XMRV and chronic fatigue syndrome: Insanity

This is insanity, people.

Scientific insanity.

Moved right from ‘this does not make sense‘ and ‘youre acting like a bitch‘ to ‘this is insane’.

#1– Lead author of the Reno XMRV–>CFS study is holding a live-streamed press conference at Hotel Mar Monte on Friday.

*blink*

This is insanity. They have no evidence connecting XMRV to CFS in anything but a casual manner, and yet she is giving a presentation/Q&A to CFS patients. Insanity.

Furthermore, the people ‘hosting’ this talk, ProHealth? What is this? What is this crap? Pages and pages and pages of powders and potions and crap.

Why in gods name would any scientist with any sense of self-worth agree to this event?

I mean, I ‘debated’ Lenny and his magic tuning forks, but that was for lulz. Im assuming Mikovits is serious about this.

Insanity!

#2– I am completely baffled by VIPDX super awesome NEW diagnostic test. Okay, old test was PCR. Fine. I mean, sure it had a false positive rate of 1:25, where the false positive rates of HIV-1 tests are 1:250,000 (at worst), but whatever, it ‘worked’.

Dudes switched to ‘viral culture based tests’.

WHAT?

Viral culture is an old-school way of diagnosing viral illnesses. By ‘old-school’, I mean 50-60 years ago, and they did it because they did not have technology like ‘immunology’ and ‘PCR’. Today, when you go to the doctor to get tested for Mono or flu or HIV-1 or herpes, they use todays technology– usually immunology (cheaper) but sometimes PCR (more accurate, but also more expensive).

Example– How we do HIV-1 testing.
1. You are PCR positive right after you get infected. ONLY the viral RNA (and DNA) is there.
2. Next, you are ELISA positive. The RNA/DNA is there, and its making proteins.
3. Finally, you are Western Blot positive. Viral RNA/DNA/proteins are there, and you are making antibodies to HIV-1.

Sure PCR(1) is ‘the best’, but its more expensive (especially Real-Time), so today you can just do a quick HIV-1 test to look for antibodies(3).

The only people who do viral culture for HIV-1 are research labs. They arent doing it for diagnostic purposes, they are doing it to isolate single viruses (well, their genomes) for us to study in the lab.

On no planet is viral culture ‘better for diagnosis’ of HIV-1 than PCR/ELISA/WB.

Though technically, once viral culture did give me an advantage over PCR– I infected a cell line that was labeled ‘uninfectible’ with HIV-1. I got about 50 infected cells out of a several billion cells, which is WAY below my detection threshold for PCR, and the threshold of every other HIV-1 researcher that had used this cell line. The only reason I know those 50 cells were infected was because my HIV-1 makes cells glow green when they are infected.

But, unless these patients are infected with viruses that contain EGFP, I really cannot imagine how viral culture is ‘better’ than PCR.

Furthermore, MLV is notorious for contaminating cell lines. Its not just TZM-bls, you can go to PubMed and find a number of papers that suggest routinely checking cell lines for MLV, like we regularly check for mycoplasma.

Its insane that theyre switching from PCR to culture.

Furthermore, gf01 kindly left some test results in a comment here:

Only one was postive for XMRV with both the PCR and culture test.

Seven more were positive with only the culture test.

Seven were negative for both.

We already know that 1:25 PCR results are going to be false positive, yet more patient samples were culture positive than PCR positive, which can only make sense if your friggen cell line is contaminated with Plain Jane MLV.

*blink*

This is insanity.

This is pure insanity.

Im out until someone from another lab publishes.

ADDED 1-22-10: After listening to most of this presentation and Q&A, I have lost all faith in the Reno research group. I will elucidate why later when my blood pressure goes down and I take half a bottle of Xanax.

Comments

#1 qetzal
January 20, 2010

My prediction: they switched to the culture test because their PCR test stopped showing reproducible XMRV in CFS patient samples the way it “should.”
#2 Joe A.
January 21, 2010

It would seem to me that most CFS patients are sick for a long time before realizing that the ailment is more than just having the flu. It would seem to me that antibodies have formed and therefore it would not make any sense to do a PCR or ELISA type test for CFS. So a Western Blot type test would seem to be more appropriate for CFS patients.
#3 dreikin
January 21, 2010

I could see how tests 1 & 2 worked, but couldn’t figure out why / how you’d use 3 for antibody detection.

Then I read the wiki article and hit myself for the obviousness of it:
Use serum as the primary antibody and load the gel with known antigen..

@Joe A.:
The PCR and ELISA should still be positive, else there’d be nothing to worry about because the virus is apparently missing it’s DNA/RNA and proteins, which makes it rather non-functional.
#4 Joel
January 21, 2010

Apparently, Lenny Horowitz’s fave journal evar is in danger of getting canned (ht: T. Ryan Gregory).
#5 isomaticize
January 21, 2010

Whoa. Deep breath. You forget to take your Ritalin this morning, Erv? Perhaps you should take a cue from the current crop of CFS therapies and try some cognitive behavioral therapy, or maybe some transcendental meditation?

It’s beyond pointless to conjecture, at this early stage, why VIP has switched from a PCR to a culture test. But I do feel the urge to respond to your somewhat conspiratorial gum-flapping.

I believe VIP has reacted, albeit a bit belatedly, to the appearance of a conflict of interest. Vincent Lombardi, the head honcho at VIP, is rather prominently tied to the Science paper. VIP is the only lab in the country offering the test. CFS patients are among the most vulnerable and desperate. The $650 XMRV tests were unlikely to be covered by insurance. It appears VIP finally realized that the confluence of the factors listed above presented an ethical dilemma. They seem to have responded to this by figuring out a way to offer a cheaper test. It is irresponsible of you not to mention that the culture test is $200 cheaper than the PCR.
#6 LanceR, JSG
January 21, 2010

@isomaticize: Reading for comprehension? Yer doin it wrong.

