XMRV and chronic fatigue syndrome: For your enjoyment-- A magic trick.

Ladies and gentlemen, a magic trick*.

I am going to take two pieces of data, from two independent experiments, establishing 'proof' of two different concepts, presented in to different formats and to different events...

... And turn them into the same figure.

*waits for the astonished mummers to simmer down*

In my left hand I hold 'Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome', a Science paper from 2009.

Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome

We can ignore parts of this paper-- they have been retracted, as it seems some samples were contaminated in a rather curious (strategic?) manner. Which is fine, because what I want you, the audience, to focus on is Figure 2:

i-2b43758e27bf90730176b0c81aa5fb68-Science Figure 2.png

Specifically, Part C:

i-cb8eb8e265b6b88d61ef774a574e2e46-Science Figure 2, zoom.png

Lets zoom in on it, to get a nice, clear image. Actually, lets zoom in on the bottom part of that figure:

i-c5e626b967ed434d7c79d3980fe7156c-Science Figure 2, zoom 2.png

Its quite clear, there are 8 lanes.

1-- Normal
2-- Normal
3-- 1235
4-- Normal
5-- Normal
6-- 1236
7-- Normal
8-- SFFV-infected HCD-57

Here is the figure legend:

(C) Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) or from CFS patients (lanes 3 and 6) were analyzed by Western blots using rat mAb to SFFV Env (top panel) or goat antiserum to MLV p30 Gag (bottom panel). Lane 8, SFFV-infected HCD-57 cells. Molecular weight (MW) markers in kilodaltons are at left.

Not hard to interpret, right? Some cells from healthy donors do not express XMRV Gag protein, a couple CFS patients do express Gag protein, and a positive control does express Gag. It provides evidence to support the claim that CFS patients PBMC are infected with XMRV, and are capable of producing viral proteins.

Nothing out of the ordinary. *wink*

Now, in my right hand I hold Slide #13 from a presentation a Miz Judy Mikovits recently gave in Ottawa at the IACFS/ME 2011 conference, graciously provided to us by Miz Jamie Deckoff-Jones. A round of applause for Miz DJ, everyone!

*waits for the applause to die down*

i-62022694ec7582de8dc72d025444770d-IACFS13.png

Another fairly straight forward figure. Again, 8 lanes:

1-- Normal
2-- 2905 PBMC
3-- 2905 PBMC + 5-AZA
4-- Normal
5-- 1674
6-- 1674 + 5-AZA
7-- Normal
8-- SFFV-infected HCD-57

Again, PBMC from normal individuals do not express XMRV Gag proteins... but this time, though the CFS patients did not initially express viral Gag proteins, when treated with an epigenetic modifier, they could induce Gag expression. Fairly straightforward explanation for why some patients might *appear* to be negative, but with a bit of lab trickery (we do this stuff all the time in labs), we can make a hiding virus come out and play.

How nice for us all, right? *wink*

Lets zoom in a bit:

i-12e861b44c0be2b96d7ad55f5bc59a2d-IACFS13, zoom

And fiddle a bit with the brightness/contrast:

i-79b669f0e379e44949dd75183a5b9b20-IACFS13, zoom, edit 1

Science is all well and good-- Two figures, one providing support of the claim that two patients, 1235 and 1236 are infected with XMRV, the other figure showing two patients, 2905 and 1674 might appear negative, but become positive after treatment with an epigenetic modifier. Neat, but so what?

Well, heres the *really* good part!

Now, watch carefully or you will miss the trick, ladies and gentlemen!

i-a1721540aae8cdd36fda3c6f399e2ba1-Comparison1.png
i-47c7973822ab40942fd40618b2cd9179-Comparison6.png
i-ccc51a5d1fbc3dec63233e07349c8292-Comparison7.png

Thats some mighty fine purple.

But how about an alternative view!!! I think Ive made my point, I just like how the far-right blob looks like a rubber ducky:

i-fa3b2ddc701b2403bd15c5a745534d20-Comparison5.png

*BOOMANDHUGEPLUMEOFGREYSMOKE*

TAH DAH!

Two bits of data describing and explaining to two entirely different things... and yet I can make the two images look identical!

I AM MAGIC!!!

Am I magic...?

...or is this a case of arrogant, bold-faced, lazy-ass scientific fraud perpetrated by an apparent pathological liar?

You be the judges, ladies and gentlemen.

I know what my opinions are, but I would very much like to hear your thoughts.

* Though much of this magic trick is my own creation, the original idea was not mine. That individual/Those individuals do not wish to step forward at this time (and rightly so), but should they ever want to take credit for this observation, I will *happily* give it to them. Its wonderful, something I myself missed.

But to all you frauds out there-- remember this: Dont. Fuck. With. Scientists. Individually, scientists are smart folks. And even smart folks get screwed over now and then. But together, we are always smarter than you.

Always.

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More like this

Doesn't the label say:
"WB670 α XMRV RT 10 sec 4/23/09" ?
If it is really picking up reverse transcriptase then does nayone know what size should it be?

OMG, one of the commenters on the Science Insider article is talking about taking bleach/vinegar (=chlorine gas) baths to kill your skin's microflora because the "pheromones" they release cause disease. Then he talks about midi-chlorians, says filming Star Wars was his idea and then piles on more non sequiturs by talking about his supposed IQ and modelling for Good Will Hunting. If it didn't make me think he were mentally ill, I'd be laughing my ass off.

Sigmund,
Yes, but as ERV and others have pointed out, the slide doesn't include enough controls to be interpreted. What I'm asking is, has anyone actually cultured normal PBMC or PBL with 5-azacytidine, and seen human endogenous retroviruses come out, or transcripts or proteins appear? Just curious.

ERV (@495)

As you are working on ERVs, don't you want to do an experiment where you treat ordinary PBMCs and cell lines with 5-Azacytidine and look whether an antibody against MLV gag similar to Lombardi's picks that up? As Science have to clean up their self-created mess, they may actually take a short communication like that...? Or at least it add a nice part to your thesis. But don't forget decent controls!

OWE

@jeff

"My pubmed scan turns up examples in mouse cells, some human cell lines, and lymphocytes from patients with some illnesses."

Which maybe suggests there's a connection between this duplicity and the controversy over who exactly the patients in the paper were.

Not sure if this is the relevant comparison but MLV RT is listed as 71kDa, so I think that the gel is Gag. From somewhere.

By Richard Jefferys (not verified) on 05 Oct 2011 #permalink

For the lulz, I give youuuuuuu:

A review by Ruscetti and Mikovits in which they discuss DNA methylation in relation to cancer and viral infections!

http://www.ncbi.nlm.nih.gov/pubmed/12724212

Sadly my VPN peer is down, so I can't read it and quote some of the most incriminating paragraphs :(

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

ERV,
I had missed your answer to my first question. I'll wait for further discussion tonight.

@Richard Jefferys & friends,

Yeah, I looked up MuLV and found the same thing; expected size for RT was around 71kda. That's why I'm wondering. I write the temp on all my experiment when it's relevant because...well because being anal is fun and you never know when the info can come in handy but that's just me =D.

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

I started looking around at the correct molecular weight of bands that you should see on the gels for the different XMRV proteins. In the Lombardi paper they show Gag as p30, a 30kd protein with a few higher bands. In the original WPI scan that has been going around labelled anti-XMRV RT, the bands there are the same, 30Kd with a few higher bands. According to this paper by Isla Singh, Figure 1 shows the correct MW for different XMRV proteins. (http://www.pnas.org/content/106/38/16351.full) Gag should be 62kd, RT should be 75 Kd. Neither of which are the size in the western blots going around or in the Lombardi paper. The protein that is 30kd in XMRV is Capsid. I think that this is another serious problem with the paper. Wrong size protein for what they are claiming.

My interpretation is that this was doped in protein to get a clean gel. its just not the right size to be RT. Maybe these are just doped virion preps in the correct lanes to show bands where they wanted them?

By Virology prof (not verified) on 05 Oct 2011 #permalink

Could "RT" stand for rabbit? Ila Singh certainly had a rabbit anti-XMRV raised against whole virus, therefore mainly recognising Gag.
OK, I know the paper says goat anti-MLV, but the hand written labels say anti-XMRV, and I'm not inclined to give much weight to the contents of Lombardi et al. All that (and subsequent activities) is likely to be good for in the long run is as a nice case study in an ethics course.

By Perplexed (not verified) on 05 Oct 2011 #permalink

@Virology prof, #505

You totally lost your virology prof cred. Gag is cleaved into multiple subunits, including CA (capsid), MA (matrix) and NC (nucleocapsid). A polyclonal serum against gag would recognize all of the subunits.

The gel is likely of *some* gag proteins, likely from an ERV origin.

Sincerely, a *real* virology prof

www.colgate.edu/gholm

ghholm,

Correct me if I'm wrong, but they specify (in the 2009 paper) that the antibodies for that gel were "goat anti-Rauscher MLV gp70 Env, p30 Gag and p10 Gag (provided by NCI)". Wouldn't that indicate some specificity for the 30KDa band rather than the whole uncleaved gag?

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

"that gel" = "their gels", sorry.

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

But, yes. That does look to be capsid (by weight anyway), so I'm not sure what the RT would indicate in the labels.

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

a little off the current topic but..I see some of the bad science forum members here.. I'd like to say BRAVO to your xmrv/WPI forum, I'm a frequent lurker but not a registered member..so I cannot post my thanks over there!

By mary (abbie's ilk) (not verified) on 05 Oct 2011 #permalink

PS @508:
If they raised polyclonal antisera against the p30 gag product (i.e. capsid), those Abs should bind to the uncleaved gag as well. A monoclonal might bind to a portion of the protein that is obscured in the full-length, but polyclonal sera will contain many different antibodies, some of which should bind full-length.

Sorry for the double post:

I am guessing that RT is room temperature, probably either for the blocking/primary steps of the immunoblot. Sometimes I will run blots where I am short on time and stick the primary antibody on overnight, which I will do in the cold room. If I run the gel and blot it the same day, I'll do it at "RT" on the bench. It will affect the signal and background noise in the blot, so some properly detail-oriented researchers might denote this on the film so that if they need to repeat it, they can use the appropriate conditions.

Right, I guess I'm wondering whether they are mAB or not. They don't specify (as far as I can tell) although they do specify mABs for other products. Still wondering about the RT but I'd bet it doesn't refer to reverse transcriptase, personally. I'm gonna vote for Room Temp =P

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

@513
It would seem odd if they were so precise in their gel labeling, given their attitude to the rest of the scientific process. Given the tangle they got themselves into, perhaps they should have labelled the gel with what it was going to be used for rather than what they actually did (which, as we now know, is not germane). At least that would be consistent with their approach to writing a manuscript!

By Perplexed (not verified) on 05 Oct 2011 #permalink

Never heard that about the temperature and noise relation. Ah, so much to learn, still. Thanks ghholm.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

Funnily, I just looked into my Virology textbook, and while there are no gamma retroviruses known that infect humans and cause disease, there are indeed gamma ervs in the human genome, like Erv-3 and S71 related sequences.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

Just found this, which shows, I assume, purified XMRV proteins for use in developing antibodies.

http://regist2.virology-education.com/1XMRV/docs/24_Bagni.pdf

Slides 6 and 7 are relevant (and produced with some of the antibody from Ruscetti, I assume).

The major band in the Fig. 2C gel might be a p30-ish (CA) band. Don't know what the larger bands represent, probably incompletely processed gag precursors.

copied from Corante, commenter named "Pigsy"

Abbie Smith has been sounding the deathbell on XMRV since the paper was first released. She is scrabbling to make it a reality. She cannot control herself and her outbursts really are becoming an embarrassment to science. Each obsessive blog post she writes screams personality disorder. It's my understanding that Oklahoma University are in talks to eject her from her graduate program.

hmmm...oh well, you'd think the cranks would just accept their error and move on...guess not..

By mary (abbie's ilk) (not verified) on 05 Oct 2011 #permalink

In all fairness, that statement is accurate, mary. But this has actually been in the works for a long time. Long before XMRV and Judy Mikovits.

I have been having discussions with the University for about 5 years now, and its been decided that after I get my papers accepted (with others in the works), and write and defend my dissertation, I will be ejected from the university with a PhD.

They keep promising me that this is true, but there is always 'one more experiment' to do :(

LOL!!!

Any chance RT could be someone's initials? Everyone I work with writes initials on everything.

RT has to be Reverse Transcriptase. There really is no other logical explanation. This is just how you label blots.

By Virology Prof (not verified) on 05 Oct 2011 #permalink

@476 Sigmund

Thanks.

What I do not understand then (maybe Abbie will explain this later) is that the BWG conclusion was no XMRV/MLVs and yet that WB along with the rest of those slides in Ottawa were trying to say 'There might not be XMRV but there is HGRV'?

If it is all wishful thinking on their part - with nothing having been produced or published to endorse this (even Lo and Alter) - then feel free to say so ;)

Somebody here (not clear to me) states:
"Abbie Smith has been sounding the deathbell on XMRV since the paper was first released. She is scrabbling to make it a reality."

This is flatly incorrect. I recall that ERV's initial response to the Science 2009 Lombardi et al paper was not negative. She initially gave the researchers the benefit of the doubt, and only had minor critical comments about unclear PCR bands and other minor technical items. At first blush, without a careful reading, the science looked good to her.

Only after Dr. Mikovits made unprofessional statements accusing other researchers of intentionally "skewing" results in the first "replication/reproduction" studies did ERV go caustic and "snarky". She has generously answered many highly technical questions for myself and non-scientist others over the last years in a clear and easy to understand manner. She uses examples, and some of them are pretty amusing and funny.

If I were a government official, I would never hire her as a diplomat, but I am sure she will become a very good scientist in her chosen field.

Ok, looking at slide 6 of the Bagni presentation:

#1 The bands in the Mikovits picture have to show gag, if they show any retroviral protein, because all pol and env cleavage products are bigger than the Mikovits bands.

#2 The bands of the Mikovits picture don't match the size of XMRV (VP62) gag cleavage products. Compare to the direction of the individual cleavage products in the whole gag: http://www.uniprot.org/uniprot/Q27ID9

possible sizes of gag cleavage products are:
whole gag 64.1 kDa > MA-p12-CA 56.4 kDa > p12-CA-NC 49 kDa > p12-CA 41.3 kDa > CA-NC 39.3 kDa > CA 31.6 kDa > MA-p12 24.8 kDa > MA 15.1 kDa > p12 9.7 kDa > NC 7.7 kDa

the two upper bands on the Mikovits gel are slightly below 38 kDa, the lowest is between 31 and 24 kDa. None of that matches. Even if Mikovits/Ruscetti used monoclonal AB against one of the cleavage products, there are still bands missing, most importantly the whole gag band.

So, what is in the bands? I'm betting on gag of an gamma erv with shortened overall peptide sequence and maybe mutated cleavage sites.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

I'm sorry, the Protease (PR) of pol and a cleavage product of the transmembrane protein are smaller than gag products, but nowhere in the size category of the Mikovits/Ruscetti bands.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

Abbie, I hear yah on the "1 more experiment"

I'm planning on a march ejection myself, but I'll be damned, I cannot get this paper done without "one more experiment"

FML.

I think we may be in danger of complicating things unnecessarily with this antibody question.
In my lab we write "RT" on the blots frequently - it's short for "room temperature".
As for the size not matching the predicted gag cleavage size exactly, well that's sort of what you get with inherently variable biological systems. Come to think of it, having the bands look identical and at the exact predicted size would be more cause for suspicion than if there were some variation.

Quote Judy Mikovits:

And she chose to relabel a 'normal, untreated' portion of the image with a patient number because the data were the same. "It simplified the slide primarily for a patient audience," she says. "This is not in anyway inappropriate for a presentation as long as the data are correct, and they are."

Shorter: "I dont have a problem lying to patients."

Yeah, CFSers. Im the 'bad guy'. *I* am the bad guy.

Instead, the authors referred to the samples as being 'activated'.

'Activated PBMC' means the cells were treated with PHA/anti-CD3 antibodies/something to ACTIVATE them.

You would think someone with her supposed background in HIV-1 would be well aware what 'activated' would mean to a retrovirologist reader, but she really meant something different and its not that big a deal anyway, rite? *flipshairandgiggles*

FFS.

Quote from the Nature article/Mikovits:

Mikovits says that the Science paper didn't mention the azacytidine treatment because that detail was not necessary for the publication. Instead, the authors referred to the samples as being 'activated'. But for her presentation, she wanted to emphasize that the addition of methyl groups to viral nucleic acids may have prevented the virus from being detected using standard assays. Azacytidine strips off those methyl groups and, Mikovits argues, can boost viral gene expression.

Booooooogus! They activated their PBMC with PHA and IL-2, standard practice for inducing proliferation in T cells. The subsequent references in the paper to "activation" are implied to refer to that treatment. To imply now that something else was done to "activate" the PBMCs, which was not disclosed in the paper, much less that that "activation" is a compound that induces expression of ERVs and was only done to patient samples and not controls, is completely unfathomable. You can keep digging, Judy, but you ain't gonna dig your way out of this one!!

And 'activated' then still only meant 'activating' the patient samples and not the controls, without any mention of this.

That's a lot of leaving out data for someone who insists on PERFECT REPLICATION.

Errr...
"And she chose to relabel a 'normal, untreated' portion of the image with a patient number because the data were the same. "It simplified the slide primarily for a patient audience," she says. "This is not in anyway inappropriate for a presentation as long as the data are correct, and they are."

Soooooo, it's ok to relabel data to something that it isn't as long as it saves you time and looks right...got it... Man, this will save me SOOOOO much time when putting together our next publication. Take notes, ERV, you don't have to do "one last experiment" anymore!

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

"Mikovits says the 'RT' on the blot simply meant 'room temperature'"
That's what I guessed a few posts back.
Mind you, now that she has said it herself I'm suddenly less confident of my own argument!
The 5-AZA question is still the one that will sink her. Nobody who works with epigenetics or virology will assume anything other than this is a critical treatment that was deliberately hidden in the Science paper.

"Critics have also argued that the original, handwritten labels, which include the letters 'RT' suggest that the blot had been stained for reverse transcriptase, another viral protein altogether. But Mikovits says the 'RT' on the blot simply meant 'room temperature'."

Crap, now I don't know if I should still believe it or not... I mean, yeah she confirmed what I thought but at this point that really isn't comforting =P

By Poodle Stomper (not verified) on 05 Oct 2011 #permalink

@ ERV, ghholm: Don't bash her for this simple mistake! after all, mitogenic treatment + 5-Aza is much more "activating" than 5-Aza alone, as this compound will only clear Methyl-C from proliferating cells. *muhahahahahaha*

congrats on making Nature too, ERV!

"
Those who have been critical of the Science article1 say all of this simply strengthens the argument in favour of retracting the entire paper. "I have a copy of that paper on my desk," says Stoye. "It has a line through Fig 1. It has a line through Fig 2c. Where is the next line going to be? Is there going to be anything left?"
"

No Mr. Stoye, ther isn't.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

Dear Alan writes

I question the reasoning behind the ad hominem attacks and language used by you.

I've not cleared my thoughts on this with horrible, inept science wannabe that is Abbie Smith of ERV, but I think I have a partial explanation why a nobody, a knownothing, a bitch like her would write mean things about one venerated, honorable Judy Mikovits: Mikovits is a lying, ideological bitch whose chicanery has hurt real live human beings who are already suffering the living hell of having a disease. She has marginalized them as people being worth due respect and attention by our greatest attempts to solve the riddle that plagues their daily lives.

She lied.

For her own edification.

She tarnished the work, lives and fields of people who are searching for answers in earnest, diligently focusing their compassion and shared pain with their brothers, sisters, mothers, fathers, sons, daughters, cousins and neighbors.

And she hurt people.

And, I'm just guessing here, Abbie is pissed off about it.

Don't you worry your pretty little head, Abbie Smith will make a fine scientist. Nay, she will continue to be a fine scientist as she's shown in her humble position as a graduate student in a different field that she's willing to step up and demonstrate bravery, fidelity to the greatest of our scientific ideals and unfettered honesty.

Unlike Mikovits, Smith will always have a role to play in science. Mikovits has one more role to play, and only one, in science: when she dies alone, the pathetic shell of what could have been a very different life had she only decided to be honest, she can donate her body to serve as a cadaver at some medical school somewhere. It is there in that moment, in that decision that she will have yet one more opportunity to be of any use to science.

While she's alive, she is forever tainted because she lied. She creamed her data. We do not forgive this. We do not forget this. Cadaveric utility is all that awaits her future in science. Period.

It's a faked link, be careful.

Now both Ruscetti and Mikovits explained it's the same image of the same gel, but just with different labels for privacy reasons. Ok, sounds plausible.

Maybe I'm just missing something here, but didn't they forget to explain why two healthy donor control samples in Lombardi et al. are suddenly coded as being patient samples without 5-AZA in the presentation (bands 2 and 5)?

What exactly did the third set of labels said?

Beyond that, if the most successful treatment is CBT/GET then for most people CFS is a psychiatric/lifestyle issue. The End.

Does not compute.

Conditions like chronic pain also respond somewhat to psychiatric treatment. Doesn't mean the condition psychiatric in nature - actually it's the other way around. These people happen to be depressed because of pain, not in pain because of depression.

Similarly, always being tired is not very good for your psychological wellbeing. I speak knowingly, having been chronically tired for over 2 years (nothing diagnosed yet, does not look quite like CFS). Things like sleep apnea, which can produce intense fatigue, can induce depression.

Another thing is that the classical CFS patient :

a) was quite active before the illness started

b) does not respond well to placebo, which rules mostly rules out psychosomatic disorders or hysterical conversion

And to be clear, I'm perfectly aware that if you are literally totally out of shape; exercising is difficult. Not only difficult, but painful and with long recovery times. There is no free lunch and the if you want to get better you are simply going to have to work for it.

The thing is most of these people, as well as I, know very well the difference between being out of shape and their present condition.

It frustrated me to no end to hear people say this to me - because I have been out of shape and have trained quite heavily before (I used to run 10k regularly), and freaking know what it should look like. What it should not look like is feeling like you recently had chemo when you went on a 30 min walk.

@Sigmund
Thanks!

So it looks like the presentation had the wrong labels. So if that's true, the new slide doesn't say anything about the necessity of using 5-AZA to detect virus. Only 2 patient samples, both positive and both had 5-AZA, but nothing to compare them with.

Justicar, that's harsh.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

To follow up a claim made by Mikovits in the Nature story:
"And she chose to relabel a 'normal, untreated' portion of the image with a patient number because the data were the same. "It simplified the slide primarily for a patient audience," she says. "This is not in anyway inappropriate for a presentation as long as the data are correct, and they are."
So changing the label from a normal control to a patient sample is fine because it "simplifies" things for the audience.
If both are simple negatives then one can understand (but not ethically condone) the logic here.
However, look at the previous slide to the contentious one.
http://i51.tinypic.com/254ykwz.jpg
It details the problem of viral latency and suggests reactivation in necessary to see evidence of viral infection.
Therefore it is very much relevant that you show 5-AZA treatment reactivating the virus and the only way to do that is to show the same patient sample with and without 5-AZA.
It is therefore a gross misrepresentation to simply label one of the untreated normals as the untreated patient lane.

And when I say "his site", I obviously mean "her site". Ooops. My apologies Dr Deckoff-Jones.

Lo Alter ADMIT that the controls and patient sera were collected under totally different circumstances. Mikovits does not admit this very important KEY piece of data. This is terribly misleading. Science should demand to know where the controls sera came from, and why this was not explained in the original paper. I have it on very good authority from a WPI source (that I cannot reveal for fear of retaliation) that the samples were purchased from a serum bank. Peterson did not collect control samples. Obviously this is an important difference like that should have been explained. Also the fact that 20 of the patients probably were cancer patients, many of whom had fatigue for years leading up to the cancer diagnosis. Judy was studying this with Dan Peterson because many of his long term CFS patients ultimately developed cancer - especially those with persistently reactivated viruses such as EBV and HHV-6.

It's kinda 'way harsh' dude.

"many of whom had fatigue for years leading up to the cancer diagnosis." Well that fucking sucks. Why didn't WPI pursue the persistent activation issue? Did they pick up XMRV contamination while looking at that and then just ran with it because it was sexier?

Way harsh, I mean mostly this part:
"when she dies alone, the pathetic shell of what could have been a very different life had she only decided to be honest, she can donate her body to serve as a cadaver at some medical school somewhere. It is there in that moment, in that decision that she will have yet one more opportunity to be of any use to science."
I hope she quits science and the papers are retracted, too, but talking about her death...

Ronnie, it also means that it is possible that treating normal controls with 5-AZA may've shown the same bands! The experiment, like they conducted it, demonstrates nothing at all!

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

So according to that Nature article if Ms. Mikovits is correct RT stands for Room Temperature. However, the guy who actually did the blots says

The antibody used to detect p30 was originally made to detect reverse transcriptase, he says, but instead recognizes p30 and its precursor so it was used for this purpose.

Ok then.

By EdinScientist (not verified) on 05 Oct 2011 #permalink

It's not like I said someone should kill her. But at some point down the path of life, she will--as will you and as will I--hit a rocky gravel road with an ominous sign reading "Dead end ahead". And then we'll hit that end.

Whenever that is for her, from this day to that she has no function in science. She can elect sometime between now and then to have her body used for research after she hits that end.

I suppose it might be harsh to note she's done in science. If it's harsh to note as much, I have no sympathy or reservation about as the ability to keep her name in good stead was within her control: she only had to not lie. She made her choice, now she gets to embrace the consequences.

@EdinScientist

Word is Mikovits retracted her earlier statement.

Be careful, Justicar. This kind of "she will pay" banter about Judy is the type of thing Wessely and others in the UK used to make their media case that ME patients have been making death threats against them. If you don't watch out, "ERV commenters and virologists" will be added to the list of "crazy extremists" the media likes to portray as being involved in this field.

By Impatient (not verified) on 05 Oct 2011 #permalink

@Kemist: it's pretty well established that pain can be a psychiatric symptom (see depression, PTSD and fibromyalgia).

If you read that paper on placebo response you'll see that the placebo response was low for psychological treatments, but much higher for physical treatments such as intra-venous placebos.

EdinScientist, I think the reverse transcriptase protein is expressed initially as part of a large precursor protein that also contains gag. The various functional parts are separated by proteolytic cleavage. In that case it is plausible that an antibody against the precursor might work against p30 gag.

@558
So she is still making stuff (stronger words are available if you prefer) up as she goes along or just never had a clue what was going on in the lab?

By Perplexed (not verified) on 05 Oct 2011 #permalink

@561
Makes you wonder how they made the anti-RT (if that is what it really is). Personally I would express some RT in bacteria, purify it and inject it into a rabbit (mouse/sheep/goat etc) and you'd get serum that (hopefully) recognised RT and unprocessed gagpol precursor. It shouldn't pick up mature p30 capsid. But then it is hard to know how any of their reagents were generated or used.

By Perplexed (not verified) on 05 Oct 2011 #permalink

@Perplexed

Sorry, that was just a very bad joke.. :-(

So, to make it even worse, I retract it.

EdinScientist: reference?

Sigmund:
No, RT is part of the "pol" polyprotein, p30 is part of the "gag" polyprotein. Antibodies created to recognize RT shouldn't recognize p30 or its precursors (the p30 precursors are the different not fully cleaved forms of gag).
If they do, something is wrong and they shouldn't have used the antibodies.

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

But someone has said the antiserum was intended to pick up RT (quoted by Edinscientist) or maybe I need to improve my ability to recognise sarcasm in text format?

By Perplexed (not verified) on 05 Oct 2011 #permalink

@ 559 So how angry do you think is acceptable?

Right now I am fuming. I am not going to call people names on a blogs or forums, not my thing, I not going to e-mail anyone anything nasty. I'm just going to have to eat boxe's of Zantac.

Supplement pushers and 'gut doctors' make me mad, but what makes me madder are people who use the respectibility of Science to uber quack.

So what is an appropriate response to this - seriously?

from this day to that [Mikovits] has no function in science

I dunno. Shyh-Ching Lo has a track record of junk science with his HIV denialism, but that didn't seem to stand in the way of general acceptance of the Alter / Lo paper.

By herr doktor bimler (not verified) on 05 Oct 2011 #permalink

as much as I love reading the great science happening here...I kinda miss V and Gerwyn's unique science and I find myself popping into their facebook page every now and then....

I love the title of this one: "Gerwyn scotches rumor..."

LOL, never mind what science or nature says...but Gerwyn....

By mary (abbie's ilk) (not verified) on 05 Oct 2011 #permalink

Has anyone noticed the credits on the image in the ScienceInsider article? It says "Credit: Science, Lombardi et al; Judy Mikovits". I'm guessing that Science credit is for the original image from the tipster. Is that a correct interpretation?

@mo (one of Abbies's elk)
You are probably correct. I know that RT is synonymous with Pol and that Pol is expressed as a gag-pol polyprotein that is further processed to realease the reverse transcriptase and an integrase, but there is another gag polyprotein and I was unsure which one contained p30.

@ 568:
Yeah, and there's Kary Mullis too. Subtle difference with Mikovits: she forged data and published it as though it was real research.

I'm not familiar with their publications, but I should probably be. And if they've pulled anything like this, well, someone should take out the trash.

Oh, pol is expressed as a gag-pol polyprotein. but antibodies against RT still shouldn't recognize p30/CA, because they are in distinct not overlapping positions in the polyprotein and persumably you make anti-RT by injecting recombinantly expressed RT into lab animals (and then other, long to type stuff).

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

@Mary
But does anyone believe Gerwyn still exists? His presence in the forums has been reduced to occasional messages to the faithful, delivered via his devoted V99 - if I remember correctly, with only brief snippets of analysis. Presumably he spends his days on the run from the science mainstream; hiding out in the Black Mountains, struggling to get the truth out, always fearing the day a crack team of grad students finds him and subjects him to an improperly optimised PCR.
The world is truly a less colourful, albeit marginally saner, place.

By Perplexed (not verified) on 05 Oct 2011 #permalink

Sigmund, I saw your post after I osted my last slight correction.
p30 = CA, Capsid protein, in the middle of gag :)
http://regist2.virology-education.com/1XMRV/docs/24_Bagni.pdf
Slide 6

RT is not symonymous with pol, pol codes for 3 enzymes which are also processed by cleavage: N- Protease (PR), Reverse Transcriptase (RT) and Integrase (Int) -C

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

@mary

I have good news for you: the mecfsforums are again accepting new members.

@Perplexed

The real truth: Everybody knows that V99 is really Judy Mikovits.

By Anonymouse (not verified) on 05 Oct 2011 #permalink

And if they've pulled anything like this, well, someone should take out the trash.

Lo's previous time in the limelight was in the early 1990s when he decided that the real cause of AIDS was a new mycoplasma that his PCR tests were detecting in every patient he checked. Lots of headlines, lots of time wasted by people trying to replicate his results.
You still get people in the fringe CFS boards blaming everything on Mycoplasma fermentans incognito (see also whale.to). And bio-warfare experiments.

By herr doktor bimler (not verified) on 05 Oct 2011 #permalink

[brain trickling out of ear]

By Perplexed (not verified) on 05 Oct 2011 #permalink

>The real truth: Everybody knows that V99 is really Judy Mikovits.

Is this an actual hypothesis or a joke?

it's pretty well established that pain can be a psychiatric symptom (see depression, PTSD and fibromyalgia).

Of course, but it can also be a cause of depression - think failed back surgery, or any orthopedic condition gone wrong.

I work part time in the disability insurance business, and from what I've seen many permanently disabled people with chronic pain end up with depression and a high suicide risk. The depression was not there initially; it comes after the years and years of untreatable pain, and makes them feel even worse.

And I wouldn't be too fast in assuming fibromylagia is a purely psychiatric condition. Actually it's pretty mixed up : for a lot of people with fibromyalgia and no other condition (lupus, polyarthritis, and the like), their disease started with an orthopedic condition for which pain was badly managed. Seems withstanding pain for too much time might program your brain for pain even if the damage is repaired.

What I'm saying is : don't assume the psychiatric treatment response means a condition is mostly psychiatric. Your state of mind is affected by you overall health. If you are constantly in pain or tired without any answer or hope of effective treatment it is bound to make you depressive at some point.

I'm an formulations scientist, not a biologist and certainly not a retrovirologist, someone explain to me how not knowing that 5-AZA was used changes things regarding the Science paper at time of submission. Basically I understand how things after Ottawa are really screwed up right now due to this now infamous gel. I also understand that a normal+5-AZA lane was needed also in the original gel and that's a big shortcoming regardless.

I guess what I'm asking if Fig. 2c in the Science paper had originally contained 9 lanes, the extra being normal+5-AZA, and lanes 3 and 6 were labeled +5-AZA, how would that have changed the interpretation of the gel vs. how it was reported at the time and why?

@anon #580

It still changes everything about the interpretation of the paper. If XMRV is a true infectious disease, spread from person-to-person, there is no way that adding 5-AZA should be necessary to induce expression of XMRV proteins. Even if it was, it would still raise questions about all kinds of other artifacts caused by 5-AZA treatment. I doubt the paper would have ever been accepted into Science if that was disclosed.

Our money is on Normal + 5-AZA showing the same 3 bands as Patient + 5-AZA. Just wait for ERV next blogpost ;)

By mo (one of Abb… (not verified) on 05 Oct 2011 #permalink

@Anon 580:

I'm not an expert, but I think Abbie explained this at least one in prior posts. IIRC, our genome has a lot of ERVs scattered all over the place, and one method used to suppress expression of their genes (the ones that ain't broke due to mutation) is to methylate them. If you treat with 5-AZA, you remove the methyl groups blocking transcription, and all of a sudden normal cells start expressing the proteins encoded by these genes (like GAG, etc)

So, showing that cells from a CFS patient express GAG after 5-AZA treatment alone is not evidence that they became infected with XMRV or any other non-endogenous retrovirus, as what you see could be expression due to ERVs (endogenous retroviruses). Perhaps if they showed that CFS patient's cells differ from non-CFS people's cells in the amount of RV proteins made in response to 5-AZA, then that might be some evidence for an infection by something new. But not a comparison of normal untreated against CFS treated.

That is why Ruscetti's (and JM's) statement that the fact of 5-AZA treatment in the gel in question was not relevant to the Science paper is, (to be diplomatic) perplexing. The whole point of that part of the figure was to demonstrate that cells from CFS people are different than normal: different because they express GAG. If only the CFS patients cells were treated with 5-AZA, then the gel does not demonstrate what they claimed it demonstrated.

Anon,
The human genome contains many latent retroviruses. In some cases, drugs like 5-aza can activate the expression of these endogenous retroviruses. The fact that 5-aza was added to the patient samples raises the possibility that the results are due to the activation of endogenous retroviruses in the genome. To see whether the results have anything to do with CFS, one would have to treat all the samplesâ from both patients and controlsâ with the drug, and find that only the CFS samples showed a response. There is no way the paper would have been published had the reviewers known that some samples had been treated and others left untreated.

OK, mo. I think I see what you're getting at. I'll try and show some patience.

ghholm, so if (and I realize that this is a big if) in my imaginary Fig. 2c, the normal+5-aza had been "clean" and lanes 3 and 6 were labeled +5-aza then it would not have been as clear that XMRV was present, since any number of retroviruses could have given a similar WB, right? I guess as I think about it also, wouldn't you need normal+5-aza and PBMC+5-aza also to have all the combinations covered?

There is a new article at Phoenix rising about Mikovits' firing. It doesn't delve into the figure debacle but it touches on a lot of the other issues - such as JM's accusations against other labs and the gereral reaction of the virology community. No mention of Abbie, I just don't think he could bring himself to do it. Baby steps.

