Just when you think XMRV-->anything could get none more dead, it manages to get deader.
When the possibility arose that there was a new pathogen circulating in humans, especially in the human blood supply, lots of labs from all over the world started looking for it.
Unfortunately, no one could find XMRV anywhere, except for very specific labs.
So the US government got the idea to:
1-- Collect patient samples from the labs that say they can find XMRV. Known positives.
2-- Collect negative samples from patients *everyone* in the study group, including the WPI, agree are negative. Known negatives.
3-- Create 'blanks' artificially spiked with XMRV. Positive controls.
4-- Code everything so no one knew what any sample was 'supposed' to be.
5-- Send these samples out to labs. Who can find XMRV in the positive controls and CFS patients, when they dont know which samples are 'supposed' to be positive.
Here are the results of that study:
Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study
Shorter--
XMRV? He dead.
1-- The labs that cant find XMRV in patient samples can find XMRV when it is there:
Of the nine labs that tested the samples, only one lab could not reliably detect XMRV in the positive controls (blank samples spiked with XMRV): The Whittemore Peterson Institute
2-- Of the nine labs that tested the samples, only two found XMRV in any experimental samples (CFS and healthy controls):
WPI and NCI, the two groups that have published the 'XMRV-->CFS' Science paper.
Los group ('MLVs-->CFS' PNAS paper) called all experimental samples negative.
3-- WPI and NCI 'found' XMRV at equivalent rates in the negative controls and the CFS patients:
WPI called 8/15 negative controls 'positive'. They called 6/10 of their own 'positives' positives. They called 5/5 Lo et als positives positive.
NCI called 10/15 negative controls 'positive'. They called 5/10 WPIs positives positive. They called 2/5 Lo et als positives positive.
A wink is the same as a blink to a blind man.
4-- WPI and NCI 'positive' results did not correlate:
WPI called Negative Patient #10 positive. NCI called Patient 10 negative. NCI called Negative Patient #13 positive. WPI called Patient 13 negative. Over and over.
5-- WPI and NCI contradicted their own results:
WPI Patient #2-- WPI called this patient negative on 2/3 assays. Positive by one assay once, but not twice. NCI called Patient #2 negative on two assays.
WPI Patient #1-- WPI called Patient #1 negative. NCI called them positive on one out of two assays. But the 'positive' result was only positive 1/2 times the procedure was replicated.
The only people who can 'find' XMRV, cant really find XMRV. One could not make the 'positive' results in this paper a bigger train-wreck if one actively tried. XMRV is not out there, and even the labs that 'can find it', cant really find it. For the *millionth* time: There is no reason to believe XMRV is a real pathogen.
Not that any of this is stopping Judy Mikovits:
The leader of the team that conducted the study, Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, resolutely maintained that her lab had no evidence of contamination and that it could repeatedly ï¬nd the virus with its techniques."The conclusion of the Blood Working Group was that we don't have a reproducible assay to detect XMRVs in the blood--not that they weren't in the patients at all," Mikovits says.
Mikovits and Ruscetti, who have become increasingly isolated from the broader scientific community, now say their original paper erred by focusing on a single XMRV isolate that turned out to be a contaminant. They say that isolate is but one of many XMRVs, which belong to a still larger family of gammaretroviruses.
The new findings give her "great pause," yet she suspects they're but a speed bump. "I haven't changed my thinking at all," she says. And she worries that the Blood Working Group conclusions will confuse people with CFS, some of whom got wind of the results early in the blogosphere and contacted her in a panic. "I had 15 suicidal patients call me last week," she says.
Mikovits to this day contends that the Lo-Alter paper confirms Lombardi et al. and insists that from the beginning, she viewed XMRV as one of many gammaretroviruses, which includes the MLVs, involved with CFS.
At a meeting on 14 December 2010, the working group discussed the results of the second stage of its study, which again did not support Mikovits's findings. Her lab had found XMRV in a sample from a healthy person who all labs agreed beforehand was negative for the virus.
Mikovits had an explanation. The false positive was caused by a postdoc who mistakenly used the same needle twice to lyse cells and shear DNA, contaminating the sample. She dismisses the error as trivial, the result of working late at night on a weekend because of repeated power failures in a new building, coupled with intense pressure from the working group to get results quickly. "People make mistakes, and we reported it as a mistake," she says.
