XMRV CFS UK study #II

[Gerwyn]

First of all, there must be agreement on the hypothesis. This will have to be that XMRV is involved in the neurological disease ME, rather than in some ill-defined research diagnosis named CFS.

Of all people diagnosed with CFS, at least 50% does not have ME. This number will be much higher, right up to 100%, if you take patients from clinics that do not adhere to the WHO classification of ME, because ME patients will avoid these clinics if they can. There are a lot of such clinics in the UK.

It is essential for any replication or validation study that the diagnosis is correct, that it has been confirmed that the patients are in fact ME patients. No CFS criteria will do this, they have to be tested medically, and this has to be done rigorously.

i completely agree Guido No neurological/neuroendocrine symptoms then it cant be ME even post exertional malaise would do at a push but that must be the minimum requirement

 

[Esther12]

I agree with KFG, I didn't think there was anything wrong with the new study either. They didn't exactly replicate the WPI's techniques - but we'll have those studie closely co-ordinating with the WPI to do that. These other studies are still interesting. I've read the criticisms in this thread, but as far as I can tell, they do not explain the total absence of XMRV postives amongst CFS patients in this study. I'm still hopeful that the WPI's work will lead on to something, but at this point it's not sensible to assume that it must be those scientist's who are getting opposing results who must have done something wrong, and the WPI must be right.

 

[Bob]

I agree with KFG, I didn't think there was anything wrong with the new study either. They didn't exactly replicate the WPI's techniques - but we'll have those studie closely co-ordinating with the WPI to do that. These other studies are still interesting. I've read the criticisms in this thread, but as far as I can tell, they do not explain the total absence of XMRV postives amongst CFS patients in this study. I'm still hopeful that the WPI's work will lead on to something, but at this point it's not sensible to assume that it must be those scientist's who are getting opposing results who must have done something wrong, and the WPI must be right.

Esther, I completely disagree with you... if you go back and read through this entire discussion thread closely, you'll see that the latest study has been exposed for its flaws in methodology.
It is very clear to me that this study was not capable of finding XMRV, and it didn't.
And, the research team have not demonstrated their competence in finding XMRV with positive control samples.
The more we scrutinize it, the more it seems to be a haphazard study, and all they have shown us is that they aren't capable of top quality research because they can't detect this retro-virus.

Whereas the WPI science is solid, thorough and competent. If you look at all of the information out there, you'll see that it can't be disputed.

I agree with KFG insofar as we have to rely on the science, and I truly believe that, at last, the science and truth will win the day.
I understand everyone's fears about XMRV getting buried (I have the same worries), but the WPI's science is rock-solid, and they really know what they are doing.
There isn't any doubt amongst credible scientists that XMRV exists now... there's loads of viral scientists getting involved with this now... loads of them, all across the planet.

 

[Katie]

I agree with KFG, I didn't think there was anything wrong with the new study either. They didn't exactly replicate the WPI's techniques - but we'll have those studie closely co-ordinating with the WPI to do that. These other studies are still interesting. I've read the criticisms in this thread, but as far as I can tell, they do not explain the total absence of XMRV postives amongst CFS patients in this study. I'm still hopeful that the WPI's work will lead on to something, but at this point it's not sensible to assume that it must be those scientist's who are getting opposing results who must have done something wrong, and the WPI must be right.

What did you make of the argument that white blood cells needed to be cultured first to boost the copies of XMRV to detectable levels, I found this point convincing so I'd be interested in your take as I'm not well versed to make a counter point.

 

[Gerwyn]

I agree with KFG, I didn't think there was anything wrong with the new study either. They didn't exactly replicate the WPI's techniques - but we'll have those studie closely co-ordinating with the WPI to do that. These other studies are still interesting. I've read the criticisms in this thread, but as far as I can tell, they do not explain the total absence of XMRV postives amongst CFS patients in this study. I'm still hopeful that the WPI's work will lead on to something, but at this point it's not sensible to assume that it must be those scientist's who are getting opposing results who must have done something wrong, and the WPI must be right.

How would you explain the complete absence of xmrv in CFS patients but their presence in "healthy controls".Is having CFS protective in some way? why do you think that they selected these controls.I,m not saying that they deliberately did something wrong but in any objectively measurable sense their approach was unscientific because they assumed their methods would work but didn;test that assumptiomn in any way and they did not use the same methodology which is a scientific prerequisite

Even a CFS diagnostic error of 100% would not explain the absence of virus in the cfs group unless the controls had somehow been" souped up" In fact this contol groups blood would be a soup of endogenous retros.So we dont know if their method could detect xmrv at all apart from the four cases they "felt" were due to XMRV

 

[MEKoan]

I've read the criticisms in this thread, but as far as I can tell, they do not explain the total absence of XMRV postives amongst CFS patients in this study.

Posted by George (a very, very good dog, indeed!)

3)and the antibody test did work on the healthy controls who had mounted an antibody response but not on the those who are ill because they would not have antibodies.

Sneaky penguins!

I want to commend everyone for a dialogue which is not only extremely intelligent and informative (thank you, thank you, science nerds!) but also remarkably civil given the enormous stake we all have in the outcome.

I would happily invite anyone to read over our shoulders and I would proudly say: This is my community.

 

[Countrygirl]

Abraxas;47323]Countrygirl, see here too for some discussion of the French study: http://forums.aboutmecfs.org/showth...ects-for-the-treatment-of-retroviral-diseases And here: http://forums.aboutmecfs.org/showth...escape-virulence-factor-encrypted-in-envelope

You folk are brilliant! Thanks.

Thank you, too, for all the information on this thread. It is invaluable for those of us who do not have a scientific background. :Sign Good Job:

I see that Dr Judy is asking people to put questions to her about this second study. Gerwyn.........are you there? Hint, hint

best wishes,

C.G.

 

[Robin]

The trouble is that this "debate" isn't only about science, it's also about politics. Maybe you are unaware of the political situation surrounding ME in the UK? Well believe me there's been lots of "funny" stuff gone on over the years so maybe give those of us who have lived through decades of this "funny" stuff some credit that we can ask questions about the genuineness of a study etc. For what it's worth I think that this latest study isn't disasterous and I believe many of the researchers are genuine and want to help research XMRV further and work with others. This is good. So you can't keep science and politics seperate with ME. They go hand in hand, more's the pity. People who have seen the political shennanigans before have every right to express their worries and opinions, just as much as yours. [It's not up to you to decide what's right to post and what's not. What makes you and your ideas so very special? You're not better than anyone else.
...

Moderator note: Just ask Kim suggested above for KFG to watch his tone, I'm going to ask you to do the same. The parts I've bolded above are personal attacks.

All opinions and points of view are welcome here, as this is an open forum. We do not moderate for content. The purpose is so that the people reading the threads can get a variety of opinions and make up their own minds. However we do moderate for personal attacks. When disagreements happen it's natural to want to lash out at the person in discord, but, here we ask that you address the argument itself rather than the person making it.

Everyone is welcome to review the forum rules here. If you see a personal attack in thread the best thing to do is to click the "report post" on the bottom left hand of the post rather than engage in argument yourself. Thanks.

Remember that none of us are retrovirologists here, thus everything posted is opinion and speculation.

 

[Esther12]

What did you make of the argument that white blood cells needed to be cultured first to boost the copies of XMRV to detectable levels, I found this point convincing so I'd be interested in your take as I'm not well versed to make a counter point.

I'm not well versed in these techniques either, but from my reading of the various science blogs/sites, it seems that CFS patients arethe only ones to rubbish the study. From my understanding, the shorter period used for culturing might explain a lower detection rate, but the total absence of XMRV detection would still be very surprising. It seems like something strange is going on with our ability to detect XMRV, and I still think it's quite possible the mistakes have been occuring on the WPI's side. I worry that some people are thinking that those who find XMRV are on our side, and those who do not are opposed to us, and this will lead to a misreading of the available evidence.

 

[Bob]

...from my reading of the various science blogs/sites, it seems that CFS patients are the only ones to rubbish the study.

Maybe this is because CFS patients are experts in their field, and have been following science more closely than others.
XMRV has already been detected in the UK; Judy Mikovits has stated that the same rates of detection are holding up in the UK.
So therefore, I am satisfied that this research team were incapable of detecting the XMRV virus. And they have no proof that they can, unlike the WPI team.
They simply failed to carry out good enough research or a replication study. Isn't that the end of the story in relation to this latest study?

 

[Lily]

I just got caught up on the posts. Especially the scienciy stuff that Gerwyn and others have posted. This virus seems to be a bit of a penguin in comparison to other viruses. (Birds got to fly, fish got to swim and viruses have to ___________ fill in the blank) XMRV proves that conventional thinking will kick your butt every time. (grins)

The way I understand it the differences are;

1) XMRV makes only 1 or 2 viri to send out once it has infected a cell. Meaning that a PCR with a sensitivity of 16 is not going to pick it up. (I think the lowest level of detectable HIV is 20 copies per cell but that's using a blot test rather than PCR I don't know what the PCR copy number is. In general HIV and HTLV however produce at 50 copies or better per cell.)

2) XMRV does not mutate by more than a few nucleotides. Unlike HIV which can throw off 20 or 30 quasi species within a two month period.

3) XMRV is around 8100 nucleotides in length and varies not more than 8 to 10 nucleotides in structure. HIV however is around 9200 and has only 11 stable gene sequences. The rest are subject to change.

4) XMRV requires some type of trigger in order to begin replicating at higher volume. HTLV is like that as well, requiring a specific set of genetics in order to become active, while HIV just needs to get past the immune response and it goes wild.

So taking these differences into account and the breakdown of DNA at the cellular over time which happens with all blood samples it seems the following might be true;

1) In order to find XMRV in blood, the blood needs to be fresh and a large volume of blood needs to be collected in order for a PCR to pick up anything. (Which supports the WPI assertion that at least 20 ML of blood less than 24 hours old would be necessary for when they were doing the PCR testing.)

2) Culturing the blood - causing the infected cells to divided and therefore stimulate them to create copies. (the little budding particles) is the best way to up the number of copies so that the PCR can detect them.

3) Once you culture the blood however and get a good bunch of cells tossing out their extra viri then there is no need to use PCR you should be able to detect the viri growing in the culture. (Hence the WPI stopped relying on PCR once they were sure they had the right culture test set up)

Developing a serology or antibody test is where the science is right now. If I understand correctly you can create a serology or blot test which can pick up protein sequences that XMRV manufactures via the envelope but not an antibody test.

The problem with the antibody test is that healthy people will have an antibody reaction but XMRV is able to fool certain people (genetics??) so that they don't mount an antibody response and thus become ill.

(My guess on this is that the virus pulls a bait and switch. It lays dormant in the system except with the host is ill. The illness is the trigger that stimulates the virus to replicate and infect new cells while the host immune system is busy looking the other way at whatever virus its fighting at the time. That would argue for an older virus that's been around for awhile. Sneaky little penguins. (grin))

So these differences have to be taken into account in designing any study. The last two studies that looked for XMRV in CFS/ME patients.

1)didn't use fresh blood,
2)didn't take into account that older blood would need to be cultured in order to raise the number of copies to a detectable level with PCR.
3)and the antibody test did work on the healthy controls who had mounted an antibody response but not on the those who are ill because they would not have antibodies.


In conclusion the two tests from the UK (actually only one because the Weassel one doesn't count (big grins)) were designed much the way one might design a test for say HTLV or HIV. The uniqueness of the XMRV virus wasn't taken into account. Considering these studies were actually designed and conducted in November/December it could well be that specifics of the XMRV virus were either not known at the time or overlooked in the rush to study the possibility that XMRV could play a role in CFS/ME.

But riddle me this. Once some of the specifics were known, why publish? I can understand why Wessel et al published and I just feel really sorry for the people involved, but why Dr. Kerr and company?

And why do anything that would compromise the opportunity to study the possibility of XMRV as a causative agent in CFS/ME? The retroviral model works to perfection as a cause for CRS/ME it dots all the i's and crosses all the t's. Books have been written and hypothesis formed that a retrovirus will one day come to light and describe this illness in it's entirety. I understand why WPI would publish up front and take their chances. If this isn't "the retrovirus" then it's missing a mighty good chance.

Heck we've got people trying to pull out ancient HERVs as the answer to CFS since no one could find a real live retrovirus, the model works so well. What ever the truth is in the end, I'm surprised that UK published back to back negative studies. This is a great shot for getting the ill treated and back to the salt mines of working. (grin)

The only thing I can think of is the time frame/monetary cost ratio. It will require 5 to 10 years to develop a drug therapy (using the HIV/AIDS model, maybe as little as 5 for us) and that could translate to billions with a b in benefits for people with the virus currently.

So are the studies meant to slow the CFS/ME population down, discourage them from getting tested and using the results to get benefits? I suppose the several hundred thousand spent on a study is well spent in that case. But there is no way that Dr. Kerr and company would comply with such a deal. Would they?? I can't picture it but maybe I'm idealistic.

If they can delay testing in the UK by even a year it could give them time to put policies in place that might protect the NHS from getting hit for a lot of money right away until the budget could be set up to handle the influx of claims. I don't know. It's something to ponder. And the politics don't really matter in the long run. Like Katie said, "they are but a fart in the breeze".:sofa:

Perhaps we underestimate the power of the government and the size of that fart.

