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The most scientific thing to do is to wait for the Lipkin and BWG studies

omerbasket

Senior Member
Messages
510
I'm pretty much shocked by the results of Singh's study. I didn't really think of an option that she won't find XMRV/HMRV.
I read most of the study - and as a non-scientist it indeed looked, and still looks to me as a study that was done with many many efforts.

I trust almost nobody regarding that matter, but ofcourse I trust Dr. Singh much more then any of those other scientists in the negative studies until now. I don't say it could not be that any of the members in the study interefered and caused false negative results - but in my opinion, this is unlikely.

However, I did not believe either that all of the scientists involved in the negative studies until now wanted not to find the virus. It's possible, but not likely (in my opinion), and it's also possible that some of them really didn't want to find the virus, but I don't thinkl it was all of them. And yet, I continued to believe in XMRV/HMRV. Why was that? It was because even when a scientist really wants to find the truth, it does not mean that he will find it. I believed that there is something wrong with the negative studies - something that perhaps no human being knows.

Dr. Singh's study did look very rigorous, but it wasn't a full replication. So that, too, is missing, and I wonder - why go into that many efforts without first replicating the first study? The first study was very rigorous, with many efforts, but it seems that Dr. Singh's study was done with at least the same amount of efforts. So why not spending these efforts of making a complete replication study, and then you can still use other methods and methods to check for contamination and argue that the positive results that you got from methods of the original study (if you found positive results) were due to contamination, or cross-reaction, or whatever other reason. This was not done - and my fear is that with any negative non-replication study we are approcahing a stage in which people would do what Coffin said - leave XMRV behind. It might save some money if XMRV is not a real human infection, but it might also be an extremely huge mistakes - if tens of millions and hundreds of millions would continue to be infected with a pathogenic virus that the scientific community does not recognize as a real human infection.

It's very important that a replication study would be done. However, I think that what's more important is that the BWG's and Lipkin's studies would be completed and would be published. I think that these atudies, especially the Lipkin one, has the best potential to tell us who was right in this huge argument and who was wrong. If the samples are processed exactly the same way, are then blinded, and the WPI and Lo's lab can still find positives in 67%-98% of the patients (that they don't know that they are the patients) and "jsut" in 3.7%-6.8% of the controls (that they don't know that these are the controls) - or in percentages close to this, than the "XMRV is a real human infection" argument would be a much stronger argmunet than the "XMRV is a laboratory contaminant that does not exists in humans" argument, and if they find it equally in patients and controls, or more in controls than in patients, than the "XMRV is a laboratory contaminant that does not exists in humans" would be much stronger than the "XMRV is a real human infection" argument.

Many scientists would say that they don't understand how it's possible that all of these negative studies were wrong, especially studies so rigorous like the Singh study. On the other side of the road, scientists like Dr. Mikovits, Dr. Ruscetti, Dr. Lo and Dr. Hanson would say that they don't understand how it is possible that what they found was due to contamination, after all of the things that they did that showed it is highly unlikely (there are many many things - I'll mention just some of them: All the negative controls in the Lo/Alter study; The finding of those viruses in 7 out of 8 patients 15 years later; The huge difference between the controls and patients - in both the WPI/NCI study and the Lo study; The negativity of the mtDNA assay, which at least in the Lo/Alter study was shown to be more sensitive than the IAP assay; The antibodies that the WPI found, and the way that they found them that showed that it's unlikely to be a cross-reaction; Etc.). But the main sentence that I take from the Singh study, a sentence which can be improtant to each side of the argument, is this one:
We also suggest that any planned studies proposed to screen for XMRV carefully check their reagents, equipment, and all possible - and seemingly not possible - sources of contamination with exogenous XMRV and mouse DNA.

This is very true regarding contamination, but it is also very true regarding other things, and the most important one (alongside with contamination) is the possibility that the negative studies missed positive people, meaning, they checked a positive sample and found it negative - and did that with many samples. The contamination theory supporters might think it to be "seemingly not possible", but the main word here is "seemingly".
Therefore, I really think that the BWG and Lipkin studies would be our best chance of knowing whether the seemingly not possible was actually very possible. And I believe that the good scientific approach here would be that scientists would wait for the results of those studies before coming out with statements about XMRV/HMRV being real or false. Anything else (which would be said - I'm not talking about what one would think, that's probably impossible to tell yourself to stop thinking something) would be unscientific and political.
 

Cort

Phoenix Rising Founder
Well thankfully, two replication studies are underway :). We've always said the BWG and Lipkin studies are the most important. I think the weight of evidence against XMRV working out is really strong BUT - the BWG and Lipkin studies are kind of a line in the sand type deal. If the WPI can identify the CFS patients from the others in those studies - then researchers have to do a turn around....the ball is in their court :).

