LABORATORY #1–
Dr. Myra McClure recently did an interview with ABC Australia on XMRV an what its doing in humans. You probably dont know who she is– shes just a normal scientist, like the thousands of others going in to work every day that youve never heard of. *shrug* Apparently we are supposed to believe that this woman is a liar, a fraud, a cheat, and accepting bribes, and while that is difficult to believe with any normal, average scientist, its even more difficult to believe after reading the transcript of her interview.

I would quote some ‘interesting’ or ‘controversial’ parts, but its not really either. Its just a nice, level-headed, informative interview. I could see Bossman or any of my professors or any of the HIV-1 researchers I know saying the same things.

The one thing I think is funny/noteworthy is how McClure got involved with XMRV–>CFS. Her lab studies retroviruses, and they were already looking for XMRV in preserved prostate cancer biopsies. She gets a call from another lab saying ‘Hey, would you look for XMRV in our stuff?’ and shes like ‘Sure, whatevs.’

We do that stuff like that all the time. We are the only lab on campus studying retroviruses, so other PIs are like ‘Hey, we see Phenomena X with breast cancer, would you look for Phenomena X in HIV-1 infected cells?’ ‘Hey, we see ____ with influenza vaccines with our adjuvant. Could you try this with your HIV-1 pseudoviruses?’

Everyone does this in science. Its actually a running joke among grad students– these little side projects you do for other PIs inevitably work faster/cooler than your goddamn thesis project.

So McClure thought her ‘big controversy’ was going to be that she could find XMRV in British prostate cancers (no one else can find it in them, in Europe), then she does this silly little two week experiment for another lab, and suddenly shes a liar, a fraud, a cheat, and accepting bribes. hehe.

LABORATORY #2–


Then we have the lead investigator for the Whittemore Peterson Institute, Judy Mikovits.

Now, I was perfectly fine with the fact that Mikovits does not speak for WPI, any more than Peter Deusberg speaks for the University of California.

But apparently, the batshit doesnt fall far from the cave.

Last week, the president of WPI, Annette Whittemore (mummy of the oh-so-fatigued Andrea ‘Fuck all of you and if you don’t stop talking about me Im going to sue all of you for defamation of character. I know who you are . I know where you work . Im really Tired of the crap your writing .’ Whittemore) did, quite possibly the most bizarre thing I have ever seen in science.

The president/CEO of a private corporation wrote a ‘challenge’ to McClure, and did the most politically savvy thing I can think of– posted it on the snake-oil website ProHealth, and on the WPIs facebook page.

:-/

Imagine, for a moment, the CEO of Pfizer wrote a ‘letter’ like this to a laboratory that couldnt replicate the results they just published for a new ‘wonder drug’.

Imagine, for a moment, that say, Beatrice Hahn wrote a ‘letter’ like this to a laboratory that couldnt replicate her ‘wonder results’.

I have a great imagination, but I cant imagine it. Because it would never happen. To quote a brilliant HIV-1 researcher I frequently correspond with, the CEO of an organization “should not be even sending such a letter, let alone posting it publicly anywhere”.

Another called this train-wreck “highly inappropriate”.

I call it flat out stupid.

Public tantrums like this please the scientifically illiterate crowd, but so do Creationists presentations. Who gives a shit about the scientific illiterate if you are the CEO of a ‘scientific’ organization? All this scene has done for the WPI in scientific circles is put everyone on high-alert for the ‘credibility’ of results coming out of their lab.

And you probably shouldnt have a non-scientist CEO making ‘scientific’ challenges to normal, everyday scientists like McClure:

One might begin to suspect that the discrepancy between our findings of XMRV in our patient population and patients outside of the United States, from several separate laboratories, are in part due to technical aspects of the testing procedures.

…We believe that there exists compelling evidence to spur additional scientific review, especially in light of the fact that our team of researchers also discovered XMRV in the blood of 3.7% of our non contact controls.

*sigh* I know WPI and/or their associates read my blog, and yet they continue to make errors like this. Let me correct this issue for the millionth time.

PCR is one of the most basic procedures one can do in a laboratory. There is a high school kid who just started volunteering in our lab. Im going to show him how to do PCR today. This is basic, basic shit.

Lets say we are going to look for the EGFP gene in the DNA cells infected with my neat HIV-1. I used a stupid little computer program to design the primers we will use to look for/amplify the EGFP gene. This stupid little computer program does not give you ONE set of primers. It gives you dozens of options. You pick one, optimize it, and YAY, you have some PCR reagents optimized.

Now, lets say instead of looking for the EGFP gene, we are going to look for… gag! The exact same thing happens– stupid little computer program, lots of options, pick one, optimize, YAY!

There is nothing mystical or magical about having one particular set of primers to look for a sequence. Hell, the sequences you are looking for dont even need to match up all that well to the sequence you are looking for– there is always some room for variability. I can use the same gag PCR primers for numerous variants of HIV-1, even though ‘WARBLEGARBLERETROVIRUSMUTATES!’

So here is what we are dealing with– McClures lab has a set of primers they are using to detect XMRV sequences in old, paraffin-embedded prostate cancer biopsies… and they can find XMRV. When they look in PBMC from CFS patients… they cant find XMRV. There is no scientific explanation for this other than there is no XMRV in the CFS patients PBMC DNA.

Then we have a problem with the statement from WPI: “…our team of researchers also discovered XMRV in the blood of 3.7% of our non contact controls…”

No, ‘your team’ didnt. No one has found XMRV in the blood of anything, actually.

‘Your team’ used your PCR reagents and found ‘XMRV proviruses’ in the DNA of PBMCs from 3.7% of the healthy controls. ‘Your team’ then subsequently could not find any XMRV proteins or any anti-XMRV antibodies in those healthy controls, implying your healthy controls were not infected with XMRV currently or in the past, implying that your PCR primers have a high false-positive rate.

A XMRV ‘test’ that would be acceptable in HIV-1 circles finds XMRV in 3 of 2,851 (0.1%) healthy controls, which should make WPI happy because that only increases the significance of their association (9 of 18 (50%) CFS patients had anti-XMRV antibodies) (though it complicates the epidemiology), but theyre too fucking stupid and too fixated on ‘getting even’ with all these ‘mean labs out to get them’ to understand the science theyre pushing and its implications.

So, thanks, yet again, WPI crew, for giving all of us a real world example of What Not To Do in science.

Comments

  1. #1 Sili
    April 19, 2010

    *tsk*tsk*tsk*, ERV.

    The proper expression is “Kw*k them sideways with a Leica rangefinder.”

    Mmmmh – I do loves me some angry ERV.

  2. #2 Sili
    April 19, 2010

    HAH! I got caught in moderation.

    It was the reference to he who must not be named, right?

  3. #3 ERV
    April 19, 2010

    Probably 90% of the comments on this post (and all XMRV posts in the future) will be moderated for some reason or another.

    I dont handle being threatened well.
    :)

  4. #4 Sili
    April 19, 2010

    I dont handle being threatened well.

    Good.

  5. #5 ImagingGeek
    April 19, 2010

    Silly Q here, but why are multiple primers, amplifying different regions of the gene, not used? As you mention, primers can be quite non-specific, meaning the results from any one primer can be questionable. But if you have multiple primer pairs, amplifying different parts of the gene(s) of interest, and you do/don’t see product in most of the samples, it becomes a lot less likely your result (positive or negative) is erroneous…

    …just my $0.02, from a guy who only uses PCR to make GFP-fusion proteins…

    Bryan

  6. #6 Prometheus
    April 19, 2010

    I noticed Judy was scheduled to speak at the Edinburgh Hematology conference on the 21st.

    This presents amusing possibilities.

    1. The Icelandic volcano keeps her playing video poker at McCarren International until it is over.

    2. The Edinburgh volcano decides to lose its dolerite plug and the good doctor becomes the new foundation of the National War Museum of Scotland.

    Of course she could arrive safe and sound and decide to amuse the locals with some blender gimmicks that ingratiated her to the denizens of the yacht club.

    This would, in a land of single malt and cold water, lead to her being greeted with the classic Midland Valley hospitality that formerly favored King Duncan and David Rizzo.

    All in all, based on her recent derision of a lady of a Sept of the bloodthirsty Clan Macleod(Myra McClure)it should be an interesting trip.

  7. #7 qetzal
    April 19, 2010

    I agree that Whittemore’s approach is pretty heavy-handed. Certainly not how these things would normally be handled. On the other hand, maybe it’s good that she’s stepped in. I suspect things could easily have been worse if Mikovits had been the lead. At least Whittemore didn’t repeat any allegations of fraud and conspiracy.

    In any case, I think the best outcome might be for McClure to follow through with the sample & reagent exchange, and for both labs to try both assays on replicate samples. Assuming, of course, that both sides can agree to a well-controlled test plan that will likely resolve the discrepancies. If I had to bet right now, I’d bet that the WPI results are some kind of artifact, but it’s much better to prove it one way or the other with data, no?

    BTW, “the batshit doesnt fall far from the cave” is one of the best lines I’ve seen in years!

  8. #8 Prometheus
    April 19, 2010

    Shucks.

    I don’t mind being held for moderation….or for any other reason.

    *blushes*

    *is hit with frying pan*

    Is it just me or does anyone else hear this in their heads when ERV blogs on CFS:

    http://www.youtube.com/watch?v=6-pmpgrYQgs

    P.S. Dr. Mikovits honored as the Caber Catcher at the 50th Edinburgh Hematology conference?

  9. #9 gf1
    April 19, 2010

    Yay – XMRV gossip!

    re McClure interview:

    I thought Simon Wessely had said that they’d approached him for samples? Now McClure is saying it was the other way around?

    She sounded like she was playing her study down a bit too, at the time it was released she was all: “The WPI shouldn’t have released their results so quickly – you need to be a thousand percent sure” now she’s: “Oh, it was only a two week thing for us, and we could well have got it wrong because of cohort issues.”

    I was a bit surprised she was so forthright when her study came out though, so maybe she’s just reverted to normal.

    re WPI: I just expect them to act like this now. It seems like they’re uninterested in appearing professional to other scientists. If it turns out they’re right, it will have all been quite funny. If not, I can’t imagine they’ll be publishing in Science again. OH – and they mentioned testing the Dutch samples, with this not being mentioned in the final Dutch paper. Is this sort of thing normal? (Irritatingly, their results could show they’re work is right, or could show they’re just ending up with random positives – I’d have wanted to get more samples tested, and use controls unrelated to the patients).

    Oh, and re PCR and XMRV: So what’s going on with the prostate cancer stuff then? Were their technical problems with the Germans, etc, ability to detect XMRV with PCR?

  10. #10 Prometheus
    April 19, 2010

    Shucks.

    I don’t mind being held for moderation….or for any other reason.

    *blushes*

    *is hit with frying pan*

    Is it just me or does anyone else hear this in their heads when ERV blogs on CFS:

    http://www.youtube.com/watch?v=6-pmpgrYQgs

    P.S. Dr. Mikovits honored as the Caber Catcher at the 50th Edinburgh Hematology conference?

  11. #11 Galileo
    April 19, 2010

    ERV-
    I’m intrigued by your comments and sometimes they seem to make scientific sense. Though most science and science criticism is best written up as as a paper and peer-reviewed rather than blogged. But, I think you should probably refrain from saying mean things about people, in general, on your blog. It is incredibly unprofessional. Could you also post some of your research results, recent papers and CV so the rest of the scientific community who thinks that open access is more than just acting like a mediocre, out-spoken scientist on a blog can comment on your work. Thanks.

  12. #12 ben
    April 19, 2010

    Galileo you’re an idiot. As a scientist myself I’m growing increasingly weary with this horseshit that scientists are supposed be a group of poised professionals. The best scientists I know are basically sociopathic assholes who are quick to tell me when I’m being a fucking tard. Why the fuck do you think tenure was invented. Its because smart assholes are fucking useful and its retarded to fire them if they tell the wrong administrator they’re an asshat.

    This post your CV shit is fucking stupid. If you’re the kind of fuckwit who need to see a CV to tell if someones talking shit then you’re fucked. Linus Pauling had two fucking Nobel prizes for fucks sake and he went off his head about megadoses of vitamin C is his old age. Kary Mullis invented PC fucking R and you’d think he was a goddamned retard to listen to him talk now.

    Mikovits is a fucktard, her science looks shitty and unconfirmed. Its legitimate to call her a fucktard on a fucking BLOG. It may not be acceptable to write a letter to the editor of Science saying “Mikovits is a fucking tard” but you can be certain that any papers trying to replicate her experiments unsuccessfully will be full of rather dry phrases that say in essence “Mikovits et al., are full of the most egregious type of shit”. If you are horribly offended by this shit it’s your right to fuck right the fuck off.

  13. #13 Galileo
    April 19, 2010

    Ben- My point about posting science and results and a CV was called sarcasm. I was mocking ERV for being what we call “judgmental” and hiding behind the internet. This type of judgmental stuff is often in newspapers related to things like politics and religion. Check it out.

    PS. Your grammar sucks- but good job using fuck in lots of exciting ways.

  14. #14 ERV
    April 19, 2010

    ImagingGeek– Not a stupid question. The WPI paper itself included two PCR primer sets for gag, and then another set for the env gene (which might have given differing results, its hard to tell from the Science paper). This is a very, very stupid thing to be ‘challenging’ over.

    qetzal– *curtsy*

    gf1– FOR REAL!! I can make it about a month without another XMRV-CFS-drama-llama, but much longer than that and I get twitchy.

    I dont think McClure is playing anything down (or was playing anything up). WPI was (is) trumpeting all over that XMRV=CFS, yet McClure had 128 CFS patients with no XMRV. 0% is a very, very different number than ’67%’ (or what was it Mikovits was saying at one point? 97%??) when you are talking about the epidemiology of XMRV and putative treatments for CFS patients. The WPI should not be saying theyve got this shit nailed down, McClure is aware of her limitations *shrug*

    Regarding prostate cancer– you know, I dont recall Robert Silverman even once bitching about other labs ‘not using The Holy Blessed Primers’ or the ‘Sacred PCR Master Mix’… When hysterical whack jobs arent involved, science isnt so… dramatic. You just keep doing what youre doing and eventually everybody figures shit out. I mean, weve been playing this game with MMTV for years, you simply dont see these accusations/’challenges’ being made with any other virus, with any other putative human disease.

  15. #15 Prometheus
    April 19, 2010

    Galileo,

    Ben’s grammar sucks less than your grasp of sarcasm.

    P.S. But good job of lurking, in order to avoid making an ass of yourself. <—Sarcasm.

  16. #16 pochoams
    April 20, 2010

    Erv

    All the time that I try to read one of your post, I have to stop, and I get discouraged to finish it, you know why? Because of your heavy language and your aggressiveness and lack of respect towards CFS patients or the ones that are trying to help.

    I am I CFS patient myself, and I think you deserve jail for saying what you do and laughing of Andrea Whittemore calling her the “I am so tired”. When you laugh about her, you are already insulting a community of sick people that suffer from CFS. Would you laugh the same way of people that has aids, cancer or MS? Would that be crossing the line? You have crossed this lines in many ways, and you have become what we call in Spain a trash journalist, very far away from the professionalism, ethics and scientific profile that you claim you have by the way you write.

    I remind you that this month CFS has been recognized in Ontario as a neurological disease, It has been forbidden in Canada to donate blood from CFS patients in order to avoid XMRV contamination of Blood Banks, and it has been manifested by WPI and recognized by the Dutch Investigators that XMRV was found in the patients of their study, which means they lied to the press when they published their results without revealing this details. Contamination was excluded because there was an immune response to the virus in the lab.

    Don´t even answer me, I only read part of you because you are in google alerts on CFS news, not because you interest me whatsoever…

    Life is a paycheck, and I hope that what you do comes back to you in form of CFS/ME

  17. #17 Henry
    April 20, 2010

    OK So why can McClure find XMRV in prostate cancer samples but not in cfs blood samples. One possible very simple explanation relates to the tissues examined. In a study of Monkeys infected with XMRV although the monkeys were infected via the blood apon harvesting (ugh poor things)the blood had either very little or completely undetectable levels of XMRV. The lymph organs were a different story. Also affected were the lungs etc. In a study of prostate cancer where the plasma was tested for XMRV also it was usually completely clear. So this might explain why Mikovits has to culture it from lymph cells and retest. The simple fact might be that their is very little XMRV in the blood and sometimes none detectable. As was the case in the monkeys and XMRV +ve prostate cancer. Surely Myra can work that out. Some of her statements have seemed very unprofessional to me. She stated that she was shure 1000 % CFS patients did not have XMRV. I am not a scientist in any way but even I can see the possible significance of the Monkey study finding XMRV in organs and often not at all in plasma.

  18. #18 Shirakawasuna
    April 20, 2010

    Galileo, you should probably do your research before pretending to have witty (lol) criticism. ERV is hardly anonymous.

    But hey, knock yourself out being like other creepy XMRV+CFS commenters and attacking the grad student out of a faulty sense of hypocrisy rather than addressing the topic.

  19. #19 pochoams
    April 20, 2010

    I see that you censured my comment, because is not in here, and I see additional comments since I placed it. I did not expected more from you actually… you like to make nasty remarks, but you do not accept educated ones to yourself.

  20. #20 oregano
    April 20, 2010

    “But apparently, the batshit doesnt fall far from the cave.”

    ERV is a perfect example of that! Consumed by jealously, or maddened by fumes? WPI has never said XMRV causes CFS, so why keep telling that lie?

    McClure’s samples came from Simon Wessely, the psychiatrist who has dedicated his career to denying the biomedical facts of ME and who is paid by UNUM, famous for denying disablity to people who have paid their premiums. She was set up by him and now she’s realizing it and backpedaling like crazy. His mistake was in cleaning the samples so well that there was ZERO XMRV. The rest of the world, ie Japan, has found at least 1.7% in BLOOD.

