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April 7/8 NIH State of Knowledge Conference - watch online to show our support!

Rrrr

Senior Member
Messages
1,591
oh, this notice on the MassCFIDS website says that Dr. Bell was at the NIH conference and will be giving his assessment of it at his April 16th lecture in boston.

http://www.masscfids.org/news-a-events/288

Dr. David Bell, April 16 2011

Dr. David Bell, noted CFIDS/CFS researcher and pediatrician, will present Current status of XMRV Research and Comments on the NIH April State of Knowledge Conference" on Saturday, April 16, 2011. Dr. Bell will have just returned from the State of Knowledge Conference, a 2-day event bringing together researchers, clinicians, government officials and patient advocates.

Register now!
(You can also register family members and friends)

Note: Please pre-register for this event. The building is secured, and entry will be easier if your name is on the list. Please bring a government-issued photo ID with you.

Download/print the flyer - color version

Download/print the flyer - black & white version

This lecture is co-sponsored by the Massachusetts CFIDS/ME & FM Association and the Massachusetts Department of Public Health at the Hinton State Laboratory Institute. It will be held at their facility, 305 South Street, Jamaica Plain/ Boston, Massachusetts 02130. Registration will begin at 1 p.m. There is plenty of free parking and the auditorium comfortably holds a large group, so please pass the word.

If you would like to receive notification about this conference via email, please sign up for our Newsletter email list if you have not already done so.

Get directions to the Hinton State Laboratory Institute. Free parking is available on Saturdays. The location is also accessible by public transportation. The building is handicapped-accessible.

There is a ten dollar voluntary donation for non-members. Become a member online now, or join at the lecture.

A video of the lecture will be posted later on the website. Newsletter subscribers will be notified when the video is available. We also plan to do a written summary of the lecture.
 

Sing

Senior Member
Messages
1,782
Location
New England
Hi, all.

I was one of the regular posters on this forum who was able to attend the workshop. I gather that many of you were able to follow the action via the web, so you know how the talks and the discussions went. I'll just give some impressions.

First, I would say that there were about 100 people total in the main conference room. I didn't check how many were in the two smaller rooms. The NIH staff people were very pleasant and helpful.

The schedule was pretty full with quite a few relatively short talks, and not a lot of breaks. I think the idea was to be able to hear from as many people as they could fit in, and to cover the main "knowledge" areas, involving people from NIH as well as the main ME/CFS researchers and other major stakeholders, including PWMEs/PWCs.

In order to promote new intramural (inside) research on ME/CFS within the NIH institutes, it is necessary that individual NIH researchers become interested in studying this disorder. So one goal of the workshop is to expose some of them to research on this disorder.

Another goal is to try to promote more extramural (outside) research. This requires having money available, of course, but also encouraging researchers to put in the work required to submit good grant applications, because they have to compete with grant applications for research on a large number of other diseases and subject areas. It's kind of a chicken-and-egg problem. Unless researchers believe there is a good chance to get funded, they won't put in the effort needed to get a grant application together, which is substantial, and which they often aren't paid to do, so they have to fit it in. And, of course, unless good proposals come in, not much ME/CFS research will get funded, which then discourages more applications, etc. So this spiral has to be broken. Another tough problem.

At the workshop, they tried to have time for discussion, but quite a few speakers used up their discussion time because they had more to say than would fit into their time slots. This is typical of scientific conferences, in my experience.

I think the mood was generally pretty upbeat, though you are aware that there were some contentious discussions, and there were also some pretty heavy and heartfelt talks.

My impression was that the NIH people as well as the "outside" attendees were all motivated to try to accomplish something constructive. Of course, one must always keep in mind that we are all very human, and that while everyone may share a common goal, it is still true that "where you stand depends on where you sit."
Another apt old saying is that "honest people can have honest differences of opinion."
O.K., Rich, so much for the cliche's!

I got the feeling that the chain of command in HHS and NIH have gotten the message that ME/CFS needs more attention, and that they are inclined to give it more. At the same time, they can see that the Congress is moving in the direction of tightening up the pursestrings, and they don't know how much wiggle room they will have, so they aren't making any commitments.

It's pretty clear that we can't expect the NIH to re-establish so-called centers of excellence at universities or med schools, as existed a few years back. The view among the management there is that these were very expensive and didn't produce a lot of worthwhile results.

They want the various researchers to communicate and collaborate across the institutions involved, so that they can take advantage of all their expertise. This will be challenging, in my opinion, because the various researchers will have to submit independent grant applications, presumably in competition with each other. Given that, it's not easy to develop collaboration and cooperation. It's a tough problem, especially when there isn't a lot of money, and it's a zero sum game. I do think there was a lot of value in bringing the people together, though, because the better they know each other, the easier it will be for them to communicate.

As far as the technical aspects of the workshop were concerned, I think it did a pretty good job of covering what is thought to be the general "state of knowledge" concerning ME/CFS, except for one area, which happens to be one I think is pretty central to the pathophysiology of ME/CFS, and that is the metabolism, and particularly the energy metabolism, and (you guessed it!) good old methylation! I think I will write to Dr. Mangan about that, because I think an incorrect perception was conveyed that everything is fine with the basic metabolism, and that is really not so.

Oxidative stress wasn't really mentioned, as far as I can recall, and there wasn't a discussion of mitochondrial dysfunction. I would have loved to have raised these points, but as you probably noted, the audience in general was not given the opportunity to comment, and none of the "experts" who had seats at the conference table brought them up. This was not too surprising, because these have not been major research themes among the U.S. researchers.

