XMRV found in ME/CFS samples from "all of Europe"

[Wonko]

only if you understand numbers

 

[pictureofhealth]

This sounds weird. CFS Patients clearly don't have an immunological status comparable to AIDS, e.g. no low T-Cell counts. Does anybody know more about how to interpretate this statement?

Regards

Hello FormalScientist,

Yes it does seem a bit general! For a start, the HIV causing retrovirus is a lentivirus and the XMRV/MLV related viruses are gammaretroviruses - from what we know so far - so the causative agents are different.

Forgive me if the following is phrased unscientifically (I am not a scientist) & I do not remember the details of all the findings that have been posted recently - we are getting to the fortunate point where we are now about to become inundated with exciting new scientific date left right & centre ...

The other question is - do the different retroviruses (retrovirii?) infect different parts of the human immune system/immune cells - there is some evidence in CFS/ME that this might involve replicating ?B-cells - & do they insert themselves in different parts of the genes?, and if so, are the immune responses in ME/CFS are going to be different to those in HIV/AIDS and between different patients?

(One forum poster recently noted that ME/CFS patients receiving chemotherapy for cancer often had an improvement in their ME/CFS symptoms and wondered whether this was due to the XMRV/MLV infected B-cells being 'knocked off'? Dr Mikovits and team note that it is possible that immune system activation after immunisation may trigger an increase in XMRV/MLV replication in the body - the XMRV etc takes advantage of the immuno protective process.)

I think the immune processes in ME/CFS will turn out to have their own set of complications and intricacies which may or may not apply to HIV/AIDS. Will straightforward ART actually work for ME patients, or will a combined approach with Ampligen be more useful - or something else entirely?
Will the advancement of research in ME/CFS related infections also increase our understanding of HIV/AIDS?

Just to complicate the picture - XMRV/MLV's have been found in HIV patients too.

So I'm wondering if the statement was just v general one at this stage to generate interest - until more info is forthcoming at the XMRV Conference or studies are published.

This is why it is so helpful that HIV/AIDS scientists, researchers and physicians are also going to be at the conference and are getting v interested in this new area of research. The insights and research of physicians like Dr Nancy Klimas, who have both AIDS and ME/CFS patients in their practise, are going to be particularly helpful.

Dr Mikovits has said that there is only x1 immune abnormality that shows up 100% of the time in XMRV ME/CFS patients (was it related to Interferon Alpha?). I'm afraid I didn't make too much of an effort to remember until its been a. published or b. corroborated elsewhere - as immune markers in ME/CFS seem to change with every new study - although I have much more faith in the WPI than in anyone else so far.

Also, I know that Dr Mikovits and others who are presenting at the XMRV Conference, which starts tomorrow, will have many further revelations about their findings to date, which have been many since the original Science study - and specific immune abnormalities may be one of them.

 

[FormalScientist]

Hi,

So, 10% in the immune suppressed but 67-98% in the CFS patients. Isn't that a blow to the speculation of XMRV/MLV only taking hold because our immune systems are allegedly compromised due to other causes (eg psychological stress)?

Well, you mean the 10% reported by Fischer et al? I think the results of this study regarding differences between "healthy" and "immunocompromised" patients are not stastically significant. The groups have been way to small for that. In fact AFAIR one positive patient more or one positive patient less would have changed the results about 3%; this means that it is not possible to decide if the prevalance in immune suppressed patients is really slighly higher oder just about the same as in healty people. But however, this backs your position So i think iff the 67% hold true (i'm really not sure about that after the Lo/Alter paper), youre right.

So I'm wondering if the statement was just v general one at this stage to generate interest

Hm, i'm afraid that thats exactly the point. But "generating interest" by press releases claming things that arent provable is not the way to go. I'm not in the medical field (okay, a least not in the way it is normally considered) but i guess the medical science community really does not like such a behaviour, and they are absolutley right about that. There's way to much bias in the field, in either direction, i'm really afraid that this will later turn out as a boomerang for us.

Regards

 

[anciendaze]

Well, you mean the 10% reported by Fischer et al? I think the results of this study regarding differences between "healthy" and "immunocompromised" patients are not stastically significant. The groups have been way to small for that. In fact AFAIR one positive patient more or one positive patient less would have changed the results about 3%; this means that it is not possible to decide if the prevalance in immune suppressed patients is really slighly higher oder just about the same as in healty people. But however, this backs your position So i think iff the 67% hold true (i'm really not sure about that after the Lo/Alter paper), youre right...

I can agree about statistical significance, but I want to point out a 'Catch 22' in the field. Up until now, you couldn't get funding to run rigorous studies with enough patients to be statistically significant. If you did small studies, you couldn't get them published in good journals. On the other hand, we now have a collection of papers from studies which did get published without actually demonstrating the ability to detect infected human beings anywhere.