Sure PCR(1) is ‘the best’, but its more expensive (especially Real-Time), so today you can just do a quick HIV-1 test to look for antibodies(3).

Sure sounds like mentioning that it’s expensive to me… The point ERV is making is not the cost of the tests… This investigation isn’t even at the point of developing a test for the general public. They are supposed to be at the “Let’s see if this is real” stage, and they’ve skipped straight to the “OMG! CFS is a virus! Buy our test!” stage.

Insanity.
#7 ERV
January 21, 2010

Joe– Even end-stage AIDS patients have anti-HIV-1 antibodies. If they are end-stage AIDS and havent been diagnosed previously, even an ‘indeterminate’ WB result would get them an ELISA and PCR test.

You still wouldnt do viral culture.

Lance– You are too kind, as clearly Im being a sneaky bastard. I linked directly to VIPDX press release where they talk all about their awesome *NEW* test:

I am completely baffled by VIPDX super awesome NEW diagnostic test.

See, put it in plain sight so you wouldnt see it. Berry berry sneaky. *Mr. Burns fingers*
#8 Prometheus
January 21, 2010

In the interest of saving time….

How dare you cast aspersions on MITOCHONDRIA IGNITE™! If it were not for liberal daily doses MITOCHONDRIA IGNITE™ and Crisler CardioFuel I would have been consumed by creeping morgellons from the all the contrails.

My beloved beautiful super smart wife’s distant cousin’s dog groomer’s infant daughter…

*inserts heart wrenching anecdote or biblical parable*

You are just a person who claims to be a “graduate student” and you need to educate yourself by spending more time on internet support forums before you go around pooping on the work of your SUPERIORS.

“By ‘old-school’, I mean 50-60 years ago, and they did it because they did not have technology like ‘immunology’ and ‘PCR’.”

Oh yea. You know what else is 50 or 60 old? Mr. Potato Head. That’s right the inanimate tuberous plastic spokesperson for the American Cancer Society is obsolete by your arbitrary ‘religion of science’ standards.

I hope you get whatever the syndrome is that you probably haven’t mentioned because then you will be singing a different…..

blah blah blah

*wall of links to unrelated old articles, echo chambers and hugboxes*
#9 Jon H
January 21, 2010

I think Mikovits has been using a bit too much Euphoria(TM)
#10 qetzal
January 21, 2010

isomaticize:

I believe VIP has reacted, albeit a bit belatedly, to the appearance of a conflict of interest. Vincent Lombardi, the head honcho at VIP, is rather prominently tied to the Science paper. VIP is the only lab in the country offering the test. CFS patients are among the most vulnerable and desperate. The $650 XMRV tests were unlikely to be covered by insurance. It appears VIP finally realized that the confluence of the factors listed above presented an ethical dilemma. They seem to have responded to this by figuring out a way to offer a cheaper test. It is irresponsible of you not to mention that the culture test is $200 cheaper than the PCR.

Let’s see. We have an uncertain and disputed link between XMRV and CFS. Even if there is a link between XMRV and CFS, we have no data that XMRV is causal. Even if XMRV is causal, we have no data on whether antiviral strategies could be beneficial for CFS, or how best to implement them even if they are.

So what’s the rationale for offering *any* XMRV test to the public? Especially one that’s not clinically validated!There’s no way to interpret the results or decide what (if anything) they should mean for treating the patient!

Should we be impressed that WPI and VIPDX have decided to sell a medically useless test that’s cheaper? No, we should be disgusted that they’re offering any XMRV test to vulnerable and desperate patients, when the results have no medical value! Even if their test cost $1, it would be a waste.

I’ve got a much better idea for them. QUIT SELLING XMRV TESTS TO PATIENTS. Focus on proving (or disproving) any causal link between XMRV, and researching whether anti-XMRV treatments might ameliorate CFS. Once that’s done, THEN they’ll be justified in selling XMRV testing to patients.
#11 isomaticize
January 21, 2010

If you’re intimating that VIP is trying to make a buck off CFS patients, please state that opinion directly.
#12 qetzal
January 21, 2010

They’re making money off whoever pays for their tests. I presume that’s mainly CFS patients.

And yes, I’m aware that they’ve pledged to funnel all profits back into their research. Do you think that justifies charging patients for a medically useless test?

Note that I am NOT intimating that either WPI or VIP are running a scam or being intentionally unethical. Instead, I think they’re so caught up in what they’re doing, and so convinced that they’ve discovered the secret to CFS, that they’re not thinking clearly. But their presumed good intentions don’t change the fact that selling this test to patients is wrong.
#13 gf1
January 21, 2010

@ERV re “We already know that 1:25 PCR results are going to be false positive”

Is that just based on the detection of XMRV in healthy controls? I thought a few papers connected to XMRV in prostate cancer have also been picking up XMRV in the general population at 2-4%. I guess they could be false positives too, but isn’t it a bit early to say?

re the Mikovits talk and selling tests: You need to remember that CFS patients are desperate for information. Once the Science paper was out another commercial company started offering XMRV tests right away, so I can understand the WPI thinking it would be sensible for them to offer them too. The WPI also seems very connected to patients groups, and has recieved a lot of charitable support from them, even if that were not the case I don’t think there’d be anything wrong with Mikovits giving a talk to patients (depending on what she actually says).