Thanks all for your responses. I get it now.

anon,

If I was reviewing the paper, I'd want to see matched untreated and 5-aza treated PBMC from both normal controls and patients, and i would want to see at least 3 of each. Even then, if it was totally clean in the normal controls and blazing hot in the patients, I'd still be a little skeptical of what else 5-aza might be doing in conjunction with CFS, so I wouldn't buy that panel by itself. I'd want to see other evidence confirming that the 5-aza treated PBMCs behaved normally (equal percentage of dead/dying cells, equivalent expression of some normal cellular genes) etc. Ideally, I'd also like them to have used a more XMRV-specific monoclonal antibody, that wasn't already known to cross-react with proteins from other retroviruses (though this might not be feasible, given how similar these proteins are among these viruses). IF those controls were performed, and if all the other data was sound, I'd still be skeptical about the virus association with CFS, given the need for powerful chemicals to show productive virus infection, but I would probably approve the figure for publication.

LOL! @477 wanna be ilk, thanks for pointing out @550. I think we earlier commenters missed it since I'm guessing maybe the comment was held for moderation if that was Former client of Judy's first post. Thanks Former client of Judy.

This also puts a big question on the judgment of K. Loomis of HHV-6 Foundation who put Judy and Annette together, and who also helped Dr. Montoya at Stanford get started with his current CFS/herpesvirus research and treatment.

LOL @577 Anonymouse.

By Smurfette (not verified) on 05 Oct 2011 #permalink

Something has gone horribly wrong.

You all are learning things.

Not just learning things-- learning things and understanding them well enough to accurately describe those things to other people.

WHAT HAVE I DONE???

@486 mo, yes I understand that the virus budding can be caused by demethylating agents such as 5-AZA derepressing ERVs. My question in @466 was actually about when did we first have the hunch from clues about the secret activation ingredient. I wondered a long time ago about Judy's meaning of "activation" and possible doublespeak and I'm not even anything close to a retrovirologist. I was wondering if Abbie had the hunch 1.5 years ago when she asked the Brainstorm Challenge question:

1-- Lets say youve isolated white blood cells from CFS patients. You treat these cells with chemicals that interfere with normal DNA/histone methylation. What do you think will happen? Do you think that is a good diagnostic test for retroviral infection?
The Reno groups decision to use this as a diagnostic test is absolutely baffling.

By Smurfette (not verified) on 05 Oct 2011 #permalink

Abbie, I'll tell you what you've done. You've gone and fucked up a perfectly good internet.

Now we'll have to start an entirely new internet so things will be as they were (and should be).

Dick move, Abbie!

Herr Doktor @ 578, I was a young teenager back then. So, I wasn't at all interested in this stuff back then.

Shouldn't you make the third name of yours professor?

Smurfette-- Yes, Ive had this hunch for a long time. A friend just sent me an old email I sent him:

From: Abbie [mailto:@gmail.com]

Sent: Friday, January 22, 2010

OHMYGOD THEIR 'CULTURE METHOD' IS STRIPPING OFF HISTONE/DNA METHYLATION AND LOOKING FOR VIRUSES!

YOU CAN FIND A BILLION ERVS ACTIVATED AFTER YOU DO THAT OMFGBBQWARBLEGARBLE!

--Abbie

Once again demonstrating that I am the Maya Angelou of 4chan. Also, Im psychic.

Alternatively, I am more than slightly insane, but I pay attention in class and when I read papers and actually learn things and understood the implications of what she was doing and used that information to correctly discern their protocol despite their lack of honesty.

Or some combination of the two.

MattK @588: so, WPI was a victim of happenstance, and Mikovits was just ill-suited to being a director? Well, I agree with the latter. I'll be bold - anyone who's willing to misrepresent data is ill-suited to being that. Even further on a limb! They're ill-suited to science.

I love this nugget: "Dr. Mikovits decision to cast XMRV research into an âus vs themâ mode engendered an environment of distrust that, in some eyes, ended up validating negative (and unfair) assumptions about people with ME/CFS. "

No. The behavior of some people towards scientists who didn't obey Mikovits lead the perception that those people, and those people only, were and are first rate assholes. No one but a handful of kooks on some blogs here and there is saying anything disparaging in the slightest against anyone who has any disease, or possible disease, for having that disease. Many people are saying that some people who have the disease are acting like assholes, and should knock it off.

"WPI, of course, was quickly engulfed in a controversy that would have tested the most experienced director."
No, an experienced director (err, read honest) wouldn't have had this controversy because said researcher wouldn't be going around lying about data sources, and forging data to publish.

Ugh.

Why did I even go read that shit. Now I'm pissed off all over again.

"the Maya Angelou of 4chan" *spits coffee* So are you goint to make business cards or save it for an epitaph?

David,

About two years ago I met all the criteria of CFS. To make a long story short, all it turned out to be was a chronic B12 deficiency brought on by years of using an acid blocker (omeprazole). The fix for this (after the b12 shots) was to take a daily (massive) dose of the vitamin. I take literally sixteen thousand times the RDA daily.

And apparently this is pretty common, so I'm not sure where you are getting your info from.

The US army is even investigating omega3 supplementation as a way to address the high suicide rate. Specifically, they found that servicemen with low DHA levels were 62% more likely to commit suicide.

The western diet is rich in calories (and chemicals) only. Otherwise it is very nutrient poor.

John,

RE: the PACE trial, I'm not at all surprised that CBT didn't work very well. It doesn't work very well for depression either. But it helps, somewhat. We are still in the dark ages when it comes to recognizing and treating mental illness.

(Not just to anon, but continuing my thought in #583): if the labels on the raw figure are correct (http://i56.tinypic.com/23r7fwx.jpg), then it's not just the Science paper figure that fails to show what they claimed; the actual experiment also doesn't support what was claimed in the conference presentation. In the conference figure, lanes 2&3 and 5&6 are presented as pairs of experiments on two different patients: with and without 5-AZA treatment. The raw figure label indicates that only lanes 3 and 6 are from CFS patients, and only they got the 5-AZA. (The Science figures says 1,2,4, & 5 are normal controls.)

So neither version of the figure presented to the outside world (Science paper or conference presentation) corresponds to what was actually done. And what was actually done does not support the claims made based on the two versions of the figures presented.

ERV- Hah, cool. I vaguely remember reading about their culture method somewhere and being confused, but I guess I was confused because I was expecting it to make sense. Like I was also confused by the labels on the slide in question until you pointed out it was a stupid gel. Your version of the gel you would have run @53 immediately makes sense when looking at it. And now I understand why their's is a stupid gel. I'm going to take a guess why it's missing normals treated with 5-AZA.

I need to check out what this 4chan is.

By Smurfette (not verified) on 05 Oct 2011 #permalink

Justicar, yeah, I totally disagree with Abbie on that topic so thanks for ruining it for me.

Smurfette, no!!!!! Just google image search for "4chan/b" - it sort of makes more sense than actual 4chan.

@Kemist,
Sounds like we both have a bit of confirmation bias here.

My experience with the classical CFS patient:

a) is a morbidly obese middle-aged woman

b) is trying to get disability payments from the state

So I guess I should really add "fraud" to the list of potential culprits as well (and type-2 diabetes now that I think of it).

Re: Placebo response. If you check the literature, vague, CFS-like symptoms are actually very commonly reported for *any* placebo, regardless of what is being treated. Hence my unrepentant skepticism.

If I was going to take a guess at what exactly the psychiatric issues were here, I would suggest its an intersection of severe depression, hypochondria and narcissism.

Or, in layman's terms, "I feel like major shit, so I must have this new trendy disease that even SCIENTISTS can't figure out because I'm special".

EvilYeti, you didn't have all the symptoms of CFS because one of the defining symptoms is the absence of a known physical cause like a B12 deficiency. If you had an incompetent work-up that didn't find your B12 deficiency, that doesn't mean you had CFS, you just had an incompetent diagnosis of CFS. Your anecdote that you fixed your B12 deficiency has nothing to do with CFS.

CFS is a real disorder with real symptoms that do not respond well to any conventional treatments and don't respond well to any treatments that have been tried. It doesn't respond to B12 treatments. Here is a trial where they compared IV nutrients to placebo and found nothing significant.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894814/?tool=pubmed

They did find a big placebo effect. That is not surprising to me because the placebo effect is mediated by neurogenic production of nitric oxide and my hypothesis of CFS is that it is due to low NO.

http://daedalus2u.blogspot.com/2007/04/placebo-and-nocebo-effects.html

ERV: "Once again demonstrating that I am the Maya Angelou of 4chan"

Are you a griefer?

Because this whole thing is about the closest real-world equivalent to griefing someone on SecondLife by causing a rain of cocks to fall during their big-media interview.

this is what I understand from that post.

@MattK

that's brilliant! Why have I never heard of BadLipReading before?

MattK, those are really good comments you've been writing on JDJ's blog. I do think they're helpful. It just is taking people a while to get over the shock.

I don't know how JM converted the community into such a cult. She must have been quite the vitamin saleswoman.

Do people here take EvilYeti's comments seriously? It's a lot of trouble to combat that kind of crap, but I'll do it if I must.

Lisa, in your case I'll suggest you are more of the paranoid schizophrenic type. I hope you are seeking professional help.

Haha, Wikipedia sort of explained 4chan to me, and yes it melted my brain in about 5 seconds.

EvilYeti- morbid obesity is an exclusionary condition for CFS. Everything I've seen in Pubmed comparing BMI of CFS and healthy people says there is no difference. Although everyone I know and have seen with CFS is actually underweight or skinny, including those with public photos, the one who cannot be named, and authors Toni Bernhard and Laura Hillebrand.

By Smurfette (not verified) on 05 Oct 2011 #permalink

@Lee - HT to http://jonfwilkins.blogspot.com/2011/09/whats-good-is-to-get-these-goat…

@Lisa - I hope they are helpful for some people. I'm pretty sure they are going to get sick of me sooner or later. It absolutely boggles my mind that some people are cutting the rope on anyone - WPI, Peterson, Jamie, their fellow commenters, all the 'traitor' virologists - for just one chance to keep their rationalizations for Mirovits alive for a few more days. I mean, you can see monolithic obstinant irrationalism all over the internet where people will gang up on outsiders and support each others delusions, but many of the CFS crowd doesn't seem to be like this (obviously some are) - they just have this bizarre attachment to Mirkovits and are willing to do any mental deal to avoid what is obvious to everyone else. Some get to the point where they are starting to say "hey...wait minute..." but at the smallest opportunity they're back to defending her (most often to themselves). Some seem to have tried to accept at face value the 'explanations' offered in the Science piece. 'I was really starting to worry that Judy was a big fat fraud, but now she says she isn't so I believe it' sort of thing. You know that they know, some just can't admit it. How the heck did she inspire so much, as it turns out undeserved, loyalty over only a couple years? Demonizing anyone who says any different I guess. She must have poisoning the well down to an art.

Note to Smurfette: if you are going to start using 4chan, start by browsing /b/ and reading Encyclopedia Dramatica to catch up on your memes. After a while you'll want to move to one of the special interest board. I personally enjoy /sp/ and /sci/ the most.

and the beat goes on...(that song is stuck in my head for some reason)

..ERV has still not divulged how the last images on her site came to exist. This person is obligated to retract her defamatory statements regarding Frank Ruscetti and Judy Mikovits. ERV must also now reveal the true facts behind the doctored gels....

You are repeating your statements in two places. Choose one. The final images are doctored. New artefacts not present in the published gels have appeared and they no longer sync with those published gels. ERV has made defamatory statements regarding Frank Ruscetti and Judy Mikovits, which are completely untrue

FYI..these are recent comments!

By mary (abbie's ilk) (not verified) on 05 Oct 2011 #permalink

From Gerwyn Morris on the XRx forum:
"To allow the raw lombardi data to fall into hostile hands is a crime against humanity"
So "crimes against humanity" now includes genocide, torture, slavery and, most importantly, 'showing the data that supports the conclusions in your paper'.
I'll have to try this the next time I get an awkward reviewer's comment!

@565 Its in the nature article

http://www.nature.com/news/2011/111005/full/news.2011.574.html

Which also includes a telling quote about the conference slide:

'And she chose to relabel a 'normal, untreated' portion of the image with a patient number because the data were the same. "It simplified the slide primarily for a patient audience," she says.'

By EdinScientist (not verified) on 05 Oct 2011 #permalink

Do people here take EvilYeti's comments seriously?

I am no expert in trolling or this "irony" thing that the kids do today, but I do think EvilYeti is pulling your chain.

By herr doktor bimler (not verified) on 05 Oct 2011 #permalink

@EdinScientist

"It simplified the slide primarily for a patient audience,"

Ugh. Longer version: it's okay to lie to this group over here, because they're not really smart enough to handle the truth, and the message is more important than getting the details right.

I really dislike it when scientists "dumb down" their work for the public because they feel the public can't handle the truth. Even if the subject matter is difficult, it is encumbent on the scientist to present accurate data in a way that aids understanding, warts and all. If it takes a bit longer for outsiders to grasp the issues, then so be it. Abbie manages it very well here, and as we see here non-experts can still get their heads around it.

"Simplifying the data" is not an excuse for a dishonest presentation, no matter who the presentation is for; it never has been, and never will be.

Virology Prof @ 523:

RT has to be Reverse Transcriptase. There really is no other logical explanation. [...]

I think I've identified the problem: You're expecting logic from people who didn't even bother to make a negative control where it is painfully obvious that one is needed. ;)

I have noticed that some (or one?) of the anonymous contributors over at JDJ's blog are now taking the position that the Lombardi et al. data is now "compromised". Now that Mikovits is permbanned from the WPI lab, the idea is that the "haters" (being Whittemore, Coffin, ERV and, of course, her ilk) can do whatever they want to do with the pictures that are on Mikovits's hard drive...

As one person stated:

Now we have the Raw data and original materials of Lombardi et al. in hostile hands claims of multiple copies and altered images will become the norm.

Now, forgive me for advancing far-fetched theories, but it is almost certain that at least one of the prominent posters over at mecfsforums have been "fed" condidential information before. Given this, I wouldn't be surprised if this conspiracy tripe is being spread because a certain someone may be afraid more discrepancies will be discovered upon investigation of the other (original) figures.

Oops,

The WPI replaced the picture showing Judy and Vincent on their home page!

http://www.wpinstitute.org/

The people shown now look very serious and professional.

They still have the link to their XMRV research, though...

OWE

OK, I'm back regarding the question of the significance of Fig. 2c.

Correct me if I'm wrong, but...

As originally published in Science, Fig. C does support an interpretation of XMRV being associated with CFS, part of that is due to the fact that no 5-AZA was described, indicating a pretty high viral load, one consistent with infection. (I'm assuming that all the other patient data was similar and contained in the supporting information.) And certainly not due to erv's since the normal lanes were clean.

If, however, it had been described correctly including the use of 5-AZA then a qualified person would stop and say a) how do you know these bands aren't due to erv's since the proper control weren't run, and b) the need for 5-AZA does not seem consistent with levels necessary to induce infection.

Right?

@623 and @616 - That is V99. He or she has basically been replicating that with small mutations constantly since the Science article came out and derailed her/his previous eye-popping denial - two gels under the same exact conditions will turn out exactly the same. It's been altered photos and compromised data ever sinse.

Re: 'XMRV +' ME/CFS patients just not giving up- I question how much it is to do with blind devotion to Mikovits, but rather how much it is to do with the positive XMRV results they received from VIPdx.

Imagine being so sick for so long, having doctor after doctor look at you with disgust, having your family, friends, etc., abandon you, not being able to cook and/or care for yourself, having to go on disability (if you're lucky enough to get it), having to depend on your spouse, parents, etc., for basically everything, being homebound and isolated and not able to do even trivial tasks much less anything substantial without feeling like you got ran over by a truck for days, weeks or even months afterwards, having ignorant people who don't know the first thing about ME/CFS constantly saying you are malingering, crazy, a hypochondriac, etc., plus living with the knowledge that not only is there not being very much done at all in the entire world in regards to proper biomedical research and treatment but instead there actually are certain disproportionately influential groups of psychiatrists and psychologists who use fucking imbecilic methodological techniques in order to try and prove their longstanding assertion that you really suffer from 'dysfunctional illness beliefs' and a phobic avoidance of exercise, and then receiving confirmation in the form of a positive test that you actually are infected with a newly discovered retrovirus, which you paid hundreds or possibly even thousands of dollars that you don't really have to spare on. Perhaps some people haven't yet or just plain won't allow themselves to consider the possibility of something not being worth the paper it's printed on.

Plus there's just an element of torches, pitchforks and the whole mob mentality thing as well. It's like some dystopian post-apocalyptic movie or book where some dipshit is rummaging through a garbage heap and telling the wide-eyed onlookers all sort of shit they're making up straight out of their head about the things they're finding or some maniac preacher telling people that they're going to go to hell if they don't follow directions. Some people just like to be led.

Anon @ 625- not only that, but if the end result of the 5-aza experiment was that regular detection techniques wouldn't be able to find XMRV, then why was the entire basis of the paper that you could find XMRV with regular detection techniques?

Disclaimer- I have no experience with PCR.

By anonymous (not verified) on 06 Oct 2011 #permalink

John, there's a good bit of that. But it's also that for a period of about 15 years (after the de Freitas retrovirus was discredited), the disease was pegged by officials as something mild and caused by psychological factors. And that filtered down to medical schools (which is why most doctors dismissed CFS patients' complaints) and media (with virtually no coverage between 1995 and 2009).

So then XMRV comes along. Whenever a story breaks, there are hundreds of newspaper articles on it in one day. The NIH starts giving out grants and holding conferences. The implication (regardless of whether it makes scientific sense) that CFS is almost the same as AIDS since they're both caused by retroviruses gives the disease legitimacy.

So it's not wholly surprising that patients would have latched onto a retroviral explanation and be slow to give it up. That includes JDJ (who's also the mother of a patient). Increasingly though, I think that Mikovits consciously took advantage of this, in a sociopathic way, which makes me even more suspicious with regard to what's likely to come out in terms of her actual "scientific" work.

From Wikipedia, "Mind Control."

1. People are put in physical or emotionally distressing situations;
2. Their problems are reduced to one simple explanation, which is repeatedly emphasized;
3. They receive what seems to be unconditional love, acceptance, and attention from a charismatic leader or group;
4. They get a new identity based on the group;
5. They are subject to entrapment (isolation from friends, relatives and the mainstream culture) and their access to information is severely controlled.

Will somebody please please isolate the retrovirus that causes delusions of grandeur and persecution complexes manifesting themselves in 200+ word run-on sentences.

We appear to have an epidemic.

By Prometheus (not verified) on 06 Oct 2011 #permalink

@ Lisa -- mind control???? Mikovits? More like V99 is the Jim Jones of the me/cfsforums.

By Anonymouse (not verified) on 06 Oct 2011 #permalink

@Smurfette,
So fat people can't have your special disease now? They can get AIDS, diabetes, cancer, gout, psoriasis, etc but not CFS?

Seems kind of bigoted if you ask me.

@daedlus2u,
Checked out your blog. Shine on, you crazy diamond!

EY, the fun part with that definition of CFS - if anyone actually finds a physiological reason for CFS, CFS goes puff. Think god and the babblefish. As for daedalus, as long as it doesn't involve NO he's always very interesting and reasonable; you learn to mentally block out the NO parts.

I don't think anybody had any sort of blanket loyalty to V99. More just that people were too intimidated or afraid to disagree. The brain dysfunction in severely ill CFS patients is extreme, and that allows people who seem to know what they're saying about topics that require specialty knowledge to get away with a lot.

The "Welsh Wizard" was far more a Jim Jones figure. But it wasn't just him, and he was in frequent contact with Mikovits.

I don't think anybody had any sort of blanket loyalty to V99. More just that people were too intimidated or afraid to disagree. The brain dysfunction in severely ill CFS patients is extreme, and that allows people who seem to know what they're saying about topics that require specialty knowledge to get away with a lot.

The "Welsh Wizard" was far more a Jim Jones figure. But the group-think dynamic didn't just revolve around him, and he was in frequent contact with Mikovits.

An interesting point is that v99 lists his/her activity level as "8" on the forums. Apparently this is based on David Bell's 0-100 scale, where 10 means "Severe symptoms at rest; bedridden the majority of the time. No travel outside of the house. Marked cognitive symptoms preventing concentration."

So if v99 is this disabled, and is bed-bound, how on earth does he/she have the energy to write all this stuff?

Actually, I think Lisa has a point about the mind control. I just think it is a result of preexisting circumstances rather than any sort of conscious strategy.

There's a certain subset of CFS patients who have extreme orthostatic intolerance (preventing them from standing or even sitting up), and in some cases extreme noise and light sensitivities. To the extent that they still retain some cognitive functioning, lying in the dark and typing on the computer is basically the only thing they're capable of doing.

I don't know enough about V99 to know if that's the explanation, but it's possible.

@John,
ProTip: If someone suggests you are suffering from psychiatric issues, responding with a long, rambling paranoid rant does not help your counter-argument.

Thanks for the "work-phobic" idea, though. It's a very elegant solution. Also a good explanation for the malady that is affecting about 1/3 of my co-workers.

CFS has nothing to do with V99, Gerwyn or Kennedy are just bitter losers who would rather be big fish in very tiny ponds than actually do anything remotely useful with their lives. It's entirely possible to have cancer and still be a twat.

By frozenwarnings (not verified) on 06 Oct 2011 #permalink

MattK -- the distressing situations and social isolation were pre-existing. But the one explanation (retrovirus), new identity (XMRV+) and unconditional love from a charismatic leader seem pretty deliberate.

John, your post made sense to me (although some punctuation would have made it more legible). Yeti's trolling you.

Lisa@#638

"To the extent that they still retain some cognitive functioning, lying in the dark and typing on the computer is basically the only thing they're capable of doing."

If you leave off the bit about cognition you have just described half of the internet.

"extreme orthostatic intolerance"

What? You get this from prolonged periods in zero gravity or being in a coma for a month. The treatment is bobbing around in a pool for an hour a day.

By Prometheus (not verified) on 06 Oct 2011 #permalink

ERV's right. I'm learning a lot here. Much of it I believe. Some if it I don't. Like @577: V99 = JM? Metaphysically impossible. JM's MO is to constantly change the story so no one can follow it, understand it, document its holes (except ERV) without being confronted by yet another version of the ultimate truth. In contrast, V99 pathologically sticks to the same script (possibly inspired by JM) over and over and over again, using different names, avatars and forums to drum the same message in. (Mind control? Yes!) Until she/he changes it and then the process starts anew. In fact, naming V99's aliases and memes would be a great drinking game. Virtual happy hour anyone?

By wanna b ilk (not verified) on 06 Oct 2011 #permalink

wanna - I think the V99 = JM thing was a joke.

"The articles on OI start on Page 7."

Ok.

Huh.

They are addressing POTS. POTS is caused by extended bed rest i.e. exaggerated deconditioning and the Mayo Clinic has been prescribing "drink a lot of water and bob around in a pool" for years.

One of my great grandmothers had Chronic OI for sixty years. Then she finally gave up her corsets.

Another great grandmother had persistent headaches in her late 90s. She was five feet tall and her hair was over six feet long.

meh.

Using secondary agonomia in developing a symptomatic profile?

Okay, you might as well include self serving prolix anecdotal gobbledygook in internet comments as a tertiary indicator in the profile.

It is as distended as saying inflammation of the cervical curve is caused by unilateral deafness or that poorly executed craft projects should be a criteria in the diagnoses of long term marijuana use.

But whatever....

By Prometheus (not verified) on 06 Oct 2011 #permalink

And the Mayo Clinic has _such_ a good track record in helping CFS patients that we should trust their suggestions about how to treat their symptoms.

Right.

Prometheus @643, yes, extreme orthostatic intolerance, aka positional hypotension. It is caused by inadequate regulation of blood vessel tone between lying down and standing up. When you try to stand up and the blood pressure in your legs goes up (because now there is a higher gravitational head of blood above them), they don't increase their tone in response. They expand due to the higher pressure and much of your blood flows down to your legs, leaving not enough for your brain.

Guess what regulates blood vessel tone?

People with CFS have this because their regulation of the fundamental pathway that regulates blood vessel tone is messed up.

Read the stuff that I sent you.

Can I ask a question of the folks here? Obviously you can chase me away if it's inappropriate.

Here's an article that suggests that there may be a link between ALS and the cyanobacteria toxin BMAA:

http://discovermagazine.com/2011/may/22-seafood-toxins-causing-als-alzh…

And here's an article suggesting that a retrovirus may be linked to ALS, but that "another factor is needed to cause disease as the blood relatives have similar prevalence of retrovirus, but do not have ALS" and that "the presence of reverse transcriptase activity âmay be an epiphenomenon, linked to another (as yet unknown), pathogenically important factor.â

Does it make any sense to you all (based on what's known about how retroviruses work) that BMAA would somehow be causing this virus to become problematic?

I ask because (anecdotally) there seems to be a really strong correlation between exposures to large amounts of toxic mold (which, like BMAA, is a ionophore biotoxin) and CFS. But toxic mold clearly does not cause the symptoms of CFS.

Toxic mold is really inflammatory though, and XMRV was/is said to activate with inflammation. Do other retroviruses (endogenous or exogenous) that haven't been discredited as being associated with CFS do that as well?

Does this make any sense as a paradigm, based on what is known about retroviruses? If so, what would you suggest in terms of trying to getting other people to explore it or exploring it myself?

Thanks very much for any help any thoughts folks can provide. I'll go away now.

lisapetrison at yahoo

@ 629

"So it's not wholly surprising that patients would have latched onto a retroviral explanation and be slow to give it up."

Fixed it for you:

"So it's not wholly surprising that some patients would have latched onto a retroviral explanation and be slow to give it up."

Lisa-- ERVs and ALS

To those of you waiting for an update--
Ive decided against posting any more about the science of this particular incident until it is resolved (though I will be talking about the politics). I know Judy reads this blog, and she has recently said some things that make me think she is taking cues from what she reads here. Not from me. From you all.

Maybe not, but I am unwilling to allow my commentors to be used to fashion make-shift life-rafts for anyone.

Abbie--

Can I come back and ask the question later?

Or if anybody has any ideas, would they please be willing to write to me at some point?

Thanks....

Oh, sorry, Lisa-- Of course you all can keep talking and such. If I thought things were really bad I would close the thread.

I just wanted people to know why I did not post an update (as it was mentioned upstream) and for people to be aware that their own personal hunches/ideas on this issue might (I very much stress the might, I dont know) be a functional hivemind of ideas for someone painted into a corner.

Yeah, maybe we should all keep quiet until the investigation is done.

By frozenwarnings (not verified) on 06 Oct 2011 #permalink

It was that room temperature comment, was it not, ERV? Good thing she forgot to instruct Frank "sheâs as honest a scientist as Iâve ever metâ Ruscetti about it...

But no, I think we should just keep posting our hunches and ideas, even if it could completely exonerate Mikovits. In fact, the more I think about it, the more it seems that homologous recombinaltion tiniker could easily explain everyting.

Clearly the right response is to come up with the most idiotic reasons possible to see if they try and use them :p

We saw the slides at treatingxmrv, Mikovits bases her defensive actions on the comments here... It's symmetry!

By mo (one of Abb… (not verified) on 06 Oct 2011 #permalink

I am unwilling to allow my commentors to be used to fashion make-shift life-rafts

Good. Inflated human skins are vastly over-rated.

By herr doktor bimler (not verified) on 06 Oct 2011 #permalink

I've seen it all now.

Note to Smurfette: if you are going to start using 4chan, start by browsing /b/ and reading Encyclopedia Dramatica to catch up on your memes.

Like I said, Abbie: you've gone and broken a perfectly good internet. But there are powerful, mysterious forces trying to repair your damage!

Lisa, you don't need a retrovirus to cause bad symptoms if you have a neurotoxin. Neurotoxins can cause bad symptoms all by themselves.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814816/

The typical mechanism for neurotoxins is mitochondrial inhibition. MPTP (1-methyl 4 âphenyl 1,2,3, 6-tetradhydropyridine) all by itself is enough to cause Parkinson's. The mechanisms is that it is specifically toxic to dopamine utilizing neurons. It inhibits complex I which causes mitochondria failure.

Rotenone is a neurotoxin that inhibits complex III. It has been used to catch fish. Put it in the water and the fish become paralyzed. Put it in rats and they develop PD and AD like symptoms.

The mechanism is when complex III is inhibited there is a lot more superoxide generated, and so the basal NO level is lower (that is the main thing that superoxide does). With lower NO, then mitochondria biogenesis is lower (NO is what triggers mitochondria biogenesis), with less mitochondria biogenesis, over time you end up with fewer mitochondria, which generate basal levels of ATP by raising their membrane potential which generates more ATP with fewer mitochondria, but at a lower efficiency. With fewer mitochondria generating ATP, you don't have reserve mitochondria to tap into when you need to turn your metabolism up, so you can't. It isn't a question of will, if you don't have the mitochondria to generate ATP, you can't move your muscles that use ATP to move. You can try, but then you can get ATP depletion below what is necessary to keep the cells alive, and so they die. That also hurts a lot and if you push yourself that far, it takes a lot longer to recover (if you do).

Being able to push yourself to where you kill muscle cells is a âfeatureâ that lets you better escape from a bear (or die trying). It is not a useful feature if you are trying to simply retain good health.

There is a new article at Phoenix rising about Mikovits' firing.

In which we learn that "Dr. Mikovits had impeccable credentials" BUT she is later described as "someone with no experience in the field".
If that's an impeccable credential, I should hate to see a peccable one.

By herr doktor bimler (not verified) on 06 Oct 2011 #permalink

It doesn't matter what JM says now. The shit has hit the fan. This appears to be fraud of the multi-million dollar type. The only thing that matters now is what people say under oath in a court of law.

The only statement about what âRTâ means that matters is the statement by the person who wrote it on the gel and then only when that statement is made under oath before a tribunal with legal authority to impose penalties for perjury.

This won't end up like Wakefield, where things got dragged out so long that the original pathology slides and all photographs could get mysteriously lost and the only entity that lost money was the government in paying lawyers to sue vaccine manufacturers and those lawyers funded Wakefield to generate evidence.

When JM testifies, under oath, she will either take the fifth amendment or she will have to answer questions like how many times she refreshed Abbie's blog on 10/06/2011. Since she doesn't seem to be very savvy about computers and stuff (by leaving the original slide in the powerpoint presentation), she probably doesn't know how to hide her tracks in the intertubes from discovery in a criminal and/or civil proceeding. She will either have to tell the truth, or be caught in lie after lie after lie.

My suggestion to JM is to get a lawyer at a big law firm, give them everything that you have in writing or in electronic format for safe keeping (so no one can say you deleted or changed it), have them put it in the big firm safety deposit box, buy a new laptop and start from scratch. I would suggest turning over copies of your hard drive to your lawyer every week or so, so there is a complete record of what you are doing on it, every website you visit, every email you write, log every step you take with GPS too. The only way what you say will be believed is if you have data to back it up.

RE the politics: Iâm only allowed to make one comment per blog entry on X Rx, but I want to explain why Iâm so pissed at JM. So Iâm going to put it here.

Iâm going to put aside for the moment the idea that she purposely contaminated the CFS samples and not the control samples in the original experiment. Maybe it was a random occurrence. (Actually, I still think itâs within the realm of remote possibility they found something real in that experiment, because the âCFSâ patients in that first study were much more sick, with specific bizarre symptoms, than the CFS patients used in other studies. Maybe they had something go active in the blood when ordinary CFS patients only have it in tissues. Obviously itâs exceedingly unlikely, but maybe not absolutely inconceivable.)

And though the slide controversy in this blog seems really suspicious, Iâm going to put that aside too.â¨â¨

The real problem is that JM knew at least 18 months ago that their tests were not distinguishing CFS patients from controls. Obviously they went back and re-ran the tests many times. (Or if they didnât go back, that was equally bad.)

So all the time Mikovits was accusing other scientists of conspiracies and ineptitude, and all the time WPI was getting patients to send donations and pay for $500 tests out of their disability checks -- she knew the whole thing was based on a falsehood.
â¨
Even if she didnât fake anything, it doesnât make any difference. At least, not in terms of morality (which is sometimes different than ethics).

Why all patients arenât seeing it that way yet, I donât understand.

The ridiculous thing is that if sheâd just owned up a couple of months after the study that the results werenât holding, and said she wanted to look more at HGRVâs, things would have been fine. Patients would have remained committed to her (look how many are still committed!) and colleagues in the community would have respected her. So itâs just really weird.

â¨What could she have been thinking?

I'm pretty sure the second quote refers to Anette Whittimore not Mirkovits, although you are right, it is not particularly clear.

Deadalus,
My suggestion to JM is to get a lawyer at a big law firm, give them everything that you have in writing or in electronic format for safe keeping (so no one can say you deleted or changed it), have them put it in the big firm safety deposit box, buy a new laptop and start from scratch. I would suggest turning over copies of your hard drive to your lawyer every week or so, so there is a complete record of what you are doing on it, every website you visit, every email you write, log every step you take with GPS too. The only way what you say will be believed is if you have data to back it up."

The problem she'd have with this is that she has no access to the lab or her notebooks at this point and, it is anything like where I work, you can't take notebooks or things like that out of the lab to begin with...Sucks to be her at this point, eh?

By Poodle Stomper (not verified) on 06 Oct 2011 #permalink

D2... sometimes having a high priced, big fancy lawyer is not helpful..A family member holds the distinct pleasure of being accused of fraud, being fired, called before congress twice, being stipped of credentials, having every paper he authored labeled as scientific misconduct, and having his NIH funding pulled..It was an effing mess.

He fought for years to regain everything..eventually winning, received a big settlement, of course,his science was eventually validated..unlike how this will play out.. I don't think even with a high priced image maker and pr she will ever regain any status in science.

Like everyone else..taking notebooks, computers, even doodles are not allowed to leave our lab..they are not considered my property..

By mary (abbie's ilk) (not verified) on 06 Oct 2011 #permalink

@RRM 659
I think you are on to something here...RT might stand for recombinaltion tinkering.

Jon H @ 608

Are you a griefer?

Because this whole thing is about the closest real-world equivalent to griefing someone on SecondLife by causing a rain of cocks to fall during their big-media interview.

Was it penises or dildos? Certainly it was something phallusy, but we must take pains to convey information correctly.

mary (abbie's ilk)@#671

"... sometimes having a high priced, big fancy lawyer is not helpful.."

Blasphemer.

By Prometheus (not verified) on 06 Oct 2011 #permalink

Maybe Dr. Judy can get a show on Oprah's network, or write a column on "Health" for the Huffington Post. Maybe she can join Wakefield on his lecture circuit.

Or go back to selling vitamins, this time to CFS sufferers with the promise that they will "help you beat the retrovirus."

Unfortunately these jokers are just the latest in a long line of scammers and pseudoscientists who have been involved in CFS over the years. Patients are partly to blame for fawning over anyone who 'proves' that CFS is physical even if it is shockingly bad science. The scientists that are doing real science generally get death threats and hate mail because they're not publishing what the patients want to hear.

I keep thinking that I should come up with some scam to sell to CFS patients...the only thing stopping me is my pesky conscience (although I'm thinking it would probably be ok to scam douchebags like v99 and his ilk).

I really find it funny that patients suffering from a supposedly debilitating illness can nonetheless muster the energy to send hate mail and death threats to any scientist who says something they don't want to hear. I'm no expert, but I probably wouldn't be surprised if there were a link between borderline personality type disorders and "Chronic Fatigue Syndrome". It would certainly explain the delusions and persistent sense of personal victimization.

Speaking of personality disorders...

It's OK TD. This is so fucking stupid it makes my hair hurt. I think you're generalizing unfairly... but damn some of them make it hard. Just think, that guy is a moderator - hasn't said anything - he's been studying the issue carefully for days and crafting a lengthy response with weighty deliberation and comes up with this towering monument to to follies of motivated reasoning. Christ, don't these people spare a thought to their own dignity?

@Lisa,
In the interest of full disclosure, I should mention I work at a top science (particularly in the health sciences) research institution. While I don't personally do research in this area, I'm a science 'geek' and pay attention to where the grant money is flowing.

And to that effect, CFS/ME aren't even on our radar. Neither is XMRV, which I hadn't even heard of until this post. I tend to take a market-based approach to things and if there was serious interest in this stuff, we would be building labs to study it. But there simply isn't. The public seems to like stem cells though...

