• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

XMRV Buzz - Take a Deep Breath/the Big XMRV Meeting, Singh On XMRV, Sample prep?

Cort

Phoenix Rising Founder
A Big Buzz from a Big Day

Phase II of BWG Study is Complete (Really!) - The CFIDS Association today announced that the oh so important (and time consuming) second section of the BWG’s study focusing on sample preparation and sample storage is complete and that the results will be announced at the BWG’s meeting, just 3 days from now (Dec 14th) (gulp). The meeting is open to the public (if you happen to be in Gaithersburg, MD) but is not webcast; just three days later, though, a CFIDS Association webinar (register here) will feature two members of the BWG who will talk about the results and where they go from here.

Dr LeGrice reported they were looking at contamination issues although that has never been explicitly stated. Still, if contamination was to occur it would presumably occur during the sample preparation phase. At the very least the Group should be able to tell us how to prepare and store an XMRV sample such that it does not disappear. This suggests they should be able to indirectly tell us if any studies inadvertently destroyed XMRV during the sample preparation/storage phase. Discuss the meeting here

Meeting Agenda - XMRV and the MLV’s will be the second topic on the meeting agenda. That discussion will take place from 1-3:30 pm EST. There will be nine presentations; Dr. Mikovits will make one of them. Here they are:

A. Introduction and Background, Indira Hewlett, Ph.D., DETTD, OBRR, FDA (10’)
B. Summary of Current Research on MLV-related Human Retroviruses and Disease Association, Jonathan Stoye, Ph.D., NIMR, UK ( 25’)
C. Recent Studies of Epidemiology of MLV-related Human Retroviruses:

i. U.S. Study, Shyh-Ching Lo, M.D., OCTGT, FDA (15’)
ii. U.S. Study. Maureen Hanson, Ph.D., Cornell University (15’)
iii. UK Study, Judy Mikovits, Ph.D. Whitmore Peterson Institute (15’)

D. Animal Studies: Potential Transfusion Transmission of MLV-related Human Retroviruses, Francois Villinger, Emory University (20’)
E. Update of Blood XMRV Working Group Activities, Graham Simmons, Ph.D., BSRI (15’)
F. Prospective and Retrospective U.S. Donor Surveillance Studies, Michael Busch, M.D., Ph.D., Blood Systems Research Institute (15’)
G. Assay Development Efforts on MLV-related Human Retroviruses, Rachel Bagni, Ph.D., National Cancer Institute (20’)
XMRV in Spain: Part II - details on the Spanish study have shown up and our surmises were correct; XMRV has been found in CFS, HIV and healthy controls in Spain. The sample size was very small - so any prevalence figures are very preliminary. This is not a ‘study’ so to speak; it was an attempt - after all the controversy - to see if they can find the virus. They were able to do that and it appears they will now start testing more people. We should keep in mind that they were looking for XMRV in an somewhat different set of cells- the B Lymphocytes - than everyone else has been looking in (PBMC’s). PBMC’s contain B Lymphocytes but no one has actually signaled out this group of cells and tested it.

It’s difficult to ascertain prevalence even in this small study because they reported the incidence of XMRV in cell lines rather than patients and some patients (n=11) obviously contributed more than one cell line (n=21). XMRV showed up in 3 x’s as many patients as controls using the env protein, in equal numbers of controls, CFS and HIV using the gag and twice as many CFS patients (50%) as HIV and healthy controls using the pol protein. The researchers noted the difficulty in determining prevalence -and that that was not their aim - but thought prevalence in CFS might end up, based on these early results, similar to the WPI - approximately 67%.

What we have here is a mishmash that indicates how uncertain the science is. Ideally we would want everyone who tested positive for one XMRV protein to test positive for another one. In fact, ultimately, that is how the testing will work - one positive test never denotes a positive; it has to be confirmed by another test. That is clearly not happening yet and a major goal, of course, will be to tighten up the tests so that consistent results are found across all of them.

They do suggest that B-lymphocytes could be a reservoir for XMRV; ie a place where XMRV is replicating more (or rather is actually replicating) and, in which, it is easier to find- which would be a really significant finding; however, the initial report stated the XMRV was found in very low amounts.

The most important to take away from this effort, though, is that the Spanish researchers have been able to find XMRV and they have found it in B Lymphocytes - an intriguing cell with the success of a small Rituximab trial and the herpesvirus infections found in some people with ME/CFS.