I have no idea if the XMRV/ CFS link will hold up, and it would be surprising if CFS was actually caused by a retrovirus; but at this point the behaviour of the WPI should be compared to that of other researchers connected to CFS as well as a scientific ideal. CFS is a really good example of what happens to the scientific process when patients, doctors and society need to base their decisions upon an understanding of an illness when the available evidence doesn’t allow us to sensibly come to one. We’re terrible at dealing with just ‘not knowing’ in these cases, and often it’s those most willing to make exaggerated claims of certainty which rise to prominence. It’s a mess, and it has been for quite some time. The WPI are playing that game, and it makes them look silly to those unfamiliar with it. It is silly. But that’s the way it is.

I don’t know why the WPI think it’s better to use culture tests than PCR, and would be interested to hear their explanation. I have a vague memory of reading that PCR tests don’t seem to work very well for Lyme disease, and culture might be better. But Lyme is another disease which seems surrounded by quackery so that could well be rubbish.

Ps: I’ve just checked Wikipedia – the source of all my scientific knowledge – it mentions PCR not being reliable for Lyme, but doesn’t mention culture tests as a preferable alternative.

PPS: Actually Wikipedia linked to this, which does say “Of these, culture of B. burgdorferi sensu lato undoubtedly offers the best confirmation of active infection and has been increasingly used as a diagnostic modality by many researchers on both sides of the Atlantic.”: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1195970/?tool=pmcentrez

I could well be confused by that article though, and I gave up half-way through. I don’t understand why PCR could have trouble with certain viruses or if this might apply to XMRV.
#14 isomaticize
January 21, 2010

CFS is an ailment characterized by a lack of laboratory abnormalities – this is the single most decisive factor when it comes to funneling incapacitated CFS patients to shrinks for talk therapy and Prozac. In other words, normal blood tests and normal scans lead to psychiatric diagnoses and the unfortunate stigmas attached. Normal blood tests and normal scans also lead to a steadily increasing spurning by family and friends – which adds insult to injury for the patient. With this in mind, a positive XMRV test is paradoxically a huge comfort to those afflicted with CFS. Even if it has 0 clinical significance.
#15 Prometheus
January 21, 2010

#14 isomaticize

You appear to be dipping a toe in the res ipsa loquitur pool and I don’t think it is your intention to pigeon hole CFS sufferers that way.

Please slap a couple of caveats over your generalizations because they are popping out of your dialectic maidenform.

Think of the children.
#16 qetzal
January 21, 2010

A positive XMRV test is paradoxically a huge comfort to those afflicted with CFS. Even if it has 0 clinical significance.

That may be so, but only because patients are assuming the test ‘proves’ that there really is something physically wrong with them. In fact, the test does no such thing.

The test isn’t clinically validated. We can’t even say what the false positive and false negative error rates are. Any result, positive or negative, is medically uninterpretable. And that’s without even worrying about whether XMRV is really connected to CFS, whether it’s causal, etc. etc.

You’re just re-affirming that patients are spending money under the mistaken belief that they’re getting useful information relevant to their condition. I can understand and excuse CFS patients for wanting to get this test. I can’t excuse WPI or VIP for offering it.
#17 isomaticize
January 21, 2010

Lame, Prometheus, to pull out the pc card. Nothing I wrote is inaccurate.
#18 gf1
January 21, 2010

There are all sorts of exciting abnormal test results which seem to show up with CFS patients. That doesn’t exclude a diagnosis of CFS (indeed, the IC XMRV study put out a clarification to say that their patients do include those with a number of abnormal findings). These results haven’t led to a diagnostic test for CFS and rarely lead to a useful guide for treatment, nor do they (imo) prove that CFS is not a primarily psychological condition.
#19 isomaticize
January 21, 2010

Gf, there are not, to my knowledge, “all sorts of exciting abnormal tests results which seem to show up with CFS patients”. If that were the case, the furious debate about the etiology of CFS (psychic turbulence manifested vs. multi-system disease process) would simply not be so animated. Sometimes, CFS patients end up with referrals to immunologists and infectious disease docs, and sometimes those referrals lead to tests which reveal decreased NK cell activity, unusual HHV-6 and Epstein Barr antibody activity, reduced or absent ESR, etc. But the argument about the etiology CFS is not over the interpretation of these abnormalities.

However, when one considers all of the information, the immunological profiles, antibody levels, onset and duration of symptomatology, and now XMRV status, a picture begins to take form, albeit a smudged, impressionistic picture.

Personally, I think both sides are right. I think CFS exists at the interface of the psychic and the physical.
#20 isomaticize
January 21, 2010

qetzal: “My prediction: they switched to the culture test because their PCR test stopped showing reproducible XMRV in CFS patient samples the way it “should.”"

Laughable conspiracy theory. Please elucidate the VIP-Oswald connection in your next post.
#21 Prometheus
January 21, 2010

#19 isomaticize

“Lame, Prometheus, to pull out the pc card. Nothing I wrote is inaccurate.”

I was joking, screw the children. I would agree that every thing you wrote is accurate if it is 1957.

Psychiatric treatment is no longer regarded as voodoo that stigmatizes you as being doomed to bark at people or knit things that are not there.

If you are right about the interface, psychiatric treatment is a palliative proposition that is not only legit but necessary. Why perpetuate old bigotries by claiming people are being “funneled to shrinks”.

If your family and friends “spurn” you then it has a lot less to do with CFS than having a crappy support system or just sucking as a person and in either case psychiatric treatment is a damn fine idea.

