XMRV CFS UK study #II

[oerganix]

Hello there.

My post was not intended as a lecture nor an attack. If you think no-one was being unfair on the Retrovirology study you might want to re-read a number of the posts. Take it easy. It's very disheartening to try to keep the debate scientific and have words like "attack" thrown at what I thought was a very reasonable post.
This is why I don't post very often !

Your post was pretty strongly worded, in that you said this second study had absolutely nothing wrong with it, while other knowledgeable posters have pointed out some things that may be wrong with it. You are right that emotions are running high and that is partly because there is such a well-documented history of scientific fraud and abuse coming from the medical establishment in UK. Keep it real, you said. Good advice, but what is real is still subject to debate. Hugs to you, too, even if they're not an addition to the science being debated here.

 

[valia]

As most people on this board know I tested positive for xmrv by culture with VIPdx. I am a UK positive.


The last few days I have been asking myself questions about what all of this means.
I am left thinking several things.

Did WPI get it wrong. I can not see how. I have looked and looked and looked again at all the evidence put out there and can see no valid reason to doubt them.

That then brings me back to why is no xmrv been found in the UK so far by others.

People have been questioning the criteria used in the UK and can tell you in my case apart from a test over 20 years ago that showed I had coxackie B I have had absolutely no testing. I was given a label of Post Viral Fatigue Syndromme or PVFS and that remained so in my medical records until recently. The denial of ME for decades in this country is the reason for that not the nature of my illness. There has been a question regarding the severity. I have ranged over the years from as good as 80% to as bad as 20%. Would my XMRV results been different at 80%?

Since getting tested I have been considering what my next step should be personaly. One of the things I keep coming back to is diagnosis and tests. I would like to be assed useing the Canadian Consensus. My immune status checked and so on and so on. I know it seems backward but I am still left here not knowing the answer to fundemental questions about the nature of how this disease has affected me apart from my syptoms.

This will not happen here in this country as still all that is offered in treatment is CBT and GET with no testing allowed.

In this climate how am I or anyone else ever going to get to the truth?

joy

Your post seems to have been missed joyscobby, I wouldn't get too stressed out at this stage the British studies have neither proved or disproved anything, but hopefully someone will come along soon and give you a better response than I can.

 

[Quilp]

Hello there.

My post was not intended as a lecture nor an attack. If you think no-one was being unfair on the Retrovirology study you might want to re-read a number of the posts. Take it easy. It's very disheartening to try to keep the debate scientific and have words like "attack" thrown at what I thought was a very reasonable post.
This is why I don't post very often !

Please KFG you must post as often as you can. I like nothing better than for people to pull apart my posts because it gives me a different way of looking at things. Don't be disheartened, you have a lot to offer and you are just as entltitled to an opinion as the next guy.
Sure things get a little hot now and again, so what ? That's life right ? Remember, you can please some of the people some of the time..........

Thanks, Mark

 

[Bob]

Please KFG you must post as often as you can. I like nothing better than for people to pull apart my posts because it gives me a different way of looking at things. Don't be disheartened, you have a lot to offer and you are just as entltitled to an opinion as the next guy.
Sure things get a little hot now and again, so what ? That's life right ? Remember, you can please some of the people some of the time..........

Thanks, Mark

KFG, I agree with Quilp... please keep contributing KFG...
I appreciate your messages... we are all allowed to disagree with each other... and it make for better discussion if we disagree sometimes.
Sometimes people mis-read the intentions behind a message, and as lots of emotions are running high, so sometimes people will get frustrated on the forum.
Bob

 

[sarahg]

Please KFG you must post as often as you can. I like nothing better than for people to pull apart my posts because it gives me a different way of looking at things. Don't be disheartened, you have a lot to offer and you are just as entltitled to an opinion as the next guy.
Sure things get a little hot now and again, so what ? That's life right ? Remember, you can please some of the people some of the time..........

Thanks, Mark

Yes, please! don't go away. You do have a lot to offer. We must all remember that on all sides, the only way anyone ever changes their mind is to have someone disagree with what they think. We must also all remember that it would be terribly boring and pointless to get information from someplace where everyone agrees with everyone else. Disagreement is how we learn.