XMRV in Lymphoid Tissue in Macaques - They also showed XMRV can grow in the lymphoid tissue of Macaques . Lymph tissue is an area Dr. Mikovits has speculated could emerge as a reservoir ie a site of increased XMRV replication. That isn’t clear yet but the Spanish team did report that was no evidence that XMRV’s presence there was resulting in the deaths of immune cells -or altering immune functioning. Viruses often replicate furiously inside a cell, kill it and then swarm to the next one…Or the immune system recognizes an infected cell and responds to it. Neither of these scenario’s showed up in this early look at lymph tissues of macaques.

Functionality - The researchers did note, though, that XMRV could be interfering with cell functionality which actually fits in very well with ME/CFS. Immune cell numbers and composition do not appear to be radically affected in CFS - The Klimas/Fletcher studies, on the other hand, suggest that, cell functionality is quite impaired in NK cells and possibly T-cells which could be explained, on e would think, by a kind of smoldering infection characterized by low rates of replication. (Nothing seems to come easy in CFS….plummeting cell numbers aka AIDS would have quickly convinced researchers of the immune dysfunction in the disorder - and quite a few studies have been done - and they have never really shown up…Instead, impaired cell functionality has shown up - a much more difficult and subtle factor to spot.)

Huber and McClure Studies On Their Way - It almost seems like every upturn for XMRV is immediately followed by a downturn. Both Dr. Huber’s and Dr. McClure study - both of which are focusing on contamination - will reportedly be published in the near future.

A Still Missing Piece - the Alter/Lo Work
- The sequencing work Dr’s Alter/Lo are doing will be very important given how critical their study was for XMRV. Further sequencing will nail down, presumably for good, where the genetic sequences they found came from. Dr. LeGrice reported that the sequencing would be ‘easy’ but he didn’t state how long it will take. Completely sequencing the virus was an important part of the WPI's study. Shortly, hopefully we will get a definitive report on where the sequences they found came from; mouse or man?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Thanks for the info Cort.
I'm wondering if it's wise for me to get excited about the BWG's Phase II announcement...
It could be a very very big day for us...
But then again... We keep getting disappointed by the speed of progress with XMRV research, and I wouldn't be surprise if they had an 'inconclusive conclusion' to announce, such as "We've completed the Phase II study, but the results are inconclusive."
Oh well, only a couple of days to wait now.
 

Cort

Phoenix Rising Founder
XMRV Buzz: Racaniello Retracts/Miller Jumps In/Retrovirologist Superteam To Form Rebuttal/Annette, Judy on Nevada Newsmakers

by CORT on DECEMBER 23, 2010[EDIT]
Dr. Racaniello Retracts Statement About XMRV and CFS showing an admirable commitment to the pursuit of the truth Dr Racaniello made an abrupt about face regarding his statement that the four papers were probably the beginning of the end of XMRV and CFS. His new blog XMRV and CFS- Its Not the End paints a very different picture andemonstrates just how difficult a subject this is. Dr. Racaniello runs a research lab he is well versed in this field yet this is what it took for him to alter his opinion:

I read the papers over again, and began checking XMRV sequences in Genbank. I also began an email correspondence with authors of three of the four papers, and spoke with my virology colleagues here at Columbia. As a consequence of this additional research I decided that my initial impression of the papers was incorrect, which is evident in my post entitled Is XMRV a laboratory contaminant?

This is difficult stuff! He does believe that the new papers do highlight the dangers of contamination but they do not imply that the positive results from the WPIs or other studies were contaminated. He is fully in line with Dr. Coffin, here, who co-authored two of those papers.

Upon re-reading three of the four Retrovirology papers it became clear to me that they show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised by these findings. Clearly any new studies done on XMRV should keep in mind the potential for contamination from PCR kits and murine nucleic acids.

Three of the papers were nothing but warnings; the Hue paper was the most substantial one and the one that bothered him the most but here, again, he was able to find reasons, some of which the WPI mentioned in their rebuttal, why the Hue paper might not apply to the WPIs findings. He seems to be indicating, oddly enough, that some XMRV isolates appear to be laboratory contaminants while others do not was an amazing twist in an already very complex field! However, this is a twist that should be able to accounted for one would think simply by analyzing the different strains (?). Vectors from the MoMLV virus appeared to be used in gene therapy, by the way, which is one reason they might be present in labs. The WPI, however, said the type of mice Hue described have not been used in their labs.