The accidental-origin evidence hasn't convinced Mikovits.
"It's all contamination," Coffin concluded, which outraged Mikovits. "How can John Coffin shut down research like that?" Mikovits shouted during one interview, her blue-gray eyes shooting fire. "He's not God!" She speculates that perhaps the U.S. government, afraid of the huge consequences of a widespread XMRV outbreak, was trying to discredit her work. "We can't afford another public health crisis," she said.
With help from Peterson, UCSF virologist Jay Levy examined 43 patients who tested XMRV-positive at WPI. Peterson says he wanted to help his former colleagues at the institute. "I went to Jay Levy to prove them right," he says. All samples tested negative. Again, Mikovits said the study was flawed.
"They didn't do one thing we did," Mikovits says.
Mikovits says it is irresponsible to dismiss the link between XMRVs and CFS at this point. "Anyone who says this is a lab contaminant has drawn the wrong conclusion and has done a disservice to the public," she says. Okay, maybe not as many CFS patients have XMRVs as they initially reported, but she's still convinced that a gammaretrovirus is in at least 20% or 30% of them. "I know of hundreds if not thousands of people with evidence of this infection, from what we've done over the last 3 years," she says. "I don't know what it means. And I'm gong to keep looking for in vivo reservoirs like the ones seen in the macaques, and I'm going to try to figure out mechanisms of pathogenesis, epigenetics, or other things. I'm not going to stop studying it.
To which I reply:
Textbook Kook.
I also found this bit of the article interesting:
Intrigued by the RNase L link to XMRV, Mikovits and Lombardi--who by then had joined WPI as well--met Silverman in October 2007 at a prostate cancer conference in Lake Tahoe, where they discussed the possible role of XMRV in CFS. Silverman was happy to collaborate and sent WPI a clone of the virus, known as VP62.
I bet Silverman is, shall we say, 'regretting' giving Mikovits VP62. It appears the plasmid grew legs and 'walked' into the CFS samples, and only the CFS samples, that came out of the WPI... what a crazy random happenstance... But thats a different story for a different day...
- Log in to post comments
I'm glad I checked here before hitting send. I was just about to e-mail you a question about the talk.
To the rest of you: you can't be first, but you can be next.
The link under "shorter" returns a rude message from youtube. Your link is apparently "malformed".
:)
So now that is over, what about doing some real epidemology on CFS? Crazy, how they ended up with testing for a pathogenic retrovirus first, by taking some rather convoluted paths. Whatever, now this disease has more attention from scientists, though retrovirology is probably the wrong discipline for this disease altogether.
What wrong wit you? I say you he dead.
My old elementary school teachers had another term for that; an "F".
"Of the nine labs that tested the samples, only one lab could not reliably detect XMRV in the positive controls (blank samples spiked with XMRV): The Whittemore Peterson Institute"
haha thats fucking incredible
You forgot the most Failblog-worthy observation in the whole paper: the WPI could not perform their much-ballyhooed cell culture assay on the blinded samples because ...
... wait for it ...
... their cell lines were contaminated with mycoplasma.
After getting over the hilarity of my Starbucks encounter today (detailed at my place and on twitter), and looking into the neutrino faster than light story, I realized that I missed being fraught with guffaws. So, I rolled up my sleeves and tweeted the following, for you, Abbie:
How can Judy Mikovits, call herself a scientist? If I were the WPI, I would fire her.
What should have been put to rest a long time ago has resulted in two years of a lot of wasted money, time and energy that could have been used more productively for the CFS/ME, community, which includes me.
Will the WPI be willing to refund all the money for their bogus test? Will they ever gain credibility after this? I wouldn't go there if you paid me.
You could say not all has been lost in the last two years, as CFS/ME is now on the map. But at what cost and it doesn't begin to make up for the sturdiness and setbacks perpetrated by the idiots who wouldn't know the scientific method if it hit them up the side of the head.
The real advocates will have to work twice as hard to repair the damage.
Thanks ERV.
Well, at least it indicates that Mikovits was nice enough to give Lo a guided tour of the WPI lab.
And great blogging again, ERV. Personally I am surprised by Frank Ruscetti's reaction. Mikovits is par for the course, but I had expected she would be standing alone in her religious confidence after disastrous Phase III results.
