The Race to Retract Lombardi 2009...

[kurt]

With Silvermans retraction of his sequences from the Lombardi 2009 Science paper, the people running the 0/0 studies have huge problems.

The VP-62 sequence is now known not to correspond to the gammaretroviruses detected by Lombardi et al. It is also known that Silverman's primers are capable of detecting the VP-62 plasmid and NOT capable of detecting the gammaretroviruses which exist in the Lombardi CFS patients.

I disagree, there is no trouble for the 0/0 studies in the Silverman sequence problem. If everyone had just run gag and env sequences, as WPI did,then maybe this would cause some issues. Fortunately, most of the 0/0 studies used broader, and more sensitive tests, including the pol gene, which MUST be present in a viable virus, even if it is integrated in the host DNA. And the pol gene is stable in the entire MLV family (it is the 'conserved portion' of the viral genome that is required for replication and can not mutate or the virus loses viabillity). Therefore, the specific VP-62 MLV sequence that was retracted is not changing the general conclusions. The 0/0 studies overwhelmingly demonstrated that there is no MLV family in ME/CFS patient samples, contradicting the WPI hypothesis.

The WPI and NCI tried to use Silverman's primers on the patients who tested positive for their nested PCRs, but could detect nothing. A great number of the 0/0 studies used Silverman's primers alone or in combination and thus their negative findings are invalid.

Not true, the negative findings are still valid, they were testing more than what WPI had tested, these labs used more sensitive and more modern tests than WPI, and they tested for the conserved portion as I mentioned above, which WPI did not. This is false logic, Silverman's primers are not the only variable here, and you can not conclude that their failure invalidates all the 0/0 studies, just not true.

The slide being so viciously attacked demonstrates that the viruses are normally in a latent state which is maintained by methylation of the provirus. If one removes the methyl groups as shown by the experiment in the slide and the virus becomes active.

That gel showed nothing significant and is far less important than the PCR testing which has conclusively ruled-out MLV species infection in ME/CFS blood.

So what, says a chorus of voices - well, the virus or viruses are integrated into G-C rich areas called CpG islands. These are extremely difficult if not impossible to amplify using standard PCR approaches.

Maybe in the 1990s that would have been true, with older PCR test designs like those WPI used. However, modern PCR testing, like was used in most if not all the 0/0 studies, takes this into account, they know about the G & C rich areas, their triple hydrogen bonds, and can extract the DNA sequences successfully.

Any PCR which has been adjusted to detect the VP-62 clone in a spiked sample would not have a prayer of detecting a human MLV related gammaretrovirus integrated into such a region even if the virus did have the same sequence as VP-62 which it or they do not.

As just mentioned, the DNA was properly amplified, and some of the studies tested against live XMRV viral samples, so in fact they had no trouble detecting MLV integrated into human cells, including in the G&C rich areas. And again, unlike WPI the outside labs tested the pol gene, so does not matter whether VP-62 was 'recalled' or not, its pol gene is the same as the rest of the MLV family, by definition it has to be, or it is not in the family.

Thus the combination of Silvermans retraction and the discovery that demethylation can activate the virus or viruses in question completely invalidates ALL the negative 0/0 studies

I've already disproved this claim. There is ABSOLUTELY NO TRUTH to the above statement and nothing has been invalidated except the original WPI hypothesis and the Science study.

Stoye, Coffin and ERV and their ilk must get Lombardi retracted at all costs before the scientific community as a whole realize that.

So there is a conspiracy here? Why on earth would these people conspire against us? They would not, and have not, and the facts can speak for themselves to those who know the science, or have access to credentialed researchers, which I was lucky to have two years ago.

I realize some people want to continue propping-up their hopes for XMRV, or now for some other MLV/HGRV, but they need to look somewhere else than what was presented here. The argument that Silverman's retraction invalidates the 0/0 studies is not based on fact.

 

[kurt]

Why don't they just change the title to "[preliminary] evidence of HGRV infection in pwME" or whatever title the data support. I agree that without sequencing of the HGRVs the paper doesn't tell us as much, but it still contains valuable, scientifically valid information. Why retract it then? It seems there is only calls for paper retraction when there is fraud. So why retract Lombardi when there are no calls to retract all hundreds of fraudulent papers and book chapters on ME by Wessely et al.? There is certainly bias against bona fide ME research and this is an example of it.

I don't think the Science paper can be rescued and expect a full retraction at some point. And fraud is not the only reason for retraction, if researchers can find alternate explanations for most or all of the findings, then they should retract the paper. That is what will probably happen in this case. Personally I think the excitement about the gels is excessive as those were not very important to the primary issue, which is whether PCR can detect the sequence of XMRV in CFS patient blood. Even though I don't believe XMRV, MLV, or HGRV have a prayer of a chance of explaining ME/CFS, I think we need to leave WPI and Mikovits alone at this point, let them re-trench. We don't need to set a vindictive precedent in ME/CFS research. What will that tell future researchers?

