Article: Comedown at CROI: XMRV and CFS at the Conference on Retroviruses and Opportunistic Infectio

Article: Comedown at CROI: XMRV and CFS at the Conference on Retroviruses and Opportu

You can view the page at http://forums.aboutmecfs.org/content.php?377-Comedown-at-CROI-XMRV-and-CFS-at-the-Conference-Retroviruses-Opportunistic-Infections-Boston

 

The news according to some sources is trending in the wrong direction. The people actually studying XMRV and related retroviruses are certainly not stopping their work.

Also you did not mention positive XMRV presenters requested permission to speak at the conference, but they were denied. Only the contamination studies were presented.

I know Dr. Mikovits abstract was not accepted. Dr. Ruscetti's team did have a paper. The irsiCaixa team had some somewhat positive news. Do you know who else was not accepted?

 

I know Dr. Mikovits abstract was not accepted. Dr. Ruscetti's team did have a paper. The irsiCaixa team had some somewhat positive news. Do you know who else was not accepted?

Just a warning - I have an interview coming up that is not going to look favorably on XMRV's chances either. (Neither will it rule them out completely). I'm reluctant to put it out without the other side having a change to respond and I've sent it to Annette and Judy; Judy unfortunately is too busy right now to respond. I've also contacted the WPI's PR office to see if they can find someone to provide their side.

 

Thanks for this well done analysis, Curt. Between this and Vincent Racaniello’s TWIV podcast, I have a much better understanding of the issues discussed at CROI. Neither the summaries on the CROI website nor Suzanne Vernon’s highlights were very illuminating.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-comfficeffice" /><o></o>
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[Dr. Deckoff-Jones] ended her blog by suggesting that many other recombinant retroviruses are possibly infecting humans around the world by the same process and that it's quite plausible that vaccines containing infectious human retroviruses have going out for over 50 years.<o></o>

<o> </o>
I agree with Dr. Deckoff-Jones that none of the contamination theories explain why they would find XMRV in ME/CFS patients’ blood samples at a higher rate than healthy controls, in a blinded study. Nor have they explained how a lab contaminant can produce an immune response in patients. Those are major questions that those who are saying XMRV is merely contamination should be called upon to answer. <o></o>
<o> </o>
However, Dr. Deckoff-Jones loses credibility with me and weakens her own argument when she brings up the vampire theory of Hilary Koprowski’s oral polio vaccine as the source of HIV/AIDS. First of all, that “theory” wasn’t published in a peer-reviewed journal, it was published in Rolling Stone magazine. And it was thoroughly disproven in studies published in Science and in Nature. They shot it point blank with silver bullets and drove a stake through its heart, but it won’t die. If we are going to ask to be taken seriously, we need to do better than that. <o></o>
<o> </o>
Origin of AIDS: Contaminated polio vaccine theory refuted http://www.nature.com/nature/journal/v428/n6985/full/428820a.html<o></o>
<o> </o>
Vaccine Theory of AIDS Origins Disputed at Royal Society<o></o>
http://www.sciencemag.org/content/289/5486/1850<o></o>
<o> </o>
Disputed AIDS Theory Dies Its Final Death<o></o>
http://www.sciencemag.org/content/292/5517/615.1.summary<o></o>
<o> </o>
Polio vaccine samples not linked to AIDS<o></o>
http://www.nature.com/nature/journal/v410/n6832/full/4101045a0.html<o></o>
<o> </o>
Credible arguments demand credible sources. That’s why if Simon Wessely said that gravity exists, I’d check it with another source before I’d believe it. <o></o>
<o> </o>

 

Here's the view from within the CROI conference according to an HIV clinician, as reported by Mindy Kitei:

"As far as the XMRV presentations, the physician said it was glaringly obvious to him and to others that the opposing side—those who have found the retrovirus XMRV in ME/CFS patients and in prostate cancer patients—wasn’t being heard."

http://www.cfscentral.com/2011/03/croi-redux.html

 

Dr Coffin seems now to be clearly in the contamination/recombinant camp, yet this piece from 1997 shows that he knows full well about the wide host range, specificity, recombinant characteristics and pathogenicity.

"Retroviruses are unique among animal viruses in that some groups exhibit considerable polymorphism in receptor usage among otherwise closely related viruses. Relatively minor differences in ASLV Env sequences alter the biological properties of the ASLV protein, changing the receptor to which the virus binds and changing its host range”

"The nomenclature for the MLV host range is more complicated, with viruses defined as ecotropic (infecting only mouse cells), xenotropic (infecting only cells other than mouse) polytropic, or amphotropic, depending on the species distribution of suitable receptors. Viruses of both the latter two groups can infect both mouse and non mouse cells of many species"

"The sequences that determine the host range have been mapped to the amino-terminal region of SU. Because of the large numbers of MLV env genes in the mouse genome MLV recombinants carrying altered env sequences arise frequently in the mouse and these recombinants have a central role to play in pathogenesis"

http://books.google.co.uk/books?id=...QQ6AEwBw#v=onepage&q=mlv recombinants&f=false

Page 57, column one.

