When scientists are creating tests to detect viruses, they need to balance two factors:

  • Sensitivity
  • Specificity

A ‘sensitive’ test is no good if it cross-reacts with other proteins/viruses/antibodies. A test with high ‘specificity’ is no good if you miss 3 out of 10 infections.

Of course, then you need to worry about cost (a perfect test is unusable if no one can afford it) and speed (acute diseases need fast diagnoses, and who wants to wait 3 months to find out if they have a life-altering chronic disease?), and other factors.

So scientists normally use tests that view a putative disease from lots of angles, reducing the odds we are making mistakes by looking for one thing the wrong way–

  • Look for antibodies to the virus
  • Look for viral antigens
  • Look for viral RNA and/or DNA

Each of these tests have variations (antibodies to what? what viral protein? viral genomes? proviruses? which part?), and when you put them all together, the odds of someone being falsely labeled ‘POSITIVE’ (or ‘negative’) drop lower and lower and lower.

One thing about these XMRV ‘tests’ and their reported ‘results’ is that some of the scientists reporting ‘positives’ are not thinking critically, at all, about what they are saying regarding the sensitivity and specificity of their tests.

Prime example, the WPIs latest bitchfest press release regarding other labs findings (or lack thereof):

6. The UK authors were unable to detect XMRV, even though 4% of healthy individuals were found to be infected in the US. Japanese scientists detected XMRV in 1.7% in healthy blood donors in Japan.

This statement is completely and utterly misleading to the general public. Comparing these results is comparing apples to oranges.

The WPI found 8 of 217 (3.7%) of their healthy controls were PCR positive for the gag gene. Only 11 healthy controls were PCR tested for both the gag and env gene. Only one person was gag positive (9%), none env (0%), 0 out of 16 (0%) healthy controls expressed viral antigens on white blood cells, 0 out of 5 (0%) had viral antigens by Western blot, 0 out of 12 (0%) had cells that could produce infectious virus, 0 of 7 (0%) of healthy controls made antibodies to XMRV.

If we are going to compare apples to apples, we need to compare the WPIs antibody results with the Japanese antibody results.
In healthy controls:

WPI: 0 of 7 (0%)
Japanese group: 5 of 300 (1.67%)

We can then compare these two results to the Second British paper, which also looked for antibodies in healthy controls:

UK #2: 25 of 395 (6.33%)

Ummm… so, technically, the second British group found more ‘XMRV’ than the other two groups, including the WPI. But they dont believe their results.

Know who I believe?

Big Pharma.

Us PhDs have lots of tricks for detecting a virus in the lab, and individual PhDs might want to see/not want to see certain viruses (**WINK!!**) but Big Pharma doesnt give a shit. If the virus exists and is a threat to humans/agriculture/whatever, Big Pharma will industrialize our lab ‘tricks’ and turn them into large-scale diagnostic tests with error rates (false positive/false negative) numbers as low as physically possible. I mean, there is a reason every kit I buy has in big letters “FOR RESEARCH USE ONLY!” “NOT FOR CLINICAL USE!” etc.

Big Pharma has this shit covered in clinical labs.

Turns out Abbott Diagnostics (the makers of OxyContin!) has been working with Emory to create a reliable XMRV detection system. They screen blood for antibodies to three XMRV proteins: gag p30, env gp70 and env p15E. Their results from screening the general population in the US?

Abbott: 3 of 2,851 (0.1%)

I believe that. Not only because of their stringent ‘positive’ guidelines and 100% sensitivity in detecting antibodies in animal models, but because that number, 0.1%, makes sense.

HIV-1, a big deal, is found in about 0.3% of the US population.

0.1% for XMRV in the general population makes a hell of a lot more sense for a brand new blood-born/STD retrovirus than 4%, 1.7%, or 6.3%.

This tiny number does reinforce my suspicions that XMRV doesnt transmit via saliva, though.

And then theres that pesky fact that XMRV has not been established as a causal factor for any human disease.

:-/

Comments

  1. #1 D. C. Sessions
    February 22, 2010

    A ‘sensitive’ test is no good if it cross-reacts with other proteins/viruses/antibodies.