BTW, I think your statement about retracting all the nonsense studies, particularly the psych studies, is brilliant. We seriously should have a campaign to get those out of the literature.

 

[barbc56]

I don't think the Science paper can be rescued and expect a full retraction at some point. And fraud is not the only reason for retraction, if researchers can find alternate explanations for most or all of the findings, then they should retract the paper. That is what will probably happen in this case. Personally I think the excitement about the gels is excessive as those were not very important to the primary issue, which is whether PCR can detect the sequence of XMRV in CFS patient blood. Even though I don't believe XMRV, MLV, or HGRV have a prayer of a chance of explaining ME/CFS, I think we need to leave WPI and Mikovits alone at this point, let them re-trench. We don't need to set a vindictive precedent in ME/CFS research. What will that tell future researchers?

BTW, I think your statement about retracting all the nonsense studies, particularly the psych studies, is brilliant. We seriously should have a campaign to get those out of the literature.

Kurt, I'm not sure that a campaign to do this would actually be fruitful or were you saying this tongue in cheek?

Better, would be a another study, designed around the criticisms of the PACE study. This is not saying going in with a set of preconceived assumptions but a hypothesis building upon the existing research, using different criteria or methods to see what results would occur.

Probably wouldn't happen, but certainly food for thought.

I certainly agree about not setting a vindictive precedent. Whether based on fact or not, the notion that we are all out for blood will not help the research continue.

 

[Angela Kennedy]

The main thing is to find out if we have retroviruses. Anyone doing research could have asked WPI about the methods for the slide in question. It's probably printed somewhere. Dr. Mikovits usually confirms what Gerwyn says about science. V99 was wrong about the slide being different but anyone could make up their own mind about that. I think there was previous mention of changing the patient ID numbers, maybe in the early prohealth video presentation (which was half transcribed). About believing all the scientists who know all about PCR, I wonder if they read all the papers involved and MLV literature themselves? Most of the studies try one method which they find does not work. They don't try looking another way.

One of the biggest criticisms from the beginning by the science community is that WPI offered the test. From the patients point of view, we wanted it, even if it was experimental, and we knew there were many delays in Lombardi's lab figuring it out, and they dropped PCR very early. Scientists should appreciate that she has been against it from the start. I hope the Lombardi and Mikovits papers are in the library here for patients.

Thanks Citybug,

The only thing I would say that I believe V99 was NOT saying the slides were different. V99 was saying at least aspects of the slides were the same but that this was not in itself a problem.

But I believe there is also concern about 'doctoring' of the images put up by ERV? Just to confuse matters even more!

I do think it's funny now that some people are trying to deem other people's position unreliable on the basis of whether they judged a poor, fuzzy image 'the same' or 'different' (not you citybug).

 

[jace]

Hi Esther, you said

From what I saw, V99 was posting on behalf of Gerwyn, and started by claiming that the images were not the same.

But that is not the case, V99 is a young woman, often posting in a hurry from a smartphone (and not always so that her meaning is clear) and Gerwyn is an older man, housebound and as sick as any of us. They are not the same person, and cannot be conflated, so my points stand.

Angela pointed out

The only thing I would say that I believe V99 was NOT saying the slides were different. V99 was saying at least aspects of the slides were the same but that this was not in itself a problem.

But I believe there is also concern about 'doctoring' of the images put up by ERV? Just to confuse matters even more!

removed wrong information.

I hear good things about Rich Van K's protocol. Methylation may well be one key. I'd like to see that worked on, as well as a blinded, well funded and monitored clinical trial of ARV's. All I want for Christmas is a cure that works....

 

[Firestormm]

Morning Jace,

I am afraid V is wrong about that. The figure in question was 2C and the legend from Lombardi et al reads:

'(C) Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) OR from CFS patients (lanes 3 and 6) were analyzed by Western blots using rat mAb to SFFV Env (top panel) or goat antiserum to MLV p30 Gag (bottom panel). Lane 8, SFFV-infected HCD-57 cells. Molecular weight (MW) markers in kilodaltons are at left.'

http://www.sciencemag.org/content/326/5952/585.full

That of course is Lombardi et al. The headings were different on the Ottawa slide although the experiment was the same.

 

[jace]

Spot on Fire. Bit too early in the morning, I should have checked my copy of Lombardi 2009. I have now. I have also removed the misleading info in my previous post.

 

[Sam Carter]

... The WPI and the NCI had, up until BWGIII, not had VP62 or the 22rv1 cell line in their labs. Silverman's prostate cancer sequences still stand. ...

