Dr Vincent Lombardi

[cfs since 1998]

It's all about supply and demand. The 6 week waiting list just to get a test kit would seem to indicate the price is not too high at this time, but too low, actually. WPI did say they are working with Quest and Labcorp so testing could become more widely available and cheaper soon. And once there are widespread concerns about the blood supply, the price of testing will plummet like a rock.

 

[kurt]

Supply and demand?

It's all about supply and demand. The 6 week waiting list just to get a test kit would seem to indicate the price is not too high at this time, but too low, actually. WPI did say they are working with Quest and Labcorp so testing could become more widely available and cheaper soon. And once there are widespread concerns about the blood supply, the price of testing will plummet like a rock.

A shortage of test kits? Test kits are nearly the same for every type of blood draw. In this case probably a basic purple top tube (EDTA). They do not even need kits, they could simply send instructions for the lab to draw, pack and ship, and most labs can do that. Maybe there is some other reason for the delay.

Like I said above, this is all being played like the typical medical research game.

 

[cfs since 1998]

A shortage of test kits? Test kits are nearly the same for every type of blood draw. In this case probably a basic purple top tube (EDTA). They do not even need kits, they could simply send instructions for the lab to draw, pack and ship, and most labs can do that. Maybe there is some other reason for the delay.

There is a 6-week wait to get a *kit* because they can't *perform* that many tests all at once.

 

[kurt]

Kurt,

Check into murine leukeimia retrovirus (MRV) and what it does to mice. If indeed XMRV is a real replicating human retrovirus with genetic similarity to MRV, and it is established that there is a significant linkage to ME/CFS (2 big ifs), then it will be the real deal.

Actually I suggest you check on what MRV does in humans, which is exactly nothing. In fact, MRV is being considered as a therapeutic agent, for gene therapy in humans.

See: http://www.virologyj.com/content/1/1/14

As far as whether XMRV might be the 'real deal,' this depends on the binding site of XMRV in humans, which might be different from the binding site of MRV in mice. Also, there may be DNA differences between mice and men, so what is blocked in a mouse is not what will be blocked in a human. We can not make assumptions like this, viruses do many different things to different hosts. XMRV will be found causal if someone finds a binding site in PWC, figures out what DNA is blocked, and can connect that problem with specific CFS pathologies. Then they have to prove that XMRV is a necessary pre-condition for CFS, which is difficult since they can not run live tests.

Meanwhile the buzz about a retrovirus will cause some people to try anti-retrovirals, even before any causal connection is proven. Perhaps this is all serendipity, and something unexpectedly helpful will emerge from a treatment trial. I hope so, but will maintain my attempt at objectivity in the meanwhile. What I hope NOT to see is someone getting rich off of some useless patent and a lot of people with CFS being taken down a blind alley yet again. Or worse, a patented treatment that works but is unfordable to the majority of PWC. We don't need more Ampligen quagmires, either make something we can all afford or find a sponsor who will pay for our treatments, or go play somewhere else...

 

[kurt]

There is a 6-week wait to get a *kit* because they can't *perform* that many tests all at once.

Really? CLIA labs can perform hundreds of PCR tests every single night. What type of technology are they using? This is not giving me confidence in VIPDx or WPI for that matter.

 

[cfsme23]

Really? CLIA labs can perform hundreds of PCR tests every single night. What type of technology are they using?

Maybe they simply don't have the staff to adminster the tests, doesn't necessarily have to be the technology that is the limiting factor.

 

[Warbler512]

Who's pushing who?

This is starting to get crazy. Wasn't a commercial test supposed to be 6 months away? It would take time just to verify that Quest and Labcorp are doing it properly - time well spent. So, now this shortcut to the research lab, which can't provide the "kits" for 1-1/2 months. Maybe they don't have a lot of folks (not Tom Folks). But what's gotta be in these kits? A styro-pack is helpful; a lot of doc's offices don't just have those sitting around waiting for patients. Why not just wait till they've got 'em then?

Who's driving the "demand" here? Are we supposed to thing WE are driving it, in panic or exuberation? That would not necessarily be good.