Methylation was mentioned a few times in the context of gene expression, but not in the sense of a methylation deficit. In fairness, there are no peer-reviewed publications on the methylation deficit in ME/CFS, so anyone who is just reviewing the published literature is not going to find it. There is a lot in the literature about oxidative stress, though, and some about mitochondrial problems.

The other thing that was missing, in my opinion, and has been absent in ME/CFS conferences in the past, is an effort to pull all the pieces together into a coherent model for the pathogenesis and pathophysiology (that is, how the disease gets going, and what the ongoing disease process is). What we have is specialists in various aspects all minutely examining their piece of the elephant, with nobody stepping back to try to visualize the whole animal! Until that is done, I think progress will be slow.

I can understand why this isn't done. Everyone is much more comfortable staying inside their "boxes" than stepping out and talking about things about which they are not expert, risking that someone else will shoot them down. Also, I don't think many people are "generalists," with a broad enough scope in their understanding to be be able to see the connections between things well enough to figure out how the pieces of the puzzle fit together. I think the person who is closest to doing this (beside myself, of course! :D is Gordon Broderick, and I had a good talk with him and encouraged him in what he is doing. By the way, he has an engineering background, too!

With regard to the burning issue of XMRV, I guess you saw and heard the dialog. Harvey Alter did a wonderful job of summarizing the issues today, I think. It does sound as though the "round robin" comparisons of measurements on aliquots of the same blood samples that are planned are being carefully thought out and executed, and hopefully they will settle the issue. Unfortunately, this will take quite a bit of time to accomplish, but there appears to be no other way in which this can be done.
I know that this long time requirement is not happy news for PWME's/PWC's, especially those who know they are XMRV-positive.

I met Elizabeth Unger, and you know what? She's really not an ogre!

John Coffin didn't seem like one to me, either. I think he was coming from the point of view that XMRV couldn't be causal for ME/CFS if it developed from two other viruses coming together at a time later than when ME/CFS was first known to appear, and he had reasons to believe that this did happen at a later time. However, it seems to me that XMRV could still be associated with ME/CFS cases after it developed, and could be a contributing cause after that time, even if it were not present in earlier cases.

As you may know, my hypothesis is that several types of stressors, including viruses and retroviruses, but also other biological stressors as well as physical, chemical, and psychological/emotional stressors can be involved in producing the onset of ME/CFS, so this would fit into my hypothesis very well. XMRV does not have to be the exclusive cause of ME/CFS, but could be a current contributor.

I had the chance to talk to quite a few other people there, including people we know and love from this forum (which was a lot of fun), and of course, passed out my propaganda, as I usually do. I brought 100 copies of the slides from my talk at the Yasko Protocol Conference in Boston last summer, and most of them were picked up by people at the workshop.

All in all, I think it was a worthwhile experience, and I'm glad I came. It remains to be seen what the results will be over time.

Best regards,

Rich

Many thanks, Rich, for your impressions! This ought to be on a separate thread, I think.

I too am a generalist, and specially appreciated Gordon Broderick's approach and talk. Here are the questions I feel are key:

1. What started it? Could be herpes viruses, mono, enteroviruses, XMRV, etc.

2. What is keeping it going? What is directing the steady, ongoing state of poor functioning and illness?

3. What can treat it? What can stop the illness pattern and make it revert to a healthy pattern of functioning?

The old model of just trying to identify one cause and then assuming that is all you need to know--then you can make a vaccine and develop a drug to knock out that one bug--this model may not cover the case. There are probably multiple possible causes which then result in a similar holding patten of illness with the symptoms we are familiar with.

What is this holding pattern and what directs it--what are the control points?

How to convert one pattern of functioning back to a healthy pattern?

These are the main questions and approaches in my view.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Natelson was being a real jerk. He kept butting in to every conversation to reiterate his insistence that CFS is in the brain and only the brain. He said flat-out in his presentation that there is no immune involvement in CFS, that his group "stopped looking for [immune markers] because they never found any", and ignored the very polite efforts of Klimas and others to point out what a large body of research he was ignoring. Totally pigheaded.

Mikovits was SO NOT COOL in dealing with him, though. She was rude, insulting, childish, yelled across the room (while he was talking) that his research (not the proteomics, the more recent study looking for XMRV in spinal fluid) was "totally flawed" etc. Granted, he was being a d***head, but she didn't improve matters by sinking below the level he was at.
It's a shame this happened. Besides XMRV i think his study is the most interesting thing around and i really hate seeing them fight each other.
 

medfeb

Senior Member
Messages
491
Like Rich V, I also had the opportunity to attend the NIH conference and agree with many of the points that Rich made. I was impressed with the effort that went into organizing this conference, with the range of well known speakers and with the general quality of presentations and discussion. Certainly there were differences in scientific perspectives which sometimes led to some passionate exchanges but thats not that surprising when there is so much at stake and still so much to be learned. I saw those as honest scientific differences which very sadly are going to take a little longer to resolve.

I was really excited to see the work presented on system biology by G. Broderick. I understand the concerns with using the Witchita data set, but I think the scientific techniques used are going to become key to unraveling the etiology and treatment options for ME/CFS.

Like Rich, I dont remember seeing any reference on energy metabolism, mitochondrial dysfunction or oxidative stress. He makes a good point about this not being a focus of US researchers.