Anyway, not to trivialize your condition, but even after reading your references I haven't seen evidence that CFS isn't anything other than a misdiagnosed existing condition, a psychiatric disorder or most likely an intersection of the two. As such this qualifies as a "First World Problem" and not something I'm much concerned about. Especially when there is still that whole malaria and HIV epidemic in Africa thing.

That said, I'm still open to it being a novel condition. I'm sure its within the realm of possibility that there could be some autoimmune disorder that interrupts the ATP mechanism in some fundamental and obscure fashion.

Anyway, so I think I've thought up a good experiment to test this hypothesis. Assuming its a psychiatric or neuropsychiatric disorder then all patients should respond favorably to treatment with a good therapeutic dose of Benzedrine.

If its not a disease of the mind/brain for at least some patients, then Benzedrine isn't going to work at all.

Googling has turned up that Benzedrine is indeed effective for some patients, which means very simply that for them its a psychiatric disorder. And so is depression for that matter, which is one of the leading causes of death in America (suicide), so I'm not sure why CFS patients are so quick to trivialize that diagnosis.

As an aside, I'll comment that very real downside of the internet is that it can act as a sort of "force multiplier" with the various patient support groups that are popping up. For psychosocial illnesses these things are like a petri dish and create what is known as a "shared psychotic disorder".

http://en.wikipedia.org/wiki/Folie_%C3%A0_deux

I can't tell if Yeti is being forthright here or if he's just trying to get me to react. No matter though. There are lots and lots of top-level medical people who think just like what he's describing, and so he very well may work for the Mayo Clinic or some such.

The CDC played a neat trick, giving the disease this name and defining it with those vague symptoms. As marketing challenges go, I've never come across a more difficult one.

Here are the articles from the literature on amphetamines. The descriptions are abbreviated, but the PMID's are included if you want to look up the articles.

Does the fact that people with a particular disease respond a little bit to such drugs, in short-term studies, mean that their disease is caused by psychological factors, do you think? I mean, REALLY?? Wouldn't anybody feel a little more energetic in the short-run on bennies??

This seems the same thing as the exercise argument: yes, insofar as people can get a little exercise without being harmed by it, it's good for anybody. But hardly a cure, and thus hardly indicative of a cause, I don't think.
*
Valdizán Usón JR, Idiazábal Alecha MA. Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate. Expert Rev Neurother. 2008 Jun;8(6):917-27. PMID: 18505357

The use of immediate-release methylphenidate in CFS was shown to be helpful in one small study.
*
Young JL, Redmond JC. Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study. Psychopharmacol Bull. 2007;40(1):118-26. PMID: 17285103

ADHD medications can be effective in CFS.
*
Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006 Feb;119(2):167.e23-30. PMID: 16443425

The amphetamine derivative methylphenidate was better than a placebo at relieving fatigue and concentration disturbances in a minority of CFS patients.
*
Olson LG, Ambrogetti A, Sutherland DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Psychosomatics. 2003 Jan-Feb;44(1):38-43. PMID: 12515836

A short trial suggests that dexamphetamine may be useful in the management of CFS.

daedalus2u: Thanks for the concise explanation. I'm going to put that in my files to share with people. I wish that doctors and researchers specializing in CFS were as open to the idea that toxins actually are causing the disease as you seem to be. Almost to a person, they seem determined to believe that CFS is a viral disease. The epidemiology clearly is more indicative of a toxin, and (as you say) the mechanisms also are consistent, but it's a real battle to change anybody's mind. Apparently I have to raise some money and run some basic studies demonstrating a CFS-biotoxin connection myself, so that's one of the things I'm working on now.

MattK: Most of the people on these boards are the sickest of the sick, and this disease does a real number on the brain. And the emotions. If we posit for a second (as daedalus did) that it's a disease caused by neurotoxins, then that makes sense. Only because I was really fucked up in those same ways, for a really long time, do I have any patience for it.

@682
Stimulants are part of the quiver of tools a patient can use to meet the demands of short demanding work obligations or to show up at an important function seemingly intact. Better something like Nuvigil/Provigil than Benzedrine, which affects personality more dramatically.

The problem is that the patient pays dearly to recover afterwards, sometimes for a long time. That does not mean CFS patients that respond to stimulants briefly have a psychological disorder; how would you leap to that conclusion?

Most CFS patients don't trivialize psychological factors or bonafide psych patients with such illnesses. They just do not want an unwarranted and unsupported psych rap to deal with. Its common sense, not politics. Psych patients can be incarcerated and/or treated against their will with anti-psychotics or ECT. Not to mention the social stigma. Why sign up for it if it does not fit and is not supported by evidence based data?

TylerD - I think there is a paper finding a correlation between BPD and CFS but then I think there are also papers that don't find links with psychiatric disorders. As for sending hate mail and death threats, yes it is possible to do that while bedridden, but yes, it does also seem that the crazy forum has some psychosis involved. I can believe that they probably have both. Seriously, typing a couple paragraphs uses very little energy. For a healthy person, that is like 0.1% of your physical energy expenditure of the day. When I started commenting on this blog two years ago, I had to lie down for an hour between typing two sentences and it would take me 3 hours to leave a comment of this length, and that was my entire day. I'm quite a bit better now, thus the multiple comments, but I still can't easily sit up for more than 2 hours without having to lie down again, so I guess it depends on your definition of debilitating.

EvilYeti - I actually agree that people with morbid obesity or some of the other exclusionary conditions such as schizophrenia could probably still get CFS, but I wasn't arguing about what the definition should be or why they exclude them, just what it is. That is the definition used by the disability screeners so I fail to believe that your classical CFS patient exists.

After reading V99 posts, it's hard to tell what is trolling.

By Smurfette (not verified) on 06 Oct 2011 #permalink

1. "At the July workshop, Dr. Mikovits also presented preliminary data showing that 20 patients of the 101 in the study have lymphoma, a rare form of cancer. The link between XMRV and lymphoma is still being investigated, but it raised the possibility that XMRV may be associated with other cancers in addition to prostate cancer. NCI's Dr. Le Grice said studies will be launched to determine whether XMRV is associated with other diseases. At the Whittemore Peterson Institute, Dr. Mikovits said they also found XMRV in people with autism, atypical multiple sclerosis and fibromyalgia."

Cancer-Causing Virus Linked to Chronic Fatigue
BY AMY DOCKSER MARCUS
OCTOBER 12, 2009.

source- http://online.wsj.com/article/SB125501227713473525.html

-----------------------------------

2. "Since reliable, consistent information about the Science cohort has not been forthcoming, I have carefully analyzed data provided in the Science paper, its supplement and public presentations by two of the authors. The WPI investigators conducted a number of assays to detect XMRV DNA, protein, infectious virus and antibodies against XMRV. I used the patient ID numbers provided in the paper's figures to track results. Of the 101 CFS subjects reported in the paper, results for the various assays are shown for only 32 CFS subjects. Of the 32 CFS subjects whose results for any of the tests are displayed, 12 CFS subjects were positive for XMRV on more than one assay. The other 20 CFS subjects were documented as positive by just one testing method. Using information from a public presentation at the federal CFS Advisory Committee, four of the 12 CFS subjects (WPI 1118, 1150, 1199 and 1125) included in the Science paper were also reported to have cancer â either lymphoma, mantle cell lymphoma or myelodysplasia. The presentation reported that 17 WPI repository CFS subjects with cancer had tested positive for XMRV. This once again raises questions about the lack of detailed clinical characteristics of the CFS subjects included in the Science paper, and the differing public reports about where the samples originated."

Playing A Weak Hand Well
Suzanne D. Vernon, PhD
Scientific Director
The CFIDS Association of America

source- http://www.cfids.org/xmrv/070110study.asp

-------------------------------

3. Q: Were any patients with lymphoma mentioned in the XMRV study?

A: Blood samples from the WPI repository were chosen at random and there were no patients chosen with lymphoma or mention of lymphoma in this study. Another preliminary study was done at a later date that had nothing to do with the XMRV Science publication.

source- http://www.wpinstitute.org/research/research_biobank.html

--------------------------------

4. Q: Did any of the samples used in the original study come from patients who ultimately developed cancer?

A: Yes, one.

source- http://www.facebook.com/notes/whittemore-peterson-institute/xmrv-testin…

------------------------------

5. From the NCI's Center for Cancer Research 2009 CCR Scientific Advances-

Detection of a retrovirus, XMRV, in blood products of patients with neurological diseases and cancer â submission by Francis Ruscetti, PhD
Reference(s): Science. 2009 Oct 23; 326(5952): 585-9

source- (webpage no longer online, a saved copy does exist)

(Note- Not sure what the exact import of the title is, since although the reference given is the WPI's XMRV/Science paper, Science was contacted and asked if the WPI/XMRV paper had ever had this or any other title than the one it was published with, which Science said it had no record of this. Given the above inconsistancies though, it kind of raises some questions)

----------------------------------

6. By comparing information in the 'XMRV Association with CFS' presentation given to the CFSAC on October 29-30, 2009, with Table 4- 'XMRV detection results of 101 patients' in 'Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome' in the Journal Virulence, at least 12 patients from the original XMRV/Science study had cancer, although its impossible to tell exactly due to only 93 patient numbers being listed in the table and not the full 101 stated. One more patient number which was listed as previously having had cancer in the CFSAC presentation, 1199, is included in Tables 1 and 2 but not Table 4. The cancer status of one of these patients, 1125, was known as far back as the year 2000.

sources-
6a. WPI patients w/ cancer, taken from pt. 5 of 'XMRV Association with CFS' presentation given on October 29-30, 2009-
pic- http://i54.tinypic.com/11aicyc.jpg

6b. 'XMRV Association with CFS' - Part 5- presentation given to the CFSAC on October 29-30, 2009- (see Slide 1)
http://www.hhs.gov/advcomcfs/meetings/presentations/peterson_1009_pt5.p…

6c. 'Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome' Virulence 1:5, 386-390; September/October 2010- (see Table 4)
http://www.landesbioscience.com/journals/virulence/MikovitisVIRU1-5.pdf

6d. WPI 1125- http://i55.tinypic.com/2a8f495.jpg

By anonymous (not verified) on 06 Oct 2011 #permalink

I just read on X Rx that JM has the patents for XMRV testing. Is that the case? (Sorry if it's been discussed here -- there are a lot of comments on the thread.)

If so, how much money has she likely made from each test done (or in total from testing) so far? If she's found guilty of wrongdoing, is there a way to get that money back from her?

From MattK's link @681

Finally: IMO the biggest issue that has caused so much consternation on this forum in recent days is the readiness of sceptics to selectively attack specific types of researchers, but not others, at the slightest pretext.

Yes, I tend to treat different kind of researchers differently. The lying, data falsifying charlatans get nothing but scorn. Those who are simply fuck up and get something wrong but own their errors and retract them get to keep my respect. It's not a crime to make a mistake. It's easy enough to read something wrong, misunderstand, fail to recognize an otherwise obvious problem because of perspective. It sucks this happens, but it happens honestly and what is one really going to say? Sorry, Dr. so and so, but we require that you be practically perfect in every way?

Lying about it? Falsifying data? Scamming people? Fuck you; it's game over. It's a pity there isn't a hell for people like that to go to.

Clearly, none of you has thought sufficiently carefully about the "RT" in question. Given her demonstrated tech-savvy approach to sourcing modern technology (ie photoshop), it's immediately obvious that RT is the standard abbreviation "retweet".

(sorry, the best use of homologous recombinaltion tiniker was used, and I missed thinking of it. Odd since it's in my twitter profile.) *sniffle*

ERV, can you send me a private email address of you?

By mo (one of Abb… (not verified) on 07 Oct 2011 #permalink

Lisa, I'm not sure about the money involved for holding the patent but, lots of researchers hold or file patents..ie: Ila Singh and her co authors filed for a patent for an assay they developed for xmrv, of course, this led to the patients stating she was now biased, in for the money, yada, yada, yada.....

Levi (and other pt's)..It's too bad the vocal part of me/cfs are not using this time to garner some media attention. (I know the guy from PR website has said the same..) Instead, the vocals are still pushing back against the scientists and claiming we are somehow bad people for tearing the science paper apart but not the pace study..

I would think they would be trying to use this to their advantage..

By mary (abbie's ilk) (not verified) on 07 Oct 2011 #permalink

We are tearing Mikovits paper apart because we are molecular biologists and we don't know shit about psychiatry. Let the psychs deal with that. And of course because it is bad science and was published in Science

By mo (one of Abb… (not verified) on 07 Oct 2011 #permalink

@WTF #677 "Patients are partly to blame for fawning over anyone who 'proves' that CFS is physical even if it is shockingly bad science."

That rather comes close to 'blaming the victim". I've argued long and hard on M.E/CFS forums that 'we' suffers do indeed have a responsibility to be scientifically literate. However given the generally very poor grasp of science (Karl Popper - who's he ?) and the lack of basic logic skills, amongst the general population, expecting an exceptionally high level of comprehension from a patient group that suffers an illness characterised by cognitive deficits might be considered unreasonable.

M.E/CFS patients have been poorly served by science in general and medicine in particular. M.E/CFS crosses medical discipline boundaries, offers little in the way of quick research 'reward' and doesn't command public health urgency (not fatal, not communicable, doesn't affect infant health, and is conflatable with conditions of aging and occupational ill health). Against this background any researcher who says 'yes this illness is real and it is important' is bound to be seen very positively by many patients. Indeed it's probably only cynical, sceptical old misanthropic bastards like me that would look at bit of promising research and question everything from the researchers' parentage to their use of the semi colon and all the science in between.

Patients do have a responsibility to educte themselve and to be objective about research, but science, and particularly medical science could do a lot more to engage with those in whose interests it is supposedly working. And those who seek to promote the cause of scepticism might also give some thought to how the general cause of sceptical enquiry has been promoted (or rather has not) by the denigration of M.E/CFS sufferers over the past 30 years. The consistent appeal to the authority of the non science of psychiatry on the part of M.E/CFS sceptics, has been a particularly egregious double standard given the way that M.E/CFS patients have been criticised for not accepting psychiatric labelling.

The reason no-one (who took an interest) is tearing apart the PACE Study and the psychiatrists is because after reviewing the evidence, by reading the papers, checking up on the scientists, reading the abuse from the numbnuts advocates we decided that the numbnuts are talking out of their arses and are prejudiced against anyone and anything that might suggest any psychiatric angle to CFS.

By frozenwarnings (not verified) on 07 Oct 2011 #permalink

No, PACE has methological flaws.

By mo (one of Abb… (not verified) on 07 Oct 2011 #permalink

@Mo

Just click the "contact" bar above.

Mary -- I don't have any problem with scientists having patents for things. I've just been sitting here for the past couple of days trying to figure out what Mikovits' motivation could have been to make all this stuff up (if she did). It seems like a lot of trouble to go through just for its own sake. If there were a lot of money involved, at least that would be an explanation.

frozenwarnings -- Just because people act crazy doesn't necessarily mean that their illness has a psychological cause (though positing that is certainly understandable). Both neurotoxins and parasites can cause emotional/psychological changes that reverse when the irritants/pathogens are addressed, and both of those appear to be factors in CFS.

Lisa, no-one knows whether CFS is a psychiatric or a physical illness, NO-ONE, and until they do I'd be massively grateful if all the amateur scientists would shut the fuck up.

Also, you clearly have no clue what mental illness is, or you wouldn't describe it in such terms. Mental illness is as real as cancer or measles, it is not something to be ashamed of, and it is not something that should be used as a term of abuse as you have just done.

By frozenwarnings (not verified) on 07 Oct 2011 #permalink

The patent is interesting. There are two applications, US20110151431 and US20110117056 (just search on freepatentsonline to find them).
One is based on antibody based detection methods for XMRV antigens and the other is based on diagnosis of diseases associated with the virus.
Of particular interest is the fact that both applications contain several figures from the Science paper as evidence to support their claims. One of these is the famous figure 2C - in the patents they are retitled 2D - with the following description:
âLysates from normal PBMCs (lanes 1, 2, 4, 5 and 7) or from subjects WPI-1235 (lane 3) and WPI-1236 (lane 6) were activated for 7 days with PHA and IL-2 and then analyzed by Western blot using rat anti-SFFV env monoclonal antibody (top panel) or goat anti-R-MuLV p30 (bottom panel). Lane 8: SFFV-infected mouse HCD-57 cells. Molecular weight markers are shown on the left.â
In other words they are clear what activation means - it's the standard PHA and IL-2 treatment - yet they again leave out the fact that 5-Aza has been added to the patient samples.
If they have read the application form they should be aware that "willful false statements and the like so made are punishable by fine or imprisonment, or both under 18 U.S.C. 1001 and that such willful false statements may jeopardize the validity of the application or any patent issued theron"
Oh dear.

Lisa, all the long term effects of anything can only happen due to the short term effects changing the long term regulation of physiology. All of physiology is under control. When that control is messed up, so is physiology. All of the control in physiology is self-regulating, that is there is automatic gain control. If the automatic gain control is out of whack, so is physiology.

Anything that lasts for a long time (like CFS) is due to long term not good regulation of physiology. Switching of physiology to a bad regulation can happen from a lot of short term effects, like infections, bacterial or viral, but infections that are intercellular (like syphilis, Lyme, Q-fever) are more effective at causing long term regulatory changes which is why they can cause long term symptoms. The symptoms can persist even after the infection has been cleared. That is because physiology now has a new âsetpointâ. To get physiology working correctly again, the âsetpointâ has to be reset back to ânormal.â

Stimulants are not going to work for CFS (IMO). They don't fix the regulation, they just mask the symptoms of fatigue without changing the underlying regulation. Masking the symptoms of fatigue just causes people to over exert and cause damage. Stimulants are the opposite of what is needed.

EvilYeti, stop embarrassing yourself. You didn't read Lisa's references. If you did read them and did understand them, there is no way you could honestly come to the conclusion that CFS is a misdiagnoses of something else.

Ironic that on a thread discussion research fraud you would lie about reading 600 references and think no one would notice. Dunning Kruger strikes again.

Frozenwarnings -- I'm extremely sympathetic to those who have mental illness. I feel bad if what I said came across as abusive, since it wasn't my intention to criticize them in any way.

Lisa, I'm sure, just a little tired of the prejudice against those patients by the twat advocates, or as I like to call them Twatvocates, and others who equate being a tosser (V99,GE,AK)with having a mental illness.

By frozenwarnings (not verified) on 07 Oct 2011 #permalink

Interestingly, psychological disorders get a lot of respect in these days. Certainly a lot more respect than CFS (which a good many people still think is something really mild and due to laziness).

Probably that's because a lot of people with psychological illnesses have gotten much better with psychotropic drugs and then have publicly stood up for themselves and others with their condition. On the other hand, almost no severely ill CFS sufferers ever get substantially better, and thus remain too sick to do anything except write random comments on message boards.

Therefore, to some extent it might be in CFS patients' best interest to state ('fess up) that they have a mental disorder. They'd likely get a lot more sympathy that way.

The problem is that insofar as people (scientists especially) keep thinking that the disease is psychological, they're never going to look into physical causes.

I agree that some of the patients on the CFS forums are abusive toward people with psychological conditions, and am always am sorry to see that happen.

Old arguments, can't be arsed debunking again.

By frozenwarnings (not verified) on 07 Oct 2011 #permalink

There are only business reasons to get patents. If you are not going to try and make money from an invention, there is no reason to try and patent it. Simply publishing it anywhere is enough to ensure that no one else can patent it.

A patent on a made-up test is of zero value. All a patent can do is block someone else from making, using or selling what ever it is that you have patented. If you have patented something useless, then no one is going to want to do it anyway.

A useless patent may have value if you are trying to scam investors.

@ RRM: Thanks, emailing now.

@ Sigmund: Nice find, Mikovits, Lombardi, the Ruscettis and Silverman are on US20110151431 and all of them except Silverman are on US20110117056.

quote from US20110117056:
#####
Examples of anti-retroviral agents that can be used to manage or treat an XMRV-related neuroimmune disease or an XMRV-related lymphoma include, but are not limited to, acyclovir, penciclovir (famciclovir), gancyclovir (ganciclovir), deoxyguanosine, foscarnet, idoxuridine, trifluorothymidine, vidarabine, sorivudine, zidovudine (AZT, ZVD, azidothyidine, e.g., Retrovir), didanosine (ddI, e.g., Videx and Videx EC), zalcitabine (ddC, dideoxycytidine, e.g., Hivid), lamivudine (3TC, e.g., Epivir), stavudine (d4T, e.g., Zerit and Zerit XR), abacavir (ABC, e.g., Ziagen), emtricitabine (FTC, e.g., Emtriva (formerly Coviracil)), entecavir (INN, e.g., Baraclude), apricitabine (ATC), tenofovir (tenofovir disoproxil fumarate, e.g., Viread), adefovir (bis-POM PMPA, e.g., Preveon and Hepsera), multinucleoside resistance A, multinucleoside resistance B, nevirapine (e.g., Viramune), delavirdine (e.g., Rescriptor), efavirenz (e.g., Sustiva and Stocrin), etravirine (e.g., Intelence), adefovir dipivoxil, indinavir, ritonavir (e.g., Norvir), saquinavir (e.g., Fortovase, Invirase), nelfinavir (e.g., Viracept), agenerase, lopinavir (e.g., Kaletra), atasanavir (e.g., Reyataz), fosamprenavir (e.g., Lexiva, Telzir), tipranavir (e.g., Aptivus), darunavir (e.g., Prezista), amprenavir, deoxycytosine triphosphate, lamivudine triphosphate, emticitabine triphosphate, adefovir diphosphate, penciclovir triphosphate, lobucavir triphosphate, amantadine, rimantadine, zanamivir and oseltamivir, raltegravir (e.g., Isentress), elvitegravir (e.g., GS 9137 or JTK-303), MK-2048, maraviroc (e.g., Celsentri), enfuvirtide (e.g., Fuzeon), TNX-355, PRO140, BMS-488043, plerixafor, epigallocatechin gallate, vicriviroc, aplaviroc, b12 (an antibody against HIV found in some long-term nonprogressors), griffithsin, DCM205, bevirimat, and vivecon. For example, one or more of AZT and cidofovir can be used to manage or treat an XMRV-related neuroimmune disease or an XMRV-related lymphoma. As another example, an interferon (e.g., interferon-β) can be used to manage or treat an XMRV-related neuroimmune disease or an XMRV-related lymphoma.
####

So Mikovits, Lombardi and Ruscetti have the patent on treatin CFS patients with antiretrovirals, not the WPI or the Whittemores.
Who wants to report them to the patent offices?

@ Frozenwarnings: Ctrl + F this thread for PACE and read what they did wrong in the posts above.

By mo (one of Abb… (not verified) on 07 Oct 2011 #permalink

Has JM made money from the XMRV testing that has already been done? Or was she just drawing a salary so far?

Annette Whittemore will be answering questons on the WPI facebook page today (Friday) at 10 am Pacific time. Questions can be sent in advance to info@wpinstitute.org.

http://www.facebook.com/pages/Whittemore-Peterson-Institute/154801179671

It might be helpful if people who know better than I what the right questions might be would ask them.

mo@707, the names on the patent are for show, what matters is the assignee. And that's the WPI.

@WTF #677 "Patients are partly to blame for fawning over anyone who 'proves' that CFS is physical even if it is shockingly bad science."

That rather comes close to 'blaming the victim".

I have to politely disagree with the implications that claim carries. The situation is more complicated than the situations for which that phrase is typically used.

In this case, the victims in question are victimized twice: once by CFS, and a second time by an unscrupulous and/or incompetent researcher who tells them what they want to hear and reaps their worship and adoration. No one is blaming these people for their first victimization, by CFS (well, except for a few like EvilYeti, who doesn't represent the rest of us.)

But for the second victimization, why is blaming the victim incorrect?? You could argue that a CFS patient is too befuddled by their condition to be able to think critically but really, they're behaving just as Wakefield groupies do, and Wakefield groupies are doing it of their own free will. I don't think CFS patients can blame all their bad decisions on the disease.

By Antaeus Feldspar (not verified) on 07 Oct 2011 #permalink

The patent was filed on October 9th 2009.
Almost immediately a Twitter account called XMRV started sending out alarmist tweets about the virus and promoting the WPI.
October 14th 2009 "Up to 10 Million already infected with XMRV Virus - retrovirus linked to both Prostate Cancer and Chronic Fatigue Syndrome"
October 15th 2009 "Thinking about US blood supply -- if 10 Million people are infected with XMRV virus and don't know it, is global blood supply tainted?"
October 16th 2009 "Great PowerPoint presentation on history of retroviruses on the WP Institute site: "
November 9th 2009 "Testing for XMRV available at VIPdx "

I've never been a Mikovits fan, and to the best of my recollection the only positive thing I've said about her was to concede that she did seem smart.

But I NEVER saw this coming! So I don't think it's fair to blame other patients for not seeing it either.

As for the "groupie" thing -- this is Week #1 and people are still in transition. Things are already shifting a lot. So just give it some time.

@mo "Ctrl + F this thread for PACE and read what they did wrong in the posts above."

Not remotely interested in reading anymore biased patient opinions on PACE thankyouverymuch. Read them all, read the paper, read the scientists' commentaries. Perfectly good piece of work, needed doing. It didn't say what the twatvocates wanted it to say so they have been banging on and on and on about it ad nauseum, while knowing jack shit about how research is conducted.
n
Please don't waste your energy.

By frozenwarnings (not verified) on 07 Oct 2011 #permalink

@Lisa 708,

I suggest the following questions:

- did Annette KNOW that Judy did not reveal the real methods used for the Science paper?

- is/was her daughter taking antiretrovirals?

- will Annette now write apologies to McClure and van Kupppeveld etc and publish these like she did with her accusations the other day?

OWE

mo, that is a patent application. It doesn't become an enforceable patent until it issues. It probably never will. It costs money to continue the process to try and get a patent. If the issued patent is of zero value, that is throwing good money after bad.

Lisa,

To be clear I'm affiliated with the University of California.

It's a common misconception that amphetamines give you energy. All they are doing is monkeying with your brain chemistry. The energy was already there. In fact, Benzedrine was once prescribed as a (very effective) anti-depressant. Unfortunately, it turned out to have abuse potential and be habit forming.

So, if brain drugs work; this is a brain problem of some sort. Either a disease of the brain, a disorder of the mind or some intersection of the two. Which again, and I can't stress this enough, doesn't make it any less serious or real. Depression is one of the top killers in America.

Anyways, I'm a minimalist by nature and I'm really not seeing enough of a difference between CFS and a more established mental illness like major depressive disorder to warrant cause or concern. Given that depression and narcissism are often joined at the hip; I'm not at all surprised some depressives have deluded themselves into thinking they have a "special" illness.

daedalus2u,
I'm unimpressed by your degree from GoogleU. I'm familiar with "death by citation" and will not play that game.

I've been dealing with individuals like you since my Usenet days. We've even defined the phenomenon:

http://rationalwiki.org/wiki/Crank_magnetism

OWE-- As nasty as the stories Ive heard about the Whittemores are, as nasty as Annette has behaved during this fiasco, as nasty as The Princess Who Cannot Be Named has been to me-- I cannot imagine they understood what was going on, even if Mikovits told them.

My parents dont understand what I do, and Ive told them a million times. Its a different language.

And I cant imagine anyone *knowing* it was a farce putting themselves/relatives on antiretrovirals or that Ampligen crap or whatever else.

I can believe that they were fooled like everyone else.

But I also didnt even consider the fact Ruscetti was in on this, so, shows what I know, dont it?

I suggest "Are you aware of the unmentioned use of 5-AZA or other unmentioned reagents in any other published experiments"

@ ERV: Aside from fanpost, I sent you some speculative stuff, I would like if that's possible or if I'm just cranky there.

By mo (one of Abb… (not verified) on 07 Oct 2011 #permalink

Levi,
I'm completely open to the idea that CFS is simply a logical reaction to our societies bias and discrimination against mental illness. Comments like "I'm sick, I'm not crazy!" prove this. Epithets like "crazy" themselves are discriminatory and bigoted.

Consider the following two statements as an example:

Obama is a n!gger.
Mel Gibson is crazy.

Both statements are unambiguously pejorative. However, the second is socially acceptable while the first is not. Google even suggests "crazy" if you type "Mel Gibson is".

And I'll say this again, and continue saying it until it is no longer the case, that this sort of discrimination is the single biggest bias in our society.

CFS patients that perpetuate this bigotry are only acting against their own best interests. They are the ones denying that they are sick, not people like myself.

I read through Hooper's objections to the PACE trial last night, and they are pretty much all nonsense. He makes some howlers such as saying that CFS/ME has been shown to be a âproven organic brain diseaseâ (it hasn't).

Sure, there is no proof that CFS is psychiatric, but there is a lot of anecdotal evidence that it is. Unlike what Lisa says, many severely affected patients have recovered after undergoing psychological treatments. Even the press release for the PACE trial mentioned one person who had completely recovered after CBT.

#710 I certainly wasnât advancing the notion that using oneâs own ill health as a basis to excuse personal responsibility was acceptable and Iâm surprised anyone would have read it that way. The point I made, was that it is unreasonable to expect M.E/CFS patients to be any more scientifically literate than the general population given that: many of us patients are affected with cognitive dysfunction, and that as a patient group we have had precious little in the way of scientific support for understanding of the condition. I have no love for the Wakefieldisation of M.E/CFS â itâs why I started blogging (albeit stalled) about the cultification that is going on http://cfsmirror.blogspot.com/2011/01/saints-and-demons-in-cult-of.html . But if science and sceptical bloggers/posters are going to treat M.E/CFS patients as antiscience wooisters and denigrate them as if they are irrevocably stupid, then itâs only the crazies and the rhinocerous hides (câest moi ?) who will feel able to mix it up on the Internet. If the objective (and as a pro science, natural sceptic I hope it would be) is to provide effective challenge to the cultification of medicine, then engagement with those who are attracted to the cults is essential â turn it into a war and the vulnerable will run for the protection of the cult bunker.

@ WTF:

I've just been looking in to PACE. I would assume that Hooper's complaint has a lot of nonsense in it (I've read some of his other stuff), but it looks clear that the PACE researchers had classed patients as back to normal, even when they were more ill than was needed to be classed as suffering from severe and disabling fatigue at the start of the trial. The paper I posted earlier has further exaggerated these improvements in arguing for more funding to be spent on psychological treatments.

Do you have a link to that press release? There's some audio from their press conference I've found on the Lancet website, but I'm interested in how they sold it to the media.

Lisa, I suggest you ask:
"Considering the results of the recent Science paper that "current assays do not reproducibly detect XMRV/MLV in blood samples" - including testing done at the WPI, will there be a refund made to those patients that paid for an XMRV test?"

Erv - can you comment on why she would claim antiherpetics for use against XMRV? As far as I know, they're all inactive against HIV or HTLV-1. Why would you bother to claim them against XMRV?

Also, why do think Ampligen is crap? For XMRV, I understand but I thought it's mechanism was intersting/unique and I always thought they should have tried it in combination with antivirals (like ganciclovir in CMV or such) since it induces interferon through the TLRs. Argueably, interferon-beta mechanism of action in MS patients is nothing better than a broad spectrum antiviral and its activity in patients tracks with MxA induction. So IF (and I stress if) CFS was caused by a virus, Ampligen might show some benefit, no? But I readily admit I don't know much about it. I also know that it's run into development problems.

Disclaimer - I don't have CFS and have no horse in the Ampligen race.

@ERV 717
It's the Ruscetti bit that really bugs me. I can kind of see how an inexperienced PI (Mikovits) could get drawn into this sort of exaggeration/fabrication (not that it excuses her behaviour), but why would someone with Ruscetti's record do something so stupid. I assumed he must have been given doped samples that he treated in good faith, apparently not... it beggars belief. Sadly the XMRV scandal is likely to overshadow his contributions to IL-2 and HTLV and that's a real shame.

By Perplexed (not verified) on 07 Oct 2011 #permalink

Not a virologist. Don't feel sorry for Ruscetti. If he was worried about his legacy he should not have participated in such gross miconduct. It will be interesting to see his exact level of involvement.

EvilYeti, when you have spent 10,000 hours researching CFS, or anything get back to us with your "expert" opinion. There are no shortcuts to expertise. You can do 40 hours a week for 5 years, or what most experts (like ERV) have done, 80 hours a week for 2.5 years. That you are unable to tell the difference between me and a crank is due to Dunning Kruger. I will let you google that in case you don't know what it is.

You are right, the âenergyâ that stimulants seem to invoke was already there. But it was already being used for something; that energy was already being used to keep the person alive and to repair the normal wear and tear that simply staying alive causes. Turn off that repair, and all of a sudden you have a burst of âenergyâ. That burst of energy can be useful if you happen to be being chased by a bear. Under that circumstance turning off repair so you can escape from the bear is a good plan. If you don't escape you are dead, so turning off repair could save your life. That is what stimulants do. That is what the extreme fight-or-flight state does.

That is not what CFS patients need. The problem that CFS patients have is that they have been in the equivalent of the fight-or-flight state for too long. Their repair pathways have been down-regulated for so long that there has been a âresetâ of the control systems that regulate those pathways and the state that leads to an acute burst of energy leads to chronic energy insufficiency because the pathways that generate energy (mitochondria in the case of ATP) get tired and wear out and need to be replaced. But it takes ATP for the pathways to repair themselves. If a chronic fight-or-flight state keeps diverting ATP away from repairing those pathways, they continue to deteriorate.

If you had read even a little of the CFS literature, you would know that CFS patients have what is called âexercise intoleranceâ. That isn't just getting tired, it is having your muscles die when you push them too hard. Your body will let you push your muscles until they start to die. That is a âfeatureâ. The reason it is a âfeatureâ, is because if you are running from a bear, it is much better to escape with muscles with infarcted and necrotic spots than to be caught with intact muscles. Sort of like what happens during a heart attack, the heart continues to beat, even as it dies and you end up with a heart with infarcted and necrotic spots. But that is a lot better than ending up with an intact heart that has stopped beating, because then you are dead in a couple minutes.

When the 2009 Science article broke in the WSJ, it got my attention. I had long since given up on the possibility that science or medicine was going to get anywhere with CFS, and stopped following research work on it. In late Oct 2009, Dr. Mikovits she spoke at UOP about her research in a small room with about 30 people in it. I was there. It was recorded, but the WPI blocked it from ever being released, and no transcript was ever issued. She covered a lot of ground in an hour or so, with slides of budding virus and several fairly expansive unpublished claims about her XMRV research.

While the details of her presentation did not precisely fit my understanding of the illness from knowing many patients stories and history, I was quite interested and frankly concerned that I might possibly be infected with a cancer-causing retrovirus. She was quite coherent, and seemed to sincerely believe in what she was talking about.

I was particularly interested in the early efforts for pre-screening of CFS patients using Virochip technology and Random Forest Algorithms that I believe she alludes to here:
http://www.mediplanet.be/nl/node/9160?if=9160&utm_campaign=1108155038&u…

Apparently, the CFS patients that were used in the Science 2009 article were not part of this pre-screening effort. However, I wonder whatever happened to that work, and what the details of it were. Do virologists actually use the Virochip in practice? Someone here should know.

Not wanting to wait to know if I was infected or not, I paid my $650 for testing with VIPdx, and was given a negative result for PCR and culture tests. Although I was promised a free follow-test for XMRV antibodies, I never got that result, and do not care about it anymore. I will never bother to test for anything again unless the test is FDA approved. I have learned my lesson.

This whole episode makes me sad, but I am ready to drop it and just carry on. Lets just say that my previously very low expectations for any possible clarity about CFS have now been seriously reduced.

Regarding the PACE trial.

From here:

But one of the trial participants, a 27-year-old man from Northamptonshire, said the trial had changed his life. "It's like night and day," he said. "I owe so much to the trial, it's unbelievable."

There is nothing deceptive about the physical function scoring - they clearly say in the text that they increased it from 60 to 65 to increase participation. The important point is that the study found that CBT did improve patients' health from baseline (and did so more than the other treatments).

@Levi #728

Apparently, the CFS patients that were used in the Science 2009 article were not part of this pre-screening effort. However, I wonder whatever happened to that work, and what the details of it were. Do virologists actually use the Virochip in practice? Someone here should know.

