• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Science asks authors to retract XMRV/CFS paper

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Kurt, do you think that there might be difficulties detecting any gene sequences of XMRV, with established PCR technology, if the virus has already integrated into human DNA? (WPI use a low specificity test to look for the virus.)

Also, would you agree that if the viral copy number is too low in the blood for PCR to detect, then it would not be detected? (WPI culture the samples.)

Anyway, this is opening up old arguments, so I'm content to just agree that we disagree, and look forward to finding out more answers in the coming months, whether in terms of XMRV research, or general ME research.
 

kurt

Senior Member
Messages
1,186
Location
USA
Kurt, do you think that there might be difficulties detecting any gene sequences of XMRV, with established PCR technology, if the virus has already integrated into human DNA? (WPI use a low specificity test to look for the virus.)

Also, would you agree that if the viral copy number is too low in the blood for PCR to detect, then it would not be detected? (WPI culture the samples.)

Anyway, this is opening up old arguments, so I'm content to just agree that we disagree, and look forward to finding out more answers in the coming months, whether in terms of XMRV research, or general ME research.

Those are technical questions a biological researcher could answer better than I can. However, given that PCR is used regularly to find gene sequences that are 'integrated' in human DNA, such as in forensic analysis or simple genetic studies where just a few target genes are being looked for, I believe the answer to the first question is that PCR should not have difficulty finding integrated sequences. The way I understand PCR, they strip out ALL the nucleic acids, which means all the sequences in a sample. Should not matter whether those are present in viral or host strands. My 13 year-old son can do that, learned how in science class at school, anyone can separate out human DNA.

The second question is a bit of an oxymoron, because if the viral copy is too low for PCR, then WPI should not have found 67% positives with their nested PCR test reported in the Science article. However, assuming that the viral copies are below a given detection threshold, of course, then it could not be detected by that PCR test. The problem though is that PCR properly calibrated and run can detect as little as a single copy in a sample, in some cases. Of course there is variation in how well each test is design and the environment in which it is run. But given the calibration methods built into PCR test design, this should all easily be found out, how sensitive a test really is.
 

Jemal

Senior Member
Messages
1,031
If it was just a few people at the WPI, I think I would have lost hope by now.

However, there are many good scientists in the XMRV camp. Alter, Ruscetti, Silverman, Klein, DeMeirleir, Hanson, Bieger, etc. Even Singh is still in the XMRV camp. She hasn't found XMRV in CFS patients, but she still believes in her cancer work, like Bob said. And even Switzer found some XMRV now and ruled out contamination.

If there ever comes the time when several of these scientists start to state that XMRV is contamination, then I will believe it is over. I don't think it's that time though, far from it (seeing that none of the co-authors of Lombardi et al wanted to retract). Hopefully we'll know more in a few days, when news comes from the retrovirology conference and symposium.

The two most important studies are still standing: Lombardi et al has not been retracted and Alter has stated that the Lo/Alter research is still sound as well.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Well, what if the contaminant was added in the lab somehow, because of a reagant for example. The sample is then contaminated.
My question still stands I think: is it possible the WPI are detecting non-XMRV-specific antibodies?

I am playing devil's advocate here by the way! If the WPI is detecting XMRV specific antibodies, great.
Yes, sure, no problem, but as you've said those antibodies are produced by the body, so it doesn't matter at all if the lab or reagents are contaminated, unless it's contamination with antibodies (which i've never heard of).
It would in any case mean that something in the body of people with ME/CFS is measurably different than in healthy people.
Or am i misunderstanding you?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
It would in any case mean that something in the body of people with ME/CFS is measurably different than in healthy people.

That's a good point eric... I hadn't actually thought of that before... Even if the antibodies are not XMRV specific, they are still in CFS patients, and not in normal controls, so they could at the very least be used as biomarkers... But they do suggest that there is a MLV-like virus in CFS patients, and not in normal controls, even if they are not actually specific for XMRV. I hadn't really thought about their significance in those terms before.
 

