Sue J Blog: NJ CFS Conference - Update on XMRV by Dr. Mikovits

[Otis]

This is mind-blowing and thought it deserved it's own thread. A must read.

ETA: The original blog and some corrections to the original post can be found at http://livewithcfs.blogspot.com/

Here are some of the biggest points.

UK XMRV Study

• WPI started a study in March 2010 to look for HMRV (Human MLV Related Viruses - both X and P) in UK ME/CFS patients.
• The study included 50 patients with ME who met the Canadian Consensus Critera, 50% male and 50% female, along with 50 controls. It was a blind study.
• The 100 samples were tested blindly by two labs who had never worked with MRV or mice (to ensure there was no possibility of contamination).
• The labs first tested plasma and 48% of the ME plasma samples were positive for XMRV (all were also tested for mouse DNA and were negative). Other samples were detectable only after culturing (some sort of special sample preparation). In some samples, only the virus was detectable; on others, only the antibodies were detectable. Multiple testing methods were necessary in order to find all of the XMRV positive samples.
• In all, 80%of the ME patients in the study were positive for XMRV.
• 4% of the controls were also positive for XMRV (in line with the original WPI study).
• Dr. Mikovitz emphasized that the XMRV was very difficult to find. They have learned that subtle differences in storage, handling, and testing make a big difference and that multiple methods must be used to find it all.

XMRV Family Studies
(This is the part of the day that totally blew my mind)

• In January 2010, WPI did a study using samples from Dr. Cheney's clinic in Dallas. They tested not only CFS patients but also their families, including children, parents, and siblings.
• 81% of the Cheney CFS patient samples were positive for XMRV.
• Ready for this? 50% of all family members of CFS patients were also positive for XMRV, whether they had any symptoms or not.
• They constructed family trees for each family. In addition to people with CFS, they also looked for family members with cancer and autism.
• They found XMRV positive: parents with CFS kids; kids with a CFS parent; kids with autism.
• In all, 54% of the parents tested were XMRV positive, 59% of the children tested were XMRV positive, and 82% of the kids with autism were XMRV positive. They detected additional XMRV positive people in 16 of 17 families tested who had 1 member with CFS.
• Detection of XMRV in these samples required multiple testing methods to find it all.
• They have no idea how XMRV might be transmitted between family members.
• By the way, the possible link between CFS and autism is not new. Other researchers have suggested it in the past because they see similar immune system dysfunction in kids with autism.

Politics?
(This part is really disturbing to me. I like to believe that people are generally good and do what they believe to be right. I know that's not always the case.)

• Are you wondering why we haven't heard about the amazing studies conducted by WPI in the UK and with families from Dr. Cheney's clinic? Dr. Mikovitz says no one will publish them. She said they keep submitting papers to various publications and they keep getting turned down.
• Dr. Mikovtz said what's happening with XMRV and CFS reminds her very much of the early days of HIV research. She said that just like back then, she has a drawer full of scientific studies no one will publish, but she will just keep on conducting studies and putting them in the drawer until things change.
• Dr. Mikovitz also said that some of the people who've been suggesting contamination are people who were involved with the original studies and who saw all of the original data, including those which proved contamination was impossible.
• Other speakers also mentioned that politics are involved. The prevailing theory seems to be this: if the CDC confirms that XMRV, a new, dangerous, and transmissible retrovirus, is present in people with CFS (and the CDC has estimated the number of adults in the US with CFS to be 4 million), then they have a huge public health crisis on their hands.
• Dr. Mikovitz says that the evidence of XMRV in CFS is actually stronger than the evidence of XMRV in prostrate cancer because of the more extensive testing methods used to date.
• Rumor is that the National Cancer Institute (NCI) has been told by someone high up in the government to pursue whether XMRV is involved in prostrate cancer but should distance themselves from CFS. Though I hate to believe something like this could actually happen, the speaker from NCI at CFSAC last week was the one who suggested that contamination might be responsible for the positive XMRV results in CFS. Dr. Mikovitz said that person was on the original team that found XMRv and has seen all of the data proving contamination is impossible.

 

[August59]

Thanks Otis - That's some very interesting information. Quite enough to make me want to choke the $#% out of someone. I thought all along that Dr. LaGrease(!) was spending an inordinate amount of time playing the contamination game, to the point that it was very irritating to watch. If the science behind XMRV is going to be subdued like HIV was, then we need to scream like the HIV people did. I hope some of Dr. Mikovits unpublished studies can someday be used to prove neglect by the government and guilt proved in civil court.

