Possible Smoking Gun? XMRV, CFS, Silverman in Chicago Tribune

[Cort]

One thing this article tells me is that whatever you do not, DO NOT get on Trine Tsoudero's bad side....Whew!

http://www.chicagotribune.com/health/ct-met-chronic-fatigue-xmrv-20110317,0,6116823.story?page=1

The key thing, though, is the startling comment from Silverman, the researcher who discovered XMRV...that his lab or one close to it - did use 22RV1 at one time, contrary to previous reports.

Possible Smoking Gun - That does potentially set up a straight line from his lab to the WPI...It's still circumstantial but if he passed them samples or reagents or whatever....he could have passed them XRMV as well. In this scenario the WPI didn't do anything wrong - they didn't contaminate anything - XMRV was passed from him to them and he got it from 22RV1.

Well see how it turns out. There is no smoking gun right now - just the possibility of one. Just because he has 22RV1 in his lab doesn't mean XMRV jumped into his prostate tissues - lots of labs have 22RV1 cell lines. If it got into his tissues a good question would be why it got into his and not other labs. Lot's of if's.

It may be important to determine what, if any materials he shared with the WPI and when he shared them.

We'll know where he's really at when he comes out with whatever paper he comes out with but he's being very honest right now...He is the guy that started this after all.

Cancer biologist Robert Silverman, a key researcher at Cleveland Clinic's Lerner Research Institute who worked on studies that linked XMRV to chronic fatigue syndrome and prostate cancer, told the Tribune his lab had stored a cell line known to harbor XMRV and he was working to determine if contamination occurred. Virologists who have examined work by Silverman and others have raised serious questions about contamination, an unfortunate but not unusual mishap in the field.

"I am concerned about lab contamination, despite our best efforts to avoid it," Silverman wrote in an e-mail, adding that similar cell lines "are in many, many labs around the world. Contamination could come from any one of a number of different sites."

......................

The viruses, according to research Pathak presented at the Boston conference, recombined in a cell line called 22RV1 to create a new retrovirus — XMRV — sometime in the 1990s. The work is in the publication process.

That widely used cell line had been stored in Silverman's lab before he found evidence of the retrovirus in the prostate tissue of patients with a form of prostate cancer.

"22RV1 cells were once previously (more than a year earlier) grown in my lab but were being stored in a liquid nitrogen freezer at the time, and not the same freezer used to store prostate tissues," Silverman wrote in an e-mail. "At the time it was unknown that 22RV1 cells were infected with XMRV."
..........

Scientists have been reluctant to shut the door completely on the possibility that XMRV really is tied to human disease. Some questions remain unanswered, said Racaniello, of Columbia University. "I don't think it is time to put a lid on it," he said. "You have to carry the whole thing to its conclusion."

"

 

[WillowJ]

comparasin to Watergate, a deliberate fraud, is a very poor analogy. This is and has always been a good-faith effort on the part of the positive XMRV side (not so much for all of the negative XMRV side). I had come to expect better from Racaniello.

 

[liquid sky]

Looks like the politics are not going to go away. Too bad these scientists can't just let the science work out the truth, instead of trying to preempt it.

 

[FunkOdyssey]

The contamination theory is invalidated by the dramatically higher prevalence of xmrv in sick patients vs. healthy control samples. Contamination has no such discriminatory capacity.

And it's just common sense. You don't need a PhD in retrovirology to figure that one out.

 

[markmc20001]

Goes to show...

uggghhh.

no fly zone

 

[ixchelkali]

Yada yada yada, Trine Tsoudero keeps singing the same old song. Ironic the way she harps on patients getting ahead of the science, when she's not willing to wait for science to run its course before she declares XMRV is history.

I think we should just ignore her. She likes to play bait the patients.

 

[urbantravels]

You know, I just don't feel like giving that woman any clicks today. Wake me when a real science reporter gets something in print.

 

[eric_s]

I don't think the fact that Silverman has had that cell line in his lab is anything close to some sort of proof for contamination. Don't labs work with viruses all the time? So i think experienced people will know how to avoid and check for contamination. If just the presence of a virus in a lab would be a problem then a lab testing for HIV, for example, could not be used for any further HIV related work anymore after testing one positive sample (put a bit extremely).