 

[hvs]

However, the more likely scenario in my view is that XMRV turns out to be just another co-factor

How would it work that it's a co-factor that for most intents and purposes only shows up in CFS patients? We're so very very special that we alone somehow take this thing along for the ride?

We take all kinds of things along for the ride, it's true. But they also show up in normal people (EBV, HHV-6, etc.). And we demonstrate all kinds of neat biological tricks that most other folks don't (second treadmill test abnormalities, etc.) But none of those are potential causes.

Even if it turns out to be "just another co-factor," a possibility to which I'm open but for which I've never heard a logically sound argument, it certainly is a deadly one.

 

[Eric Johnson from I&I]

> CLIA labs can perform hundreds of PCR tests every single night.

True, but this is an unstudied agent. It has unknown dangerousness in the lab. They are probably doing a lot of the stuff inside a BSL-2 safety cabinet and being vigilant, which is kind of a pain. Many infections have occurred through lab accidents. Even more have occurred in medical personnel, even with agents not casually contagious.

It being an unestablished test and a new public health situation, they also are probably very anxious not to mess anything up. They are probably quite worried about potential contamination from mice. They are probably sequencing a lot of what they find to make sure it isn't something from mice, and running all kinds of uptight controls on every batch, maybe running each blood sample more than once.

 

[kurt]

> CLIA labs can perform hundreds of PCR tests every single night.

True, but this is an unstudied agent. It has unknown dangerousness in the lab. They are probably doing a lot of the stuff inside a BSL-2 safety cabinet and being vigilant, which is kind of a pain. Many infections have occurred through lab accidents. Even more have occurred in medical personnel, even with agents not casually contagious.

It being an unestablished test and a new public health situation, they also are probably very anxious not to mess anything up. They are probably quite worried about potential contamination from mice. They are probably sequencing a lot of what they find to make sure it isn't something from mice, and running all kinds of uptight controls on every batch, maybe running each blood sample more than once.

Well maybe, but CLIA labs can do hundreds of HIV PCR tests overnight too, and that is a pretty dangerous organism. XMRV has not been proven to be dangerous. They SHOULD be worried about contamination though, that is an interesting thought that they might be sequencing samples. But that is still pretty much automated.

I remain skeptical. What seems more probable is that other labs they are working with, or maybe even the CDC is not confirming their results, and they are trying to figure out why. Or maybe the test is just going slower for reasons you mentioned, and I am just too jaded from a decade of false hope from research announcements :0

 

[Eric Johnson from I&I]

> Well maybe, but CLIA labs can do hundreds of HIV PCR tests overnight too, and that is a pretty dangerous organism.

HIV is fairly safe in the lab because of its low infectiousness per virion. It's handled on the open bench, not in a safety cabinet. I'm not sure but I think maybe "only" three people have been infected in research labs (probably way less than have been contaminated with it and escaped). That's not so many considering it's $3 billion a year, 10% of NIH's budget. $30 billion per decade: that's a whole lot of bench jockeys juggling HIV. And many times more have been infected with hepatitis viruses, highly infectious on a per-virion basis.


> XMRV has not been proven to be dangerous.

But it also hasn't been proven to be fairly lab-safe, from blood. Not many people get blood-contaminated in everyday life, so the epidemiologic facts tell us nothing about how dangerous the blood is (if it is communicable at all from saliva, it's probably not highly communicable that way). Were I not probably infected with XMRV already, I would be far more comfortable handling HIV at this point. It's pretty easy to lose a tiny fleck of fluid from a pipet. HIV is a known quantity in the lab (all possible lab infections have been investigated and reported, of course).


> They SHOULD be worried about contamination though, that is an interesting thought that they might be sequencing samples. But that is still pretty much automated.

It's semi-automated, and you have to pore over the readout a good deal, looking at the analog signals to make sure everything's right, and wonder if you got artifactual mutations from the PCR (if you're using Sanger). In this case, every nucleotide counts if you are trying to make sure you haven't "caught a mouse" with your PCR. If they catch a mouse in public their prestige and credibility will eat dirt, that's the bottom line.


> I remain skeptical. What seems more probable is that other labs they are working with, or maybe even the CDC is not confirming their results, and they are trying to figure out why.