@laurie
This whole XMRV (whatever) thing has meant MORE money and MORE kudos for WPI and Knickerfits not less - at least not in those circles that they seem to care most about fleecing.
The WPI may see donations slow or even dry-up but they will be out with something BRILLIANT again the following day - UNLESS people start returning the 'snake-oil' they have been sold.
But you're right 'real advocates' really will end picking up the pieces from this because science cannot afford to be anything other than objective, and Knickerfits already has her funding secured (and a drawer FULL of as yet unpublished papers just proving EVERYTHING).
The WPI will (already have) centre on their 'Clinic' which will prove nothing more than any other 'quack-shop' on the planet whose doctors take just a little more time with their patients and 'seem to genuinely care' and who are not adverse to discussing (even prescribing) extra special drugs - because 'we care' - and charging through the nose for it but 'all for a good cause - have a nice day' kerching!
Even when 'Lipkin' (IF 'Lipkin' ever) comes home and bares all - Knickerfits and the WPI will keep on truckin' in some way, shape or form: I betcha ;) But I know what you mean.
@laurie
The problem is that Mikovits lost it. Supported by a quite impressive number of "CFS patients" even if she will get fired, she will blame it on conspiration from the US government.
How said that something so OBVIOUSLY WRONG is not going to leave us soon, but continue to live in the mind of some crazy people out there.
Laurie:
When I dream, it's of a pony.
typo.. How SAD...
Now now, Popi4. Don't be sad about a typo.
This week on 'The Joy Of Typing', Bob explains there aren't mistakes, just happy little accidents.
Oy, Allan, NOT NOT NOT defending the WPI, BUT, mycoplasma contamination is both common and FAST in cell culture. I mean, if I'm in the lab I get the evil eye if I come anywhere near the cell culture people, what with my dirty yeast and such.
Scientific evidence stopping a kook? Well, Hulda Clark comes to mind. Not that it caused her to change her story, but the terminal cancer did stop her. Especially that scientific finding that she had http://www.google.com/url?sa=t&source=web&cd=4&sqi=2&ved=0CDwQtwIwAw&ur…
@Jason I certainly know how easy it is to get mycoplasma contamination in cell cultures (been there, done that). However, when you've screamed your lungs out that YOUR cultures couldn't possibly be contaminated with XMRV (which is much, much, much easier to contaminate things with, as Ila Singh and others have shown), and that you've checked for all kinds of contamination and found none, and then you turn around and say you have a contamination problem, well, you get the irony, right?
First, hats off to Silverman who was man enough to retract his figures based on the evidence supporting contamination. It isn't an easy thing to do and must suck big time.
Secondly,
Hmm, then why is it that when Mikovits' group does it exactly the way they "do it" blinded that she can't seem to reproduce her own results? The answer: she blames a post-doc. Wow, classy. No wonder she has no credibility in the science community anymore.
That whole first excerpt is just brimming with fail. You can actually see her hammering the Career Self-Destruct button...over...and over...
And yet if you go over to some CFS forums (http://www.mecfsforums.com/index.php/topic,9576.15.html) people are still blindly supporting her and using their misunderstanding of the science to justify their faith in her. Sad. It takes to little to convince people of one thing and so much more to convince them that they are wrong =(
@Poodle: that is exactly the point. it is like no evidence can convince someone anymore. and I thought we were past the medieval era - obviously not.
Ill have a post up tonight (tomorrow morning?) on Silvermans retraction.
Spoiler: Good on Silverman, hes fine. Others? Others are starting to smell fishier by the minute...
Hey, since I brought up the retraction first that means I get credit as co-primary author for tomorrow's post...right?
=D
crap..push the wrong button..and post gone...*geez*
"âThey didn't do one thing we did,â Mikovits says."
That one crucial thing must be "take money from snake oil salesmen".
Wait a cotton-picking-minute!
You have it ALL WRONG!
'IT' isn't 'XMRV' that Knicker-fits can find and nobody else can!
No no no [waggy-finger]!
'IT' really is something completely different as the intrepid and loyal Dr D-J is only to happy to reveal to the faithful:
http://treatingxmrv.blogspot.com/2011/09/when-going-gets-tough.html
@ Laurie The real advocates will have to work twice as hard to repair the damage.