 

[Cort]

If this is from Dr. Mikovits it does present what I would think are some key points

Perhaps the most important issue to focus on is the low level of XMRV in the blood. XMRV
is present in such a small percentage of white blood cells that it is highly unlikely that either UK
study’s PCR method could detect it using the methods described. Careful reading of the Science
paper shows that increasing the amount of the virus by growing the white blood cells is usually
required rather than using white blood cells directly purified from the body. When using PCR
alone, the Science authors found that four samples needed to be taken at different times from the
same patient in order for XMRV to be detected by PCR in freshly isolated white blood cells.

• They need to activate and grow the white blood cells in order to find the virus
• They need to look multiple times to find it

I wonder if its quite unusual for a study to do that - I assume they usually take one pass (?). On the hand it says 'sometimes' - so the virus often pops on the first pass. That would suggest that the first idea- that they need to grow the white blood cells first - is the one that could explain the zero results.

 

[garcia]

"Our culture has a tendency to deify science"

Really ? I think the opposite is true. The fact that Barry Marshall swallowed a bunch of bacteria and made decades of doctors look stupid by proving that Helicobacter Pylori and not stress or spicy foods caused ulcers was science at its best. And he received the Nobel prize for it. Barry Marshall was, above all, a good scientist.

I agreed with your earlier post (on the need to not attack the scientists responsible for this study). But I have to disagree with you here. Barry Marshall didn't make decades of doctors look stupid. At least not at first. He made himself look stupid. No one believed him. They thought he was a mad-man. A maverick. A loose-cannon. He did his swallowing of H. Pylori in the mid-80's, but it was only as late as the late 90's that antibiotics became the routine prescription for stomach ulcers. And actually Marshall was only the latest in a long line of pioneers stretching back as far as 100 years who had discovered the bacterial cause of stomach ulcers (See "helicobacter pioneers"). Of course in the end he was proved right and won the nobel prize (2005), but it took a long, long time. It's not so much that the old-guard changed their minds, but that they were replaced by a younger generation who were never taught the old untruths.

We have to differentiate between the scientific process itself (which I agree is the deductive reasoning process par excellence) and the academic version of Science, which is as much about ego/politics as anything else.

Whoops! I also meant to add to any brave souls still reading this - do not despair. The ME/CFS question is solvable and it will be solved. Science is, quite frankly, horrendously slow. The WPI are genuine in their efforts. So are a lot of other researchers out there. If the only thing WPI achieve is to bring the illness to the attention of many good scientists then that in itself will be a major achievement. Let's see what happens !

I totally agree with the above, especially the bit about Science being horrendously slow. Over 100 years for H. pylori.

 

[Dr. Yes]

Cort:

I haven't seen that LadyBug; its very interesting - where did it come from?

Ladybugmandy:

cort..it was attached to an email from dr. mikovits.

Cort:

If this is from Dr. Mikovits it does present what I would think are some key points

It certainly does. Ladybugmandy, could you please elaborate on the source? Is this an early copy of a release from the WPI?

Cort, have you found out yet where it came from?

If it is from WPI, it is the most significant thing posted on this thread; whatever it is, it raises very important points about the methodology, echoing or expanding on what we have been saying here.

(Post #242 in this thread, by the way)

 

[Gerwyn]

"Science needs to be interrogated just like anything else"

Interrogation is the essence of science. My problem is that there is an underlying current in some of these posts that the WPI being interrogated is somehow a conspiracy. If they're wrong, they're wrong. If they're right, they're right. Then again, they may only be half-wrong or half-right, but let's not go there....

"Our culture has a tendency to deify science"

Really ? I think the opposite is true. The fact that Barry Marshall swallowed a bunch of bacteria and made decades of doctors look stupid by proving that Helicobacter Pylori and not stress or spicy foods caused ulcers was science at its best. And he received the Nobel prize for it. Barry Marshall was, above all, a good scientist.

I think there's still a possibility that the WPI could end up in a similar position - going against the tide and getting the truth. But there's also the possibility that they're just plain wrong. Science will provide the answer, and I wouldn't have it any other way. But not every other XMRV study on Earth is fair game for conspiracy theories just because it gets different results from WPI.
Gerwyn has made an excellent point regarding the length of time involved in one of the tests - that's a scientific issue and not an "attack" on the Retrovirology people.