So why not spending these efforts of making a complete replication study, and then you can still use other methods and methods to check for contamination and argue that the positive results that you got from methods of the original study (if you found positive results) were due to contamination, or cross-reaction, or whatever other reason.

I haven't looked at the exact methods but according to Raccaniello was in part a replication....I think there's a disconnect between us and retrovirologists. My guess is that they think methods improve as the research goes on and they would rather use those methods than the original methods. I think they also feel that different methods using different techniques can find all sorts of viruses -so why not XMRV? They have the virus to study, after all - and should be able to use it to devise tests to find it.

Alot of studies, for instance, have looked for the pol gene - I don't think it was in the original study but it is the most conserved; ie least likely to change over time (and therefore miss in a test). That is one test that should work in all types of XMRV and because of that its not surprising that lots of groups have used it. Of course alot of groups have looked for the env gene.

One of the big differences with the Singh study was the use of culture for six weeks....
 

omerbasket

Senior Member
Messages
510
My guess is that they think methods improve as the research goes on and they would rather use those methods than the original methods. I think they also feel that different methods using different techniques can find all sorts of viruses -so why not XMRV?
The importrant words are in bold. Don't "think". Don't "feel". You're human and you can be wrong. Use the right scientific process to ensure that you're mistakes won't hurt others. Do everything, and I mean, everything, the same, to ensure that there isn't some thing that you don't know of that causes you're results to be false.
 

Daffodil

Senior Member
Messages
5,875
i am so saddened by this ila singh study. she knows this virus and how to find it. now what will happen to us?

has anyone heard anything about how the glaxo smith kline study is going?

perhaps dr. mikovits knew this ila singh study was going to come out and thats why she decided to focus on finding treatments for the virus rather than spending all her time trying to prove it exists, to placate the medical establishment?
 

omerbasket

Senior Member
Messages
510
Sue, I really tend to trust Dr. Singh's intentions, but it's still very possible that she really wanted to find the virus, and went threw great efforts, but still missed a virus that was there. She herself said before that we probably already found all the viruses that are more easy to find, and now we might have to deal with viruses that are harder to find. So perhaps it's harder to find XMRV than even she thinks? Perhaps in a clinical sample, it has important mutations that makes it impossible to find? And why she did not use a serological method that was proven to be able to find XMRV in clinical samples?

It's not only that it saddenes me that she did not make a replication study - it also saddenes me that instead of calibarating her assays against the samples from positive patients that were found to be positive by the WPI, she decided to check them with the methods that she already had. Samples from positives can be used for two things:
1) To try and validate that they are positives - which is what Dr. Singh did.
2) To calibarate your assay until it's able to find all of the samples from previously described positives, to be positive. Than you know that you have an assay that is sensitive enough.

I too am intersted about the GSK study.

But again, I repeat: Scientists don't know how to cure all cancers. They don't know how to cure MS. It's possible that they don't know how to reliably find XMRV or it's variants. So Dr. Singh, although I trust her intentions, might just not know how to find a virus that is there (after all, she never demonstrated her ability to find XMRV in clinical blood samples, except for what seems as a positive due to contamination in this study of her's).
It seems that there are a number of labs (and I'm focusing on the WPI's lab, Dr. Ruscetti's lab and Dr. Lo's lab) that can find it many times - They think that they are finding a virus that is really in the patients, others think that they are finding a laboratory contamination. Therefore, studies like the BWG and Lipkin studies are very much needed.
 
Messages
13,774
Anyone know when we're due some news from the BWG?

To me, it seems pretty unlikely that the WPI did manage to stumble upon an effective way of finding XMRV, and all these big studies failed... but it's still possible, and testing the WPI's methods in the way the BWG is doing was something we were wanting done ages ago. Hopefully that will clear this all up.
 

Jemal

Senior Member
Messages
1,031
To me, it seems pretty unlikely that the WPI did manage to stumble upon an effective way of finding XMRV, and all these big studies failed... but it's still possible, and testing the WPI's methods in the way the BWG is doing was something we were wanting done ages ago. Hopefully that will clear this all up.

Indeed, this seems less and less likely. And I also agree it could still be possible. They are groping around in the dark, or so it seems.
 

*GG*

senior member
Messages
6,389
Location
Concord, NH
Anyone know when we're due some news from the BWG?

To me, it seems pretty unlikely that the WPI did manage to stumble upon an effective way of finding XMRV, and all these big studies failed... but it's still possible, and testing the WPI's methods in the way the BWG is doing was something we were wanting done ages ago. Hopefully that will clear this all up.

