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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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October 4, 2011

XMRV: This Is Not Good

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Posted by Derek

If you haven't seen this XMRV news, then you should. The very day after I wrote my most recent post on the subject came this one from ERV over at Scienceblogs.

There are two key figures in it: one from the original Science paper, showing infected patients expressing XMRV Gag protein (a sign of viral infection). And the other was presented recently by Judy Mikovits at a conference in Ottowa. It shows a different experiment - Gag protein being expressed in some other patients only after treatment with 5-azacytidine. The problem is. . .well. . .I'll let you go see for yourselves what the problem is. It most definitely needs explaining, and the explanations had better be good.

Update: continued unraveling. Mikovits herself has been fired from her research institute, apparently for other causes.

Second update: The Chicago Tribune is on this story, breaking it to a wider public. For a link to the alleged third version of the Mikovits figure, see the comments to this post below.

Comments (88) + TrackBacks (0) | Category: Infectious Diseases


COMMENTS

1. RRM on October 4, 2011 6:55 AM writes...

Here's the third version with the original scribblings attached:

http://i56.tinypic.com/23r7fwx.jpg

Does not seem to support the Science "version"....not good at all indeed...

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2. Mutant Dragon on October 4, 2011 8:56 AM writes...

That is truly alarming indeed. Appalling might be a better word. Congrats to ERV or whoever picked up on that one.

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3. opsomath on October 4, 2011 9:10 AM writes...

For a sunny-side take on the XMRV thing (which we already knew was circling the drain, although it's dismaying to hear that the original report might be based on research misconduct) I would just like to say that it's awesome to see the blogosphere playing such a fast and effective role in research review. Crowdsourcing FTW.

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4. deceased on October 4, 2011 9:13 AM writes...

Haha, I'm awaiting an iStockPhoto service with scientific figures.

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5. Anon on October 4, 2011 9:14 AM writes...

So an administrator can force you to give up your exclusive items? Is this new? Cell lines, mouse models, etc at the will of politics??

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6. Science Not Sermons on October 4, 2011 9:21 AM writes...

Sorry, I can't stop laughing. You guys are really going to listen to a puerile, self-aggrandizing science graduate who is desperate to jump on the fame wave? Abbie Smith, aka ERV, from Oklahoma University, is well known for her lack of professionalism and integrity, having called Dr. Mikovits a c**t and mocked and ridiculed sick and dying patients on her blog. Go ahead, look at her blog, read every post (and comment) relating to XMRV/CFS and tell me she doesn't ooze envy and venom. Come on guys, you can do better than this!

The obvious answer is that Dr. Mikovits, being under a tremendous amount of professional and personal pressure (dismissal imminent etc - which incidentally is because she objected to VIP Dx selling unvalidated tests), simply made a mistake on the power point. No need for loony conspiracy theories.

It might be of some interest to readers that the majority of patients still believe very strongly that an HGRV is responsible for their illness; no amount of blog posting and media rants/sermons is going to make that go away.

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7. johnnyboy on October 4, 2011 9:22 AM writes...

Amazing.
I give it a couple of hours before comments start appearing down below saying that Mikovits is obviously being framed in a character assassination plot masterminded by the forces of evil (big pharma, the government, vampires - take your pick)

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8. johnnyboy on October 4, 2011 9:24 AM writes...

oops - even quicker than I thought !

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9. monoceros4 on October 4, 2011 9:27 AM writes...

"It might be of some interest to readers that the majority of patients still believe very strongly that an HGRV is responsible for their illness."

Wow, I get to vote on the etiology of my illnesses! I want my high blood pressure to be caused by eating lima beans; it'll be easier to treat that way. Where's the ballot?

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10. Anon-Y-Mouse on October 4, 2011 9:27 AM writes...

Anon #5: If you have funding from NIH (she does), you agree to give any research samples to other investigators. Based on what I have read, she wouldn't do this and an administrator stepped in.

If she doesn't like the NIH rules on sharing (data and materials), then don't take their money.

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11. startup on October 4, 2011 9:38 AM writes...

#6 "majority of patients still believe very strongly"

Does not the same hold true for vaccine/autism crowd?

