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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.

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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.


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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.

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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.

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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.

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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!

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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 surrounding ME/CFS, prejudice that it cannot be a real, physical, terrible disease. I think that is clouding the judgement of Derek and others here. I have news for you, ME/CFS is a real, physical terrible disease, any comment, any denial by thought or word, should make the owner of them so utterly ashamed that they have no place in civilised society. Now the real question is having made such comments, as Stoye, Smith, Wessely have done - what do you suppose the response, denial denial denial and attack attack attack at both the people finding proof or an apology.....

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53. Henry on October 5, 2011 11:44 AM writes...

Derek wrote "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."

I don't think you realise Derek, it has been proven by thousands of medical papers since the 50's that ME is a physical viral disease. Even in 1978 they knew that the pathogen could be transfered to monkeys. Autopsy studies have shown clear viral lesions in the spinal chord of those that have died from ME/CFS.

You need to appreciate that your disbelief as an "intelligent, competent person" is as distasteful as disbelief in the holocaust. A defence that such belief is held by one that is "intelligent" is not a defence it is actually a condemnation of those that hold it. Please read some of the decade of real research into ME.

Please watch this film. The truth and belief are sadly often misplaced.
http://www.youtube.com/watch?v=eLNKEXIVDdI

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54. drug_hunter on October 5, 2011 12:24 PM writes...

Hi Derek --

From Wikipedia: "Although classified by the World Health Organization under Diseases of the nervous system, the etiology (cause or origin) of CFS is unknown, and multiple psychological and physiological factors may contribute to the development and maintenance of symptoms. There is no diagnostic laboratory test or biomarker for CFS."

And yet you've just been equated to a Holocaust denier.

I'd suggest it isn't worth it to post anything in the future on this syndrome. The "discussion" isn't really going anywhere. I'd rather have a spirited debate on polywater or cold fusion.

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55. Trep on October 5, 2011 12:30 PM writes...

@Henry

What does any of that have to do with the issue at hand? What we are concerned with here is that a scientist knowingly published misleading data, leaving out important methodological information and important experimental controls, in one of the most prestigious scientific journals in the world.

Either this was:
A. Intentional, and thus scientific fraund,or
B. Unintentional, and thus the scientist is incompetent and does not understand basic experimental design.

In either case, you do not want this person researching and publishing on an important disease.

The reason people here are reacting so strongly is that this type of behavior is extremely offensive to anyone with any interest in science.

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56. Phoebs on October 5, 2011 12:56 PM writes...

You also need to be aware that the field is highly politicized. Other retroviral hypotheses have been shut down before the research could be concluded. The previous researcher was involved in a serious car crash that left her disabled. The work was never concluded. She too was hounded. Why? Why are the British Medical Research Council's files on ME/CFS closed (i.e.. unavailable to the public) until 2071? Why are psychiatrists with vested interests (links to UNUM, Department of Work and Pension and the Ministry of Defense)allowed to dictate the field and ignore over 5,000 biomedical papers? Why does the British government say they accept the World Health Organization's classification that ME is a neurological condition and yet treat it as psychiatric? There is a lot more to this story than meets the eye and with all due respect you know nothing about what is really going on here. The politics is far-reaching and engulfs the whole field.

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57. cynical1 on October 5, 2011 1:21 PM writes...

I have done a literature search and, aside from the XMRV reports, there are no reports of gamma retroviruses in ME/CFS in the scientific literature that I can find. While there may be some work in progress (outside of XMRV), it has not been published nor, of course, replicated by others in the field as of yet. So, therefore it would be scientifically foolish to assume that association exists at this juncture and downright stupid to ingest antiretroviral medications for some time to come. Unfortunately, the XMRV link to CFS/ME has been debunked irrevocably. That is simply a fact at this juncture. Some of us were quite excited when it was first published. I have spent about half my 26 year career working on antiviral drug discovery. Trust me, none of us are excited about XMRV anymore. It's sort of like cold fusion. Everyone got excited and then it turned out to be a bunch of sloppy experiments that noone could replicate. Deja vu......

I do appreciate the frustration of the ME/CFS patients and their caregivers. I myself (a medicinal chemist) am watching my wife die of late stage multiple sclerosis. Now that money is being made on drug therapies, things have improved somewhat but for many years MS research languished and was sidelined completely at all of the major pharmaceutical companies. My wife and I both know that her disease will kill her long before an effective therapy is developed for her late stage MS. Bitching about that isn't going to change any of it either.

