Daily Beast: Interview with Mikovits who tells her side of events...

currer

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Cheer up, biophile!
In fact I think that "XMRV" and the publicity around it has given this disease a tremendous boost. All publicity is good - there is no such thing as bad publicity. It has attracted a tremendous amount of interest among researchers who hed never heard before of ME and there are many new initiatives in research. Plus the Rituximab finding. I dont know whether the Norwegians would have investigated the one patient with CFS who improved on Ritux if it had not been for all the publicity on XMRV.
Improvement on immune/cancer therapies like rituximab, has been reported before in ME - no-one has taken time out of a busy clinical schedule to run a study on it though, until all the furore on XMRV.

No the future will be different for us now, so dont get despondent.

Whatever our opinions about Dr Mikovits research I think all posters here must agree that XMRV has led to a tremendous amount of research interest in ME. This is the best thing that could ever have happened for our neglected disease.
 

currer

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I seem to remember this being discusses before. But I think Dr Mikovits wanted to get her research published in high quality journals .
After the forced Science retraction - I doubt she can publish now.
 

Firestormm

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I' not sure to what extent the furore surrounding XMRV/MLVs can be said to have increased research interest in ME specifically. Research into XMRV/MLVs definitely and into contamination certainly, even (especially) a heightened awareness of ME and the extent to which this remains a largely neglected severely debilitating and costly illness.

But I think the connection of XMRV/MLVs with ME and perhaps retroviruses and ME has diminished significantly and will remain so until such time as a paper is published that again attempts to link a retroviral infection with ME and can stand up to criticism. Hopefully, the XMRV/MLV tale will prove helpful in this regard as a lesson that ensures anything in the future will be more credible.

What we have seen are largely mopping up exercises. Awareness about ME generally has certainly been increasing over recent years and this alone has been leading to greater research emphasis targeting the condition specifically. Would this have happened anyway without XMRV/Lombardi? Hard question to answer but yes, I think it would. Awareness has though been given a boost - unfortunately it hasn't always been as positive as we might have liked but this has proved of little consequence.
 

Bob

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I' not sure to what extent the furore surrounding XMRV/MLVs can be said to have increased research interest in ME specifically. Research into XMRV/MLVs definitely and into contamination certainly, even (especially) a heightened awareness of ME and the extent to which this remains a largely neglected severely debilitating and costly illness.

What we have seen are largely mopping up exercises. Awareness about ME generally has certainly been increasing over recent years and this alone has been leading to greater research emphasis targeting the condition specifically. Would this have happened anyway without XMRV/Lombardi? Hard question to answer but yes, I think it would. Awareness has though been given a boost - unfortunately it hasn't always been as positive as we might have liked but this has proved of little consequence.
Good points Firestormm.

You may well be right that research into, and awareness of, ME would have increased anyway, without XMRV.

In any case, research into ME seems to have almost exploded over the past year. I can't quite believe the number of top-quality research projects that are being proposed, or are already being carried out.

Perhaps the timing of XMRV is partly a coincidence, but I'm pretty certain that XMRV has brought ME to the attention of new researchers who wouldn't have taken an interest otherwise, and that it has increased awareness of the nature of ME (i.e. more scientists have realised that it's a serious and neglected physiological disease). Alter and Lipkin are the best examples of this.

I'm not in a position to quantify how many new researchers have taken an interest in ME. Maybe it's only Lipkin and Alter. But maybe XMRV has also meant that existing researchers, such as Dr Peterson have been able to attract more interest and funding than they were able to before.

But the CFIDS Association of America (CAA) have repeatedly stated that XMRV has been good for ME, and that XMRV has helpfully raised the profile of ME. They are in a much better situation than me to assess it.
 
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There were several articles published that said the retrovirus was found in 2008 when they found it in the original 2 blood samples. That was well before this 2009 issue when most of the work had already been done, and the paper was on it's way to Science.
 

biophile

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I'm not being too despondent. I lost most of my youth to illness, I do not want to lose my middle age years to it as well, and so far that is shaping up to be a real probability judging from the research progress I've seen since diagnosis. I do think the overall situation is improving but too slowly, every step of the research seems to take years, and then years for another step, and so on. Add more years for translation into medical practice once something is validated.

I'm not convinced that the XMRV/MLV saga has lead to "a tremendous amount of research interest". Yes, it did increase interest and that is good, but it is difficult to say how much practical value this had on actual projects. Yes, there are some interesting projects going on but it is difficult to say whether or how much the XMRV/MLV saga helped. The only example that comes to mind right now is the Lipkin pathogen study, and getting Lipkin on board was a positive. Of course, there is probably much I'm not aware of. Even then, many of these interesting projects will take years to reach fruition.