Don Ganem talked about the ViroChip (a microarray-based platform for the detection of viral nucleic acids) at the American Society for Virology meeting this summer. My impression is that it is still under development, and has been used to test proof-of-principle concepts but has not been widely deployed (if at all) for diagnostic purposes. But as I am not involved with clinics at all, I don't have any information beyond that.

#720 'Annecdotal evidence' - please ! Annecdotally XMRV is a serious infection.

Psychiatry is not science, it uses science sure, and has come to be reliant on truely scientific medical disciplines such a neurochemistry for actual medical validity, but psychiatry is all anecdote. When did anyone ever image the 'super ego' or locate the Id ? Psychiactric medicine is a socially necessary conceit that exists to fill a gap between, on the one hand, the ameliorative effects of adaptive behaviour on otherwise painful emotion experience, and treatable illness, on the other. Talking therapies ( more frequently informed by Psychology than Psychiatric practice) are effective in assisting the development of adaptive behaviours for those whose distress has an emotional base. For all other mental health interventions there is total reliance on neurochemistry or neurosurgery, with Psychiatry effectively being merely society's behavioural compliance police - managers of those whose distress causes them to pose a threat themselves or others -or who just cause upset to the public. Neurochemistry and neurosurgery are scientific disciplines from which definitive diagnoses of ill health may drawn, Psychiatry per se has no such foundation and it is a falsity to present Psychiatry as being competent of describing nosologically consistent illness characteristics. Society needs Psychiatry, but we should not confuse the meeting of that need with the provision of scientific medicine. Psychiatry is social work for socially inconvenient mental distress, it's time to stop treating Psychiatry as though it had equal standing to scientific medicine.

Levi - that is the first time I think I have heard a patient state on this blog that they undertook said 'test'. So thanks for that.

I didn't but could easily have done in the early years I suppose. For me it never added up especially the hype - but more so the actual 'findings'.

Easy to say that now of course though I have been ever since it was published. I was wondering if you are considering a complaint or perhaps even raising the matter when the Science paper is retracted perhaps?

@ WTF re PACE:

It was not changing the criteria for severe and disabling fatigue to a score of 65 that was deceptive, it was telling the press that patients were back to normal following treatments when they scored just 60. In the protocol for the trial a 'positive outcome' required a score of 75, and recovery needed 85. No wonder they wanted to promote their results with anecdotes.

There's now this new paper arguing for more money for CFS to be spent on CBT/GET because PACE showed that 30-40% of patients recovered following treatment - I really have no idea how they've managed to justify those figures to themselves, as even if you somehow decide a score of 60 should count as 'recovered', only 28 and 30% of patients scored that highly after treatment. Whole sections of CFS research seem totally detached from reality, and I'm not surprised this has led to some patients distrusting the news about XMRV.

In Vitro: I agree with much of what you say, but while it isn't perfect, psychiatry is all we have. I know many people suffering from depression who have a very difficult time recovering, even the ones who are open to psychological factors being relevant. The fact that you seem so anti-psychiatry also puts up a red flag for me.

While I don't like anecdotal evidence either, at some point you have to wonder why all these patients are getting better and some recovering completely after CBT and similar treatments. This is a scientific fact (unlike 'XMRV is a serious infection', which is wishful thinking). Occam's razor would suggest that psychiatric causation is the best explanation.

gf1: I couldn't find the paper you mentioned. Of course it would be deceptive to say that CBT results in 30-40% recovering if many of those would have been defined as 'recovered' before the trial! Does the paper actually say that?

I also agree that CBT isn't terribly effective for CFS - even placebos seem to be more effective.

However, based on the evidence it does seem that CBT is moderately effective for CFS, and no matter how you spin the PACE trial it does show an improvement from baseline.

Jack,

I think I have said it here before. I have attended Dr. Mikovits presentations personally on two occasions. I have also followed the XMRV developments over the past couple of years. I could certainly be wrong, but I believe she was trying to help patients. I don't know how this happened, but personally I will let it go.

And typically I am a hard a$$ about such things, as well as being a lawyer myself. Hey, I am not the only sympathizer. One of her fiercest professional critics, Dr. Andrew Lloyd, is saying this:

"I feel bad for Judy [Mikovits]," says Lloyd, who worked with her at the National Cancer Institute in Maryland. "She got trapped by this difficult disorder and the damned XMRV."
http://www.theaustralian.com.au/news/health-science/fatigue-syndrome-ta…

I think that people that have actually met the woman like I have are more likely to cut her some slack. Patients are tougher mentally than many think. We are used to seeing research "trainwrecks", albeit nothing quite this spectacular.

This may be totally irrelevant, and I apologise in advance if it is. I have to admit to not having been able to read every single comment here, as I have severe CFS and difficulty reading.

However, I wanted to add something about Mikovits. I gave blood to her UK study which was looking for the prevalence of XMRV in UK CFS patients. The study hasn't been published, and I have no idea if it has been completed. There is a private forum for study participants, and at one point, Judy sent a message to participants which basically said words to the effect of " don't worry if you test negative -you will still be positive. And every time we get a negative result we will keep re-testing until the result is positive." This study recruited patients on a first-come, first- served basis,
through the Phoenix Rising forum and Facebook. Patients didn't have to provide evidence of a CFS diagnosis, they just had to say they had it.

It was all beyond crazy and the patient group is still waiting for Judy to save them. She made lavish promises in personal emails about providing treatment to the bed bound in the UK, and fierce attacks about the UK scientists who "failed" to find XMRV.

I am of course breaking confidences in that private forum to tell you this, but I am furious about the manipulation of desperate people, the roller coaster of raised hopes and false expectations; the money donated to the WPI, and the tainting of research into the field of an illness which has already attracted so much controversy and caused so much suffering. I consider myself lucky that I at least identified Mikovits as "unusual", unprofessional and a bit of a crank early on, but still upset by this train wreck.

Today I had lunch with Staci Stevens, an exercise physiologist from Stockton University specializing in CFS, so we talked about CBT/GET. She states that CFS patients are different from every single other patient they've ever seen on exercise intolerance.

If you push CFS patients to exercise as hard as possible (which for them is not very hard) for 3 minutes, their measures (e.g. the type reported in her study below) look the same as anybody else's after they exercise as hard as possible.

The difference is that if you bring CFS patients in the next day, and especially if you get them to try to exercise _again_, their numbers all go to hell in a handbasket. It's so dramatic that people not trained in CFS will insist that the machine must be broken. And in some cases, the test causes people to relapse for weeks or months.

I just bring this up to suggest that this disease has a lot of weird crap going on beneath the surface. Some of the symptoms (e.g. fatigue) may look like what normal people, or depressed people, experience -- but if you look at the underlying physiological phenomena, they're very often not the same at all.

*
VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 2010 Feb;19(2):239-44. PMID: 20095909

Following an exercise test, all the normal sedentary controls recovered quickly (within 24-48 hours) while none of the CFS patients did. Symptoms the patients reported after the test included fatigue, light-headedness, muscular/joint pain, cognitive dysfunction, headache, nausea, physical weakness, trembling/instability, insomnia and sore throat/glands.

@WTF: I'd assume that CBT would be shown to be moderately effective for almost any condition where outcomes are measured using questionnaires.

All the uncertainties that surround CFS and how to measure changes in the condition can be tinkered with in ways which alter outcomes, and this makes it very difficult to say what changes are truly meaningful and worth spending limited funding on pursuing.

This is the paper that cited PACE to claim: "Evidence from a recent evidence trial of cognitive behavioural therapy and graded exercise therapy indicated a recovery rate of 30-40% one year after treatment." http://www.biomedcentral.com/content/pdf/1472-6963-11-217.pdf

The PACE protocol, with the initial outcome criteria, is available here: http://www.biomedcentral.com/1471-2377/7/6

Levi

Yes you are of course correct. Having (or developing) a thick skin comes with the territory. Its' just such a hard lesson to learn, and re-learn and learn all over again.

And 'science' comes with that veneer of respectability, add into the mix something like what has happened in terms of propaganda and scaremongering - and who can really blame the patients.

It is those who kept this beast rolling that are to blame not those who have been 'duped'. I mean it could have all worked out. But it is one of those incredibly annoying things - no one will ever prove those who want to believe that a retrovirus is the 'cause' of anything, wrong.

At least never to their complete satisfaction. Just look at what all this has caused in the past week - and the retraction hasn't even happened yet! I see Annette is taking questions on Facebook. Last I looked it wasn't going well. About time the federal agencies got involved with it if you ask me - but there we go...

'Although human gamma retroviral studies have presented many complicated challenges, we feel it is important to continue this line of research for now.'

'Many of you have questions regarding the blood working group. The purpose of this phase of the BWG study was to determine if current assays could reproducibly detect XMRV/MLV in blood samples.

"They concluded that these results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted."

It is important to note that the results reported in the blood working were not based on the testing methods that are used in the clinical laboratory.'

WTF?!

Continued:

'regarding the Lipkin study: We're currently in discussions with Dr. Lipkin and our team of researchers to determine the best way to move forward.'

I bet you are...

'Regarding XMRV testing at VIP Dx. All tests offered by VIP Dx laboratory are clinically validated. '

'We have offered Judy access to any necessary materials she needs to answer the concerns of the journal Science. WPI is not in possession of Judy's notebooks.'

'We're sorry if Judy offered to include you in studies which are already full. However, we'll make announcements on the WPI website when new studies are open for enrollment.'

'The cirumstances regarding the cell lines that were sent to Dr. Lombardi have been misreprensented by Judy. These cell lines were ordered for Dr. Lombardi's research and had nothing to do with the institute's RO1.'

EvilYeti, about Benzedrine making CFS cases feel better:
So, if brain drugs work; this is a brain problem of some sort.

Evidently a lot of normal people are also suffering from Benzedrine-Deficiency Syndrome, because it makes them feel better too.

By herr doktor bimler (not verified) on 07 Oct 2011 #permalink

I've been following this situation closely from a perspective that differs from those I've seen here. I work at a laboratory and went to grad school in microbiology, but at this point I'm in communications. And this is a cautionary tale if I've ever seen one.

With so much emphasis being placed on translational research these days, biomedical lab work is being brought ever closer to the patients themselves. And while I think and hope that this will be a good thing overall--faster progress from bench to bedside, as it were--it does add pressure to the findings of researchers who are used to working in more basic science. And increases the potential for overreaching (to be diplomatic) when making claims for discoveries.

I have no stake in the ME/CFS/XMRV mess, but it seems clear to me that there's no way JM or WPI should have been able to commercialize products and/or work directly with CFS patients on the basis of their Science paper before more due diligence was done. A lot more. I don't know what the regulatory framework would look like, but I foresee more damage of this kind if such practices are allowed to continue.

There are many people suffering from terrible diseases out there. Sadly, it seems that there are also a few researchers who will throw them a lifeline before being certain it really is made of rope, not fluff. And while sharp-eyed folks like ERV (or ONCO or AUTIMM or whoever the watchdogs are for other fields) will catch them at it eventually, more scrutiny and sooner sure seems like a good idea.

gf1: that paper is by completely different authors, so even if it is misrepresenting the PACE trial results it hardly invalidates them!

The fact remains that some patients have completely recovered after undergoing CBT, and the research shows that it is better than other treatment approaches. It beggars belief that patients want to kill off the only treatment that has proven to be effective.

Lisa: you might want to have a look at the PACE trial, which found that CBT and GET significantly reduced exercise intolerance (although they did not actually test it - I believe they simply asked patients if they still had the symptom). Also, you might want to look into overtraining syndrome, which also seems to feature exercise intolerance.

Deb, very sorry for your experiences. Your comment is very relevant. I think a healthy person would have some trouble following this thread in it's entirety. Retesting until one gets the results they want is not a valid way to collect unbiased data. If you are inclined, you may want to ensure that some of this correspondence that you aluded to is preserved. I'm sure that almost everyone reading would be extremely interested in seeing it, but I'm not sure if you would be under any legal constraints (anyone else have an opinion?). I wouldn't want to get you in trouble.

@daedalus2u,
Let me make this clear, I'm ignoring your personal attack out of deference to ERV and a long-standing policy of not interacting with NetKooks in that manner.

Speaking of Dunning-Krueger, you claim that CFS patients are in an excessive "fight or flight" modality. Guess what, we already have a word for this condition. PTSD or panic disorder. See:

http://en.wikipedia.org/wiki/Fight_or_flight_response#Negative_effects_…

I'm completely open to the idea that this could cause fatigue over a long period of time if left untreated. While your ATP theory is interesting, its still unproven and as always the burden of proof is on you. Sorry.

And speaking of delusional disorders...

http://en.wikipedia.org/wiki/Delusions_of_grandeur

Know any "Inventors of Mythic Proportion" that might fit that description?

If you look at the results of the PACE trial, virtually all of the endpoints overlap. In other words the 95% confidence limits overlap or almost overlap.

In clinical trials there are two types of âsignificanceâ, statistical significance and clinical significance. You can have statistical significance without clinical significance.

If you have a diet trial, with 100 people, and all of them lose 0.1 pounds, that can be a âstatistically significant change, if everyone does lose 0.1 pounds, then the mean has changed and the standard deviation is small. That is all you need for âstatistical significanceâ. But a weight change of 0.1 pound is not clinically significant.

If the confidence limits overlap, then the result is not considered âsignificantâ in a statistical sense. If the patients don't come back to quality of life or functionality approaching ânormalâ, then there isn't ârecoveryâ in a clinical sense.

Maybe their can't be ârecoveryâ in a clinical sense yet. Someone with an amputated leg can't ârecoverâ near normal functionality, but that doesn't mean they don't need the best treatment they can get. But the best treatment doesn't result in ârecoveryâ unless the leg has grown back.

It would be disingenuous to compare crutches and a peg leg with a proper prosthesis, find the proper prosthesis is better than crutches or a peg leg and then characterize the proper prosthesis as ârecoveryâ.

What Lisa has said about post exercise malaise is correct. It is a robust finding and you can see it happen on fMRI. You can see increased ATP depletion in the muscles of CFS patients.

âWe have offered Judy access to any necessary materials she needs to answer the concerns of the journal Science. WPI is not in possession of Judyâs notebooks.â

Those two sentences oddly contradict each other. Did they give the notebooks to someone else to investigate, that they are not in possession of them?

that CFS patients are in an excessive "fight or flight" modality. Guess what, we already have a word for this condition. PTSD or panic disorder.

I think you will find that PTSD involves damage to glutamergic pathways in the hippocampus. It's a bit of a design flaw for the brain to use a signal (glutamate) that is actually neurotoxic when overstimulated, but that's Intelligent Design for you.

AFAIK, this is not the case in CFS, so PTSD has nothing to do with daedalus2u's speculation, and there is no reason to bring it up (other than trolling, of course).

By herr doktor bimler (not verified) on 07 Oct 2011 #permalink

Lisa,
Going with the hypothesis of CFS as a phobia of exertion or exercise, the absolutely worst possible thing you could do would be to have patients "exercise as hard as possible".

This is tantamount to torture and a good reason why an "exercise physiologist" has no business treating people with mental health issues. She should be ashamed of herself.

To make a simple analogy, this would be like forcing someone with aquaphobia (a morbid fear of water) to swim laps for a couple minutes. Of course they are going to have a huge regression and freak out even worse when you drag them to a pool the next day.

The right way to treat a phobia is with baby steps. First, talk about water, swimming, pools, bathing etc. Talk about the fear itself and its origins. Then move on to maybe pictures of water, or a short video. Then viewing a body of water from a distance. Then maybe sticking a toe in the shallow end of a pool.

If the patient starts showing a stress response at any point, call it a day.

Interested parties might note that what I've just described is basically CBT/GET.

@WTF:

At the start of the PACE trial, patients needed to have a score of 65 or under in order to be included and classed as suffering from severe and disabling fatigue. In the protocol, a score of 75 indicated a positive outcome, and a score of 85 indicated recover. By the end of the trial, those scoring 60 were classed as back to normal by the PACE trial researchers.

This group was then described as cured and recovered in the resulting coverage of the PACE trial.

As a separate issue, we now have a more recent paper which takes this group, describes them as recovered, and also increases the numbers of patients in this group from 28/30% to 30-40%.

The most recent paper was not by the PACE researchers.

Although Esther Crawley, who played a key role in promoting the more recent study, and her claim that "Treatment is effective, but people are still waiting three years before they access a specialist service" drew my attention ("Hmmm... depends what you mean by 'effective'. A bit misleading without explanation"), has worked closely with them, and had co-authored a response to the BMJ with Peter White, lead author of the PACE trial, in the few months between the publication of PACE and the publication of this new article.

It would not be fair to claim that this more recent paper invalidates the findings of the PACE trial, but they both seem to take a similar approach to truth and honesty, and combine to make particularly inaccurate claims about the efficacy of treatments available for CFS, which, if taken seriously by policy makers, would be likely to lead to a disproportionate amount of the funding being directed towards the provision of those treatments provided by the authors. Indeed, the more recent paper may have been prompted by the realisation that the results from PACE were so poor that it would be difficult to justify paying for CBT/GET for CFS according to conventional methods, so Crawley has been promoting this new 'recovered' rate, and claiming "Our findings are important because they show the long-term cost to society, which must be accounted for in estimates of the cost-effectiveness of ME or CFS interventions and service provision." Esther Crawley is also the chair of the British Association for CFS/ME, a quasi-independent organisation which seems to take the lead in promoting CBT/GET for CFS in the UK.

Nothing invalidates the fact that CBT seems to bring about minor improvements in questionnaire scores from CFS patients, but there does seem to be a serious problem with the honesty of certain researchers associated with promoting CBT/GET for CFS, and so long as that remains the case, I entirely understand why so many patients want to stop money being directed in this direction.

There are positive anecdotes for all sorts of treatments, for all sorts of conditions. A number of those promoting CBT and GET for CFS seem to be taking the same approach to evidence as all the other woosters, and I'm not surprised that this has left many CFS patients feeling unable to trust researchers, even on unrelated matters like XMRV.

Iâm still digging in to PACE, and the complaints that are being made about it. I suspect that there could be more problems to come.

EvilYeti, and your pontificating about CFS and calling it psychogenic when you haven't read the literature is what? I have read the literature. I do know what I am talking about. That you are unable to understand what I have written when I write it out and offer citations to back it up is about you and your deficiencies. So where is your âproofâ that CFS is psychogenic?

I think what offends ERV more than snarky name calling is people who pontificate about science when they don't know jack shit (and who happen to be wrong), and especially when they are trolling and calling people with serious diseases delusional and crazy, just for the lulz. That is what you are doing. You are being a CFS denialist. Denialists are not welcome in science based conversations because they have nothing to contribute, they just add noise. Why don't you listen and learn until you do have something to contribute?

It is not possible for someone to have read the CFS literature fairly (and understood it) and come to the conclusion that CFS is purely psychogenic, purely âin the mindâ, or purely due to mental health stuff. I know because I have read the literature and know that a fair reading of that literature can't result in any other conclusion.

So if my ATP hypothesis is wrong, show me some data that disproves it? The CFS literature does show reduced ATP in the muscle and brains of people with CFS. There is reduced ATP in the PBMCs of CFS patients too. That is why those PBMCs often have bacteria, mycoplasms and viral crap that is not fully cleared.

If you were a real scientist, you would know that no hypothesis is ever âprovenâ. Just a couple of weeks ago there was some data that called into question General and Special Relativity. I happen to think that data has some problems, but all hypotheses are always open to testing with new data.

EvilYeti @682 states:

"In the interest of full disclosure, I should mention I work at a top science (particularly in the health sciences) research institution. While I don't personally do research in this area, I'm a science 'geek' and pay attention to where the grant money is flowing.

And to that effect, CFS/ME aren't even on our radar. Neither is XMRV, which I hadn't even heard of until this post."

Er, Yeti what area DO you actually do research in for UCSF? Maybe there is another Wikipedia reference you can provide that will help. I liked that last one that had a section about "Battle Trance".

Here's a backgrounder that I put together about CFS & Exercise Intolerance, including the PACE trial. It's intended to provide factual material about the topic to journalists, but others may be interested in it as well.

https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B7A3…

It includes a brief overview essay; about three dozen comments from doctors and researchers specializing in the illness; a summary of methodological problems in the PACE study; summaries of about 50 studies on exercise intolerance in CFS; and links to a few media articles.

It's still in development and I've not distributed it very much yet, so it will be interesting to hear comments from people her about it.

I did have a discussion with Staci about the ethics of the exercise challenge test in these patients. It's for diagnostic purposes only, of course. She says people are grateful to her for the diagnosis, "even when they're in bed for six months afterwards." I was a little horrified at that. But apparently people are so desperate to have people believe that their disease is "real" (e.g. not laziness) that they will go through all kinds of torture to get official approval.

Once this center knows that people have CFS, they train them how to control it by having them wear a heart rate monitor all the time. Apparently if the heart rate is kept low all the time, PEM doesn't result. (Unfortunately, in some patients, crawling to the bathroom spikes the heart rate way up and causes a crash.) So they are providing some benefits to people rather than solely torturing them.

daedalus: I'm afraid you're suffering from the same bullshit syndrome that you're accusing EvilYeti of having :)

I've read the CFS literature at least as well as you, and I've come to a different conclusion. Although I don't believe that it is entirely psychogenic, that seems to be a fairly large part of it.

You seem to be under the mistaken illusion - like many of the psychiatry haterz - that the mind and body are somehow separate.

And I don't believe EvilYeti is a troll...his concept of CFS is understandable given the confusing picture we have.

EvilYeti, CFS is not âexercise phobiaâ.

http://www.ncbi.nlm.nih.gov/pubmed/15992572

If you knew the literature, you would know this. You don't know this because you don't know the literature. Those ideas you are having, they are not coming from knowing the literature, from having facts and tying them together with logic. They are coming from Dunning Kruger.

If this was any other condition, I'd assume Evil Yeti was a troll. For CFS, probably not. It's like we've seen the last two decades worth of flawed CFS theories regurgitated in two days.

Peter White based CBT in PACE on a fear/avoidance model of CFS. Prior to the results coming out, he released one of the papers showing that CFS patients don't seem to have an exercise phobia:
http://www.ncbi.nlm.nih.gov/pubmed/15992572

No WTF, I don't think you have read the CFS literature as well as I have.

There is no such thing as "mind", there is only brain. What is called the "mind" is simply an emergent property of that assembly of matter.

"There is no such thing as "mind", there is only brain. What is called the "mind" is simply an emergent property of that assembly of matter."

Please don't let this thread be hijacked by a property dualism versus epiphenomenalism debate.

"Please don't let this thread be hijacked by a property dualism versus epiphenomenalism debate."

But this is our chance to finally settle it!

Especially when we're talking neurotoxins and certain pathogens (like toxoplasmosis), the line between physical and mental is not that distinct.

For instance, if you expose people to a really moldy building for long enough, a high percentage of the population (about 25%) will start to experience depression. Antidepressants or talk therapy might help a bit, at this point. But considering that the people wouldn't have gotten depressed without that toxic exposure, I'm having a hard time saying that the depression they're experiencing is "psychological" in terms of causality, even if it does meet the official criteria of being a "mental" or "emotional" condition.

So what I'd like to see is people taking all diseases seriously and trying to look at a wide range of possibilities about what could be done to fix them. In CFS (see my CFS & Exercise Intolerance paper), no type of psychotherapy and no type of exercise therapy ever has made more than a slight difference (e.g. 10% after 14+ sessions and 52 weeks), even if you put aside the many methodological problems of the studies.

So clearly that's not a solution for this disease. Taking other approaches to look for what might be the solution thus seems appropriate.

And I don't believe EvilYeti is a troll

I liked his initial claim on this thread, that CFS is actually undiagnosed pernicious anemia... a disease noted for being usually fatal if undiagnosed and untreated.

By herr doktor bimler (not verified) on 07 Oct 2011 #permalink

daedalus: I'm pretty sure I've read the literature at least as well as you, but let's not get into a dick contest.

Of course the 'mind' is the sum of all the particles flying around in your head. The issue is whether psychological factors can influence the body - for example the immune system. You seem to believe that it cannot, even though it is a pretty solid scientific fact. You seem to be weaselling around that fact by whining that we don't really understand the mind.

Lisa: I'm not sure where you got your data, but your 'study' contradicts the conclusions of the major reviews on the subject.

Also, if you read those studies on mold/depression you'll see that psychological factors are likely the cause - they talk about 'lack of control' and 'mold related health problems such as wheezing' resulting in the depression. There is no plausible science suggesting that the mold itself directly causes the depression (as you seem to believe).

I think I've taken about as much of this crap as I can handle.

Lisa, this is a nice summary. I like this quote.

âWhere I have real reservations about the trial concern what was not said rather than what they do say and the implications that follow from recommending exercise as treatment for ME/CFS without fully explaining what the results of the study really show. Walking for 6 mins at 2-2.5 mph is something even the very sick patients we see could actually do but this does not mean they are able to take on exercise in the traditional sense. If they were cardiac patients, such results would be interpreted to indicate that they would likely benefit from a heart transplant.â
Christopher Snell, Ph.D.

It is comments like this that lead me to understand that one of the problems is insufficient mitochondria. Mitochondria have a limited lifetime. They need to be replaced when they get tired. What triggers the generation of new mitochondria is nitric oxide.

http://www.ncbi.nlm.nih.gov/pubmed/16825426

If you don't have enough mitochondria, the only thing that will fix that is getting mitochondria. The only way to get more mitochondria is to trigger mitochondria biogenesis. The only way to trigger mitochondria biogenesis is with nitric oxide.

With reference to Deb's comment re how JM dealt with the UK patients:

I've been thinking about JM's MO. Consistently, it's gone something like this:

She would talk to people and be really sympathetic and empathetic and available. The tagline was always, "I just want to make sure you guys are okay."

She would figure out what the hot button issue was for people. In a lot of cases, that was just the possibility of getting well through a pill, but in some cases it was much more specific. For instance, she promised at least one institutionalized patient (who had no hope of ever being rescued by anyone else) that she would get them into the first official ARV trial. For certain people who wanted research into toxic mold (not me, I never interacted with her), she asked a lot of interested questions and asserted, "Once the retrovirus is established, that's something that we're definitely going to look into." And of course, the biggest coup of all was how she convinced the Whittemores that her work would turn into a magic cure for their daughter and create a legacy for them.

So based on these promises, she got people to do all kinds of things for her. Patients put together forums and wrote blogs and organized petitions and donated money and defended her so vehemently that no one could say a word against her. (Apparently the Whittemores joined her in encouraging this.) And the Whittemores (who apparently now are extremely close to bankruptcy) gave her everything they had, even though the original design of the center was supposed to be something unrelated to retrovirology (a "center for excellence" concept).

The interesting thing is that if you look at what she actually did for people, across the board, it was _absolutely nothing_. Just grandiose promises.

This is really screwed up.

But I still wonder what she was getting out of the whole thing. I have to think that somehow it was fixed so that she ended up making a whole lot of money out of the deal, far beyond her official salary. Exactly how this might have worked is unclear to me so far though.

WTF, I am pretty sure you haven't, but fine. There is no mind, there is only the brain and only physiology. Of course the brain and physiology of the brain affects the physiology of the rest of the body. All of physiology is coupled together and control (to some extent) from the top down by the CNS. It has to be that way from a control standpoint.

If you are running from a bear and need every last molecule of ATP to escape, your body will shut off all non-essential systems until you have escaped, been caught, or dropped dead from exhaustion. The detection of a bear chasing you is done by the brain. It is the brain that triggers the fight-or-flight state which will let you run yourself to death. The immune system can consume a lot of ATP and a lot of glucose. If you are running from a bear, you need to shut that off or the bear might catch you.

Normally when your immune system is activated, your body doesn't want you to use up ATP and glucose, so it induces these sickness behaviors, the feelings of fatigue that people get when they are sick.

That fatigue is âonlyâ a feeling, it is a feeling that your body induces so that you don't waste ATP and glucose doing stupid things when you should be resting in bed. But your body will let you âpushâ through that fatigue and pain; feelings of fatigue and pain are signals to your brain that you are exceeding safety limits. The body only has limited capacity to generate glucose and ATP. If that limited capacity is exceeded, cells die and if enough cells die then whole organs die. That is what happens during sepsis, the organs need more ATP than they are able to produce, so they die. If you were in sepsis and had to run from a bear, you could, for a short distance until you dropped dead. Diverting ATP and glucose away from healing and the immune system is why âstressâ causes wounds to heal more slowly and why âstressâ makes people recover from illness more slowly. Physiology is doing triage on resources and allocating them according to the resource priority heuristic built into physiology by evolution. Most of that is from a billion years ago or longer, so you are not going to change it through force of will.

While the âfatigueâ is only a âfeelingâ, the insufficient mitochondrial capacity to produce ATP is not a âfeelingâ, it is a physiological limit that is (in the moment) immutable. You can push yourself to consume the last few molecules of ATP; your physiology will let you do that, but what happens then is that your muscles start to die. That is why people with heart attacks end up with infarcts, pieces of dead tissue in the heart. Usually a heart attack hurts like hell, until the muscle tissue actually dies, and then it can't transmit pain signals any more. The absence of pain during a heart attack is not a sign that things have suddenly become ok, it is a sign that you are at death's door.

Feelings of fatigue are a symptom of CFS. The cause of the fatigue is the lack of sufficient ATP for the muscles to not experience fatigue.

WTF, you do know that the coupling between the brain and the immune system goes both ways? Things that affect the immune system (like histamine reactions in the lungs) also affect the functioning of the brain. Why wouldn't a big immune system activation like an asthma attack cause sickness behaviors just like any other kind of big immune system attack? Most of the sickness behaviors (like feeling sick, weak and fatigued) are there to modify behavior of the organism so they stay within physiological limits. If those limits are degraded (due to immune system activation), why wouldn't physiology signal degraded limits with fatigue and pain?

herr doktor bimler,
I mentioned "pernicious anemia" because that's exactly what I was diagnosed with by my doctor. Maybe he should have specified "non-clinical". Anyways, I'm apparently not dead. And even if you have the clinical version its fairly easy to treat assuming you catch it in time, with the caveat that you will be taking shots or supplements for the rest of your life.

The scientific consensus is there is no consensus, so the jury is officially still out. And assuming the reality is that its primarily a psychogenic disorder that is most likely always going to be the case within our lifetimes, given our primitive understanding of mental health issues.

So, if any of you want to devote your lives to chasing ghosts, be my guest. I prefer to work on real problems. We should consider ourselves lucky that someone like ERV is willing to devote resources to uncover fraud like this.

That said, my personal opinion (which of course I'm entitled too), is that while the symptoms of CFS are unambiguously real, the etiology is not consistent and likely a myriad of sources. Including but not limited to:

Lifestyle
Misdiagnosis
Malingering/Fraud
Mental health issues

Within the mental health area we have all sorts of potential culprits; anxiety/depressive disorders, phobias, schizophrenia, etc. All of which are very real and very serious in and of themselves.

I'm really bothered how some of you are so eager to dismiss a psychogenic etiology as fluff. For some age groups, mental health issues are a top killer.

re:daedalus2u#757

Thanks for the reference!

Turns out I was an optimist, CFS isn't entirely an exercise phobia. Its also a 'work' phobia. Some of these patients are literally terrified of doing anything at all:

"Patients with CFS were more fatigued and sleep disturbed than were the controls and noted greater effort during the exercise test. No statistically significant differences were found in either heart rate or GSR both during a normal day and before, during and after the exercise test. Patients with CFS were more symptomatically anxious at all times, but this did not increase with exercise."

These people should be treated with Xanax, if anything.

Re: Your ATP woo-woo. I'm absolutely certain the ATP process of sedentary, bedridden patients would be different than someone that gets a healthy amount of exercise. Given you think the burden of proof is on me to prove your hypothesis wrong is only more evidence of your ignorance of scientific process and delusions grandeur/persecution.

And what's with the anti-psychiatry stuff? Are there some closet Scientologists here?

Yeti: Serious question. I'm wondering whether you think other diseases for which the cause is not yet known are psychological too. What about autism, Parkinson's, ALS, cancer, Alzheimer's? Or Mad Cow Disease? And if you don't think those are psychological, what makes them different from CFS?

RE this comment:

>Patients with CFS were more fatigued and sleep disturbed than were the controls and noted greater effort during the exercise test. No statistically significant differences were found in either heart rate or GSR both during a normal day and before, during and after the exercise test. Patients with CFS were more symptomatically anxious at all times, but this did not increase with exercise.

That's exactly what I was talking about with Staci today. Indeed, CFS sufferers don't look different on physiological measures during or immediately after exercise. It's on the following day that the differences emerge. And if you get them to exercise on that following day -- that's when the measures really light up.

So a lot of these studies aren't measuring the right things to get an effect.

EvilYeti has GOT TO BE a troll. Seriously, his/her comments are just too perfect!

By Impatient (not verified) on 07 Oct 2011 #permalink

I am left to wonder where folks like CFS expert and champion of those with personality disorders Mr./Ms. Yeti of UCSF,together with the CDC, FDA, or NIH actually where during past CFS trainwrecks such as a decade or so ago when some 300+- desperate CFS and Fibromyalgia patients were put under the knife by surgeons in the USA for "Chiari Malformation", which was treated with major brain surgery:
http://www.masscfids.org/resource-library/9/172

If all CFS patients are most likely to be dealing with psychological problems that they can be talked out of, given some exercise tips, and sent on their merry way, how do you reconcile that? Did you protest to the AMA or other authorities? Why don't the elite medical or scientific journalists write about stuff like that? I would love to see some scientific follow-up studies on those patients.

Hopefully, it was off everyone here's "radar" or they were too young and otherwise occupied instead of being selective about their criticisms about the bad science that has been surrounding CFS for decades.

Lisa,

Like many people you don't seem to appreciate the difference between diseases of the mind, diseases of the brain and diseases of the body.

Autism is a developmental disorder.
Parkinson's is a degenerative disorder.
ALS is a neurodegenerative disease.
Cancer is a malignancy.
Alzheimer's is a form of dementia.
Mad Cow Disease (BSE) is a neurodegenerative disease.
(verified with WikiPedia)

All these diseases present a fairly unambiguous pathology.

CFS does not. As noted in this very thread, even the activists can't agree exactly on what it is. One person says it strikes formally healthy people and then another claims its a "post-viral" disorder. Or that fat people don't get it (???).

Well, which is it? You can't have it both ways. And as mentioned, if you define CFS as anything *not* having an etiology then it essentially becomes meaningless.

Anyways, what you buddy Staci is doing is borderline criminal behavior. She is obviously not a mental health professional or a physical therapist, which is what these people really need.

If you push a convalescent patient too hard they are going to be a wreck the next day. This much is obvious. You can't compare people that don't move to people that do.

If you've had any experience with physical therapy you would know that you start with something simple and work your way up. Like bobbing around in a pool, as mentioned.

As mentioned in the study, if they are suffering from anxiety during exertion this sounds much more like a nervous disorder than anything else. Doesn't make it any less real. But if anyone really wants to get better I would suggest treating it as such.

Something that should be made clear about mental illness, especially those of the narcissistic/depressive specrum; is that it is a very difficult and in some cases impossible to treat. To a large extent because the patients won't accept that they actually have a problem and/or they don't actually want to get better.

Levi,
I'm not at UCSF. Good school, though.

I'm a computer scientist by trade and I consult on various research projects around campus, including bioinformatics research. I'm just pointing out where the grant money is/is not going these days. This current debacle isn't going to help that. Look at what Pons and Fleischmann did to cold fusion research for example; meaning they killed it.

I also don't know how much more clear I can make it that mental illness is a huge problem and very difficult to treat. I'm somewhat more clear why CFS patients are hesitant to admit they may suffer from mental illness given the amount of discrimination in our society, but it doesn't make it any less true.

#710 I certainly wasnât advancing the notion that using oneâs own ill health as a basis to excuse personal responsibility was acceptable and Iâm surprised anyone would have read it that way. The point I made, was that it is unreasonable to expect M.E/CFS patients to be any more scientifically literate than the general population given that: many of us patients are affected with cognitive dysfunction, and that as a patient group we have had precious little in the way of scientific support for understanding of the condition.