I would also like to have seen time spent pulling all the pieces together in an integrated fashion. But I am encouraged because I saw a lot of interest among the presenters in finding ways to collaborate together going forward on projects across their siloed disciplines, finding ways to better share their data and research, etc. It will be challenging for all the reasons Rich states but absolutely necessary to make progress with such a complex disease. I really got the sense that the NIH and participants all understand that.

All and all, a great conference. Kudos to the NIH and Dr Magnan for pulling this together.
 

richvank

Senior Member
Messages
2,732
Email to Dr. Mangan concerning workshop and energy metabolism and his response

________________________________________
From: richvank@aol.com [richvank@aol.com]
Sent: Saturday, April 09, 2011 11:00 AM
To: Mangan, Dennis (NIH/OD) [E]
Subject: Appreciation for the workshop

Dear Dr. Mangan:

I want to tell you that I found the NIH State of the Knowledge Workshop on
ME/CFS during the past two days to be extremely helpful.

You put together a very comprehensive review of what is known about ME/CFS, and
included the whole range of stakeholders. Thank you very much on behalf of
myself, and I know that I echo the views of many others in the research,
clinical, and patient communities as well.

I hope you will also convey to Drs. Pinn, Anderson and Collins my appreciation
for the seriousness with which they are addressing ME/CFS.

There is, however, one area that I would like to mention that I dont feel was
adequately covered in the workshop: the energy metabolism. I think the
impression was given, particularly in the session on exercise and muscle
function, that there are no serious issues in the energy metabolism in ME/CFS.

In fact, there is considerable evidence of serious dysfunction in the energy
metabolism in ME/CFS. There are have been numerous papers published in the
peer-reviewed literature over the past few years providing evidence of oxidative
stress in ME/CFS, as a PubMed search on the keywords chronic fatigue syndrome
and oxidative stress will show, and this is a key indicator of problems in the
energy metabolism. I would also like to draw your attention to the paper by
Myhill et al., attached, in which it is shown that mitochondrial dysfunction is
quite severe in some cases of ME/CFS, and that there is a direct relationship
between mitochondrial dysfunction and severity of the illness.

While the wide variety of published evidence supporting the presence of
mitochondrial dysfunction in ME/CFS has not been adequately reviewed in a
peer-reviewed journal, it is quite substantial, ranging over 1) muscle biopsy
combined with ultrastructural examination of mitochondria; 2) measurement of the
status of mitochondrial nutrients and response to their supplementation; 3) gene
expression studies; 4) indicators of abnormal processing of the substances that
normally serve as substrates for the mitochondria (oxygen; fuels, including
carbohydrates, fats and protein; and ADP); and 5) indicators of abnormal
production of the substances that constitute the normal products (ATP, carbon
dioxide, water, heat and reactive oxygen species). The interpretations and
conclusiong offered in the various papers are in some cases conflicting, and I
suggest that this is largely due to differences in cohorts as a result of the
case definition problems that were well discussed at the workshop.

In a disorder in which fatigue and post-exertional fatigue are so prominently
present, I think it is obvious that one area that should be thoroughly explored
is the energy metabolism, and I dont feel that the ME/CFS research community as
a whole has adequately investigated this, or made it an important part of their
thinking.

In view of this, I want to urge you to ensure that the problems in the energy
metabolism in ME/CFS are not ignored in the NIHs appraisal of the state of
knowledge of this disorder.

Again, thanks to you and all the others at the NIH who produced this excellent
workshop. I have been a full-time ME/CFS researcher for 15 years, have attended
the previous two NIH workshops on ME/CFS as well as six other conferences
devoted to this disorder, and this is the best get-together I have attended on
this topic.

Best regards,

Rich Van Konynenburg. Ph.D.
Independent Researcher
Livermore, CA




Rich---

So noted. Thanks for the kind words and keeping us posted on the scientific
basis for this illness.

Dennis

Dennis Mangan, PhD
Chair, Trans-NIH ME/CFS Research Working Group
Senior Research Advisor
Office of Research on Women's Health, OD
National Institutes of Health
301 496-9006
 

richvank

Senior Member
Messages
2,732
Hi, Sing.

Thanks for your post. I agree with your selection of key questions. I don't know if you were wondering about my proposed answers to them, but I will sketch out my current thinking, for what it is worth, below:

Many thanks, Rich, for your impressions! This ought to be on a separate thread, I think.

I too am a generalist, and specially appreciated Gordon Broderick's approach and talk. Here are the questions I feel are key:

1. What started it? Could be herpes viruses, mono, enteroviruses, XMRV, etc.

***I think it is a genetic predispositon combined with some combination of a variety of stressors, the combination different in each case. These include the biological stressors, including the ones you listed, as well as physical, chemical, and psychological/emotional stressors. I've come to this view after studying quite a few cases over the past few years. All these stressors impact glutathione, and I think that's where they come together to contribute to the onset.

2. What is keeping it going? What is directing the steady, ongoing state of poor functioning and illness?

***In my view, it's a vicious circle that is set up by the initial drop in glutathione in someone who is genetically susceptible. This vicious circle includes glutathione depletion, a functional deficiency in vitamin B12 because of loss of protection of B12 by glutathione, inhibition (or a partial block) of the methylation cycle, resulting from the B12 functional deficiency, and draining of folates from the cells, via the "methyl trap" mechanism, as a result of the partial block of the methylation cycle, with which the folate metabolism is linked. When the partial block in the methylation cycle becomes established, it drains sulfur metabolites down to their excretion forms, sulfate and taurine, and there is insufficient cysteine to bring glutathione back up. This locks in the vicious circle and makes ME/CFS a chronic condition.