A European research team this week reported being unable to find any evidence of XMRV in the blood of people diagnosed with chronic fatigue syndrome and their healthy peers, the latest in a stream of studies in which researchers looking for the retrovirus in the blood of both sick and healthy people have come up empty. Others have reported no evidence of the retrovirus in the blood of patients who were previously found to be XMRV-positive.

Trine Tsouderos also doesn't seem to be aware of the 2 new positive XMRV/prostate cancer studies published this week in the Journal of Urology. Or does she only doubt the association with ME/CFS? Either way, the positive prostate cancer studies provide evidence for the virus being in the population.

 

[omerbasket]

Wow, Cort, good for you not to jump ahead.
Perhaps he even sent the FDA the PMRVs. And also Cornell.
And perhaps the WPI sent the contamination to VIP Dx, and they sent him to RED labs, and it also interfered with Dr. De-Merleir's work.
And what about the work of Hohn when he did manage to find XMRV in respiratory tract secretions? And the work of Dr. Singh... And Dr. Danielson... And those others who had found it in prostate cancer...
And wow - that virus is some kind of a virus, huh? I mean, managing to produce antibodies from just contaminating samples in the lab? Perhaps we should call it a mega-virus.

Wow, man, thank you, Cort, if it wasn't for you I wouldn't have known about all of the abilities of this extraordinary mega-virus!
Fantastic!

 

[LaurelW]

Yada yada yada, Trine Tsoudero keeps singing the same old song. Ironic the way she harps on patients getting ahead of the science, when she's not willing to wait for science to run its course before she declares XMRV is history.

I think we should just ignore her. She likes to play bait the patients.

What ixchelkali said. I don't even bother to read her articles any more because I can tell you exactly what she's going to say. She's a lousy reporter with an agenda to push.

 

[omerbasket]

What ixchelkali said. I don't even bother to read her articles any more because I can tell you exactly what she's going to say. She's a lousy reporter with an agenda to push.

I agree. I also think that we should ignore her and her articles.

 

[kurt]

Looks like the politics are not going to go away. Too bad these scientists can't just let the science work out the truth, instead of trying to preempt it.

No matter how often people say this is 'politics', it is not. This is a scientific challenge, not a political battle. There ARE political battles we have to fight, this is not one of them.

The contamination theory is invalidated by the dramatically higher prevalence of xmrv in sick patients vs. healthy control samples. Contamination has no such discriminatory capacity.
And it's just common sense. You don't need a PhD in retrovirology to figure that one out.

Umm, actually yes you do need a strong science background to understand this one. There are ways for contamination to be different in various samples based on differential handling, different sources, and even interactions of reagents with specific DNA segments. This has happened before.

There could also be explanations somewhere in the middle ground, hopefully someone with the budget will run the tests necessary to track down the answers.

 

[FunkOdyssey]

Umm, actually yes you do need a strong science background to understand this one. There are ways for contamination to be different in various samples based on differential handling, different sources, and even interactions of reagents with specific DNA segments. This has happened before.

Could you provide some examples?

 

[eric_s]

I do think there is politics involved or however one wants to call it. I don't know what the motives are, they might even be justified (at least in some cases), but i see too many things that don't look as if they happen "just like that".

It would also not be too much of a surprise, this is potentially a very big deal (a new human retrovirus), so how could there not be any politics?

 

[Cort]

I do think there is politics involved or however one wants to call it. I don't know what the motives are, they might even be justified (at least in some cases), but i see too many things that don't look as if they happen "just like that".

It would also not be too much of a surprise, this is potentially a very big deal (a new human retrovirus), so how could there not be any politics?

Where would the politics be coming from? I would guess from people who would stand to lose (downplay it) and who would stand to gain if XMRV is found (push it). Losers would probably include insurance companies, behavioral therapists and psychologists (altho even they work)

The gainers would be the pharmaceutical companies (new drugs) and the retrovirologists. Now I grant you that this far into the field retrovirologists have begun to take up positions and now THAT comes into play but they didn't start out that way...

What about the idea in the research community that CFS is a psychological disorder? How does that effect the search for XMRV? That would effect it by having retrovirologists being reluctant to study it because, after all, its a psychological disorder. As we've seen, though, the retrovirology community has been very happy to study XMRV - the studies are continuing to pour out - and ironically, for the CFS bashing theory, it was a paper on XMRV in CFS that kicked all this activity off....there was not alot of work being done on XMRV before the WPI produced their paper.