 

[leaves]

This blog is so distressing...
That Mikovits can not get her stuff published... wow
i must admit that in general i have a great deal of confidence in the (progress of ) science, but this is fear at work it seems;

Reviewer1: Oh this paper studies xmrv and cfs, oh but that is like very contested right, 'cause no-one has replicated wpi yet, oh let's not publish it then; we dont want to look silly...
Reviewer2: YEAH maybe this women just makes the xmrv all up
Reviewer1: YEAH or her lab is contaminated

sigh...
I really hope this replication is done soon, and positive, and published, seriously...

 

[Sasha]

Wow. Just wow.

That's appalling that Dr Mikovits can't get this amazing stuff published. I have been thinking for a while that publication bias (well-established in science) and publication delay (inevitable in science journals, even if by a few months) is not working in our favour, given the speed at which research in this area is happening. At this stage of XMRV confusion, the shortcomings of the publication process are really getting in the way of science and in the way of helping patients.

I've been thinking it would be much better if the scientists involved would agree to forget about normal publication and instead set up their own web-based repository for publishing on XMRV as soon as studies are ready to be shown; they could also provide all the necessary background details on methodology that are so important to establish why there are differences between labs, because on the web there are no space restrictions like there are in paper journals.

Of course, they'd lose the prestige of getting published and the downside might be that such publications wouldn't be seen as authoritative. But we desperately need to have scientists sharing knowledge as fast as possible. Maybe it's reached the point where it's worth the trade-off.

 

[Jemal]

I do worry a bit... HTLV-1 and 2 are other retroviruses and I get the feeling they have been shoved under the rug. At least HTLV-1 causes disease, but basically you can't get treatment if you are infected (because many infected people don't get sick and it also might take years before symptoms pop up). I hope XMRV isn't shoved under the same rug as well...

Someone tell me the WPI still has allies, right (besides us)?

What might also work for us is that it looks like XMRV has infected many more people than HIV and HTLV.

 

[eric_s]

But aren't those the UK study and the Cheney study that were presented at the XMRV workshop?

So we have heard about them. They just haven't been published yet. It's hard to believe nobody wants to publish them, when they publish negative studies. I guess a positive one, if it's credible, would be much better for a paper. I think there should be enough incentive to publish... i can't understand this.

Either way, i don't think we will tolerate sh* for an indefinite amount of time. I'm now waiting for the Lipkin, Alter/Lo and Singh studies. We have heard it's less than 3 weeks before we hear something from the Blood Working Group and i think we should also hear from Singh or one of the others i mentioned before the end of the year, don't remember which one.
But if things seem to be getting stalled for reasons that are not in our interest, i say we will put some fire under their a*es. Right now, i'm ok with how things are going, i don't like to hear that papers don't want to publish, but apart from that, i don't have a problem, i'm just impatient and wish we would have more certainty.

If there is some deliberate silence now in order to avoid panic, but work is going at full speed, ok... But if they don't want to help, then we will have to act. We are too many (those with CFS/ME alone) and all the potentially XMRV+ healthy people have every interest in the world to know about XMRV. We could do a lot.

 

[Wonko]

I'm not sure that setting fire to public health officials is the way to go - but I'm open to reasoned debate on the subject lol

I'd be interested in the reasons for refusal to publish - I'm not sure on the process - never having published a paper myself - but surely if a paper is refused then reasons would be given and possibly suggestions as to how to make it publishable would be given? at least from the more reputable journals

 

[eric_s]

Don't worry, it's just a metaphor we use in my country . But if they don't act in our best interest, we should make them feel the heat. Not the scientists, but people in office. At this time, i think things are going ok, as i've said, but we have to watch of course.

 

[Sasha]

I'm not sure on the process - never having published a paper myself - but surely if a paper is refused then reasons would be given and possibly suggestions as to how to make it publishable would be given? at least from the more reputable journals

Hi Wonko - all peer-reviewed journals (i.e. journals that get submitted papers assessed by other scientists in the same field) normally provide the peer reviewers' reports to the study's author but the editor's decision can be:

(a) publish,

(b) publish if the author makes specified revisions to the paper, based on the reviewers' comments or

(c) reject on the grounds that the paper wouldn't be of acceptable quality even if revised, or isn't interesting enough, or isn't appropriate for that particular journal.

A time-honoured way of an editor getting rid of a paper they don't like is to send it to reviewers who they know won't like the paper either and can be trusted to recommend its rejection. In highly polarised fields of science it's very easy to identify reviewers in "the other camp".

 

[August59]

But aren't those the UK study and the Cheney study that were presented at the XMRV workshop?

So we have heard about them. They just haven't been published yet. It's hard to believe nobody wants to publish them, when they publish negative studies. I guess a positive one, if it's credible, would be much better for a paper. I think there should be enough incentive to publish... i can't understand this.