3. What can treat it? What can stop the illness pattern and make it revert to a healthy pattern of functioning?

***One has to lift the partial methylation cycle block with a combination of active folate and high-dose B12. This will break the vicious circle in most people who have it, based on our clinical study with lab testing. Supporting nutrients may also be required.

The old model of just trying to identify one cause and then assuming that is all you need to know--then you can make a vaccine and develop a drug to knock out that one bug--this model may not cover the case. There are probably multiple possible causes which then result in a similar holding patten of illness with the symptoms we are familiar with.

***I agree with this. Fixing the methylation cycle block alone doesn't do the whole job for most people with ME/CFS. One also has to specifically treat the entrenched issues, such as toxins and infections that were either part of the initial combination of stressors that brought about the onset, or that accumulated during the illness, when the immune and detox systems were dysfunctional. I also think that there usually needs to be work on the digestive system, to correct the dysbiosis and intestinal permeability. In some cases, this must be done first, before the methylation cycle can be dealt with, because the person is not able to absorb nutrients well enough to supply the methyation cycle with what it needs.

What is this holding pattern and what directs it--what are the control points?

***The main one is the enzyme methionine synthase. Raising its activity with folate and B12 is key.

How to convert one pattern of functioning back to a healthy pattern?

***I think I've already covered that above.

These are the main questions and approaches in my view.

***I agree with you, and others may of course offer different answers to your set of questions, but I think I have a pretty good basis for the answers I've offered.

***Best regards,

***Rich
 

Enid

Senior Member
Messages
3,309
Location
UK
Please guys we are relying on you there (when the slugging is done amongst them - as long as they find).
 

serg1942

Senior Member
Messages
543
Location
Spain
Hi Rich,

Thanks So MUCH for your report! Sushi and I were rooting for you during the two day-home-couch Conference :sofa::sofa:, as the camera was frequently focusing at Dr. Klimas, and therefore at you, as you were right behind! :)

We were thinking exactly the sameWhen they were talking about the problems to deliver oxygen to blood, I didnt understand why anyone raised the known issue of oxidative damage in the mitochondria I mean, the closer they were of treating this subject was when they said Lets replenish our ATP levels, when they announced the launch time

Also, we really missed what you say: someone trying to put the knowledge together, in order to show the whole picture, and by doing so, to try to really understand the pathophysiology of the disease I wish you could have raised some of your questions...

I would like to bounce something off you We are living through very exciting times for CFS research. XMRV or other retroviruses and their relationship with old known infections, new genetic techniques that could change the way biomarkers, viruses hunting technics, etc. will be assessed, higher than ever attention of the media to CFS, new and promising treatments like GcMAF...

We have all the above, however, on the other hand, we have even more questions than before.. Why is GcMAF helping (it is definitively helping many PWCs, including myself)? My leukocytes and lymphocytes levels are higher than ever (they were low, and now are in the middle of the normal range), while my vit D 0.25 that was low is almost normal, while the vit D 1.25 that was high is already normalAnd I know that my previous pattern of vitamins D is associated with chronic infections and autoimmune diseases, while Vit D is necessary for the innate immune response... How does vit D relate with CFS pathophysiology, and how these observations fit with your theory?

As you know, I havent been able to tolerate the methylation support for the past 2 years. However, if I am improving, my methylation status must be improving by other means

Also you know how well LDN worked for me, as well as for many PWCs. I think it may be preventing an excess of inflammation while on GcMAF, although I am a bit concerned about whether it could be also preventing GcMAF for fully working

It comes to my mind a very logical question: When should I resume the methylation support?

These are just a few ideas/questions from the top of my head, but of course therere many other unknowns to be answered.

One of the things you have pointed out as something missing from the conference has been someone trying to put the pieces together Soooooooooooo, what I am trying to subtly say (well, maybe no so subtly :), is that we nominate you to try to put together these new exciting, but unfortunately scattered news

Your Spanish fan club (Sushi, Sergio, et al) :victory:
 

Enid

Senior Member
Messages
3,309
Location
UK
Sergio - someone putting the pieces together now (amongst scientists) would be the best ever news. What is it that tips the balance and allows progression. Any thoughts anyone with all we have so far.Many systems into "meltdown" - so why ? as we try to treat the individual symptoms. 11 years ago my Neurologist said "viral" - now we are finding them.
 
Messages
13
Location
madrid
Not shame at all, someone has to do the dirty job, and thats Judy.

It's a shame this happened. Besides XMRV i think his study is the most interesting thing around and i really hate seeing them fight each other.

This was totally necessary, She told him the truth, saying that his study on XMRV was based on 2 samples, and was a bad study and totally flawed, the tuth never hurts, is simply unavoidable. This arrogant man needed that remark, just because He did a good study on the proteins found in the brain, does not imply that the immune system is not involved. Besides, how can He possibly claim that XMRV is not present in CFS patients when He was not testing the blood in the first place? The positive studies were done in the blood, not in the cerebro spinal fluid, therefore, He can not claim anything, because there is no validation for his conclusions, and even less when He tested ONLY 2 samples! Judy might be stubborn, ok, but We need that! We need to be heard, I am feed up of the political bullshit...We need someone to strike at the table and get attention of cluless people that do not see beyond their own egos.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
This was totally necessary, She told him the truth, saying that his study on XMRV was based on 2 samples, and was a bad study and totally flawed, the tuth never hurts, is simply unavoidable. This arrogant man needed that remark, just because He did a good study on the proteins found in the brain, does not imply that the immune system is not involved. Besides, how can He possibly claim that XMRV is not present in CFS patients when He was not testing the blood in the first place? The positive studies were done in the blood, not in the cerebro spinal fluid, therefore, He can not claim anything, because there is no validation for his conclusions, and even less when He tested ONLY 2 samples! Judy might be stubborn, ok, but We need that! We need to be heard, I am feed up of the political bullshit...We need someone to strike at the table and get attention of cluless people that do not see beyond their own egos.