I have watched patients post literally volumes of text while I followed this sad debacle in science. However, I would humbly suggest that all that energy, passion, and activism has been sorely misdirected. That resource should have been solely directed at increasing disease awareness and research funding and not arguing with scientists who do this stuff for a living. Period. We all know that CFS/ME involves a differential diagnosis with few to any accepted biomarkers. As a consequence, CFS umbrellas a heterogeneous patient population at best. Since I also read MS blogs, I can say that the CFS community is being misrepresented to the scientific community by a very vocal but very misguided minority. Or at least I hope it's a minority.

As for ERV/Ms. Smith's blog, regardless of her predilection towards alienation of some groups/scientists, her scientific analysis of the data of this disaster has been accurate. As for her blogging style (for which I'd much rather read Derek's), I would guess that she has probably raised quite a few eyebrows even in her own profession. But that is her problem and should not be a priority for the CFS community. The WPI derailed it's own efforts long ago. CFS patients should understand that biomedical scientists will always take a very dim view of anyone who shares the stage with Jenny McCarthy at an Age of Autism conference. Even if Dr. Mikovits was a brilliant pioneer in her field, she would probably be dismissed for that alone and arguably so. But if she was brilliant, she would know that wouldn't she?

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58. Mu on October 5, 2011 1:36 PM writes...

So, you think the situation for CFS research would improve if you let fraudulent research go unchecked? The fall of Lombardi might kill Lo and Alter, it might not. But if you had let the MXRV ghost chase continued unchecked, at some point the truth would have come out (this is science, people hate to fail and look for answers). And the whole CFS-retrovirus research area would have become so toxic no one would have looked at it again for a hundred years.

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59. Vince on October 5, 2011 1:53 PM writes...

When disagreement with the XMRV hypothesis is characterized "as distasteful as disbelief in the holocaust" (#53. Henry, above), it becomes clear that these folks do not put a priority on being taken seriously.

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60. Science Not Sermons on October 5, 2011 2:11 PM writes...

You have no proof that this is fraud and you only defile yourselves by continuing to saying so publicly. You are all increasingly sounding like participants of a kangaroo court. It's a trial by social media. Next you'll be shouting "Witch". Have you any idea how ridiculous you sound? http://www.youtube.com/watch?v=TAFVALRWDyk&feature=player_embedded

Until it has been investigated and I see proof from individuals who aren't associated with ERVs blog, I'll believe it.

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61. Anonymous on October 5, 2011 2:19 PM writes...

Re the Alter paper this is an extract from the science magazine article

"More setbacks followed. A week after the
working group meeting, Retrovirology published
four devastating papers online that
together made a compelling case that a contaminant marred both the
Lombardi et al. and Lo-Alter studies. Two reports co-authored by
Coffi n looked for XMRV and MLV in both CFS and prostate cancer
patients; every positive sample they found also harbored mouse DNA,
suggesting that a reagent had become contaminated. Another report
put a fi ner point on it: Researchers discovered MLV—at least 97% similar
to the Lo-Alter viruses—in a commercially available enzyme used
in a PCR kit. Some speculated that perhaps the patient samples were
handled more than the controls."

Not sure who authored the third that discredits the Lo-Alter

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62. Anonymous on October 5, 2011 2:21 PM writes...

4th paper

"The fourth study, led by Greg Towers at University College London,
was even more damning. It was a follow-up to an earlier report,
published in the April 2009 issue of the Journal of Virology by
Miller’s group, that described the discovery of XMRV in a cell line
called 22Rv1, which was derived from a human prostate cancer patient.
At the time, Miller thought the fi nding supported the theory that the
virus infects humans, as he assumed the original prostate tumor used
to make the cell line harbored XMRV. Now Towers’s team had compared
the genetic sequence of XMRV from different 22Rv1 lines with
reported sequences from patients.
The cell line viruses proved ancestral to those in patients. There
was also more genetic diversity in viruses from different 22Rv1 lines
than different patients, precisely the opposite of what should happen if
the virus infected humans: Immune system pressure typically forces a
virus to diversify as a means of escaping attack. Towers concluded that
XMRV never infected humans and that the cell line virus had somehow
contaminated the patient samples."

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63. MTK on October 5, 2011 2:45 PM writes...

@60,

I will agree with you on one point, "fraud" is probably too harsh a word at this point. That connotes some sort of malfeasance which has not been proven.

However, at a minimum Dr. Mikovitz misrepresented the gel at least once and maybe twice. Lombardy et al omitted important experimental details which would a) effected interpretation of the gel, and b) made it hard to replicate the experiment.

That may not be fraud, but its shoddy science. Combine that with the results from the Blood Working Group, Levy's paper, and all the other negative reports and you've got real problems.

I said it in comment #13, and I'll say it again, I don't think Mikovitz intentionally committed a fraud. Just the fact that all the labs including hers were involved in the Blood Working Group study tells me she truly believes.

Somehow though she's lost control here. Her contention in the Science article that Coffin "turned against her" is telling. (Coffin says he never turned against her, just the hypothesis.) She's now self-identified with the hypothesis and can't separate the two.

In poker parlance, she's all in, which means you either have the goods or bluff your way out. (By that I'm not implying she knew she had nothing, but rather that she believed she had a winning hand.) The Blood Working Group called that bluff and she had a losing hand.

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64. Hap on October 5, 2011 3:29 PM writes...

It's a trial by social media. Next you'll be shouting "Witch". Have you any idea how ridiculous you sound?

I wasn't aware that evidence was less reliable when, say, transported by Pony Express than when shown on the interwebs. Talk is cheap, and cheaper on the internet than most other places, but evidence is not. Since others have corroborated the identities of the two figures, well, complaining that evidence impugning your desired hypothesis is invalid because a blogger brought it up is either the old "shooting the messenger" fallacy, the older "ad hominem" fallacy, or the even older "if I don't want to see it, it isn't there" fallacy.

About sounding ridiculous, well, I have a kettle I think you should meet. I'm sure you'll be good friends.

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65. PJ on October 5, 2011 4:16 PM writes...

The same slide has been used, yes, we all agree and so does Ruscetti but there is a big leap from that to fraud and the more you shout 'witch' the less inclined people are to listen to you.

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66. Hap on October 5, 2011 4:28 PM writes...

I don't know if it's fraud, but it's sure in the vicinity (maybe a suburb) - see #63. It is not just a slide shown mistakenly, since it was relabeled - someone had to have consciously remarked it. Lots of irreproducible data and a key figure used as data for two separate contentions doesn't leave all that much wiggle room for either the PI or her hypothesis.

It doesn't seem like there's much yelling, other than by people who wish XMRV to be the cause of some of the CFS spectrum of diseases. Data doesn't need to yell.

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67. MaryMS on October 5, 2011 6:22 PM writes...

While we have the attention of some young virologists, please take a look at this. It is not Retrovirus v. Nothing.

There is a lot of research on OTHER viruses from different families. Yet that never gets discussed. These are things that have been documented for years. And immune and/or antiviral treatment helps the subset of patients who have immune defects and active viruses. But once you have been tagged with CFS, nobody wants to look at this other evidence.

So after you are through with this particular argument (which is not over, but I hope will become lower profile), try to take back with you what we need research on. Young scientists, if you can crack this disease you will win prizes, because it is extremely complex.

2-day VO2 MAX stress test (Snell, Pacific Labs) abnormalities
Abnormal cytokine patterns
Abnormal SPECT scans
37kDa Rnase-L abnormality
Natural killer cell dysfunction
EBV as a trigger
Mold as a trigger
Active HHV-6 Variant A
Active HHV-7
Active Cytomegalovirus
Active Coxsackie B (an enterovirus)
Active parvovirus

And the question of chromosomally integrated HHV-6.

This would not be a mystery disease if more research was done on the biomarkers, immune defects, and pathogens known to be associated in a subset with the severe form of the disease.

When you get through with this topic, please move on to the other evidence that remains ignored. One million adult Americans have this disease. It occurs in cluster outbreaks. What is going on here?

Don't just tear down - search for answers.

Thank you.

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68. Henry on October 6, 2011 4:00 AM writes...

@drug_hunter, Wikipedia, the font of all knowledge.... and who wrote that on wikipedia??? I can't believe you just quoted wikipedia as "evidence."

If you had actually spoken to patients, clinically treated them, done the research on the biomedical findings that have been seen in people with ME/CFS you would realise that it has been conclusively shown that ME/CFS is an active biological disease process that is caused by an agent that is infectious. Whilst the precise virus has not been identified yet there is more than enough evidence to establish the above.

What is unacceptable is the denial of illness when such denialists simply parrot the dogma of others. Dogma that originates from a group of psychiatrists that have the position and influence to have their views circulated through the media. Views that are inclidentaly grotesque and vile in modern society.

Has Derek seen one single severely affected ME sufferer, has he done even the slightest research on the over 5000 peer review papers that prove - not opinion - but prove a biological illness caused by an infectious agent?

The question is of course rhetorical because we know full well that Derek has not done any such investigation, he has simply chosen to report the repugnant dogma of others, which ironically is exactly what you have just done by quoting wikipedia.

Perhaps Derek would like to visit a serevely affected patient dying with ME/CFS in their last hours of life and tell them -

"I disagree, I don't believe your illness"

Then when the autopsy findings show lesions in 75% of their spinal chord, lesions that look similar to known viral lesions, Derek can visit the parents and say -

"Plenty of intelligent people agree with me, I deny your illness is viral"

And then when the parents ask, but on what evidence do you base this, Derek can answer -

"Oh I haven't looked at any evidence, I just know because its written on wikipedia."

ME/CFS patients are being denied the right to life, the right to treatment, the right even to access to medical treatment, whilst suffering terrible pain, terrible neglect - for anyone reasonable person such denial and treatment is the most serious abuse of human rights.

Research needs to be done of true ME/CFS sufferers, on the homogenious cohort of very severely affected patients with clearly identifiable disease. Not on patients with 4 of 6 CDC criteria symptoms that could quite literally have anything.

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69. Henry on October 6, 2011 4:56 AM writes...

Incidentally those very same ME/CFS patients with proven viral like lesions of their spinal chords, died because they were forcibly removed from their families, they were incarcerated against their will in mental hospitals, and they were experimented on with unproven ideas of forced exercise or dangerous psychotrophic drugs such as Clozapine. In effect this is patients with undeniable physical viral illnesses being tortured to death.

I sometime wonder whether we are living in the 21st century when people like Derek and others on this site can deny the illness. When there is all this talk about a silly image that was presented by Mikovits, yet absolutely no discussion of the real issue at the heart of this, that of the abuse of ME/Patients and lack of biomedical research on properly defined patients.

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70. drug_hunter on October 6, 2011 6:21 AM writes...

Henry, I'm sympathetic (as is Derek, and I think everyone else on this board) to the suffering of people with any kind of illness. We have, after all, dedicated our lives to the attempt to develop cures for life-threatening diseases.

And people, like you, who have suffered or watched family members suffer, are of course in pain and it is natural for you to be impatient and lash out. We all get it, and many of us have experienced it firsthand.

And we know that people with poorly understood illnesses are often mis-diagnosed and mis-treated. Lots of people have mysterious illnesses that cannot be properly diagnosed, and it is a horrible feeling. CFS sufferers are not alone in this.

And I think you would also find that many of the people you are attacking on this board have themselves studied this disease far more than you realize, and/or have watched friends and family members suffer it.

And Derek never said "I don't believe you have a disease."

And the people on this board care a great deal about scientific integrity, and the incredibly negative impact it has on scientific progress, which is why we get obsessive about things like (potential) fraud. That discussion thread has nothing, in fact, to do with this specific disease, and it is a mistake to connect the two.

And despite all of what you've written about viruses, there is no diagnostic test for CFS. Period. I used the WikiPedia entry as a shorthand, efficient way to summarize what the mainstream medical community thinks about this syndrome. In that regard, I think an earlier post by "cynical1" was correct -- "I would humbly suggest that all that energy, passion, and activism has been sorely misdirected. That resource should have been solely directed at increasing disease awareness and research funding and not arguing with scientists who do this stuff for a living. Period. We all know that CFS/ME involves a differential diagnosis with few to any accepted biomarkers. As a consequence, CFS umbrellas a heterogeneous patient population at best." There is NOT a medically accepted group of patients who, as you say, have a well-defined disease that the world is ignoring. The viral evidence is NOT considered conclusive by the many many scientists who have studied this. Maybe we are all being stupid and missing some medical clue but we're not evil and we are not denying you your human rights. When you equate anyone who feels this way to a Holocaust denier; when you suggest we are callous; when you suggest we are clueless about the suffering of these patients; when you say we are all tools of the evil psychiatrists; you are simply mistaken. And its a tad off-putting.

Last point, as I think others have said, we all would be ECSTATIC to find that any subset of CFS patients had their disease caused by a virus. Then we'd know what to do! When XMRV hit the news, my organization for example immediately began working on the xray structure of the protease and testing old HIV compounds. We didn't waste a day. Maybe we jumped the gun -- but we were truly excited that there might be something extraordinary we could contribute. So if the evidence is ever there for any specific virus(es), we'll jump back in immediately. We would love to help CFS patients.

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71. Cusp on October 6, 2011 6:33 AM writes...

Actually, you are wrong - there is an array of tests used to define the different phenotypes, take the Tilt Table Test for example - strangely, in the UK they suggest doctors NOT perform this on their ME/CFS patients. I've been diagnosed with ME/CFS with a POTS phenotype and have been on heart medication to rectify the problem. And wouldn't you know, I'm now able to keep upright - which is kind of useful if you want to lead a normal life. Might I suggest that your understanding on the subject is a bit behind the times, drug_healer. I know you're not suggesting that you know more on the subject than patient advocates, surely not?

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72. MTK on October 6, 2011 7:13 AM writes...

Cusp,

Actually I think you are wrong. Drug hunter said that there was no diagnostic test for CFS and that is correct. The Tilt Table test is not a diagnostic for CFS. The Tilt Table test is a diagnostic test for dysautonomia, not CFS.

Let me provide some quotes as evidence.

CDC: "there is no blood test, brain scan or other lab test to diagnose CFS, it's a diagnosis of exclusion"

Mayo Clinic: "There's no single test to confirm a diagnosis of chronic fatigue syndrome. "

CFIDS: "Q. Is there a diagnostic test for CFS?
A. No, there is no blood, urine, or imaging test to diagnose CFS. The keys to diagnosis are identifying a characteristic pattern of symptoms and excluding other possible causes."

Wisconsin ME/CFS Assoc. : "There is no blood test, no X-ray and no laboratory test that is diagnostic of CFS yet."

So I'm not exactly sure which times drug hunter is a bit behind. And in fact, the a large part of the whole hoopla over XMRV was so that a diagnostic could be developed.

So the last two quotes are from patient acvocacy groups. I know you're not suggesting that you more on the subject than patient acvocates, surely not?

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73. MTK on October 6, 2011 7:49 AM writes...

Henry,

Who in this blog or the comments has ever denied that CFS is real? I honestly don't know what you're talking about. I don't see a single commenter here suggesting it's not real.

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74. Cusp on October 6, 2011 10:17 AM writes...

I said there are several tests available to define the specific phenotypes but most aren't used..yet they exist. I didn't say there was one test to define ME/CFS because it's more than one illness. The science is there but because of the politics it is not being used. And with all due respect the CDC do not have a true handle on this disease and neither for that matter do some of the advocacy groups - especially those closely-associated with the government.

As for dysautonomia it is co-morbid condition of ME/CFS. One third of sufferers has a dysregulated autonomic nervous system. But you knew that, right? Looks like you didn't have enough time to scan Wikipedia fully. Try again.

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75. Anonymous on October 6, 2011 10:54 AM writes...

Hey Cusp - dystautonomia is also a comorbidity in many psychiatric disorders. Any comment on that genius?

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76. Cusp on October 6, 2011 11:22 AM writes...

I'd be interested in seeing the references, Anonymous. There are many different forms.

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77. Cusp on October 6, 2011 11:29 AM writes...

I'd be interested if ataxia, myoclonus, slurred speech, tremulous, paresthesia, seizures and paralysis are also considered psychiatric? Because these are also some of the other symptoms of ME/CFS. Always interested in hearing the views of educated trolls.

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78. Anonymous on October 6, 2011 11:29 AM writes...

Current opinion in neurology (2006), 19(1), 41-8.

It's also a comorbity in plenty of other conditions. So using it to diagnosis CFS/ME would be, in a word, stupid.

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79. Cusp on October 6, 2011 11:31 AM writes...

Ah, so you are quoting from a paper 5 years old. That explains things.

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80. Cusp on October 6, 2011 11:39 AM writes...

Dark ages and dumb-ass are the words that come to mind. Oh how the feeble-minded doth like to troll.

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81. MTK on October 6, 2011 1:12 PM writes...

