Vincent Racaniello to me (with permission to post)

[Mya Symons]

Vincent Racaniello to me
show details 11:24 AM (2 hours ago)

No problem, but use the version below. I wanted to correct a slight
ambiguity in the original.


It's possible that XMRV arose in a lab and infected people. But since

the virus seems to have arisen in a lab in the early 1990s, according to
Dr. Pathak, it's not

clear how it could cause CFS before that date. If there are different
XMRVs out there, very different from the ones isolated to date, that
would solve the problem. Those different XMRVs would not have arisen

from the mice that Dr. Pathak studied. But so far we don't have

evidence for such different XMRVs. Dr. Mikovits has talked about them
but I've never seen the data.



On Sat, Mar 12, 2011 at 1:19 PM,

- Show quoted text -

 

[Esther12]

Thanks again Mya.

 

[urbantravels]

But since the virus seems to have arisen in a lab in the early 1990s, according to
Dr. Pathak, it's not clear how it could cause CFS before that date.

OK, but are we taking this latest hypothesis as established fact? It's not even based on published research, and Prof. R. says he doesn't want to discuss un-published research on his blog, and has in fact called into question the conclusions in several pieces of *published* research, notably the Hue paper (which he changed his initial take on, after reading it more carefully and discussing it with colleagues.) So why is this mere conference presentation suddenly being treated as so convincing?

 

[Mya Symons]

OK, but are we taking this latest hypothesis as established fact? It's not even based on published research, and Prof. R. says he doesn't want to discuss un-published research on his blog, and has in fact called into question the conclusions in several pieces of *published* research, notably the Hue paper (which he changed his initial take on, after reading it more carefully and discussing it with colleagues.) So why is this mere conference presentation suddenly being treated as so convincing?

I agree. I am not understanding the whole theory that XMRV came about only in the 90's. We have been using lab mice for 40 years or longer, correct? Who is to say that this combination of viruses, or something similar, could not have happened twice or even more than twice?

 

[anciendaze]

One point about this hypothesis, which has been determinedly ignored, is that the sequences from which chance recombination is said to have taken place were 99.4% homologous to XMRV itself. These are very unlikely to have arisen independently. Nor are they likely to have remained so similar for thousands of years, or even centuries. When SIV jumped to humans, the resulting HIV-1 became about 50% homologous to SIV in about a century. This points to a common ancestor, very similar to XMRV, recent enough to still be around.

Once again he is talking about very different XMRVs, while assuming the PMLV found by Lo and Alter is completely unrelated. At this point we have arguments about as few as five nucleotides difference. Even the "very different" XMRVs he is asking for would differ by only hundreds of nucleotides. This is within range of rapid recombination.

I view the recombination/contamination argument as an "own goal". If they can prove it happened once, they will need convincing arguments similar recombinations producing new highly-infective pathogens are highly unlikely, otherwise they are going to find a lot of medical research limited to special containment facilities. They also need to find that common ancestor, which looks more similar to XMRV than anything else.

The common factor in the contaminated facilities is prostate tissue from human patients. I believe the place to look for the ancestor is in human patients.

 

[ukxmrv]

Mya, you asked about lab mice. Breeding has been going on for a long time. It was popular in the 19th century. Modern day lab mice can be traced back to the Castle/Lathrop and Little mice of roughly 70 - 100 years ago.

http://research.jax.org/mousegenetics/history.html

 

[Mya Symons]

Once again he is talking about very different XMRVs, while assuming the PMLV found by Lo and Alter is completely unrelated. At this point we have arguments about as few as five nucleotides difference. Even the "very different" XMRVs he is asking for would differ by only hundreds of nucleotides. This is within range of rapid recombination.

The common factor in the contaminated facilities is prostate tissue from human patients. I believe the place to look for the ancestor is in human patients.

I am trying to understand all this. Would you say that because XMRV replicates very slowly unlike HIV, which replicates very quickly, that when they look for an XMRV that is "different" from the one they are referring to, there would not be much difference when comparing the two?

One more thing. Lets say hypothetically that XMRV is only passed from a contaminated cell line in a vaccine and not from human to human. Wouldn't we be looking at a more similar virus infecting all who test positive. I am assuming that a virus passed from human to human would have more differences because it would have done more replicating???? (because the virus would have done some replicating in the first human before it was passed on to the second, so there would be more differences from the original)

 

[anciendaze]

I am trying to understand all this. Would you say that because XMRV replicates very slowly unlike HIV, which replicates very quickly, that when they look for an XMRV that is "different" from the one they are referring to, there would not be much difference when comparing the two?

No. Hypermutation of latent provirus is well established. This is a natural defense against retroviral infection which goes on the whole time the provirus is there -- whether or not it is replicating. The sequences found in the early studies were very similar because the codons altered by hypermutation enzymes are likely to become synonyms for the same amino acid. Hypermutated sequences can still yield replication-competent virions. This is a major finding which should shake up a great deal of research. Recognition of this has been very slow.

For the most part we just don't know the degree of natural variability because we lack data on wild-type virus. Most available data come from cultured cell lines. The wild-type data we do have is subject to stringent selection. Part of this comes from the "culturing" phase of preparing samples for PCR, or natural activation of infected immune cells as part of immune response. (If you don't do this "culturing" step, and your patients don't exhibit natural activation of PBMCs, you are unlikely to detect virus in blood via PCR.) Other samples are tested entirely by culturing, which is highly selective.

One more thing. Lets say hypothetically that XMRV is only passed from a contaminated cell line in a vaccine and not from human to human. Wouldn't we be looking at a more similar virus infecting all who test positive. I am assuming that a virus passed from human to human would have more differences because it would have done more replicating???? (because the virus would have done some replicating in the first human before it was passed on to the second, so there would be more differences from the original)

If virus were present in vaccines, its sequences would reflect the processes, facilities and batches in which it was made. Culturing virus is itself highly selective, which would reduce variability. A long development process would, however, likely result in different strains in different vaccines, even different batches of the same vaccine. If you don't know the virus is there, you can hardly control it. The question can only be settled with more data.

My own opinion is that documentation and samples are set up to detect such contamination. Most data we have on previous problems comes from this source. What I believe I see are previously infected patients responding in a variety of ways to a variety of immune challenges. There is a correlation in time between vaccination and symptoms because vaccination is an intentional challenge to an immune system. My guess is that the infection was already present, but latent and asymtomatic. However, I am not an authority, and you would not believe me if I were.