i agree totally, we need someone like judy, shes not going to let someone walk over her, if she just rolls over and does what they say then we are back to 1994 again and we're going nowhere fast like the last 30 years.

cheers!!!
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
Rich,

Thank you so much for the report of the conference and especially for writing to Dr. Mangan. I was going to try to work that into my weekend or week somehow, but now that I know you have done it I know it's okay if I don't. I do hope Dr. Mangan is able to include that information in the final report coming out of this conference.

best,
Willow
 

Cort

Phoenix Rising Founder
I agree. I do think that Coffin is a top-tier scientist. I think he went into this open minded and hopeful, and that the evidence he saw changed his mind. But I don't think it's good science to say that it IS contamination at this point. Say that we have evidence that it COULD BE contamination. But there are too many maybes still out there. Nancy Klimas asked a couple of good questions. "What about the difference in prevalence between controls and subject?" Well, the samples COULD HAVE BEEN handled differently. But were they? That's just hypothesizing. You shouldn't abandon research based on a hypothesis, you should do the study and find out. Since he is now hypothesizing a negative, that it's contamination, he has to meet as big a burden of proof as those who are proposing that XMRV is a human infection, and he hasn't. He is speaking prematurely, and there's too much at stake here if he's wrong. He should be saying "Wait for the Lipkin study," not "Leave XMRV behind." Or he should be trying to find out if it really is contamination.

Actually the samples in the first study were handled differently; the WPI gathered up the patient samples and got the other samples from the a blood bank....The big question for me is how the internal tests you would think the WPI must be doing have checked out...Dr. Mikovits has said they have checked 1,000's of samples....but how many controls? If I was them - unless I was absolutely positive about everything (and there's no way I would be positive about everything given what has been going on) I would be bringing controls in there regularly to ensure that their protocols are correct and I imagine that they've done so...That is the most important factor for me and it's one, unfortunately, that is not publishable...We shall see in the BWG and Lipkin studies about those controls.

The head of our Immunology Department congratulated me on being able to not contaminate the controls and only contaminate the patient samples in literally the thousands that weve done now, says Mikovits. http://www.biotechniques.com/news/W...-for-XMRV-detection/biotechniques-311717.html
 

Cort

Phoenix Rising Founder
Yes, I thought I heard Judy M. say that it would be a couple of years, and she said something about how long it would take her to run her part of the tests. I think she was saying that we shouldn't wait that long to be moving the science forward.

Alter said the Lo Lab is very small - just two assistants - and that it would take them six months of devoting all their time to the Lipkin study to get through it. He said they are so cautious about contamination that they're afraid to bring in more equipment or more assistants. I asked him if Lo doesn't find anything 40% way through the samples (after 4 or 500) if he would just quit :) and Alter kind of sounded like, if he was in charge, that he would consider that. It's a very big task for a small lab. I don't know why they need THAT many samples...the WPI sounds overwhelmed and so does Lo. Of course the WPI is culturing this time - which takes up to 42 days (altho Dr. Mikovits has reported they have a much quicker test. In the presentation she said it will take them two months per sample).

It took the WPI months to get back the BWG samples in phase I and II - they were always the last lab to get them back in...I imagine it will take a long time for them to get through them.
 

Cort

Phoenix Rising Founder
Tuller's actually a stringer, he's not an NYT staff writer. So his pieces don't appear with great regularity.

I would hope that he will be allowed the opportunity to do a big article about the conference, which would mean both a longer lead time and probably specific placement (say, in the Tuesday science section.) Nothing "breaking" was discussed at the SoK as far as I can tell, so there's not much reason to do a quick turnaround article.

As for Amy Dockser Marcus, she did a quick blog hit about the Mikovits/Coffin smackdown yesterday, but I also *hope* she'll have a longer piece appearing in the WSJ about the conference. It seems they've been running her other long pieces on Saturdays, but who knows.

I asked him about that and he said he didn't know. I didn't get the idea that anythings going to happen. He's actually associated with the public health department in Berkeley and, as urbantravels noted, is a 'stringer' not a staff member. Amy I think missed either most or all of the second day but David was there almost to the end.
 

Cort

Phoenix Rising Founder
Compare to Coffin and his whining and his raised angry voice and the way he just spoke over everyone and got louder and louder. There was an angry man and why can't he be "hysterical" instead. The difference is that Coffin was angry about and for himself - he doesn't care about patients. There was nothing in his speech and there is nothing in his work to help us in any way. Exactly what has he done for us and exactly what will he be doing in the future - nothing.

Who wants to defend Natalson and his "XMRV" testing? why not speak out. Silence is the wrong thing to do here.

Dr Mikovits did a great job. She's allowed to be impassioned and angry. These emotions are appropriate for the situation and I only hope that I would have half her courage in the same circumstances.

If you read "and the Band plays on" you will find lots of emotion expressed at conferences and meetings by doctors. Mainly male doctors and no one remembers them as being hysterical or judges that their emotions were inappropriate and ill expressed.