We are a far cry from being treated as mainstream. The gap between research funding and public attitudes vs societal burden and patient reality is still rather staggering. So I'm starting to back away from my previous more optimistic stance about the short and medium term future and agreeing more with the notion that nothing has really changed much. Many of us had hoped that the XMRV/MLV saga would open the floodgates of funding, but this never happened, and unlikely to happen if the Lipkin study on XMRV/MLVs is a null result (which I expect it to be).

I think I read somewhere that while government spending on CFS in the USA increased slightly during the XMRV/MLV phase, this was only because of XMRV/MLV research which was allocated funding from other departments, while the money spent on CFS research from the usual allocation actually went down. In other words, overall funding was temporarily supplemented by XMRV/MLV research but otherwise it was basically business as usual. And that "business" is the starving and neglect of CFS research funding and paying mere lip service about taking CFS seriously. Of course, this does not account for any increased private interests that may have eventuated into funding for projects.

I was however somewhat surprised when the UK's MRC announced addition funding on top of the £1.6M. But as I've said elsewhere, it will take more than that for the taste of decades worth of biomedical neglect to wash out of my mouth. I do feel that we are seeing early signs of the beginning of the end of the cognitive behavioural model of CFS and the stifling dominance it has had on certain sections, but we are far from out of the woods.

I disagree that there is no such thing as bad publicity. The public relations surrounding XMRV/MLV and the hype/spin surrounding the PACE Trial has further sunk the reputation of the patient advocate community. We are now in a situation where it seems perfectly acceptable for CBT/GET proponents to publish verifiable errors and even slanderous lies in medical journals without the need for correction. When it comes to public relations, the medical profession basically has us over a barrel while the rest of society cheers them on, laughs at our complaints, or is looking the other way. I do not think our reputation could sink much lower without actual acts of violent terrorism or some patient advocate groups transforming themselves into alien spaceship cults which blame ME/CFS on spiritual forces.

I would find it highly disappointing if Mikovits et al never bothered to submit to PLoS once during this whole controversy. There is a phrase, "beggars cannot be choosers". When no one else will publish your papers and certain people in your field just want you to STFU and GTFO, you are clearly a "beggar" of sorts until vindicated, regardless whether you are correct or not. Refusing to submit to PLoS in such a situation would demonstrate an irresponsible stubbornness which may set back the scientific process. Fortunately, Mikovits was involved in the Likpin study.
 

Bob

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If a paper is not published it's most likely because it didn't get past peer review or wasn't up to standard requirements to be published.Conspiracy theories are a too simplistic way of dismissing a theory as situations are really more complicated than that. Stronger proof is needed.

Here's an opinion from Denise O'Keefe (my emphasis):
Official O'Keefe Lab blog & (other) cool stuff


Novel MLV-GAG sequences detected in blood samples of ME/CFS patients

From the Hanson lab, this paper published today in PLoS ONE describes a study carried out with meticulous attention to detail and proper use of controls while analyzing ME/CFS patient samples for murine-leukemia related viruses. Although novel MLV-like GAG sequences were isolated and sequenced from the patient samples (as opposed to controls collected from the same sites) Lee et al. concludes that it is not possible to determine the origin of these sequences, although the samples were not contaminated with mouse DNA at a detectable level. First, bravo! to the Hanson group for being able to get anything published that might go against the current dogma regarding MLV-like viruses in human samples published -- I guarantee you that there are people with similar data whom don't want to torture themselves by attempting to publish. The fact is, that it seems somehow MLV-like nucleic acids somehow end up in patient samples quite a bit, albeit at exceedingly low levels. Theoretically, even if there was an MLV-type infection in a human, it would be rapidly eliminated (unless of course we don't know everything about the immune system yet). I wonder if it is possible that such viruses could hide somewhere in the body, not replicating much - perhaps killing host cells occasionally resulting in a release of (potentially degraded) viral nucleic acid that is ultimately detected in the blood stream. I haven't analyzed these sequences yet compared to those we have detected in tissue samples from BPH patients, but seeing as our sequences were recently published on the USPTO website, someone else will probably try that. The link to the Hanson paper is here --
Link to O'Keefe's blog:
http://okeefe-lab.blogspot.com.au/2012/05/novel-mlv-gag-sequences-detected-in.html


And an opinion from Dr Cheney (my emphasis):
Changing status of XMRV / HGRV research