    Maybe not quite. Assuming that its false negative rate is “acceptably” low and it’s cheap enough, it would be a handy way to reduce the candidates for more specific but more expensive tests.

    That’s the kind of calculation blood banks use, for instance. Economics count.

    Scientifically, though, it would be pretty damn worthless.

    This quibble brought to you by a poor schlub who’s been doing yield improvement for the last several weeks and enjoys sharing the pain.

  2. #2 qetzal
    February 22, 2010

    From the linked abstract, it appears that the 3 positives were people with antibodies to all three viral proteins, yes? Were there many/any people who were positive for only 1 or 2 viral proteins?

  3. #3 chester copperpot
    February 22, 2010

    A ‘sensitive’ test is no good if it cross-reacts with other proteins/viruses/antibodies.

    It depends if these proteins / viruses / antibodies can be reasonably expected to be present in the sample to be tested. A test for a disease endemic to the northern latitudes of the United States may have acceptable specificity even if a strong cross reaction occurs in the presence of antimalarial antibodies.

  4. #4 SC
    February 22, 2010

    And I’m not so positive that you would know if I was positive (no matter how positive you think you are):

    ‘Organ and Cell Lineage Dissemination of XMRV in Rhesus Macaques during Acute and Chronic Infection’

    http://www.retroconference.org/2010/Abstracts/39855.htm

    “Results: Both methods were concordant for the detection of XMRV in the various organs tested and showed a wide dissemination of replicating virus even when the plasma viral load was undetectable”

    AND

    ‘XMRV: Examination of Viral Kinetics, Tissue Tropism, and Serological Markers of Infection’

    http://www.retroconference.org/2010/Abstracts/39393.htm

    Conclusions: “These data suggest that lymphocytes are a primary target for replication persistence (low grade replication) of XMRV in the absence of detectable plasma viremia.”

    At least in these two studies, XMRV was present “in the absence of detectable plasma viremia”.

  5. #5 TotallyUncool
    February 23, 2010

    I’d been wondering about Big Pharma’s probable role in something like the XMRV/CFS ball of confusion — I’d kind of come to the conclusion that in their own not-so-charming-way, they would actually turn out to be the closest thing around to neutral players.
    They can’t make money off of an endless Is Too!/Is Not! squabble, and they’ve got a much bigger stake in assuming that a condition is medical (rather than psychosomatic), so they won’t throw themselves in on the “it’s all in your head” side, but they are constrained to produce something that will jump through all of the regulatory hoops (which means that it has to deliver something).
    So for them, striking gold is either identifying the actual cause of a condition, or at least coming up with something which will produce a measurable improvement in patients who have it — and that usually means having at least some concept of what the cause is, even without a detailed understanding of how it works.
    So if they do seriously get involved in research on a condition like CFS, they actually have a strong motivation to find the genuine cause, and to steer clear of the politics.
    (None of which constitutes even half a cheer for or against market rigid and unrealistic ideological dogma economics; it’s just good to have some idea of who wants what when you’re in the middle of a tricky situation.)

  6. #6 gf1
    February 23, 2010

    @TotallyUncool:

    In relation to XMRV, I think you’re right about Big Pharma.

    More generally though, I think it’s quite possible for them to develop drugs for CFS without knowing what causes it. That seems to be what happened with fibromyalgia, and there’s some CFS drug which has been jumping through regulatory hoops for a while. They can come up with vague claims about how there drugs work, but it seems quite acceptable to not really know.

  7. #7 ERV
    February 23, 2010

    Thank you SC for linking to the exact same pages I linked to in my post. You really are on top of the ball, Ace!

    Those are all papers from the exact same experiment Abbott was a part of (you will note ‘Abbott’ listed as an author institution on them as well). Contrary to animal liberation psychos, scientists dont blithely run through monkeys like Kleenex. We squeeze as much data as we can from every primate used in any experiment, with individual labs using their expertise to look at specific angles of the disease/pathogenesis/virology/etc.