I thought they both got angry at times and both interrupted at times and both tried to speak over each other at times...
 

Cort

Phoenix Rising Founder
This was totally necessary, She told him the truth, saying that his study on XMRV was based on 2 samples, and was a bad study and totally flawed, the tuth never hurts, is simply unavoidable. This arrogant man needed that remark, just because He did a good study on the proteins found in the brain, does not imply that the immune system is not involved. Besides, how can He possibly claim that XMRV is not present in CFS patients when He was not testing the blood in the first place? The positive studies were done in the blood, not in the cerebro spinal fluid, therefore, He can not claim anything, because there is no validation for his conclusions, and even less when He tested ONLY 2 samples! Judy might be stubborn, ok, but We need that! We need to be heard, I am feed up of the political bullshit...We need someone to strike at the table and get attention of cluless people that do not see beyond their own egos.

I don't know what she meant by that. My guess is that she meant two samples or strains of XMRV. Natelson used 43 patients in his study

javascript:AL_get(this, 'jour', 'Ann Neurol.');
Ann Neurol. 2011 Feb 4. doi: 10.1002/ana.22389. [Epub ahead of print]
Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia-related virus.

Schutzer SE, Rounds MA, Natelson BH, Ecker DJ, Eshoo MW.
Departments of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ. schutzer@umdnj.edu.
Abstract

Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murine leukemia-related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the central nervous system would have greater significance than in blood because of the integrity of the blood-brain barrier. We examined cerebrospinal fluid from 43 CFS patients using polymerase chain reaction techniques, but did not find XMRV or multiple other common viruses, suggesting that exploration of other causes or pathogenetic mechanisms is warranted. Ann Neurol 2011;


javascript:AL_get(this, 'jour', 'Ann Neurol.');
 

Cort

Phoenix Rising Founder
Here's my take on XMRV and the Conference:

It wasnt surprising at all to see things get heated with Dr. Coffin and Dr. Mikovits both at bat at the State of Knowledge Workshop.

The moderator, Dr. Alter, handled his job with humor and flair. Stating that he was no King Solomon and was certainly unable to determine whos baby XMRV is at this point; Dr. Coffins or Dr. Mikovits - Dr. Alter gave a times a wry and clear-headed assessment of where the Workshop was after the Mikovits and Coffins representation
Each side had their points. Dr. Mikovits can point to no evidence from contamination after extensive testing of samples and reagents, loads of blinded controls that have tested negative for XMRV (or contamination), antibody, protein, PCR and culture findings, and the fact that theyve never used the 22Rv1 cell lines or any of the other materials that been found to be contaminated

Dr. Coffin, on the other hand, can point to evidence that positive XMRV results in other labs have been due to mouse DNA contamination using a test the WPI does not run (IAP) test, and to studies showing that XMRV was created in a lab sometime between 1992-1996. He can show that XMRV is not found in mice (ie did not jump into humans) but that XMRV precursors can be found in a very few mouse strains and one of those strains was used to create the 22RV1 sample. He can also show that all the published XMRV strains are very much alike which suggests they did not infect humans.

Dr. Coffin seems to think that even given the evidence to date the WPIs XMRV must be a contaminant (but cant prove it) - while Dr. Mikovits appears to think that, whatever else anybody else has found, her evidence indicates that the XMRV in her samples must have come from the patients (not the lab). They are really making very different arguments.
The one thing everybody seems to agree on is that the contamination issue will be resolved by the BWG and Lipkin studies.

[video=youtube;hWN3rkbXCm4]http://www.youtube.com/watch?v=hWN3rkbXCm4&feature=related[/video]Q and A When asked by Dr. Jason to try and explain the disparate results Dr. Mikovit stated that the biggest reason was patient selection; ie the other studies are not studying patients infected with XMRV. She stated that the PCR was not the basis of the first paper and that the other groups are doing the PCR wrong; in particular, they are focusing on VP62 - the original sequences in the GeneBank and she mentioned the annealing temperatures. She noted that the Lo/Alter did follow their nested PCR protocols and did find something. She also stated that no one has done the culture or the antibody tests in as detailed a fashion as they did in the original paper. She also noted that 6-8% of patients have hypermutated XMRV sequences which have been altered by cellular enzymes which wont show up on the standard tests either.

Dr. Coffin on the Negative Controls Dr. Klimas asked Dr. about the pattern of negative controls and positive patients; how that be due to contamination? Dr. Coffin noted that the Lo/Alter samples came from two separate sources -so that could be explained there and that even when the tests were run in the same lab that the samples were still collected in different tubes and under different conditions and suggested that the use of heparin in tubes was a risk factor for mouse contaminationBasically he said that the possibility of contamination from tiny, tiny bits of DNA means that both the controls and the patients have to be treated exactly the same waysame type of tubes, same chemicals, same reagents and that studies (Lipkin) are being set up to do this.

Coffin on Antibodies - Dr. Klimas asked Dr. Coffin how patients could have an antibody if an antigen ie an XMRV protein was not available. After saying that he wasnt going to talk about antibodies because he wasnt doing work on them on XMRV Dr. Coffin actually talked quite a bit about them. With regards antibodies he noted that the early HIV antibody tests were quite poor and that one (current test) has a lot of false positives - which is why positives on two different antibody tests are required to give a diagnosis. He said he didnt want to deny the possibility that the antibody test is picking up another virus eitherand noted that the WPI uses very broad antibody tests that are designed to be very reactive ie they are designed to pick up a spectrum of viruses and that Dr. Mikovits had just noted that their test picks up Friend virus which he said was way off the tree on a very different branch.and that most of the PCR reactions would not detect that virus because it is so distant ie; they may not be picking XMRV or related XMLVs at all.