A test that means nothing other than the opportunity to wave a piece of paper and shout “See see see I told you I was SICK!”, when it indicates nothing of the kind, is not a comfort, it is pandering to a bias born of desperation.

It is the kind of comfort offered by psychic surgery or shaking a magic eight ball until “outlook is favorable” floats to the top.
#22 Tristan
January 21, 2010

Isomaticize @ 14:

CFS is an ailment characterized by a lack of laboratory abnormalities – this is the single most decisive factor when it comes to funneling incapacitated CFS patients to shrinks for talk therapy and Prozac. In other words, normal blood tests and normal scans lead to psychiatric diagnoses and the unfortunate stigmas attached. Normal blood tests and normal scans also lead to a steadily increasing spurning by family and friends – which adds insult to injury for the patient. With this in mind, a positive XMRV test is paradoxically a huge comfort to those afflicted with CFS. Even if it has 0 clinical significance.

And what of those who get a negative result?
#23 Prometheus
January 21, 2010

“And what of those who get a negative result?”

Funneled, stigmatized and spurned.

Quem deus vult perdere, dementat prius.
#24 qetzal
January 21, 2010

isomaticize #20:

No, not a conspiracy theory, but unsupported and un-charitable, I admit.

It’s just that the more I hear from the WPI folks, the more they sound like true believers who are absolutely convinced they’ve found the Holy Grail of CFS. They act as if they know that XMRV causes CFS. Since they already “know” that, offering XMRV tests to patients makes perfect sense to them.

Furthermore, any information that contradicts what they “know” is automatically wrong. Hence the allegation that the UK group intentionally skewed their study design to avoid detecting XMRV, supposedly at the direction of UK insurance companies (!).

But I admit my speculation about the culture test was mean-spirited and over the top. I take it back and apologize.

Now you: please elucidate how it’s ethical to sell XMRV testing to patients given what we currently know. And if it’s not, as I strongly maintain, why do YOU think they’re doing it?
#25 isomaticize
January 21, 2010

Tristan, see Prometheus for the answer to your question.

Prometheus, awfully pollyannaish of you. First off, antidepressants and talk therapy have not shown to effectively treat the multitude of symptoms associated with CFS. Secondly, there is hardly a more pitiable situation then being sick with a mysterious, undiagnosable ailment and being (chose your verb: funneled, shipped, teleported) bounced to the shrink.

“Psychiatric treatment is no longer regarded as voodoo that stigmatizes you as being doomed to bark at people or knit things that are not there.” So wrong.

“If you are right about the interface, psychiatric treatment is a palliative proposition that is not only legit but necessary. Why perpetuate old bigotries by claiming people are being “funneled to shrinks”.”

Ok, show me the evidence that it works.

“If your family and friends “spurn” you then it has a lot less to do with CFS than having a crappy support system or just sucking as a person and in either case psychiatric treatment is a damn fine idea.”

Wrong. The isolation that creeps up on, and potentially overwhelms the CFS patient is the norm, not the exception.

“A test that means nothing other than the opportunity to wave a piece of paper and shout “See see see I told you I was SICK!”, when it indicates nothing of the kind, is not a comfort, it is pandering to a bias born of desperation.”

Okay, but it is premature to conclude that the XMRV test belongs in that category. However, many of the pseudo-diagnoses found in the DSM would qualify.
#26 qetzal
January 21, 2010

There is no question that the XMRV test belongs in that category at the moment.

Maybe that will change in the future (and I sincerely hope that it does), but WPI/VIP are selling the test now. So again I will ask: do you think that’s justified?
#27 isomaticize
January 21, 2010

Qetzal, it’s quite simple, really. I make the decision to give the WPI and VIP the benefit of the doubt. I remain impressed by the original paper published in Science. I choose not to be cynical. Is there the appearance of an ethical dilemma? Yes. I’ve already said that. But let’s keep our perspective: a minute fraction of the CFS population is shipping their blood to Reno. No one is moving to Tahiti from the loot they bank doing XMRV tests. Unfortunately, for CFS suffers, false hope just might be better than no hope.
#28 JMG
January 21, 2010

Unfortunately, for CFS suffers, false hope just might be better than no hope.

So, if the WPI and VIP are helping CFS sufferers out of the goodness of their hearts (and to the benefit of medical science), they should practically be giving away these tests, right? Perhaps charge patients just enough to cover costs, maybe try to get these test covered my insurers? Because it offers something of hope to CFS sufferers. Or something.

As an individual who currently is working for a small company that has flirted with ideas like this (in diagnosing pain and fibromyalgia), these arguments ring hollow. If the test is good, and the link is there, then develop it further in the research arena. Charging people who are feeling desperate for answers in order to “help” them is not ethical nor cool.
#29 isomaticize
January 21, 2010

You do realize, right JMG, that theoretically it could take decades of XMRV investigation to conclusively nail down the relationship between that virus and CFS? It could take half a lifetime. That is not an exaggeration. Would you be willing to wait? There is so little chance that XMRV is the sole cause of CFS that frankly it’s barely worth even contemplating. But CFS sufferers benefit from any provable correlation – and the Science paper went a long way towards proving one. To be clear: not only has there been no known cause of CFS, there have also been no provable corollaries – not EBV, not HHV-6, etc. While these other viruses do appear to reactivate in some CFS patients, their rate of reactivation is nowhere close to 67%.
#30 JMG
January 21, 2010

Developing a link to XMRV and CFS could, as you say, take a lifetime. It could also take less than ten years, if all the evidence is there and adds up (which it may or may not be). Even if it does take decades, wouldn’t you prefer to wait to know for sure that a diagnosis or treatment is valid than rush into something that could be proven incorrect within a year or two? Disproving a hypothesis such as XMRV->CFS could occur within a few years. If that happens, then what about the CFS sufferers? Will they just say to themselves “Darn. Better luck next time”? Or would they get angry that they were “lied” to?