That's quite possible. I hope not!

I'm kind of a jaded type. I didn't even hear about that "cryptovirus" thing until last week! And I thought I knew what was going on, ha ha. So now I'm even 2% more jaded than before. What's funny is that I couldn't even find out how it tanked, in 20 minutes of googling, but obviously it tanked. But this is different from that or even from DeFreitas. The opinion of Coffin and other National Academy virologists is worth a lot. Ya don't trip and fall into the National Academy. That cryptovirus guy had some lab down in Mexico, which is kind of like, hmmm... OK. It's not like that automatically makes him a joker, it just changes the odds.

 

[Eric Johnson from I&I]

> XMRV will be found causal if someone finds a binding site in PWC, figures out what DNA is blocked, and can connect that problem with specific CFS pathologies.

This is mistaken. Not all retroviruses have a specific integration site. XMRV doesnt. Integration that disrupts an important gene can cause cancer, but viruses have many other ways to cause disease (they may even cause cancer in other ways).


>The big profits will follow in patents and licensing later

There's no patent on XMRV, I checked last week. I dont know if viruses are patentable, but even if so, XMRV definitely can't be patented now because it has already been communicated. If you want to patent, you can't blab -- at all. Maybe you meant drugs for treatment. There will definitely be patents and mountains of dough when it comes to treatment.

 

[PoetInSF]

Who's driving the "demand" here?

People who desperately need/want to say: "see? I have a real disease!"? Keep in mind that there is no xmrv-cfs causality and treatment, yet. What bothers me is that people who should know better is peddling this not-yet-necessary test to desperate people at $$$. You have to wonder why.

 

[kurt]

reposte - XMRV integration site

> XMRV will be found causal if someone finds a binding site in PWC, figures out what DNA is blocked, and can connect that problem with specific CFS pathologies.

This is mistaken. Not all retroviruses have a specific integration site. XMRV doesnt. Integration that disrupts an important gene can cause cancer, but viruses have many other ways to cause disease (they may even cause cancer in other ways).

Eric, where did you hear that XMRV does not have an integration site? I read one XMRV study for prostate cancer that did suggest several binding sites, including adaptive areas and also a site that blocks the paracrine mechanism DNA in the neuroendocrine tissue. But my point was simply that if a specific site and blockade were found, and connected to CFS symptoms, that WOULD be rather conclusive. Short of that, causality will be hard to prove. And certainly XMRV may attack both randomly as well as specifically to a favored integration site, at the same time.

But since you seem to know a lot about this, here is a question. I know everyone is talking about immune disruption, and they are finding the virus in the NK cells, etc. But we know from AIDS that damaged immune function does not produce CFS, at least not until the last stage of the disease, and we are not in that situation. So logically doesn't that argue that XMRV must do something else, if it is really pathogenic in CFS? And if it is reliably producing CFS I think that a random disruption is highly unlikely. What do you think?

 

[Eric Johnson from I&I]

Well, I see no real reason at all to buy it -- but I'm very glad to have the option to do so or not, strictly as I please, with my own money that I produced by my own labor. And I'm glad to let everyone else decide for themselves. This test doesn't hurt other people, or society. Therefore, it doesn't need to be justified any further. I'm glad such things are legal, and also glad they're available.

Many peoples' CFS cases have been doubted, a little or a lot, by their spouses or relatives -- as to them having a real disease or not. (I've been accused of malingering myself.) Might this test affect their spouses' thinking, even without 10 confirmatory papers having come out, to date, in high-rated journals? Absolutely. Even in areas amenable to scientific investigation, not everything we do is based on ten confirmatory papers, or on any other strong standard of certainty. I think this is 80% likely to be the cause based on what we know now, and if you think otherwise, I'm glad to just agree to disagree. One trillion tests have been sold to CFS patients, and in my opinion the were ALL less worthwhile than this one. That's why I haven't bought any of them, or this one!

Nevertheless, I'm not at all sure that the this test's availability will produce a a net measurable good. Who knows? But having freedom to make your own choices using your own standard is a non-measurable good, and a crucial one. That good consists largely in increasing your dignity, and so helps give life its meaning. Under that view of things, selling this test is a good thing.