If you want to talk down science or the scientific process - which is by no means perfect but by far the best way to do things - count me out of your forum. I also agree 100% with everything you said about science being done by imperfect people who make mistakes, and I apologise if I gave any other impression.

Whoops! I also meant to add to any brave souls still reading this - do not despair. The ME/CFS question is solvable and it will be solved. Science is, quite frankly, horrendously slow. The WPI are genuine in their efforts. So are a lot of other researchers out there. If the only thing WPI achieve is to bring the illness to the attention of many good scientists then that in itself will be a major achievement. Let's see what happens !

i dont believe the researchers in britain are insincere so here is some more science

The limit of detection of the PCR method used is between 50 -100 cfu per ml assuming one virus starts one colony. The titre of xmrv is about 100cfus per mll.Now if you initially draw blood the infectivity half life is about 5 hours so if you leave it overnight you are down to less than 10cfu,s per ml .You then freez and rethaw which loses a further 50%(MLV studies).Detecting XMRV using that PCR method without preculture is going to be something of a struggle even assuming equal distribution in the blood!

 

[Countrygirl]

Are these claims true?

I have just read on the WPI facebook page that Dr Judy is stated as saying that she is working with the German scientists who failed to find XMRV in the prostate cancer research last autumn. It is claimed that they are going to repeat the negative tests with her guidance. Anyone know if there is any truth in this alleged collaboration?

Another very recent post claims that the French are also involved in researching how to prevent XMRV from replicating. I hadn't heard this.

Sorry if this is just rumour.

 

[omerbasket]

"Science needs to be interrogated just like anything else"

Interrogation is the essence of science. My problem is that there is an underlying current in some of these posts that the WPI being interrogated is somehow a conspiracy. If they're wrong, they're wrong. If they're right, they're right. Then again, they may only be half-wrong or half-right, but let's not go there....

"Our culture has a tendency to deify science"

Really ? I think the opposite is true. The fact that Barry Marshall swallowed a bunch of bacteria and made decades of doctors look stupid by proving that Helicobacter Pylori and not stress or spicy foods caused ulcers was science at its best. And he received the Nobel prize for it. Barry Marshall was, above all, a good scientist.

I think there's still a possibility that the WPI could end up in a similar position - going against the tide and getting the truth. But there's also the possibility that they're just plain wrong. Science will provide the answer, and I wouldn't have it any other way. But not every other XMRV study on Earth is fair game for conspiracy theories just because it gets different results from WPI.
Gerwyn has made an excellent point regarding the length of time involved in one of the tests - that's a scientific issue and not an "attack" on the Retrovirology people.

If you want to talk down science or the scientific process - which is by no means perfect but by far the best way to do things - count me out of your forum. I also agree 100% with everything you said about science being done by imperfect people who make mistakes, and I apologise if I gave any other impression.

Whoops! I also meant to add to any brave souls still reading this - do not despair. The ME/CFS question is solvable and it will be solved. Science is, quite frankly, horrendously slow. The WPI are genuine in their efforts. So are a lot of other researchers out there. If the only thing WPI achieve is to bring the illness to the attention of many good scientists then that in itself will be a major achievement. Let's see what happens !

Personally, I tend to suspect and question any research that throws us back to the situation in which we are right now. Why? Because I suspect that among good scientists and persons, there are persons there which has an interest in keeping us sick. For example: A scientist that based his career claiming that ME/CFS is caused by something else than a retrovirus. Or a doctor which is a ME/CFS expert and that many of his pateints are ME/CFS patients. It's not that I'm saying there are no doctors who would rather make those patients healthy than get their money every time they come back to the clinic. Maybe it's even the opposite - most of the doctors do want their patients to be healthy even if it's not good for them (the doctors) finiancialy. But I have a suspicious that there are doctors out there that prefer the money over their patient's health. And what about the drug companies? I believe that there are drug companies that can make money if XMRV is found to be the cause of ME/CFS (but than, it would really be the cause, because you can't forge such a thing for long. You can, possibly, make people forget about XMRV by doing some research that allegedly shows it's not the cause of ME/CFS, even if it really is the cause), but there are also drug comapnies out there, that many of us buy their expensive drugs for years and tens of years - and I don't think us getting healthy is good for those drug companies finincialy. I don't know if they can do something about it, but I don't rule out the possibility that they can.