The phrase "blaming the victim" is usually used to mean "placing responsibility for avoiding a misfortune on one who suffered the misfortune, who could not have reasonably avoided it."  I never meant to suggest that all M.E/CFS patients who have followed poor scientists like Mikovits fall instead into the category of "people who could have avoided the misfortune in question, by using common sense" - but are there some who do fall into that category, with no reasonable excuse?  Yes, I think so.  (I should mention that I've been reading Deckoff-Jones' blog the last few days, if you're wondering who the "some" might be.)

I'm not saying that M.E/CFS patients should be able to look at a Western blot and say "Why, those elevated levels of isopopopreptin are indicative of subnormal levels of sub-Q enzyme, which completely demolishes the Arcturus hypothesis of supermethylization!"  (You can probably detect that I can just about tell a Western blot fro  a Western omelette and there my expertise in this subject stops.)  What I'm talking about is just sense, like "If ten groups do the same experiment and only one group gets result X, then most probably result X isn't the right answer" and "If group X's 'scientific tests' can only identify samples correctly when they can see what the samples are supposed to be; their scientific tests probably aren't really telling them anything at all."  I'm not saying that everyone should have known from the start that Mikovits was full of manure, but anyone who looks at the evidence and doesn't smell the fish now has no excuse.  And even though one of the side effects of M.E/CFS is cognitive dysfunction, that cognitive dysfunction is not that excuse for the people I'm talking about.  Look at Deckoff-Jones' blog.  If the folks there could put half the effort into thinking critically about Mikovits' work that they've put into devising complicated conspiracy theories to explain away the blatant evidence of wrongdoing, they'd be dropping JM like a week-old mackerel.

By Antaeus Feldspar (not verified) on 07 Oct 2011 #permalink

Posted on Deckoff-Jone's blog -- probably by V99

"ERV is a HIV student. She has no knowledge of gammaretroviruses and how most viruses propagate. These viruses use colonal expansion, not reverse transcriptase. This is why they can none to little sequence diversity. HTLV has been known to not alter over successive generations in families. People need to recognise that this is a highly specialised field, with very few with the knowledge necessary to grasp why there is nothing unique about HGRVs as a potential cause of multiple human diseases. Frank Ruscetti and Judy Mikovits are uniquely placed to be experts in this new field."

Would any of you most knowledgeable scientists care to respond to this utter crap.

It seems it's such a highly specialized field that only Gerwyn and V99, Mikovits and Ruscetti are capable of understanding it.

By Anonymouse (not verified) on 07 Oct 2011 #permalink

EvilYeti @775 states:

"...if you define CFS as anything *not* having an etiology then it essentially becomes meaningless."

Good thinking Yeti. Nothing makes my eyes glaze over quicker than patient debates about the myriad different definitions of ME/CFS/Whatever. Researchers must have a tough time of them. Diagnosis by exclusion is a nightmare process for both patients and clinicians. And very expensive for insurers, etc.

If you go back to the original medical works on ME by Lord Acheson and his Elk in the 1950's, they did not diagnose ME that way. They observed symptoms and used clinical judgement. But then, they were often dealing with epidemics rather than sporadic cases of the illness so diagnosis was probably easier. For reasons unknown, the larger epidemics seem to have disappeared in recent decades.

Anyway, if as you say, a diagnosis of CFS is essentially meaningless, I fail to understand how you can make blanket generalizations about all CFS patient's collective mental state(s). Maybe I am missing your point, and you are merely voicing concern for people afflicted with mental illness in general.

EvilYeti: did your doctor actually measure your b12/MCV/MCHC levels? Or was the diagnosis just based on symptoms and history?

Yup, troll.

If you do a google search on S Stevens, you would find that she is one of the authors of the just published paper titled Myalgic encephalomyelitis: International Consensus Criteria.

Which is pretty good. All of the symptoms can be explained by low NO, even the joint hypermobility. Bone stiffness is determined by NO. When bone is strained, the deformation causes fluid flow in the crevices in the bone, that fluid flow causes shear which activates nitric oxide synthase (just like how shear activates eNOS in the vasculature). The high NO causes bone-cells to deposit bone mineral where the NO level is highest, the place where there is the most strain. If you have a lower basal NO level, then it takes more strain to produce NO at the level that activates the osteoblasts, so the bone-stiffness-setpoint is to a lower stiffness. That is what causes osteoporosis too.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/abs…

She is the founding director of the Fatigue Laboratory.

http://www.pacific.edu/College-of-the-Pacific/Departments-and-Programs/…

Which has a pretty high caliber set of researchers. She also has a bunch of papers listed in PubMed. That might be a good place to do a clinical trial on raising NO levels for people with CFS.

No one is saying that mental health is not important and should not be treated. CFS is not a mental health problem, it is a physiological problem.

Pretty lame troll. You might want to check that the things you call "obvious" are in fact even plausibly correct.

Actually, I'm really impressed at the depth of knowledge that EvilYeti has gained over the past couple of days. He's managed to go to the literature, extract the main arguments of the theories that generally make CFS patients feel upset and frustrated, and summarize them succinctly on this board.

I don't know if this is just a project to annoy people or if it's what he actually thinks, but I do really respect the diligence that has gone into the prep work.

Some people are going to believe what they want to believe, regardless of whether the hypotheses have been discredited. Like, that "our Dr. Judy" really cares about CFS patients and that CFS is caused by XMRV. Or that CFS is caused by exercise and work phobia.

Much better to pick the low-hanging fruit -- change the opinion leaders and then the masses, and the rest of the population will follow.

EvilYeti is reminding me of someone...wait...wait...

oh, I'm thinking of V99!

By Impatient (not verified) on 07 Oct 2011 #permalink

@Levi; see #633

So if I have Munchausen's syndrome and feign the symptoms of CFS; I actually have CFS it up and until someone figures that out. Then the CFS diagnosis goes *poof*.

I'm a scientist and a big fan of the scientific process/method. Unless I'm missing something, the scientific consensus is that CFS is a real syndrome with an unknown etiology and no known biomarker or objective diagnostic test.

I accept this.

If I'm wrong or missing something, even and especially something current, please let me know.

Now, for me personally, the vague and non-specific symptoms are enough for me to suspect this is a psychiatric disorder of some sort. For the "chronic" patients at least.

And that is absolutely not a 'blanket' statement. There are all sorts of psychiatric issues that could express themselves as CFS. Such as:

Major depressive mood disorder
Bipolar disorder
Munchausen's/Malingering
Anxiety disorders
...within which we have phobias, PTSD, panic disorder
Personality disorders (avoidant, narcissism)
Somatoform disorder (hypochondria, pain disorder)

And as someone whom has lost a family member to suicide not to long ago, I'm not particularly keen on how quick CFS activists are to trivialize mental health issues.

Any one of those issues is enough to ruin one's life. Having multiple ones would be a living hell.

Their symptoms are all unambiguously "real", including the physical sensations of pain/fatigue.

What is absolutely not helping matters is the explosion of online patient support groups which are outright rejecting this diagnosis. As I've mentioned, its a Folie à deux on the global scale. Horribly dangerous.

There are even new "Internet" diseases springing up, like the morgellons phenomenon. see:

http://www.morgellons.org/

Otherwise known as "Delusional parasitosis"

http://en.wikipedia.org/wiki/Delusional_parasitosis

(Just don't try and tell them that!)

WTF: I remember having a blood test.

The only medication I take is a proton pump inhibitor, so it made the diagnosis pretty straightforward.

I don't have the greatest diet so the two may be unrelated.

I've taken a proton pump inhibitor daily for years. If I miss even a single dose my (severe) acid reflux returns that day.

Hm... I guess I think I can believe that the Whittemores were fooled too. @717 ERV
Either way, I'm pretty sure they don't understand the science.

At the same time though, they were recently seen on TV talking about some secret magical treatment that brought some patients from wheelchair back to life, including herself.

I'm inclined to agree with IVI that the forums are not too far from a cross-section of society in scientific literacy. I've posted this before, that only about 1% of the population has a college-level science education.

By Smurfette (not verified) on 07 Oct 2011 #permalink

back when I was still reading his/her (who am I kidding, obviously a him) posts (or the replies), EvilYeti was much more entertaining than V99.

Smurfette - I'm not sure having a college education is the issue. In fact I would submit that most of the damage on the forums is done by people who (or a portion of whom) have some level of post secondary science (maybe engineers? they are highly prone to Dunning Kruger IMO). In this situation where it is beginning to become obvious what is basically going on, even without a biology degree (I think... I have one so...maybe not), the deciding factor seems to be metacognition. Those that do it figured out the jig was up last week (or sooner). Those that don't have it are not able to muster the objectivity needed. Whatever education they have (an MD or high school bio 20 years ago) is used to rationalize and provide confidence to their self delusion. In fact the higher education probably just makes their rationalizations more convincing. The critical question in all these things is, can you teach people metacognition? A more proximate question is, how many will, given a bit more time, reach the acceptance (or more likely the pissed the fuck off stage) stage and how many others will become the chosen believers that will defend Dr. Judy until the sun goes out?

mary - I can't speak for CFS patients on the forums but I know that Dr. Montoya at Stanford thinks various herpesviruses may be involved in CFS and that they may not always be detectable in the blood even if they are in CSF.

By Smurfette (not verified) on 07 Oct 2011 #permalink

@ Deb 737

Thanks for telling us about your experience. That 'UK Study' was ever shrouded in secrecy and I noticed that the WPI were apologising - to some extent - for Mikovits' promises in that regard.

I am guessing that you too have found it difficult at times talking about your misgivings. Whilst Forums can never claim to be representative of any 'community' they seem most certainly to have contained far more WPI/Mikovits defenders of the faith than people willing/able to ask questions.

Quite shocking in so many respects. And yet when those who were coerced need the support most - the door has been shut upon them. Disgraceful behaviour. Shame on Mikovits and shame on WPI!

On-line discussions about the nature of 'CFS' are usually pretty pointless as there's unlikely to be any one cause, much of the research is rather poor, and different groups can end up studying different patients anyway. The uncertainty that surrounds the condition and those who suffer from it tends to be used as an excuse for promoting any old pet theory or prejudice.

Generally those who do not suffer from this sort of condition are more drawn towards explanations which place responsibility with the patient: lifestyle, obesity (?), malingering, de-conditioning, fear of activity, failing to accept that they have emotional problems... and it is very often these sorts of theories that end up being imposed upon patients, despite their lack of supporting evidence. Lisa's exaggerated view of the dangers of mould is unlikely to lead to such a self-satisfied feeling of superiority.

Regardless of the cause of disability for those diagnosed with CFS, patients deserve to be treated honestly and fairly. It shouldn't be acceptable to lump them all together, and treat them as if they all suffer from a fear of activity, unless there is good evidence that each individual patient does have a fear of activity (and it seems that almost none of them do). Taking this position does not to stigmatise mental health problems; or require a refusal to accept that any CFS patients could, possibly, have a fear of activity; it just applies the basic levels of respect that we would expect to be applied to any other group of people, to CFS patients.

The uncertainty that surrounds CFS should not be used as an excuse to start making unsupported claims about a group of people which may harmfully promote prejudices and mistreatment.

EvilYeti,

This current debacle isn't going to help that. Look at what Pons and Fleischmann did to cold fusion research for example; meaning they killed it.

Not intending to drag this thread too far off topic, but cold fusion research is still going strong in many places (perhaps not where you are) and it is still promoted through the medium of bad science and bad experimentation. Google Andrea Rossi cold fusion to get some of the latest research containing trivial flaws.

And, importantly, Pons and Fleischmann had no impact whatsoever on the "real" research going on in parallel - the various implementations of "hot" fusion (laser inertial confinement, magnetic confinement etc) have been spending money like it's going out of fashion :^)

I doubt scientists are short of good ideas on what to do next to investigate CFS. As ever the challenge is how to focus those funds where they will do the most good. And that isn't always possible to know without hindsight. *shrugs*

MattK - Yeah, I'm familiar with a couple of those characters you're probably referring to on the PR forums. A few have PhDs in a social science or non-science, and a few have some level of computing background, none of which requires any biology education. I don't think I've actually seen anyone else on the forums with a biology major. And hey, engineers should know that engineering is not science. :) (Most need 1 year of physics.) I wonder if Dunning-Kruger is a chicken/egg kind of thing.

By Smurfette (not verified) on 08 Oct 2011 #permalink

Many in the CFS community seem honestly perplexed at why they should be unhappy with Judy Mikovits.

Would anyone here be willing to summarize it for them, in simple language?

Thanks.

@Deb #737

Thanks for sharing.

I must say this doesn't come as a surprise. For instance, check this comment by a patient:

far as i am concerned, we are all positive. dr. mikovits (bless her heart) told me she is convinced i still have it but its in my tissues. i tested neg on everything - includiing the older antibody test.

Stupid and irresponsible.

WTF- As someone in their early 30s with pernicious anaemia, I can tell you that it is not easy to get a diagnosis. It tends to happen in the over 60s, and a 28 year old woman presenting with inability to move, parasthaesia, fatigue, psychosis, etc is immediately written off as "Oh you've got this thing called fibromyalgia or chronic fatigue syndrome". Luckily I worked in medicine and knew these were diagnoses of exclusion, but it still took five solid years of badgering doctors and demanding further tests to find out what the real problem was.

By the time I got my diagnosis I'd lost the use of my legs to SACD caused by the b12 deficiency. Six months more without treatment would have killed me. To add insult to injury, nobody knows how to treat or maintain PA in non-aged patient groups. You're put on a 12 week injection cycle when really it should be on alternate days until no further improvement can be made.

It's my experience that makes me wonder how many alleged CFS patients have been misdiagnosed but don't realise everything else needs to be ruled out first.

Oh and the real punchline? This has happened to me before, twice. The first time I had a rare neurological disorder and the second time the diagnosis was ultimately Crohns disease. Different doctors every time. They simply believe that young people can't really be ill, and slap them with a dustbin dx.

The princess speaks to the masses as Whittemore Peterson Institute (on Facebook): "I am very disappointed with adults making disparaging remarks about my family and WPI. I understand every one is upset about the loss of Judy none more than me. So please stop attacking me and my family's extremely hard work for the last 22years of living with this disease. You are making judgments. I'm allowed to make a judgment about what I think is appropriate to post here." and "I need to explain something of course it's personal. My family , my friends and suffering patients around the world have built WPI with blood, sweat and tears. My parents have dedicated all of their resources to this institute. Their precious time including their weekends , their holidays. We love every employee that comes into WPI. Support and care for them as though they are family. When my Mom said a divorce she meant it this is painful , sad and extremely disappointing for all of us. Kellen , Annie, Angee, Katie, Debi , Carli, Mike , Marguerite, Vinnie, Max and and many others care so deeply for our friends out there suffering. We kinda do take criticism and angry rants personally. We are so very sorry you are struggling, sad and sick. Our mission is to find successful treatments . If it makes me look impartial by describing who I truly am , where my heart is , or where my dedication lies I apologize. This is my hope, my dreams and my future too. I look to WPI to help my family ,my friends and all of you. Also future generations including someday I hope mine. I am dedicated to this cause for the rest of my life so is my family. These diseases will not win this battle. Neither will egos. We are a team. There is not one person that makes WPI successful it is everyone. I will miss Judy and I have told her so. I send nothing but positive healing thoughts to all of you and Judy." and "Kati business as usual. For example Mom is preparing for new doctors at the clinic, I'm on Facebook and Twitter and answering mail, Annie , Kellen and Angee have already left. Vinnie is in his lab with Svetlana and Marguerite. Statements and Q-A's are being worked on. Lipkin study is being worked out , we are planning our next Walk N Roll and Mom will be working all weekend ;) so will I on speaking to patients with whatever I can answer. We are moving forward on every front. The WPI is open. Vinnie is interim research director. We will keep on keeping on. Although personal attacks have been very challenging. rumor patrol would be nice :)"

That's enough for me. All's forgiven. But I do want to know which branch of translational medicine they are pursuing with the practice of sending "nothing but positive healing thoughts." Wonder if that works for all the same things that antiretrovirals were supposed to cure?

By wanna b ilk (not verified) on 08 Oct 2011 #permalink

Okay, Yeti, now you're talking.

IMO, it's not so much that some diseases are mental and some are physical, and that CFS needs to be in the "physical" camp.

It's that the more that you dig, the more it becomes clear that just about all serious diseases -- regardless of whether they're currently considered "mental" or "physical" -- likely have a physical cause (e.g. pathogens or toxins).

Certainly, schizophrenia has something physically wrong. The idea that somebody would become schizophrenic because their mom didn't love them enough or to get on disability is absurd. Ditto severe manic-depression and other serious mental illnesses. And while genetic susceptibility may have something to do with it, that's not the whole issue either (twin studies suggest).

And that being the case, it seems reasonable to think that people suffering from milder versions of those same conditions also might be affected by underlying physical problems (specific pathogens or toxins). So maybe there is no such thing as "psychological" illness at all, and it's all physical.

Probably that's an exaggeration. Some sorts of depression do seem to be triggered just by psychological factors (such as stress or bereavement). Dissociative Identity Disorder seems (according to those who "believe in" it) to be specifically associated with childhood abuse.

And certainly, as is the case with almost all physical illnesses (like ulcers or herpes simplex outbreaks), it may be that psychological stress can serve as a trigger for the underlying condition.

All that being said, CFS is different than things like schizophrenia and manic-depression because the symptoms are physical as well as emotional/mental.

Unfortunately, the Fukuda case definition allows in really mild CFS sufferers (as well as a few people who likely have other things), while people who are really sick with severe CFS very rarely participate in any research studies. If there were in the literature any studies just on people with the severe form of the illness, it would become much more clear how "physical" this illness really is.

Lisa,
I'm not disagreeing with you. And you should add "poor nutrition" to the list as well.

I'm also of the opinion that most auto-immune diseases are simply a side effect of an inability of the body to properly detoxify itself.

I saw you mentioned autism. There will probably be a 'smoking gun' irrefutably linking the growing autism problem to environmental pollution within the next decade (if not sooner). Particularly due to mercury from coal fired power plants and organophosphate pesticides.

elburto,
Sorry to hear about your health problems. Auto-immune disorders are terrible. I'm lucky enough to have access to world-class healthcare for free, which is why I was diagnosed early.

Makes me wonder how many other life-threatening conditions are "mansplained" as CFS by quacks like MattK?

Good points, @801

I was horrified by some of the theories proposed for schizophrenia e.g, in Abnormal Psych 101. Family tension, lack of love, trips into the innersphere...

It was obvious to me that it was brain damage. This is what people with CFS dont like about psychiatry - its history of mumbo - jumbo psychobabble. It's nothing to do with fear of being labeled with a mental disorder per se. Every person I know with CFS has the deepest empathy with people with mental problems, since they suffer similarly from societal stigma, and unfortunately abuse as well at the hands of professionals. They are no way participating in some kind of 'I not one of those freaks' kind of thing.

Nice to see some real scientists properly addressing these trolls. In response to yet another "Abbie will never find a job with her potty mouth blogging" post at the Nature site, I liked this response:

Abbie, if you are looking for a job you are welcome in my lab. Very astute of you to notice these differences!

2011-10-07 01:37:19 PM Posted by: Theodora Hatziioannou

Yeah, this campaign is working just perfect. Keep it up, gang.

I'm also of the opinion that most auto-immune diseases are simply a side effect of an inability of the body to properly detoxify itself.

o.O

This by itself is a good reason to ignore EvilYeti on all things biological and medical.

Yikes.

Certainly psychiatry is very misunderstood, and even the psychiatrists only have a vague idea about the interactions of genes, behaviour and other factors in causing illnesses such as depression. Psychological factors do seem to have more of an influence on depression than schizophrenia, for example. You can just lump all 'mental illnesses' together. I have family members suffering from both schizophrenia and depression, as well as CFS.

I think a big problem is the misconception that psychological factors cannot cause physical symptoms...Lisa seems to be under this misconception, but I believe that it is a very prevalent idea in today's society, even among many doctors.

nsib, #806, yes exactly. The mercury causes autism idea has wasted much more research $$$ than the XMRV causes CFS idea and has driven many people away from autism and vaccine research. With the "vaccines cause autism meme" the anti-vax hysteria has also caused deaths from preventable diseases.

There is zero data to suggest any connection between autism and mercury, and much data to suggest the absence of a connection.

EY @#803, you sure are doing good trolling. I just looked through the thread and MattK had no comments that could have been interpreted as quackish (in contrast to your many). Trying to misrepresent that you knew something about biology and medicine because you had an association with an institution that did a lot of that kind of research? Huh?

@807 - To what extent psychological factors can cause physical symptoms is the academic battleground that CFS finds itself in at the minute. Its like Nature versus Nuture. Sure its a complex multivariate combination of both. Yet that conclusion is unecessary for say explaining Downs syndrome, and genetics can be ignored in a discussion of the effects of abuse and social deprevation on children.

There are some academics psychologists who emphasise the dominance of psychological factors, others the biology. Illness is a combination of both, you are going to get pretty down if you get cancer, but the psychology is irrelevant when you get a broken leg, and you want it fixed.

Personaly, I think the evidence for psychology - causing physiological problems is actually not that strong, beyond the effects of stress, and bad life events. I think some psychologists would like it to be greater, hence them looking out for other phenomenon, like ulcers (wrong), or M.S (wrong) or maybe C.F.S ? (wrong?!).

@800 So Vincent Lombardi is Research Director then at least for now - figures. I mean who else would?

Perhaps he will confirm that his 'tests' were no different to Knickerfits and that she endorsed them at every opportunity? It seems this is the latest mud-slinging competition to hit the streets.

Personally, the 'test' was never worth the paper it was printed on and certainly not the unsubstantiated claims associated with it.

When will whatever you have in the US by way of legislature step in? Or are these 'tests' excluded because they are allegedly 'experimental'? Bloody daft state of affairs.

Many in the CFS community seem honestly perplexed at why they should be unhappy with Judy Mikovits.
Would anyone here be willing to summarize it for them, in simple language?

Making them unhappy (with Mikovits, or about anything else) is not a high priority for me.

By herr doktor bimler (not verified) on 08 Oct 2011 #permalink

One thing that we should all be able to agree on is that if psychology does have physical effects on someone, those physical effects can only occur through physiology. That is there must be some physiology that psychology is affecting that is then having those physiological effects.

Physical effects don't just *happen*, they only *happen* because there is physiology that causes them to happen (or there is a lack of physiology that prevents them from happening).

There are a great many neuropsychiatric disorders that are made worse by âstressâ, schizophrenia, autism, PTSD, depression, anxiety, OCD, dementia. Presumably there is something about stress physiology that exacerbates the adverse symptoms of those neuropsychiatric disorders. Stress also makes a number of physical disorders worse, cardiovascular disease for example, kidney failure, liver failure. Stress slows down healing.

Presumably there are common pathways between what stress is doing and what is causing/not causing these disorders.

It turns out that *stress* is a low NO state.

http://www.ncbi.nlm.nih.gov/pubmed/12070451

It also turns out that every disorder that has been tested that is known to be made worse by stress is also made worse by other things that lower the NO level.

I was at a talk the other day by Bruce McEwen on the role of stress and neurodevelopment. He really emphasized that the stress response pathways that cause adverse effects are on all the time.

http://newswire.rockefeller.edu/index.php?page=engine&id=1153

That is what they are there for, to differentially regulate neurodevelopment to change the phenotype of the brain to affect how it responds to its environment. There is no threshold, they are on all the time. That is why bullying is so damaging, especially to people who are already vulnerable.

@EvilYeti: CCSVI is currently looking like a bit crock of pseudoscientific waste-of-time shit along the same lines as XMRV. I could of course be wrong, but I would be willing to bet you money that it turns out to be crap. Also I'm slightly skeptical that your diagnosis of pernicious anemia is accurate, as it doesn't seem to have anything to do with

@daedalus: I'm not sure what your point is, or how helpful your theory is even if it is correct. Of course stress involves physiology, that isn't in any doubt. But if stress is causing problems, then it seems that addressing the stress is the most useful way of helping the patient. Your comments seem illogical by saying that stress and CFS are states of low NO, but that CFS isn't caused by stress (if I'm understanding you). Your attitude seems to be "that's just the way the brain works, no use using behavioural treatments as that is just blaming the patient".

daedalus2u,
It is patently offensive for you to paint me as an anti-vaxxer. A troll if fine of course.

Beats a crackpot!

http://math.ucr.edu/home/baez/crackpot.html

Anyway, methlymercury is a known toxin and its negative effects in large doses is well established. See:

http://en.wikipedia.org/wiki/Methylmercury#Human_health_effects

Now, what is not know is what the effects of prolonged exposure to low levels is. Especially to fetuses and children. And, surprise surprise, its been implicated in auto-immune disorders.

Sorry for the derailment but I want to make it clear I'm not an anti-vaxxer.

(That should be "big crock", not "bit crock")

I think its great that for the most part, folks here, including ERV, that could have a legitimate gloatfest are not choosing to pile on the general CFS community. While research on CFS will probably be stalled for a long while because of the XMRV saga, the needs of patients won't go away. The most immediate unmet need is actually not research, it is the lack of available clinicians, and lack of coverage by medical insurers,as well as the minefield of the disability system which often does not recognize the illness as legit.

Clinicians have to put up with even more pushback and hassle from the entrenched scientific/medical orthodoxy than patients get. Treating CFS patients is risky to careers for a number of reasons, and if you are an M.D. and choose to treat them, it is likely to become a full-time pursuit to the exclusion of other simple and perhaps more satisfying types of practice. The key M.D.'s in the field charge huge sums of money, which are always paid outside of insurance plans. Cash up front. Those patients are usually drained of all savings in a relatively short time. They pay because they are desperate.

If you bother to actually delve into the matter, you will find that the psychological approach and psychiatry have not been very helpful to CFS patients over the decades. Research that colors CBT and/or GET as effective typically is often biased and overstates the benefit(s), if they actually do exist. Psychiatry is typically employed to deny patients any medical assistance and/or insurance disability benefits, since diseases without organic basis are often excluded or limited for support of that type. CBT as it is used for treating CFS patients, is merely a process of the "therapist" arguing and browbeating patients into submission about their symptom perceptions until patient finally just shuts up and stops complaining.

Exercise improvements or limitations and/or lifestyle modifications are mastered by most patients intuitively over time. No real need for GET. Many patients have a background in athletics, and actually push themselves too hard with exercise until they get feedback data such as heart rate monitoring and make adjustments.

If any scientist or researcher manages to ever actually make a real major finding that sheds light on the mystery of CFS, that would be great. At this point, I doubt that most patients will be expecting much. I would really like to see stuff like the NO hypothesis explored and researched with adequate funding. If its wrong its wrong, then you start again with another theory. It should not take a complete scientific trainwreck to look at the latest data and evidential support for a theory, change your minds, and move on.

@ 813 - Of course, otherwise you fall into dualism.

B.T.W - is there anything the NO theory cannot accomodate...?

(Just tuggin' - as I work through your complex literature.)

I don't know about this stigma of mental illness. Around here, it is cool to have a therapist, and in some circles uncool to not have one. CFS patients are getting a lot more shit for either not going the psychology route or not believing that it is the main cause and only treatment. It seems to me the stigma is the other way around.

Also, half of California is affiliated with UC.

By Smurfette (not verified) on 08 Oct 2011 #permalink

@WTF: CCSVI may very well be a crock. Or it might not. I definitely wouldn't say its pseudo-scientific. Its gotten some of our scientists interested, at least.

I also wouldn't say that the XMRV->CFS hypothesis was pseudo-scientific. Turns out it didn't stand up scrutiny, which is fine. It becomes a pseudo-scientific crock when the activists refuse to let it go, though.

Maybe a better hypothesis would be a HERV->CFS link, which I kind of hinted at.

Re:Pernicious anemia. Defined thusly:
"Pernicious anemia refers specifically to vitamin B-12 deficiency resulting from a lack of production of IF in the stomach."

I'm not saying I had the full-blown auto-immune disorder (which is fatal if untreated). I just said I had a b-12 deficiency possibly caused from years of using acid blockers.

EvilYeti, look at the Faroe Islands mercury studies and autism studies. Grandjean did a 1000 cohort, consecutive cord blood mercury study, the highest quartile had 40.4 micrograms per liter mercury in cord blood. That is 249 infants had more than 200 nM/L mercury in cord blood. Is that a low dose?

In the 2 year cohort that included those tested for mercury at birth, there were ~1400 children. There were 5 with an ASD, 3 with Aspergers and 2 with autism.

Sorry to call you anti-vax, I apologize. From your whinging about toxins and mercury, I thought you were one of the anti-vax crowd. If you don't want to be lumped in with the anti-vax crowd that whinges about toxins, then don't whinge about toxins.

WTF, CFS is caused by a dysregulation of NO physiology that has shifted the basal NO to a lower level (my hypothesis). Chronic stress for long periods can do this, but it takes a long time and doesn't always. The more usual cause is stress during immune system stimulation. I think that is the major cause of Gulf War Syndrome which I think is indistinguishable from CFS. There was no âinfectionâ, it was the multiple vaccines given in a war zone under very high stress (my hypothesis). If you compel mitochondria to put out ATP while there is immune system activation, you are going to croak them. Croak enough and you will get multiple organ failure and die, croak slightly fewer and you survive but with CFS. That can happen in just a day and is a pretty frequent outcome in people who survive sepsis or ARDS.

David, the more I work on it, the bigger and more complex it becomes, and the more it explains. Not what I expected when I started, but that is where the data is taking me. I am working on a paper which I hope to submit within a month which will explain it all and why physiology is that way ;).

@Deb: thank you for sharing that. Repeating negative tests until you get the "right" answer is about the biggest statistical sin a scientist could commit. I hope you've kept copies of all correspondence about the study.

@Faye "Many in the CFS community seem honestly perplexed at why they should be unhappy with Judy Mikovits.

Would anyone here be willing to summarize it for them, in simple language?"

I'm not a viroligist or any kind of specialist, but the following is my understanding of the core issues that are ringing alarm bells for me: If we trust the labels on the original lab gels as accurately describing the experiment that was actually done, then the experiment was so badly controlled that it couldn't tell you anything at all. This gel has since been presented as the results of two very different experiments. The methods section of the Science paper was missing a crucial step, which would have shown the reviewers that the experimental design was poor and would also have allowed other researchers to properly replicate the experiment. It is likely that if the gel was presented with accurate labels and methods, it would never have been published in a high-ranking journal; millions of dollars of research wouldn't have been wasted on a goose-chase and patients would not have been induced to spend large amounts of money on an unverified test.

I do not know exactly what role Mikovits played in each step of this, but she was the head of the lab and is therefore responsible. On top of all this, she made all kinds of allegations against independent researchers who could not replicate her work and made promises to sick people that outstripped even the mislabelled evidence.

A competent and ethical scientist ensures that the experimental design is adequate to test the hypothesis (i.e. contains proper controls); the methods section includes all the steps you undertook; the results are fairly and accurately presented and that public discussion of the experiment does not go beyond the evidence. Sadly, you can't trust the results from a lab that doesn't stick to these basic rules. I'll leave you to decide whether to trust the work of Mikovits and colleagues.

By Pipsqueak (not verified) on 08 Oct 2011 #permalink

Smurfette,
My initial snarky comments re: CFS were based on my own limited exposure to it, which I admit is not much. I tend to avoid the professionally ill when I can.

I have seen marketing material for drugs to treat fibromyalgia which were just rebranded psychiatric meds (which is fine by me assuming it works).

I've since checked and one of these (Cymbalta) is undergoing phase II/III trials as a treatment for CFS. So apparently the medical establishment is treating this disorder as psychological.

And again, I can't stress enough that this doesn't make the syndrome or its symptoms any less "real" to those suffering from it.

What irks me is the sentiment (echoed here) that somehow a disease being "all in your head" is pejorative. Depression is all in your head, too. So is the grief we feel when a loved one takes their life from mental illness.

A big problem I see with these patient advocacy groups (especially the online communities) is that they have a very vocal population of narcissist depressives. These individuals are almost impossible to treat as they very simply want to be sick. This is why they are so quick to insist that CFS is untreatable; as the manifestation of the disease is integral to their sense of self.

@Levi: CFS clinicians are part of the problem. For the most part they prescribe either unproven or downright kooky treatments on gullible, desperate patients.

It's simply not true that CBT and GET research is all 'biased'. It actually sounds like you know nothing about CBT at all. CBT is never about 'browbeating' if it's done properly.

evilyeti @823 " were based on my own limited exposure to it, which I admit is not much. I tend to avoid the professionally ill when I can."

Well thats the problem. I live in Oxford in the U.K, and have met many people, and every person with CFS I have met have been intelligent high fliers who push themselves everyday to do as much as they can, and understand as much as they can, and are humble self effacing people, ex-academics and proffesional types, all of whome were previously A1 high fliers - and aside from being depressed about thier predicament, are largley free from any psychiatric co-morbidities.

My population survey is biased though isn't it? ...its sampled from white middle class section of an academic city - i.e people I know.

So I can't use my experience to generalise to the whole patient population either, and I am not going to.

But its tempting isnt it - argument via anecdote?

EvilYeti - Cymbalta is not solely a psychological medication. It "is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes)" and "ongoing bone or muscle pain such as lower back pain or osteoarthritis (joint pain or stiffness that may worsen over time)." Do you think diabetic neuropathy and osteoarthritis are all in the head? Serotonin and norepinephrine do not only affect psychology. Also, I don't believe depression is all in the head.

By Smurfette (not verified) on 08 Oct 2011 #permalink

daedalus2u,
There are environmental pollutants that have negative health effects. I actually try and avoid using the term 'toxins' because its been co-opted by ideological axe-grinders. That doesn't mean they don't exist.
As I mentioned, there may be an established causal link between industrial pollution (particularly from coal fired power plants) and autism at some point: See:

http://www.sciencedaily.com/releases/2008/04/080424120953.htm

Smurfette @819,

A fair number of CFS patients in the US have therapists and use them for the appropriate and legitimate problems and issues that are within the scope of those professions. The view that psychologists or psychiatrists are reviled by all CFS patients is a myth. Many patients can't afford a therapist or get to therapy because they are too ill. My point is that psychology/psychiatry is at best only marginally beneficial to CFS patients for helping with CFS.

Some psychiatrists have been very helpful in cases where they realize the CFS patient is not likely to have a classic "mental illness" and needs a complete workup to rule out other possible illnesses that may even be treatable. These M.D.s do the heavy lifting for the exhausting and tedious route of "diagnosis of exclusion". Sometimes they are instrumental in uncovering arcane diseases like pernicious anemia, anti-phospholipid syndrome, atypical MS, sneaky cardiac/vascular problems etc.

In the UK however, most GP's refer the suspected CFS patient directly to to a psychiatrist without much testing or attention from specialists. Those psychiatrists then turn directly to the CBT/GET treatments for CFS patients. This saves a lot of money for the public health system. Any disability benefits are usually limited and are tied to compliance with the program and measured patient "progress".

In the U.K., CFS patients who are "hard cases" get harsh treatment, including being sectioned and incarcerated, forcefully given strong anti-psychotic drugs, and humiliated by hospital staff members. That is probably less than helpful.

Often, the prolific published research for CFS by certain key "psych lobby" psychiatrists with vested interests in CBT/GET therapies is not evidence based, and is completely farcical. It does not meet typical standards for scientific rigor, and usually casts CFS patients in a very poor light. So, many CFS patients protest such publications.

I suspect there are actually a fair number of CFS patients that get a clue about what they are in for in the long haul with the medical orthodoxy, and bypass or escape into a psychiatric diagnosis like Major Depressive Disorder. This allows them to get some disability, get the rest they need, and even have some sort of diagnosis to explain why they can no longer function very well. I don't think you are going to see much research on that.

829 Levi - thats a good summary of the current state of play.

Not sure about people actually consciously escaping into a psychiatric diagnosis, but I am willing to assume it has happened. Right now paradoxically you'd be better off.

WTF @824 states:

"It's simply not true that CBT and GET research is all 'biased'. It actually sounds like you know nothing about CBT at all. CBT is never about 'browbeating' if it's done properly."

WTF,
You are 100% correct if you apply your specific qualifiers to my general statements. Not ALL CBT/GET research is biased, but a lot is published by vested interests.