Jemal

Senior Member
Messages
1,031
Well, it looks like the antibodies could be very telling then, so that's good. I wanted to paste this bit in as well, it's more evidence why the antibodies are not random antibodies:

The WPI serology test can only be picking up the SU protein of an MuLV. The antibody to SFFV (spleen focus-forming virus) only reacts to that protein. Mouse DNA or ERV's cannot make whole virions, so the protein will not react.

So more evidence for a new human retrovirus, originating from mice.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Well, it looks like the antibodies could be very telling then, so that's good. I wanted to paste this bit in as well, it's more evidence why the antibodies are not random antibodies:

The WPI serology test can only be picking up the SU protein of an MuLV. The antibody to SFFV (spleen focus-forming virus) only reacts to that protein. Mouse DNA or ERV's cannot make whole virions, so the protein will not react.

So more evidence for mouse viruses.

I didn't quite understand that Jemal... Have you got any further info on that?
 

markmc20001

Guest
Messages
877
Let's all be honest one minute here.

The Concensus on the forums might just be, there is no Concensus! Show me the poll that shows what the concensus is around if XMRV has been given a fair shake?

Doesn't help when one side lobbies the government, has an unlimited budget, hires news relations, has a media group called "SPIN", and is flatly ignoring the scientific methods.

Everybody is really kidding themselves trying to debate this stuff at this point. We all know what's up, it's just a matter of what the general public believes. Some are still watching fox news, but many more know what is up.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
XMRV and autoimmune disease

That's a good point eric... I hadn't actually thought of that before... Even if the antibodies are not XMRV specific, they are still in CFS patients, and not in normal controls, so they could at the very least be used as biomarkers... But they do suggest that there is a MLV-like virus in CFS patients, and not in normal controls, even if they are not actually specific for XMRV. I hadn't really thought about their significance in those terms before.

Hi Bob, here is the paper I was thinking of earlier:

http://precedings.nature.com/documents/4669/version/1/files/npre20104669-1.pdf

We have numerous proteins in the body that anti-XMRV antibodies could attack. This raises four options. First, they are really attacking XMRV. Second, its an autoimmune issue, we are attacking ourselves. Third, we are seeing foreign proteins from a range of microbes, some of which might be pathogenic - and we have antibodies to those.

Option four is the most interesting. We are making anti-XMRV antibodies, but those antibodies are attacking our bodies - viral induced autoimmune disease. There has to be a reason why XMRV proteins are so similar to ours, and this could be it. As we attack XMRV, we attack ourselves, damaging our capacity to fight the virus.

These options are not mutually exclusive. All four could be right, although option four is really just a hybrid of option one and two.

Bye
Alex
 

Waverunner

Senior Member
Messages
1,079
The antibody argument seems to be a very valid argument in my eyes. I hope they discuss it in twiv today.

Jemal said:
However, there are many good scientists in the XMRV camp. Alter, Ruscetti, Silverman, Klein, DeMeirleir, Hanson, Bieger, etc.

I spoke to two of them during the last month and for me it seems that they backed off a little bit. Both of them more or less said that there can be a connection between XMRV and CFS but at this point of time it is premature to say so.

EDIT:
my opinion: Contamination has to be looked for but the much bigger problem is that XMRV could just be another co-infection like other herpesviruses and because of a weakened immune system PWCs get infected by it. If the weakened immune system is cause rather than consequence of a viral infection then we are at the beginning of CFS research. No diagnosis, no treatment.
 

currer

Senior Member
Messages
1,409
retroviruses are not just another co-infection. They are quite different from viruses.
Only two other human retroviruses exist. If we have found a third human retrovirus, it is big news.
 