While the CDC group now says they have demonstrated this ability, I'm not aware of any published result in which they detected XMRV in blood from an infected human. Their entire claimed ability seems to rest on artificial positive controls and two tissue samples from prostate cancer. This is not a good basis for claiming much of anything, let alone the sweeping conclusions blazoned across the title. If they were going to ask us to trust them, there was no need to publish in a scientific journal.

If this misconduct meets with official approval, you can scarcely expect others to remain austerely academic. I'm afraid this well was poisoned long ago. Sorting out the mess will not take place in quiet. That opportunity passed about 25 years ago.

 

[pictureofhealth]

I think I shall withold further comment about this press release and Dr Merleir's claims until I hear the details from the Conference. There is so much excitement in the air at the moment that it is easy to get caught up in the frenzy. I think his team have been using the WPI/VipDx test for finding XMRV? I do look forward to hearing the details and sincerely hope he is right. I have to say though, given the staggering array of disabling symptoms in the 2 illnesses (ME/CFS & HIV/AIDS), his unpublished claims about the presense of a retrovirus make a lot more sense to me, than some of the published rubbish which passes for serious science coming out of the UK (spot the bias). Some of the 'comments' from certain scientists and commentators in the BMJ have become a tad 'snarky' recently. De Merleir at least is genuinely helpful and pleasant I hear.

 

[Mark]

Hi FormalScientist, welcome to the forums. Just wanted to come back on the last point you made there and echo what anciendaze said, really...

But "generating interest" by press releases claming things that arent provable is not the way to go. I'm not in the medical field (okay, a least not in the way it is normally considered) but i guess the medical science community really does not like such a behaviour, and they are absolutley right about that. There's way to much bias in the field, in either direction, i'm really afraid that this will later turn out as a boomerang for us.

Assuming acceptance that some things may have been handled in a somewhat unconvential way...

What I think might help to think about is: Do you really think that any of the people involved in the type of behaviour you're referring to are unaware of these principles? I think it's quite obvious that everybody involved understands these basics of scientific protocol very well, and understands the downsides that might come from 'bending' those rules a little. I'm not a scientist but even I understand all these rules - I'm sure they haven't bent them lightly. The thing is, they get all that, they know the problem, but basically anciendaze is right, these were things that simply had to be done. The blame for that reality lies elsewhere. And it has to be said that on every such point of principle, I've seen "the other side" of the argument doing the same sort of things, and much, much worse, but you never hear them criticised for it. I don't know if it will boomerang back on us, I would hope that if the truth is allowed to get out then science will do its job and sort things out so that what is true is what wins out. But in this area of science, I'm afraid I doubt there was another way. At the least, that's what they must have felt.

 

[FormalScientist]

Hi,

some wise posts here, i have to think about some things said a bit more :Retro smile:

Let's hope the conference brings some news that connects the results of the different studys somehow. From my more logical then medical point of view the study situtation is a big mess at the moment. Really nothing fits together. Nothing.. I think this is really critical. At the moment WPI is still the only institute in the world who found XMRV in CFS. They have to explain at least the results of the Lo/Alter study in relation to their own results. At the moment i don't see how this could work out without changes to their original claims.


I have to try to get some sleep now, foggy day.

Regards

 

[Mark]

FS, I know where you're coming from when you say it doesn't quite seem to fit together, but all I'd say is that the closer you look into it - and the more you listen to the actual people involved and their story of events, and get the explanations, their answers to explain the condundrums and apparent inconsistencies - the more it really does start to fit together. I agree there seems to be a piece missing, but already a compelling picture is emerging, for me at least. I think part of the problem is that you can't explain the bits and pieces without reference to a much larger picture - for example, you have to understand an awful lot about the details of the differences between cohorts and definitions, and the politics and the various players as well, and the history, as well as the science itself, to begin to see how everything fits together. I'm really hopeful that at a purely scientific level the conference this week will fill in masses of those gaps; the inconsistencies between different groups will have to be resolved and explained and the conference should go a long way towards doing that. Not that, like everything, it won't raise as many questions as it answers, of course....

 

[pictureofhealth]

The scientists on this forum will correct my choice of words if I'm wrong, but as I remember it, Dr Alter seemed happy that they were onto the same family of viruses, or strains of viruses, as the WPI and has personally said that he and his team (Lo et al) at the NIH 'fully support' the WPI's findings. He also mentioned the word 'infection' in his press interview (NIH Q&A on their website).

Perhaps viral mutations and geographical distribution can help to explain different variations. Also we really don't know the original source of the XMRV & MLV's and that could potentially explain different variations in a family of viruses.
(btw I don't agree that geographical distribution can explain an apparent lack of XMRV & MLV's anywhere - most people travel to far flung reaches of the globe nowadays and viruses don't need visas to enter countries! The idea that XMRV could be in the States but not in UK is daft IMO given the traffic between the 2 and not just human traffic, birds, mosquitoes etc).