    These studies dont say anything about Chronic Fatigue Syndrome, which is why its not in this post title. Youll also note that “At least in these two studies, XMRV was present “in the absence of detectable plasma viremia”.” means that the UK group should have found XMRV if it was there, as they were looking for XMRV proviruses in PBMC.

  8. #8 qetzal
    February 23, 2010

    WPI’s In The News comment from Feb 18 (third one down at the moment) contains this intriguing statement (emphasis added):

    Perhaps the most important issue to focus on is the low level of XMRV in the blood. XMRV is present in such a small percentage of white blood cells that it is highly unlikely that either UK study’s PCR method could detect it using the methods described. 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. When using PCR alone, the Science authors found that four samples needed to be taken at different times from the same patient in order for XMRV to be detected by PCR in freshly isolated white blood cells.

    I’ve gone through the Science paper multiple times now (including the Supplementary Material), and I can’t find that information anywhere. Can anyone else find it?

  9. #9 SC
    February 23, 2010

    @ERV – Did I say one word about CFS in my post? Nope.

    And yes, those are the same links that I suspect you became aware of at least in part from my earlier post in the thread on the second UK study.

    Same study and yet not a word from you on how XMRV was found in reproductive and lymphatic tissue and yet was difficult to detect in blood. Gee, wouldn’t an objective and dispassionate analysis of this work have included at least an acknowledgment that this bug may present some unique challenges when it comes to detecting its presence in blood samples?

    Keep up the objective and oh so informative work, Ace!

  10. #10 ERV
    February 23, 2010

    SC– Do you understand the difference between looking for a virus, and looking for proviral sequences in PBMC?

  11. #11 cynical1
    February 23, 2010

    @qetzel: They stimulated B-cell proliferation in multiple rounds using NIH 3T3 cells expressing CD40L. I am not a virologist but I believe that this is what they were referring to in your quote above. Presumably, multiple rounds of proliferation are necessary in order to detect and/or generate sufficient virus to infect their immortalized prostate adenocarcinoma cell line. I have not read the other UK paper though to see if they did something similar. I believe that this type of protocol is similar to inducing EBV infection of freshly isolated PBMCs. Perhaps I missed something though. I’m just a chemist so don’t jump down my throat.

    As an aside, Purdue Pharma makes Oxycontin, not Abbott (Diagnostics).

  12. #12 John
    February 23, 2010

    re: big pharma- “…and they’ve got a much bigger stake in assuming that a condition is medical (rather than psychosomatic), so they won’t throw themselves in on the “it’s all in your head” side, but they are constrained to produce something that will jump through all of the regulatory hoops (which means that it has to deliver something)”

    I wouldn’t say so at all. They already have numerous quasi-useful(depending on who you ask) SSRI’s and whatever other brain chemical drugs they have, so all they have to do is conduct a few clinical trials(which they can and do change the design of midway through based on the results of other trials) until they hit the magical ‘statistical significance’ numbers and from there claim a ‘significant improvement’ in the patient groups. Big money big money no whammies big money YES!

    Since the drugs are already developed and approved there’s minimal investment involved with the potential payoff of millions of more individuals to prescribe these drugs to. It’s really a no lose situation for big pharma to just wait around and let someone else do the heavy lifting in regards to pathophysiology, although I agree that big perm, er big pharm, will be a major player in the coming years now that a target has been identified.

  13. #13 qetzal
    February 23, 2010

    @ cynical1,

    I see several places where they discuss stimulating and culturing PBMCs. What I don’t see is any indication that PCR ever used DNA from cultured PBMCs rather than DNA from directly isolated PBMCs. In fact, their Methods section states:

    The PBMC (approximately 2 x 107 cells) were centrifuged at 500x g for 7 min and either stored as unactivated cells in 90% FBS and 10% DMSO at -80 ºC for further culture and analysis or resuspended in TRIzol (Invitrogen, Carlsbad, CA) and stored at -80 ºC for DNA and RNA extraction and analysis.

    To me, that implies DNA isolation was only from directly isolated PBMCs.