 

[Eric Johnson from I&I]

> Eric, where did you hear that XMRV does not have an integration site? I read one XMRV study for prostate cancer that did suggest several binding sites

Actually, I saw something like that too today, I think. You're probably right, I probably totally misunderstood this other paper I looked at (which I will try to relocate).


> But my point was simply that if a specific site and blockade were found, and connected to CFS symptoms, that WOULD be rather conclusive. Short of that, causality will be hard to prove. And certainly XMRV may attack both randomly as well as specifically to a favored integration site, at the same time.

I see what you mean: proving that it is pathogenic in that particular way would be sufficient, but not necessary. I thought you meant it was necessary (you may have been a little ambiguous).

 

[Eric Johnson from I&I]

> and also a site that blocks the paracrine mechanism DNA in the neuroendocrine tissue.

Do you know that is, more exactly? You aren't talking about the thing involving cortisol and other hormones, are you? Because that is something different, not related to the integration site.

> But we know from AIDS that damaged immune function does not produce CFS, at least not until the last stage of the disease, and we are not in that situation. So logically doesn't that argue that XMRV must do something else, if it is really pathogenic in CFS? And if it is reliably producing CFS I think that a random disruption is highly unlikely. What do you think?

I don't know. I'm sure lots of AIDS patients have fatigue, but do they all? I donno. HIV is slowing reducing their helper T cell counts, by an unknown mechanism, for a long time. But they don't really get co-infections (or symptoms) until their helper T cell count drops below roughly 200 or 400 or so. I'm sure the threshold varies a little by individual. But before that, they are fine, with maybe a subtle immune deficiency at most.

Because the mechanism of depleting the helper T cells is still unknown, I'm certain it hasn't been uncontroversially connected to anything having to do with HIV's integration.

Proving causality is a very gray area, and HIV itself is a great example. Like most infections, it hasn't satisfied Koch's postulates, whose satisfaction is sufficient but not necessary to prove causation. As a matter of fact, there's really no straight up, extremely simple and rock solid sequence of logic that proves that HIV causes AIDS. But there are so many near-rock-solid clues that the non-causalists are now, justly, very very far out of the mainstream. But you can't just explain it in two sentences, it's complicated and even a summary would take a page or so.

Basically, many studies find EBV in 100% of lupus and MS patients. It's also in almost all healthy people, like, I dono, 95%? So EBV is considered a nice possible cause for those diseases, but faaaaaaaar from certain. But other than that, NO microbe has ever, in all of history, been found in essentially 100% of patients, unless it was so common that it's in most healthy people -- like above 50%. Here we have something that's in essentially 100% of patients, and 26.5 times more common than it is in controls. So yeah, it might not be the cause even if Mikovits et al. is totally confirmed -- but this would be unprecedented. It's hard to say what the chances of this are, other than "not big."

 

[Eric Johnson from I&I]

Aha, is this the paper you looked at Kurt? It mentions some of the stuff I think you mentioned: "a model in which XMRV may contribute to tumorigenicity via a paracrine mechanism." It's also the one I had looked at.


"In the prostate cell line, XMRV integration is characterized by a strong preference for transcription start sites, CpG islands, and DNase-hypersensitive sites, all features that are frequently associated with structurally open transcription regulatory regions of a chromosome. Integration of XMRV is also preferred in actively transcribed genes and gene-dense regions within the chromosome."


So if I understand, it has preferences for a number of *types* of sites, but it does not zoom in to any single site or handful of sites. Maybe that was what you meant, I'm not certain.

In the 2nd to last paragraph they explain the whole paracrine mechanism thing.

 

[Advocate]

>
I didn't even hear about that "cryptovirus" thing until last week! ... That cryptovirus guy had some lab down in Mexico, which is kind of like, hmmm... OK.

Cryptovirus thing? Unless I'm the only one who doesn't know, please tell us.

 

[Eric Johnson from I&I]

I don't even know! It's that off the wall. I was shocked that I hadn't heard about it. One of the CFS research charities was funding it, and nothing was ever published. There was a press release by said charity. And I found zero info on why the whole thing vaporized. At least it didn't drag on very long.