I’m just of the opinion that even if scientific research is slow (and cumbersome sometimes), it will definitely be worth the wait.
#31 Vene
January 21, 2010

JMG, it’s not just that patients will feel like they were lied to, it’s that jumping to conclusions too fast only helps to spread disinformation. If the conclusion is wrong not only is there the problem of informing doctors and the public, but of disavowing them of an incorrect idea. And getting rid of a wrong idea can take a damn long time, which only means it takes longer for CFS patients to get real treatment.
#32 spit
January 21, 2010

I’d really prefer, personally, that these tests weren’t available at all at least until XMRV testing is well understood. Right now, there’s no way to know how much to trust these tests used diagnostically. We don’t even seem to have testing nailed as far as research goes. So even disregarding that we don’t know whether any correlation will hold up, even the flat positive or negative results aren’t trustworthy right now.

That said, I can’t blame any patient for wanting to know whether they might have a newly discovered and probably contagious retrovirus that may soon be implicated in various serious ailments. They could be spreading this to their sexual partners, and they almost certainly don’t want to be out giving blood, say. We don’t have the foggiest idea what this virus does, but it’s probably nothing lovely, and there are perfectly reasonable factors in wanting to know if you’ve got it even if you know the research is still shaky as hell and aren’t aiming for immediate treatment. Don’t assume that all patients are morons.

Science moves on a timescale of years to decades. Patients have to deal with tomorrow and next week. There’s a balance between understanding the limits of the science and simultaneously not feeling like you’re just waiting around for the next 10 – 20 years for somebody to finally say something definitive. Watching your life go to shit and knowing that there’s not a damn thing you can do about it is crappy, and nobody should be surprised that people don’t want to do it endlessly without at least trying to find something out about why.

And getting rid of a wrong idea can take a damn long time, which only means it takes longer for CFS patients to get real treatment.

I’d probably be in agreement, if there was any real treatment. There isn’t. That’s part of the problem.
#33 Vene
January 22, 2010

So, when there isn’t real treatment, then why don’t we just throw homeopathy at them? Throwing ineffective treatment at a patient is just going to waste time and money as well as lead to them mistrusting the medical system because (surprise!) it didn’t work.
#34 SC
January 22, 2010

YEP, While only 60% of the lecture actually made it on the web (the rest will be posted on Monday or Tuesday at http://www.prohealth.com) I have to agree, that really was the ranting and raving of a psychotic lunatic!

That ERV is a complete whack job.

Listen when the lecture is posted next week and enjoy watching ERV saw off the limb that she climbed out on all by herself.

ERV – Being a scientist does not mean that you’re implicitly as ass. That’s all on you.
#35 SC
January 22, 2010

The ironic (and somewhat amusing) aspect to ERV’s EMOTIONAL rants is that she probably has more to lose here than I do. IF XMRV does pan out and JM is working with half the people she says she is, ERV is going have one hell of a time working with anyone in this field.

I do have to admit that the idea of ERV trying to eek out a living waiting tables at Chili’s with such a charming personality does bring a smile.

Now ask me about the ‘immune dysfunction’ data on the original Science paper and I’ll tell you where to find it.

And lastly, I never implied that studying a different cohort was cheating (ERV – your words). I said that the UK paper wasn’t looking at the same cohort. And while I know that doesn’t account for the complete absence of XMRV in the UK study, it does mean that the results are not a valid replication of the WPI study.

Now everyone, back to the ERV circle jerk!
#36 jon H
January 23, 2010

“I have to agree, that really was the ranting and raving of a psychotic lunatic!”

Whatever, SC. Spend all your money at ProQuack.com, if you want.
#37 KAL
January 24, 2010

Is anyone on here familiar with the actual biomedical research on PubMed? Citations anyone? Evidence? Understand the difference between a replication study and a validation study? The importance of studying homogeneous research groups?

ERV this was before your time, but in 1982 JAMA published an article saying that is was not possible that AIDS was caused by one virus. Although HIV had not yet been discovered and there were no diagnostic tests it did not mean it wasn’t a disease now did it?

But there was plenty of stigma to go around regarding patients (most people had never even met a patient, but they had an opinion) and scientists were very resistant to any evidence that did not support their viewpoint. In fact, ERV, your work would have no doubt been on the receiving end of similarly uninformed rants.

“I’m out until someone from another lab publishes” Are you including the National Institute of Cancer and the Cleveland Clinic in your rant? They both independently validated the testing in Lombardi et al. You seem confused. What specifically is your beef with them and their work? Or are they exempt because they are men? Without commenting on the science it should be pointed out that Dr. Mikovats has been working in the field of virology for more than 20 years at prestigious institutions. You?

As for more science, yes there are many XMRV studies in progress done by scientists of both genders and the findings will most likely be mixed because of protocols used, geographic issues, or failure to study the same patients. For example, Erlwein et al did not say whether their patients had the specific RNaseL abnormality found in other patients with XMRV – both CFS and prostate cancer.

Regardless of the findings, they hopefully will further the actual science although uninformed bias will undoubtedly fuel more rants such as the ones on this blog.

Move on ERV and focus on the process of becoming a professional. You’re not there yet.
#38 DoodleBug
January 24, 2010

Interesting comparison.