 

Thanks for this well done analysis, Curt. Between this and Vincent Racaniellos TWIV podcast, I have a much better understanding of the issues discussed at CROI. Neither the summaries on the CROI website nor Suzanne Vernons highlights were very illuminating.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-comfficeffice" /><o></o>
<o> </o>
<o> </o>
I agree with Dr. Deckoff-Jones that none of the contamination theories explain why they would find XMRV in ME/CFS patients blood samples at a higher rate than healthy controls, in a blinded study. Nor have they explained how a lab contaminant can produce an immune response in patients. Those are major questions that those who are saying XMRV is merely contamination should be called upon to answer. <o></o>
<o> </o>
However, Dr. Deckoff-Jones loses credibility with me and weakens her own argument when she brings up the vampire theory of Hilary Koprowskis oral polio vaccine as the source of HIV/AIDS. First of all, that theory wasnt published in a peer-reviewed journal, it was published in Rolling Stone magazine. And it was thoroughly disproven in studies published in Science and in Nature. They shot it point blank with silver bullets and drove a stake through its heart, but it wont die. If we are going to ask to be taken seriously, we need to do better than that. <o></o>
<o> </o>
Origin of AIDS: Contaminated polio vaccine theory refuted http://www.nature.com/nature/journal/v428/n6985/full/428820a.html<o></o>
<o> </o>
Vaccine Theory of AIDS Origins Disputed at Royal Society<o></o>
http://www.sciencemag.org/content/289/5486/1850<o></o>
<o> </o>
Disputed AIDS Theory Dies Its Final Death<o></o>
http://www.sciencemag.org/content/292/5517/615.1.summary<o></o>
<o> </o>
Polio vaccine samples not linked to AIDS<o></o>
http://www.nature.com/nature/journal/v410/n6832/full/4101045a0.html<o></o>
<o> </o>
Credible arguments demand credible sources. Thats why if Simon Wessely said that gravity exists, Id check it with another source before Id believe it. <o></o>
<o> </o>

There are also studies saying that CBT and GET can cure CFS:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/abstract

 

Dr Coffin seems now to be clearly in the contamination/recombinant camp, yet this piece from 1997 shows that he knows full well about the wide host range, specificity, recombinant characteristics and pathogenicity.

"Retroviruses are unique among animal viruses in that some groups exhibit considerable polymorphism in receptor usage among otherwise closely related viruses. Relatively minor differences in ASLV Env sequences alter the biological properties of the ASLV protein, changing the receptor to which the virus binds and changing its host range

"The nomenclature for the MLV host range is more complicated, with viruses defined as ecotropic (infecting only mouse cells), xenotropic (infecting only cells other than mouse) polytropic, or amphotropic, depending on the species distribution of suitable receptors. Viruses of both the latter two groups can infect both mouse and non mouse cells of many species"

"The sequences that determine the host range have been mapped to the amino-terminal region of SU. Because of the large numbers of MLV env genes in the mouse genome MLV recombinants carrying altered env sequences arise frequently in the mouse and these recombinants have a central role to play in pathogenesis"

http://books.google.co.uk/books?id=...QQ6AEwBw#v=onepage&q=mlv recombinants&f=false

Page 57, column one.

I don't think this negates anything Coffin is saying. He is accepting the idea that XMRV is the result of a recombinant event and its been clear for quite a while that recombination between MLV species occurs that increases pathogenecity. There is even some evidence I believe that MLV genes can jump to other viruses entirely and increase their pathogenecity.

I think what Coffin believes is that a recombinant even in the laboratory (not in the body) created XMRV. I don't know if he actually said anything about the contamination question - ie whether or not XMRV got into the patients or into the patient samples - but this time, he didn't suggest otherwise when that idea was presented. (Of course we only get such a brief look at the whole thing....)

 

Thanks Cort, enormous patience for us a little longer.

 

Thanks for all the work on this, Cort, and all others who have provided analysis on these bizarre developments. It's a lot to wrap one's head around.

This whole thing makes me very happy my ME/CFS hubby does not use the computer. I'm sure not gonna tell him about this mess until the dust clears, and it looks like it may be awhile.

Patience, patience, said the vulture. sigh.

