XMRV: This is what you should do if you mess up

In 2006, long before ERV was a twinkle in my eye-- A really cool paper was published in PLOS Pathogens:

Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant.

They found a 'new' retrovirus, XMRV ('new' to humans, old to mice).  A new retrovirus in prostate tumors.  Especially in prostate tumors that had a defect in an anti-viral protein, RNASEL.  Not only was the idea that there was another human retrovirus out there incredible, it was an incredible finding for patients-- if a virus causes prostate tumors, then antiretrovirals could prevent prostate tumors.  Like the HPV vaccine-->cervical cancer revolution for women, XMRV treatments would be revolutionary for men (not that the HPV vaccine isnt a boon for men too).

It was an incredible finding, and six years later, that one paper has over 100 citations.

Incredible.

Unfortunately, I mean that word literally:

Definition of INCREDIBLE: too extraordinary and improbable to be believed

It turns out that finding was, in fact, too good to be true.  Several groups figured out that one could 'find' XMRV... when they were really finding contaminating mouse DNA.  'XMRV' wasnt really there as a genuine human pathogen causing human disease.  Several groups hypothesized that 'XMRV' was the result of the original prostate cancer tumor, CWR22, being passaged in mice to turn into the 'prostate cancer cell line' 22Rv1.  Pre-XMRV-1 and Pre-XMRV-2, found in mice as ERVs, could recombine to create 'XMRV'.

But these were ad hoc hypotheses.

We needed one particular experiment to 'prove' once and for all XMRV was not 'real'-- What did the original tumor, CWR22, look like?  Was it infected with XMRV, or was it clean?

That very experiment was done by the very lab that put out the original paper:

Absence of XMRV and Closely Related Viruses in Primary Prostate Cancer Tissues Used to Derive the XMRV-Infected Cell Line 22Rv1

Robert Silverman-- The scientist on the first paper.  The scientist who retracted his laboratories contributions to the infamous 'XMRV-->CFS' paper after doing his own experiments and determining his initial findings were false (with both the experiments and the retraction being entirely done on his own accord). This same guy did this work, which absolutely establishes that XMRV is not found in the wild in any capacity.

Here is what they did-- The first 'hint' of XMRV came from a prostate cancer cell line, 22Rv1.

So they went back and looked at the DNA of the original tumor used to make 22Rv1-- They were looking for any evidence of XMRV.

Remember how we figured out HIV-1 was older than we thought by looking at tissues embedded in paraffin?  This group did the same thing, except with XMRV-- Paraffin embedded prostate tissue from the patient tumor used to make 22Rv1.

There was no XMRV DNA.

None.

No mouse DNA either-- The original prostate tissue was not contaminated.  XMRV was probably created during passage of the tumor in nude mice, exactly how Paprotka et al hypothesized.

XMRV is not a genuine human pathogen.

Dr. Frankenstein Silverman killed his monster, and I really couldnt be more proud of him.  This is exactly what you do if you make a mistake in science: You fix it.

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*loads up the ME/CFS Forums whilst heading to the kitchen to pop some popcorn*

Fuck, I'm out of popcorn.

By Optimus Primate (not verified) on 30 May 2012 #permalink

Yes I agree. That's why Dr Frank Ruscetti and Dr Judy Mikovits have set the record straight.....

Its an MLV-like virus. A MOUSE VIRUS. A Gammaretrovirus.

Let's stop wasting time - millions are perhaps affected by this.
Let's pull all the resources we have and stop this virus now before it destroys anymore lives.

By Gammaretrovirus (not verified) on 30 May 2012 #permalink

How many more people have to die before someone does something.

By Crafter Kate (not verified) on 30 May 2012 #permalink

@Gamma and Kate,
People have been doing something about it. It just turns out that the data isn't what you guys want. It doesn't matter, though. What you'd like and what really is are two completely different things. XMRV was a contaminant. It was an interesting contaminant but a contaminant nonetheless. It joins the other Human Rumor viruses that have popped up now and again, giving tantalizing but inevitably false hope to many. As for "MLV-like virus", there is no reliable evidence for this either. The problem is that you are too wedded to your idea to see it for the failure that it is. Science however moves on to better and more fruitful hypotheses that actually have a chance of solving the problem. If you were genuinely interested of finding out the truth about CFS, you'd welcome the elimination of a failed hypothesis, not lament it.

