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

[omerbasket]

Scientific arrogance

Exactly what I think. The problem is: They think they know it all. They don't imagine that maybe there could be something that they didn't think about, or something that they were wrong about, which could make a difference.
Or that perhaps it's more than one thing (some of the studies, for example, DID find XMRV, just in very very low percentages - So, perhaps, had they have a more strict definition for the patients, they would have found it more - and had they combined it with the best assays, they would have found it in percentages that are similar to those found by the WPI/NCI and NIH/FDA).

Bob, I think I disagree with you about "we better not have full replication studies". I think that the problem is with scientists who say that "replicated the WPI/NCI's work and didn't find XMRV", when in fact they haven't replicated the methods. Full replication means full replication. I guess that at least at first we shell not require 100% full replication, and just 99% full replication - and that is because there is at least one thing that is not reasonable to do right now: To take patients' samples and store them for 2-3 years (as the WPI used for their "Science" study samples that were collected between 2006-2008). We should, however, demand, probably, that they would wait at least a couple of days between collection and testing - as it was shown in the BWG's work, until now, that it might make a lot of difference.
But in all other aspects - they can replicate. Perhaps we cannot demand them to by the same PCR machine (I mean - the same type from the same brand), but we can ask them to include the same kind of patients, collect the blood into the same kind of tubes, process it as it was done in the "Science" paper, test it as it as done in the "Science" paper and with all of the tests used there, and also use tools and kits which are the from the exact model and brand that the WPI/NCI used in the "Science" paper. And also: If they think that they don't understand something, or don't know how to do something - or that there is a slight chance for that - they must contact the WPI/NCI for guidance.

If they have done that and found nothing - well, I would still think that they should collect samples, store them for a couple of years, and test them again - with all of the methods used in the "Science" paper (and with same type of patients and stuff like that - everything the same, this time, 100% replication, perhaps besides the model and brand of the PCR machine) - but the chance of that giving a different result would be small, perhaps tiny.

But so far, no one has tried to fully replicate the WPI/NCI study.

 

[Bob]

Exactly what I think. The problem is: They think they know it all. They don't imagine that maybe there could be something that they didn't think about, or something that they were wrong about, which could make a difference.
Or that perhaps it's more than one thing (some of the studies, for example, DID find XMRV, just in very very low percentages - So, perhaps, had they have a more strict definition for the patients, they would have found it more - and had they combined it with the best assays, they would have found it in percentages that are similar to those found by the WPI/NCI and NIH/FDA).

Bob, I think I disagree with you about "we better not have full replication studies". I think that the problem is with scientists who say that "replicated the WPI/NCI's work and didn't find XMRV", when in fact they haven't replicated the methods. Full replication means full replication. I guess that at least at first we shell not require 100% full replication, and just 99% full replication - and that is because there is at least one thing that is not reasonable to do right now: To take patients' samples and store them for 2-3 years (as the WPI used for their "Science" study samples that were collected between 2006-2008). We should, however, demand, probably, that they would wait at least a couple of days between collection and testing - as it was shown in the BWG's work, until now, that it might make a lot of difference.
But in all other aspects - they can replicate. Perhaps we cannot demand them to by the same PCR machine (I mean - the same type from the same brand), but we can ask them to include the same kind of patients, collect the blood into the same kind of tubes, process it as it was done in the "Science" paper, test it as it as done in the "Science" paper and with all of the tests used there, and also use tools and kits which are the from the exact model and brand that the WPI/NCI used in the "Science" paper. And also: If they think that they don't understand something, or don't know how to do something - or that there is a slight chance for that - they must contact the WPI/NCI for guidance.

If they have done that and found nothing - well, I would still think that they should collect samples, store them for a couple of years, and test them again - with all of the methods used in the "Science" paper (and with same type of patients and stuff like that - everything the same, this time, 100% replication, perhaps besides the model and brand of the PCR machine) - but the chance of that giving a different result would be small, perhaps tiny.

But so far, no one has tried to fully replicate the WPI/NCI study.

But so far, no one has tried to fully replicate the WPI/NCI study.

No, they haven't, and perhaps a competent scientist should attempt to replicate the WPI's study.
But I'm not sure that they would get it exactly right, and if the results were negative, then we would be told that this is proof that the WPI is definitely wrong, and that it was contamination, blah blah blah.

I wonder how common it is for an exact replication study to be carried out, down to the tiniest detail?

XMRV research is developing very slowly, and more positive information and knowledge is being gathered about XMRV all the time.
In another year's time, we might know a lot more about XMRV than we do now, and although we didn't know XMRV research was going to turn out exactly like this, we did guess that it might take a few years before treatments were available.

But if we had just one other positive study, it would help us immensely.

Lo's video presentation was very interesting (I recommend watching it)... He described how he tried to copy the WPI's methodology closely, and explained that even when people think that they are replicating the WPI's study, they might not be, because small differences (such as a difference in the 'annealing temperatures' and 'magnesium concentrations') can make a big difference in the results. It's interesting, after hearing him say that, that he is the only scientist to get positive results. His talk gave me a lot of confidence in the research, and made me realise that Lo's study probably was a replication study, but unfortunately (unfortunate in the short term) he detected a slightly different strain of MLV-related viruses. It now turns out that Judy has also detected PMRV's and other MLV-related viruses, or HGRV's, so it looks like there might be a wide variety of strains causing disease.

