody tests. That seemed like a very powerful study. What the WPI really needs, though, is for a completely independent lab to come with their results. I just think that's necessary.

The BWG results were not very convincing - its really hard to reconcile the good antibody results in the UK study with the really poor antibody results during the small BWG test. If the NCI had been right then I would thought 'aha'! they got it but neither they nor the WPI (according to what Dr. Mikovits said) were able to figure who was positive and who was negative consistently. On the other hand I know that was a very small test and a really preliminary finding. - so you can't draw firm conclusions from that either.

We won't really know until the BWG blinded test - I know someone said it's not necessarily the end all and be all - but I think that will have huge consequences; either XMRV starts forward on new legs or it's kind of over. That'll be a direct test - its not circumstantial evidence, its not theoretical - it'll be very black and while. I imagine that breaking those codes will be an incredibly intense moment for all involved. I would be a nervous wreck....

Thanks about the bulk sequencing. I don't what that it is - I had never heard of that before .....so maybe some variation was missed....I will have to look at Paprotka's paper - the latest paper is the one, of course, that all the controversy has stemmed from.. It is only one paper and I assume that it needs to be validated. It is certainly possibly to get carried away in the sweep of things - and I do sometimes.

I agree that the cytokine evidence is helpful...and I think we can all acknowledge that the antibody tests have to work out for it to really play a role. Hopefully they will.

Interviews - I have an interview with Satterfield from Coop Diagnostics coming out. I've also asked Dr. Mikovits for an interview and I provided both her and Annette with the Satterfield interview in advance.

My goal - My goal is to deal with the evidence in as rigorous and objective a manner as possible and not to be tied to any outcome..to presuppose nothing, really and try and walk the evidence down and see where it leads. That is definitely a work in progress! but it is something to reach for.

I do realize that everyone has their own interpretations and everybody's interpretation is valid.

I think it may be a rather turbulent couple of months. My guess is that just about everything will end or come to a climax with the BWG study. Until there are going to be differing opinions and differing interpretations. Accepting some interpretations is a struggle for me at times...I get worked up.

I recognize that we are all coming from a bit different places and they are all valid interpretations and will try to remember that and honor that on the Forums.

 

[SilverbladeTE]

Why are there so many conspiracy theorists amongst us? Is that another symptom of CFS?
.

Oh with me it's loooong story/history

great grandpa fought in WW1, so fighting in mud drowning trenches of France in British army.
He and his mates kept finding the Germans had lovely, well-made concrete bunkers unlike the British mostly crap ass ones and trenches deep in mud guys drowned in.
In the German bunkers they'd used cement bags from their construction as flooring to keep mud/dirt down.

So as war ended they were going back home and found this ENORMOUS underground bunker complex the UK high command had made, it even had a freakin' stable, so the gentry could ride aroud on horse back after tiffin, what ho!
And again, same cement bags...
And then on the docks in Belgium, cement bags: same company had supplied BOTH sides during the war.
To say he was angry at that treachery is an understatement.

That and other crap he and others suffered (like making him go back to unexploded charges in the mines that blew him up twice) made him an ardent Communist, lol, no wonder he hated the stupid "System".

Lots of other stuff like that in family and personal experience makes you see how bloody stupid, greedy and cowardly things end up going
Human Beings always take things to extremes in groups: Power corrupts, absolute power corrupts absolutely.

I don't believe in some vast super-powerful "Illuminanti" crap, just...plain old crap en masse

 

[Rooney]

Power corrupts, absolute power corrupts absolutely.

Go Lord Acton!

 

[VillageLife]

As Kathy Jones (NIH) said, there is a lot about XMRV/MLVs that does not conform to what has been assumed to be known about murine retroviruses.

Of course, thats because its a lab-made retrovirus

 

[Cort]

Oh with me it's loooong story/history

great grandpa fought in WW1, so fighting in mud drowning trenches of France in British army.
He and his mates kept finding the Germans had lovely, well-made concrete bunkers unlike the British mostly crap ass ones and trenches deep in mud guys drowned in.
In the German bunkers they'd used cement bags from their construction as flooring to keep mud/dirt down.

So as war ended they were going back home and found this ENORMOUS underground bunker complex the UK high command had made, it even had a freakin' stable, so the gentry could ride aroud on horse back after tiffin, what ho!
And again, same cement bags...
And then on the docks in Belgium, cement bags: same company had supplied BOTH sides during the war.
To say he was angry at that treachery is an understatement.

That and other crap he and others suffered (like making him go back to unexploded charges in the mines that blew him up twice) made him an ardent Communist, lol, no wonder he hated the stupid "System".

Lots of other stuff like that in family and personal experience makes you see how bloody stupid, greedy and cowardly things end up going
Human Beings always take things to extremes in groups: Power corrupts, absolute power corrupts absolutely.

I don't believe in some vast super-powerful "Illuminanti" crap, just...plain old crap en masse

The wonderful old Brit class system....

 

[CBS]

If it's so innocuous, why bother getting tested? That's what I'm wondering.

And what if Stoye tests positive? What is going to do, go on ARVs?

He's been one of the lead voices screaming at very sick CFS patients about the irresponsibility and danger of using ARVs (I know of only 4, maybe 5 CFS patients who have blogged about using ARVs).

He tests positive and I'm calling BS on it. I suggest we demand that he contact his compatriot, PW and see if he can get enrolled in some of that CBT and GET.

 

[CBS]

The wonderful old Brit class system....

I'm going to ask that you retract that statement. It's a cop-out and its prejudiced. We have just as much of a class system here.

 

[VillageLife]

these highly contagious man-made retroviruses

I think this has to be one of the biggest and saddest days in the history of the disease ME CFS.
here are 20 million people who may have been accidentally infected with a human retrovirus made in a lab.
What a very very sad situation.
Some people are bed bound because of this virus, others have no job, no money and there whole life has been destroyed, the suffering that these people have gone through.
I feel like I want to cry but If I start I dont think I will be able to stop.