Dr. Mikovits jumped in and argued for more variability (and research) stating this is the first time in retrovirology that weve ever defined a virus on a single sequence. She believes that any xenotropic murine related virus that is infecting human cells is a possibility and she followed that up by stating that their antibody test was the only test that would have picked up a gamma retrovirus called EG 75. Dr. Coffin interrupted to say that his test would have easily picked up EG 75. Dr. Mikovits noted that here was another member of the family that reacted with their test but then Dr. Coffin stated his assays would not only detect and differentiate between those two viruses but any virus on that tree; apparently the XMLV/MLV tree.

According to Dr. Satterfield the WPI started out with a broad antibody test that reacts with various MLV viruses with the belief that it should pick up XMRV as well. My guess is that Dr. Mikovits believes researchers should stick with that broad test (some of them have, actually) instead of using antibody tests developed off of strains of XMRV. She believes the broad antibody test will pick up different strains of XMRV such as the pMLVs Alter/Lo picked up. Satterfield appeared to argue that with better characterization of XMRV the current tests should actually pick up more XMRV than the WPIs original test. Dr. Mikovits appears to believe the opposite.

Dr. Mikovits said Chao (?) showed integration had occurred and Coffin stated that one of part of the study had been shown to be contaminated. Then she noted that the WPI uses a different cell line than 22RVI and they test it every week and its clean every week and they do everything they can to control for contamination. She said theyve used phlebotomists to gather the blood from patients and send it out to other labs which have found the virus. At one point she said that thousands of people have tested positive for XMRV in six other studies far more than we would have imagined -which would suggest a great deal more work has gone on than has been published.

Gene Variability - and a Missed Opportunity - Dr. Coffin said, well, if we can get these other sequences into GenBank where other people can look at them then we can do an analysis on them. This is a key, key point. Dr. Mikovits has said we have the variability data and we cant get it into GenBank and heres Dr. Coffin stating just get them into GenBank and well take a look at them .Its a shame that another question was asked and we didnt hear Dr. Mikovits publically tell Dr. Coffin that they have the variability into the Bank and cant get it into the Bank and what his response would have been.

Dr. Coffin noted that the NCI is now looking at patients who were reported to be positive by the WPI and is doing an extensive workup on them using the many assays the NCI has developed. He noted that the NCI devoted a huge amount of resources to work on XMRV. (It was the NCI that characterized all XMRVs proteins (as I remember) so that they could develop antibody test for them. He said the studies will go on on XMRV and MLV related viruses until they can be sure that they have gotten to the bottom of it.

Dr. Alter then noted that, yes, Dr. Coffins data was quite compelling but there is still the issue of proving that contamination is present when these labs are doing everything they can to show that its not. The low lab used extremely sensitive PCR, then IAP #1 and IAP #2 and never found anything. How do you explain that?

Coffin s Personal Appeal - at the end of his presentation Dr. Coffin made a personal appeal to the ME/CFS community. He noted the disparaging comments on many blogs questioning the integrity of researchers who are unable to find XMRV. He called that painful and then basically said that the research community was beside itself at the opportunity to translate their decades of study on MLVs into researching a virus that could infect humans. Dr. Coffin, of course, early on penned a very positive editorial on XMRV and called the paper as good a first as you can get. He also appeared on short notice at the first CFSAC meeting after the finding and testified at length. His endorsement of the initial finding was a feather in XMRVs cap given his stature in the community.

A Talk with Dr. Mikovits - I asked her about the Satterfield interview and she felt he was simply wrong. She had explanations for every question I asked. - most of which I could not comprehend - particularly at the speed at which Dr. Mikovits is capable of talking.

She stated that her move to Translational Research Director was due to the recognition that this was the next step for her. She suggested that a few amino acid alterations in the LTR regions of the virus (as I remember :)) would be enough to make the antiretrovirals that are currently available ineffective in humans.

That does make sense given that XMRVs fate will come down to the BWG and Lipkin studies and other outside studies. If thats true then focusing on treatment and letting the pathogen detection studies play themselves out is the next logical step for them.

The completion of the Lipkin study, unfortunately, appears to be a long, long way off because of its huge sample size (1300 samples - (each sample is done in intriplicate) which will, far overtax the WPIs capacity.(Dr. Alter said much the same thing about the Lo lab - its a small lab with just two assistants. They could add assistants or machines but things are so touchy right now with the contamination issue that Lo isnt willing to bring in anything new or change anything.Dr. Alter said doing all Lipkins samples would take the Lo lab six months of concentrated effort.

This is a huge effort and a huge commitment of time and resources for a small lab. (Do they need to do all the samples to get a clear finding?) The WPI is actually in worse shape than Lo because they will be culturing which magnifies the time element greatly - hence Dr. Mikovits comments that itll take two years to get everything done.

[video=youtube;Dktu4RR5QEU]http://www.youtube.com/watch?v=Dktu4RR5QEU&feature=related[/video]
Dr. Mikovits stated she has been unable the get the genetic variability data published and into GenBank so that the researcher s can start using it in their analyses (she stated there are just six fully sequenced strains of XMRV) but she does have two papers coming out; one on an immune signature associated with XMRV positive patients and one on an antibody for test for XMRV. (The antibody test will not feature Dr. Bagni at the NCI.) She noted there are researchers doing exact replicates of the WPI experiment (Univ of Alberta and De Meirleir and others). Both she and Annette Whittemore remain very confident in their findings.