Dr Mikovits is about to present a reportedly positive study from the UK done I believe by 2x different US labs. (The bloods did not pass via the WPI labs as far as I know - so these are findings from other labs & help to rule out 'contamination' by WPI).

Dr Bishop from UK did find MLV's in her negative XMRV study but did not recognise the significance until the Lo et al paper at NIH. She is now about to embark on a 200+ REPLICATION study of UK ME/CFS patients using WPI full protocol as used in the original Science paper.

In any case, as per my post above, we will all know much much more by the end of this week. How exciting is that??!!!

 

[Mark]

Just one 'for example' - the CDC samples were the last drops of a hugely controversial set of samples from patients recruited over the phone and assessed using definitions that seem to specifically exclude the symptoms that researchers like the WPI team consider to be cardinal symptoms. Also the tubes they used for that study are believed to be very unhelpful for this specific test (see Dr Vernon's strong statement on that subject). So when we find that all that Alter saw in that group of samples was an extremely weak trace signal in about 10% of them, it's conceivable that what we're seeing is a cohort of patients none of whom have what the WPI would call CFS, using tubes that almost completely kill off the thing you're looking for, and leave you just with a mere trace of the roughly 10% background rate in the general population. It looks pretty close to making sense. It's almost as if there are two different worlds here, and they are looking at each other as if through a mirror. It's very weird, but it does make more and more sense the more you look at the biomedical side of the argument, and as I say, look for answers to the challenging questions about the WPI and Alter's studies from the researchers themselves...those are my personal tips, anyway...

 

[julius]

Hi,

some wise posts here, i have to think about some things said a bit more :Retro smile:

Welcome to the forums.

We can always use more intelligent, open-minded people.

 

[anciendaze]

I second Julius' post.

If the whole illness suddenly becomes clear and simple to you, I think that will be a first. This beast keeps surprising nearly everyone who thinks about it, and tests their ideas against data. There have been far too many people who have said, in effect, this illness ought to do thus and so, then become frustrated when it does not. If it weren't for us damned patients, who refuse to get well when people tell us we ought to be well, it would have been discarded as too difficult a research topic for the state of the art.

One heuristic I've found useful is this, if it behaved according to the 'textbook cardboard' of other illnesses, it would have been dealt with much earlier. Start looking for possible fallacies in common assumptions and you are likely to find them. The classical example is Komaroff's old statement that the fact that people could simply come down with a 'flu' and still be sick a year later struck him as remarkable. Classical disease is supposed to either 'resolve' or progress to some obvious pathology in that time. This is taught despite known exceptions, e.g. in rheumatology and MS, because most of the time, for most patients, it is true. This convenient rule of thumb is not a law of nature.

 

[Bob]

Just one 'for example' - the CDC samples were the last drops of a hugely controversial set of samples from patients recruited over the phone and assessed using definitions that seem to specifically exclude the symptoms that researchers like the WPI team consider to be cardinal symptoms. Also the tubes they used for that study are believed to be very unhelpful for this specific test (see Dr Vernon's strong statement on that subject). So when we find that all that Alter saw in that group of samples was an extremely weak trace signal in about 10% of them, it's conceivable that what we're seeing is a cohort of patients none of whom have what the WPI would call CFS, using tubes that almost completely kill off the thing you're looking for, and leave you just with a mere trace of the roughly 10% background rate in the general population. It looks pretty close to making sense. It's almost as if there are two different worlds here, and they are looking at each other as if through a mirror. It's very weird, but it does make more and more sense the more you look at the biomedical side of the argument, and as I say, look for answers to the challenging questions about the WPI and Alter's studies from the researchers themselves...those are my personal tips, anyway...

Ah, finally someone's explained to me the possible implications of the 'weak trace signals'... I didn't know that it worked out at 10% either... intriguing...

Interesting post generally Mark, thanks.

 

[Francelle]

In reference to the questioning statements about the tube collection method of some of the newer XMRV studies – such as the CDC study…I’m a bit puzzled!

Surely the ‘old’ specimens that were used by the WPI and the more recent NIH study, may also not have been collected with the ideal tubes seeing that they were collected so long ago & before they went into the deep freeze for storage!

Anyone enlighten me?

 

[anciendaze]

In reference to the questioning statements about the tube collection method of some of the newer XMRV studies such as the CDC studyIm a bit puzzled!

Surely the old specimens that were used by the WPI and the more recent NIH study, may not have been collected with the ideal tubes also seeing that they were collected so long ago before they went into the deep freeze!

Anyone enlighten me?

At the time those specimens were collected, careful researchers were already using the heparin-injected 'green tops'. This was true of the samples sent to DeFreitas in 1992. Why some later researchers have used a haphazard variety of collection techniques is for them to explain.