True,if its done by a SKILLED therapist who is not in a hurry, browbeating is not a part of the therapy. A number of therapists do resort to it though because they are unwilling to gain patient rapport and help a patient tease out and mutually look at negative thought processes carefully.

Probably, most of the observed and statistically significant patient gains in the CBT/CFS arena are attributable to the few most skilled therapists. Sadly, most patients in the UK will never get treatment by those people because impending cost saving measures will force less effective measures such as online CBT:
http://www.online-therapy.com/cbt-online-therapy-cognitive-behavioral-t…

Perhaps there is a silver lining in this cloud. Maybe CFS patients can be gainfully employed as online CBT therapists. Some of them I have met on CFS forums are very persistent debaters that have ground me down to silence on more than one occasion.

However, enough CBT research

EvilYeti, that is a terrible study. There is no credible research associating mercury exposure with autism. There is much research that discredits any association of mercury with autism. Only quacks and scam artists are still pushing the mercury causes autism scam.

Inhaled mercury from power plants is not a significant environmental exposure route for mercury. The major mercury exposure comes from eating fish. Texas is not known for fresh water fish production. The counties that release high mercury levels are also counties with large populations.

If you look at the actual paper, the urban-rural difference dependence was twice the mercury release dependence. There were no actual measurements of mercury. Mercury from a power plant goes up the stack and doesn't come down in the near proximity.

In the 1950's, it was discovered that the teething powders that parents were giving their children were causing what was known as âpink diseaseâ. Pink disease was one of the leading causes of death in children, something like 25% of childhood deaths were caused by pink disease. Over a thousand children died from pink disease. Pink disease was caused by teething powders that contained mercury. Usually it was mercury chloride, HgCl. Usually teething powders contained a grain of calomel, that is 65,000 micrograms of HgCl per dose. Often children were given multiple doses. Many millions of children were given mercury containing teething powders per year before they were taken off the market. The exposures to mercury now are tiny compared to what they were from teething powders in the first half of the 20th century. Where was the autism when mercury exposure was thousands of times higher?

Mercury doesn't cause autism.

EvilYeti - How do you differentiate between butterflies in the stomach and a stomachache?

There are different types of fatigue. Unfortunately, English uses the same word for them. I don't know but I have never met a depressed person who could not actually stand up or hold a cup.

By Smurfette (not verified) on 08 Oct 2011 #permalink

EvilYeti, you are not going to learn the difference between Major Depression and CFS by reading wikipedia. These are things that clinicians spend years learning about. It isn't something that you can just pick up by reading a few articles.

Depression is not the same as being sad. It is not the same as being not happy. It is something that is extremely difficult to explain to someone who has never experienced it. It is a state where you feel so bad and are in such psychic pain that killing yourself to end that pain is a completely rational and logical thing to do. If you can't understand being in that type of mental state, then you can't understand depression. Most people can't understand depression. That is a good thing for them. It is bad for people who actually have depression which is not understood.

A pretty good analogy would be that depression is like feeling sad, the way CFS is like feeling tired.

835 I remember seeing some doco about a majorly depressed patient. After trying to kill himself (for the nth time), they transplanted his organs and brought him around - he was really pissed off!

Can you imagine being that bad - so bad that you wake up being angry that someone saved your life! I was astounded - sometimes we speak about things we know nothing about.

Yeti @830 asks:
"Levi,
Can you explain to me how one would differentiate between major depressive disorder and CFS? See:

http://en.wikipedia.org/wiki/Major_depressive_disorder#Symptoms_and_sig…

Are CFS patients happy and fatigued vs. sad and fatigued? I don't get it."

Yeti,

In a word, no, I can't explain something like that, its way above my pay grade. They are not even mutually exclusive illnesses. At least a subset of CFS patients experience either/and panic attacks/MDD within the first year of illness onset, just like in the case of MS, Parkinsons, or any number of other neurological illnesses. Presumably due to the CNS insult.

MDD eventually self-limits if the patient does not commit suicide. CFS often does not self-limit, and its course is not very predictable. Go read the old ME literature of the 1950's. Ramsay, Acheson at al. for background. Most CFS patients do not have regular thoughts of suicide like MDD patients, although after enough negative life changing events, some wish they were dead on a regular basis.

Physical fatigue is not actually the main problem with many patients,it really varies. Brain fog/mental fatigue/cognitive impairment can wreck your career, even if you manage to show up at work. Symptoms can shift over the years. Long term CFS patients often have heart valve problems, and MRI's often reveal reduced brain volumes. Not the case with MDD.

They are both serious illnesses, although MDD is far more treatable at this point, with some promising new anti-depressants like amitifadine, a triple reuptake inhibitor (TRI) in the pipeline. You asked a good question, sorry I can't really answer it.

The difference between CFS and depression that seems to be accepted amongst everyone who is familiar with the disease (excepting the Wessely School of psychologizers) is that CFS involves exercise intolerance and post-exertional malaise.

For instance, as I mentioned earlier, Staci Stevens described to me how if you do exercise challenge test two days in a row, CFS patients look fairly normal on the first day but totally fall apart on all the physiological measures on the second day.

She states that no one other than the CFS patients do that. NO ONE, regardless of what kind of other illness or level of health they have.

The problem is that some people get sick for a long time after doing that exercise challenge test. So that's a hell of a way to get a diagnosis.

@WTF - PA symptoms are intractable fatigue, cognitive problems, night sweats, symptoms that worsen on exertion, weakness and muscle pain, orthostatic intolerance, clumsiness, fever, palpitations, nausea, weight loss and many other symptoms. These are all symptoms I've heard mentioned by people labelled with CFS and fibromyalgia. Like I said, PA that presents before senescense is more severe and presents differently to the type seen in older people, so is often not diagnosed until a great deal of damage has been done. Despite regular blood tests (because of medication for other conditions) my b12 stores were almost completely depleted and I was roughly six months from death. People still assume my problem is fibro, or CFS, because it's so common in the circles I roll in.

@EvilYeti - I'm British so in theory I have access to free and great healthcare. Sadly many doctors refuse to see overweight women as sufficiently human, even if their weight problem is the result of a misdiagnosed endocrine disorder! My father and brother were diagnosed with cancers so miniscule that they had day surgery, after complaining of fatigue and random
aches. The same doctor let my mother's uterine cancer grow unchecked for two years, and wrote me off as (his exact words) "a spoilt mental case who needs to learn her place" when I complained about the symptoms that indicated my Chiari Malformation and syringomelia.

I'm lucky now to have a doctor who is chronically ill himself, and while this makes his schedule somewhat erratic, it means he has a lot of experience with being fucked about by doctors.

The funny thing is that I paid to see a private rheumatologist this year, and he was the one that said I had chronic fatigue syndrome and recommended homeopathy. I screamed blue bloody murder at him and demanded blood tests, which luckily showed my lack of b12. So I've lived to fight another day, and to wonder how many poor buggers are in the same boat I was.

Smurfette - I had a relative with a depressive disorder who was virtually catatonic. She couldn't do a thing without suffering for days with pain and exhaustion, she complained that even sleeping made her tired. Having her hair brushed made her cry. Ultimately what changed everything was a prescription for an SSRI. Ten days after her dose was titrated up to the maximum she was walking around. Obviously she was weak from years of doing nothing, she had muscle wastage and tired easily for the first couple of years, but she eventually recovered. She was the reason I studied psychology actually, because the whole mind/body interaction that essentially crippled her was something I needed to learn more about. The mind can do some bizarre things, with psych disorders inducing anything from apparent blindness to paralysis.

Congratulations everyone, I'm actually *more* convinced CFS is a mental illness than ever! (tennis clap)

Smurfette,
Cymbalta is a serotoninânorepinephrine reuptake inhibitor, which is classified as an anti-depressant, which in turn is a "psychiatric" medication. Fail.
If CFS patients are too fatigued to stand up or hold a coffee cup, then they are too fatigued to use a computer or participate in a study. Ergo every single reference provided is invalid. Fail.

daedalus2u,
I'm descended from Ashkenazi Jews, so mental illness is in my blood, literally. Both my fathers grandparents and his youngest brother committed suicide. My cousin (his nephew) is schizophrenic. I've suffered from multiple major depressive episodes in my life. I *wish* I didn't understand it as well I do and would not wish it on anyone.

Fail.

And I provide references from WikiPedia as they are:

a. Convenient and appropriate for amateurs like yourself.
b. You don't have access to the journals I do.

Fail 2X.

Levi,
If you can't provide a clear and unambiguous criteria for differentiating CFS from MDD and patients respond positively to the same treatment and medication, then they are the same thing. Fail.

Lisa,
Unless you are comparing invalids to other invalids, your experiments are meaningless. Fail.

I've given you folks the benefit of the doubt, but I still see no evidence that it is anything other than...

A. A misdiagnosed medical condition. Like pernicious anemia.

B. A misdiagnosed mental health issue. Probably either MDD or a nervous/anxiety disorder.

My personal opinion is that its a narcissistic depressive disorder, which would explain the reluctance to accept a psychiatric diagnosis as well as the lack of suicidal ideation. Narcissists as a rule don't think anything is wrong with them (mentally) and think they are too important to kill themselves.

Anyways, I think I've given myself chronic fatigue fatigue at this point and will retire from this discussion.

EvilYeti - Yes, Cymbalta is also a psychiatric medication but not only. You cannot however deduce that if Cymbalta improves a condition, then that condition is psychological, as you tried. And sorry, but a cup of liquid weighs more than the absence of a cup of liquid. And yes, many CFS patients are too ill to participate in studies.

By Smurfette (not verified) on 08 Oct 2011 #permalink

Yeti: It IS invalids to invalids.

Staci's tests look at all kinds of people -- those in congestive heart failure, end-stage cancer patients, etc. etc. The CFS patients are the ONLY ones who have their measures fall apart on the second day. Other kinds of patients may start out low on day 1, but they don't have a huge drop on day 2.

The level of disability of CFS patients is a variety of levels, from mild to severe. And their measures on the day 1 testing reflects that, with the severely affected patients doing worse.

But ALL the CFS patients, even those mildly affected, have all their measures fall apart on Day 2. And nobody else, however sick they are, ever does. So that's why "post-exertional malaise" is considered definitional for the disease.

elburto - Thanks for sharing your description of nearly catatonic depression. I actually know a few people who have had severe depression, enough to be hospitalized, or virtually paralyzed in bed for days. Their fatigue and exhaustion still seems different to me though it's hard to describe. I have had mild depression once before. While emotionally exhausting and sleep-exhausting which do feel like a sort of physical exhaustion, I don't recall it being physically as in muscularly exhausting. Personally, I went running when I was depressed and that worked for me.

By Smurfette (not verified) on 08 Oct 2011 #permalink

@ 825 Lisa - just the beginning I think - though isn't it wonderful to see so MANY supporters revealed and in their true colours too ;)

The 'debate' seems to now be more on here about 'CFS is it mental is it physical?' Always bores me I am afraid and yet it always happens.

Personally, I couldn't give a fig how you classify it. In the UK CFS/ME is a long term neurological condition with unknown cause as defined by the Dept of Health. Though there is talk (has been for a long time) about merging neurology with psychiatry again - who cares?

On average I have a psych-evaluation every year. There has never been anything diagnosed other than associated depression which generally occurs in my case upon relapse and I think this is pretty understandable.

Conventional anti-depressants do not overcome the primary diagnosis and never have done in the decade I have been so diagnosed. Relapses for me are triggered by a viral infection and it was a virus that set me off on this course in the first place.

Sometimes I shake off subsequent viral infections and sometimes I don't. 'It' is a chronic illness. You learn to live with it. Though relapses are hard to handle. I didn't self-diagnose I was afforded this diagnoses and whatever they suggest by means of help - I dutifully try.

Couldn't care less if these greater 'brains' want to fight and claim sovereignty of my condition. Just would like more help please and help that is more effective than that presently on offer. And preferably help that doesn't involve any snake oil.

Ta very muchly :)

Here's one back on topic ;)

We mentioned Dr Snyderman before I think. Question: how does one determine that his use of ARVs have anything to do with him feeling better with regard to his CFS?

'âThere is no plausible explanation for my results other than that treatment of a retrovirus improved my leukemia and my CFS. There is nothing about my clinical picture to say this is an unusual phenomenon.â'

http://trialx.com/curetalk/2011/10/micheal-snyderman-xmrv-positive-judy…

And I provide references from WikiPedia as they are:
a. Convenient and appropriate for amateurs like yourself.
b. You don't have access to the journals I do.

This is the kind of genuine pride-in-worksmanship trollery I like to see. It's what distinguishes artisanal handmade trolling from the off-the-shelf generic variety.

By herr doktor bimler (not verified) on 09 Oct 2011 #permalink

With all due respect to Dr Snyderman, he has chronic lymphocyte leukemia, not CFS. Good for him that antiretrovirals seem to be helping his CLL and that his fatigue from his CLL has gotten better.

For people with CLL, maybe antiretrovirals are a reasonable experimental procedure. Maybe there is an unknown virus that is causing his CLL as several researchers seem to think. Good that it is being studied. Maybe something will be learned about CLL.

CFS patients don't have CLL. Fatigue is a generic symptom. Just about every disorder has the symptom of fatigue. Liver failure has the symptom of fatigue. Primary biliary cirrhosis has symptoms that are indistinguishable from CFS. Treating people with liver failure with antiretrovirals would just kill them faster.

@lisa: from what I have seen, post-exertional malaise in CFS is not that simple. Sometimes patients are tired the next day, sometimes it takes a few days, and sometimes they go through periods where it doesn't happen at all. Also, as I mentioned before, post-exertional malaise happens in overtraining syndrome, which seems to be similar to CFS.

I think the mental/physical thing is unhelpful and is just polarising patients and researchers. From what I can see, CFS seems to be a stress illness - similar to PTSD, but not the same - that seems to mainly affect over-achievers. It is a neurological disorder in that the brain structure is likely changed (in the same way it is with PTSD). But behavioural and rehabilitative treatments like CBT/GET are likely to be helpful.

Even in disorders such as autism (which is probably not caused by stress or any other psychological/behavioural factors), behavioural treatments are helpful. The same is true for schizophrenia I believe. This shouldn't be much of a surprise because the brain is quite plastic and can be changed through behaviour. I refer you to this page:

http://en.wikipedia.org/wiki/Neuroplasticity

@ 840 "My personal opinion is that its a narcissistic depressive disorder, which would explain the reluctance to accept a psychiatric diagnosis as well as the lack of suicidal ideation."

Ok, my personal opinion is that its, ummm, err, lets see, off the top of my head, err, a sublimation of the super-ego into a trans-idealisational state of 'ego metamorphosis', were the Id transfers fears of illness state anxiety into a fixated transference of implied causality as divorced from the reality of self-perpetuance by a mother fixated nuerosis, induced by an anal phase developmental, premature nipple-withdrawal.

Test that!

Above someone said that only Wessely thinks that CFS is a manifestation of depression, and that's rather unfair on Wessely, as he let go of that theory over a decade ago because of HPA research showing opposite results for the two, although his abandoned theories are still affecting the way that CFS patients are treated.

If CFS is stress related, I expect that being treated as if you are depressed when you are not is going to be rather stressful. Behavioural therapies can be helpful for all sorts of illnesses - but they can be quackery as well. The clearly misleading claims made about CBT/GET are getting many patients rather irate, but that none of those claiming to take a psychiatric approach to CFS seem concerned. They seem more interested in making money out of this condition than treating patients fairly.

While we're chucking random made-up theories about, maybe CFS is what happens when someone has any type of fatigue problem, gets sucked in to the nonsense that surrounds CFS, and ends up permanently stressed and exhausted because their anger at it? While I'd be amazed if that were true, the state of CFS research needs to be cleaned up anyway, and funding for those making these misleading claims stopped. Hopefully XMRV will bring some attention to the topic, and lowers the tolerance for quackery in CFS.

@gf1: stress and depression are highly related...stress tends to cause depression. A majority of CFS patients list depression and anxiety as symptoms. And yes, many patients do seem to stress themselves out with their hate for CBT and the like. It seems reasonable to assume that that could be a perpetuating factor.

And please stop throwing around ignorant bullshit like "They seem more interested in making money out of this condition than treating patients fairly."

@ WTF: Given that Esther Crawley has just released a paper which claimed PACE showed that 30-40% of patients recovered with CBT/GET (a claim you said it would be fair to describe as deceptive), has been claiming that this paper is important for assessing the cost effectiveness of the treatments she is promoting, and she is the chair of BACME, it seems entirely fair to point out that she has a financial incentive for misrepresenting the efficacy of the treatments she is being paid to provide. Those involved with psychiatry are just as likely to be swayed by self-interest as anyone else.

If CBT/GET for CFS were promoted in a more honest way, I expect that this would cause rather less stress and anger amongst patients. That none of the psychological researchers involved with CFS seem to recognise this is rather worrying.

Agreed gf1, there is a definate 'take your medicine' attitude with these people. And if its not for you, or you are quite happy with your own pacing, or have a carer that can cope its quite frankly a pain in the arse having to stick to these regiments and sit in on these quite frankly patronising sessions.

There is a bogus quack element to CBT, as with all therapies, and this, plus the patronising 'do this or stay ill ' attitude is just a bit much for smart people sometimes to be honest - especially when it is carried out by snarky people who dont believe you are really ill anyway.

@gf1: if you check my comment I never said it was dishonest. I said it was dishonest if the facts you gave were correct (which I haven't checked). Even if you don't believe the conclusions and analysis of the PACE trial, you can see from the results that it is effective.

@david: I'm not sure who you are talking about. Simon Wessely, for example, has stated many times that patients do have a real illness with real symptoms. It just seems to be patients who are spouting this "not really ill" meme (which is ironic).

In fact, it is patients themselves who are inviting derision from people like EvilYeti, by having these screwed up, angry, anti-science notions about psychiatry and the like. However it is only a minority of patients who have these beliefs - in my experience the majority of patients are happy to consider psychological factors in their illness, and they seem to be more likely to recover (yes, more anecdotal evidence FWIW).

WTF, some people dont need psychologists. Simple as that. Its not some anti-science notion of psychiatry, or some meme.

Some people just dont need or want CBT, the same way some Cancer patients dont need or want it. They are psychiatrically A1, they dont need someone else telling them what to do each day, pacing or GET or whatever for them - they can do it themselves. They just want the fatigue and pain stopped.

@ WTF: Maybe you should take the time to check the facts before you make any further comments, or try to accuse anyone else of ignorance? John's post here was a good starting point.

You need to use a rather limp definition of 'effective' to apply it so baldly to any of the therapies assessed by PACE. If we were to assume, as above, that the dishonest way in which CBT/GET has been promoted may be a perpetuating factor for CFS, and that there is some opportunity cost to their research and provision, then it seems quite likely that they've done more harm than good (for patients anyway).

It's entirely possible that psychological/behavioural interventions are a sensible priority for CFS research. If that's the case, funding should only be provided to those researchers who realise the importance of communicating honestly with the media and their patients, and speak up against those who fail to do so. The tolerance of quackery for CFS, and break down of trust it has led to, needs to be stopped. That misleading claims seem so much more acceptable in psychology than virology could explain why so many patients do not want to be placed under the care of psychologists.

To anyone interested, I have a more extensive write-up of the role of NO in CFS from the standpoint of the fatigue compensatory pathways. My hypothesis of CFS is that it is not so much something causing more fatigue, but rather the lack of the fatigue compensatory pathways to compensate for what ever caused the fatigue in the first place. If physiology doesn't compensate for fatigue, then you will always be fatigued.

If you send me an email at the email address at my company website, nitroceutic dot com, I will send you the CFS writeup. This is much more extensive than the blog post on NO and CFS that I have and is the background to a proposal that was never funded (even though it got high marks).

I can't resist, the derp is too strong...

re:blaming the patient.

The customer isn't always right. Same goes for the patient. For somatoform disorders, the patient is not only never right, they will often actively fight against being treated. Sound familiar?

There has been controversy raging for decades from patient advocacy groups fighting to classify obesity as a disability. The standard claim being that obesity is a disease and not a consequence of lifestyle.

The government has literally spent millions investigating these claims. And guess what, 100% of the test subjects were eating 2-3 times what they should (at least) and leading entirely sedentary lifestyles. There were literally no counter-examples.

And you know what? The patients *still* wouldn't accept it. Or would post-hoc rationalize it by saying they might as well overeat because they were going to get fat anyway.

I'm not making this up. So my question to you is, at what point do we stop listening to patients and start listening to science? How many millions/billions should we spend before we give up?

You absolutely cannot trust these patient advocacy groups or their collective self-diagnosis/delusion. Not only can you not trust them, but they are almost guaranteed to be wrong.

It gets worse when you are dealing with the narcissistic-depressive types because they literally *want* to be sick. They are professionally ill. Having CFS is their job. I'm not surprised these people are impossible to treat.

So what you are saying EvilYeti, is that my spouse that I have cared for, for 20+ years, is having me on.

They want me to suffer as well, and I am a big sap for falling for it.

Should I ask to get them sectioned? I'm pretty annoyed by that, but feel better that you have blown the dust from my brain.

I'm mad though. Wait till I confront that narcissistic little....

@daedalus2u,
Since you want to throw stones, I got another WikiPedia link for you:

http://en.wikipedia.org/wiki/Crank_%28person%29#Common_characteristics_…

...virtually universal characteristics of cranks include:

1. Cranks overestimate their own knowledge and ability, and underestimate that of acknowledged experts.

2. Cranks insist that their alleged discoveries are urgently important.

3. Cranks rarely, if ever, acknowledge any error, no matter how trivial.

4. Cranks love to talk about their own beliefs, often in inappropriate social situations, but they tend to be bad listeners, and often appear to be uninterested in anyone else's experience or opinions.

You are 4 for 4 dude.

Anyways, I wanted to comment on your claim that I have to 'study the literature' to understand CFS, or at the very least, understand the scientific consensus.

I'm not qualified to read the (non-psychiatric) lit. on CFS. I'm not a researcher in the health sciences. Neither are you, obviously. And it doesn't matter.

The point of the peer-review process and the building of consensus is so that the experts can pool their resources, check each others work, check it again and arrive at a conclusion that the rest of us can have a high degree of confidence in.

As a rule, I go with the consensus and have yet to be disappointed. Of course, historically the consensus does change over time. And I'll change my view right along with it when that happens.

So this is the consensus is it?...

"It gets worse when you are dealing with the narcissistic-depressive types because they literally *want* to be sick. They are professionally ill. Having CFS is their job. I'm not surprised these people are impossible to treat."

You have not addressed my point, should I call my spouses bluff? Seriously, she's taken me for a ride. I dont know what to do...call a shrink?

David,
Did you miss the dozen or so times I've stated that:

1. Mental illness is as real as any illness, as are the ensuing symptoms of fatigue and pain.
2. Our collective understanding of the diagnoses and treatment of mental illness is still in the Dark Ages.
3. There is bigotry and discrimination against the mentally ill at all levels of our society, including and especially within patient advocacy groups that are themselves victims.

By fighting a psychiatric diagnoses for a problem that is psychiatric in nature, you are only hurting the patients. We need to accept what this actually is before the scientists can develop drugs and therapies to treat it. It's 2011 and we are only just getting drugs in the pipeline to treat CFS.

Btw, narcissism is a personality disorder. When it shares a co-morbidity with depression is when you run into trouble. I should probably clarify that its only the most vocal activists that exhibit narcissistic traits. As WTF suggests, this is probably a minority of the patients.

Off-topic, but if want a textbook example of narcissism, look at Rebecca Watson. The red flag of NPD is an inability to handle criticism while simultaneously finding fault in others.

Yeah, OK, thanks.

For all you know I could be a retired Neuropsychologist.

But you have somehow completed the circle and brought it back round to Rebecca Watson, so I'm outta here.

Some good posts, enjoyed the whole XMRV post mortem.

A bit of Scientific history.

Bye.

( 863 oh and it would be by Proxy wouldn't it, I never said I was ill)

Yeti,

Gut Yontif. No disrespect is meant, and only if this applies to you, hoping that your fast was an easy one.

WTF - Would you like to cite the research that supports your overachiever hypothesis? I believe the current consensus is that CFS risk is the same across all classes. Although overachiever and class are not the same, that is the data we have. When I look at the CFS forums, it really doesn't strike me as overachievers....

I think it's possible that CFS is more visible in overachievers when you consider the fact that among certain demographics, the average TV watching time is upwards of 8 hours per day.

The overtraining syndrome is interesting too. It does sound similar although from what I have read, it seems to be less severe and more self-limiting.

By Smurfette (not verified) on 09 Oct 2011 #permalink

@perplex, #725

JM is everything but not an inexperienced PI. She worked long time with Frank Ruscetti in the lab, and even inexperienced researchers should know how to behave in a scientific controversy.

However, it was also possible for Frank Ruscetti to change his mind aböut XMRV, like Coffin or even Silverman did - but he did not.

Again, even somebody how did indisputable brilliant work in the past should accept that in science being work is quite possible and can happen to evreyone, like ERV repeatedly pointed out.

Look at Robin Weiss, how they dealt with the "Discovery of a new human retrovirus" (Voisset C, Weiss RA, Griffiths DJ, Human RNA "rumor" viruses: the search for novel human retroviruses in chronic disease).

That's a very good example how science should happen. XMRV and JM is not.

Just a quick point on the Dr Snyderman, chronic lymphocyte leukemia (CLL) issue. I have worked in CLL research in the past. It is, for the most part, a rather indolent disease. A lot of CLL patients don't tend to require any drug intervention (apart from treatment of opportunistic infections) and those that do tend to take something like fludarabine or a monoclonal antibody, alemtuzumab, that binds to the marker CD52, present in mature lymphocytes but not stem cells.
I noticed that Dr Snyderman is Zap70 positive. This means he expresses a protein, Zap70, that is present in the more aggressive subgroup of CLL. This subgroup generally is treated more actively as their disease tends to progress much quicker than Zap70 negative cases. Interestingly treatments such as alemtuzumab have a side effect of reactivating certain viruses that may be present in the patients lymphocytes (such as cytomegalovirus). It is plausible that a general antiviral treatment might have an indirect effect of suppressing this side effect of CLL treatment rather and I think this is a better explanation than a gamma retroviral cause of CLL.
By the way the etiology of CLL is unknown but it's distribution is very different to CFS. Most CLL sufferers are elderly males (CLL, the most common leukemia in the western world, is almost unknown in people below the age of 55)

@ David - you're chatting with someone claiming to be following the scientific consensus - who is also saying that CFS is a narcissistic depressive disorder (which aint even a fringe theory as far as I'm aware). It's not worth your time. This sort of trolling should just be ignored... 'CFS patients don't want to get better, if you're trying to help care for them you might just be trying to adopt the sick role by proxy, they're professionally sick and can't be trusted... what? If that seems unreasonable, then you're stigmatising mental health issues. That is so insulting.'

@ 868 Camaro - thanks for reminding me of that paper it looks quite interesting and have downloaded and added to the pile ;)

@ 869 Sigmund - interesting I had not heard that before. Though for some the 'excitement' I guess stems from 'XMRV' being discovered in cancer tumours ergo all cancers carry 'XMRV' Dada!

Actually there seems just as much reason to say retroviruses are responsible for all disease and are carried by all humans ;)

Do you think they will revisit those prostate cancer discoveries in light of the contamination issues or is it separate and protected from the CFS association contamination?

@Jack

You may want to go for the short version:

A cautionary tale of virus and disease

RA Weiss

PMID: 20920148

... already at this time there was enough to think about and bring the pro-XMRV/CFS people back to the lab to verify their own data.

@ 869 Sigmund, that is interesting about CLL. Prostate cancer is often pretty indolent too. Chronic inflammation also occurs in prostate cancer. Is it possible that the inflammation is reactivating ERVs and they are an effect and not a cause?

This is pure speculation, but might demethylation of DNA in the case of inflammation be a âfeatureâ? If there is an infection, what better way to try and fix it than to dredge through the genome and randomly reactivate little bits of things that were once viruses, get them to express as proteins and âvaccinateâ the host with these bits?

Autoimmune sensitization is characteristic of some chronic inflammatory diseases, and usually is not the earliest symptom (i.e. it looks like an effect and not a cause), like antinuclear antibodies in primary biliary cirrhosis.

v99 posted this on behalf of Gerwyn (Gerwyn flounced the forum and is now using his toady V99 to post his garbage). Can people comment on this post.

"With silvermans retraction the people running the 00 studies have huge problems.

The VP-62 sequence is now known not to correspond to the gammaretroviruses detected by Lombardi et al. It is also known that Silvermans primers are capable of detecting the VP-62 plasmid but NOT capable of detecting the gammaretroviruses which exist in the Lombardi CFS patients. The WPI and NCI tried to use Silvermans primers on the patients who tested positive for their nested PCRs but could detect nothing. A great number of studies used Silvermans primers alone or in combination and thus their negative findings are invalid.

The slide being so viciously attacked demonstrates that the viruses are normally in a latent state, which is maintained by methylation of the provirus.

Remove the methyl groups as shown by the experiment in the slide and the virus becomes active.

So what! everyone says.

Well, the virus or viruses are integrated into G-C rich areas called CpG islands. These are extremely difficult if not impossible to amplify using standard PCR approaches.

Any PCR which has been adjusted to detect the VP-62 clone in a spiked sample would not have a prayer of detecting a human MLV-related gammaretrovirus integrated into such a region even if the virus did have the same sequence as VP-62, which they do not.

Thus, the combination of Silvermans retraction and the discovery that demethylation can activate the virus or viruses in question completely invalidates ALL the negative 00 studies.

The enemy must get Lombardi retracted at all costs before the scientific community as a whole realize that.

permission to repost granted
« Last Edit: Today at 11:52:20 AM by V99 »"

By Anonymouse (not verified) on 10 Oct 2011 #permalink

Anon--

All things are possible if you have no idea what you are talking about, and Gerrrrwwwyyyn/V99 have no idea what they are talking about.

*shrug*

I mean, that is like a generic Creationist comment-- they have *wrong* down to an art. For every two lines of stupidity they pump out, it takes two hours for a scientist to correct it.

If you want a real response to that, I will have to give it its own post. If you are just curious as to what I think about it, thats easy: There is nothing remotely cognizant in that comment, much less anything scientifically accurate. Its a word-salad of scientific terms.

Someone needs to explain to v99 that not mentioning the supposedly all-important demethylation also completely invalidates Lombardi.

Like ERV said, you can answer to this with just *rolf* or you have to teach basic molecular biology for 2h.

My only short repsonse to these kind of PCR blabla is the following: Lombardi et designed their PCR using only VP62 sequences.

{...}it takes two hours for a scientist to correct it.

I liked how Racaniello recently answered another word-salad from the froums:

Your comments should be deleted because they don't contain a shred of truth.[...] However I'm leaving the comment here so that others can see the misinformation that pervades discussion of CFS.

http://www.twiv.tv/2011/10/02/twiv-151-dear-twivers/#comment-325127347

Smurfette,
If you go with the 'overachiever' hypothesis this might be related to "burnout"

http://en.wikipedia.org/wiki/Burnout_%28psychology%29

Assuming a psychiatric etiology, as mentioned I'm sure there will be lots of co-morbidity. Depression, stress and anxiety are best buddies.

And again, I don't know why you are so quick to trivialize NPD or depression. You need to understand narcissism before you have even a small chance of treating it (which is very difficult).

Anyways, I'm thinking a better course of treatment for CFS would be CBT + GET + meds. Of course, trying to figure what the right meds are is going to be challenge. And it may turn out the meds need to be 'tuned' based on what the individual is experiencing. Right now we are basically doing the "throw spaghetti at the wall" thing.

The biggest laugh though is the inference that because some details were 'missing' - all the no find 'replication' attempts are invalid - and this fact must be quickly covered up before it gets out.

ERV -- yes I would like some sort of real response to the "gerwyn/v99" post as it has been posted on all sorts of forums and blogs and people believe this crap, they don't question that the two idiots are just wrong.

By Anonymouse (not verified) on 10 Oct 2011 #permalink

Oh gosh, I can give it a quick shot!
"Well, the virus or viruses are integrated into G-C rich areas called CpG islands. These are extremely difficult if not impossible to amplify using standard PCR approaches.Any PCR which has been adjusted to detect the VP-62 clone in a spiked sample would not have a prayer of detecting a human MLV-related gammaretrovirus integrated into such a region even if the virus did have the same sequence as VP-62, which they do not."

EXCEPT!!!!!! You aren't designing your PCR primers to amplify the CpG repeats. You are designing them to amplify the sequences within the viral genome itself, which does not consist of a bunch of CpG islands.

V99 is an idiot with no knowledge of biology who appeals to the authority of another idiot with no knowledge of biology. It's a classic example of the blind leading the blind.

By Poodle Stomper (not verified) on 10 Oct 2011 #permalink

To go along with the above post, one should note that a lot of genes are located right by a bunch of CpG repeats. It's one of the ways our cells use to shut them when they aren't needed. Yet, we can amplify the genes themselves very easily. I can find a specific example if you'd like =)

By Poodle Stomper (not verified) on 10 Oct 2011 #permalink

EvilYeti,
I suggest Cleare et al 1995 for your edification. Depression and CFS are physiologically different. Prolactin is high in CFS and low in depression in response to serotonin and cortisol is low in CFS and high in depression. CFS patients respond differently than depressed patients to dexamethasone suppression tests as well. (both low and high-dose) I think the result is that MDD are dexamethasone non-supressors and CFS are dex supersuppressors but I am not sure without looking it up. I hope this settles your little depression vs CFS question.

OK, now I'm getting a bit too into this (fortunately I'm waiting on an incubation to finish so I'm using this as lunch break. Looking back through some other papers, there is one (which ERV had actually mentioned in 2008) where the authors did PCR using generic genus-specific primers (not virus strain specific) and found the contaminating viruses just fine, including an...wait for it...wait for it...MLV!

So yeah...PCR can detect integrated MLVs just fine.

Suck it Gerwynnnnnnn and v99!

By Poodle Stomper (not verified) on 10 Oct 2011 #permalink

Oh PS, the paper was "Identification of Gammaretroviruses Constitutively Released from Cell Lines Used for Human Immunodeficiency Virus Research " by Takeuchi, JOURNAL OF VIROLOGY, Dec. 2008, p. 12585â12588.

By Poodle Stomper (not verified) on 10 Oct 2011 #permalink

trying to correct gerwyn/v99 with any corrections generally leads to nothing but frustration cuz they will just talk around the correction and then kennedy will come along and ask you why you are trying to cause problems and give you a psych/social speech that ends with "why didn't you attack the pace trial" yada yada...

but since I like to know the correct science many thanks to ps and camaro providing some..

I had the greatest laugh at the petition circulating asking WPI to take SWMNBN back, clear her name and to blame everyone else but her for any problems..they are shooting for 100 sig's 100 out of the millions of sufferers..ROFL (not at the pt's of course, but at this silly attempt!)

By mary (abbie's ilk) (not verified) on 10 Oct 2011 #permalink

Mary @887,

You are involved with MS research, am I remembering right? If so, I would be interested on your take as to why MS research seems to easily endure various scientific theories being tried on for size and then politely abandoned without all of the drama, pain, and figurative tooth-pulling that takes place time after time with CFS research. And without pissing off researchers and scientists en masse for the most part.

Speculative aspects of MS research, at least the stuff I have read recently seems to be at least as far-ranging and controversial as CFS research. They even cover the same ground sometimes:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170536/?tool=pmcentrez&ren…

Levi - of course you can see the symptoms of M.S through a microscope. The cause remains uncertain. There is nothing so clearly seen in M.E. and every new breakthrough is hoped to provide this - some easily sean pathology and, at last, the end of the psych debate.

Without making any judegments I'm guessing this is the difference.

I wonder who Racaniello meant by "others" because it's certainly not CFS patients who can tell what is misinformation.

EvilTroll - I never even mentioned NPD. I'm the one who said therapy is cool around here, remember? Most CFS patients do not fit the criteria for depression. You are trying to argue that they have depression without the evidence, or some kind of depression that is not depression. With that kind of reasoning you can find whatever you want to imagine... WMD, XMRV, etc.

By Smurfette (not verified) on 10 Oct 2011 #permalink

Oh PLEASE someone try and bang some sense into Gerwyn/V99 re their latest web release! Gah.
(Who called V99 Toady? LOVE it!)

Thanks poodlestomper for donating your lunch break to share some insight.

The messedupforums are doing a HUGE DISSERVICE to the ME/CFS community and it's sweet relief to come here and get some real science.

What Jules (892) said.

V99 the toady is posting all sorts of bullshit on behalf of the flounce king Gerwyn. It's not only on the mecfsforums but on a bunch of forums and a few blogs. I belong to some of these forums and would love some good answers to debunk the fraudster team of Gerwyn/V99. Many people reading their messed up science don't know enough to know that's it's all so very wrong. One should immediately know it's wrong cause it's written by Mikovits lovers. Anyways, somebody please post a good response that joe average non-scientist can understand because those two uber morons are doing a huge disservice to the Universe.

By Anonymouse (not verified) on 10 Oct 2011 #permalink

@ levi..

yes, MS is my field and perhaps externally it seems like researchers, md's, and pt's survive different theories but internally we can have disputes as vocal as the me/cfs appear.

right now, we have pt.s flying to Mexico to have the base of their skulls cracked open (and dying in the process) cuz of the latest "scientific breakthough".. I want to punch that man in the mouth..

the advocacy groups seem to leave the science to the scientists and do not take a roll in explaining or advocating a theory until there is a scientific consensus.

but in any patient group you are going to have militants however, since MS can be "seen" (as David said). we can physically measure a change and evaluate treatments better than me/cfs. ie: If ar's were a viable treatment, we should be able to see/measure an improvement very easily.

me/cfs has great scientists involved in it's research unfortunately, perhaps out of desperation, these have been shouted down by a few.

By mary (abbie's ilk) (not verified) on 10 Oct 2011 #permalink

beccaf22,
Thanks for the reference to Dr. Cleare.
I found the following reference very helpful and enlightening:

http://www.iop.kcl.ac.uk/iop/prt/cfs.htm

While I understand the subtle difference between CFS and depression now, given the high co-morbidity I suspect they more in common than not.

Other than that Dr. Cleare is arguing the same position I am.

@Levi:866,
While I appreciate the kind words, my grandmother became an unrepentant atheist after her parents committed suicide due to Shoah-guilt. Since then our family and YHWH haven't exactly been on speaking terms.

Anyway, I read up on amifitadine. Sounds promising.

While studying it a (very dim and flickering) light bulb went on in my head. Has there been any serious study of Provigil(aka Modafinil) as a potential treatment? I've tried it and its a pretty amazing drug; you get the clarity/focus of amphetamines without the unpleasant psychosis. If CFS is at its core some type of anxiety disorder this could an effective way to address the fatigue/fog aspect in a safe manner.

Yeti @896 states:

"While studying it a (very dim and flickering) light bulb went on in my head. Has there been any serious study of Provigil(aka Modafinil) as a potential treatment? I've tried it and its a pretty amazing drug; you get the clarity/focus of amphetamines without the unpleasant psychosis. If CFS is at its core some type of anxiety disorder this could an effective way to address the fatigue/fog aspect in a safe manner."

Good thinking Yeti. I have occasionally used both Provigil and its newer racemic isomer Nuvigil. I have spoken with other patients that have too. They are not used by most clinicians for lots of reasons, and they are really expensive and not on many insurers approved drug formularies.

Read my statement upstream in this thread @685 about this topic. Also revisit daedalus2u's comments about CFS and stimulants @701, which reflect my personal experience with them. There are a number of working CFS patients, at least part timers. For them, if it comes down to economic survival and they must "whip the horse" so to speak, Nuvigil/Provigil might make sense. The drugs do not actually do much for the cognitive difficulties, but they can keep you on your feet, at least temorarily. Although they do have some abuse potential, I doubt that would happen with CFS patients since they will eventually just collapse using them.

Mary @ 894,
Thanks for your response, I am very sorry to hear about those MS patients dying under the knife like that in Mexico. Both CFS patients and MS patients can become desperate for a cure or the possibility of substantial improvement I guess. Its very dangerous when it gets to that point for obvious reasons.

To all the bored other folks seeing OT posts, I will throw out this informational tidbit; at a professional luncheon presentation yesterday in Ireland, I am reading in the forums that Dr. Mikovits defended herself about the slide issue that kicked off this thread. You will be able to buy the DVD of it for $15. Reportedly, she has a grant and a new research gig in Canada. I have not confirmed any of this though.

@Levi @EvilYeti If provigil works for you then you don't have ME/CFS. Sleep Apnea maybe but not ME/CFS. It is NOT psych-somatic. We are talking about normal patients with no prior psycho-somatic disorder from all walks of life come down with ME/CFS after a pots viral infection. They can be athletes, CEO's, doctors, medical researchers, nurses, academic professors, firefighters, police officer, commercial pilots etc. cut down in the prime of life after a viral illness.

Damned by Acronym
http://www.dailymail.co.uk/debate/article-1246859/MARTIN-SAMUEL-Lynns-l…

Anonymouse, regarding your earlier question up the thread about XMRV, MLV's, HTLV, 'HGRV's', etc-

As usual, some nugget of truth is being used to simultaneously explain and ignore all sorts of specific, individual and non-connected topics. In this case, the nugget of truth is that HTLV apparently does not have very much genetic diversity, since it apparently multiplies by cell mitosis and not reverse transcription like HIV does. (I might have the terminology wrong as I have no experience with PCR, this is just based on what I remember reading throughout this whole thing)

This could potentially coincide with/provide an explanation for the situation regarding XMRV, which also shows exceedingly little genetic diversity. However Gerwyn et al are using this fact to explain all sorts of things in relation to the XMRV/MLV argument, even arguments that disagree with other arguments they are currently espousing.

For instance while Gerwyn et al point out how HTLV has very little genetic diversity, at the same time they are using the Alter/Lo MLV findings in an attempt to show that 'HGRV's' do in fact have genetic diversity.

Also, the situation with Alter and Lo's MLV's does not even really discuss the issue of genetic diversity, or lack thereof, in the MLV sequences they reported finding, the situation with Alter and Lo's MLV sequences is in regards to how the Alter/Lo group looked up 8 patients from the cohort the original samples were collected from and re-tested samples taken from these individuals 15 years later, with 7 of 8 of these patients re-testing positive for MLV. The sequences from these new 'positives' also had 'genetic diversity', which implied at the time that these patients did in fact have an ongoing retroviral infection. Upon further phylogenetic analysis however, the daughter sequences were found to be fundamentally different from the parent sequences, to the point where two seperate groups which re-analyzed the results concluded that one could not have come from the other. It has nothing to do with genetic diversity or lack thereof, it has to do with fundamental differences in parent and daughter sequences. I think that the two groups which re-analyzed the results said that for the samples to really be legitimately from the same patients, each of them would have had to clear the original infection and get infected again with a completely new virus or something like that. ERV has written a blog post about it, I think.

So based on my understanding of the issue, and I emphasise again that I have no education or experience on the topic, the 'HGRV's' that are constantly referred to by the pro-XMRV group are in fact a) XMRV and b) other recombinant cell line contaminants, each of which is its own distinct virus with exceedingly little genetic diversity, as well as c) the Alter/Lo MLV sequences, which are commonly regarded as simple contamination from murine sources, and d) all the other sources of contamination which have been observed thus far such as contaminated reagents, contaminated DNA columns, contaminated this, contaminated that... (I basically have forgotten just how many sources of contamination have been shown to exist, much less all of the other potential sources of contamination)

Thus 'HGRV's', I think in the minds of many, if not most, observers, are simply a collection of artefacts from various sources which are falsely being asserted by the pro-XMRV crowd to comprise a distinct and newly discovered class of retrovirus, when in reality 'HGRV's' are just a legend based on a disparate collection of relatively unrelated findings.

"Anyways, somebody please post a good response that joe average non-scientist can understand because those two uber morons are doing a huge disservice to the Universe."
Anybody who works in molecular biology can tell in a second that those guys are simply making stuff up. For a start they seem to be promoting as idea that XMRV integrates into a GC rich region of the genome and becomes hypermethylated which will then make PCR difficult.
That statement alone shows them to know zero about molecular biology.
Methylation has no effect on genomic PCR.
GC rich regions themselves (with or without hypermethylation) can be a little difficult (but certainly not impossible) to amplify by PCR - but that is besides the point - the integrated sequence will have exactly the same sequence whether it integrates into a GC rich or a GC poor genomic location and will amplify just as easily in either location.
Someone on the other forums keeps complaining that "trizol" was not used by other labs so they cannot replicate the culture conditions.
That also shows they know nothing about molecular biology.
Trizol is an agent used to kill and lyse cells during the isolation of RNA (for example to extract total RNA for RT PCR). If you intend to culture cells then trizol is about the last thing you would add since culturing cells means growing them (which can be affected by the act of killing them, which is what trizol does!)
The basic problem with this whole issue from a molecular biology point of view is that the techniques that currently exist for detection of viral sequences ARE good enough for this sort of hypothesis. There should be no need to do elaborate culture techniques to show the presence of integrated viral DNA sequence.
Why 5-AZA treatment was not performed by other groups is blindingly obvious to a molecular biologist. The central question was whether the virus was present at all in the patients, not whether it was latent or active. Unless you prove it is there at all then there is no reason to test its latency.
I think Abbie pointed out a crucial point a few weeks back. I am a genomic biologist - I can take sequence, say from a virus, and find out things about it in a couple of minutes that help in thinking about experimental tests and in interpreting others results. One of the things I noticed about XMRV is that it is very similar to multiple integrated mouse ERVs. Basically its very similar in sequence to multiple loci all over the mouse genome.
Any contamination of patient samples with mouse DNA will likely give a positive for two reasons. 1) Mouse DNA is present in small amounts in many laboratory reagents (DNA purification columns etc) and 2) Nested PCR was used by Mikovits - which gives about a 1 billion fold increase in sensitivity.
There are other issues that make those who work in clinical molecular biology a little wary. For a start the patients do not seem that similar to the sort of patients who are at higher risk of other retroviral infections (drug users, transplant recipients, gay men, children whose mother has the disease etc) In addition they don't seem to be at a much higher risk of diseases that an integrating virus would promote (such as leukemias and lymphomas.)
Now this does not mean to say that CFS/ME is not a real disease or that there may not be some sort of viral link. For example we might hypothesize that the disease may be caused by an over-reaction of the immune system to a viral or bacterial infection that results in the damage to specific structures (say in the brain or in some specific group of cells that we haven't discovered yet) but the hypothesis that it is caused by XMRV or a similar retrovirus that infects the lymphocytes of sufferers has been tested and no reliable evidence produced to back the claim.
The only study that is backed by the evidence of V99 and Gerwyn Morris is that of "Kruger, Justin; David Dunning (1999). "Unskilled and Unaware of It: How Difficulties in Recognizing One's Own Incompetence Lead to Inflated Self-Assessments""

So once we've eliminated all those "CFS patients" who respond to CBT/GET, anti-psychotics, anti-depressants, analeptics etc.

How many "real CFS patients" will be left?

By Mike Kelly (not verified) on 11 Oct 2011 #permalink

a personal letter from SWMNBN can be found on the FB page of The Academy of Nutritional Medicine...perhaps a new employer?

By mary (abbie's ilk) (not verified) on 11 Oct 2011 #permalink

In other news, the forums are open again. I've spotted the following message from Judy:

I am writing this note today to reassure everyone who consented into the Research program of the WPI including but not limited to the 5 year R01 pathophysiology of ME/CFS, that as Principal investigator, I have the legal right to continue that research at another institution and to take with me the samples and materials and supplies purchased for the sole purpose of that research. Since the sudden closing of the WPI research program on September 30th, I have been in active discussion with several institutions who are enthusiastic about the opportunity to participate with me in this important research. I strongly encourage you to voice your support by emailing me at jamikovits@gmail.com. As you know, your consent form stated that you could withdraw from these studies at any time. The funding agencies need to know that you will withdraw your consent if the research is not done under my direction and thus two years of precious samples and resources will be wasted. Emails from participants in support of me continuing my research will greatly help me. I deeply appreciate not only your participation in my research but also your ecards, emails, encouragement and most importantly your trust in my integrity during this difficult time.

Judy

If I understand her correctly (who does?), she says she can/will continue the study in question, but at the same time asks participants to withdraw their consent if the study is being continued under the direction of 'someone else' (read: WPI)?

Does she actually mean to say that the NIH is still to decide on this matter and she is asking patients to put pressure on the NIH to choose for her?

Mikovits was speaking at the 'ME and Fibromyalgia International Conference 2011' last weekend. It was held in Tullamore in Ireland. Her talk was on the "Virological and immune evidence of Human gamma retroviral infection in ME"
I wonder if she updated her powerpoint presentation!
I guess that's where the new statement from her comes from (considering it seemed to be specifically targeting the UK and Irish patients)

I notice that Gerwyn has responded to my post above by posting what looks like a random paragraph from the 'Disney book of basic PCR for ten year olds'

"G-C pairs in the helix are held together by 3 hydrogen bonds as opposed to two with A-T opposing pairs.
C-G rich regions can cause the polymerase to stall.
The other problem is that the two strands tend to re-anneal quickly once denatured and need a longer denaturating time in the first place.
Annealing has to be quick and polymerisation rapid before the strands re-anneal. This means that the magnesium coenzyme needs to be reoptimised to maximise the performance of the enzyme via active site modification and the salt and buffer concentrations also need to be optimised to maximally stabilize the primer template dimer."

Honestly, it's like listening to a ten year old trying to explain how to land a space shuttle.
Gerwyn, if you are reading this, you know nothing about PCR.
Any difficulties in amplification of a particular sequence will be specific to that exact sequence. In order for a viral sequence to be difficult to amplify due to high GC content the viral sequence ITSELF must have a high proportion of GC. Whether it integrates into the most PCR-resistant CpG island in the genome makes not an iota of difference.
Why?
Because the primers you use will not be specific for this CpG island - they will be specific for the viral sequence which is NOT GC rich.
Any GC rich segment of DNA will have minimum effect on any sequence more then a few tens of bases away so 99% of the viral sequence (and 100% of the regions that are tested in PCR assays) will not be affected by the GC content.

#874

Just some short remarks more about the âinvalid PCRâ stuff â but this is more a try of a logical explanation than of molecular biology:

1. XMRV was discovered using micro array techniques
2. the first full length provirus genome (VP35) was reconstituted of several PCR fragments amplified from tumor cDNA using primers derived from murine type C retrovirus (MTCR) and SFFV
3. a second full length genome was done in that way -> VP42
4. with just two PCRs from a third tumor cDNA they assembled the VP62 sequence, which was later cloned in pCDNA3.1 (Dong et al 2006)
5. all the other cases of XMRV+/PCa were determined using nested PCR with Primers based on the VP62/VP42/VP35 sequences, which are that particular region of primer binding identically
6. Lombardi et al based their primer only on the plain VP62 sequence and foundâ¦

⦠of course VP62 (the contaminating plasmid) which explains the nearly identically sequences published with the 2009 paper â there was no sequence variation in all CFS patients! Never ever!

Therefore it is absurd to argue that somebody wonât find XMRV because the primers are based on VP62.

The sequences variation they postulate (but never published) was then, like the sequences of poly- or pm-tropic MLV found by Lo/Alter just out of the contaminating murine DNA, see explanation by Coffin in one of the last talks by him.

So, in conclusion, originally XMRV was found with primers not made for XMRV but for MTCR and SFFV and Lombardi/JM themselves used the VP62 sequence to establish their PCR.

(And no my incubation period is over ;-)

Mike- from the non effective treatments discussed so far on this blog i would imagine all of them.
As a 6 year sufferer of it after having EB virus( i was unable to walk as i had no feeling from the waist down- complete pain and orthostatic intolerance from the waist up) i couldn't speak quite often, sometimes my arms wouldn't respond, they were too tired to lift- i couldn't wake for hours but could hear, it was like being in a coma......this was until i took chinese herbal remedies within two weeks i was on my feet, speaking in normal conversation and i could walk and feel my legs... i missed out on so much of my daughters life because of this illness, yet some doctors still say it's psychiatric- and yes the PACE trials were completely rigged because they excluded people who actually exhibit signs of ME, i had all the signs of the canadian criteria the PACE trials used the incorrect Oxford Criteria.(this just shows people with fatigue and a bit of depression, which is common in many illnesses- no signs of viral onset)... it was a well timed and politically motivated study that doesn't show any value whatsoever. I am inclined to think of psychiatrists as scam artists

RRM@903, JM's problem is that by law, the grant belongs to the WPI. The WPI can propose a new PI to the NIH, and the NIH can accept or deny, and, at worst, kill the grant. The NIH cannot move the grant to a new institution without WPI's consent.
JM is trying to put pressure on WPI to consent to the move by threatening to have patients withdraw their consent. More of JM's "my way or the highway", it's taking on the air of perceived religious prosecution.
It stays to see if this is to be able to continue the research or in order to force a destruction of samples in order to prevent a reanalysis (so my guess is that by now the samples are under subpoena by the ORI).

Sigmund,

Trying to explain to Gerwyn why he's wrong is like trying to explain nuclear physics to a 3 y/o. It just won't work. He has a classic case of Dunning Kruger where he is not only ignorant of biology, but he's so ignorant as to be ignorant of his ignorance. It's not an easy thing to escape ;-)

By Poodle Stomper (not verified) on 11 Oct 2011 #permalink

@M.E.: if you recovered after taking chinese herbal remedies, it sounds very much like you had a psychosomatic illness.

Contrary to the comment above, EVERYONE has prior psychosomatic illness. If you have never had a psychosomatic illness I frankly don't believe you (or perhaps you don't have a prefrontal cortex :)

As for depression vs CFS: first, depression is a symptom whereas MDD is a diagnosis. Anxiety and depression as symptoms are very common in CFS - surveys show that between 60% and 90% of CFS patients suffer from those symptoms. Second, just because CFS is not the same as MDD doesn't mean it is not similar. The low cortisol finding is interesting, because the only thing that is known to cause that is stress (also Addison's disease, but that is different from CFS).

#874

Just some short remarks more about the âinvalid PCRâ stuff â but this is more a try of a logical explanation than of molecular biology:

1. XMRV was discovered using micro array techniques
2. the first full length provirus genome (VP35) was reconstituted of several PCR fragments amplified from tumor cDNA using primers derived from murine type C retrovirus (MTCR) and SFFV
3. a second full length genome was done in that way -> VP42
4. with just two PCRs from a third tumor cDNA they assembled the VP62 sequence, which was later cloned in pCDNA3.1 (Dong et al 2006)
5. all the other cases of XMRV+/PCa were determined using nested PCR with Primers based on the VP62/VP42/VP35 sequences, which are that particular region of primer binding identically
6. Lombardi et al based their primer only on the plain VP62 sequence and foundâ¦

⦠of course VP62 (the contaminating plasmid) which explains the nearly identically sequences published with the 2009 paper â there was no sequence variation in all CFS patients! Never ever!

Therefore it is absurd to argue that somebody wonât find XMRV because the primers are based on VP62.

The sequences variation they postulate (but never published) was then, like the sequences of poly- or pm-tropic MLV found by Lo/Alter just out of the contaminating murine DNA, see explanation by Coffin in one of the last talks by him.

So, in conclusion, originally XMRV was found with primers not made for XMRV but for MTCR and SFFV and Lombardi/JM themselves used the VP62 sequence to establish their PCR.

(And no my incubation period is over ;-)

After reading the mecfsforums a bit, I've decided that Trizol to them, is like Jesus is to Christians. It's the holy magic that turns their wishes into reality.

Dr. Judy sinking to new depths.

<>

I have to think that the NIH, and the scientific community in general, will not be pleased with this attempt to manipulate study subjects.

wtf- no- my symptoms were not psychosomatic, i have functional tests which show the effects of my muscle weakness and recovery before and after- the herbs i took were designed for the issues i had which were physical, not mental- M.E. is not a psychosomatic illness- although it may be fashionable for some circles to explain anything they don't understand as psychosomatic, it is a neuro immune one as defined by the WHO, i hope that makes it clear, there is very little evidence to suggest otherwise unless you can show me

@M.E. - psychosomatic symptoms ARE physical (not mental) - that is the definition of psychosomatic :)

Any time you are under stress or depressed, for example, you have "neuroimmune" symptoms. Also, if you subject rats to psychosocial or physical stress in the lab you will produce neurological and immune symptoms - this is repeatable and not really in any doubt. Occam's razor...there is no plausible reason why herbs would fix your muscle weakness, while there is good evidence that it could be psychosomatic.

i give up lol, there will be no convincing you to read the effectiveness of certain herbs to alleviate physical symptoms in any chinese journals, there is very plausible reasons why herbs would detoxify the nerves, and remove inflammation (the same as any western drug)- my symptoms don't ease with lack of stress- i don't have any stress- i still have ME, it just i am now the walking dead,... if this is the case MS and Autism are psychosomatic illness too... psychsomatic is a lazy diagnosis there is organic disease in the tissues of dead ME sufferers- read Sophia Mirzas case, nerve root ganglion inflammation of the spinal cord.... so why is it, it takes people to die of this illness before it gets taken seriously..keep quoting occums razor until you over use it, but please use your brains that you've all been blessed with to develop physical tests for this illness... i beleive methylation tests are a good starting point, as is mutations of MTHFR gene which allows this process of the mitochondria to be disrupted.. i cannot know if the process is directly influenced by any kind of virus like others seem to think, but i don't rule it out either .. so ihave to disagree there is plenty of evidence that it is NOT psychosomatic and plenty that herbs do work if you use a qualified herbalist

so JM is saying "I have the legal right to continue that research at a different institution" and

"The funding agencies need to know that you will withdraw your consent if the research is not done under my direction"

Why do they need to know that if legally they cannot take the research away from JM because of her "legal right".

Why does she need patients to threaten them to make them do something they legally MUST do?

Since it still doesn't seem to have sunk in, she doesn't have the legal right. From NIH's website:
The NIH awards R01 grants to organizations of all types (universities, colleges, small businesses, for-profit, foreign and domestic, faith-based, etc.). The R01 mechanism allows an investigator to define the scientific focus or objective of the research based on a particular area of interest and competence. Although the Project Director/Principal Investigator writes the grant application and is responsible for conducting the research, the applicant is the research organization.

She's contradicting herself within a few sentences.

She has a lot of confidence in her ability to bamboozle people.

No doubt she will be proved right

@ 920 Mu,

It's OK it had sunk in. I was attempting to highlight the fact that she was contradicting herself.

ie she was making a claim to a legal right (which you show to be not the case) while asking patients to support a threat which wouldn't be necessary if she had that legal right.

@923 David,

Good link about that topic. Since some folks here may have reading difficulties and not fully understand my previous posts about this topic, I will add this:

"Ritalin and modafinil, two currently available compounds, operate on primary psychological states that in turn affect cognitive operations (attention and memory), but there is little evidence that these effects translate into improvements in complex cognitive processing."
http://www.sciencedirect.com/science/article/pii/S0091305710004077

I would use the analogy of "study drugs" that grad students may be familiar with. They may help you stay awake to cram and catchup on studies you don't otherwise have time and energy for. But it is foolish to use them for a test. Better to rest up, sleep well, and eat right instead.

M.E.:

i give up lol, there will be no convincing you to read the effectiveness of certain herbs to alleviate physical symptoms in any chinese journals

Is there some reason you can't name the actual herbs? "Certain herbs" seems like a rather broad category to go read up on.

Abbie I personally don't think it necessary for a separate Gerwyn/V99 thread.

The responses above are cool and word is getting out anyway, plus it would only add to several ego's if you did and who wants to shine any more light on any of those mentioned?

Tomorrow will add another spin and we still haven't heard anything from those who actually signed off on the BWG paper to say 'OMG we forgot Trizol!' :)

If Knickerfits now things this 'new' HGRV is airborne etc. then let her prove it with a paper. In fact it would be interesting to see any paper with her name on it that supports anything she said at Ottawa or anywhere else for that matter.

Of course she won't publish anything because... it's a conspiracy don't you know ;)

What a great thread this has turned out to be. Off now to look at your previous Gerwyn rebuttal :)

Levi @924 - Yeah I get your analogy. I have often come accross people with CFS think back to the days of "study drugs" and wonder. I'm sure when up against it there are things that would be useful - but with the caveats you outline. I wonder how many 'self-medicators' there might be though?

The funniest post yet by V99 who I have decided is clearly insane.
----------------------------------------------------------
John Coffin knew about the use of AZA 2 years ago
« Reply #372 on: Today at 11:29:26 AM »John Coffin had the slide for the best part of 6 months.

He saw all the original data and he was even in the audience where the use of AZA on PCR negative patients in Lombardi et al. was discussed 2 years ago.

The labelling of the slide was an editorial issue as frequently happens in the real world.
-------------------------------------------------

And then, another poster who is equally disturbed posted this:

Coffin peer reviewed Lombardi et al in the SCIENCE paper in 2009.

*Does it makes sense he potentially circulated or knew about the slide and gave it to ERV (extremist blogger/student who calls Mikovits the C-Word) - twice.
*Does it make sense that Mikovits is then 'reported' to SCIENCE the very journal that he peer-reviewed for?
*Does this stuation benefit Coffin?

If so, what a co-incidence....
If so, does this look good for Coffin's professional Integrity?

FOLLOWED BY THIS:

Stoye's comments were certainly well timed and oddly over the top, as if there is a desperation to wipe out the 2009 Lombardi paper.

Didn't Coffin mentor Stoye?

A strange co incidence as Stoye is employed by the UK Medical Research Council (MRC) who fund the UK Wessely school of Psychiatry and have the British official secrects act locked over ME files until 2073.

------------------------------------------------------------
So much for their private part of the forum. Oh the insanity of it all.

By Anonymouse (not verified) on 11 Oct 2011 #permalink

Jack-- Well, people have asked for the science, and Im a sucker for requests. If people want to know, I have to tell them to the best of my ability.

But its not 'addressing' Sir Gryyyynnn. Its addressing science that people want to understand. I am under *no* illusion that he has the ability to learn. Im still working on it, though-- well see if people are still interested once its done, lol!

Anon-- They are missing the most obvious (thus correct) explanation. I am actually AI created by Simon Wessley (in collaboration with the Japanese and aliens) several years ago. I mean, the 'ERV' program started in 2006 via the blog, the 'Abbie' voice was finished in 2007 (optimized from GLaDOS), but the actual mobile 'Abbie Smith' AI droid that presents at conferences and such wasnt completed by the Japanese until a couple of years ago.

Now that the 'Abbie Smith' program is complete (retraction of the 2009 Science paper), Abbie will 'graduate'.

Think about it.

Think about it.

IT ALL MAKES SENSE NOW, RITE???

@ERV

Actually, I thought about that before, but I concluded that if you were created, the conspirators would have made you likeable.

Of course, now that I see that Simon "der Führer" Wessely has (co-)created you, I admit is was silly of me to dismiss the theory on that basis.

Well, one thing is for certain.

Whomever trained ERV's neural network felt that a mirror of sciencemag.org, 4chan and few episodes of "Spongebob Squarepants" was adequate.

One thing I have learned from reading comments at 'treatingxmrv' is that snarks / boojums / human gamma retroviruses are not subject to the usual high mutation rate (and hence cannot be discarded as lab artefacts, even when attempts to sequence them all look suspiciously identical), because they "replicate by clonal expansion" * rather than by infection and reverse-transcription.
In other words, they behave just like ERVs.

At the same time, the CFS and leukemia caused by these snarks & boojums can be treated by drugs that block reverse transcriptase.

At this point my head started hurting so I went back to work.

* Or "colonal expansion" according to one comment ::::::

By herr doktor bimler (not verified) on 11 Oct 2011 #permalink

@ME,
I don't like using the term "psychosomatic" precisely because very few people actually understand what it means.

It is well known that stress can compromise the immune system and lead to opportunistic infections:

http://en.wikipedia.org/wiki/Psychoneuroimmunology

So chronic stress becomes chronic infection and ultimately chronic fatigue. Treat the stress and you treat the fatigue.

Re:drugs and side effects.

I'm not denying this. But patients and their caregivers may ultimately need to decide whether the risk is worth it.

Soooooo...if ERV is just an AI used by aliens can I...errr...borrow... the android that made those appearences on Youtube for...emm research...just for an hour or so?

By Poodle Stomper (not verified) on 11 Oct 2011 #permalink

So, is EvilYeti actually on the non-psycho patients' side? He's systematically working through every failed explanation and proposed med. Provigil? Lol.

If so, good job, EY.

So, virologists, are you done with V99/Gerwyn/Jamie/Judy yet?

As it's obviously NOT VP62, what MIGHT it be?

Haven't heard an hypothesis worth testing yet here, other than ill-informed psychobabbling outside your areas of expertise.

By Impatient (not verified) on 11 Oct 2011 #permalink

Here's a question for you learned types- In the following XMRV-related patent application, it says the following-

Example 3
Cells

In Vitro Expansion of Primary B-Cells.

NIH 3T3 cells transduced with a retroviral vector expressing CD40L were maintained in Dulbecco's Modified Eagle's Medium (DMEM) (Invitrogen) supplemented with 10% calf serum (CS) (Lonza) and 1% Pennicillin, Streptomycin and L-Glutamine (Invitrogen) at 37° C. with 5% CO 2 . To stimulate B cell expansion, Ë3.5Ã10 6 NIH3T3-CD40L cells were trypsinized (0.25% trypsin with EDTA) (Invitrogen), resuspended in 3 mL medium and irradiated with an absorbed radiation dose (rad) of 9600 using a Cesium 137 Irradiator. Cells plus 7 mL medium were added to a T75 cell culture flask (Corning) and allowed to adhere (2-3 h) to the flask surface (optimal density Ë50%). CD19+ B cells were isolated from PBMCs using immunomagnetic bead technology (Miltenyi Biotec). CD19+ cells were separated from 10 8 freshly isolated PBMCs by positive selection with a purity of >95% according to the manufacturer's protocol. After magnetic separation, CD19+ B cells were added to an irradiated NIH3T3-CD40L monolayer and incubated at 37° C. with 5% CO 2 . Cultures were monitored for B cell proliferation and split 1:5 every 72-96 h onto freshly irradiated NIH 3T3-CD40L monolayer. CD19+ primary B cells were cultured and expanded in primary B cell expansion media: Iscove's Modified Dulbecco's Medium (IMDM) (Invitrogen)+10% FCS (Atlanta Biologicals), 1% Penicillin, Streptomycin and L-Glutamine (Invitrogen), 40 ng/mL interleukin 4 (IL-4) (PeproTech, Inc.), 50 μg/mL holo-transferrin (Sigma) and 5 μg/mL insulin (Invitrogen).

Given that Dusty Miller's group found that NIH3T3 cells harbor the 'left half' of XMRV, and will produce PCR products from supposedly 'XMRV-specific' primers, is it weird that the WPI uses NIH3T3 cells in the fashion described above?

One of the more long-standing arguments of the pro-XMRV group is that 'the WPI never had the 22rv1 cell line on its premises', and therefore could not have been contaminated by XMRV. However the WPI has stated on several occasions that they (or Ruscetti, or whomever) do have three or four B-cell lines derived from ME/CFS patients which do constitutively produce XMRV. The WPI would probably say the XMRV came from the patients, while a more skeptical observer might be more inclined to think that the cell lines became contaminated after the fact and themselves could potentially be a viable source of contamination.

Also, Silverman did send WPI the VP-62 clone, so isn't that another potential route of contamination? Do infectious clones have to be propogated, and therefore pose a risk of contamination?

Thanks.

@evil Yeti
'chronic stress becomes chronic infection and ultimately chronic fatigue. Treat the stress and you treat the fatigue'

If that were the case i would be cured, i repeat i have no stress, the chronic fatigue- chronic stress treatment scenario is not orthoganal, we need to investigate why a permanent change has occured within the mitochondria..why does it occur in some not others.. its not science to put it in the stress wastebasket, many people have stress and don't succomb to infection. the defining symptom is 'does not improve on exercise, but gets worse' this is how it ruled out from being a psychosomatic disorder because all this can be demonstrable and not just taken on faith.... a psychsomatic disorder/ mood disorder/ stress related depression improve with exercise...

other types of depression with an organic basis ( this is a symptom of disease not the disease itself) can very often be attributed to anaemia- it is not stopped by thinking pretty thoughts or exercise, it is with iron and b vit supplemenation- well the list goes on really, i don't see how people keep getting their knickers in a twist over it being psychosomatic when it is not perpetuated by the thought process or the psyche. There is for the umpteenth time more evidence to suggest an organic disruption in cellular metabolism than any psyche disorder, it should be a criminal offence to treat this illness as a psyche disorder... furthermore to keep say it is a somatoform disorder is laziness and an insult to the scientific process of medicine, so many disorders were thought to be somataform until they were thoroughly investigated - H pylori- causing stomach ulcers etc. I wish the medical establishment got off their high horse and stopped peddling belief systems of hysterical proportions.

Thanks Abbie.

Well here's the 'excuse' presented in Ireland. They call it a 'paper' I call it 'desperate'...

https://www.facebook.com/notes/the-academy-of-nutritional-medicine-aonm…

'Virological and immune evidence of Human gamma retrovirus infection in M.E.

On the second anniversary of the publication Dr Judy A Mikovits presented a paper regarding evidence supporting infection of ME patients with Xenotropic MLV-related viruses at the Fibromylagia ME conference in Tullamore, Ireland... '

@John, 935

Thanks for this interesting observation. In their angry letter to Bruce Alberts referring to the voluntary retraction, Mikovits states vehemently that
"No murine cell line was grown in the WPI labs prior to the submission of the
Lombardi et al. manuscript"!!!!!!! (Exclamation marks by me). To me, this sounds somewhat contradictory to what the patent application says. But I am sure, there is a reasonable explanation for this.

Further, in the supporting online material that came out together with the Lombardi paper the legend to Fig S3 says
"Figure S3. Detection of cloned XMRV-VP62 using a rat mAb to SFFV Env and a
goat antiserum to mouse NZB xenotropic MLV. A. Lysates were prepared from
XMRV-VP62-infected Raji (lane1), LNCaP (lane 2) or Sup-T1 (lane 3)..."

Therefore, they were clearly working with VP62 in their labs! The stage was set...

OWE

NIH 3T3 cells, being mouse derived, have multiple copies of integrated murine gamma retrovirus sequences. It would be a nightmare to try to prevent contamination in a co-culturing experiment with human cells, especially if you used nested PCR.

@Sigmund

That depends on the way you're doing the detection of XMRV.

Using the 24nt deletion in the gag leader sequence - which was reported to be unique for XMRV and is not found in endogenous MLVs - as a target for PCR can just produce false-positives due to VP62 plasmid DNA contamination, or with DNA from a few very special nude mouse strain as demonstrated recently by Paprotka et al in the "origin of XMRV" Science paper.
Other PCR strategies, e.g. the Lombardi as well as the Silverman primers are very sensitive for false-positives due to endogenous MLVs.

That's the tricky point, if you are too specific you will miss the so called "variations of HGRV", if you are not specific enough you'll find a MLV-like virus wherevery you are looking for one ;-)

Comon, this should be easy to control for, just do negative control PCRs for your feeders without adding B cells.

By mo (one of Abb… (not verified) on 12 Oct 2011 #permalink

"Comon, this should be easy to control for, just do negative control PCRs for your feeders without adding B cells."
In theory, yes. However, what if you work in a laboratory where control cells occasionally change, at a moments notice, into patient cells (with or without 5-Aza!)?

@933
"So chronic stress becomes chronic infection and ultimately chronic fatigue. Treat the stress and you treat the fatigue."

You mean treating stress is equivalent with treating an infection?

By just wondering (not verified) on 12 Oct 2011 #permalink

@M.E.: it's not a 'criminal offence' to treat it is a psych disorder. There are many patients who have fully recovered after treating it as such. If you're too closed minded to consider the possibility there is no point discussing it further.