@ERV, I have a great deal of respect for Dr. Silverman. I've said it before and I'll say it again: it has to suck to retract a paper, especially one that lead to so much time and resources being wasted. I very much respect his ability to do so. I wish all scientists had as much integrity (instead of those manufacturing data and/or recycling gel images).

By Poodle Stomper (not verified) on 30 May 2012 #permalink

It doesn't appear that they've retracted the original paper yet. I wonder if they plan to, or if it's just stuck in the journal pipeline...

By Carl Zimmer (not verified) on 30 May 2012 #permalink

@CarlZimmer I tested positive for an MLV. I have written to scientists all over the world and asked if they are prepared to test a tissue sample from me, not any of them are willing too.
Every scientist says to me they are not doing any more work on this subject.

By Crafter Kate (not verified) on 30 May 2012 #permalink

Crafter Kate, scientists don't like wasting their time on things that don't exist. There is a whole corpus of papers now on a contaminant that came from the xenograft. They have unambiguously demonstrated that XMRV was a lab-created contaminant that has no association with any disease in humans.

About the only thing of interest left is to study the process that created XMRV. It could teach us some more about retrovirus evolution.

Chris,

Sandy Ruscetti's antibody recognizes all polytropic, xenotropic, & ecotropic viruses.

By Sunflower (not verified) on 30 May 2012 #permalink

@Sunflower,
That paper does not say that there are MLVs in the blood of those patients. The title may be misleading but that isn't what the paper says at all. Perhaps you could get ERV to do a write up on that paper (hell, I could give you a brief run down if you were genuinely interested in what it really says) but it does NOT say what you seem to think it says.

@Kate,
How did you test positive when there is no test on the market that tests for it? If you took the WPI test, I think you should know that the junk they sold was in no way specific to anything. Their own tests were shown not to be reproducible so I wouldn't worry too much about the results (wherever you got them).

By Poodle Stomper (not verified) on 30 May 2012 #permalink

@Carl,
I'm not even sure it's needed to retract the original paper. In a way, the paper did show interesting data. They did find a new retrovirus (albeit a lab made one) and at this point in time, I think anyone remotely respectable in science knows that the XMRV idea is a dead end.

By Poodle Stomper (not verified) on 30 May 2012 #permalink

Sunflower, that must be one very interesting antibody. It would have so much cross-reactivity to be useless for identifying anything.

You don't retract a paper for wrong conclusions unless you're data or methodology are bad too. They correctly and repeatably identified the virus in the cell line. Only the conclusion that it was tumor related and not an artifact of the cell line creation was in error, and they fixed that with the control experiment and published it.
Compare to the infamous Wakefield Lancet paper. That the conclusion (measles vaccine causes autism) was wrong was proven quickly via epidemiology; the paper was retracted only after it was shown that the methodology was shoddy and that the data was unreliable.

The Lipkin Study will be released June 30th. Hopefully this debate will be ended, even with the militant conspiracy theorists.

By Ronald Roberts (not verified) on 01 Jun 2012 #permalink

Ronald-- Considering Judys inappropriate relationship with patients, the fact she hasnt 'shared the good news' with them yet is, hopefully, a good sign this is almost over.

Abbie-

It is, but there are some reports that she had to sign an agreement to support support the results of the study to be allowed to participate. Unfortunately some of your 'friends' at the toxic forum are already speculating about a 'detailed and fierce plan for if it is negative'. All hope is lost for them.

By Ronald Roberts (not verified) on 01 Jun 2012 #permalink

Erv,
Ah, unfortunately, if this was only true. Most of the toxic members have moved over to the peoplewithme.com forum.

Actually, Gerwyn is now channeling himself through V99 who has devoted an entire thread to you and why based on 'your blog post' Coffin and Paprotka are wrong..blah, blah, blah....

Now don't be shocked. I think ERVs latest blog on XMRV is brilliant
http://peoplewithme.com/thread-1196.html

If Lipkin's results are negative, then he is part of the great conspiracy to cover-up.

Ops, above should read: 'and why' should be after 'your blog post' not before...and yes, I can type...sometimes. :-)

@Ronald Roberts

This speculation is based on the following quote by Lipkin:

"My condition on accepting this charge from the NIH and the clinical and laboratory investigators is that each participant agree to unconditionally accept group criteria for defining cases to be used in this study. Laboratory investigators were also required to unequivocally endorse their results at the conclusion of the study. "

That's not exactly what is speculated. Still, I feel this will be a "way out" for those still arguing that there are HGRV's out there if (and this is a large if) Mikovits would admit she was wrong all along after publication.