Jemal

Senior Member
Messages
1,031
I spoke to two of them during the last month and for me it seems that they backed off a little bit. Both of them more or less said that there can be a connection between XMRV and CFS but at this point of time it is premature to say so. Contamination has to be looked for but the much bigger problem is that XMRV could just be another co-infection like other herpesviruses and because of a weakened immune system PWCs get infected by it. If the weakened immune system is cause rather than consequence of a viral infection then we are at the beginning of CFS research. No diagnosis, no treatment.

Who did you speak to if I may ask Waverunner? And did they think XMRV could be contamination or are they more worried the virus could be a co-infection? Those are really 2 different things, because if they are looking into the co-infection, that means they think XMRV is real and are trying to determine if it causes disease.

retroviruses are not just another co-infection. They are quite different from viruses.
Only two other human retroviruses exist. If we have found a third human retrovirus, it is big news.

I fully agree with this statement. Retroviruses are not innocent infections. They are infections for life and most retroviruses compromise the immune system in the long run. That we only found 2 retroviruses in humans so far, is really telling.

I still think XMRV is the puppetmaster.
 

currer

Senior Member
Messages
1,409
Hi Bob, here is the paper I was thinking of earlier:

http://precedings.nature.com/documents/4669/version/1/files/npre20104669-1.pdf

We have numerous proteins in the body that anti-XMRV antibodies could attack. This raises four options. First, they are really attacking XMRV. Second, its an autoimmune issue, we are attacking ourselves. Third, we are seeing foreign proteins from a range of microbes, some of which might be pathogenic - and we have antibodies to those.

Option four is the most interesting. We are making anti-XMRV antibodies, but those antibodies are attacking our bodies - viral induced autoimmune disease. There has to be a reason why XMRV proteins are so similar to ours, and this could be it. As we attack XMRV, we attack ourselves, damaging our capacity to fight the virus.

These options are not mutually exclusive. All four could be right, although option four is really just a hybrid of option one and two.

Bye
Alex

These arguments have been used as a model of causation in other diseases, rheumatioid arthritis or lupus for example.
There are many potential auto-immune diseases.
Unfortunately, there has been no success finding a viral cause for these, either.
I think we end up back with Robin Weiss's rumour viruses again.
 

Jemal

Senior Member
Messages
1,031
These arguments have been used as a model of causation in other diseases, rheumatioid arthritis or lupus for example.
There are many potential auto-immune diseases.
Unfortunately, there has been no success finding a viral cause for these, either.
I think we end up back with Robin Weiss's rumour viruses again.

I just can't believe, that our immune systems, that have been protecting us for so many generations, are now attacking our own bodies. I have the feeling something else is happening, a virus perhaps. I am not saying that all auto-immune disease have another cause, but I think many will.
 

currer

Senior Member
Messages
1,409
Let's all be honest one minute here.

The Concensus on the forums might just be, there is no Concensus! Show me the poll that shows what the concensus is around if XMRV has been given a fair shake?

Doesn't help when one side lobbies the government, has an unlimited budget, hires news relations, has a media group called "SPIN", and is flatly ignoring the scientific methods.

Everybody is really kidding themselves trying to debate this stuff at this point. We all know what's up, it's just a matter of what the general public believes. Some are still watching fox news, but many more know what is up.

You said it, Mark. I agree.
I think we have to establish whether or not XMRV is a cause, as the WPI believe, before we pursue other options.
I dont think XMRV will go away as easily as that, even though there is massive political pressure to do so.

In fact, as Alex says, the two theories, Auto-immunity and XMRV are not mutually exclusive, but I do not want to see political pressure prioritising one theory over the other.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Hi Bob, here is the paper I was thinking of earlier:

http://precedings.nature.com/documents/4669/version/1/files/npre20104669-1.pdf

We have numerous proteins in the body that anti-XMRV antibodies could attack. This raises four options. First, they are really attacking XMRV. Second, its an autoimmune issue, we are attacking ourselves. Third, we are seeing foreign proteins from a range of microbes, some of which might be pathogenic - and we have antibodies to those.