Hi Jace,

To respond to one particular point in your post, I'm fairly sure the WPI/NCI did have VP62 in their labs. It's actually documented in the supporting online material for Lombardi:

p7

"""""""""""""""
Lysates were prepared from XMRV-VP62-infected Raji (lane 1), LNCaP (lane 2) or Sup-T1 (lane 3).
"""""""""""""""

Jon Cohen and Martin Enserink also mention it in their article 'False Positive':

"""""""""""""""
She soon enlisted Ruscetti, who had worked in Gallo's lab when it
discovered HTLV-I, to screen blood samples from Peterson?s patients
for viruses. Intrigued by the RNase L link to XMRV, Mikovits and
Lombardi -- who by then had joined WPI as well -- met Silverman in
October 2007 at a prostate cancer conference in Lake Tahoe, where
they discussed the possible role of XMRV in CFS. Silverman was
happy to collaborate and sent WPI a clone of the virus, known as VP62.
The institute could use it as a reference to start hunting for the virus in
CFS patient blood samples that Peterson had stored.
"""""""""""""""""""

 

[Esther12]

There's nothing there to support your assumptions Esther, where is it?

The BWG does not say that this was a test to see if XMRV/HGRV's could be found using the same conditions as the original papers.

I never thought that this was an attempt to exactly re-create the conditions of any of the past papers. Seeing as the samples from patietns and controls had come from different sources, they would not want to do so.

I assumed that the study was designed to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. To support this assumption we have the fact that the BWG said:

Studies will evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility; assess performance on specimens represented in existing blood donor repositories, and determine the prevalence of XMRV in donors.

When you say "I can see nothing" what I hear is "I cannot prove my assumptions".

It was not my claim I could see nothing in support of. You had said:

The BWG was never designed to see if any lab could distinguish controls from positive patients. It was designed to see if a test could be found to work under bulk conditions - it failed and the disgrace is that we do not have a test.

I keep asking why you think this. I'm really interested to know. What has led you to believe this?

If the BWG merely wanted to replicate the Science paper or the Alter/Lo paper then they would have provided the same conditions right from the choice of blood tubes and control of all the process in the labs.

They didn't do this. This is no test.

They didn't want to do that. They wanted to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. It's possible that some part of the collection process needs to be done in an inexplicably specific manner, but we have no specific reason to believe this is the case, or to believe that Mikovits or anyone else had requested different collection procedures prior to the BWG test being carried out.

I'm not saying that there is any conspiracy here. It may be that the conditions were never going to work. I'd like to see a proper post-mortem by all the parties explaining exactly what went wrong. I have no idea why it didn't work. Dr Mikovits spoke briefly at the IiMe conference about her concerns on their blood tubes and contents. She said that they were asked to develop tests under those conditions and that it was not the blood tubes/contents they would have used.

The paper published was the post-mortem.

With Mikovits's name on it, they concluded:

In summary, our study demonstrates that no XMRV/PMLV
assay in any of the nine participating laboratories could
reproducibly detect XMRV/P-MLV in fifteen subjects
(fourteen with CFS) who had previously been reported as
XMRV/P-MLV-infected usually at multiple time points and
often by multiple assays (2, 4).

If there was any identifiable problem with the process, they and she could not find it. It could still be an error, but this is the sort of study I've been wanting done since the Science paper first came out (although the size of the sample was apparently limited by difficulty getting known positives from WPI and Lo/Alter), and I can't see any reason to believe that the results are in error.

The end result is that we don't have a test for HGRV's in the blood supply (bad) but at the same time to claim that the results have any bearing on Lombardi et al and Alter/Lo is just a feeling and a theory. Also to claim that it was designed to have a bearing on these papers isn't supported by your postings from the papers.

The end result was:

In summary, our study demonstrates that no XMRV/PMLV
assay in any of the nine participating laboratories could
reproducibly detect XMRV/P-MLV in fifteen subjects
(fourteen with CFS) who had previously been reported as
XMRV/P-MLV-infected usually at multiple time points and
often by multiple assays (2, 4).

That does have a bearing on the likely accuracy of both the WPI and Lo/Alter papers.

I always understood the BWG was to test rapid throughput tests specifically for bloodbank use.

I dont think it was concentrating on the kind of analysis required for research on a novel retrovirus.

Why do you think that?

But that is not the case, V99 is a young woman, often posting in a hurry from a smartphone (and not always so that her meaning is clear) and Gerwyn is an older man, housebound and as sick as any of us. They are not the same person, and cannot be conflated, so my points stand.

V99 sometimes seemed to be posting on behalf of Gerwyn, and often writes in a similar way, so I'm often unsure who the true source is. It could be that V99 just garbles Gerwyn's opinions, but the new claim that Silverman's retraction invalidates all of the negative studies, including those like Singh who had followed up on the work from Lo/Alter, seems similarly inaccurate.