December 5th, 2011, published in Public Relations
There is still no consensus in either direction for the existence or non-existence of XMRV associated with CFS cases. Studies out of Europe (Belgium and Germany) and the US (Cornell) as well as elsewhere which are separate from WPI, FDA and NCI are demonstrating evidence that cannot be due to a mouse contaminant for XMRV association with CFS. The strongest supportive study to date was reported by Dr. David Strayer out of Hemispherex Inc, (Philadephia, PA) at IACFS/ME in Ottawa and showed that 7/8 CFS cases and 2/17 controls were positive for XMRV using Next Generation Sequencing (NGS) technology available at Roche Labs in Germany. NGS is not susceptible to mouse contamination and demonstrates that XMRV is in fact integrated into human DNA which means it is a human virus. The Science (Lombardi et al, 2009) study still stands as the best evidence that this virus is transmissible from cell to cell and the studies out of WPI and Belgium demonstrate an immune response (antibodies) to XMRV and a cytokine profile (WPI) that suggests it is pathologic.
I expect that Next Generation Sequencing or NGS, which does not have the flaws of PCR technology in evaluating a poorly understood human virus(es), will be the best way forward to a consensus as to the question of association of CFS with XMRV/HGRV. This preliminary report out of Germany using NGS as well as human immune response data supports the association of XMRV with CFS, despite the flaws exposed in the current primary PCR technology used to define this scientific debate which appears very messy and excessively bio-political to date.
Link to Cheney's blog:
http://www.cheneyclinic.com/changing-status-of-xmrv-hgrv-research-2/843
 

ukxmrv

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I would find it highly disappointing if Mikovits et al never bothered to submit to PLoS once during this whole controversy. There is a phrase, "beggars cannot be choosers". When no one else will publish your papers and certain people in your field just want you to STFU and GTFO, you are clearly a "beggar" of sorts until vindicated, regardless whether you are correct or not. Refusing to submit to PLoS in such a situation would demonstrate an irresponsible stubbornness which may set back the scientific process. Fortunately, Mikovits was involved in the Likpin study.
I've wondered that myself but thought that the WPI and contractual agreements may have had something to do with this
 

Bob

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We are a far cry from being treated as mainstream. The gap between research funding and public attitudes vs societal burden and patient reality is still rather staggering. So I'm starting to back away from my previous more optimistic stance about the short and medium term future and agreeing more with the notion that nothing has really changed much. Many of us had hoped that the XMRV/MLV saga would open the floodgates of funding, but this never happened, and unlikely to happen if the Lipkin study on XMRV/MLVs is a null result (which I expect it to be).
I don't blame you for not feeling so optimistic biophile.
I agree that the progress of research is always very slow.
And the XMRV situation is at a particluarly delicate place at the moment.
I have a feeling that Lipkin might throw up some novel MLV-sequences and yet have a conclusion that some of us aren't comfortable with. So, it might have the worst kind of inconclusive results. (But this is pure speculation.)
Anyone who wants to see the MLV research continue, is bracing themselves for the aftermath of the Lipkin study.

So, at the moment, I'm trying to focus on all the research that isn't related to MLVs.
I do tend to have an optimism nature, but I am actually feeling optimistic at the moment, looking at the wide body of research in the pipeline.
There does seem to be a surprisingly large amount, and wide variety, of high quality and very interesting and promising research in the pipeline, with funds to make it happen. Like you said, even in the UK, things seem to be changing a little bit.

I disagree that there is no such thing as bad publicity. The public relations surrounding XMRV/MLV and the hype/spin surrounding the PACE Trial has further sunk the reputation of the patient advocate community. We are now in a situation where it seems perfectly acceptable for CBT/GET proponents to publish verifiable errors and even slanderous lies in medical journals without the need for correction. When it comes to public relations, the medical profession basically has us over a barrel while the rest of society cheers them on, laughs at our complaints, or is looking the other way. I do not think our reputation could sink much lower without actual acts of violent terrorism or some patient advocate groups transforming themselves into alien spaceship cults which blame ME/CFS on spiritual forces.
I suppose I come at this from an optimistic point of view, as well. I don't think that CFS could have been in a worse place than it was, so I don't believe that the negative publicity did us any harm. For those ignorant and cynical people who thought that we just have personality disorders, then any negativity just reinforces their wilful ignorance. But the publicity about the serious nature of ME, that came with the XMRV research, probably opened up minds about the nature of ME, and changed minds in a positive way. Harvey Alter (just as a high profile example) even said that he had new understanding about the disease. I had the feeling that he had never encountered ME in any meaningful sense before XMRV.