And above all of this - It's possible for scientists to just be wrong. Or, they might be right. But for me, when there are questions being raised about the quality of the science, and when I don't know if the scientists had pure motives, I can't trust them.

 

[Orla]

Yes she is working with the Germans as far as I know (she mentioned this in her prohealth talk).

Also re the French:
http://www2.cnrs.fr/en/1698.htm

 

[_Kim_]

Hello there.

My post was not intended as a lecture nor an attack. If you think no-one was being unfair on the Retrovirology study you might want to re-read a number of the posts. Take it easy. It's very disheartening to try to keep the debate scientific and have words like "attack" thrown at what I thought was a very reasonable post.
This is why I don't post very often !

The reason your post sounded like a lecture is because you are telling us how we should behave/feel. If you take out these few comments, THEN your post would be received as reasonable. You have some good points to make. It's the bolded comments (including the 'take it easy' one above) that are objectionable.

Originally Posted by KFG

People are getting a bit lost here.

There is absolutely nothing wrong with the Retrovirology study. These were good scientists doing their best to investigate the possibility of XMRV infection in CFS patients. They didn't find it. Let's stop trying to pick apart good science carried out by good people. There is no conspiracy involved with this group. I'm quite sure they felt keen disappointment, as most of us do.

It's not impossible that this virus is behaving in an unusual way. The conflicting Prostate studies suggest this as a possibility. It may be that a very specific test is required to detect it. If that's the case, the assays being developed by NIH and others may clarify this. On the other hand, a new form of contamination may have occured. Again, this will become clear in time. As long as investigation of these and other possibilities is continuing, and it is at present, the truth will be found. The truth is all that matters. Contamination ? Okay - that would be extremely depressing but research in other areas would continue. XMRV-associated illness ? Okay - let's get busy understanding it and looking towards therapy.

All that matters here is the truth. That is what science is all about. That is what the Retrovirology study was about.

When CFS patients start attacking objective scientific research then credibility goes out the window. Keep it real. More data is coming. If the WPI are wrong, they're wrong. If they're right, they're right. It's difficult not to become too emotionally involved but good science isn't done that way.

And finally, before anyone tries to criticise science once again, can I say that Psychiatry is one of the least convincing branches of science - unfortunately ME/CFS has been claimed by this profession, so we have some of the least "scientific" people trampling all over us. Psychiatry is not good science, for the most part. Good scientists will resolve the ME/CFS situation. But boy is it taking a long time.

 

[alice1]

I was so sad when I read that the Lancet( a British Journal and very respected) announced a disclaimer regarding vaccines and
Autism.There are many Doctors who still believe there is a total connection.
I'm not sure who I'm suppose to listen to anymore but I'm really hoping like everyone else they find xmrv and fast.

 

[Sparklehorse]

Hello there.

My post was not intended as a lecture nor an attack. If you think no-one was being unfair on the Retrovirology study you might want to re-read a number of the posts. Take it easy. It's very disheartening to try to keep the debate scientific and have words like "attack" thrown at what I thought was a very reasonable post.
This is why I don't post very often !

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.

By the way, do you really think that "there was nothing wrong" with the latest study? Really? Not even the fact that it wasn't a replication study? Surely it deserves to be taken to task for that very fact? Or don't you think so? Gerwyn and others have backed up their views with scientific information. Have you backed up any of your comments saying that there was nothing wrong with the study with scientific facts too?

 

[Countrygirl]

Orla;47309]Yes she is working with the Germans as far as I know (she mentioned this in her prohealth talk).

Also re the French:
http://www2.cnrs.fr/en/1698.htm[/ur...me by. :ashamed: I must do better. :worried:

 

[Abraxas]

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

 

[Guido den Broeder]

On the other hand my interpretation of her statement is that it's bad news for most of us; she's not taking the Retrovirology study to task for bad techniques; instead she's suggesting indirectly that XMRV is found in only a small subset of patients - and unless researchers start explicitly identifying those patients and testing THEM the whole thing is going belly up.

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.

 

[Gerwyn]

There is a reason that scientific research involves strict adherence to this protocol---depart from it and we end up with this goddammed awfwl mess

 

[George]

It's a penguin

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: