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We can ignore parts of this paper– they have been retracted, as it seems some samples were contaminated in a rather curious (strategic?)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.

Comments

  1. #1 FWD
    October 11, 2011

    @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-lasting-legacy-victims-ME.html

  2. #2 John
    October 11, 2011

    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.

  3. #3 Sigmund
    October 11, 2011

    “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”"

  4. #4 Mike Kelly
    October 11, 2011

    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?

  5. #5 mary (abbie's ilk)
    October 11, 2011

    a personal letter from SWMNBN can be found on the FB page of The Academy of Nutritional Medicine…perhaps a new employer?

  6. #6 RRM
    October 11, 2011

    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?

  7. #7 Sigmund
    October 11, 2011

    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)

  8. #8 Sigmund
    October 11, 2011

    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.

  9. #9 Camaro
    October 11, 2011

    #874

    Just some short remarks more about the „invalid PCR” stuff – 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 found…

    … of course VP62 (the contaminating plasmid) which explains the nearly identically sequences published with the 2009 paper – there was no sequence variation in all CFS patients! Never ever!

    Therefore it is absurd to argue that somebody won’t 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 ;-)

  10. #10 M.E.
    October 11, 2011

    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

  11. #11 Mu
    October 11, 2011

    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).

  12. #12 Poodle Stomper
    October 11, 2011

    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 ;-)

  13. #14 WTF
    October 11, 2011

    @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).

  14. #15 Camaro
    October 11, 2011

    #874

    Just some short remarks more about the „invalid PCR” stuff – 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 found…

    … of course VP62 (the contaminating plasmid) which explains the nearly identically sequences published with the 2009 paper – there was no sequence variation in all CFS patients! Never ever!

    Therefore it is absurd to argue that somebody won’t 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 ;-)

  15. #16 ErkELK
    October 11, 2011

    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.

  16. #17 Joe
    October 11, 2011
  17. #18 M.E.
    October 11, 2011

    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

  18. #19 WTF
    October 11, 2011

    @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.

  19. #20 M.E.
    October 11, 2011

    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

  20. #21 autiemum
    October 11, 2011

    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?

  21. #22 RRM
    October 11, 2011

    @autiemum

    That’s also how I understand it.

    There was some discussion about this at the forums and now the topic has been deleted (or moved to a non-public place). Perhaps the message was not intended to be public. It’s still available through this facebook site though:

    http://www.facebook.com/permalink.php?story_fbid=176398142443000&id=122950357787779

  22. #23 Mu
    October 11, 2011

    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.

  23. #24 autiemum
    October 11, 2011

    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

  24. #25 autiemum
    October 11, 2011

    @ 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.

  25. #26 David
    October 11, 2011
  26. #27 Levi
    October 11, 2011

    @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.

  27. #28 windy
    October 11, 2011

    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.

  28. #29 Jack
    October 11, 2011

    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 :)

  29. #30 David
    October 11, 2011

    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?

  30. #31 Anonymouse
    October 11, 2011

    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.

  31. #32 ERV
    October 11, 2011

    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???

  32. #33 RRM
    October 11, 2011

    @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.

  33. #34 EvilYeti
    October 11, 2011

    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.

  34. #35 herr doktor bimler
    October 11, 2011

    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 ::::::

  35. #36 EvilYeti
    October 11, 2011

    @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.

  36. #37 Poodle Stomper
    October 11, 2011

    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?

  37. #38 Impatient
    October 12, 2011

    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.

  38. #39 John
    October 12, 2011

    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, ˜3.5×10 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 ˜50%). 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.

  39. #40 John
    October 12, 2011

    link for the above patent application, DETECTION OF XENOTROPIC MURINE LEUKEMIA VIRUS- http://www.freepatentsonline.com/y2011/0151431.html

  40. #41 M.E.
    October 12, 2011

    @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.

  41. #42 Jack
    October 12, 2011

    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/presentation-summaries-from-tullamore-conference-2011/239186932797309?notif_t=note_reply

    ‘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… ‘

  42. #43 OWE
    October 12, 2011

    @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

  43. #44 perplexed
    October 12, 2011

    A letter from Judy Mikovits, apparently posted today:

    http://niceguidelines.blogspot.com/2011/10/new-message-from-dr-mikovits.html

    Is any of this likely accurate?

    (This woman is a real piece of work.)

  44. #45 Sigmund
    October 12, 2011

    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.

  45. #46 Camaro
    October 12, 2011

    @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 ;-)

  46. #47 mo (one of Abbies's elk)
    October 12, 2011

    Comon, this should be easy to control for, just do negative control PCRs for your feeders without adding B cells.

  47. #48 Sigmund
    October 12, 2011

    “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!)?

  48. #49 just wondering
    October 12, 2011

    @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?

  49. #50 ERV
    October 12, 2011

    Proper controls?

    Pulleeze. That is *so* not germane, mo.

  50. #51 WTF
    October 12, 2011

    @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.

  51. #52 ERV
    October 12, 2011

    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.

  52. #53 Prometheus
    October 12, 2011

    “….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-know-therefore-aliens.jpg

  53. #54 RRM
    October 12, 2011

    @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.

  54. #55 ERV
    October 12, 2011

    Which he helpfully posted here, I was just too star-struck to read it, apparently *facepalm*

    Thanks for the reminder, RRM!

  55. #56 RRM
    October 12, 2011

    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?

  56. #57 ERV
    October 12, 2011

    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.

  57. #58 o
    October 12, 2011

    @RRM

    Is it possible to post the link where Mikovits said that?
    Just for my records…

    Thank you

    OWE

  58. #59 M.E
    October 12, 2011

    @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?

  59. #60 RRM
    October 12, 2011

    @OWE

    The critique by Moore (and Shuda BTW) can be found at the “post-publication peer review site” F1000:

    http://f1000.com/signin?target=1166366

    It’s behind a pay wall, but you can sign up for a free week trial, I believe. The comments (as well as Mikovits’s response) are also copied/pasted at this CFS site:

    http://cfs-facts.blogspot.com/2010/02/xmrv-discussion-on-faculty-of-1000.html

  60. #61 Jason
    October 12, 2011

    if ERV is GLaDOS-derived… can you please post a vid of your singing the turret opera =)

  61. #62 daedalus2u
    October 12, 2011

    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!

  62. #63 WTF
    October 12, 2011

    @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.

  63. #64 Poodle Stomper
    October 12, 2011

    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.

  64. #65 Levi
    October 12, 2011

    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

  65. #66 M.E.
    October 12, 2011

    Interesting conclusion from the House of Lords on this http://www.meassociation.org.uk/?p=8383

  66. #67 M.E.
    October 12, 2011

    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

  67. #68 mo (one of Abbies's elk)
    October 12, 2011

    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.

  68. #69 DM
    October 12, 2011

    @ 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

  69. #70 Jack
    October 12, 2011

    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?

  70. #71 WTF
    October 12, 2011

    @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.

  71. #72 Levi
    October 12, 2011

    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

  72. #73 WTF
    October 12, 2011

    @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 :)

  73. #74 spit
    October 12, 2011

    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.

  74. #75 DM
    October 12, 2011

    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

  75. #76 John
    October 12, 2011

    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%20compliant%20-%208-5-11.pdf

  76. #77 mary (abbie's ilk)
    October 12, 2011

    @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..

  77. #78 spit
    October 12, 2011

    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-misdiagnosis-of-narcolepsy/

    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.

  78. #79 John
    October 12, 2011

    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.

  79. #80 WTF
    October 12, 2011

    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).

  80. #81 John
    October 12, 2011

    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.

  81. #82 RRM
    October 12, 2011

    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….

  82. #83 WTF
    October 12, 2011

    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.

  83. #84 spit
    October 12, 2011

    @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.

  84. #85 spit
    October 12, 2011

    @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.

  85. #86 herr doktor bimler
    October 12, 2011

    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.

  86. #87 spit
    October 12, 2011

    @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.

  87. #88 WTF
    October 12, 2011

    @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.

  88. #89 spit
    October 12, 2011

    @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.

  89. #90 David
    October 12, 2011

    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.

  90. #91 RRM
    October 12, 2011

    Trine Tsouderos tweets:

    BTW: Story coming tomorrow, or possibly Friday. An update to a story I have been writing about for some time.

    http://twitter.com/#!/ChicagoScience/status/124246572606296064

    Retraction time?

  91. #92 daedalus2u
    October 12, 2011

    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 “fight or flight” 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. “Low” 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.

  92. #93 David
    October 12, 2011

    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.

  93. #94 Poodle Stomper
    October 12, 2011

    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

  94. #95 daedalus2u
    October 12, 2011

    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-failure.html

    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 “fuse” 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 “problem” is the inability of the fatigue compensatory pathways to deal with what is causing the feelings of fatigue.

  95. #96 WTF
    October 12, 2011

    @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.

  96. #97 David
    October 12, 2011

    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.

  97. #98 ERV
    October 12, 2011

    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 :)

  98. #99 daedalus2u
    October 12, 2011

    You don’t need any kind of mitochondrial “fault” to get CFS. Perfectly normal people with perfectly normal mitochondria can get CFS. The problem with mitochondrial research is that you have to take samples of the mitochondria you want to study. Sometimes people take mitochondria from blood cells which are completely different than mitochondria from other tissue compartments. Even so, this study did find mitochondria problems.

    http://www.ncbi.nlm.nih.gov/pubmed/19436827

    I don’t like the use of neutrophils as the mitochondria source. It might be ok, but mitochondria problems in neutrophils are not what is causing exercise intolerance. That is being caused by mitochondria in muscle. There could be coupling between the mitochondria in neutrophils and in muscle. I am not aware of any research on that coupling. If there is coupling, it is probably mediated through NO because NO is what regulates mitochondria biogenesis and just about everything else about mitochondria.

  99. #100 ERV
    October 12, 2011

    RRM– Im pretty sure she is just going to tell everyone Im an android, but the aliens will just wipe everyones memory, so I dont know why shes bothering.
    :P

    I seriously have no clue. You know Id be all up in here or BadScience about to pee my pants, leaving cryptic comments until someone guesses if I did.