As for the stuff relating to the PACE Trial, I don't believe that any decent or intelligent scientist would believe the nonsense that came from Wessely about the nature of our patient community. I mean, does any scientist or medic, who has any integrity, really believe that ME patients are nothing but a bunch of dangerous medical-terrorists? The psychiatrists just sound more and more desperate, and more and more ridiculous, the more they say these days, and I'm hoping that they are rapidly losing their influence. I don't see how they can retain any influence after the PACE Trial results are fully understood by the medical profession.

The lies and misinformation relating to the PACE Trial are a problem, but the facts are on our side, and I hope that they will be known by the time of the NICE guidelines review. Not only did the PACE Trial demonstrate that CBT and GET were useless for 87% of their cohort of heterogeneous CFS patients (and possibly next to useless for the other 13%) (and possibly harmful for many as well, once we have the details of the deterioration rates), but it also convincingly and conclusively destroyed their theoretical model of CFS/ME, in a very expensive allegedly "top quality" medical trial.

I would find it highly disappointing if Mikovits et al never bothered to submit to PLoS once during this whole controversy. There is a phrase, "beggars cannot be choosers". When no one else will publish your papers and certain people in your field just want you to STFU and GTFO, you are clearly a "beggar" of sorts until vindicated, regardless whether you are correct or not. Refusing to submit to PLoS in such a situation would demonstrate an irresponsible stubbornness which may set back the scientific process. Fortunately, Mikovits was involved in the Likpin study.
I don't understand this situation either. PLoS is a respectable journal anyway. But maybe they won't publish anything either. Just because they have a different publishing model, and receive money to publish, doesn't mean that they publish everything that comes their way. They still have a peer review process.

But we've been promised a lot of stuff, and told a lot of stuff, over the past few years, and since none of it has come to fruition, I wonder how much of it still stands.
 

FancyMyBlood

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Cheer up, biophile!
In fact I think that "XMRV" and the publicity around it has given this disease a tremendous boost. All publicity is good - there is no such thing as bad publicity. It has attracted a tremendous amount of interest among researchers who hed never heard before of ME and there are many new initiatives in research. Plus the Rituximab finding. I dont know whether the Norwegians would have investigated the one patient with CFS who improved on Ritux if it had not been for all the publicity on XMRV.
Improvement on immune/cancer therapies like rituximab, has been reported before in ME - no-one has taken time out of a busy clinical schedule to run a study on it though, until all the furore on XMRV.

No the future will be different for us now, so dont get despondent.

Whatever our opinions about Dr Mikovits research I think all posters here must agree that XMRV has led to a tremendous amount of research interest in ME. This is the best thing that could ever have happened for our neglected disease.
The research of Mella and Fluge has nothing to do with the XMRV findings. The first open label study on 3 patients was already conducted and published before the XMRV findings and the RCT was already planned based on the findings in those 3 patients. XMRV has nothing to do with.

I agree with you though that the XMRV plublicity gave the field a boost. Although the research state of this disease couldn't get any worse :(
 

Mula

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I seem to remember this being discusses before. But I think Dr Mikovits wanted to get her research published in high quality journals .
After the forced Science retraction - I doubt she can publish now.
The retraction would not impede publication of research, but what would Dr Mikovits be able to publish considering her notebooks are held and other related material is with the institute.
 

Firestormm

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Possession of those notebooks did not cause her to consider the possibility of a contamination source even when she did have access to them - at least not until July 2011 we are now told. I am not sure what it is in them that folk seem to think prevented her from doing 'something' she couldn't otherwise do before she was sacked. I have also been wondering how she managed to participate in the 'Lipkin Study' without this apparently vital resource. Seems rather strange. Oh I suppose they are important, but what will prevent the publication of any future research in this direction from Mikovits is not a lack of possession of her notebooks in my opinion but a lack of employability.
 

currer

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The research of Mella and Fluge has nothing to do with the XMRV findings. The first open label study on 3 patients was already conducted and published before the XMRV findings and the RCT was already planned based on the findings in those 3 patients. XMRV has nothing to do with.

I agree with you though that the XMRV plublicity gave the field a boost. Although the research state of this disease couldn't get any worse :(
You're right
http://clinicaltrials.gov/ct2/show/NCT00848692
this gives the start date as June 2008. I think I associate the two studies because Fluge and Mella did include an XMRV test in the second piece of research and I remember them talking about it at last year's Invest in ME conference.

But since we now know that there are other sequences out there, it could be that their PCR sequencing was too specific
http://forums.phoenixrising.me/inde...virus-in-patients-with-bph.18674/#post-284096
 

barbc56

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Possession of those notebooks did not cause her to consider the possibility of a contamination source even when she did have access to them - at least not until July 2011 we are now told. I am not sure what it is in them that folk seem to think prevented her from doing 'something' she couldn't otherwise do before she was sacked. I have also been wondering how she managed to participate in the 'Lipkin Study' without this apparently vital resource. Seems rather strange. Oh I suppose they are important, but what will prevent the publication of any future research in this direction from Mikovits is not a lack of possession of her notebooks in my opinion but a lack of employability.
Soit on.