  21. #21 ben
    April 20, 2010

    No, Galileo I think I know exactly what the fuck your shitty point was.

    Shorter Galileo “ERV is a grad student with not too many publications so her points aren’t valid and she should shut the fuck up. Also shes mean and unprofessional, what a bad scientist, nobody listen to her. Mikovits published in SCIENCE!!!! she’s the tits and the best scientist.”

    Although your stupid-assed appeal to authority may fly in other circles its an unbelievably poor argument to make to most scientists.

  22. #22 Heidi
    April 20, 2010

    BRAVO! Excellent use of sarcasm! A post full of personal attacks questioning professionalism. Are you sure you do not want to change your major?

  23. #23 qetzal
    April 20, 2010

    Galileo writes:

    I was mocking ERV for being what we call “judgmental” and hiding behind the internet.

    So let me get this straight, “Galileo.” You’re anonymously mocking ERV for anonymously mocking Whittemore & Mikovits?

    Very humorous; thanks for the laugh! If you don’t already work for the Discovery Institute or some similar outfit, you should definitely give them a call. You’re a natural!

  24. #24 Jacqueline
    April 20, 2010

    @Henry
    So this might explain why Mikovits has to culture it from lymph cells and retest.
    Where does this say so in the original article? I only see enrichment (purification) for PBMC’s (not only lymphocytes) before doing PCR. And Fig 1 only shows (very strong) bands after the first, not the second, PCR round. Why are only the Cleveland samples shown?

    Or did I miss something?

  25. #25 qetzal
    April 20, 2010

    Jacqueline,

    Subsequent to the Science paper, WPI claimed that they usually needed to culture PBMCs before they could detect XMRV by PCR. (See point 7 of the second Feb. 18 In the News item here.) However, my careful reading of the Science paper shows no such claim. The do mention culturing PBMCs, but not for PCR.

    I’m really not sure what’s up with that seeming contradiction. If they really did have to culture the PBMCs to detect XMRV by PCR, you’d think that would have been important enough to state explicitly in the paper, right?

  26. #26 Jacqueline
    April 21, 2010

    Thanks @qetzal. Now I know where this came from (a comment on my blog said the same).

    So the news (you link to) tells us:

    Careful reading of the Science paper shows that increasing the amount of the virus by growing the white blood cells is usually required rather than using white blood cells directly purified from the body.

    So it should be in the Science paper, mmm…. But we can’t find it.

    Yes sure, EVERY detail should be in the paper and especially crucial details: The need for culture, how often you have to PCR before getting a positive result, or in other words how many copies are present in each sample. You need to know the sensitivity of the assay (spiking PBMC with XMRV).
    If they need to culture and test say tenfold for one sample to become positive, then you know the XMRV will be below the detection limit of a normal PCR and you just detect it by chance, once in 10-100 samples.

    What’s more: if there is so little virus that you barely can detect it, why does fig. 1a (“representative sample”) show strong bands after just 1 round in nearly every CFS patient?
    Again why were only Cleveland samples shown? What did Cleveland get? Who says there is no contamination here?
    And why aren’t CSF and controls on the same gels? (and isn’t the researcher blinded to the samples.)

    Btw I’m not very impressed by the McClure PCR either. Use of whole blood, no spiking, no sensitivity given, no good controls and very weak bands. (and there is something wrong with the lanes, I think they called the ladder a positive sample).

    The last two papers are better with regard to the PCR.

  27. #27 ERV
    April 21, 2010

    Henry– The simple fact might be that their is very little XMRV in the blood and sometimes none detectable.

    There is no XMRV in blood. There is no lab anywhere that has seen it. Anywhere. Which is why Annettes claim of ‘our team found XMRV in the blood!’ is completely and utterly wrong. Its like having a typo in a snarky remark about someone elses typo– it just makes you (in this case, Annette and WPI) look stupid.

    She stated that she was shure 1000 % CFS patients did not have XMRV.

    Her samples dont. You optimize your own PCR reagents before you do any experiment with any patient samples, and with Real-Time PCR, I can get down to detecting ~10 copies of HIV-1 in 1,000,000 cells. If less than 10 in 1,000,000 PBMC in CFS patients are infected with XMRV, and you ‘have’ to culture them to infect more cells for days/weeks with chemicals to alter the epigenetics of the cells to get >10 damn cells infected… what kind of ‘disease’ potential are we talking about here? What exactly are we looking at?

    I am not a scientist in any way but even I can see the possible significance of the Monkey study finding XMRV in organs and often not at all in plasma.

    The paper analyzing XMRV dissemination in non-human primates is not published today, much less 5 months ago when UK Cohort #1 was published. There are problems with every paper ever published, but time-travel shouldnt be one of them ;)

    Jacqueline– Why are only the Cleveland samples shown?

    I know, right?? And what samples were sent to Cleveland? They said ‘Detection of XMRV was confirmed in 7 of 11 WPI CFS samples at the Cleveland Clinic…’ after they talk about WPIs positives. So of the 67% WPI found ‘XMRV positive’, they sent their positives to Cleveland for confirmation, and Cleveland could only confirm 63.4% of the 67%– ie only 43 of the 68 ‘PCR positive’ were actually positive. 43 of 101 CFS patients were XMRV PCR positive, and WPI has an alarmingly high false-positive rate, as I previously noted regarding their definitely not XMRV positive ‘PCR positive’ healthy controls.

    Or did they randomly send Cleveland 11 samples. Eleven. Not 10. Not 25. Not 50. 11.

    LOL, wut?