The idea that PCR amplification could itself cause increased variability in 22Rv1 making it look like the ancestor to XMRV indicated just how complex all this is. Willow on the Phoenix Rising Forums has provided a way this could occur.

I was initially more troubled by the fourth paper by Hue and colleagues. There are four major findings in this paper (gag PCR primers are not specific for XMRV; the virus is present in 5 human tumor cell lines; two XMRV isolates are nearly identical to a virus from the human prostate cell line and also contain an insertion from the murine retrovirus MoMLV; and there is more nucleotide diversity in viral sequences from 22Rv1 cells than in all the patient XMRV sequences). The fact that two XMRV isolates seem to be laboratory contaminants judged by the presence of MoMLV sequences was initially unsettling until it became clear that other XMRV isolates do not have this insertion. That leaves the fourth finding that XMRV from 22Rv1 cells appears ancestral to, and more diverse than, all the human XMRV sequences. I decided that this result was less troublesome than I had originally believed, in part because it is not clear that the differences among the 22Rv1 viruses did not arise during PCR amplification.

He concluded the blog with an apology and stated that the research on XMRV and CFS must proceed and, in fact, called for it to increase.

My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination.

In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others. I would like to apologize to anyone who was offended, angered, or disappointed in any way by my statement to the Chicago Tribune. It is my goal to educate the public about virology, and clearly I did not do that very well.

There are at least two lessons that you can take away from this incident. First, that I make mistakes, and that Im willing to admit it. Everyone does, including scientists. Second, if I had difficulties interpreting these papers, how would non-scientists fare?

The Chicago Tribune quickly printed his retraction

Respected Retrovirologist Tackles XMRV/Retrovirology Superteam Formed to Rebut Claims the biggest news of the day, however, was not Dr. Racaniellos retraction but EcoClimbers statement on the Phoenix Rising Forums stating that the Retrovirology papers have prompted noted retroviriologist Dr. Dusty Miller at the Fred Hutchinson Cancer Research Institute in Seattle, Washington to dive into his lab to investigate the contamination claims which he does not believe will pan out and will apparently be part of a XMRV retroviral superteam that will rebut the claims in an organized fashion. By suggesting XMRV was a contamination wherever it appeared Hues paper stepped on a lot of toes. It was Silverman, after all, who discovered XMRV in March of 2006 and since then has published 12 papers on it. Klein has been a co-author of several his papers and, of course, Dr. Ruscetti who is very well respected in the field, was a co-author of the Science paper.

These researchers may very well be doing lab work to specifically counter the Hue papers findings. Ecoclimber stated

I talked to Dr. Dusty Miller. His lab is currently in the stage in testing and experimenting and gathering the evidence to rebut their claims. He states he can refute their claims. He will be getting together with Ruscetti, Silverman, Klein, Smith and others to post their rebuttal as a group against the negative papers.

Annette Whittemore, Dr. Mikovits on Nevada Newsmakers meanwhile Dr. Mikovits and Annette Whittemore appeared on Nevada Newsmakers to counter the claims of contamination that have been raised by a rather lazy media. Annette painted ME/CFS in broad terms it is a complex illness that the WPI believes is infectious, involves many pathogens and affects the neuroimmune system and Dr. Mikovits noted the WPI has had interactions with researchers in countries around the world including Norway, Belgium and Spain. Dr Mikovits asserted that multiple tests are needed to detect XMRV because no single test (ie the PCR results in Retrovirology) is accurate enough. (Dr. Lipkin made a similar point in an email).

Dr. Mikovits noted that they were well aware of the potential for contamination to skew the results, which, of course, is doubly true given co-author Dr. Sandra Ruscettis background in mouse retroviruses and Dr. Mikovits close connection to the Ruscettis. Annette Whittemore stated that the Retrovirology papers do not change their findings and that we are moving forward in a positive way. She also noted that they were not apprised of the results before they were published suggesting that the original authors are usually give a bit of lead time to respond to negative papers published regarding their findings. Dr. Mikovits noted that any large discovery is going to lead to a lot of pushback because the best science always leads to more questions than answers and thats what has happened. (Has it ever.The XMRV discovery pushed researchers into fields and into digging up questions that they had never asked before.)