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12. Ugly on October 4, 2011 9:53 AM writes...

"Does not the same hold true for vaccine/autism crowd?"

Think harder.

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13. MTK on October 4, 2011 10:01 AM writes...

@6,

I don't know if I'd call Ms. Smith puerile, self-aggrandizing, or however you may want to characterize her, but that's hardly the point here.

The Science paper and the slides from her talk are in the public domain and we can all examine the figures ourself. They're clearly the same gel, yet Dr. Mikovitz presented them as different gels from different experiments. It's pretty damn easy to see that they are the same gel by looking at the "noise" in the gel, for example, the streak in lane 3 and some of the faintly visible spots in lanes 4 and 5.

Now perhaps Dr. Mikovitz just got the wrong slide copied onto her Powerpoint presentation, but even if that were true she should have recognized it immediately, since the gel would not have properly supported the purported experiment this came from due to the lack of a positive control.

Add to all this, the inability of other labs to repeat her work, the inability of WPI labs to correctly identify XMRV infected samples, her unwillingness to share samples with other researchers, the fact that XMRV sequencing that ended up being nearly identical to the VP62 plasmid she was provided previous to the Science work, the partial retraction of the Science paper, and you've got yourself a snakepit wrapped up in a hairball.

I guess what I'm saying SNS is that the weight of the evidence is going one way and it isn't against Ms. Smith. I'm actually quite sure that Dr. Mikovitz started this all in good faith, but somewhere along the line she stopped being a scientist and started being a proselytizer. The problem with proselytizers is that the ends justify the means, which nearly always leads to bad things.

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14. Ugly on October 4, 2011 10:11 AM writes...

MTK - can you explain the findings by Alter and Lo? MLVs were found to be in the blood of ME/CFS patients by government scientists - one of which was the co-discoverer of Hep C.

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15. InfMP on October 4, 2011 10:34 AM writes...

Correction: Ott A wa is the capitol of Canada.

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16. MTK on October 4, 2011 10:39 AM writes...

What's there to explain in Alter and Lo?

They found MLV's, but no XRMV, in their samples which was in direct contradiction to the results of Lombardi and Mikovitz, who initially reported >60% of CFS samples contained XRMV, but has upped that considerably as time has passed.

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17. Ugly on October 4, 2011 11:48 AM writes...

Please. They found retroviruses in the blood - several different types. XMRV is a retrovirus. There are retroviruses in the blood of ME/CFS patients and this needs to be addressed.

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18. MTK on October 4, 2011 12:04 PM writes...

Ugly,

Did Alter and Lo find XMRV association with CFS? Did Lombardi and Mikovitz associate XMRV specifically with CFS? Simple questions.

Alter and Lo did not confirm Lombardi.

And yeah XMRV is a retrovirus, so what? There are thousands of known retroviruses, most of which do not result in any human disease state.

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19. KAL on October 4, 2011 1:04 PM writes...

Ms. Smith's juvenile and unprofessional potty mouth aside, these are serious questions that deserve serious answers.

As for patients, given the proven cognitive dysfunction in ME/CFS combined with a lack of science background I'm sure it is difficult for patients to sort out conflicting messages.

While none of us get to vote on what causes the disease we have contracted, it perhaps needs to be pointed out that patients, regardless of the disease in question, are the expert on their own experiences and major stakeholders in the science - even if they are not scientists.

Think about it. If you don't have a disease, it is easy to make facile comments and move on with your every day life. Patients don't have that option.

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20. Hap on October 4, 2011 1:54 PM writes...

No, but facts don't really care how people think or feel - they just are. If the figures are identical, and there is a laundry list of other issues with the research connecting XMRV to CFS (as in MTK's comment 13), well, it's probably time to find another hypothesis.

While there is understandable reason to be emotional about CFS, there is also the problem that emotions are readily manipulable. Executing the wrong man for a heinous crime may help the living victims and families of the dead to find closure, but it is a costly and false closure. The victims of the actual criminal would probably tell them that if they could speak.

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21. Ugly on October 4, 2011 2:02 PM writes...