  28. #28 Impish
    April 21, 2010

    The issue really seems to be that both sides are acting and talking in a way that seems to be unprofessional and therefore not helpful to the people who are clearly affected by some sort of disease. Various peer reviewed papers have shown that something physiological is going on with people suffering from CFS.
    The various transgressions by WPI and the associated people are clearly listed on this blog. From the perspective of the “other” side it seems like some of the published papers that came out afterwards looking for XMRV weren’t exactly perfect either. When traced backwards (http://tinyurl.com/24yapac) the patients used for the paper published in the BMJ had been screened to eliminate anyone who had “delayed convalescence of a viral infection”. Yet the editorial that was included with the paper described the blood as coming from a “well-characterized” or “well-defined” patient cohort that had CFS. Hopefully it is simply stupidity that caused someone to look for an infection in people screened out against having a virus but if you combine it with the strange email conversations that took place between WPI and the researchers you start to understand the letter from Annette.
    The letter from Annette probably was a mistake. However it was not a letter from the CEO of a pharma. Annette isn’t a scientist. She is a mother with a sick daughter who managed to raise money to look for a cure for her kid. It was an emotional reaction.
    My brother in law published a paper on HIV evolution and ended up getting death threats. The reason was that at the beginning of the AIDS epidemic various things were done that discriminated against Haitians. Science doesn’t care about emotions but people have them and then case caught him by surprise.
    People with CFS have been discriminated against and told that “it’s all in your head” for a long time regardless of the studies that show that it has some sort of physiological basis. Whether or not XMRV is the cause of CFS is unknown at this time. When CFS suffers see/read people question XMRV they are emotionally reacting to the discrimination that has previously happened to them. Given what they have/are going through I like it would be nice if everyone involved could think about them and temper their responses. CFS isn’t just a disease that may or may not be caused by a virus, it is a disease that affects people and when discussing it people should try and keep that in mind and be respectful and thoughtful.

  29. #29 Coatimundi
    April 22, 2010

    This is the wierdest virus ever. The in vitro papers say it replicates like mad in cell lines and spreads easily in culture. In cells with APOBEC3G it replicates and hypermutates like HIV on meth. Seriously it mutates at a higher rate than HIV-1! Which is really high! Without APOBEC it still mutates but not as much.

    So what about in vivo? It does not replicate and you can’t find it except when you use WPI’s magic PCR assay and WPI’s magic samples. Oh and did i mention IT DOES NOT MUTATE AT ALL. Check out the first LTR on NCBI NucCore. The LTR is a very mutable part of the sequence for all retroviruses. THERE ARE NO MUTATIONS!!! Not in prostate samples not in CFS samples.

    Some seqeunces are different other places but seriously when you do PCR as much as me you know, amplify 8000 bp FROM THE SAME SAMPLE, clone it, grow it up, and sequence it, and do that 100 times, you will have some mutations somewhere and they are not real.

    So wtf or are all the prostate and CFS patients in one big Sister Clarice group marriage thing at Lake Tahoe where they all infected each other the night before the blood draw. Yeah and sorry but when you smell a stinky fish in your house you complain and you don’t worry about who your offending.

  30. #30 ERV
    April 22, 2010

    Impish– The issue really seems to be that both sides are acting and talking in a way that seems to be unprofessional and therefore not helpful to the people who are clearly affected by some sort of disease.

    Bullshit. I have seen nothing non-standard from any group except WPI. The problem is, as we can clearly see from the way a certain subculture of CFS patients act on this blog, is that any criticism of WPI/Judy/their science/XMRV in general is seen as ‘viciously attacking CFS patients’. This is not true in the slightest, and Im sick of hearing this bullshit on my blog.

    The only person/persons hurting CFS patients are the WPI/Judy and they way they are presenting themselves to the scientific community.

    … BMJ had been screened to eliminate anyone who had “delayed convalescence of a viral infection”…

    This is another defining feature of this CFS subculture. Dude, you are on the blog of a goddamn RETROVIROLOGIST. And instead of asking about this (you are clearly a non-scientist), you are lecturing on it. I have already written about this: this excluded people who were exhibiting chronic fatigue from AIDS. Or CANCER. MDs cant ‘look for’, much less ‘find’ XMRV in any patient, so how the hell could ‘anyone with XMRV’ be excluded? Think about this shit for 30 seconds, man.

    Speaking of the general anti-science nature of this CFS subculture, you know who else comes on my blog and tries to ‘explain’ retroviruses to me? HIV Deniers. And Creationists.

    However it was not a letter from the CEO of a pharma.

    Really? Cause Im pretty sure she signed her letter:
    Annette Whittemore
    Founder and CEO
    Whittemore Peterson Institute

    Or is this like how the CEO of a snake-oil company or organic food company is made of sunshine and bunnies, while the CEOs of companies that arent hippy bull-shit are the equivalent of Hitler? Fuck off.

    She is a mother with a sick daughter who managed to raise money to look for a cure for her kid.

    Oh, well then, I guess its okay for her to act like a chicken with its head cut off, then. No problem if she accuses other labs of conspiracy, her poor babby is sick. BTW, her ‘kid’ is a grown ass 32 year old woman at this point, lets cut it with the ‘kid’ shit. And they are filthy rich. Annette personally contributed more to the 2008 elections than I will make, my TOTAL INCOME, in THREE FUCKING YEARS, so lets cut it with ‘scraping together funds’ shit too, shall we?

    People with CFS have been discriminated against and told that “it’s all in your head” for a long time regardless of the studies that show that it has some sort of physiological basis.

    Which has 0% to do with attacking normal, working, everyday retrovirologists. And 0% to do with anything on this blog.

    CFS isn’t just a disease that may or may not be caused by a virus, it is a disease that affects people and when discussing it people should try and keep that in mind and be respectful and thoughtful.

    “CFS, the Islamic terrorists of diseases.”

    Coatimundi– Preachin to the choir, man.

  31. #31 jack
    April 22, 2010

    regardless of who is right or wrong, it remains a pure FACT that Mikovits is way more qualified and experienced than ERV, that is pure FACT. I have no agenda of whether XMRV is real or otherwise, or what disease it is in or not in, but please get some balance on this blog.

    I am happy to read scientific discussion, and welcome it.
    But sadly the discussions on here seem to be mostly about flaming and shouting at people do have differing opinions.