AIDS: first reported in 1981, definition established quickly with minor modifications
HIV: found in 1983, established 1984
HIV causes AIDS: everyone except raving nutjobs agreed by 1986 because Gallo’s and Montagnier’s results were quickly reproduced by hundreds of laboratories.

CFS: first reported when? Nobody knows because nobody knows what CFS is. It was once called neurasthenia. It was polio-like disease in the 1930s. It was a muscle disorder in the 1950s. In the 1980s there were “outbreaks” in the United States. It is the same thing as fibromyalgia, or it is not the same thing. Some people have immune abnormalities, others do not. Some people have endocrine abnormalities, others do not. Some have psychiatric problems, others do not. There is nothing consistent about CFS. It could be fifty different things.
XMRV: first reported when? That is a question because is it a new virus or is it Murine Leukemia Virus that mutated in someone’s cell line and got spread around with samples?
XMRV causes CFS: One lab says yes, its goal was to find a CFS virus. The investigator’s advisor at NCI and the discoverer of XMRV confirm some samples have XMRV or are contaminated. Results have not been reproduced. A virus that may or may not be real may or may not cause a medical condition that nobody has been able to define well.
#39 Ben Rabb
January 24, 2010

I am laughing out loud at this nonsense:)

Smith, obviously, you are a CFS Denialist!

In all seriousness, Smith, you have done good work here at spotting greed-based, junk science, designed to shoehorn a single “cause” for CFS, and capitalize on it by selling bullshit tests. Well done, I didn’t think you had it in you, but have been proven wrong.
#40 SC
January 24, 2010

Ok, here’s the link to the XMRV Science article’s supplement on patient characteristics:
http://www.sciencemag.org/cgi/content/full/sci;1179052/DC1.

The supplement includes a review of how the authors assessed ‘immune dysfunction.’ I didn’t really expect ERV to be interested or to ask (politely of course) but thought some here might get something out of the supplement. The download link is towards the bottom of the page.

And here are a few very recent articles that demonstrate signs of immune dysfunction within carefully characterized CFS/ME patients:
Plasma cytokines in women with chronic fatigue syndrome
Mary Ann Fletcher, Xiao Rong Zeng, Zachary Barnes, Silvina Levis and Nancy G Klimas
Journal of Translational Medicine 2009, 7:96
Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects
Alan R. Light,*y Andrea T. White,z Ronald W. Hughen,* and Kathleen C. Light; The Journal of Pain, Vol 10, No 10 (October), 2009: pp 1099-1112

And here’s a replication study confirming distinct genomic characteristics of CFS patients and finding infectious correlation with CFS:

Microbial infections in eight genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME)
Lihan Zhang, John Goudh, David Christmas, Derek Mattey, Selwyn Richards, Janice Main, Derek Enlander, David Honeybourne, Jon Ayres, David J Nutt and Jonathan Kerr
J. Clin. Pathol. published online 2 Dec 2009;

@ ERV – Read them if you want, draw your own conclusions and feel free to point out their limitations or don’t read them and either choose to remain silent and ignorant (but at least you’ll stop acting like a fool) or you can keep shooting your mouth off about something you don’t understand in the least.

And lastly, yes – I was lecturing ERV on methodology. Cohorts may not be the only thing that matters (they may not matter at all when you’re using the ‘wrong’ testing methods) but, as the articles I’ve listed demonstrate, cohorts make all the difference when studying a poorly understood illness which ignorant ‘scientists’ dismiss when they couldn’t distinguish a CFS patient from someone who is just tired and depressed because of their preconceptions and inability to look beyond their own emotionally based biases. It’s called WILLFUL IGNORANCE and THAT is something amongst scientists deserving of further study by psychologists.
#41 SC
January 24, 2010

The above link to the science supplement is not working (the period at the end of the sentence got included in the URL).

This should work:

http://www.sciencemag.org/cgi/content/full/sci;1179052/DC1

My apologies. There’s no way that I know of for me to edit my original post.
#42 SC
January 24, 2010

And this on going study from Brigette Huber (Tufts) and Renee Taylor (U.Chicago):

Ancient Retrovirus May Contribute to Chronic Fatigue Syndrome, Multiple Sclerosis and Autoimmunity

http://www.redorbit.com/news/health/1447002/ancient_retrovirus_may_contribute_to_chronic_fatigue_syndrome_multiple_sclerosis/

From the Huber lab:

http://sackler.tufts.edu/Academics/Degree-Programs/PhD-Programs/Faculty-Research-Pages/Brigitte-Huber.aspx

“HERV-K18, an Endogenous Virus that Encodes a Superantigen
The human genome contains many endogenous retroviruses. One of these is HERV-K18, an element that is normally silent but encodes a superantigen when it is actively transcribed. We are studying the role activation plays in infection with Epstein Barr virus (EBV) because EBV infection activates expression of the element. In addition, because we have discovered that chronic fatigue syndrome appears to be associated with different alleles of HERV-K18, we are testing the relationship of these alleles to this disorder.”
#43 SC
January 24, 2010

Regarding the Light et. al. study referred to above: “Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects,” you might find slides # 26 & 27 posted on the CFIDS Assoc. site interesting:

http://www.cfids.org/webinar/xmrv-slides-jan2010.pdf

Also, for those of you whose won’t read the Kerr article: “Microbial infections in eight genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME),” here are two of the primary ‘Take Home Messages:’

1. Expression of 88 human genes was confirmed as being significantly different between CFS/ME patients and normal controls.