 

"The findings suggested that all existing XMRV strains (prostate, two CFS samples from the WPI) were derived from a recombination event that occurred in the Case Western Reserve University in Ohio labs sometime between 1996-1999."

In Dr Peterson's testimony before the Oct 2009 CFSAC meeting, he said that they had found XMRV in samples they had frozen and stored in 1984. If it wasn't a lab contaminate, then it can't have been created by a recombination event in 1996+. The lab contamination theory doesn't make sense to me, because of the antibody tests, and because if it were contamination, they should have found it in the same levels in controls.

 

From Cort's article:

The Fist Closes - In the Feb/March CROI Conference, Dr. Pathak of the National Cancer Institute presented evidence supporting Hue’s theory that XMRV jumped from mouse tissues into the cancer cell line. A close examination of the development of the 22RV1 cell line found that the prostate cancer tissues used to develop it originally did not contain XMRV but that it showed up after it was passaged though nude mice. This suggested, of course, that the virus came from nude mouse tissues rather than the human prostate tissues.

The discovery of two endogenous retrovirus precursors in the nude mice, which, when combined, could have produced XMRV, essentially clinched the deal for many; not only had researchers shown evidence of XMRV jumping from nude mice into prostate cancer cells they had provided a plausible scenario of how it happened.

Cort, I have a question aboutthe above analysis which are based on the conference abstact to which you refer: http://www.retroconference.org/2011/Abstracts/42508.htm

My question is which nude mice? Your article speaks as though they only examined one lot. But if you read the abstract carefully you will see that they examined both the mouse DNA from the actual xenografts samples and other nude mouse strains. From the wording of the abstract it appears they ony found the XMRV precursors (PreXMRV-1 and PreXMRV-2) in the other mouse strains. What if these precursors are not in the mouse DNA from the actual xenografts? Doesn't this undermine their argument, as they would have had to be present in the mice used in the xenografts for the recombination event to have occurred?

 

XMRV and the ego battle

There seems to be an ego battle between the two camps. Maybe the stakes are even higher, if a physical reason for this disease is overuled the Insurance companies win. My doctor, Dr Derek Enlander, has a sanguine sane approach. He says Wait . Wait until the smoke clears and a definative multilab double blind trial, using exactly the same patients is done. Include with the patient specimens negative control specimens from "boiled up" serum, and positive "spiked" specimens.
Then.. compare the results. If one lab has all positives and another all negatives then we can surmise there is a problem. If there is contamination then most of the specimens would be positive. If all are negative in one lab then maybe the lab is not performing the test properly.
Cort, interviewing "the boxing contestants " before the fight will not give us the winner, wait until there is a knock out .
Barbara


From Cort's article:


Cort, I have a question aboutthe above analysis which are based on the conference abstact to which you refer: http://www.retroconference.org/2011/Abstracts/42508.htm

My question is which nude mice? Your article speaks as though they only examined one lot. But if you read the abstract carefully you will see that they examined both the mouse DNA from the actual xenografts samples and other nude mouse strains. From the wording of the abstract it appears they ony found the XMRV precursors (PreXMRV-1 and PreXMRV-2) in the other mouse strains. What if these precursors are not in the mouse DNA from the actual xenografts? Doesn't this undermine their argument, as they would have had to be present in the mice used in the xenografts for the recombination event to have occurred?[/QUOTE]

 

There seems to be an ego battle between the two camps. Maybe the stakes are even higher, if a physical reason for this disease is overuled the Insurance companies win. My doctor, Dr Derek Enlander, has a sanguine sane approach. He says Wait . Wait until the smoke clears and a definative multilab double blind trial, using exactly the same patients is done. Include with the patient specimens negative control specimens from "boiled up" serum, and positive "spiked" specimens.
Then.. compare the results. If one lab has all positives and another all negatives then we can surmise there is a problem. If there is contamination then most of the specimens would be positive. If all are negative in one lab then maybe the lab is not performing the test properly.

Cort, interviewing "the boxing contestants " before the fight will not give us the winner, wait until there is a knock out .
Barbara

Dr. Enlander is wise indeed. That double-blinded BWG test will tell us an awful lot. I can't imagine a much more stressful situation in a workplace than cracking the code on an experiment that you know is going to tell you about XMRV and its potential for CFS. that's really something.

I think you're right - interviewing will not give us the winner - it will just tell us what the different parties think.

 

From Cort's article:


Cort, I have a question aboutthe above analysis which are based on the conference abstact to which you refer: http://www.retroconference.org/2011/Abstracts/42508.htm

My question is which nude mice? Your article speaks as though they only examined one lot. But if you read the abstract carefully you will see that they examined both the mouse DNA from the actual xenografts samples and other nude mouse strains. From the wording of the abstract it appears they ony found the XMRV precursors (PreXMRV-1 and PreXMRV-2) in the other mouse strains. What if these precursors are not in the mouse DNA from the actual xenografts? Doesn't this undermine their argument, as they would have had to be present in the mice used in the xenografts for the recombination event to have occurred?