    I assume ERV wants to be taken seriously but ERV mostly sounds like a firebrand preacher with a bad case of tourettes, and there seems a strange cult like following from her “fans” on here who seem to enjoy swearing just as much as her. I am aware my post will be responded to with the usual barrage of swearing and deconstructing, so in order to try and help ERV and her disciples please take some time to study this page, it really might help some of you as quite a few people I think ERV and a few of her disciples may have this condition.

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

  32. #32 Prometheus
    April 22, 2010

    “And they are filthy rich. Annette personally contributed more to the 2008 elections than I will make, my TOTAL INCOME..”

    And there is the real rub for me.

    I don’t care if Annette wants to spend every dime her husband has made on his “city with entitlements for 49000 residential units” in Nevada (my sister calls it “More Whiter World”). If Whittemore wants to pull the fillings out of her head and sell her plasma to further research into her daughter’s illness, good on her!

    Her motives are a little narrow but they have the potential to benefit the greater good so she would be in the clear on the ethical utilitarian scale.

    The problem is the Whittemore’s don’t use their assets to further the work so much as they use them as political leverage. They get you, Nevada and I to fund the “work”. They do it at the expense of a lot of other things in a country of dwindling tax derived research dollars.

    My money gets spent on a lot of stuff I find reprehensible and CFS research is certainly not on the reprehensible list.

    The WPI being funded by influence derived from legalized graft just rubs my fur the wrong way.

    It’s like if my property taxes went up because Burns Hargis lobbied the legislature for a gazillion dollars to fund the M.Pickens/Max Factor Institute for the Development of Facial Expressions in Cosmetic Surgery Aficionados at OSU.

  33. #33 Dr. Duke
    April 22, 2010

    The problem in not only Whittemore’s leveraging their cash to pull in government cash. It is also that there will always be pseudoscientists willing to use that cash for fame and fortune. The XMRV link to chronic fatigue looks almost like a carbon copy of W. John Martin’s “stealth virus” work also done in Nevada not so long ago.

  34. #34 Dr. Duke
    April 22, 2010

    No doubt, TEH CRAZYS who follow this type of stuff will use it to claim that if XMRV does not equal CFS and “Stealth Virusts” don’t really exist, then of course HIV-1, HIV-2 and Human Inluenza A viruses also don’t exist, or maybe they exist but are harmless or something…

  35. #35 Impish
    April 22, 2010

    Hmmm… Interesting response. I am certainly guilty of a lazy initial post as I didn’t actually bother to ready the initial study myself. After looking at it I agree with you that the screening of the people for “delayed convalescence of a viral infection” might be not a problem.

    However reading about the study did raise a couple of questions that I am honestly interested in your answer to.

    My working assumption with the amount of detail I give before I ask the question is that you haven’t actually read the Oxford and Canadian CFS diagnostic criteria and perhaps might not actually have the background necessary to answer the question, RETROVIROLOGIST or not.

    It appears to my non-scientist self that there are multiple sets of diagnostic criteria for CFS patients. It seems to be that the latest ones that I looked at, the Canadian Criteria, are designed to address problems with earlier studies that tended to include people that don’t actually have Chronic Fatigue but rather have “Unexplained Fatigue” which could very well be the result of depression, etc. Here is quote from the Canadian Criteria.

    “ME/CFS is an acquired organic, pathophysiological, multi­systemic illness that occurs in both sporadic and epidemic forms. Chronic fatigue must not be confused with ME/CFS because the “fatigue” of ME/CFS represents pathophysiological exhaustion and is only one of many symptoms. Compelling research evidence of physiological and biochemical abnormalities identifies ME/CFS as a distinct, biological, clinical disorder.” Later on it is mentioned that in CFS patients you commonly see degeneration of end organs, particularly cardiac or pancreatic failure.

    The last study from the BMJ used blood taken from a group of people who don’t meet this criteria but rather have “Unexplained Fatigue”. Here is a snip from the study that the blood was taken for… “In the present study, a multi-dimensional approach to the assessment of CFS will be used. Behavioural, emotional, social and cognitive aspects of CFS (in this case defined as unexplained fatigue) are measured”. Later in the study they note that of their study group fo 298 patients 26% of them indicated recurrent infections. Only 36% of them reported memory problems. They also mention that they specifically screened out patients taking medication for heart problems.
    In defense of the study in which the blood was taken, it was done in 1994 which is prior to the new criteria being developed. This was early days in the understanding of this illness.

    So given the background, is this the patient group that you would go looking for XMRV in? If so why or why not? Would you characterize the 2nd patient group as being characteristic of CFS patients as we now understand them in 2010? If so, why or why not?

    I understand from my relatives work that it is possible to find retroviruses in very very old samples preserved in paraffin. In your opinion would you expect to find a retrovirus in the 20 year old frozen blood samples?

  36. #36 interkin3tic
    April 23, 2010

    Wow. Virology is a lot more competitive than developmental biology.

  37. #37 Sandy Slim
    April 23, 2010

    @Impish, Fukuda and Canada are similar enough that most patients who meet one set will meet the other. Most. Maybe not all. Since it’s Friday let’s be really goofy and say only 10 percent of Fukuda patients actually have CFS Canada style. Let’s also say there is no way in hell anybody detects XMRV unless they use WPI’s PCR primers.

    Stoye and Bishop did the experiment with the WPI’s PCR primers on 300 samples, half controls and half Fukuda certified CFS. We’re being silly goofballs today, so only 14 people had “real” CFS, the rest were just pretending and don’t deserve to be in the exclusive fraternity of worthy sufferers, sarcasm. 9 or 10 should have had XMRV, right, .67 times 14? Nobody did. 0 out of 14, 0 out of 128 pretenders, 0 out of 157 controls. Then Stoye and Bishop made a fancy new qRT-PCR assay to detect XMRV even better and they validated it, unlike WPI. Still nothing.

    Maybe the deal is 10% is too high, nobody with Fukuda CFS is really sick unless they are diagnosed by the four doctors who do Canada? OK, but be careful. Keep whittling away everyone who is XMRV negative and adding diagnostic criteria like loss of spleen and heart and pancreas and soon there won’t be any patients or disease left. I can see the article abstract, “CFS, a disease affecting 68 Americans in Reno……”

    Also be careful lecturing Erv about respect for patients while implying that most people with a CFS diagnosis don’t have real CFS.

  38. #38 Prometheus
    April 23, 2010

    Ha ha ha ha.

    “I’ve got REAL CFS the rest of you are just frigging poseurs!”

    When will they start printing the T-shirts so we can tell Team Fukuda from those pretenders on Team Canadian Criteria?

    “Betty can’t be team captain she only has five symptoms!”

    This is awesome.

    What if a legitimate XMRV correlation can be established?

    What happens after you spend a decade defining yourself by a disease you demonstrably don’t have?

    Are all the people who don’t test positive gonna hang themselves from the rafters of their Mom’s garage or what?

  39. #39 ERV
    April 23, 2010

    I understand from my relatives work that it is possible to find retroviruses in very very old samples preserved in paraffin. In your opinion would you expect to find a retrovirus in the 20 year old frozen blood samples?

    The oldest HIV-1 sequences I know of were fished out of blood samples drawn over 50 years ago. I think we can agree storage conditions in 1959 were different than those available in early-mid 1990s? If the virus is there, it should have been detectable.

    interkin3tic– I think virology is competitive, but this “WPI vs everyone else in the world” thing is very non-standard. I can think of dozens of current ‘controversies’ in virology, and none of them have reached this level of asshattery, from any side. No one acts like this.

  40. #40 Impish
    April 23, 2010

    Sandy Slim, I wasn’t discussing the Bishop and Stoye study. I haven’t read it. The study I am referring to is the one by McClure who is the scientist mentioned in the blog post. I am not really qualified nor want to argue about PCR. Given ERV’s job as a RETROVIROLOGIST if she says that the whole PCR primer argument is fishy I take her word for it. Just out of interest, could either of you explain to me why/if a neutralizing antibody assay would be better or worse as a detection method?

    The point I was trying to make to ERV and which I think she agrees with given her last post, is that both sides are acting in a way that is unprofessional. The last study that didn’t find any XMRV seems flawed to my layperson’s eyes. The patient population they used doesn’t seem to match any established criteria that I could find. It took me (a non scientist) all of a 1/2 hour of poking around to find this. Yet, the BMJ wrote an editorial praising the study and its methods. I can understand rushing something to press without peer review if it was seen as important but you think they would have at least devoted a couple of hours of time to looking into the paper before writing an editorial praising its science. It is that kind of poor attention to detail that makes CFS patients angry since they have suffered through it for a long time now.

    How loud both sides are screaming about this makes me personally suspicious of both. Myra McClure is probably an innocent in this. She was just running some tests. She didn’t choose the samples. The scientists who did and then presented them as from a well-defined CFS patients seem to be either willfully or accidentally doing bad science.

    WPI speaking at an autism conference or linking anything to vaccines also seems really irresponsible.

    To date the only actual benefit for the patients is that reputable scientists like Silverman, Goff, etc. are now looking into this. Additionally, big pharma is now spending money on developing detection tests and finally CFS is being discussed at the CROI.

    I look forward to reading more well done, peer reviewed papers that advance the underlying science.

  41. #41 Sandy Slim
    April 23, 2010

    @Impish, questions. Are you talking about the McClure paper in PLoSONE or the Dutch paper in the BMJ? How are you assessing the quality of any PCR paper if you don’t know about PCR? Who cares where anybody got their samples or what criteria they used? If WPI is right there is at least 4% in the general population. There is 0%. Where do you get that the BMJ did not review the Dutch paper?

  42. #42 Impish
    April 23, 2010

    I am talking about the Dutch paper. I broke down and read the paper from Kerr, Bishop, etc. It does seem quite well done and very detailed.

    Again, I am not a scientist but it would seem to make sense that samples and criteria of patients matter? Especially if you are looking for retrovirus that has turned out to be hard to find (if it in fact exists at all).

    I am sure that if ERV was trying to study HIV evolution by looking for old samples she would try and find people who died of the common related illnesses. She wouldn’t go and get blood from a group of people of whom only 23% self diagnosed with any physical illness at all. That would be a waste of her time. Furthermore I am sure the BMJ wouldn’t praise a paper she submitted to them using such patients as “good science”. There does seem to be some sort of weird bias around CFS research.

    If that paper was in my field and was going to be published in something as visible as the BMJ I certainly wouldn’t let my name be attached to it without making sure it was really good. Even if my involvement was just running the tests.

    Frankly, the more reading I do about this it seems clear that there is money involved on both sides. WPI will get lots of research dollars if they are right. The scientists on the opposing side (not Kerr, Bishop, et. al) have and continue to get money based on it being a psychological issue. Both feel threatened hence the bad behavior. I am always amazed by how people behavior changes when money is involved.

  43. #43 lvlhded1
    April 23, 2010

    @Dr. Duke, W. John Martin proclaimed his stealth virus from USC, not Nevada. Don’t further disparage the institution clawing its way up from #49 among state research universities.

  44. #44 lvlhded1
    April 24, 2010

    Today’s shopping list at Big Lots, hoping for leftovers from the H1N1 scare: hand sanitizer, toilet seat covers, paper mask, rubber gloves. That quirky XMRV is everywhere according to the latest Q&A from Doctor Judy. It’s published in what must be an up-and-coming journal of some import since they don’t seem to need copy editors or fact checkers, but it’s one helluva read. Even though the data is unpublished, it’s got me looking for XMRV everywhere. So how will the XAND people put more pews in the new wing at UNR fast enough to accommodate autistics, fibroymalgics, cancer patients and the casual contacts of people with XMRV who spew saliva, vomit and feces? Hope I can find my supplies by the case.

  45. #45 VP
    April 24, 2010

    ERV you said:

    ” ‘Your team’ used your PCR reagents and found ‘XMRV proviruses’ in the DNA of PBMCs from 3.7% of the healthy controls. ‘Your team’ then subsequently could not find any XMRV proteins or any anti-XMRV antibodies in those healthy controls, implying your healthy controls were not infected with XMRV currently or in the past, implying that your PCR primers have a high false-positive rate.”

    If you read the paper you will see that they only tested 16 out of 218 healthy controls for protein expression and 7 of the controls for antibodies. Why would you assume that they took these from the 3.7% of controls that were positive on PCR? Logically you would have expected them to have taken these cases from the negative controls and their results are consistent with that.

    Conversley in the CFS samples they report protein expression in 19 out of 30 cases and antibodies in 9 of 18 cases. This seems supportive of their argument.

  46. #46 Nila Williams
    April 24, 2010

    I’m not a science proffessor but I am a person who’s suffered with CFIDS for 40 years..yes…40
    I think you’re flipent, narrow minded and angry remarks belong somewhere out—– of our Universe.
    Let’s stay open to ‘all persons’ working on this and let’s be positive instead of making war! This is on behalf of all of us that suffer from this disease. SHUT UP WITH THE FOWL LANGUAGE AND LET THE CHIPS FALL WHERE THEY MAY.. AGAIN I SAY…SHUT UP..NEGATIVE PUTDOWNS TO THOSE WHO ARE HONESTLY TRYING TO HELP US…DOESN’T HELP US ONE BIT..AND I BELIEVE EVERYONE IS HONESTLY TRYING TO HELP US..SO SHUT UP!

  47. #47 lvlhded1
    April 29, 2010

    http://www.wpinstitute.org/news/docs/NewMedicalDirector_042810.pdf. “WPI Announces Search for Medical Director” What will the W’s do without the P? Don’t “well-planned transitions” usually mean that a replacement is recruited before a key person steps down? In the words of Ricky Ricardo, “Judy, you got some ‘splaining to do!” Take it away Prometheus.

  48. #48 Smurfette
    April 29, 2010

    I was wondering about that letter… why would the President/CEO (and one who has no science education) write to the other lab. I wonder if they even sent the letter to Dr. McClure or just posted it for the patients.

    When you say you know that Mikovits doesn’t speak for the WPI… isn’t the WPI like 3 people? Whittemore, Mikovits, and Lombardi. Dr. Peterson just “retired” as part of a “planned” transition. Wonder who is going to be their new medical director… that should be telling.

    As the autism quackery topic is being covered simultaneously, I’ve come to realize that all they need is one or a few initially published papers and then they can have control of the quack market for several decades.

    But I’m wondering if the quackery is so glaring, then why was the Virology Blog still pretty positive about the WPI paper in a fairly recent podcast with Dr. Goff?

  49. #49 Impish
    April 29, 2010

    Apparently WPI is saying they are about to publish a 2nd paper in Science. It is supposed to be out in a couple of weeks. Given what has happened with the other studies I can’t see Science accepting a 2nd paper from them unless it has a fair amount of detail and independent involvement.

  50. #50 Smurfette
    April 30, 2010

    @42 I had heard that Mikovits was answering some questions from Science which would be published in the next edition. If that’s what they’re referring to, that doesn’t sound like a “paper”.

    Re: the batshit doesn’t fall far from the cave
    http://www.forums.aboutmecfs.org/showthread.php?3441-WPI-ethics…&p=52423#post52423

  51. #51 Eco
    April 30, 2010

    Hey everyone, let’s all nominate ERV for the Nobel Peace Prize for her great contribution to mankind for confirming and verifying that there is such a real psych disorder as ‘egomania’ by own undertaking and by diligently documenting by her own personal experience and which I might add, with great peril while furthering science by making numerous claims and comments…I know she is getting all goose-bumpy… as a lowly fucking grad student against highly esteemed PhD colleagues in the field of virology by using graciously, many of her peer review research articles placed in the most prestigious journals after her many years of experience while making negligible contribution to her own field which therefore entitles her and qualifies her to become the new director of the CDC. Hear,Hear

  52. #52 ERV
    April 30, 2010

    Heh, go to the end of that thread– They think Im Veritas.

    CSI FAIL there, Barney Fife.

    lol!

  53. #53 Sandy Slim
    April 30, 2010

    Science went out on a limb for WPI in the first place, but now they are sawing it off behind themselves. They’ve got to be careful. The paper was mediocre but exciting and high profile, so OK. Then the controversy started and nobody could replicate the results. When Science wrote a news story, it was seriously skewed to WPI. Remember the WPI company selling those XMRV tests? That company was founded by Lombardi and owned by the Whittemores. The Science reporter said the Whittemores had made a donation to the company like it was AMFAR or something, and Lombardi was just an advisor. The headline of the story was “CFS attacked again.” Now Science is giving Dr. Foot-in-mouth an opportunity to give the latest version of her story, but they still have not published letters sent in by curious and concerned scientists. What’s going on?

  54. #54 gf1
    May 1, 2010

    Reply from the Norwegians:

    http://www.umcn.nl/Research/Departments/kcv/Documents/F%20v%20Kuppeveld%20brief%20naar%20Whittemore.pdf

    In terms of the patient selection, there’s was the weakest of the studies, but I’ve seen people say the virology side of it was very strong.

    The WPI’s behavior seems crazy to me, but Goff was still sounding respectful of their work on the Virology podcast. I’m surprised that someone like the CDC haven’t arranged for a large scale blinded testing of the WPI’s methods with non-contact controls. That seems like the easiest way to see if they’re really on to something important.

  55. #55 Lee
    May 4, 2010

    The first international xmrv workshop is this September. Seems all the gang will be there, including Silverman, Goff, Mikovits, Mc Clure….to name a few.

    Mc Clure leans over her desk at the conference and yells “hey Mikovits, I haven’t forgotten that letter you wrote me!” and Mikovits will yell back “babe that’s so 6 months ago, check out all the positive papers we got published now, your paper was s*** but you wanna make friends and forget the past?” (CANT WAIT FOR SEPTEMBER!!)