When the interviewer asked Dr. Mikovits why researchers have not followed the exact methods of the original paper her reply was very interesting. She said that researchers do what they know how to do well and that they do the advances of the last decade very well but that those kinds of techniques are just not ready to take on a new virus like this. Those new techniques have replaced the old-fashioned method of culturing, which is difficult, expensive and time consuming. (Dr. Mikovits has been saying its not about the PCR for months). She said researchers think if we can detect HIV using this method we should be able to detect this virus but that is just not the case at this point, it is too early in the discovery process.

Caught in a Time Warp? This point has confused me because they did use PCR to detect the gag sequence in the original paper and PCR. of course, is described by other commentators as something virtually any lab can do. How does this laymen make sense of all this? Perhaps PCR detection of XMRV is so difficult that just the right techniques are required to find it. It could be that small things, unbeknownst to the research community now, are able to knock XMRV off and this is in fact what the NCI is looking reportedly at. In that case, until the PCR techniques are perfected then culturing and growing more virus and then studying it figuring out its little secrets and then developing the correct PCR test would seem to make sense. I am just a laymen no special expertise here trying to think through these issues. Sometimes I get it right sometimes I get it wrong; take everything printed here with that grain of salt!

Unfortunately the PCR test was regarded as the main finding of the Science paper it was what got the lions share of attention, and PCR, as Dr Mikovits pointed out, is what researchers in this field generally do now. Dr. Lipkin and Dr. Miller and others are wary of PCR as the be-all and end-all of detecting viruses, and they are pursuing other means

Annette Whittemore noted all the other groups at the NIH, NCI, Cornell and University of Utah that are moving forward. When asked about politics Annette Whittemore noted that these issues are money intensive with a lot of stakeholders and some politics is inevitable.When XMRV turns out its going to cost some stakeholders a lot of money (and, of course, make money for some others).

The Physician has been chosen and the immune signature paper will be out next year. Dr. Mikovits and Annette Whittemore and quite poised and acquit themselves and the organization well, IMHO.TE]
 

lancelot

Senior Member
Messages
324
Location
southern california
nice update cort

" Dr. Dusty Miller respected Retrovirologist Tackles XMRV/Retrovirology ‘Superteam’ Formed"

Looks like the US is going to bring home the GOLD. Suck it McClure!
 

Cort

Phoenix Rising Founder
The thing is that Dusty Miller is an old hand at murine retroviruses and he is working at one of the top Institutions in the country...and if he's convinced a) that XMRV is worth a deeper look (after all this) and is going to go to the time and effort to do that - that's a really good sign.

That he's joining the 'Superteam' is even better. I expect to see a strong rebuttal coming out at some point, I would guess in a future edition section of Retrovirology.
 

lancelot

Senior Member
Messages
324
Location
southern california
I've seen Dusty Miller rebuttal McClure in the comments sections of some XMRV papers in the past. Do you know all the players in the US XMRV Superteam? McClure would be better off listening to her own advice of not being involved in CFS ever again, but it looks like she will not be happy until she digs herself a palatial hole.

A battle is brewing between a US XMRV Superteam and a UK XMRV Shameteam. Silly brits, Americans always win!
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
reading the first few pages of this thread and I just wanted to say... whatever LeGrice may think about XMRV and whether or not we like his opinion on that, he is working on replicating Lerner's very important work. (I still can't figure out why no one has done this previously, since his papers are so astounding!) But I see Lerner's work as very important.

Even if it's XMRV and not so much EBV, the viral heart stuff is extremely important, and Lerner felt it could be a biomarker. If perchance XMRV turns out not to be causative, then someone is already working on another virus.

Even though LeGrice is not a friend of MRV, I believe he is a friend of the ME/CFS patient community.
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
The thing is that Dusty Miller is an old hand at murine retroviruses and he is working at one of the top Institutions in the country...and if he's convinced a) that XMRV is worth a deeper look (after all this) and is going to go to the time and effort to do that - that's a really good sign.

That he's joining the 'Superteam' is even better. I expect to see a strong rebuttal coming out at some point, I would guess in a future edition section of Retrovirology.

This Superteam stuff is quite interesting and exciting. Thanks for the info, Cort. (and thanks for the mention... not sure if I deserve that; was just trying to explain PCR and making basically [semi-educated] guesses).
 

Cort

Phoenix Rising Founder
reading the first few pages of this thread and I just wanted to say... whatever LeGrice may think about XMRV and whether or not we like his opinion on that, he is working on replicating Lerner's very important work. (I still can't figure out why no one has done this previously, since his papers are so astounding!) But I see Lerner's work as very important.

Even if it's XMRV and not so much EBV, the viral heart stuff is extremely important, and Lerner felt it could be a biomarker. If perchance XMRV turns out not to be causative, then someone is already working on another virus.

Even though LeGrice is not a friend of MRV, I believe he is a friend of the ME/CFS patient community.

LeGrice is! I had no idea. Wow - that is good news.....If he is doing that he is a great friend of the ME/CFS community... He has gotten dragged in to ME/CFS...Houghton I believe is interested in this as well...this is a very good sign....Willow I kiss your bark!
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
I think "crying in the doctor's office" could be its own whole topic. Even when the doctors are nice I cry. Usually somewhere around the part where I have to say something about how I feel. Hard to avoid that topic in the doctor's office.

And then they cooly observe, "you're rather teary, dear. are you depressed?" No, but how can I tell you all about my disease without shedding a tear or two?
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
LeGrice is! I had no idea. Wow - that is good news.....If he is doing that he is a great friend of the ME/CFS community... He has gotten dragged in to ME/CFS...Houghton I believe is interested in this as well...this is a very good sign....Willow I kiss your bark!

Well, I'm pretty sure it was him. I thought it was here at PR I read about it. Like all of us my memory isn't too keen, especially short-term memory, but until you didn't know, I was sure it was him. Now I have a small doubt but still 90% sure it's LeGrice. It was definitely someone who hated the XMRV theory.
 

Otis

Señor Mumbler
Messages
1,117
Location
USA
Well, I'm pretty sure it was him. I thought it was here at PR I read about it. Like all of us my memory isn't too keen, especially short-term memory, but until you didn't know, I was sure it was him. Now I have a small doubt but still 90% sure it's LeGrice. It was definitely someone who hated the XMRV theory.

I'd be most interested if you're able to dig up an old post, I'll search a little myself as you've piqued my curiosity.
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
I can't find anything about it, now (searching the Internet, but PR usually comes up fairly well on Google). Maybe I was thinking of Glasier? Only I was sure it was something new and connected to the viral cardiomyopathy specifically, and NIH-funded. And that the name had a G in it. :D And I really thought it was LeGrice...
 

Cort

Phoenix Rising Founder
It did and they were both at that meeting! I'll bet it's Houghton; he was very intrigued by Lerner's study and questioned him about it....Glaser is an investigator who's really interested in EBV but I don't think he has the clout to take on something like that...Houghton may....He later told me that he really wanted to help get a trial going. I don't know if he's able to or not - but it was a good sign that he was really intrigued by it....... LeGrice is now a member of the CFS Working Group - another big name XMRV has dragged in. Houghton won the Lasker award some time back by the way.....:)
 

George

waitin' fer rabbits
Messages
853
Location
South Texas
Maybe you were thinking about LeGrice's connection with NIH SAIC and the tool kit development?

here are the inventors of the xmrv tool kit (as found listed in this article: http://www.veteranstoday.com/2010/08...forumid=331851) and their titles, as found listed at the NCI's dept called Advanced Technology Program (ATP)., http://web.ncifcrf.gov/atp/default.a...tacts&LabID=12

Dominic Esposito (SAIC) (Cloning and Expression Optimization Head at ATP)
Alan Rein (NCI):what i found for him is his bio on NCI: http://home.ncifcrf.gov/hivdrp/Rein.html
Stuart Le Grice (NCI): his bio at NCI: http://home.ncifcrf.gov/hivdrp/Le_Grice.html
James Hartley (SAIC) (Laboratory Director at ATP)
William Gillette (SAIC) (Protein Purification Head at ATP)
Ralph Hopkins III (SAIC): found a few cancer, herpes, and other papers with his name on them. that is all i can find on him.
Troy Taylor (SAIC) (Microbial Fermentation Head at ATP)

And I can't find it now but there was a comment that LeGrice made on the SAIC website about the patient community being very amandant about looking into the virus. I think it was on that web site? It's hard to say some times. (grins)
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
I feel like I'm in an alternate reality from you all... :headache: (sad Scotsman here, or sad Scots lass) ... but I really want to say I read Houghton was working with Lerner in further research (so that couldn't be the replication), and I still think I read LeGrice was doing a replication and had a definite grant from NIH.

I really hope I didn't dream that all :D

George, thanks for the interesting info (although the toolkit links don't work)... but I was thinking of something connected to EBV/cardiomyopathy, not specifically to XMRV.