This is certainly a concern, however itâs just possible that there is enough momentum in research away from the XMRV debacle to actually carry the validity of M.E/CFS science through the fallout from the Mikovits/WPI mess: http://www.dailyutahchronicle.com/news/campus/national-institutes-of-he… http://www.biomedcentral.com/content/pdf/1741-7015-9-91.pdf http://www.mrc.ac.uk/Fundingopportunities/Calls/MechanismsofCFSME/MRC00… http://cfinitiative.org/research-programs/ The problem now is going to come from the headbangers who refuse to let go of the XMRV stuff and who are likely to continue insulting any researcher (and anyone who supports such researchers) who doesnât accept the headbangers' warped view of science
@ Popi4 How sad that something so OBVIOUSLY WRONG is not going to leave us soon, but continue to live in the mind of some crazy people out there.
Mikovits has apparently just received another US Government grant to study HGRVs and sheâs now in charge of âtranslational medicineâ at WPI so the aim seems to be to find something that isnât exactly XMRV, look for antivirals that work on ânot exactly XMRVâ and then start pumping patients with ARVs, without actually bothering to find whether any disease process is actually present and irrespective of resistance complications. Of course any patients treated at WPI have to find the cash from their own pockets and there might not be too many willing to risk that given that WPI was licensing a test which brought in something close to $1million which WPI has now been forced to ackowledge can't be validated.
I am going to miss your XMRV articles. :-(
"the WPI could not perform their much-ballyhooed cell culture assay on the blinded samples because ...
... wait for it ...
... their cell lines were contaminated with mycoplasma."
That's just priceless! I have an undergraduate virology lab in a couple of weeks, and I get them to do a mycoplasma test on their cells. We may still have a couple of places if anyone from the WPI wants to enroll....
DMc
I see some are throwing Silverman under the bus.."It's his fault, XMRV was not a contaniment until sent to his lab"..
"Judy's mistake was working with Silverman, she has nothing to gain, he has a new house to finance" "silverman named it XMRV ....he's responsible for this mess up..not Judy.."
"WPI always said what they found wasn't what others were finding..their xmrv is different, it's a different strain."
Ila got it much worse.....
I wonder if Judy screwed up bartending as badly as science...
I'm sorry this may be the end cuz.. I love your perspective!
John @ 26: or as I said on twitter yesterday - to include using contaminated samples, bad controls and protocols.
AWWWW Its not the end, you guys!
Look at how long Orac has been able to write about Wakefield!
We gonna be talking about this for a while, Im sure ;)
mary-- Yeah, after reading Silvermans retraction, I dont view him in a negative light at all. Itll be up on Monday :)
Jack @ 27: thanks for the link.
I've read through all of the comments.
There's an "MD" in there who's arguing:
position 1: it must be HGRV because I'm responding well to ARV
position 2:
This guy is treating people? Off of "well, it worked for me, and screw the labs - here's your cure" Scooby Doo logic?
/sigh
Some guy in there named Ed is holding forth, trying to talk some sense into them.
Amid all of the humor here is all the emotional discord there. Now I remember why I could never work in any field related to health. Real people get hurt by ideologues.
Bleh.
IF this neutrino thing works out, I'm going back in time to tell them all she's full of shit before they know who she is! (tongue-in-cheek)
I just knew from the moment I got sick that I had a retrovirus. What else could it be? I had all the classic symptoms Deep down in my heart and soul I knew it had to be a retrovirus, specifically XMRV. It was intuitive. I knew it was there. Even if my Ouija board and my XMRV test from the WPI hadn't confirmed this, I would still believe that a retrovirus has been responsible for my illness.
Laurie B. :>)
TBH, while the above was written by me, I first posted my response on DJDJ's blog. But it just didn't feel at home there and just in case it might get deleted......
Laurie B.
@Justicar
Yes I see what you mean. The fellow even has his own devoted thread now:
'I have something special to share with you, since hope seems in short supply today.
One of our own [?!?!] is a clear beacon of light in the fog [eh?!].
Dr. Michael Snyderman's one man experiment has been presented here before, last in April, clearly showing a prolonged remission of his CLL due to antiretroviral treatment.
Since then, he suffered a relapse, while still taking Retrovir (AZT) and Isentress (raltegravir).