    If it’s true that they usually needed to culture the PBMCs to get a detectable PCR signal, that could help explain why the two UK groups couldn’t get reproducible PCRs. But contrary to WPI’s recent statement, that doesn’t seem to be described in the Science paper. It definitely should have been, but I can’t find it.

  14. #14 ZenMonkey
    February 23, 2010

    I would post this to the CFIDS Association’s Facebook page, but given their histrionics over Dr. Harriet Hall’s superb column about this (http://www.sciencebasedmedicine.org/?p=3932), I think it’s a lost cause. The skeptics are largely keeping quiet and the believers simply will not accept that one study does not scientific consensus make.

    This is even worse than, say, homeopathy, because you’ve got actual doctors and not just easily dismissable nutbags pushing the XMRV-CFS connection, and that seems to reassure patients that, well, it must be science because real scientists are involved!

  15. #15 John
    February 24, 2010

    After watching the webcast of XMRV oral abstracts at the CROI- http://www.retroconference.org/2010/data/files/webcast_2010.htm (click ‘Friday’- the plenary session(summary of XMRV) by Goff is at the top of the list and the oral abstracts are near the middle.

    Walid Heneine of the CDC said they could not detect antibodies in the two positives(out of a hundred something prostate cancer(PC) patients) they found. Also the phylogenic tree of the positives showed they were somewhat different than the other XMRV’s from the CFS and PC patients. From the summary- “The finding of distinct XMRV suggests that multiple strains may be circulating and shows a broader XMRV diversity than currently known.”

    Also I guess I need to take back what I said about ‘heavy lifting’; watching the John Hackett, Jr. presentation from Abbott was pretty sweet, these people are methodical! The questions after Dr. Hackett’s presentation were also some of the most interesting, although one of the questions to Dr. Heneine was just like ‘are people sharing their shit? This[discrepancy between study results] needs to get worked out!’

  16. #16 gf1
    February 24, 2010

    @ ZenMonkey:

    I’ve not been able to find the CFIDS histrionics. I could just suck at google, but I did find a facebook page by a lone patient, who has just stopped posting as ‘CFIDS’ because the association asked her to. Could it have been this page you found?

    It seems like there’s been a lot of sciencey XMRV news from this conference, and a lot of it’s over my head. Damn science – getting all complicated and stuff. It seems as if a lot of the people involved are a bit unsure as to what it all means.

  17. #17 ERV
    February 24, 2010

    “… and a lot of it’s over my head…”
    gf1, you have been a great commentor, but here Im getting annoyed :)

    On the one hand, Ive got commentors like SC blazing in, balls out, not understanding what this group of studies means, trying to lecture me on them, and making silly mistakes.

    I cant work with that.

    Its like Creationists coming in here to ‘lecture’ me on ERVs, or HIV Deniers trying to ‘lecture’ me on antiretrovirals or whatever.

    Arrogant ignorance– its silly and I have zero patience with it.

    And then Ive got nice commentors like you who dont get something, but then dont ask questions! That makes me so mad!!! If you think something is over your head, ASK! Im not always quick about getting back to people in comments, but I really do try.

    ASK!!!!

    And its not just me– The folks who literally wrote The Book on virology, Virology Blog? CFSers arent asking them questions, and they cant use the excuse that they arent ‘nice’, mean ol ERV… Theyre festering in their CFS Support Groups rationalizing results/science/whatever they dont understand until it supports “XMRV=CFS!!!!”

    I would love nothing more than to clear up misconceptions about basic retroviral research for you or anyone else :)

  18. #18 gf1
    February 24, 2010

    I think I’ve been following the discussion here and at Virology okay. It’s just that there seems to have been a flurry of recent news (a retrovirus conference on at the mo?) so full of unknown terminology I don’t feel I understand it enough to ask sensible questions. I get a vague impression that the scientists involved seem a little confused, but I’m not too sure why.

    If I stumble accross any more stuff like this I’ll try to remember to copy and paste it over here so I can ask for an explanation. Thanks for being willing to try to clear things up. Pleased to hear I’m a bodacious commentor. I’ve not been following the discussions with SC, but I have noticed that he’s sometimes misunderstood and unfairly attacked.