 

[omerbasket]

I wonder how common it is for an exact replication study to be carried out, down to the tiniest detail?

It doesn't matter. Even if it's not "standard", it's the correct scientific thing to do. It will eliminate every variable that eliminatable.
But you are correct - it should be a COMPETENT group of scientists that would do that, and you are also correct that if they are not really competent, and comes up with negative results due to incompetency of their own, we might not be able to fight it, or even to know that the result is due to incompetency of the scientists in the replication study. That's why I believe that there should be at least 2-3 replication studies, to minimize such an option - although it's probably not possible to eliminate it.

Perhaps you are right - that due to what you and I have written, it's best right now if we won't have replication studies and we would wait for the BWG and Lipkin results - perhaps it would prevent us from getting a falsely negative replication study, done by incompetent scientists, that might burry XMRV for a very long time, perhaps forever (at least regarding ME/CFS). That's why I firmly believe that the BWG and Lipkin studies must be done anyway - there are numerous labs that find XMRV over and over again, check for contamination, finds nothing - even a hundred negative studies, even replication ones, don't explain why that's happening, and definitley don't prove that - and so, a study design such as the design used at the Lipkin study might be the only way to find the definite answer, although there are still question there, I think, about the type of tubes and type of proccessing they will use.

 

[toddm1960]

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

Cort I'm begaining to think that there aren't any true repilation studies under way.

 

[Bob]

Cort I'm begaining to think that there aren't any true repilation studies under way.

Hi tod,

The Lipkin study will be a replication study because the WPI are testing the blood samples themselves. I think they will also get to determine how the blood samples are drawn and how they are stored. Lipkin is only overseeing the study... He isn't carrying out the testing himself. The people carrying out the testing are the WPI, Lo/Alter and (I think) Switzer at the CDC. So the WPI and Lo will be replicating their own work, but the study is overseen by Lipkin.

I'm not sure about the exact details of the BWG study, but the WPI is deeply involved in that as well, and I believe that it is a cooperative and evolving process.

Hope that helps?

Bob

 

[Cort]

No, they haven't, and perhaps a competent scientist should attempt to replicate the WPI's study.
But I'm not sure that they would get it exactly right, and if the results were negative, then we would be told that this is proof that the WPI is definitely wrong, and that it was contamination, blah blah blah.

I wonder how common it is for an exact replication study to be carried out, down to the tiniest detail?


But if we had just one other positive study, it would help us immensely.

Lo's video presentation was very interesting (I recommend watching it)... He described how he tried to copy the WPI's methodology closely, and explained that even when people think that they are replicating the WPI's study, they might not be, because small differences (such as a difference in the 'annealing temperatures' and 'magnesium concentrations') can make a big difference in the results. It's interesting, after hearing him say that, that he is the only scientist to get positive results.

I think the big question is how close do you have to get? Do you need to use the same type of test tubes? The exact same reagants? That seems to be what its getting down to. It's hard to tell for us to tell, for sure....Almost all the studies say they looked for XMRV and then cite the Lombardi paper - but from what Bob says there are differences.

(Did Lo really mention annealing temperatures?

XMRV desperately needs a positive study. Its not just Singh; its the accumulation of all these studies - over 25 now that have been unable to pick up even the background level (6% or whatever it is) of XMRV. Could they all be doing it wrong??? Could it be that slippery??? Its baffling.

Dr. Mikovits has been mentioning how early it is yet and how long it took HIV to get straightened out. I quickly looked up the early days of HIV (225,000 studies back!) 25 years ago, and yes, the PCR test did take time to come around (it was in the early days of PCR) but once they found that antibody test and they found it pretty early - I couldn't find any problems....there was no long string of HIV negative studies.....If you think about it - problems were more likely to happen in HIV than XMRV because HIV is sooooo variable but that test worked early on........no one, unfortunately, has replicated the WPI's antibody results either....There's really very little good news.

The WPI needs one good study from one good lab. The Levy study could certainly do it; very well known and respected researcher reportedly replicating the culture protocols to a T.....That would turn things around.

 

[Cort]

Cort I'm begaining to think that there aren't any true repilation studies under way.

I think if what you mean is a lab that follows exactly the same procedures, the same reagants, the same test tubes...whatever - I think you're right - except for the BWG and Lipkin studies. Ironically, even they probably won't be true replication studies - they certainly won't do what the first study did - since that protocol was updated later - and things have probably changed since then as the science has progressed.

The important thing, though, is that the WPI will be able to use the techniques that they have found work the best......I don't think you can do any better than that.

Can you imagine being in the room when the codes are broken?.....

 

[Bob]

Can you imagine being in the room when the codes are broken?.....

Can we buy tickets? lol (But the tension probably wouldn't be good for our health!)

The Levy study could certainly do it; very well known and respected researcher reportedly replicating the culture protocols to a T.....That would turn things around.