After carefully documenting the relapse, he added Viread (tenofovir) and here are his stunning results.
This is the strongest proof of concept that we have at this time. It is possible he will be ignored, but by all rights, at the end of the day, he should be credited with changing medical history [?!?!?!]
He has been very brave and very restrained, having done nothing else for his cancer or his CFS, except for antiretrovirals.
His leukemia allows for very precise monitoring, but do not forget that he had ME/CFS for many years prior to CLL, and he has experienced clinical improvement of those symptoms as well.
It is a game changer, or should be [It is a GAME a very DANGEROUS game to be posting things like this on a public access site. How many will continue to be encouraged in the manner to take ARVs?!]'
http://treatingxmrv.blogspot.com/2011/09/reason-for-hope.html
NY Times CFS patient taking off prescription ARVs: http://www.nytimes.com/2011/09/23/us/off-label-use-of-hiv-medications-i…
Where do they get the incentive to do this? Let me hazard a few guesses...
When has science ever stopped religion? This retrovirus for CFS thing has been going on for the past 30 years and Mikovits will go on as a martyr in Hillary Johnson's bible.
Abbieeeeeeeeeee! I'm looking at the IDSA's published annual meeting program, and to my dismay it looks like they actually STILL have a session on XRMV??! How can this be true?? Did the planning people somehow fail to notice how crap it is?? I know you personally have no control over this, but I am still dismayed, and sharing my dismay on your post about XRMV=D.E.D.
Maybe the session will consist of, "Sorry, we're embarrassed about this, too. Turns out it's a load of contamination. Awkward, right? Go get some free coffee from a sponsor [if your state allows that]. KTHXBYEEE!" But somehow I doubt it.
I guess it doesn't matter. I will be listening to "Parasites that Challenge" (I'm excited to find out what/how exactly they challenge!) If the challenging parasites are somehow canceled, I'll go find some ice cubes to watch melt. But still-- seems like they could lessen the environmental impact of the whole event by canceling the what will most likely be a large volume output of hot air and methane.
Why of why did the IDSA sign them up and then keep them on board?? Is there no way to [politely] encourage people to withdraw their submission? :(((((( I thought most of the scientific community got that the XMRV thing was a bucket of fail. (I mean vet med gets it, and we're usually the last to know pretty much everything.)
TLDR: HOW IS THIS NOT OVER ALREADY???
Also, I really enjoy your blag. Please keep being awesome.
@abbie... I'm glad that you'll continue with this between WPI, Judy, and the whole slew of pseudo-virologists experts *cough* she has created! IVI has written well also...
I guess I'm going to have to brush up on HGRV's and HTVL I & II cuz it seems that this is what Judy really found...lots of nym changing going on!
@39, this is not over yet cuz unlike Ila, and now Silverman, Judy has refused to admit her science was flawed, it is always everyone else's fault, it's a conspiracy...
I do hope Judy or someone does continue and find something helpful..I"ve learned from the militants that insanity should be added to the symptom list, with treatment, maybe they can find their sanity again..
"The intrepid Dr. Mikovits went up against Darth Vader today in Ottawa. In the face of incredible adversity, she took the heat. For us. And she points the way to the next step." ...... I love that quote, it immediatley brought to mind your picture of Darth in the ocean....
Wait-- in a different version of the program, it appears that XMRV no longer exists.
YES!!
I have to question why you are all so joyous...nay, you are almost ecstatic. People are suffering...some dying. I think it's in poor taste.
And I think spiking VP62 plasmid into CFS samples to get a Science paper is in poor taste.
So there you go.
Shirah-- XMRV still on the IDSA's published annual meeting program?
NOPE!
Chuck Testa!
Others-- Regarding Dr. DJ, I think its funny she cant even get pop-literature right.
Darth Vader *is* Darth Vader due to a messiah complex (he was going to 'save' his mother and Padme) and he was plagued by paranoia (Obi Wan was 'out to get him', Yoda was 'out to get him', the Council was 'out to get him') and fits of misdirected rage, aka Judy Mikovits.
Then on the 'other side' you have the Jedi, who care more about the whole than individuals (no more so than themselves as individuals) and have a religious devotion to a higher standard, aka the scientists and Science itself.
The Jedi were 'persecuting' Darth Vader, and rightly so.