2. Gene expression in endogenous depression patients was similar to that in the normal controls.

Kerr article available here: http://jcp.bmj.com/cgi/eletter-submit/jcp.2009.072561v1

@ Prometheus – On an earlier thread you accused me of being inconsistent when referring to myself as a CFS patient. You may be right, quite honestly it’s not worth going back to see exactly what I said in regards to my own Dx. What is worth the time is to explain why I refer to myself as a CFS patient to some audiences and at other times I don’t. It has everything to do with my audience. Labels and language are used as an efficient way to convey concepts via shared understanding.

If I described myself as a CFS patient on this blog, that was an error. Far too many people here not only are ignorant as to what CFS means, but more dangerously, they think they know when they don’t and so rather than conveying a shared understanding, the term CFS here just creates confusion*. I may have explained a while ago that my Infectious Disease doc and neurologist both share the exact same understanding of CFS and that the term communicates volumes to both about what is and what is not at issue.

And so Prometheus (as well as all of those who come here – or who host this blog – to simply lecture the rest of us, spewing venomous allegations and dismissals that are really for our own good), my sincere apology for using terminology that you don’t understand.

* I not only include Dr. William C. Reeves, principal CFS investigator at CDC, amongst the ignorant, I accuse him of being the principle perpetrator of the ignorance. If all you know about CFS comes from the CDC web-page, please – do yourself a huge favor and look to the IACFS/ME and the work of the researchers I have included in the articles I have listed.
#44 ERV
January 24, 2010

SC– ScienceBlogs uses a Google powered ‘search machine’. If you put words like ‘Multiple Sclerosis’ into the little white box in the upper left-hand corner of this blog, you will realize Ive already written about the topics you are blithering about.

Also, youre weird. Several times Ive seen you take phrases Ive used addressing you, but then you put them in comments to me like you thought them up. Its quite possibly one of the weirdest things Ive ever noticed in a commentor (including Kwok).
#45 SC
January 24, 2010

@ ERV – “Also, youre weird.”

That’s your response?
#46 mel
January 26, 2010

Yeah, that’s her response. No surprise.

By now, we all know ERV & company’s response is to resort to name-calling and insult since they don’t understand the complexity of the issue, or even the compassion to care if they understand the issue before shooting their foolish mouths off.
#47 Bluet
January 28, 2010

Thank you for writing this. I appreciate your analysis. Please keep it coming.
Signed,
A CFS Patient
#48 Stephen Wells
January 28, 2010

If SC can only read three words out of every fifty (compare post 44 to 45), that may explain some things.
#49 lucy
January 29, 2010

entertaining blog you have here.

question for you – what do you think xmrv is and does? if there is ever a test that satisfies you how would researchers go about finding out what it does, if anything, to people who have it?

btw, i heard from a researcher i know that the cdc recently held a meeting to discuss how to screen the blood supply without “freaking people out” hmm…
#50 Helen
February 4, 2010

On the larger context of the politicization of scientific research, take a look at Larry Gilman’s blog entry on XMRV:

http://nolongerbythinking.blogspot.com/2010/01/all-this-has-happened-before-xmrv.html
#51 daedalus2u
February 4, 2010

I have my own take on CFS, I see it as a physiological state brought about by long term insufficient nitric oxide. There are multiple things that can cause this. Various infections, Lyme, Q-fever, various viruses, ARDS, physical trauma (as in automobile accidents, surgery), psychological abuse, chronic stress, and especially immune system activation under chronic stress. Fundamentally what happens is that long term low NO levels skew physiology in a certain direction, physiology adjusts to that skewing, the skewing becomes permanent and the new state has hysteresis and that state is the CFS state.

I have written a blog on my take on the physiology of it.

http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

I have read a lot of the CFS literature, not so much recently. I am well aware of the charges that people with CFS are somatocizing and are malingering. I think this attitude is very unfortunate and is wrong. People can somatocize and can malinger, even people with CFS can do those things, but CFS is a real physiological condition. I have sort-of followed this XMRV debate. XMRV may be a cause of some cases of CFS, it is not the only cause, it is likely not even a major cause, it might not be a cause of any CFS, it might simply be associated with CFS.

CFS is defined as fatigue without a known cause. If there is a known cause; for example dilative cardiomyopathy, COPD, obesity, diabetes, cancer, end stage kidney failure, viral infections, then the fatigue is not CFS.

What is the actual physiology behind fatigue? Is that physiology different for different types of fatigue from different causes? Is the fatigue from CFS different than the fatigue from illness, lack of sleep, cancer, etc? It turns out that the physiology behind fatigue is not well understood. There is no good understanding of any differences in the physiology of fatigue from different causes. There is no good understanding of the fundamentals of fatigue.

“Fatigue” is mostly thought of as the absence of the absence of fatigue. The default notion of fatigue is that it is something that comes from not enough rest, not enough motivation, not enough exercise, not enough of the right stuff.

My understanding of fatigue is that it is a protective mechanism, a mechanism by which physiology warns you that you are exceeding safe physiological limits and that you should reduce your energy expenditure. It is pretty obvious that there are limits to how much ATP can be produced and how much work muscles can generate by turning that ATP into work. It is intuitively obvious that physiology would have warning signals to indicate when limits are being approached.

It needs to be appreciated that those “limits” are not “hard limits”. Physiology is very complex, it does require a continuous supply of ATP, and ATP used for one thing cannot be used for something else. ATP used to produce muscle movement cannot be used by that muscle to maintain essential physiological processes. Heart muscle for example will work itself to death. During an ischemic heart attack, heart muscle will continue to try and work until it exhausts its ATP supply and necroses. That is the trade-off that physiology makes, a beating heart with necrotic spots is a lot better than a non-beating heart with no necrotic spots. An organism can survive with a beating heart with necrotic spots, it can’t survive a non-beating heart.