  19. #19 qetzal
    February 24, 2010

    ERV,

    I’m very interested to know the answer to my questions from #2 above, if you know them.

    Also interested to know if I’m off base regarding the Science paper not stating that most positive PCRs came from cultured PBMCs (#8 above).

    Finally, I hope I didn’t piss you off by by engaging with Dizzy on the earlier thread. Your response suggested you weren’t interested in seeing that discussion in the comments, so I just dropped it. (I never expected Dizzy could back up those claims anyway.)

    If I did annoy you, please accept my apology.

  20. #20 ERV
    February 24, 2010

    Oh, sorry, qetzal! I didnt mean it like that– I meant I can exchange your alls emails so he/she could email you those papers he/she was referring to! I didnt mean “TAKE IT OFF THE BLAG, BITCHES!”

    I just wanted you all to know I could (and would be happy) to put you two in contact with one another, so you dont have to post your email here :-O Sorry!

    Ill get back to you on your Q tonight!

  21. #21 SC
    February 24, 2010

    ERV – I’m sorry that I’ve pissed in the punch of your little party. I know that it was supposed to be all about you and how you could enlighten the rest of us so that we could lead wonderful and rational lives in your image. The problem that I have is that you’re not balanced in you analysis nor are you an expert on half of what you shoot your mouth off about (thanks for little lesson on ‘everything I ever wanted to know about the drug industry but was afraid ask’). I’ve been reading pharmaceutical adds in medical journals since the mid 80’s (yes, they used to put glossy adds right in the middle so that you couldn’t thumb through the journal without stopping at their add). The pharms are all about profit and that’s not an entirely bad thing but as several people have pointed out, at 23 you have a lot to learn.

    And pharma isn’t the only area where you have a lot to learn. I know you don’t give a shit about CFS. I find that ironic as you have referenced one definition (the CDC’s) and you have no idea what CFS is (and you are far from being alone in your ignorance on the matter). And yes, I do suspect that once XMRV is better understood, it could account for some percentage of ‘CFS’ (and possibly other neuro-immune disorders). As for what that percentage might be, I wouldn’t even consider a guess.

    And that is a key point in where we diverge. You use your blog, not as a place to openly exchange information or ask sincere questions but, as a loudspeaker from which to attempt to bludgeon and intimidate. You are so damned cock sure that everything you’ve read in your entire 5-6(?) years of higher education is the be all and end all (didn’t you recently post about how, if you have just given it a bit more thought, you should foreseen how four years of work on your dissertation was going to fail to support your hypothesis). If really had the makings of a good scientist, you’d spend more time asking a broad range of questions and less time ‘showing off’ and thinking it’s cute to use profanity to denigrate well meaning people (even when they have made significant errors in judgment). Your ‘PI Fail’ post reveled more your biases, how you view the world, and your immature view of what passes for discourse than it could have possibly revealed about your target. Across many of your posts, you have given everyone who disagrees with you more than enough ammunition to dismiss you as a freak. Good luck with that down the road. Perhaps the real lesson from the CROI abstracts and interviews with Coffin and Goff was the ability to suspend judgment, entertain alternative explanations, question dogma and be patient.

    People will remember this as EVR’s blog. You’re at a stage in your career when first impressions matter. I doubt that in the field of retrovirology (as opposed to a career as a blogger) you’ve been helping yourself.

    Regarding the most recent UK XMRV study, I have a lot of respect for Jonathan Kerr, a very credible scientist with an extensive record in CFS research whose recent study with Groom et al. was also a good faith effort (‘CFS’ patients don’t get to accept the results of his DNA work and then dismiss out of hand him or his participation in the Groom study). There are clearly discordant results on XMRV and hundreds of questions as well as key associations (or lack of associations) to be addressed before we know what, if any, role XMRV plays in human disease. Nothing that we exchange here is going impact the real scientists and retrovirologists who are work on this new and interesting subject. I make no assumptions that any of my posts here will change the understanding of XMRV 12 months from now.