Cusp,

I don't think you understand what a "diagnostic test" is.

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82. Jim on October 6, 2011 1:12 PM writes...

The anger that's been shown, while understandable, seems to me to be quite misguided. I know that these types of forums take on a life of their own, but every now and then it is worth looking back at where things started. The initial post was about allegations/evidence pertaining to scientific fraud. This has been an unfortunately frequent topic of discussion on this site, pertaining to diseases, chemical process...all areas of drug discovery.

I am not sure exactly how the rhetoric switched to a war of words over the perceived legitimacy of the disease, conspiracies involving witholding treatment, ignoring suffering patients and the like, but from my point of view (a researcher in the pain field) it has not done anyone any good.

As for Dr. Mikovits, she has either committed fraud or made a mistake. Further, and possibly independennt of either conclusion above, her initial results pertaining to a link between XMRV and CFS are either correct or incorrect. If she is correct, we all sincerely hope that the works leads to viable therapies for the patients. If her work is invalid - either through fraud or error (such as contamination), then no one wins. It is extremely important that the truth comes out in the end here. From what I've seen in my professional career in drug development either fradulent science or bad science make it very difficult to convince those who hold the purse strings to spend any money researching a target or therapy that has been marred by sloppy or unethical work. The demands for more research into this field that have been made in earlier posts will all be embraced by the scientists in the drug discovery field. But if things turn out the way they're looking for Dr. M, then she has single-handedly disarmed an entire community of scientists who are among the patients' allies in their quest to restore their lives.

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83. Idiotraptor on October 6, 2011 10:59 PM writes...

I just finished reading the Sept 23 Science Magazine New Focus detailing the chronology of the Mikovits/XMRV saga. Mikovits and colleagues published data which they argued showed an association between XMRV and CFS. These authors suggested the detected virus might be an etiological agent for the syndrome.

Extensive investigations by other researchers failed to subtantiate this association. Moreover, it's become apparent the origin of the XMRV is suspect and Mokovits' investigations lacked methodological rigor. Scientifically, empircally, the original Mikovits theory doesn't hold up.

End of discussion.


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84. EKD on October 7, 2011 6:21 AM writes...

With all due respect, Idiotraptor, we don't have the power or influence to dictate when the last word is spoken on the subject. This discussion is likely to continue for some time yet.

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85. Hap on October 7, 2011 10:00 AM writes...

Questions are always open - if someone comes up with new and better data, well, then trying to sort out what is going on and understand the new evidence (or to figure out if it's reliable) makes sense. Without evidence (and after all this, the evidence implicating XMRV in CFS isn't very good), the kind of discussion likely to ensue isn't going to be of interest to very many people other than mental health specialists and masochists.

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86. Ugly on October 7, 2011 2:31 PM writes...

@Hap, As important as you are, you don't speak for all concerned. Attempting to stop the discussion seems positively 'unscientific' to me, particularly when another patient passed only 2 days ago - 4 in a month, one who was only 18 years old; the beautiful soul who passed 2 days ago, only 39.

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87. Sooner on October 9, 2011 7:14 PM writes...

Myself, I have been somewhat puzzled by the use of the term 'Oklahoma University' in some of the comments about A. Smith purporting to have some knowledge of her future at that fine institution. To my knowledge, there is no 'Oklahoma University', and anyone with any inside knowledge of what such a school is doing would know the proper form of the name of the school.

The greatest school in the great state of Oklahoma, OU, has a proper name which is not, despite the acronym, 'Oklahoma University'. You will find this name in writings, such as the university web sites, that are written by people associated with OU.

Next is Oklahoma State University, also known as OSU, whose colors are orange and black, which has an inferior football team. (Boo! Hiss!)

There is also the University of Tulsa, whom we beat this year 47 to 14.

Then there are the other, even lesser schools, which if they even have a football team, do not currently have one worthy of being defeated by the power of Sooner Football. I can remember the name of three of these, and have seen more, none of which, to my recollection, is 'Oklahoma University'.

I should think that if there were another school, named 'Oklahoma University', of size and funding to employ graduate students in that area of research, I would have heard of it.

I won't speak on the science or the personalities, but I do not find an argument which uses the wording 'Oklahoma University' very convincing.

Beat Texas!

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88. Hp on November 18, 2011 8:40 AM writes...

Did RRM ever say where he got that gel from? Materials have been stolen.

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