I think a zerox machine would have solved the problem of the notebooks not being in her possession.

What I don't understand is why didn't she go beyond Harvy Whitemore to report her concern about the contamination.

Barb C.:>)
 

Mula

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Possession of those notebooks did not cause her to consider the possibility of a contamination source even when she did have access to them - at least not until July 2011 we are now told. I am not sure what it is in them that folk seem to think prevented her from doing 'something' she couldn't otherwise do before she was sacked. I have also been wondering how she managed to participate in the 'Lipkin Study' without this apparently vital resource. Seems rather strange. Oh I suppose they are important, but what will prevent the publication of any future research in this direction from Mikovits is not a lack of possession of her notebooks in my opinion but a lack of employability.
Contamination controls were built into the testing for the Lombardi paper, perhaps Dr Silverman's trouble with the plasmid had been discovered by July.

To exclude the possibility that we were detecting a murine leukemia virus (MLV) laboratory contaminant, we deter- mined the phylogenetic relationship among endog- enous (non-ecotropic) MLV sequences, XMRV sequences, and sequences from CFS patients 1104, 1106, and 1178 (fig. S2). XMRV sequences from the CFS patients clustered with the XMRV sequences from prostate cancer cases and formed a branch distinct from non-ecotropic MLVs com- mon in inbred mouse strains. Thus, the virus de- tected in the CFS patients’ blood samples is unlikely to be a contaminant.
PCR. To avoid potential problems with laboratory DNA contamination, nested PCR was performed with separate reagents in a separate laboratory room designated to be free of high copy amplicon or plasmid DNA. Negative controls in the absence of added DNA were included in every experiment.
 

alex3619

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My understanding from Judy's statement is that the contamination was potentially of patient blood samples due to storage with XMRV. Blood free controls would not have detected that as they were not the contaminated product. Bye, Alex
 

Bob

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To continue the discussion regarding whether XMRV has brought more interest and funding into the field, Firestormm found this informative blog about funding from the NIH:
http://www.occupycfs.com/2012/07/31/nih-funding-and-the-xmrv-effect/

I think it could probably be interpreted both ways (e.g. XMRV has brought in more funds and XMRV has distracted funding away from other areas), so I'm not using it to support my own opinion.

But I just thought that people who have been involved in this discussion might find it interesting.

Keep in mind that this only analyses a single source of funding.

Thanks to Firestormm for finding it.
 

jspotila

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To continue the discussion regarding whether XMRV has brought more interest and funding into the field, Firestormm found this informative blog about funding from the NIH:
http://www.occupycfs.com/2012/07/31/nih-funding-and-the-xmrv-effect/

I think it could probably be interpreted both ways (e.g. XMRV has brought in more funds and XMRV has distracted funding away from other areas), so I'm not using it to support my own opinion.

But I just thought that people who have been involved in this discussion might find it interesting.

Keep in mind that this only analyses a single source of funding.

Thanks to Firestormm for finding it.
Thanks Bob and Firestormm for finding and posting my blog post on NIH funding and XMRV. I was shocked when I ran the numbers and saw that 82% of the NIH funding increase from 2009 to 2010 was for XMRV studies. The big big question is if XMRV studies disappear from the CFS allocation in 2012, will that money stay with CFS and be spent on other things. That is a really important test and will show us a bit more about the true effect.
 

Firestormm

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The big big question is if XMRV studies disappear from the CFS allocation in 2012, will that money stay with CFS and be spent on other things. That is a really important test and will show us a bit more about the true effect.
Agreed. But. We should remember I think that the Lombardi paper claimed to have found XMRV present in healthy controls too. This meant that XMRV become more than ME. So I was not at all surprised to see funding directed in this way, and so long as the studies included 'CFS' in their title it would be classed as 'CFS' funding. What I mean is that this increased funding may legitimately be reduced once the Lipkin Study is concluded unless of course he endorses the findings and especially if he alleges the presence of XMRV/MLVs in controls.

If the connection to CFS is broken then these funds could then 'revert' to other places. Indeed I wouldn't be surprised if these were some sort of emergency funds and not necessarily an increase in CFS funding per se. What I mean is that perhaps we shouldn't view these additional funds as for 'CFS Research' as we do other studies. They might be best considered a 'one-off'.

Thanks for the article Jennie and for the accumulated piece on the Lipkin Study. Very useful.