Cort (or anyone else), do you have any more info about the Levy study?

(Did Lo really mention annealing temperatures?

Yes, he really did!

 

[omerbasket]

Cort, until there is the results of the Lipking and BWG studies, or until we would have at least 2-3 full replication studies - down to the tubes, reagents and stuff - this issue cannot be settled with negative results. If you had positive results using different methods - it could be finished without full replication studies. But if you have negative results using methods that differ from the orignial methods, even if the difference is tiny - than you haven't shown that the original study was incorrect, and therefore, the issue is not settled.

 

[Rrrr]

does anyone know, when is the levy study due to be finished?

 

[Graham]

I reckon it's a bit like hunting for wild large cats in the UK. If Y had heard that Johnny Kingdom set out some dead chickens in a particular spot on Exmoor, and the next morning found panther-like footprints all around and the carcasses gone, I would be interested and partly convinced. If I then heard that David Attenborough set out some dead chickens in a secluded spot on Dartmoor and found some tracks that were indicative of Lynx, I'd suspect they were onto something. If I then heard of ten psychologists setting out traps baited with bacon in Hyde Park who, finding nothing, declared that Kingdom and Attenborough had got it wrong, I'd ignore them. It's not simply what is found, it is the level of respect we have for the experience of the people doing the investigation, and for how thoroughly they looked. That's why Singh's study is the first for me that makes me hesitate - but not finding is not the same as not being there.

I do tend to do a line in crummy analogies, don't I? Sorry for lowering the tone.

 

[maryb]

Glad you apologised for that one Graham

 

[Wally]

The Levy study is done. It has been submitted for publication and it is now just a waiting game.

 

[Bob]

The Levy study is done. It has been submitted for publication and it is now just a waiting game.

I think I can guess the result.

Does anyone know where to find any information about Levy's study?

 

[Angela Kennedy]

I reckon it's a bit like hunting for wild large cats in the UK. If Y had heard that Johnny Kingdom set out some dead chickens in a particular spot on Exmoor, and the next morning found panther-like footprints all around and the carcasses gone, I would be interested and partly convinced. If I then heard that David Attenborough set out some dead chickens in a secluded spot on Dartmoor and found some tracks that were indicative of Lynx, I'd suspect they were onto something. If I then heard of ten psychologists setting out traps baited with bacon in Hyde Park who, finding nothing, declared that Kingdom and Attenborough had got it wrong, I'd ignore them. It's not simply what is found, it is the level of respect we have for the experience of the people doing the investigation, and for how thoroughly they looked. That's why Singh's study is the first for me that makes me hesitate - but not finding is not the same as not being there.

I do tend to do a line in crummy analogies, don't I? Sorry for lowering the tone.

Actually I love the analogy Graham - but I think you're wrong as to why the psychologists with the bacon in Hyde Park are not so plausible. It should never be because the eminent and popular TV presenter was involved, as these are appeals to authority (ESPECIALLY in the field of cryptozoology!). It should be because Hyde Park is a busy urban park where there have been no sightings of big cats, and no place for them to develop into a hidden population.

I'm agnostic on the issue of big cats on the moors by the way. I remember one woman on Richard and Judy saying she came up against a black, labrador sized cat in the dark in Scotland, and I wondered if maybe it was a black labrador she come up against.

 

[Bob]

Actually I love the analogy Graham - but I think you're wrong as to why the psychologists with the bacon in Hyde Park are not so plausible. It should never be because the eminent and popular TV presenter was involved, as these are appeals to authority (ESPECIALLY in the field of cryptozoology!). It should be because Hyde Park is a busy urban park where there have been no sightings of big cats, and no place for them to develop into a hidden population.

I agree with you Angela, but I think that's exactly what Graham meant with his analogy... He meant that we should look at the quality of the research and the methodology of the research, and not just at the final results...

I can't help feeling though, that the bacon in Hyde Park would probably have been nibbled by mice, which left mice footprints, and the psychologists would then accuse the other researchers of mistaking cat footprints for mouse footprints, and then concluded that the other studies had only detected mice, and not large cats! There would then have been a very lavish press event to announce the news, and all the eminent scientists would publicly announce how wonderfully designed the Hyde Park mouse-contamination study was. And then a multi-million dollar government-funded study to investigate large cats in Hyde Park would be announced, in order to prove that there aren't any large cats in the country.

 

[ukxmrv]

But we do get foxes around Hyde Park and they would love the bacon.

The psychologists would merely have to reclassify the foxes as being big cats - and there we are!

 

[Angela Kennedy]

I can't help feeling though, that the bacon in Hyde Park would probably have been nibbled by mice, which left mice footprints, and the psychologists would then accuse the other researchers of mistaking cat footprints for mouse footprints, and then concluded that the other studies had only detected mice, and not large cats! There would then have been a very lavish press event to announce the news, and all the eminent scientists would publicly announce how wonderfully designed the Hyde Park mouse study was. And then a multi-million dollar government-funded study to investigate large cats in Hyde Park would be announced, in order to prove that there aren't any large cats in the country.

Well - that's hard to argue against...

 

[Bob]

Well - that's hard to argue against...