The CFS paper also kicked off alot of interest in prostate cancer...and in the basic biology of XMRV as well as on CFS. I know the WPI has had trouble getting funding but the research community doesn't really seem to have cared that much that XMRV was found in CFS. It appears that they jumped on it full bore.

 

[eric_s]

I was thinking about governments and government agencies. If XMRV is causative for ME/CFS there will be a lot of questions why ME/CFS has been treated the way it has been for so long. And if XMRV is a pathogen that is in the population and the blood supply, regardless of it's role in ME/CFS, this would be a major story as well. So, certainly politicians and government officials would try to "manage" the unfolding of this story in one way or the other. How much information is released to the public and when etc. This is their job to some degree after all.

And then there is probably a lot of money to be made, if XMRV is relevant, so everybody will try to secure this for themselves. Not sharing all they know, maybe even try to discredit the competition etc. I'm just guessing, but to me all that happens does not really make sense and the explanation for this might be that there are many things going on that we don't know about and can't understand because we are not given all the information, not told the motives and so on.

 

[FunkOdyssey]

Could you provide some examples?

Still waiting for previous examples in science where in at least two separate studies, sick patients turned up positive at a consistent ratio of between 10:1 and 15:1 compared to healthy controls for a lab contaminant virus.

You might find this interesting too:

http://www.drlapp.net/meLetterMar2011.htm

Dr. David Strayer, Medical Director at Hemipsherx Biopharma, described a retrospective study of the response to Ampligen in subjects who were positive or negative for XMRV. XMRV was tested at VIP Labs, which is associated with the Whittemore-Peterson Institute, and used similar techniques as those employed by Dr. Mikovits at the WPI.

In one study, serum from 208 subjects from a previous double blind placebo controlled Ampligen study were analyzed for XMRV. About one third were positive for the virus and two-thirds were not. Activity monitoring demonstrated less activity in XMRV+ subjects. That is, they were less active and presumably more ill.

Specifically, the improvement in exercise ability was monitored in these subjects. More improvement was measured in XMRV+ subjects than in XMRV-subjects. The table below describes the percentage of subjects who obtained at least 25% improvement in treadmill exercise duration at week 40 of treatment, as related to XMRV serology:

XMRV Status Improved on Ampligen Improved with placebo Difference (AMP-PBO)
Pos (n=81) 44.7% 17.6% 27.1%`
Neg (n=127) 34.0% 25.7% 8.3%
Overall 39% 23% 15.9%

Dr. Strayer concluded that there was a 70% greater than average exercise response in XMRV+ subjects, and a 40% lower response in those who were XMRV-.

Medication use was monitored in all of these subjects as well. 53% of XMRV+ subjects were able to reduce their use of symptomatic medications, while only 32% of XMRV- subjects were able to reduce medication use.

These data suggest that subjects who are XMRV+ have an edge in responding to Ampligen, and that Ampligen may be a treatment for CFS.

So depending on whether you have antibodies in your blood to the "lab contaminant", you respond better or worse to Ampligen. Pretty cool right?

 

[katieann]

"(The FASEB Journal. 2011;25:429.3)
2011 FASEB
--------------------------------------------------------------------------------

429.3

The Retrovirus XMRV in Prostate Cancer and Beyond
Robert H Silverman
Cancer Biology, Cleveland Clinic, Cleveland, OH

Genetic evidence that the antiviral protein, RNase L, suppresses hereditary prostate cancer led us to examine the possibility that chronic viral infections might predispose men to prostate cancer. These studies resulted in identification of a previously unknown gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV). Currently, several different research teams have published both PCR-based and non-PCR-based evidence in support of the hypothesis that XMRV is a bona fide human virus. In addition, some but not all studies associated XMRV infections with either prostate cancer or chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME). XMRV replication is stimulated by androgen and inhibited by interferon through host restriction factors, such as apobec3, tetherin and RNase L. Studies in rhesus macaques showed that intravenous inoculation with XMRV caused wide-spread dissemination of the virus in lymphoid and non-lymphoid tissues (including prostate), a humoral immune response and a chronic persistent infection. While gammaretroviruses cause cancer and neurological disease in animals it remains unknown if XMRV is a cause of either prostate cancer or CFS-ME.
"

http://www.fasebj.org/cgi/content/m...29.3?sid=72eb8c6a-95d9-4d64-bf82-673acb7cace4

 

[FunkOdyssey]

Yeah... Silverman is definitely finished with XMRV. :Sign Good one: