News of replication of WPI XMRV study...

[flybro]

Precisely.

Completely agree.

Please be gentle, I'm a newbie posting in the the grown-up forums.

I've been looking hard for alternate explanations, that fit with what I know about myself and family.

The one thing I thought I might've found, which is still crap, is Fragile-X, but I would not be totally shocked if Fragile-X turns out to be the work of XMRV.

& Fragile-X dos'nt fit as well as XMRV unless I could have both Fragile-X and XAND, again my question would be does fragile-X increase your chances of having XAND. A gene marker was mentioned in Kerrs 80 gene study, that is a Fragile-X marker. But I cant understand the paper to see if it's showing a normal marker and others. Or if it showing up regulated , or down regulated.

I could be completely off the ball. I f any one reads this, and can read understand Kerrs 80 Gene science paper, could they have a look at NUFIP2 it's listed in the tables and aon the gene card thingy. But again I have no idea if it's existence in the paper, is linking a marker for Fragile-X and CFS/ME XMRV XAND. Any help would be much appreciated.

Thank you for trying to understand what I'm asking for here. I'm not sure I do.

 

[Martlet]

I don't care what causes CFS/ME, as long as they find out and can treat us ... as well as prevent others from coming down with it.

If XMRV is the cause, then I will not be personally worse off for knowing but, over time, I might be better off as they devise ways to treat it. Plus there will be good news for future generations in that there will be a vaccine against it.

 

[jenbooks]

??

I wish to put to rest the fears about mice and the rumor/belief that XMRV is part of the Lyme from ticks business.
Cecelia

I don't see why it should be put to rest yet. These viruses mutated from MLV, in mice. Since ticks are the connecting bridge between mice and humans, feeding on the blood and then regurgitating it along with their pathogens INTO the hosts' bloodstream before falling off, of both species repeatedly, why wouldn't this vector be a possible bridge for not only the mutation but jumping species?

And that the strains are different--prostate and CFS--isn't all that surprising, is it? That actually *is* evidence of mutation, I would think. Unless they're suggesting that independently the mutation occurred in separate mice and separately jumped to humans, causing a minor epidemic of prostate cancer and a major epidemic of CFS...???

 

[Sing]

Reply to Jenbooks

Hi Jenbooks,

Excuse me for sounding more authoritative than I can be with a phrase like "put to rest". This opinion may be premature.

My understanding from reading Peterson, Silverman, etc is that XMRV descended or evolved from the mouse retrovirus--a very long time ago was the estimate, based on the genetic changes. This was just their estimate. I will have to try to find these quotes for us. How and when it entered the human body, they don't know.

We share biological material with other life forms, of course. How this happens can come about through eating animals or insect go-betweens like ticks, mosquitoes and fleas, etc., etc., as you say. But the implication from what I read is that this consequential transfer isn't happening now because the mouse and human retroviruses are no longer the same thing--in other words, we aren't catching XMRV from mice.

I don't know if that helps!

Cecelia

 

[kurt]

some comments on replication possibilities

Dr Peterson answers this very concern as follows: http://aboutmecfs.org/Rsrch/XMRVPeterson.aspx

Garcia,
I thought Dr Peterson's answer was about direct mouse contaminants, and not about the possibility of MLV contaminants in media, or direct from humans running the test, or already present in the blood of the test subjects. Maybe he has addressed these other issues as well, but I have not heard of that.

But regardless, this issue can not be settled by careful analysis of what WPI has stated, or how they defend their work verbally. Only replication studies can confirm or disprove the WPI findings.

Kurt,

Nobody, least of all me, has assumed that the German study is a mis-measurement. My take on it is a guess, not an assumption. Everything is speculation at this point. My guess is based on the finding of ZERO XMRV in a population where you would expect to find at least some. Thats a red flag.

Repeat, XMRV has been found in other German studies, although at a rate less than in the US. If thier methods were correct, it follows that the German study should have found at least some XMRV. Or not. With the pros arguing among themselves, how are we lay folk to know more that they do? There is really nothing much to discuss without follow up studies, I agree with you on that point.

As for bias, I am on record here stating that I personally do not wish to be found to be infected with this cancer causing retrovirus. So if I have a bias, it runs in the opposite direction.

Levi,
Sorry if I misunderstood your viewpoint, these quick reads and posts are sometimes misleading, and who has time to go back and read every poster's history to understand their mindset... Anyway, I agree, the disparity in the German studies MAY be a red flag. But for what? Which side is in error?

And I agree with you, I would rather the pathogenesis of CFS not include a dangerous retrovirus. At this point I believe XMRV is a very unlikely explanation for CFS, for many reasons that I have posted previously (sorry, just no time to recount here). But unlikely does not mean impossible, again, we must wait.

Kurt, there was speculation here if there is xmrv in ticks, mainly because ticks feed on mice first (not deer...)
Several lyme patients have asked that question.
Also, some lyme patients wonder if the reason for treatment resistant lyme is XMRV (from ticks that feed on mice first)

Can you ask your friend to test some ticks?
Can he develop a more sensitive PCR test for lyme? (there is a lab in Poland that has a new real-time PCR test for borrelia, and some patietns have tried it and it detected borrelia DNA but after they took some grape seed extract that butst cysts. Discussion found on lymenet when searching pcr poland)

Nora,
That is actually an interesting idea that I will run by my contact, testing ticks. I know that HIV has been proven to persist for a short time in one species of African tick. But they must know what they are looking for, PCR requires a specific DNA sequence for the target, it is not a scan.

And yes, I believe he could develop a Lyme test so sensitive it would detect a single spirochete in a sample. I don't know about the cyst busting, but believe that can be done in the lab also, should not have to rely on the patient for that. I have mentioned this to him already, that there should be more sensitive Lyme testing, and a computational real-time PCR could definitely accomplish that.

Here and elsewhere it was clearly stated that the XMRV found in the CFS patients was not identical to that found in the prostate cancer samples and not identical to that found in mice. The question of lab contamination via mice was brought up when the study came out and it was settled then. These retroviruses are different! I wish to put to rest the fears about mice and the rumor/belief that XMRV is part of the Lyme from ticks business.

I have also read, via the media links thread, that XMRV is a very simple, primitive retrovirus which replicates and changes very slowly.This is the opposite of HIV which replicates and changes so fast, the drugs have to keep changing too. Because of the slow replication rate, it is thought that anti-retrovirals won't work so well for XMRV because the current design of those drugs goes after the virus while replicating. At the same time, it will be easier to develop a vaccine because of the stability of the virus, it was said.

Cecelia

Cecelia,
According to what WPI has said, the differences between the XMRV versions are very, very minor. A good computational RT-PCR test will account for that, as the newer computational tests (which WPI is not using) can predict possible mutations and scan for them. This can be done because some areas of the genome are known to be more and less stable, so that can be taken into account.

As far as contamination, there may be other MLV species that are similar to XMRV genetically that can contaminate media. There is some evidence this can happened, a study in Germany found an engineered virus in a different lab from where it had been supposedly secured. So some of these viruses can get around and cause contamination through some other vectors, perhaps even through humans. So no mice are required for contamination to occur, there can be other causes of viral contamination. Therefore ruling-out mouse involvement does not rule out contamination.

As far as slow replication, I read that as an inference to explain the lack of variation in the bug in different samples. So maybe there is an alternate interpretation for that phenomenon, some type of contamination.


A PERSONAL COMMENT - I am a little conflicted about the CDC and some other labs that already have data and have not shared that yet. On the one hand I wish they would spill the beans so we could move forward, but on the other I appreciate that they must be really, really certain before they say what they have found. I am fortunate to know an insider, and have been able to learn a lot quickly about PCR testing and what is happening with some of the replication studies. Hopefully they are working fast and furious on their write-ups and we will see some results in the next month or two. Waiting is hard.

 

[MEKoan]

A PERSONAL COMMENT - I am a little conflicted about the CDC and some other labs that already have data and have not shared that yet. On the one hand I wish they would spill the beans so we could move forward, but on the other I appreciate that they must be really, really certain before they say what they have found. I am fortunate to know an insider, and have been able to learn a lot quickly about PCR testing and what is happening with some of the replication studies. Hopefully they are working fast and furious on their write-ups and we will see some results in the next month or two. Waiting is hard.

And from another thread:

But here are the facts, I have studied this issue and this company since I know someone connected with them. Dr Satterfield worked for years with military and governments (US and foreign), including the US Dept. of Homeland Security, on various rapid test development technologies. His company, Cooperative Diagnostics, bases its methods on his work for those agencies and they have proprietary rapid test development techniques that are proven. They have the ability to accurately amplify samples far beyond ordinary PCR tests, so they really do need less sample. This is all explained on their website. Also, they have experience that probably helped them given their previous work in retroviral testing for HIV, so this was easy and fast for them. They had less learning curve probably than most other labs.

Also of interest, Dr Satterfield helped with rapid Anthrax test development, I don't know the details but can find out if anyone wants. I have suggested to them that they need to communicate better their capabilities and credentials. They are a young firm and I believe they are exactly what we all hoped would happen after the WPI announcement, highly capable scientists in industry becoming interested in CFS. And they are committed to CFS, not just XMRV, I think we will be seeing much more of their work in the near future. They have mentioned to me that they are involved in a study and hope to have a journal publication out relatively soon.

The comments of Dr Peterson are understandable as this is competition for his testing (the VIP lab is probably paying a hefty licensing fee back to WPI). But I think it is unfortunate that such acclaimed scientists would so rapidly dismiss the very thing we need in the CFS world, the growth of services for people with CFS. They should not be afraid of a little competition.

Hi Kurt,

I understand that you believe the WPI findings will likely not hold up. Is it a leap too far to assume that it is Cooperative Diagnostics are not able to replicate the WPI findings?

This information might be very useful for people who are contemplating testing through them. Some of us live on such tiny incomes but want some kind of certainty badly enough to go into debt to be tested.

I know it's possible, given your science writing, that you may have connections in both C.D. and the CDC labs.

Peace out,
Koan

 

[Sing]

To Kurt

Thank you so much Kurt for this detailed, helpful reply! Please keep us in the know, or at least, in the realm of better informed speculation.

Cecelia

 

[oerganix]

Rumors

Levi, his last paragraph hints that he's not even from the U.S., yet is able to make these glowing definitive statements about the CDC. This rumor isn't even close to being believable.



I agree that we should just bide our time and not be taken in by rumors.

I've read all the posts by that person and I'm convinced he is just a troll, probably a bored teenager with nothing better to do than bait people. I suspect he gets his laughs when people take him seriously enough to respond in anguish and anger. I wouldn't even characterize his posts as "rumor".

*EDIT*I seem to have not quoted enough of Levi's post to make it clear I am characterizing the commenter in the NYTimes as a troll, not anyone on this list. S/he signs himself "skeptic" and seems to possibly be in cahoots with one who signs herself -E. I imagine they are a couple of teenagers baiting people to see what response they can get. "skeptic" is the one who said there will be news coming out of the CDC that we won't like, etc., later saying the people who claim to have CFS can look forward to forced placement in mental institutions and ever increasing amounts of electro convulsive shock "therapy". On the other hand, maybe this is Dr Reeves schizophrenic teenage son, posting for both people. (Just kidding)

 

[Cort]

I appreciate Kurts analysis of the situation. I think we should be ready for anything. We won't know until we know. It sounds like we won't really know until several replication studies are done and they start to agree with each other.

As PCR tests have been around for a long time and they are a very important part of research and have been well studied - it would seem to be easy to replicate one but there seem to be a lot of variables when you're starting out fresh with a new pathogen test. Garcia recently transcribed Dr. Coffin's testimony (thanks Garcia! - he transcribed did Peterson's as well):

I want to emphasize that in order to do these studies it’s very important that we have standardized, uniform, well validated and reliable assays. This is really the critical issue here. And immunological assays are particularly difficult in this case. Even with HIV the well established HIV-assays still have a certain false positive rate and so it’s really critical that we know exactly what the assay is, it’s been well validated with well standardized specimens and everybody is on the same page, ideally using the same assay for these studies.

These high tech labs clearly each want to come up with the best assay for XMRV. Theres no guarantee right now that it will the WPI - each is going through the process themselves. Look how Coffin puts it: "We may win out" - its a race!

And this is one of the things we are actually working on in Frederick quite intently right now is to try to develop some assays that will fill this, but other people are as well. We may win out, they may win out but whatever happens before we can really get a real handle on this, these assays are critically important.

http://aboutmecfs.org/Rsrch/XMRVCoffin.aspx

Its clearly not an easy thing to do. It could even be that a first replication study could say 'No XMRV in CFS" and over time be proved wrong.

 

[starryeyes]

Here are the last 2 paragraphs of the link to Dr. Coffin's interview. They answer many of our questions. Well, sort of....

Transmission - We have no idea what the mode of transmission is, despite some things you may have read and in my opinion we just don’t know. The ability to easily isolate the virus from blood cells and from blood certainly implies that transmission could be blood borne. Beyond that I haven’t a guess as to what it’s being transmitted by. Bodily fluids? It’s probably not transmitted in aerosols. These viruses are not very transmissible that way in general, but we don’t know that for sure for this virus. And we don’t know the origin of this virus.

The close relationship of this virus means it almost has to have come from mice, I can’t really visualize another scenario. But is that happening today? Does it happen all the time? Is it like a hanta virus outbreak or something like that? Or did it happen once a long, long time ago and it is then transmitted at a level in the human population and of course if it is causal for the disease we don’t know what the attack rate is going to be, we don’t know what fraction of the people infected with this virus. Everybody infected with HIV eventually dies, almost everybody will die, 99 point something percent will eventually die of AIDS, if untreated. However everybody infected with another human retrovirus HTLV1, only a small fraction will actually get disease so we don’t know that for these viruses. I mean this list [of questions] could go on and on.

 

[Eric Johnson from I&I]

> And that the strains are different--prostate and CFS--isn't all that surprising, is it?

Nay Madame, I am almost sure they are not separate. Its in the very beginning of Peterson's talk at CFSAC



> [different poster:] My understanding from reading Peterson, Silverman, etc is that XMRV descended or evolved from the mouse retrovirus--a very long time ago was the estimate, based on the genetic changes. [...] in other words, we aren't catching XMRV from mice.

Negatory, Coffin opined that it might still be transferring even at this time.

 

[Eric Johnson from I&I]

According to what WPI has said, the differences between the XMRV versions are very, very minor. A good computational RT-PCR test will account for that, as the newer computational tests (which WPI is not using) can predict possible mutations and scan for them. This can be done because some areas of the genome are known to be more and less stable, so that can be taken into account.

I strongly suspect you know little about PCR or the general epistemology of the Mikovits paper. Contrary to your suggestion, there is nothing "wrong" with the "old" PCR methods. They run on the same principle as any PCR; the new "kinds" of PCR, therefore, are not separate kinds but just have various bells and whistles tacked on to the same principle.

Contrary to your statement on the other thread, the method of Mikovits, namely PCR followed by sequencing of the XMRV amplicons, is as strong and certain as *any* possible PCR-based way of working -- probably stronger, in fact. The particolored and gaily-flourescing RT-PCR techniques tenderly regarded by you, and hailed in your voluminous writings as the true millenarian PCR of All Peace, are actually not all that infallible for making sure you didnt amplify the wrong thing. RT-PCR uses fluoroprobes; these add to your confidence in having the correct amplicon. But they can bind falsely, nonspecifically. Heres a great example, maybe: they were used in the DeFreitas paper on CFS, which is probably wrong -- note that it was disconfirmed not just by CDC but also by the reputable (by our lights) Gow and Behan.

PCR + sequencing = you did not get the wrong sequence, you did not amplify the wrong thing, for sure you didnt. There is just no way. With RT-PCR, there is a way, though its very unlikely to happen.

Of course your PCR might still be contaminated! Naturally! Pray about this, while also doing your mortal best. But this caveat <i>applies equally to every possible way of doing PCR.</i>

Viola! As a full and canny (and really obnoxious) inductee of the living tradition of Science, I conjure you to believe in the mighty words of my mouth. NVLLIVS IN VERBA!

 

[perovyscus]

Although the New York Times commenter appears to be deliberately aggravating malcontents, that forum is an atypical avenue for teenage trolling.

Teenage boredom rarely leads you to the NYT. Agenda might.

There's a computer program that supposedly predicts the future based on an internet search formula, and its founders sell the answers.

"Is XMRV the causitive agent of CFS?"

If I do have this, it means my first (currently healthy as far as I know?) sexual partner gave it to me. That's devastating, too, because then it's a multi-factorial problem.

 

[Eric Johnson from I&I]

> If I do have this, it means my first (currently healthy as far as I know?) sexual partner gave it to me. That's devastating, too, because then it's a multi-factorial problem.

No offense but why do you think so hastily. Whatever you observed, it could e a s i l y be a coincidence. It takes many, many observations to show that sexual transmission of this is even possible.

 

[fresh_eyes]

FWIW, I took the Times troll as a rather canny if heavy-handed CFS person, making much of the worst-case scenarios, to make a point. I've thought the same about some comments in the Times purporting to be from a number of aggressively ignorant MDs.

Perovyscus, another possibility - Dr Klimas said in a tv interview that it's likely people have XMRV from birth.

 

[Esther12]

Although the New York Times commenter appears to be deliberately aggravating malcontents, that forum is an atypical avenue for teenage trolling.

Teenage boredom rarely leads you to the NYT. Agenda might.

I thought the NYT commentator was quite funny, in a rather malicous way (and after being terrified it was serious). They really know how to play to the worst fears of CFS patients. It must have been someone with a lot of experience with CFS, but I really don't think it's worth spending much effort trying to work out why they were posting. People are odd, and the internet lets this shine though.

 

[Esther12]

I didn't catch all those posts.

I read the last couple they made just before going to bed, and felt my heart jump. Luckily I saw the others and realised it was a joke, or else I'm sure I'd have been in for some funny dreams.

I think you're right, and it probably is someone with CFS satirising the way some doctors view us. It works worryingly well as a satire of my own worst fears and paranoias too though.

 

[Marylib]

hopefully a bad joke

Well, when I read the troll's post a hearty chuckle escaped my lips, so I am assuming it is a rather shady joke.

 

[annunziata]

The awful thing is that the situation with CFS/ME is so dire it's hard to be certain that it is a joke.

 

[Eric Johnson from I&I]

Haha, love it -- hilarious