Or I thought I was.... :confused:

:(

:D

well, Merry Christmas to anyone who celebrates!
 

illsince1977

A shadow of my former self
Messages
356
If it were easy to determine the cause of our illness via mechanized, high throughput lab tests, I think we would have had answers long ago. As Ila Singh said (paraphrasing here) the low hanging fruit has already been picked.

I'm tempted to deduce that although many labs may be very good at the techniques they use, those techniques haven't yielded useful discoveries for ME/CFS, so restricting yourself to those techniques may never produce any answers. The older technology is not necessarily the inferior technology. Each technique obviously has its drawbacks. However, newer does win out if its uncritically accepted as better simply by virtue of being newer and if older techniques are no longer taught to young researchers. Then anyone who develops a "new" malady that PCR doesn't pick up is cooked! That is until science comes to the rescue with some newer, more sensitive technology. But science fell off its white horse long ago for me because it is people who create and use the science, and these people and their theories, techniques and conclusions are evidently flawed, whether they admit it to themselves (or to us like Racaniello commendably did) or not!

It's difficult as patients to take any scientist seriously whose starting point is that there is nothing to be found and won't admit to limitations in their tools. How does anyone deserve the benefit of the doubt who has not given us and what we tell them is going on in our bodies the benefit of the doubt?
 

Cort

Phoenix Rising Founder
Twiving XMRV

XMRV Buzz from the 27th

Blood Working Group Reacts - everybody seems to feel the need to react to the four papers on contamination in the Retrovirology Journal of all about a week ago. The BWG stated, yes, of course, we and the labs are and always have been concerned about contamination and they are proceeding with phase III which will look for RNA, DNA and antibodies. Interestingly, they talk about culturing this is something that we thought that the BWG, which is focused on faster methods of detection, was not going to do but they noted how important it is to be able to culture (and isolate?) the virus itself and antibodies to it. As Dr. Lipkin noted in his comment PCR is not the end-all and be-all of testing for viruses and the BWG appears to agree.

This Week in Virology - session #112 of the Twiv podcast with Dr. Racaniello featured XMRV and the head ofthe National Cancer Institute, Dr. Alan Rein. They started off tonight with a good laugh when Dr. Racaniello told Dr. Rein they had a him on so he could clear up all the issues regarding XMRV. Dr. Rein has worked extensively on murine leukemia viruses and HIV. Dr. Rein noted that the gene sequences found by Dr. Lo and Alter were gene sequences commonly found in mouse DNA and in endogenous retroviruses. Dr R noted that they went to a lot of trouble to ensure that these are not gene sequences from mice. Dr. Rein agreed that did not think that the mitochondrial DNA test that they did was the best test for mouse DNA and felt that IAP DNA assay would have been quite a bit more sensitive.

Because one study showed it was possible for a mtDNA test to miss mouse DNA that the IAP test is able to pick up they agreed that it would be best for the positive studies to go back and retest their samples using the IAP test. (This suggests, though, that the mtDNA is completely inadequate for finding mouse DNA. Sure it's possible that it misread some samples...but how is it possible for it to misread 70 out of 100 samples? So, yes, for accuracies sake, go back and retest the samples....but to fine tune the results - not overturn them...

Variable enough? -a big question making the rounds is if XMRV (or the Lo/Alter sequences) are genetically variable enough. A replicating virus should be quite variable from person to person while a contaminant would not. XMRV does not, as yet appear to be very variable genetically. Dr. Rein noted, however, that XMRV is very different from HIV and, given that, there is really no way to tell how variable a replicating XMRV should be.

The Prostate and Dr. Singh - Dr. Rein also looked for XMRV in hundreds of prostate cells and found none. Rather disturbingly he described a process, too complicated for me to get on the first pass, in which it was possibly for immunohistochemistry samples to register as false positives. Immunohistochemistry has been Dr. Singh's bailwick; she has claimed that immunohistochemistry is more accurate than PCR in finding XMRV but Dr. Rein reported that his analysis of some of Dr. Singh's positive slides suggested that they were actually negative. Dr. Singh, appears to be using immunohistochemistry in her XMRV autopsy study. Dr. Singh, of course, was not on the program and did not have a chance to defend her study. Dr. R did note that a recent paper came out that did found XMRV in prostate cancer tisssues.....the twists and turns this field is still taking continue to be amazing.