Dr. Alter on XMRV and MLVs- in conversation and as a moderator Dr. Alter stated he is now personally leaning to the idea that XMRV was accidentally created in a lab and somehow got into the WPIs samples. Two things, in particular, seem to have struck him, the fact that the 22RV1 cell line was created using mice (he hadnt realized that) and the lack of genetic variability in the samples to date. He no longer appears to believe the MLV sequences that he and Dr. Lo found are part of a larger XMRV family; instead he believes that they are probably separate entities.

I asked him why he thought he didnt find XMRV? Looking back does he see any indication that they had made some sort of mistake? He said no - they had essentially replicated the techniques found in the Science paper (which Judy in her testimony confirmed) but that XMRVwas just not there. (Dr. MIkovits believes that the MLVs the Lo/Alter study found are part of the larger XMRV family and has stated that she has found patients with pMLVs similar to the Lo/Alter in her samples).

The Lo lab has been unable to grow out an MLV virus - which is not a particularly surprising finding - as no else over the years has been able to do that either. Attempts at showing DNA integration into tissues are ongoing at another lab but that is not an easy process either and, it turns out, is not as conclusive as we had thought.

He noted that XMRV has been and continues to be the most confusing research topic he has ever worked on - which says a lot for a Lasker Award winner whos been in the medical research field for some 40 years. Dr. Alter, by the way, stayed throughout the workshop and took voluminous notes on many of the presentations.

It should also probably be noted that Dr. Alter is not a retrovirologist (and neither is Dr. Lo) and that does mean something. These details are best understood by retrovirologists who have spent their careers studying retroviruses such as Dr. Mikovits, Dr. Coffin, Dr. Miller and Dr. Ruscetti.

Next - In the end Dr. Mikovits felt that we just need more research to sort it all out. Later she noted that Frank Ruscetti a month or so ago said..if this were HIV it would be 1983.

Its pretty clear that research into XMRV will continue and this is one of the many ways that this is not the repeat of the DeFreitas finding. Dr. DeFreitas found sequences - not a virus. Later, she reported being able to grow the virus but for whatever reason those findings were never published. XMRV, on the other hand, is a virus and the WPI was able to grow it and labs all over the world have it and research into it will continue. There is also a commitment to get at least a good part of the way to the bottom of the XMRV/CFS saga.

[video=youtube;lY91GtouXf8]http://www.youtube.com/watch?v=lY91GtouXf8&feature=related [/video]
With prostate cancer angle on the table, the NCI has poured a great deal of money into XMRV and is doing what appears to be the most intensive workup of 30 patients reported to have XMRV yet. That study is going on right now and it seems very likely well get those results long before the Lipkin or BWG study is done (sample collection is just commencing now).

Dr. Light said the Singh study has wrapped up; theres no telling when it will be published but it is finished and hopefully it will be published in the not too distant future. The University of Alberta , Dr. Joliceur, Dr. DeMeirlier and others are working away. The Glaxo-Smith Kline/CAA study is still out. Silverman still needs to report on his XMRV findings in prostate cancer. Dr. Miller may be looking at XMRV in some fashion.There is still a lot of research to come.

Whatever happens with those studies the BWG and Lipkin studies appear to be the ones that ultimately open/shut the door on XMRV and CFS. If the WPI can pick out the patients from the healthy controls then the researchers will beat a track to their lab and figure out what they are doing differently. If they cant that will indicate the WPIs test isnt working and that will be that for the broad research communities interest in XMRV and ME/CFS.
 

urbantravels

disjecta membra
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Los Angeles, CA
Where did this idea come from that our buddy Dr. Natelson's study looking for XMRV in spinal fluid was "only two samples"? By my reading, they had 43 CFS samples: the same 43 patients used in the proteomics study. Perhaps they didn't use the "right" PCR method, but that would have been a separate issue.

http://onlinelibrary.wiley.com/doi/10.1002/ana.22389/abstract

Dr. M. clearly yelled something at him, but it must have been about something else or else misheard. And yet everyone seems to be picking up and repeating the idea that it was "only two samples." Check your sources, folks.
 

Bob

Senior Member
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16,455
Location
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Where did this idea come from that our buddy Dr. Natelson's study looking for XMRV in spinal fluid was "only two samples"? By my reading, they had 43 CFS samples: the same 43 patients used in the proteomics study. Perhaps they didn't use the "right" PCR method, but that would have been a separate issue.

http://onlinelibrary.wiley.com/doi/10.1002/ana.22389/abstract

Dr. M. clearly yelled something at him, but it must have been about something else or else misheard. And yet everyone seems to be picking up and repeating the idea that it was "only two samples." Check your sources, folks.

I don't know if Judy's comments might have been related to this:

Some further information has come to light:

They had 43 patients, but they sent VIPDx a total of five vials.

The first vial had the combined DNA of 23 patients.
The second vial had the combined DNA of 20 patients + 3 negative control extracts.
The third and fourth vial contained distilled water.
The fifth was was spiked was XMRV.

Why do this? Too little DNA from each patient? Too cheap to test them all? Too confident they would all be negative?

This would suggest that Schutzer et al sent a total of two phials, containing patient samples, to VIPDx for testing, alongside running their own tests.
I'm just guessing here, but maybe Judy was refering to this?

Anyway, here's the section of video where she says it:
http://www.youtube.com/watch?v=cvo6Mj3uL1A