Nay, she will never admit she was wrong, and fall from grace with her fans, lose her 'goddess' cult status, be assigned to the abyss of nihility. To admit wrong, would leave her legally liable both criminally and civilly.

Beside her cult following will develop theories of scientific assumptions, speculations, opinions, reading tea leaves & the entails of lab mice to determine the correct solution that the earth is really flat. and xmrv does cause ME/CFS

Yeah, there may be some among the group that realizes that the whole XMRV/CFS thing was crap from the beginning but I'm afraid that the group as a whole is likely to stick their heads even further into the sand and make up more BS for why everyone is wrong except them.

By Poodle Stomper (not verified) on 03 Jun 2012 #permalink

(news from lipkin)

Tweets from: @CII722
The Center for Infection & Immunity is dedicated to pathogen surveillance & grasping how gene-environment-timing interactions contribute to health & disease.
-----------------------------

@CII722: @DeBortgjemte @JAScarb @MEAssociation The XMRV study will NOT be published on June 30. Rumors associated with this release date are false.

@CII722: @DeBortgjemte @JAScarb @MEAssociation We have begun composing the manuscript/compiling the data. Follow @CII722 for updates. Cheers!
VillageLife, Today at 4:04 PM EditReport#1Reply
VillageLife
Senior Member
Just seen more tweets from @CII722

Question from: @MyalgicEncephal: Was the original data for publication of the NIH study the 30th June? Why has it been pushed back?
#mecfs #xmrv #MRV #virology #HHS

reply from: @CII722: June 30th was an estimated date. It was never definitive.

----------

Question from: @MyalgicEncephal: Was the original data for publication of the NIH study the 30th June? Why has it been pushed back?
#mecfs #xmrv #MRV #virology #HHS

Reply from: @CII722: Hopefully the publication, which will be released relatively soon, will answer ur questions. That's all we can say 4 now.

By Sunflower (not verified) on 04 Jun 2012 #permalink

Hmm... don't think much of the decor in here ;)

'“That will be the definitive answer,” she said. “If we’re wrong and we can’t reproduce it, then we’ll be wrong, and that’s how science works.”'

Knicker-fits on 'da Lipkin study' December 2011:

http://www.nytimes.com/2011/12/23/health/research/science-journal-retra…

Huh! I shall eat my shorts if she holds up her paws and adopts the consensus position.

What's so different about Lipkin compared to the last blinded failure at replication? Even using her 'clinically validated' [wink at V99] assays it don't work.

Respect to Silverman (again)...

More from lipkin today.

-------
We will release our findings as soon as possible; however, the work is still in progress. Please note that irrespective of the outcome we have a long term commitment to you and others in the community.

By Sunflower (not verified) on 05 Jun 2012 #permalink

Sunflower, I'm curious...what will you say if the Lipkin study shows there is no XMRV/MLV-like virus in people with CFS? Will you accept the results?

By Poodle Stomper (not verified) on 05 Jun 2012 #permalink

St. Judy, say something like: I was wrong, completely wrong, and I want to apologize to

By mary (abbie's ilk) (not verified) on 05 Jun 2012 #permalink

cont....every scientist that tried to tell me I was wrong. What I found was contamination....

Never gonna happen... her statement will be so non specific that will feed her militants to continue on...cuz we would have bullied Judy into making that kind of apology....

don't know what happened that my original post got submitted before I finished....apologies..

By mary (abbie's ilk) (not verified) on 05 Jun 2012 #permalink

cuz we would have bullied Judy into making that kind of apology
Yeah, and Ruscetti. And Lombardi.

But thank god nobody is doing that.

Instead we have a plead from Abbie.

Abbie, tell me, did you email to Judy your request to do "the right thing"? Did you ask her? Kindly? And Ruscetti. And Lombardi. I'm sure, if they read this, they would immediately do the right thing.

Nobody is investigating this. Nobody is asking the hard questions. So yes, "Never gonna happen".

So we are all just pissed of commentators, reinforcing our view how evil – I tell you, EVIL! – the world is and that we can do nothing to change it. But at least we can bitch about those wacky deluded patients!