Option four is the most interesting. We are making anti-XMRV antibodies, but those antibodies are attacking our bodies - viral induced autoimmune disease. There has to be a reason why XMRV proteins are so similar to ours, and this could be it. As we attack XMRV, we attack ourselves, damaging our capacity to fight the virus.

These options are not mutually exclusive. All four could be right, although option four is really just a hybrid of option one and two.

Bye
Alex
There's a thought i had after the last Coffin paper, but i don't know if it makes sense if i speculate too much about these things. I think he says our own system renders "the contaminant" harmless. Now even if that was true (a good number of people would disagree with this statment anyway, i guess), couldn't it be that the problem is more the immune system's response and so it wouldn't matter too much if the virus can actually do something anyway?
 

Jemal

Senior Member
Messages
1,031
There's a thought i had after the last Coffin paper, but i don't know if it makes sense if i speculate too much about these things. I think he says our own system renders "the contaminant" harmless. Now even if that was true (a good number of people would disagree with this statment anyway, i guess), couldn't it be that the problem is more the immune system's response and so it wouldn't matter too much if the virus can actually do something anyway?

If I understand the paper correctly, they say XMRV could not infect humans succesfully, because the virus gets eliminated by our immune system. A lot of people disagree with this.

Anyway, what you say could be possible as well: XMRV could be relatively harmless in itself, but our immune systems hate the life of it and start a full out war. The immune system has great difficulty eliminate a retrovirus however, which leads to us being sick all the time.

XMRV being a retrovirus however, it seems less likely it's just there for the ride. It might provoke the immune system and get stronger by its response.
 

Waverunner

Senior Member
Messages
1,079
Who did you speak to if I may ask Waverunner? And did they think XMRV could be contamination or are they more worried the virus could be a co-infection? Those are really 2 different things, because if they are looking into the co-infection, that means they think XMRV is real and are trying to determine if it causes disease.



I fully agree with this statement. Retroviruses are not innocent infections. They are infections for life and most retroviruses compromise the immune system in the long run. That we only found 2 retroviruses in humans so far, is really telling.

I still think XMRV is the puppetmaster.

The co-infection was my opinion only. I didn't make that clear, sorry.

One was KDM. I know that he was very enthusiastic about XMRV half a year ago. He said that there will be a breakthrough this year and that some important studies will be published that will make clear that XMRV is a pathogenic retrovirus. When I spoke to him one month ago he wasn't enthusiastic about XMRV at all. He still thinks that there can be a connection. He will watch from the side. As far as GcMAF goes he said that even if one does not have a XMRV infection it can be very beneficial for PWCs because of their compromised immune systems.

I don't want to tell the second doctor but he has good contacts to a professor who is currently checking the blood supply for XMRV. He said that under the impression of all new contra XMRV studies and especially the Singh study he does not know what to think. If his befriended professor at the blood supply does not find XMRV or says that it is not a threat to humans he has to reevaluate his opinion about XMRV completely.
 

Jemal

Senior Member
Messages
1,031
One was KDM. I know that he was very enthusiastic about XMRV half a year ago. He said that there will be a breakthrough this year and that some important studies will be published that will make clear that XMRV is a pathogenic retrovirus. When I spoke to him one month ago he wasn't enthusiastic about XMRV at all. He still thinks that there can be a connection. He will watch from the side. As far as GcMAF goes he said that even if one does not have a XMRV infection it can be very beneficial for PWCs because of their compromised immune systems.

Thanks for the additional info.
KDM is presenting at the current XMRV retrovirology conference I think and he will be at the symposium. So I am very interested in what he will say there. I hope he is still enthusiastic and you caught him on a bad day or something :D
 

Waverunner

Senior Member
Messages
1,079
Thanks for the additional info.
KDM is presenting at the current XMRV retrovirology conference I think and he will be at the symposium. So I am very interested in what he will say there. I hope he is still enthusiastic and you caught him on a bad day or something :D

Ye, I'm looking forward to the results of the conference as well.