    So why am I here? It certainly isn’t because I am on the edge of my seat waiting for the next crumb you see fit to toss the way of your adoring patrons. I’m here because of your sensationalistic, unbalanced, and passionately anti-CFS rants. So keep up the ‘anti-anything you don’t really understand’ rants and I’ll drop in every now and piss in your punch bowl. Act like a rational member of society and I might actually ask a question or two about what you’ve learned in the last 6 years (I’m sure there are a few things I could learn). But until you want an actual dialog, don’t think that if I go away there aren’t legions who either dismiss you as a raving lunatic or who won’t enjoy dropping in to pull on your tail every now and then. It’s more than a bit entertaining (we know you’ll respond with an attack, even to the most sincere and balanced question if it isn’t inline with your assumptions and prejudices – thus lessening your credibility to an even greater degree).

    As I have said earlier, I’m waiting for the real retrovirologists to come back with some good questions and hopefully some answers. And right now there are a lot of very good people – none of whom are spending any time here – working on the questions surrounding XMRV.

    So ERV, in the end this post was all about you. I hope you enjoyed it.

  22. #22 Dave
    February 24, 2010

    Wow SC, what a noxious mix of self-importance and projection. Id say, “Hope youre pleased with yourself,” but its quite obvious you are.

  23. #23 Jason
    February 24, 2010

    Woah.

    SC: If you’re not a fan, don’t come here. No one’s making you read the content. Why feign concern about her career? I’m pretty sure she’s fine.

    Also, you wrote:
    “I’m here because of your sensationalistic, unbalanced, and passionately anti-CFS rants. So keep up the ‘anti-anything you don’t really understand’ rants and I’ll drop in every now and piss in your punch bowl.”

    Okay – so you want her to self-censor and you’ll go away? But, then she can do whatever and you theoretically shouldn’t know about it.

    How about you stop policing the internet? This is her venue to say what she wants – no one forces you to read it.

    “Act like a rational member of society and I might actually ask a question or two about what you’ve learned in the last 6 years (I’m sure there are a few things I could learn).”

    Okay, two things come to mind here. (1) despite what you just said before that, you will still read the content here (dammit! lies!). Are you sure you don’t just want to go away? Call me a sycophant, but I’m SO over your tl;dr rants. (2) Why are you the thought police? Who asked your opinion? SB has given her space here. Go troll elsewhere.

    And, for the record – I have made statements that disagree with Abbie, on here, in the past. Anything to do with “junk DNA” — not because I’m an ID proponent but because of my background in genomics, and knowing about the lincRNA study before it was published.

    I’d mentioned these things before, to Abbie, on relevant posts and was never met with disdain (though I was unable to provide the paper before it was published).

    I think ERV doesn’t have a problem with people who don’t know things and are honest about them, or know things and demonstrate that they know them — I think more strongly worded disagreement is when commenters make statements that clearly are beyond their scope of knowledge.

    Look at post 10 in this thread — ERV is clearly annoyed because you’re not demonstrating familiarity with what you are posting – how does one argue when one does not know the content they are arguing over?

    If I’m mistaken about your credentials, then by all means, please correct me.

  24. #24 SLC
    February 24, 2010

    OT but is Ms. Smith planning to comment on her favorite medical researcher, Francis Collins’, latest book? Jerry Coyne and PZ Myers have already had at it and are having a fine old time kicking Dr. Collins’ keester around the block. It will be interesting to see what, if anything, Mooneytits has to say about it.

    http://whyevolutionistrue.wordpress.com/2010/02/24/francis-collins-cant-help-himself/

    http://scienceblogs.com/pharyngula/2010/02/francis_collins_is_up_to_the_s.php

  25. #25 Vicki
    February 25, 2010

    Why is it that as soon as someone criticizes ERV’s lack of rationality and scientific method, they are accused of being “thought police”?

    Gee, hecka defensive. If you don’t want critics, why have a blog?

    I think SC demonstrates quite a bit of erudition in this forum, and I enjoy and learn from his posts.

  26. #26 Shirakawasuna
    February 25, 2010

    One thing is very clear. SC is very *concerned*.

  27. #27 Jason
    February 25, 2010

    Really, Vicki?

    Why don’t we READ what SC wrote:
    “So why am I here? It certainly isn’t because I am on the edge of my seat waiting for the next crumb you see fit to toss the way of your adoring patrons. I’m here because of your sensationalistic, unbalanced, and passionately anti-CFS rants. So keep up the ‘anti-anything you don’t really understand’ rants and I’ll drop in every now and piss in your punch bowl. Act like a rational member of society and I might actually ask a question or two about what you’ve learned in the last 6 years (I’m sure there are a few things I could learn).

    That! That is thought policing! Let me translate for you:
    “self-sensor and behave like I want you to, on your blog, and I’ll stop being a sanctimonious jackass”

    Thought. Police.
    Seriously – how is this not admission of such! And seeing as I have only seen SC post on XMRV-related topics.
    QED.

  28. #28 Optimus Primate
    February 25, 2010

    I think SC demonstrates quite a bit of erudition in this forum, and I enjoy and learn from his posts.
    Posted by: Vicki | February 25, 2010 2:11 AM

    Oh, do tell! What, exactly, have you learned from SC? Aside from how to conveniently ignore inconvenient elements of a post, make ridiculously long rants, and overlook the color of kettles at two paces?

  29. #29 vicky
    February 25, 2010

    Afraid not, Jason. Not “thought police” (oowww, scary!) by any stretch of the imagination. He’s making an argument, my dear, like everyone else here.

    Yours is a classic and transparent tactic: launch a personal attack if you can’t respond to a critic.

    And if he is a “sanctimonious jackass” — ok, sure, whatever — it’s certainly no more so than several other contributors here. And many of them don’t have half the knowledge, political perspective, or writing ability.

  30. #30 ERV
    February 26, 2010

    qetzal– Sorry, dude! Ive got tonsillitis (lol, wat?), so I havent had time to comment.

    Okay, I can only answer this from the perspective of HIV-1– We never just look for antibodies to one protein or just do one test. Anything from allergies to a recent flu shot can cause a rise in non-specific antibodies that react with ‘HIV-1′, but arent really anti-HIV-1 antibodies. Ill refer you back to that second UK paper, where they said “Yeah, we found ‘anti-XMRV antibodies’, but these arent anti-XMRV antibodies.”

    So if you tell me youve got a patient sample that is positive for anti-HIV-envelope (maybe only weakly so), but anti-HIV-gag negative? Dude everyone with HIV makes antibodies to gag, that person doesnt have HIV.

    It is actually really important that Abbott is calling ‘positive’ at “anti-3-XMRV proteins”. Anything less than that and theyre going to report a ton of false positives that might/might not be repeatable in the future.

    As far as culturing PBMC from patients to get viruses: WPI is completely and utterly failing at communicating their science to the general public.

    To detect proviral DNA in PBMC, they did not culture the cells. At least, they didnt say that in the Science paper, as you mentioned.

    No one else did either.

    No one does that for any virus.

    To detect actual virus, they did culture their cells. While that is ‘normal’ for detecting certain kinds of viruses, its extremely outdated. But, if thats what they had to do to see actual virus, thats what they had to do.

    Now, no one except for the WPI has looked for actual virus. If you cant find proviral DNA, theres no point in looking for an actual virus that is apparently an even rarer occurrence. Detecting proviral DNA is ‘Step 1′.

    Getting bitchy with the UK groups for not culturing their cells makes no sense because neither one of them looked for virus. They looked for proviral DNA and/or viral mRNA production in these infected cells.

  31. #31 ERV
    February 26, 2010

    Also, I want to live on Planet CFS where I am perpetually 23 years old.

    LOL!!

  32. #32 cynical1
    February 26, 2010

    ERV – I was curious to the answer to Qetzal’s question (#19): “Also interested to know if I’m off base regarding the Science paper not stating that most positive PCRs came from cultured PBMCs (#8 above).”