Abbie, why didn't you look into what Ruscetti did? Why didn't you "bully" him? I guess you had to much on your hands, with work and all, and running your real skeptics chat room. I understand. There is just so little one can do with ones time. And going after Ruscetti? Next thing you know, you have to go after Gallo. Can't have that if you want to work in virology in the US – would cause too much heat.

So enjoy the light entertainment here about St. Judy and her wacky fans, but don't expect any hard questions that might actually get people like her or Ruscetti into trouble.

You know what the say: You won't notice the few bad apples, if the majority of good apples just does nothing.

By Tony Mach (not verified) on 06 Jun 2012 #permalink

I'm going on record here saying that I would anticipate something alone the lines of: "In accordance with the agreement I signed in order to work on this study, I would like to say that the results seem to indicate that there is no XMRV *winkwink*. But I'm still going to keep following this avenue of research just in case."

By Poodle Stomper (not verified) on 06 Jun 2012 #permalink

Ahhh.... but will she say 'No XMRV' and then confess to 'NO MLVs/Whatever it was that I thought I had REALLY found'?

Because let's face it she didn't really want to call what she allegedly found 'XMRV' at all did she? ;)

You can bet the farm that the door will be left open for V99 and Gerwyn et al. to exploit.

There's an argument that scientists should be held to account for the thinks they say and the incitement and speculation that results.

Remember the 'aerosol' comment? And the additional scaremongering over how parents had passed this 'virus' on to their children through unprotected sex?

That huge billboard in Times Square was it? The 'millions' of 'infected' people on the planet? And them dozy 'interviews' on Nevada television with pet Sam?

If 'da Lipkin Study' 'finds' anything it will be determined to be contamination. I only hope that unlike other studies, Lipkin tracks down the source before announcing any results.

Followed up by v99's spectacularly idiotic comment, testifying to her astronomical confirmation bias:

"Anyway the NIH study is moot.
Hanson confirmed the findings again!"

Like I said, a few may realize that this is BS, the idiots won't.

By Poodle Stomper (not verified) on 07 Jun 2012 #permalink

"If ‘da Lipkin Study’ ‘finds’ anything it will be determined to be contamination"

" testifying to her astronomical confirmation bias"

Just saying.... ;)

"Just saying…. "

Just saying what?

By Poodle Stomper (not verified) on 07 Jun 2012 #permalink

Really? It needs clarifying?

Perhaps conflating the quotes was unfair to you poodle-stomper, so to be clear my suggestion to Jack is that he is suffering rather severe confirmation bias in suggesting that the Lipkin study cannot possibly find a valid viral cause or even association for ME/CFS.

As I understand it the study is not just another XMRV replication study, it is a wider search for a viral agent. If I have misunderstood that my point is undermined but not invalidated.

Arguably even if it were just a replication the point stands as the current consensus is just that and should be subject to adjustment on receipt of further data. You can reasonably argue against spending further money on additional studies based on probabilities, but this research is going ahead so it's data should be accepted with an open mind.

However my main point was that Jack seemed to be going a step further and suggesting that Lipkin cannot possibly find any real (non-contaminant) virus in this study which does not seem to be a justified view

I have no particular horse in this race, other than wanting the correct answer to be found and .research to move forward. I can clearly see that certain elements of the ME/CFS community are over-invested in certain views, but I wince when I see people reacting to that by a) tarring all sufferers with the same brush b) dismissing all research on the subject out of hand. To be fair a) does not apply specifically to this post, but b) does seem to.

The condition remains, the sufferers remain, a solution is still needed. If you believe that XMRV was a contaminant that is a perfectly reasonable view IMHO, if you believe JM is the devil, well I consider that less reasonable but still accept it, however when you start to dismiss other research into possible causes out of hand as if it is all guilty by association then I can't accept that as reasonable and I do have a horse in *that* race - I want this condition fixed.

Maybe you were merely suggesting that such research could be better targeted elsewhere, if so I can accept that viewpoint, but would ask you to understand that there is precious little money spent on researching this condition and disbanding one study such as Lipkin would most likely not redirect that money to other ME/CFS research.

In summary I am asking you not to allow your understandable frustration about events around XMRV to lead you into a polarisation against all research into possible viral aetiology for ME/CFS, unless you know something I don't :)

The "just saying" was intended to make it light-hearted as this is your turf more than it is mine and I mean no disrespect coming in here and speaking against what appears to be a general consensus.