Either way, i don't think we will tolerate sh* for an indefinite amount of time. I'm now waiting for the Lipkin, Alter/Lo and Singh studies. We have heard it's less than 3 weeks before we hear something from the Blood Working Group and i think we should also hear from Singh or one of the others i mentioned before the end of the year, don't remember which one.
But if things seem to be getting stalled for reasons that are not in our interest, i say we will put some fire under their a*es. Right now, i'm ok with how things are going, i don't like to hear that papers don't want to publish, but apart from that, i don't have a problem, i'm just impatient and wish we would have more certainty.

If there is some deliberate silence now in order to avoid panic, but work is going at full speed, ok... But if they don't want to help, then we will have to act. We are too many (those with CFS/ME alone) and all the potentially XMRV+ healthy people have every interest in the world to know about XMRV. We could do a lot.

Just wanted to make sure you read the entire blog. Especially the part where Dr. Mikovits stated that she has a "drawer full of studies that she can't get published". I took this to mean at least several more than just the UK and Cheney studies (papers).

It gets into me really bad when I know that strong science, that could in fact lead to the healing (not cure) of some PWC, exist and it hinges on whether or not it is published in a magazine (journal). Even the thought of how long it takes to get published and therefore leading to delays in possible treatment is enough to make it criminal in my mind. The process of science sure does not leave any room for compassion.

 

[Otis]

Just wanted to make sure you read the entire blog. Especially the part where Dr. Mikovits stated that she has a "drawer full of studies that she can't get published". I took this to mean at least several more than just the UK and Cheney studies (papers).

I think that would include the follow-up to the Science paper when they unblinded and found 99/101 XMRV +ive when they looked at all testing methods. Or did I miss that paper?

 

[Otis]

A time-honoured way of an editor getting rid of a paper they don't like is to send it to reviewers who they know won't like the paper either and can be trusted to recommend its rejection. In highly polarised fields of science it's very easy to identify reviewers in "the other camp".

That makes all kinds of sense.

I have not been given to think about the worst-case type of subterfuge but when you combine this with what we saw at the 1st International XMRV Conference Q&A where there was a pretty obvious "effort" to stay from the "policy" side of things. I'm also wondering if Ruscetti's questions about how to proceed had more to do with policy (read politics) obstacles than technical ones. He's and Sandy are devoted to XMRV but his ties to ME may be causing him problems too.

Now from the CSFAC we have Le Grice saying "I don't think this What Have You Done For Me Lately campaign is helping. I dont need to have [NIH Director] Dr. Collins call me and ask me, What are you doing for CFS? - reference Mindy Kitei's The Foxes Chase the Hounds.

Going back further we have Le Grice involved BEFORE the Science paper is published and saying the following in an Amy Dockser Marcus piece right after publication.

Neither study conclusively shows that XMRV causes chronic-fatigue syndrome or prostate cancer. But the National Cancer Institute was sufficiently concerned to convene a closed-door workshop in July to discuss the public-health implications of XMRV infection. "NCI is responding like it did in the early days of HIV," says Stuart Le Grice, head of the Center of Excellence in HIV/AIDS and cancer virology at NCI and one of the organizers of the July workshop.

Wow, that really worked out for the early AIDS sufferers. Rich Vank said "THis sent a chill up my spine" in a PR post at the time.

One more quote from Marcus's post

"Dr. Le Grice said there isn't enough evidence yet to suggest that people with XMRV shouldn't be blood donors but that determining how XMRV is transmitted was a critical issue. "A large effort is under way to answer all these questions," he said. "I do not want this to be cause for panic."

Still no panic. Still no blood ban.

 

[Bob]

wow, thanks Otis, for posting that...

It is really eye-opening... It explains a lot, and it has tied up some loose ends for me, regarding Judy's ongoing research.

I have been wondering for ages why we weren't hearing anything about Judy's research into Autism...
She must have lost patience and decided to talk about the research now anyway, without getting published... I'm pleased she has told us the results.

And there's also Judy's work on atypical MS which we haven't heard anything about for ages...

Autism seems to be a bit of an explosive issue for the scientific community...
The UK doctor (can't remember his name) lost his prestigious research post and his practise license, after publishing research that linked autism to vaccinations...
Maybe the journals are just too afraid to publish.
But it's not good enough.

I thought PlosOne would publish anything, seeing as the scientists have to pay to publish their work there...
I wonder if Judy has tried them.

Reviewer1: Oh this paper studies xmrv and cfs, oh but that is like very contested right, 'cause no-one has replicated wpi yet, oh let's not publish it then; we dont want to look silly...
Reviewer2: YEAH maybe this women just makes the xmrv all up
Reviewer1: YEAH or her lab is contaminated

Unfortunately it does look like that's how it works, doesn't it!