Oh-- and thank GAWD someone else is saying something about that goddamn 100% peak-shift in the damn flow data:

For example, it is usual to find in any viral infection that infected and uninfected cells exist in equilibrium as two discrete populations. In flow cytometric analysis, this is represented by a bimodal peak. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) taken from CFS patients was shown in the paper as a single peak, indicating that almost every cell was infected with XMRV.

Which is also explainable by treating cells with 5-AZA and inducing a low-but-global expression of cross-reactive ERVs, which was also probably done in Ruscettis lab because I doubt the WPI bought a flow cytometer.

"....the actual mobile 'Abbie Smith' AI droid that presents at conferences and such wasnt completed by the Japanese until a couple of years ago."

Ha! How you Simon Wessley and the other reptilians reveal yourselves. You can't be a droid because we didn't experience the uncanny valley effect during your presentations.

Nice try annunaki agent go back to Nibiru and mine your own gold.

http://weknowmemes.com/wp-content/uploads/2011/09/ancient-aliens-i-dont…

By Prometheus (not verified) on 12 Oct 2011 #permalink

@ERV

Don't know if you're already referring to this, but Patrick Moore also addressed the peak-shift issue:

he CFS peripheral blood cells have robust monotonic staining rather than the bimodal peaks that are expected from a mixture of infected and uninfected populations of peripheral blood cells. It is not certain whether this level of viremia for an exogenous retrovirus is medically possible.

To which Mikovits replied:

Although at earlier times these samples did have bimodal peaks, data shown were when most cells were virus positive.

Oh, and what Moore also addressed and which can also explained by some nice 5-AZA (at least, it seems to me), is the fact that in Figure 2b the positives were actually "more positive" than the positive control.

Now that I read it back, I see that Mikovits also made a rather "funny" statement in her reply to Moore:

The studies of
XMRV protein expression in peripheral blood mononuclear cells (PBMC) were performed after PBMC were activated in culture with phytohemagglutinin and interleukin-2 for 7-14 days to allow the virus to spread through the culture. It should have been made clearer

Am I right in finding this "clarification", again without mentioning the 5-AZA part, rather disingenuous?

They have 'clarified' their 'methods' numerous times, not once mentioning 5-AZA. Reason #927253202838 everyone is pissed.

Basically, no one can believe anything they say.

I mean, it *does not matter* to me whether they say 'I did not use 5-AZA in the flow experiments'. There is *no* reason for me to believe them. None. Theyve had so many opportunities to come clean, and they havent. They *actively chose* to withhold information, aka lie.

@RRM

Is it possible to post the link where Mikovits said that?
Just for my records...

Thank you

OWE

@WTF- is SHOULD be a criminal offense - not IS (READ) so if i had MS then i am narrow minded for not choosing psyche based therapy- thats the biggest load of BS, this is how Sophia Mirza died, please also look up Lynn Gilderdale case- i repeat they don't work for ME, they work for somatoform disorders ME is not a somataform disorder, your English comprehension is clearly not very good.
I am with a consultant rheumatologist for it- that is about as far from psyche as it gets OK? i am wondering if you're quite young as you speak like you don't have much life experience or have spoken with many people with the condition- i don't mean that in an offensive way, but it comes across as such?

if ERV is GLaDOS-derived... can you please post a vid of your singing the turret opera =)

Ha! Prometheus, you give yourself away. The reason you don't experience the Uncanny Valley with the Abbie Smith android unit is because ur one 2!

@M.E.: sorry, that was a typo, I meant to say it shouldn't be a criminal offence. The difference with MS is that it has recognised organic pathology, and it isn't linked with stress and depression as CFS seems to be. Also there aren't people fully recovering after psychological treatments AFAIK. And if you read Sophia Mirza's story you'll see that not only did she not die of CFS/ME, but there was clear and obvious psychiatric issues. However I don't think it is appropriate to discuss that any further on a public forum. PS, I'm not young and I have been looking into the research behind CFS for over a decade and have talked to many people with the condition.

I was kinda curious why the actual activation protocol wasn't specified in the Lombardi paper. I guess that explains it. I wonder what university in their right mind would even want her coming within a mile of their campus, much less have her work there.

By Poodle Stomper (not verified) on 12 Oct 2011 #permalink

WTF @960 states: "The difference with MS is that it has recognised organic pathology, and it isn't linked with stress and depression as CFS seems to be"

The problem with evidence of organic pathology is central to the bigger issues with ME/CFS. The initial ME clinicians from the 1950's like Acheson and Ramsay believed that they were dealing with an organic disease. They looked at a possible hysterical causation theory, and decided against it.

With the advent of "CFS" in the 1980's, ME was "disappeared" by the medical orthodoxy and shunted into the definition of CFS. CFS was given an impossibly broad and unworkable definition, particularly in terms of a working research definition that might lead to understanding any possible organic causation.

Avenues of research that might eventually lead to the determination of an organic basis have gotten little funding over the decades, and the established treatment guidelines strongly discourage the use of sophisticated technology that might provide traction for clarification of an organic cause:
http://www.cdc.gov/cfs/general/diagnosis/testing.html
For instance, how many patients have you talked to that have had an fMRI?

Your claim that MS is not linked to depression baffles me. I am a non-scientist, but I can google:
"Depression and fatigue are among the most common symptoms of multiple sclerosis (MS)."
http://www.ncbi.nlm.nih.gov/pubmed/21296901?dopt=Abstract

WTF- you clearly haven't read the pathology report in Sophia's autopsy- yes she was sectioned for a non-psychiatric condition. i think that is very wrong don't you. Had she not been, and given adequate care- she may be here still she may not be. It was her mother btw that was accused of a psychiatric disorder, not sophia- then they significantly back peddled. you say are well versed in M.E. i am shocked you don't know the results of this and the Lynn Gilderdale trial.. at the very least you seem biased towards psychiatry for organic diseases. again i ask is it appropos to treat MS,stomach ulcers, menstrual disorders via a psychiatric route- no i didn't think so. The trouble is crosses many different areas of speciality- it is hard for a G.P. to know which is the chicken and which is the egg. i have to go and leave now as my eyesight has declined quite badly since crashing again (yes even my optometrist will be able to show evidence of changes in the muscles in my eye pre and post crash, it isn't determined by my psyche, i am a perfectly happy bunny, depression is rarity for me thankfully, have a good evening

Yes, that control is easy to do and yes, you can't expect them to have done that correctly.
In theory, everyone of us and their aunt who has NIH 3T3 in their lab could do the negative control for fun, just order the same primers and repeat their protocol. To give them the benefit of doubt, you would have to use the same cell culture media (maybe these are contaminated with mouse DNA) but you wouldn't have to irradiate them. But you can never be sure what kind of sloppy shit they pulled with the construction of their retroviral vector.

But maybe we are just a little to harsh with them here: Not every single experiment they ever did on XMRV is bound to be fraudulent and contaminated. The good lies contain just the right sprinkle of truth.

By mo (one of Abb… (not verified) on 12 Oct 2011 #permalink

@ Jack

Re the Tullamore conference summaries.

Image caption: Dr. Judy Mikovits MD

Thought JM was a PhD, not an MD?

From JM's letter: "As you know, your consent form stated that you could withdraw from these studies at any time. The funding agencies need to know that you will withdraw your consent if the research is not done under my direction and thus two years of precious samples and resources will be wasted."

Ethics, Judy, dear?

The "IMEA" (run by a one-time lawyer) are busy letter writing on ME-CFS forum:

http://www.mecfsforums.com/index.php/topic,9918.msg0.html

Hey Mo

Neither I suppose can all the blame be laid at Mikovits' door, what about the others on that paper? Lombardi for example - don't ever hear much from him. Mind you between Mikovits and Annette one never heard much from anyone else!

I have also wondered just how much responsibility Science have to take in this? How does that work exactly?

@Levi: sorry, let me clarify. Stress and depression are not thought to be precipitating factors in MS, although there is certainly reactive depression in MS as in any other disease. Also, the etiology of MS does not seem to involve stress as it does with CFS (see the recent review by Cleare for example). Also, bear in mind that fMRI is not necessarily useful for determining organic pathology. When you just think about anything, it will show up on an fMRI. Studies show that people with depression have abnormal fMRI compared to controls (and yes, before you tell me, I am well aware that CFS and MDD show different results on fMRI and SPECT scans).

@M.E.: I did in fact read the autopsy, but if you read the details given by Sophia's mother you will see what I am talking about. Just read the story, engage brain, put 2+2 together and see what you get.

For anyone that cares or wants to understand the "Physical or Mental?" issue regarding ME/CFS, this article from a Psychiatric Journal is very comprehensive and written thoughtfully:

"I will argue that, even taking a sympathetic stance on psychological causation, there are no good grounds for saying that CFS is generally due to psychological problems. It should therefore not be classified as a mental illness."
http://apt.rcpsych.org/content/8/5/351.full

@Levi: that sums up the situation very nicely. The problem is that there isn't conclusive evidence at the moment for any causation. One of Sykes' main arguments against labelling CFS as a mental illness at this point is that there are physical triggers such as viruses. If CFS is caused by stress then obviously both physical and mental stresses will be factors. More research is needed to pin down exactly what is going on. Far from killing all research into psychological factors as some patients would like, we should be putting more money into this research. Contrary to the bullshit being peddled in certain patient forums, people like Wessely are doing a lot of research into physical causes (such as XMRV). Of course, the trolls bleated that Wessely skewed his XMRV data because he didn't give the results they wanted to hear :)

It's way back now, but I was going to write a long and complicated response to the whole discussion of stimulants, since I am actually (unlike most people posting here, I assume) on R-modafinil to treat the symptoms of narcolepsy. FYI, narcolepsy is (1) a diagnostic clusterfuck, basically relying on totally shaky-ass testing of sleep latency in a bizarre setting with electrodes pasted all over the place, (2) listed in the DSM, as it was historically treated as a psychiatric illness, and (3) pretty much understood by everybody at this point to be a brain disease, probably autoimmune. Not "psychogenic," to the extent that such a thing can be defined. And yes, it responds some to stimulants. Me on stimulants = mildly functional. Me not on stimulants = totally unable to have a conversation most of the day. You can't pop stimulants in somebody and say, hey, look, they worked, must not be physical! That's absolute crap.

Seriously, it takes a pretty amazing amount of hubris to say, essentially, "well, since we can't find the cause with a couple of tests, it must be that you just _think_ something is physically wrong with you."

None of that is to disparage real psychological conditions, many of which are very serious, many of which almost certainly involve major physiological dysfunction that we have yet to understand well. It is to say that treating people as though their clear physical symptoms are all about some mind-body hoohah because we can't see anything on a basic blood panel is just as friggin' sketchy as any of the crap coming out of the worst of the woo.

The evidence of major and debilitating physical symptoms coming from anything but the most extreme and obvious psychological illness is not frankly very compelling, nor is the evidence for such major depression causing havoc but that wouldn't be recognized by the patient actually reporting feeling, you know, depressed.

Then I got to this:

"I'm also of the opinion that most auto-immune diseases are simply a side effect of an inability of the body to properly detoxify itself." -EvilYeti

Oh dear. Scientists with various backgrounds and some working knowledge of subjects can certainly disagree on all sorts of things, make mistakes, say things wrong, think about things in funny or incorrect ways, retract, rethink, and so on. I certainly don't expect anybody to never, ever say anything sort of stupid, no matter their credentials. But that, my friend, is just completely stupid. I mean, really, really stupid. Utterly, amazingly stupid. I suggest you go actually learn something about the immune system -- at least to the level of Bio 101 -- before commenting further.

You couldn't make this up...

"WPI OFFERS TO RETURN PATIENTS BLOOD SAMPLES
If you sent your blood for research at WPI and no longer wish for WPI to have your blood to use in their research, you should send WPI a message asking that the return your blood.

Through Andrea Whittemore on Facebook, WPI has made an offer to return blood samples to those who write and ask for it. You can send your email to info@wpinstitute.org, with a copy to Annette Whittemore at annettew8@gmail.com

Sample email:

Please return the blood sample which I contributed to WPI for research purposes. I donated my blood for research by Dr. Judy Mikovits. Since Dr. Mikovits is no longer employed by the WPI, I no longer wish to participate in research at WPI.

If you prefer, you may send my blood to Dr. Judy Mikovits rather than returning my blood sample to me.

(your name)"

Message from Judy M:

"With reference to the statement by WPI to research participants to request the return of their blood samples: It is an IRB/privacy violation to send anyone but me your information. Annette and Andrea are not approved to know participants in any studies. Please DO NOT write to the WPI under any circumstances as they do not have permission to know participant identity or contact. They cannot return processed blood samples and should not have any access to identifying participant information."

More here (if you can bear it):
http://www.mecfsforums.com/index.php/topic,9912.0.html

WTF, Wessely believes that ME/CFS is the result of 'dysfunctional illness beliefs', with the supposed 'dysfunctional beliefs' in question being the patients' 'belief' that they are suffering from organic disease to begin with.

From the Manual of cognitive behavioural treatment for CFS by Chalder, T, Deale, A, Sharpe, M, Wessely, S, in conjunction with the PACE trial, 2002- "According to the (CBT) model the symptoms and disability of CFS are perpetuated predominantly by dysfunctional illness beliefs and coping behaviours. These beliefs and behaviours interact with the patient's emotional and physiological state and interpersonal situation to form self-perpetuating vicious circles of fatigue and disability...The patient is encouraged to think of the illness as 'real' but reversible by his or her own efforts' rather than (as many patients do) as a fixed unalterable disease.

Compare the above with the following reports from recent international biomedical research conferences and tell me which one is not like the other-

International Science Symposium for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome (ME/CFS)
http://www.bond.edu.au/research/research-at-bond/events/BD3_014159

State of the Knowledge Workshop on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Research Report
http://orwh.od.nih.gov/CSF%202011/SoK%20Workshop%20Report%20508%20compl…

@DM..this latest from SWMNBN has me convinced she is MORALLY bankrupt, I was thinking she couldn't go any lower, but now she is using patients to keep her grant... Take the effing grant away and give it to one of us who will use it for good..

I like that lawyer..few weeks ago he was trying to teach Rancaniello virology 101 telling him he was biased and wrong about xmrv..this week he is trying to brown nose VR cuz he found out VR is getting involved in me/cfs...but he wants VR to work with judy, not trust anyone else on the commitee, and take down his link to ERV!

Levi, how did you come out of those forums with any sanity..? It is too bad that you and others like you couldn't start your own sane forum..I believe depression in MS is the same as me/cfs,(and a million other chronic conditions) it's reactive and I think it is Montoya(?)the guy from Stanford, is who's theory I like..causative agent may not be important, the immune response is where the true problem lies..

By mary (abbie's ilk) (not verified) on 12 Oct 2011 #permalink

Philosophically, I agree with you that study into psychological issues is a fine thing to research. Fundamentally, the whole point is that nobody has any friggin' clue what causes CFS, so nothing with any possibility whatsoever should be ruled out. It's also true that it's not easy to study other possible causes without some breakthrough giving researchers some new directions to look -- which is part of why a lot of folks were so excited at the possibility that at least findings of XMRV, even if there were some flaws in the work, would provide people with some new ideas for looking at it. It would certainly help if psych weren't the _only_ direction usually getting much attention or research.

I think, though, that there's a practical reality to it that you need to keep in mind. The reality is that very, very few doctors are actually very good at saying the simple three words, "we don't know." Once you are sent to psych, as a patient, the assumption very quickly becomes that _every_ symptom that can't easily be found through a simple blood test must be caused by your psych issues. Simply put, the medical world becomes very, very uncomfortable about dealing with you at all, because they don't have an answer and would much rather just shrug and let psych deal with you.

We're not talking about reality = "maybe talking to a psychology professional while we figure this out would be a good idea, maybe it'll help, this has to be depressing anyway, and we'll keep on looking at stuff as we can and trying to find treatments that may help you better." Reality actually = "there's clearly nothing wrong with you, because we're so smart we'd find it immediately if there were, so go talk to a shrink about your problems with your mother and get out of our hair while we go on to more important matters of physical health."

In the case of narcolepsy, huge numbers of patients are first misdiagnosed -- and treated for, with sometimes heavy medications -- everything from depression to bipolar to conversion disorder. It takes the average patient like 10 years to be properly diagnosed. As an added bonus, some antidepressants effect the pathways implicated in narcolepsy with cataplexy, in ways unknown. So you've got some of these folks getting no meaningful help for years or sometimes decades, being put on a whole lot of rather nasty things with effects we don't understand, and being told by basically everybody that if they'd just stop _thinking_ they're physically sick, they'd be all better. That's years of their lives spent unable to function, and being made to feel like whiny fakers for it to boot.

And that's for a disease we do, theoretically, understand at least _some_ underlying physiology for, and can sorta kinda diagnose meaningfully if we don't write people off when their blood count looks fine.

http://queenofsleep.wordpress.com/2010/10/18/statistics-that-frightens-…

http://www.ncbi.nlm.nih.gov/pubmed/11833859

Psych treatment can be a very helpful thing for people going through the pain of illness -- lord, if you weren't depressed when you _got_ sick, I can almost guarantee you'll be depressed on and off once you are. And researching in psych is well and good, we should be open to various possibilities. But understanding all of that stuff above is important, too, if you want to actually help people, and you want to understand their reactions to some assertions of psychological connections with their illness.

The crap coming out of EvilYeti would be so ridiculous as to be taken as snark in just about any other context, but it's par for the course in discussions of this particular health issue, and that pretty much kills any thoughtful discussion on psych playing any role whatsoever.

I disagree when people say that 'no one knows whether ME/CFS is physical or psychological...' ME/CFS patients know very well that ME/CFS is not a psychological illness. It has nothing to do with bias or prejudice against people with mental and/or behavioral illnesses, its just simple fact. When I exert myself for even 30 minutes I can go 6 weeks straight of being pretty much incapacitated. There is absolutely nothing psychological about any of it, it is pure physical disease. My joints are on fire, my head aches, I feel like someone physically let the air out of me. As much as people (including myself) like to gawk at the couple dozen individuals on a certain forum who have been described as 'tossers', ME/CFS patients are lucid, rational, coherant, etc.

For someone to 'imagine' they were as sick as ME/CFS patients are, they would have to have clear seperations from reality. As a commentor said previously, there are around 1,000,000 people with ME/CFS just in America alone. With a couple dozen individuals giving the rest of us a bad name, that's around 999,950 facepalms from the rest of us.

I liken the treatment of ME/CFS patients today to the treatment of parents of autistic children some time ago. They were told that they caused their child's autism as a result of being emotionally distant, ie the 'refrigerator mother' theory or autism, prominantly asserted by a guy named Bruno Bettelheim. After a while, those parents got fed up and told Mr. Bettelheim exactly where he could stick his bullshit psych(o) notions and also just how far he could stick them. It had nothing to do with prejudice towards individuals who are emotionally distant or that there was no such thing as being emotionally distant or that they hated people who were emotionally distant. It had absolutely nothing to do with anything, but was purely to do with 'it just isn't so, you have no fucking idea as to what you are talking about and please leave us the fuck alone'. That's it.

I don't think it is a case of 'we can't find anything physical, so it must be mental'. There is pretty good science pointing to a possible dysfunctional stress system. Also bear in mind that excessive stress can cause severe physical illness with no psychological symptoms at all (see Selye's early experiments on rats for example) - we have known this stuff for over 50 years and it is basic biology, yet it seems to be unknown to many people.

Also, it is not true to say that Wessely believes that CFS is caused purely by abnormal illness beliefs. That is just one perpetuating factor, but not the whole shebang. Bear in mind that CBT is effective in helping with the fatigue and reactive depression associated with cancer and HIV, but nobody in their right mind would say that those illnesses are caused by abnormal illness beliefs (or any other psychological factor for that matter).

From the Manual of cognitive behavioural treatment for CFS by Chalder, T, Deale, A, Sharpe, M, Wessely, S, in conjunction with the PACE trial, 2002- "According to the (CBT) model the symptoms and disability of CFS are perpetuated predominantly by dysfunctional illness beliefs and coping behaviours. These beliefs and behaviours interact with the patient's emotional and physiological state and interpersonal situation to form self-perpetuating vicious circles of fatigue and disability...The patient is encouraged to think of the illness as 'real' but reversible by his or her own efforts' rather than (as many patients do) as a fixed unalterable disease.

Oh boy. How stupid can you get. From V99:

The Lombardi gel (Fig. 2C) contains only CFS patients

In case anyone missed it.
Cos I can tell people have.

All the patient data in the slide being debated are CFS patients.

The 8th lane is of course the SFFV infected cells.

Normal only means they did not express virus.

This is what the description says about the Fig 2. gels.

Quote
Fig. 2. Expression of XMRV proteins in PBMCs from CFS patients.

Permission to repost

In case the forums or any 5 year old missed it.
Cos I can tell V99 has.

The desription of Figure 2, if you, like any 5 year old, are able to read beyond the first sentence, reads:

(C)* Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) or from CFS patients (lanes 3
and 6) were analyzed

*[note that that this, Figure 2C, is the actual figure we are talking about]

I cannot believe anyone can truly be this stupid and yet be so confident that she has more knowledgde and insight into the matter than a professional retrovirologist. If she had been part of the study by Dunning and Kruger, I am sure they would have won the Nobel instead of the ig Nobel....

John, thanks for posting that again but I did see it the first time, and I have come across that before. The important point is "are perpetuated predominantly", not "caused" by. Wessely acknowledges that viruses are triggers for CFS, for example.

@John -- I don't disagree with you, honestly. But I do think there can be cascading effects once a physical illness -- especially something like a brain disease -- starts effecting emotional and behavioral factors, say. They're all in a loop with each other.

My disease is actually a sort of perfect place for seeing the nexus of all of these factors. Emotional response is an integral part of the inappropriate physiological reaction that throws people into REM or cataplexy -- something about the physiology of emotional response seems to tell the brain to go all haywire into the paralysis that would be normal in a dream state. This is part of why it's so frequently misdiagnosed as psych -- if I walk into the average doctor's office and say that my limbs go limp when I get angry, they're going to think "psychological problem," not "narcolepsy." But it is a fundamental piece of the physiology of narcolepsy, and it's a fine example of brain function being rather more complicated than either psych thinking or most current physiology seems to know what to do with.

The lines in this stuff are complicated, and there are massive links between what we call "psychology" and what we call "physiology." Those are important. Fundamentally, research on all ends is philosophically a good thing, though the reality paints a different picture.

But I do agree with you that psychological illness in such a large group causing such major physiological dysfunction seems unlikely as a root, and I completely chafe at the idea that we can declare people to be "depressed" who deny that they actually feel the symptoms of depression. Shit, if you constantly mistrust what the patient actually says they experience, then how the hell do you ever practice any medicine in the first place?

It took me several years worth of doctors -- I'm quite sure my record says something about "doctor shopping" somewhere, and they all seem to be convinced that there are hordes of drug seekers trying for years on end to be diagnosed with narcolepsy so as to experience the sheer joy of modafinil headaches -- to find one who, when she asked me whether I'd been feeling any depression, actually just believed me when I said, "you know, I've thought about it, and no, not when these symptoms hit, I wasn't depressed. I'm a little depressed now, because it's depressing, but at that time, I was actually feeling pretty content." She nodded, she wrote it down, and she's been trying her ass off to help me figure this out ever since.

Two years, it took to find that. Because they all seem to think they know better than the patient what the patient might be experiencing.

That's a major problem. If you ask somebody whether they're depressed, it's a question only they can actually answer. If the answer is no, believe them.

A lot of diseases have to run this gauntlet. Narcolepsy did, for sure. MS was psychogenic, too. So were ulcers, for that matter.

Almost never winds up being true, but they keep on doing it -- every time a physiological cause is found for a "psychogenic illness," they just pick the next thing.

An absence of evidence still isn't evidence of absence.

@WTF -- not to get into the weeds parsing an abstract to death, but I don't agree with you that that's the only important point -- whether I agree with you on its reading or not.

I think the more important point is:

"The patient is encouraged to think of the illness as 'real' but reversible by his or her own efforts' rather than (as many patients do) as a fixed unalterable disease."

People with AIDS do see some help with fatigue, sometimes, from CBT. But nobody tells a person with AIDS to think of their disease process as something they can reverse if they just _try harder_, which also carries a stigma if you actually can't reverse the process. Since you can always be said to just not be "trying hard enough."

That's a huge problem, and involves a huge set of assumptions that not only is psych a factor somewhere in the brain's cascading functions, but is enough of a root that the patient can be expected to just think their way out of feeling sick.

narcolepsy is [...] listed in the DSM, as it was historically treated as a psychiatric illness, and (3) pretty much understood by everybody at this point to be a brain disease

This is a useful reminder that the DSM is basically an occupational chart of specialisations in the psychiatric world. Diagnostic categories are not there because of any evidence distinguishing separate disease entities, but rather because a group of psychologists claimed to *treat* each diagnosis and successfully lobbied for official recognition of their professional niche.

By herr doktor bimler (not verified) on 12 Oct 2011 #permalink

@WTF -- also, re:

"I don't think it is a case of 'we can't find anything physical, so it must be mental'. There is pretty good science pointing to a possible dysfunctional stress system."

From a diagnostic standpoint, rather than a research standpoint, I can tell you anecdotally that "we can't find it, so it isn't there" is exactly what I experienced. As did a relative, who also has both the disease and some fancy letters at the end of his name from knowing a lot of shit about neuroscience. As do many, many patients, all anecdotally, because nobody has bothered to take those anecdotes and design a study that would make them into "data."

I do realize that it's different on the research end than the clinical. But the clinical is where people get screwed.

Also, markers of dysfunctional stress regulation may or may not be "psych," depending on your point of view. I don't mean to keep coming back to my own disease, it's just such a good analogy that I will do it anyway -- there are studies showing that narcoleptics (with cataplexy) seem to _process emotions differently_ than people without narcolepsy, probably as a long adaptation to having strong emotional responses start the cascade toward a cataplectic attack.

Where we draw those lines -- psychology vs. physiology -- is based on our own rather stupid set of categories, not based on much understanding of the actual physiology involved in the brain as it deals with various signals, including those from emotional centers. Dysfunctional handling of stress doesn't tell us much beyond "something in the brain's reaction to stress is wonky." That may or may not be part of some other pathway that is clearly physiologically screwed up. We don't know.

@spit: I agree that it would be incorrect to say that AIDS or MS would be cured by CBT or other psychological treatments. However there is plausible science suggesting that CFS could be (and that is certainly my anecdotal experience, FWIW). The psychiatrists aren't trying to annoy anyone, they genuinely believe they are helping CFS patients, and that is my intention as well. I just think that patients should keep an open mind about this and not reject it simply because they don't like it. As far as I can see, it is the most plausible explanation for CFS at the present time.

I think John hit the nail on the head above - many patients believe that because the symptoms are physical, it must be an organic illness. That argument is demonstrably false.

@WTF -- I don't doubt the sincere intentions involved.

But I do doubt that "plausible" scenarios involving psychological illness warrant telling patients that they would feel better if they just stopped thinking they felt sick.

I'm sure some people do feel a bit better; psychological support and some form of intervention help with almost anything, and CBT helps a lot of things at, shocker, exactly the same rate as any _other_ actual effort toward addressing somebody's concerns. The kicker in a lot of therapy is that it seems to help people to feel that they're doing something, and there are any number of places where it appears that it's the "doing something" that helps more than the actual nature of the thing that is done.

Now that I'm very sick, that makes a load of sense to me, honestly. Sitting around feeling like shit and doing nothing ("these medications are the best we can do, we'll just have to wait for more research") sure doesn't make anything feel better.

I'm also pretty sure -- or at least have a lot of reason to think -- that there are no small number of terrible ailments, post-viral fatigue, basically, that we do not understand and that do resolve, over a few years, basically on their own. They don't appear to be psychogenic, but they take a long time to get over, during which a patient will undoubtedly try any number of treatments. When they got better, as they may in a couple of years, they would probably link that to some treatment or other, when the reality is that whatever the course of the condition was had simply resolved.

Hell, we act now like the flu is no big, but given its historical effects and its ability to really fuck with the immune system, I'd not be terribly surprised if plenty of people have longish term recoveries from a bout of some specific little nasty strain of the flu. That are probably misdiagnosed, because it lasts a few years. And resolve because... we don't know. Because they do.

There are a lot of factors in this stuff. I don't think we know nearly enough about _any_ of it to just go telling people that they should just stop thinking they're sick, and then they won't be. Maybe it's true for some -- I honestly kinda doubt it, but maybe. But if you're wrong, it's flat out fucking cruel.

I dont understand WTF.

"many patients believe that because the symptoms are physical, it must be an organic illness"

You are saying that this argument is demonstably false. In what way?
All psychology is brain, hence organic. What is a 'non organic' illness? Some confusing terms here.

From my perspective, CBT is a placebo in that the therapeutic effects it has are not mediated through a direct pharmacological, physical, surgical, or other direct effect. All the effects of CBT are mediated through communication, they are mediated through the CNS. That is how all placebos have their effects mediated.

Sometimes placebos work. Sometimes they do not. Sometimes CBT works, sometimes it does not. Sometimes acupuncture works, sometimes it does not. When acupuncture works, those of us in the reality based community do not take that as evidence that there is actually such a thing as chi and that the acupuncturist achieved better balance of that chi and so the patient got better.

Similarly, when reiki works, those of us in the reality based community don't take that as evidence that there are energy fields that no instruments can measure and which physics has no evidence for, but which reiki practitioners claim they can manipulate and use to heal people.

If CBT worked every time to cure CFS, that would be one thing, but it doesn't. When acupuncture doesn't work to cure CFS, is the problem that the patient has recalcitrant chi? Or that acupuncture doesn't work for CFS? Or that placebos don't work for CFS. Or that this placebo didn't work for this particular case of CFS this particular time?

My perspective on CFS is that it relates to the regulation of the stress and fatigue compensatory pathways by the CNS. Normally that regulation is automatic and is not (particularly) under voluntary control. Placebos have their effect by triggering that automatic control.

As I see it, any chronic problem has to do with a fault in the automatic control of physiology. Either the control messed up and allowed a dysfunctional state to occur, or control messed up in that it didn't fix the dysfunctional state after it did occur. I appreciate that most people (including doctors) don't think about physiology this way.

Normally the stress and fatigue compensatory pathways are triggered following a stress, after the stressor has been dealt with. After you have escaped from a bear, you need to turn off the âfight or flightâ state and turn back on everything that got turned off as your body allocated all energy reserves to escaping from the bear. Lots of things get turned off by stress. Things that you need, like healing. The reason healing gets turned off by stress is that healing is not the highest priority, staying alive is. If a bear is chasing you, your body will turn off healing to divert ATP to those pathways that will help you to escape.

A lot of the signaling of the fight-or-flight state is by low nitric oxide. A lot of the signaling of the end of the fight-or-flight state is by nitric oxide levels going back up. If nitric oxide doesn't go back up, then you stay in the fight-or-flight state long term. Every symptom that people with CFS experience can be explained by low NO. âLowâ is relative. The normal basal level of NO is sub nM/L. That is tricky to measure in vitro. There are no techniques to measure it in vivo on the length and time scales that are important. Sort of like how 100 years ago there were no techniques to measure insulin in vivo. Just because there were no techniques to measure insulin, didn't make diabetes psychosomatic.

Some interesting informed discussion daedalus2u, then in the back of my mind came a little alarm ....'I'm gonna see NO soon...'. Sure enough it came eventually.

I will have to read your stuff, but for parsimony, it should slot simply with the basic fact that 70% of CFS patients report an infection as the trigger. Commonly 'Mono', but often bad flu. Stressful perhaps, but hardly 'low healing priority' states.

I cannot believe anyone can truly be this stupid and yet be so confident that she has more knowledgde and insight into the matter than a professional retrovirologist. If she had been part of the study by Dunning and Kruger, I am sure they would have won the Nobel instead of the ig Nobel....

The sad part is that if you lurk backwards through the posts, it turns out someone already told her that, too. Ignorance must truly be bliss =P

By Poodle Stomper (not verified) on 12 Oct 2011 #permalink

The infection route is also mediated through NO but is slightly different. Sepsis is a state of very high NO due to expression of iNOS (I discuss this on my blog in the context of mitochondrial damage in sepsis).

http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failu…

The very high NO levels raise ATP levels very high, but also shut down mitochondria most every where. The high ATP keeps mitochondria off, the high NO blocks cytochrome c oxidase so it can't reduce O2 to water. The high ATP level is maintained via glycolysis which is ok, so long as you just lie there so the puny ATP production by glycolysis is enough to keep you alive. If the ATP level from glycolysis falls, for example if you can't make enough glucose, then your mitochondria turn-on, and in a high NO environment they have to generate superoxide to destroy the NO to disinhibit cytochrome c oxidase so O2 can be reduced. Mitochondria have unlimited capacity to generate superoxide, so they do. In a high NO environment, that superoxide forms peroxynitrite. That peroxynitrite selectively nitrates a single tyrosine in MnSOD and inhibits it. This is a "feature". With MnSOD inhibited, the superoxide level goes up, the peroxynitrite level goes up, the whole respiration chain gets nitrated and shut down. This is the âfuseâ that protects cells from mitochondria making too much superoxide. In a high enough NO environment, too much superoxide will turn off mitochondria. Turn off too many mitochondria and you get multiple organ failure.

A stress-type mechanism will probably take a few weeks to lead to CFS. An infection type mechanism can cause it in a day, or even less. Usually the high NO of sepsis lasts for a day or so, and in the wild you either recover or die. In a hospital, you can survive but end up with CFS.

You can get similar effects from trauma with hypoperfusion or hypoxia. They also causes very high NO levels (by another mechanism). This can happen very fast, an hour even (depending). Depending on the details of reperfusion, you can get reperfusion injury which can also cause mitochondria damage by the same NO-superoxide mechanism.

The symptoms of fatigue in CFS are (my hypothesis) from the same mechanisms as the fatigue from other chronic disorders, dilative cardiomyopathy, cancer cachexia, liver failure, kidney failure, COPD. The âproblemâ is the inability of the fatigue compensatory pathways to deal with what is causing the feelings of fatigue.

@David: organic is a pretty well defined term...basically it means that the illness is not psychogenic. You are right in saying that everything can eventually be explained by physiology, but there is a distinction between organic illness and psychogenic. Anyway, the argument is demonstrably false because stress can cause physical symptoms with no psychological ones. As for your comment about "70% of CFS patients report an infection as the trigger": infections are stressors. When you have a fever your body mounts a stress reaction (with cortisol, adrenaline and other stress hormones) in pretty much an identical way to a psychological stressor.

@spit: I agree that we shouldn't be telling patients to 'stop thinking you're sick'. While that certainly is a factor for some patients (as we can see from the 'tossers' on the other forum), that certainly wasn't a factor for any of the patients I have talked to who have recovered. I think that this dubious theory (along with the dubious theory proposed for GET - it seems highly unlikely that athletes become deconditioned overnight) does put off a lot of patients. CBT and GET do work, but I'm not sure they work for the reasons given by their proponents.

@daedalus: CBT doesn't cure depression every time either. Research seems to show that CBT is as effective for depression as it is for CFS (i.e. only moderately effective). I think you're right in saying that CBT is probably mostly a placebo. But why do you keep going on about nitric oxide when there is pretty much no evidence of it being a factor in CFS?

My own view is that CFS is a crash of the stress system. I think that the labels "organic" and "psychogenic" fail to adequately categorize CFS, which seems to be at the borderline of mind and body. Perhaps the word 'functional' would be a more accurate term.

Well I certainly need to brush up on metabolism maybe, but I dont understand why these type of theories dont reference known mitochondrial diseases first, and see if working back from there, some way into CFS might be found.

I dont see much accepted consideration that CFS is some kind of mitochondrial myopathy. I am a bit sceptical, until I am comfortable with fully understanding your biochemistry.

Sorry if I misunderstand you at this point.

Just an editorial note-- thank you all for being patient when things get caught in the spam trap.

I dont know why 90% of the ones that get sent there are sent there, but I try to get them out as fast as I can, and I really do apologize for the sputters in conversation it causes. There just aint nothin I can do about it, so I appreciate you all just rolling with it :)