Regards,

Dai

Ah, I must have misread what it was you were quoting. I assumed that Jack was referring to them finding anything related to XMRV sequences which have been shown (quite conclusively, imho) to be lab-generated contaminants.

As for the possibility of other viral causes, I'm open to any good, reproducible data that would suggest this (or indeed any good, reproducible data that points to whatever the true cause(s) is/are) viral or not.

I didn't take your comment as disrespect, btw, I was just curious what you meant by it. As for the general consensus here, while I can't speak for everyone, I think the majority of us here agree that the evidence rules OUT XMRV, but that doesn't mean that any of us here can claim to know what DOES cause it. I can honestly say "beats the hell out of me" if anyone asks me what I think the cause would be. But I can say that the odds of it being XMRV is slim to none.

By Poodle Stomper (not verified) on 08 Jun 2012 #permalink

My understanding is that in 'da Lipkin Study' they are looking for XMRV/MLVs in patient blood.

My feeling is that they wont find it there even if it does show up initially, and I hope Lipkin et al. will track down the source of the contamination as others have done.

If - and I don't really believe this is possible (but what do I know?) - they do claim to have found 'it' in patient blood following radomised testing etc. then it will require further replication of the results post-publication.

Dai - a year ago I would have still held back from claiming XMRV/MLVs 'found' in patient blood are nothing other than contamination and that a 'chance' remained that Lombardi/Lo were on to something but not anymore.

I think the samples used in this study (funded by the NIH specifically for XMRV/MLV work) will then be used by Lipkin in further work looking more generally for viral activity paid for by (a CFS charity whose name escapes me for the moment!).

Until such time as Mikovits et al. produce another published paper that holds up to scrutiny alleging that 'some retrovirus' is present in patient blood (let alone claiming 'it' is somehow causative) - then the 'link' established by Silverman and then Lombardi and then Lo with XMRV/MLVs and human beings is dead.

The science to date has simply not held up and the speculation and incitement caused has not done anyoneany favours (except perhaps WPI in their resultant fundraising - although that lasted about as long as the 'test-kits').

I think lessons need to be learned within the science industry perhaps but it is interesting to consider that rather than taking science away from the subject of CFS this focus has rather raised it's profile.

Anyway, I shall enjoy reading what Lipkin has to say when his paper is published - as I now do reading all the science. I probably wont bother with the resulting storm that will undoubtedly result in some quarters but if I were a betting man then I'd bet on a negative result... again.

@Poodle Stomper: no arguments

@Jack: You could be right about the two studies, I may have been mixing the two in my mind. I would also bet on a negative for XMRV but I would be basing it on second and third hand knowledge so my vote does not really count ;)

As far as I know, that's the rumor but not confirmed yet.

By Poodle Stomper (not verified) on 13 Jun 2012 #permalink

Also, fyi, just because charges are dropped for insufficient evidence does not mean that she didn't do it. It simply means that the DA doesn't think he can make a case based on what he has.

By Poodle Stomper (not verified) on 13 Jun 2012 #permalink

After all, who'd want to risk their notebooks and data stolen?

By Poodle Stomper (not verified) on 13 Jun 2012 #permalink

Jack, I know Abbie's wanting Mikovits to do time, but the 'theft' charges involved very minor (financially) things. If Mikovits is going to do time, it should be for fucking fraud; namely, in her grant applications and use of grant monies. That will take a long time to fully investigate.

I'm not of the 'any time for any reason will do' crowd.

Hmm, interesting...

http://medicalxpress.com/news/2012-06-scientists-lack-protein-results-p…

Scientists from The Scripps Research Institute have shown a single protein can make the difference between an infection clearing out of the body or persisting for life. The results also show where the defects occur in the immune system without the protein and offer the possibility that targeting this signaling pathway could be beneficial for treatment of persistent viral infections in humans. Currently hundreds of millions of people around the world are afflicted with persistent viral infections such as HIV, HCV, and HBV.

Thanks Jack.

What I find nice is that the story Dr. Judy tells – like, hiding on a boat – directly contradicts what all the lying HGRV-sockpuppets (V99/Gerwyn/etc) have been insisting on.

Other than that, what Mikovits does has as much relevance to our lives as what these two criminal boat owners do:
http://www.thedailybeast.com/articles/2012/07/10/william-and-kate-honey…

Now, if I only knew whether Ruscetti has a boat.

By Tony Mach (not verified) on 26 Jul 2012 #permalink