Yeah, I would say it's still possible. What does bigness have to do with it? The science paper had a rather large sample, not sure of Ila Singh sample size. I think they have years(?) more of experience in finding XMRV, and it's not the easiest thing to detect. I haven't hitched all my hope on this, and besides it has really brought a lot of attention to our plight and other research is ongoing, so even if it does not pan out, we should not be left in the dark again!

GG
 
Messages
118
http://www.virology.ws/2011/05/06/i...m_campaign=Feed:+VirologyBlog+(virology+blog)


Late last year virologist Ian Lipkin was asked by National Institute of Allergy and Infectious Diseases head Anthony Fauci to coordinate a multi-center study of CFS patients. Newly drawn blood samples from 100 CFS patients and 100 healthy controls from around the US will be blinded and sent to three groups FDA, CDC and the Whittemore Peterson Institute and assayed for the presence of XMRV. After the recent publication by Ila Singh on XMRV in CFS patients, Dr. Lipkin sent me the following note:


Dear Vince-

We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we dont have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.

I remain agnostic. We wont have answers until the end of 2011.

The NIH will post something on our study today.

Ian
 

Graham

Senior Moment
Messages
5,188
Location
Sussex, UK
Another way of looking at it is that so far there have been three heavyweight studies, Judy Mikovitz with XMRV, Harvey Alter with a broader family group of virus, and Ila Singh with nothing found. If you look at the history of medical discoveries (or even of general scientific discoveries), it would be fair to say that the jury was still out, and that there may be something behind all of this that we have not yet grasped.
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
From the Ila Singh study:

We discovered that both recombinant Taq polymerase (Invitrogen) and the 394 Platinum Taq polymerase (Invitrogen) tested positive for IAP sequences.
Taken together, our analysis shows that certain Taq preparationscontain very small amounts of mouse DNA that can cause false-positive reactions when used inhighly sensitive assays for XMRV.

I wish that we could hear from the WPI whether they used assays from Invitrogen, and if so, whether they've tested them for mouse DNA. It would be good to get a specific answer straight from the horse's mouth.​


Suppose for the sake of argument that the WPI study is correct and not contamination. In science, even negative studies tell us something (if they are well done). Since the Singh study seems to be rigorously done, if the WPI study is correct, what would the Singh study tell us?​


 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
Well thankfully, two replication studies are underway :).


Cort did you list these two studies, and who's doing them? I may have missed it, I'd like to keep an eye out for them. These are two very important studies.
 

omerbasket

Senior Member
Messages
510
Well thankfully, two replication studies are underway :).


Cort did you list these two studies, and who's doing them? I may have missed it, I'd like to keep an eye out for them. These are two very important studies.
I join this question, again. What are the two full-replication studies?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Well thankfully, two replication studies are underway :). We've always said the BWG and Lipkin studies are the most important. I think the weight of evidence against XMRV working out is really strong BUT - the BWG and Lipkin studies are kind of a line in the sand type deal. If the WPI can identify the CFS patients from the others in those studies - then researchers have to do a turn around....the ball is in their court :).

Cort did you list these two studies, and who's doing them? I may have missed it, I'd like to keep an eye out for them. These are two very important studies.

Cort seems to be referring to the BWG and the Lipkin studies.

They are both replication studies because the WPI is involved with them both and will be using its own technology and methodology to replicate its own research.
 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
Really? So no lab is going to take the EXACT (that means everything) process from the Science paper and try to reproduce the results? That speaks volumes as to where the scientific community stands on XMRV, this must be the "good science" part I don't get again.
 

August59

Daughters High School Graduation
Messages
1,617
Location
Upstate SC, USA
Really? So no lab is going to take the EXACT (that means everything) process from the Science paper and try to reproduce the results? That speaks volumes as to where the scientific community stands on XMRV, this must be the "good science" part I don't get again.

Scientific arrogance. It appears that they are too scared to truly replicate!
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I'm not sure that an exact replication study would actually help us because there's so many variables that it would be hard to get it all perfectly right.
And then if the study was negative, then they would say that was proof that the WPI study was contaminated.
All we need, at some point in time, is for some other researcher to credibly find XMRV in ME patients.

In a video that I watched, Lo says that he followed the WPI's methodology closely, and then he found PMRV's.

Switzer of the CDC has made a small start at finding XMRV in prostate cancer patients, which I think might be helpful for us, and he says that he is going to continue his investigations. He now needs to learn why he detected XMRV in so few of the prostate cancer patients, when other have detected it in a far higher percentage. And he also needs to work out why he can't detect XMRV in the blood of XMRV-positive prostate cancer patients.

So things have happened... But it's happening very slowly.
 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
Cort seems to be referring to the BWG and the Lipkin studies.

They are both replication studies because the WPI is involved with them both and will be using its own technology and methodology to replicate its own research.


Cort is this correct? Are the two replication studies you know about the BWG and Lipkin studies?