How does this relate to CFS? If muscle doesn’t have enough mitochondria, that will show up as insufficient ATP production capacity. Basal ATP needs might be easily supplied, but extra ATP (needed to increase aerobic work production) won’t be available when needed, so fatigue will occur when aerobic exertion is attempted. Magnetic resonance spectroscopy indicates that this is the case, that people with CFS do have reduced ATP levels in their muscles and that this ATP level drops more and farther during exercise than in people without CFS.

Findings of the association of persistent viral and microbial infections in patients with CFS is not new.

http://www.ncbi.nlm.nih.gov/pubmed/12887507

The question is are those findings a cause, or an effect? My interpretation is that they are an effect of the metabolic derangement that is causing the CFS. If metabolic resources are insufficient (and they are if fatigue is chronic), then presumably physiology is still efficiently allocating those limited metabolic resources among the various tasks those resources must be used for. One of those tasks is maintaining the body infection-free. Just as a beating heart with necrotic spots is better than a non-beating heart with no necrotic spots, so is an organism with enough ATP to move but with some infected cells better than an organism that can’t move with no infected cells.

One of the most common causes of fatigue, is infection. Presumably the fatigue of infection is to limit ATP consumption by muscles, so as to allow physiology to divert that ATP to the immune system to allow the infection to be cleared. Fatigue is not caused by the infection, fatigue is the body’s response to the infection so as to divert ATP to clearing that infection.

My interpretation of the XMRV findings are that they are simply one of many possible infections that are persistent in people with CFS. They are not the “cause”, they are simply an effect. An effect that depends both on exposure to the virus, and also to CFS.

I concur with Abbie that the researchers pushing XMRV as the one true cause of CFS are hyping their research far beyond its applicability. I suspect they changed their assay from an antibody or PCR based assay to a cell based assay because the more specific assays stopped working. I suspect they stopped working because the original findings were specific to the individuals they tested and not a general finding in people with CFS.
#52 LM
February 19, 2010

I don’t think patients care much if the WPI are offering a test. It seemed they did this in reaction to another lab offer an unvalidated test. Personally, I have mixed feelings about it, but it’s not the most important thing at present.

Ignoring the test though, it appears that many researchers, world wide, find there is something to investigate. Perhaps you should leave it at that for that moment. Wait until the end of the year, a better picture may be able to be formed by then. There may even have been a replication study completed.

As for biopsychosocial, it’s funny how those that once accused patients of lying, changed their minds as more biomedical investigations were done. It is also funny that no other disease is refereed to as biopsychosocial, in this enlightened era. You either treat all the disease the same, or you discriminate.
#53 Zenbker
February 24, 2010

This commentary on XMRV/CFS has yet to touch on a critical issue for CFS/ME sufferers. The paucity of information begs a question: is it transmissible? If one suffers from CFS/ME, AND there is a [i]question[/i] that you harbor a transmissible retrovirus, the potential effect on your interpersonal/intimate relationships is enormous.

I lost a fiance because of this issue. While greater minds ponder whether XMRV is/isn’t related to CFS, those of us who suffer from this symptom cluster have real concern whether we’ll ever lead ‘normal’ lives again, and whether or not we can pass our condition on through intimate contact. I see it as a personal duty to test for XMRV; like most CFS/ME sufferers, I’ve gotten more results following my own research than I have from [i]any[/i] of the bevy of CFS ignorant/unbeleiving physicians I have consulted. My instincts have never led me wrong, and every time I’ve ignored them, I’ve paid the price dearly at the hands of a medical profession that is too enthralled with their own “doctorness” and sorely, woefully lacking in compassion. In my experience, previous comments about psychs (-iatrists or -ologists) being soul sucking leeches eager to add another color to their “spectrum” of disorders is all too true, and there is no such thing as a “benign” psychoactive medication. If you don’t believe that’s true, I suggest you consult the ever-burgeoning DSM IV.

From my perspective, if doubters put the energy into helping answer the question instead of filling their sails with doubt of others, we’d all find our answers to questions sooner. CFS sufferers don’t want to hear you grind your axes, we want answers. If all you can offer is a pissing match of your [i]opinions[/i], we’re not interested. Results are all that matters to us, and if you can’t give us a result one way or another, we’d appreciate it if you’d stow your ego and remove your hot air from an already too noisy debate.
#54 Bruce
April 3, 2010

I don’t see how additional proper research on hmrv can hurt the progress of understanding this disorder. As long as they continue poisoning all of us with unregulated industrial chemicals, new and old viruses will emerge that compromised immune systems cannot handle. Since our industry controlled government will not regulate until it is too late, we are all doomed anyway.
#55 Nila Shea
May 4, 2010

I say once again….JUST SHUT THE F UP!! I’M A LADY WHO HAS HAD THIS FOR 40 YEARS.. YOU HAVE A DEGREE, I HAVE LIVED IT!!YOU WILL FIND OUT VERY SOON THAT THIS IS NO SILLY THING THAT IS GOING ON.. THANK GOD FOR OPTIMISTS…NOW..SHUT UP!!I BET THIS ONE WON’T MAKE THE POST! NILA
#56 Liz Brown
June 28, 2010

Hello – I would like to comment – although I am not a science grad but an arts one ….

I really think that we must wait for more research – this link is very tenuous.

In any case – why would people be delighted to find that they have a horrible virus like this? They will become outcast (as were HIV people – surely?)