    Do you think multiple rounds of stimulation could explain the differences in results found by these groups? I agree with Qetzal in that it is not very obvious (at least to me) from the paper on those details. I also wonder whether that was on purpose or just a case of WPI figuring that other groups would not try to replicate so quickly, if at all.

    I read the blog for the science discussion, not the endless bickering back and forth. I have my wife for that…….

  33. #33 qetzal
    February 26, 2010

    ERV,

    Thanks very much for the informative responses! Hope you’re feeling better really soon! (Also, thanks for clearing up my uncertainty on the Dizzy exchange.)

    Regarding the anti-XMRV antibodies, I didn’t know whether Abbott’s 0.1% figure could be challenged by arguing that people with Abs to only 1 or 2 XMRV proteins were still true positives. Guess not.

    Regarding the PBMCs, I can actually see some rationale for the idea that you might need to culture them to get a positive PCR signal. Groom et al. reported a detection limit of 16 copies for their qPCR assay. IF there were only a very small minority of PBMCs carrying the provirus, they might miss it in direct assays. If the virus activates and starts replicating in culture, that could easily increase copy number above the detection limit. Without much knowledge of retrovirology, I can’t say how plausible that is, but it seems at least possible.

    So, I could accept for the moment WPI’s arguments about PCR analysis of direct vs. cultured PBMCs. What I find bizarre is their claim that the Science paper makes all that clear, when it does no such thing!

    With each new unwarranted and/or factually untrue statement from WPI, I trust their science less. Maybe that’s a bit unfair, since it’s not the bench scientists who are making these statements, but lab culture comes from the top, and the top folks at WPI seem much more concerned with image than with accuracy. Big red flag, from my experience.

  34. #34 cynical1
    February 26, 2010

    ERV – Sorry for posting my question after you had already answered it a few minutes before. I was typing up my question when I got interupted for almost an hour and then came back and hit the “post” button. Thanks for the response!!! Hope you feel better.

  35. #35 not a gator
    February 28, 2010

    ERV, I’ve seen the same comments as SC is making on SBM and other blogs. They sound like talking points to me and I am highly skeptical.

    The original paper correlating the two was really more of a “huh, that’s suggestive, isn’t it?” more than anything else. Unfortunately, there is a group of people who have a deep psychological need to believe … and hence the elaborate rationalizations. It’s kind of sad.

    XMRV was shaping up to be the hot new bug on the playground. I’m not biologist but I’ve been enjoying the papers presented so far. Too bad the very mention is turning into patient-advocacy flame bait.

  36. #36 GK
    March 8, 2010

    Perhaps SC got a bit annoyed with Erv’s apparent bias in relation to CFS. “Still no XMRV in Europe” was Erv’s neat little catchphrase for each negative CFS/XMRV study which was appearing. Despite the fact that XMRV was found in Europe – including a case in a “healthy” control – and published in 2008 (see below, perhaps other posters will bother to read this although Erv apparently cannot). Despite my repeated attempts to point this out, Erv has not deigned to respond. I think perhaps what SC would like, as I certainly would, is for Erv to take the time to read a little more before shooting her mouth off. As for negative CFS/XMRV studies, as others have tried to point out, it’s easy to mess around with your “cohort” in CFS as the diagnostic criteria are a joke. Regarding the prevalence of XMRV in CFS – if any at all – it’s likely to be a lot lower than that seen in WPI’s “Science” cohort (see previous remark).
    I might not know much about virology but I know a bit about objectivity, and lack of it, when I see it.

    http://dx.doi.org/10.1016/j.jcv.2008.04.016

    J Clin Virol. 2008 Nov;43(3):277-83. Epub 2008 Sep 27.

    Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer.
    Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, Schlomm T.

    Institute for Medical Microbiology and Virology, University Medical Center Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. nfischer@uke.de

    BACKGROUND: We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. OBJECTIVES: To determine the presence of XMRV in non-familial prostate cancer samples. STUDY DESIGN: RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. RESULTS: XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. CONCLUSIONS: XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11-17%).

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