I'd be interested in the reasons for refusal to publish - I'm not sure on the process - never having published a paper myself - but surely if a paper is refused then reasons would be given and possibly suggestions as to how to make it publishable would be given? at least from the more reputable journals

Wanting to avoid severe controversy maybe one reason for avoiding publication.

I think that would include the follow-up to the Science paper when they unblinded and found 99/101 XMRV +ive when they looked at all testing methods. Or did I miss that paper?

Yes, I've been wondering why that hasn't been published as well...

Reading what Judy has said, i think that it's a miracle that Judy's original paper ever got published at all, let alone in such a prestigious journal. How did she manage that!?!

Just wanted to make sure you read the entire blog. Especially the part where Dr. Mikovits stated that she has a "drawer full of studies that she can't get published". I took this to mean at least several more than just the UK and Cheney studies (papers).

Yes, there's the research on atypical MS as well.

 

[eric_s]

Just wanted to make sure you read the entire blog. Especially the part where Dr. Mikovits stated that she has a "drawer full of studies that she can't get published". I took this to mean at least several more than just the UK and Cheney studies (papers).

It gets into me really bad when I know that strong science, that could in fact lead to the healing (not cure) of some PWC, exist and it hinges on whether or not it is published in a magazine (journal). Even the thought of how long it takes to get published and therefore leading to delays in possible treatment is enough to make it criminal in my mind. The process of science sure does not leave any room for compassion.

Yes, thanks, i've read it. But i don't think the fact the papers haven't been published will delay the progress in the science too much. The WPI did not stop it's work because of that. And we have Lipkin, Alter/Lo, Singh and others on the case. They will publish or at least inform about their results and this should be enough to get things rolling, if the results confirm XMRV in CFS.
Alter is working on a study of 1000 subjects. Imagine if that one returns the same percentages or even higher than the first Alter/Lo paper. Things will be on fire then, i'd guess.
A private paper is of course free to publish whatever they like, so i would not call it criminal, but i know what you mean.

 

[Otis]

At the bottom of the blog in the comments, there are some important corrections suggested by "XMRV P". Time and brain cells permitting I'll see if there are any that apply to the parts I posted.

 

[August59]

Yes, thanks, i've read it. But i don't think the fact the papers haven't been published will delay the progress in the science too much. The WPI did not stop it's work because of that. And we have Lipkin, Alter/Lo, Singh and others on the case. They will publish or at least inform about their results and this should be enough to get things rolling, if the results confirm XMRV in CFS.
Alter is working on a study of 1000 subjects. Imagine if that one returns the same percentages or even higher than the first Alter/Lo paper. Things will be on fire then, i'd guess.
A private paper is of course free to publish whatever they like, so i would not call it criminal, but i know what you mean.

Dr. Mikovits comment doesn't actually say they were all XMRV papers either. I imagine Dr. Alter will do everything he can to find XMRV, and associated viruses, after some of the remarks about contamination and his previous findings being a different virus.

 

[August59]

At the bottom of the blog in the comments, there are some important corrections suggested by "XMRV P". Time and brain cells permitting I'll see if there are any that apply to the parts I posted.

Would like to hear what you think Otis, especially since Dr. Mikovits made the comments at the UCLA seminar about the "P" version being present and making treatment more challenging.

 

[urbantravels]

Where is there information about the UCLA talk? If it was on these forums I must have missed it.

 

[Otis]

Good question. Been wondering myself.

 

[Otis]

Would like to hear what you think Otis, especially since Dr. Mikovits made the comments at the UCLA seminar about the "P" version being present and making treatment more challenging.

August59,

One note "XMRV P" happens to be short for "XMRV Positive", a patient on Facebook who left the comments at the bottom of that blog. I didn't think about that coincidence...

I haven't seen anything on the UCLA seminar, I'd love a link though. :Retro smile: Pretty please.

And other than staying in a Holiday Inn Express last night, I don't play a retrovirologist by day so I'm hoping some others may have some insights.

I wouldn't think a given ARV would work on one variant but I could be wrong. Unless it's been tested really recently, and it's certainly not published, I don't think it's been tried.

Here's my best guess. Initially it was thought that a vaccine for XMRV might be easier than something that didn't show the find of rapid mutations that HIV does (and even with the P variant I don't think it's still anywhere even close) making it easier to target a vaccine. While we tend to think of vaccines as preventative they can be also be therapeutic. With two major variants the vaccine challenge is definitely greater but by how much I'm not smart enough to guess.

Otis