 

[Cort]

Thanks for the insights Gerwyn and great synopis George! (Maybe in another lifetime you were a researcher- maybe in this lifetime you were) Very interesting points - if that post was from Dr. Mikovits then it seems their response would have to mention them - they seem so convincing. One wonders, though, how these researchers could spend so much money on a technique that would probably not work - given what we think Dr. Mikovits said. Did they not read the paper carefully? That seems impossible. Did they think their techniques would pick it up anyway. Anyway, thanks for putting that together in such an understandable fashion. )

I agree with Koan; this is the type of discussion that makes us proud - we may be right or we may be wrong but we're trying to work our way through this as best we can.

 

[Sparklehorse]

So you can't keep science and politics seperate with ME. They go hand in hand, more's the pity. People who have seen the political shennanigans before have every right to express their worries and opinions, just as much as yours. [It's not up to you to decide what's right to post and what's not. What makes you and your ideas so very special? You're not better than anyone else.


The first two sentences aren't personal attacks at all! Ridiculous. Maybe the last sentence yes, but not the first two. So much for free speech, just as long as it suits certain people eh? What is the point?

Moderator note: Just ask Kim suggested above for KFG to watch his tone, I'm going to ask you to do the same. The parts I've bolded above are personal attacks.

All opinions and points of view are welcome here, as this is an open forum. We do not moderate for content. The purpose is so that the people reading the threads can get a variety of opinions and make up their own minds. However we do moderate for personal attacks. When disagreements happen it's natural to want to lash out at the person in discord, but, here we ask that you address the argument itself rather than the person making it.

Everyone is welcome to review the forum rules here. If you see a personal attack in thread the best thing to do is to click the "report post" on the bottom left hand of the post rather than engage in argument yourself. Thanks.

Remember that none of us are retrovirologists here, thus everything posted is opinion and speculation.

 

[Katie]

I'm not well versed in these techniques either, but from my reading of the various science blogs/sites, it seems that CFS patients arethe only ones to rubbish the study. From my understanding, the shorter period used for culturing might explain a lower detection rate, but the total absence of XMRV detection would still be very surprising. It seems like something strange is going on with our ability to detect XMRV, and I still think it's quite possible the mistakes have been occuring on the WPI's side. I worry that some people are thinking that those who find XMRV are on our side, and those who do not are opposed to us, and this will lead to a misreading of the available evidence.

I think the criticism from the ME/CFS quarter reflects the political culture surrounding our particular muddled illness. In the autistic community there are those with children with autism and stomach issues that Dr Wakefield was investigating similarily outraged at counter evidence of the link not only between vaccines and autism but the link between their gut issues and autism. I'm sure there's probably some tension in the MS community over the vascular research being undertaken, each scientific discovery has it's own political context. Other quarters such as the retroviral community won't use blogs and forum to air their questions, they have other avenues for discussion which are more professional and private.

I agree with you that something strange is going on with XMRV detection and that we need to focus on how to pick up the virus before we look for it in any particular illness. While I don't rule out mistakes in the WPI study, we won't really get anywhere until testing methodology reaches a decent consensus. Hopefully this is already underway. I don't think it's a case of sides with regards to finding this, I think the attitudes to the people on this study have been very pleasant, but the science is still up for analysis. The WPI Science paper has been debated and critiqued too, especially with the puzzling question of cohort which is confusing me no end.

 

[MEKoan]

Hey Cort,

I think we need to remember that this study, although just published, is already old. If they were doing the study in November, it is possible that they were simply unaware of the degree of difficulty and that they were overly confident in their existing methods. Could be.

 

[Countrygirl]

(((((((((((George)))))))))))) Can I nominate you as' poster of the day'? :Sign Good Job: Take a bow! Your explanations to me as a non-scientist are just brilliant. You should write a book called' XMRV for Dummies'. You could send a signed copy to a certain professor.......

and many pats

C.G.

 

[Bob]

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[George]

Just a Note

To be clear, I read the Second Study like 6 times and I still can't fault it's design or execution. It really is flawless in that sense. The problems outlined (by others, I just make little numbered points) are simple things that weren't highlighted in the paper and I know I had to go through like a ton of transcription to find references plus I've been spending hours comparing HTLV and HIV and taking basic virology again just to keep up with what's going on. (grin)

 

[Funkster]

George and Gerwyn

You guys are my heroes. My true heroes.

You keep my spirit up through these rollercoaster times.

Are you able to merge your highly intelligent positions into spesific questions to Judy Mikovits and Kerr concurrently?

It would be very interesting to see how they would respond to similar questions based on the two scientific papers?

Judy is asking for questions before Saturday and I guess Kerr would answer on direct questions regarding the paper as such.

I Salute You...

Best wishes

Funky Boy

 

[Quilp]

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bl***dy hell that is really strong stuff !