When the Lipkin study results are released we will then be in a position to decide whether another hypothesis is warranted.

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22. Special Guest Lecturer on October 4, 2011 2:28 PM writes...

Noise seems to be the most effective way to catch a scientific fraudster. It outed Schon, it definitively proved that Sezen's NMRs were fictitious, and now it is the random variations of a gel that get Mikovits.

To patients having a hard time digesting this news:

I have the utmost sympathy for those suffering from this disease, but your anger and frustration should be turned to Mikovits herself, whose fraudulent work has lead others down a blind alley, diverting attention and resources from research with a chance of making real progress.

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23. RetroGuy on October 4, 2011 2:38 PM writes...

You have no prove that Dr. Mikovits has committed any fraud - just the word of a graduate student. Nothing else. Cease rumour-mongering; I'm embarrassed to say I'm a scientist in this climate.

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24. CR on October 4, 2011 2:42 PM writes...

@9. monoceros4:
"It might be of some interest to readers that the majority of patients still believe very strongly that an HGRV is responsible for their illness."

"...Wow, I get to vote on the etiology of my illnesses! I want my high blood pressure to be caused by eating lima beans; it'll be easier to treat that way. Where's the ballot?..."

How dare you ridicule #6, Science Not Sermons? I think you are setting this discussion back by engaging in this type of banter.

And, BTW, high-blood pressure is clearly caused by eating broccoli, not lima beans. I'm a patient and I "know" this for a fact whether a scientist figures this out or not.

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25. MTK on October 4, 2011 2:53 PM writes...

@23 (retroguy)

What is so embarrassing?

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26. Hap on October 4, 2011 3:15 PM writes...

I'm embarrassed about lots of things, but I'm not sure why I would be embarrassed by nailing someone for reusing the same figure (the Schon Gambit). Isn't one of our jobs as scientists to detect and deal with problems in our and others' results rather than assuming they're true and ignoring any inconsistencies?

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27. Special Guest Lecturer on October 4, 2011 4:16 PM writes...

@retroguy: This is not a matter of comparing the credibility of a graduate student against a senior researcher.

The data are public domain. The Science paper is published. The slides from the conference are available. The identity of the messenger is irrelevant.

The gels are identical - the smears, the random lines, the barely there splotches - that is, the "noise" in the gel will never be exactly the same from experiment to experiment. You couldn't reproduce that spot-on if you tried, even if you were extra careful. All real data has noise. When two independent experiments have exactly the same noise, it raises a huge red flag.

The two most plausible explanations are fraud and accidental reuse of the image. This looks much more like fraud than accident, particularly if (as it looks from the image linked in comment #1) it is the Science paper that is incorrect.

I say this because a ton more thought, writing, and revising goes into preparing a paper for publication in Science than in preparing a single conference slide. Mistakes can certainly be made, but it is rather convenient that such a mistake would innocently support the desired outcome of the study.

This looks like fraud, plain and simple.

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28. dvizard on October 4, 2011 4:39 PM writes...

Well, ERV's last post about the subject already seemed to indicate serious fraud... the guy retracting his part of the old paper chose a gentlemanly way out of the story...

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29. KAL on October 4, 2011 4:43 PM writes...

@HAP Yes, facts are facts. Cognitive dysfunction in ME/CFS is a fact. The patient experience is a fact. That the same slide was labeled three different ways is a fact.

Not disputing facts at all, I have no horse in the race, simply pointing out that facts are not an excuse for being snarky.

Not to put too fine a point on it, but snarkiness and jibes, no matter who the target is, are more of a reflection of the character of the person making the comment than the target. And that cuts both ways.

As for hypotheses, XMRV has never been more than a blip on the radar if you read some 50 years of science instead of cruising the Internet. The predominant theories are in no particular order:

1. Multiple pathogens or combinations of pathogens cause the same disease - research shows that the severity of the infection has more to do with the development of ME/CFS than the specific pathogen or psychological factors.

2. CFS is an umbrella term encompassing a number of discrete diseases and/or conditions. This is where the work on improving definitions and eventually subgrouping by biomarker will make a big difference.