My reading of it is that they looked for the precursors in both nude mice and other mice strains. If the precursors were in other mouse strains then its possible that XMRV jumped from mice into humans, I suppose, even if XMRV is not found in mice (?). Which actually doesn't make sense - unless XMRV intermittently appears in mouse populations - which would make it unlikely to jump into humans.

We explored the origin of XMRV by analyzing xenograft-associated nude mouse DNA and DNA from other nude mouse strains; the data revealed the presence of two previously undescribed endogenous proviruses, PreXMRV-1 and PreXMRV-2, which contained >3.2-kb stretches of their genomes with ~99.92% identity to XMRV.

Here they show that they did find the putative precursors in some strains of nude mice - including the strains used to build the cell line.

Analysis of 15 nude mouse strains indicated that none contained XMRV, but some strains potentially used to passage the xenograft contained both PreXMRV-1 and PreXMRV-2.

Later on Stoye asked Cingoz, I guess it was, what is the chance of this event occurring outside of the laboratory and Coffin thought it was extremely low. Given the data they have now I think Coffin et al think that all the reported strains of XMRV must have been created in the lab.

 

Too bad they didn't realize they may have made an infectious virulent form. Could have saved us all some problems if they had.

 

We shall see - an infectious retrovirus is nothing to sneeze at. I'm really kind of surprised that the media hasn't picked up on the fact that its possible that medical researchers created only the third human infectious retrovirus....That's an amazing thing!

 

Thanks again Cort for breaking down this conference for us, we appreciate all the effort that you put in for us. This would be completely riveting if it weren't so frightening at the same time.

One question - I can't help but think, can't they give the nude mice a cheap hospital gown at least - geez, a litte dignity

 

My reading of it is that they looked for the precursors in both nude mice and other mice strains.

Cort, I agree with the above but I think you are missing the point I was making.

From the paper under methods:

DNA isolated from early (3rd and 7th) and later passage CWR22 xenografts consisted of a mixture of tumor DNA and nude mouse DNA

Here's the same quote you used in the above post but with a different part highlighted:

We explored the origin of XMRV by analyzing xenograft-associated nude mouse DNA and DNA from other nude mouse strains; the data revealed the presence of two previously undescribed endogenous proviruses, PreXMRV-1 and PreXMRV-2, which contained >3.2-kb stretches of their genomes with ~99.92% identity to XMRV.

From the above quotes I am reading 'xenograft-associated nude mouse DNA' as the mouse DNA from the original xenografts samples that was examined. The wording above glosses over exactly where they found PreXMRV1 and PreXMRV-2 (ie does not indicate if it was in tyhe xenograft samples or other strains of mice they examined)

Yet later in the abstract they only talk about finding the precursors in the other strains as you have corectly pointed out:

Analysis of 15 nude mouse strains indicated that none contained XMRV, but some strains potentially used to passage the xenograft contained both PreXMRV-1 and PreXMRV-2.

So what if they found PreXMRV-1 and PreXMRV-2 in other strains? Unless both of these precursors were in the mice used to passage the xenografts then surely the recombination event could not have occurred during the derivation of the 22Rv1 cell line? They say the strains with the precursors could potentially have been used to passage the xenograft. Is this not just inference? If they had found the precursors in the xenograft sample from the later passages they examined no doubt this would have been trumpeted - but that's not what's in the abstract.

All I can guess is that they are implying that one of the nude mouse strains that has the precursors might have been used somewhere between the 7th passage and the 'later' passages? If so this is all just inference. Exactly when was the 'later' passage/s? How much later was this and do they have access to the xenograft samples from passages in between? If these were examined and they didnt have PreXMRV-1 and PreXMRV-2 then would this not undermine the whole hypothesis?

 

Good close reading Megan. I can see where they left an opening for one of those precursors to perhaps have come from another strain of mouse...Yes, they definitely need to find both those precursors in the strains of nude mice used to the passage the cancer cells for the theory to work out.

 

Cort, someone tapped me on the shoulder so I watched the video. The video of the presentation clearly say that Pre-XMRV1 and Pre-XMRV2 were in the early and late xenografts - so this point looks like its not an issue after all!

Though I did notice that they said the cell lines in question had been developed to be androgen independent through castration or adndrogen deprivation (I assume this means in the mice). I guess I can't help wondering if this may also have affected the detectibility of XMRV in the early stages of the process since JM has said all along that the growth of XMRV is also affected by androgens.