God DJ is just one big bucket of FAIL.
According to the Militants or Crazies however want to call them. Th flat earth forum stated that the BWG is a hoax. I wonder if they have a point on the preservative. I don't know if this is a rumor or a fact.
1* Patients on medicines that would produce false negatives.
2* The PMBSs were not preserved in Trizol or any other preserving agent. Any virus would be dead!
3* Negative controls not screened by all labs
4* Far too small sample size to draw meaningful conclusions (9 WPI CFS patients).
5* Lo staff failure to use correct Lo et al. assay (Used failed one and not the one proven to work)
6* All other assay not diagnostically validated, and only analytically validated to a clone (VP62) that does not exist in nature.
Oh wow, "speed bump", yup heard that line used before. I guess an impenetrable concrete wall is kinda like a speed bump. I mean, it's gonna slow you down.
Mikovits will carry one, wrapped up in her own cloak of invincible cognitive dissonance. There is absolutely no way back for her without admitting she is a total failure, so don't expect her to say so anytime soon. She will alsways be able to prise out a little corner of controversy somewhere to keep her wagon rolling, on and on and on, al la Wakefield, who has stuck it out in the trenches for 14 years now, still attempting to conduct sporadic forays into enemy territory, even if he is cut down by withering machinegun fire at every turn. And as ever, he insists it will "all be over by Christmas".
Harriet,
Because we realize that the sooner this dead-end idea dies, the sooner people can continue on finding the real cause(s)? I would think that the CFS community, while perhaps distressed that this didn't pan out, would prefer to pursue finding the real cause(s) rather than stick wasting money on an idea that has been shown pretty conclusively to be nothing more than a contaminant. Judy is not helping the CFS community out one bit with her religious zealotry over the XMRV idea. It's time to move on the way science is supposed to.
Right...because when a genuine public health crisis occurs, they just ignore it AIDS.
Harriet - nobody is dying of CFS. Suicide? Yeah. Death by woo? Sometimes. But nobody has ever died of it.
Please don't bring up Sophia Mirza either. That was death from untreated herpes that spread to her spine.
While I remember - congrats to the good job by the BWG. Reminds me a lot of the debunking of "Water Memory" by Randi and friends against Jacques Benveniste (wiki page here). Looks like there are a lot of parallels. How science is supposed to work.
Talking of which, these latest results should probably be added to some of the wiki pages - perhaps by someone who has a better understanding than I have of the subject :)
Possible updates to Judy Mikovits page here and the WPI page here, both pages conveniently having "contradictory results" sections (what a surprise)
And with this many links this page will almost certainly get spam blocked! Sorry Abbie....
@El Perro
OK I'll bite :)
I haven't to be honest followed or looked into these deaths of patients with a diagnosis of 'ME' or 'CFS', but what makes you so definite in your pronouncement?
Just interested and I don't want to detract from the main debate, I just haven't picked up on this 'untreated herpes' before.
El Perro, why don't you look at the literature before you make false, ignorant and harmful statements like that. There is excess all cause mortality in people who have CFS/ME.
http://www.ncbi.nlm.nih.gov/pubmed/20038921
There is excess suicide, but virtually all of the excess mortality comes from increased cancer and cardiovascular deaths.
All of these excess deaths fit with the low nitric oxide hypothesis of CFS.
daedalus2u@#53
"All of these excess deaths fit with the low nitric oxide hypothesis of CFS."
Or just being sedentary.
meh.
Prometheus, have you read the material I sent you?
What is the mechanism by which being non-sedentary prevents cardiovascular deaths?
Presumably it is not due to exercise per se, rather it is due to the compensatory repair and rebulding pathways that are activated by exercise. Things like mitochondria biogenesis, which happens to be triggered by nitric oxide.
Two questions if I may:
Were the same assays employed in the BWG study by Mikovits and Ruscetti as were employed in Lombardi to try and detect XMRV/MLVs?
Were those same assays used in VIPdx 'tests' (the commercial ones) and those that were being offered by Unevx?
I would find it very strange if they weren't used but am no able to determine this from any of the information published.
Laurie at #9 is prescient!
I am surprised to find that apparently none of the commenters above has picked up on this piece of breaking news... Judy Mikovits has been fired from WPI.