3. ME/CFS is an uncommon reaction to common pathogens. Considerable research in subgroups shows immune system abnormalities.

4. CFS is a psychosomatic disorder (this one has even less objective evidence than the biomedical ones.)

Harvard is doing an epi study using data from the Nurse's Study. Lipkin and colleagues at the CII are doing a deep sequencing study.

Moving on, moving on.

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30. Joe on October 4, 2011 4:48 PM writes...

What happens now with what Dr Alter found? I m a patient and only care to know what is wrong with me so I can finally pursue a treatment, I don't give a hoot about personalities. Is Dr. Alter's finding significant or not?
I am in the Lipkin study, blood collection STILL has not occurred, it was moved to November last week ( supposed to have been done n April). I would not be surprised if this recent news further delays it. I hope not.

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31. Joe on October 4, 2011 4:49 PM writes...

What happens now with what Dr Alter found? I m a patient and only care to know what is wrong with me so I can finally pursue a treatment, I don't give a hoot about personalities. Is Dr. Alter's finding significant or not?
I am in the Lipkin study, blood collection STILL has not occurred, it was moved to November last week ( supposed to have been done n April). I would not be surprised if this recent news further delays it. I hope not.

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32. Hap on October 4, 2011 5:38 PM writes...

I don't know how much of the snark was directed at CFS/ME sufferers and how much at the PI. I would have said "not much/most" but enough people in the former category seemed married to the hypothesis that XMRV was the main cause (and aggressive about it) that that's probably not the case (that it's a "gotcha" to people who were aggressive without sufficient cause or data to back up their aggression).

While the snark is unkind, it's kind of like salt on a shotgun blast to the belly at this point. The main damage to ME/CFS sufferers was done when the figures were duplicated (making it harder for more honest people to get funding and wasting what little funding was given on (at best) a wild-goose chase and at worst a snipe hunt).

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33. MTK on October 4, 2011 5:41 PM writes...

It doesn't get any better for defenders of Dr. Mikovitz. Her collaborator at NCI, Dr. Francis Ruscetti, who is a co-author on the Science paper, has evidently confirmed that the figure in the Science paper and on the slide at Ottawa are one in the same.

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34. Pigsy on October 5, 2011 6:56 AM writes...

I think it was pretty clear they were the same. Very few people were arguing that they were different. That still doesn't mean it was fraud; the likely scenario is it was a mistake. Dr. Ruscetti, the co-discoverer of HTLV stands by the research.

Abbie Smith has been sounding the deathbell on XMRV since the paper was first released. She is scrabbling to make it a reality. She cannot control herself and her outbursts really are becoming an embarrassment to science. Each obsessive blog post she writes screams personality disorder. It's my understanding that Oklahoma University are in talks to eject her from her graduate program.

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35. MTK on October 5, 2011 7:38 AM writes...

Pigsy,

The editors of Science asked the authors to voluntarily retract Lombardi et al before all this came out. The authors declined to do so.

What do you think the editors of Science are going to do now that one of the co-authors has confirmed/admitted that Fig 2c does not actually represent what it was purported to represent and they knew it?

The authors explanation now is that they deemed that detail (that 5-aza was added) not to be germane. (??)

I don't know if that's fraud, but if it isn't it's about as close as you can get. IMO, getting anywhere near that line is too close.

As for Ms. Smith. Stop. OK. While her tone is certainly immature, she was right about this. At the same time you are the one propagating rumors about her at this time. Beyond stopping, your ilk actually probably owes her an apology since she was, well, correct. It would be the decent thing to do.

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36. Ugly on October 5, 2011 7:59 AM writes...

The patients certainly do not owe her an apology. They are the ones suffering for God's sake.

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37. MTK on October 5, 2011 8:08 AM writes...

Ugly,

So if one is suffering that gives them carte blanche to call another person whatever derogatory terms they want? Oh..K...

I don't know who is a patient or who isn't, but I would posit that anyone who has made personal remarks regarding Ms. Smith in this matter, essentially because they don't like her message, probably does owe her an apology, suffering or not.

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38. Fineline on October 5, 2011 8:10 AM writes...

Do you realize people are dying from this? 3 patients died this past month - one an 18 year old. Have you ANY freaking idea? Patients are besides themselves. This was their ONLY hope. No funding, no treatment, no care - in some cases severely ill and dying patients are being sectioned and placed in mental health wards to suffer untold horrors. Sophia Mirza died after this treatment. We see our friends and fellow advocates dying and no one is doing a fucking thing about it. And then you have the audacity to say we patients should apologise too Abbie Smith. Are you out of your tiny mind?

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39. johnnyboy on October 5, 2011 8:22 AM writes...

@ 35: hear, hear. CFS patients are calling for sympathy, but the crowd posting here seems singularly undeserving of it. They're not only dismissing what is at best terribly sloppy scientific work (and most likely outright fraud) as simple absent-minded mistakes; they're also launching nasty personal attacks on one of the messengers. Let's see, in just a few posts, Abbie Smith is "puerile, self-aggrandizing, desperate to jump on the fame wave, juvenile and unprofessional, mocked and ridiculed sick and dying patients, oozes envy and venom, cannot control herself, is becoming an embarrassment to science, has a personality disorder, is about to be ejected from her university." Talk about shooting the messenger.

Look, I have no chips in this game, and I think everyone in the medical community would love for CFS to be caused by a virus. And maybe it is. But it's becoming painfully obvious that XMRV isn't it. Stop latching your hopes onto a sinking ship.

Permalink to Comment

40. MTK on October 5, 2011 8:24 AM writes...

Fineline,

I said nothing of the sort.

I said those that made personal attacks on Ms. Smith should consider apologizing, regardless of whether they're suffering from CFS or any other ailment for that matter.

In fact,CFS sufferers might consider doing more than apologizing, but actually thanking her for helping to expose what increasingly looks like a dead end in terms of etiology and possible treatment for CFS.

This ONLY hope was one built on bad science at best, fraud at worse. Do you not see that? The ONLY hope was a false hope based on falsehoods, omissions, and feints.

Your anger, while understandable, is misplaced.

It should not be directed at those that help collapse this house of cards, but rather those that built it and gave you hope where none was deserved.


Permalink to Comment

41. Fineline on October 5, 2011 8:37 AM writes...

No, my anger is not misplaced. Abbie seeks to put a hold on the research that could save lives. Do you have any idea how desperately ill people are? She is taking away our lifeline. HGRVs are in the blood of ME/CFS patients. Ruscetti, Mikovits, Alter, Lo, Hansen and several other groups have found them. It wasn't just Mikovits. If you had been following the story as closely as we have you would know that. It's never just been a one-horse race. By taking out Mikovits the work won't stop but it will slow it.. and in that time lives will be lost.

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42. Fineline on October 5, 2011 8:45 AM writes...

And the last thing I will add is that some of the comments on that thread are abhorrent. The laughing, the glee, the joy -- it's really too much to bear. Where is the humanity? I had a life before I got ill. I was going somewhere. Now the only thing I can do is advocate for treatment and care for myself and my fellow sufferers. Smith's actions are detrimental to science and to the health and well-being of 17 million people.

Permalink to Comment

43. Ugly on October 5, 2011 8:59 AM writes...

@MTK, It might seem like a game to Abbie Smith and those in her echo chamber (most of whom are very young, fresh out of school) but there is going to be mass fall-out. She's talking petri-dishes, we're talking lives. It would do you good to remember that next time you're in their playing scientists -- there will be blood on your hands.

Permalink to Comment

44. Derek Lowe on October 5, 2011 9:05 AM writes...

Fineline, you're not seeing any joy from me. Remember, I work for a drug company: we would have been very happy if XMRV had turned out to be the cause of a disease, because then we could have found new effective antiviral drugs to sell. Everyone would have come out ahead.

But what do we have instead? Wasted time, wasted effort, and recriminations. If the XMRV story is as bad as it's looking, then all the patients affected should be cursing the names of the people who boosted it, not defending them in every forum they can find. I know that you're convinced that this is a viral disease, and that anything that hurts that hypothesis is a Blow Against The Truth. But you have to realize that a lot of intelligent, competent people disagree.

Permalink to Comment

45. Virology on October 5, 2011 9:22 AM writes...

You are forgetting that many of us were scientists, doctors, researchers, nurses, brain surgeons, lawyers, court judges before we got sick. Our illness doesn't suddenly mean we've grown stupid overnight. There are many intelligent, competent people who believe ME/CFS is caused by a virus...and they're not all patients.

Permalink to Comment

46. MTK on October 5, 2011 9:26 AM writes...

Fineline,

Smith's, or Coffin's, or McClure's, or Stoye's, or whoever's experiments, critiques, and criticisms are not detrimental to science, but rather an integral part of science.

Scientific research is not a straight line to truths, but rather a continuing series of dead ends, blind alleys, and fortuitous discoveries. Often the best service to finding something is recognizing the dead end early on, so an early course correction can be made.

XMRV is dead. Done. Now if HGRV's are the etiology, I assure you that having Dr. Mikovitz out of the picture will help at this point, not hurt that effort. Her misbehaviors with regard to Lombardi et al at this junction sully things. Until she can rehabilitate her image and regain credibility, it's best for everyone, including you as a CFS sufferer, for her to stay deep in the background.

Permalink to Comment

47. Lilly on October 5, 2011 9:40 AM writes...

ERV/Abby Smith has engaged in hate speech against Dr Mikovits, Annette Whittemore and WPI at least since October, 2009. She has denigrated patients, called Dr. M a c*nt, called Whittemore, the CEO of WPI and a former teacher, a housewife, and called mecfs patients crazy, among other things. There is plenty of evidence, supplied by her, of her own mental pathology. Noting that is not "shooting the messenger". It is knowing the messenger's history of distortion and hostility.

Now she finds something that may well be a mistake but all of a sudden it's "fraud."

No, no one in their right mind is going to thank her for that. She has been on a hate binge for over 2 years. She has contributed nothing positive to life on earth. It may well be that she is the fraud.

Patients already know that "xmrv" was misnamed due to an error by Cleveland Clinic. That does not negate other findings of human gamma retroviruses in this illness. That several variants of MLVs were found by Alter and Lo, and that Dr Mikovits has said from the beginning they were also finding these variants makes this path still worthwhile investigating. It has not been a "waste of money".

While cancer researchers get hundreds of thousands to do research into Tai Chi for pain in rectal surgery patients, mecfs still has to beg for the measly $1.65 per patient/per year in research. That's less than hay fever or erectile dysfunction get.

That is the scandal!

Permalink to Comment

48. Fineline on October 5, 2011 9:43 AM writes...

I know about science thanks, MTK - I have a degree in it. As Virology says - we did have careers before we got sick.

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49. Lilly on October 5, 2011 9:49 AM writes...

That Trine of the Chicago Tribune is promoting ERVs claims is no surprise either.

She also has a history of disdaining and denigrating mecfs patients and any research that seeks to find the biomedical cause(s).

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50. Orpheus on October 5, 2011 10:21 AM writes...

@47 As a sufferer of both hayfever and erectile dysfunction I find your desire to downplay my inferior quality of life quite hypocritical! Why should we have lower priority?

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51. Ugly on October 5, 2011 10:29 AM writes...

Troll.

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52. Henry on October 5, 2011 11:21 AM writes...

"Smith's, or Coffin's, or McClure's, or Stoye's, or whoever's experiments, critiques, and criticisms are not detrimental to science, but rather an integral part of science."

Sadly that is not the case when it comes to ME. Stoye, Smith and Coffin are using the media to derail the natural scientific process. Coffin, Stoye and Smith have time and again had their theories shot to pieces in symposiums and scientific debate, so where do they run - to the media, to the grubby back streets of bias, prejudice and propaganda.

Derek, and all those that have posted negative comments - you still fail to answer the simple question. Lo and Alters paper still supports the association between CFS and Human Gamma Retroviruses. Not just supports the association, but 24 out of 25 rigorously defined patients were found to be infected, that is 96%. Where is the properly conducted replication of that study?

There is far to much prejudice surroundi