I don't normally visit the other forum, and they stopped public access recently, but since this thread a few people have sent me some bits like this (posted by V99, but some from Gerwyn?):

ERV has switched the labels from one western blot in Lombard et al. that was looking for the presence of ENV protein and ascribed them to the western blot data presented by Mikovits in Canada, when that western blot was constructed to detect the presence of GAG protein. The control lane in the western blot data was for gag protein and not env protein as claimed by ERV.

There are 2 WB in Lombardi fig 2C.

The labels on the top one don't apply to the bottom one.

She, or her mysterious crapologist, has said the labels in the top slide (Env) go with the slide from Canada, which it cannot because the Canada slide is Gag.

ERV has accused Dr Mikovits of presenting western blot data in Canada which was an exact replica of a slide already published in Lombardi with the aim of decieving her audience.

This according to ERV represented Dr Mikovit's data

Its quite clear, there are 8 lanes.

1-- Normal
2-- Normal
3-- 1235
4-- Normal
5-- Normal
6-- 1236
7-- Normal
8-- SFFV-infected HCD-57


This is the equivalent wetern blot data presented in Lombardi et al.


Now this is the data presented by Dr Mikovits in Ottawa.


Do they look the same to you

ERV has assumed that the labels given to the lanes in the top diagram in figure C also apply to the bottom diagram

Had she understood any of the data, she would have realised that this is not possible, because the top diagram referrs to a western blot looking at the presence of env protein and lane 8 the control lane is a control for the env protein, while the bottom diagram refers to a western blot of GAG and lane 8 is a control for a GAG protein.

No they don't match. They have had to move the lanes closer for one and still there are reasons why they don't match.

The two WB in Lombardi are different.

Mikovits has done nothing.

The slide at the conference is gag data. The control for that is HCD-57, not SFFV. SFFV is only used for env.

The top one of the 2 WB is the one the headings go with.

Wrong labels meeker. Also, when you combine like that, you can make an elephant and a mouse look the same. The are on top of one another and you cannot possibly compare them blurry.

The numbers on the left are also not the same and they don't line up.

The point is even with a totally different experiment the slide presented in Ottowa should look identical to the diagram in figure C. Nothing to do with subterfuge just simple science.

The evidence that ERV doctored the slides in her blog is attached below

The images have been doctored. She has taken Dr Mikovits's slide and pretended to just expand it, when in fact she has altered it to fit her little conjuring trick. She has misrepresented the slide presented in ottowa.

I wonder how her supervisor feels about this. Surely this is not the standard of behaviour any institution expects from one of its students.

When I saw, there were images of clearly the same resault, but with different resoloutions and contrast, and people claiming that they were different. Wasn't the whole thread called something like 'ERV may be giving up virology because of XMRV mistakes'? The first few pages of it were like entering an alternative reality.

Thanks Citybug,

The only thing I would say that I believe V99 was NOT saying the slides were different. V99 was saying at least aspects of the slides were the same but that this was not in itself a problem.

But I believe there is also concern about 'doctoring' of the images put up by ERV? Just to confuse matters even more!

I do think it's funny now that some people are trying to deem other people's position unreliable on the basis of whether they judged a poor, fuzzy image 'the same' or 'different' (not you citybug).

There were claims that the images were different. There were claims that they had been doctored to look the same (even though everyone now acknowledges that they are the same). There were claims that different tests with the same results should have the same artefacts visible. There were claims that the labelling in Science only referred to the top half of the western blot. Anyone could see this stuff was wrong, and while you may have been uncertain about that, it should certainly mean that you no longer trust those who claim expertise on these matters, and got it so wrong.

 

[Firestormm]

Esther - that was hysterical lol x

 

[currer]

I must admit I havent followed this area of the debate in detail, because I think the information available to us is too incomplete to support the conclusions that are being drawn for it.

I trust the integrity of Mikovits and Ruscetti and I prefer to wait until I hear more from them to clarify what went on in the BWG trial.

I would just like to ask where retraction of Lombardi would get us? And why some here want a retraction of this paper?

As I have said on a couple of other threads, even retraction of HGRVs/XMRV in ME will not resolve all the problems created by the discovery that these viruses infect humans, unless Silverman is planning a complete retraction of his prostate cancer findings.

So are Ruscetti and Mikovits just the beginning? Are all findings linking HGRVs to human disease going to be retracted?
And how safe will that be, considering that we are poised to release gene vectors based on these very viruses, with all the danger of recombination and spread into the human population that will entail.

It seems to me that there must be powerful financial interests at play which stand to loose massively if HGRVs are confirmed. So it is all the more important not to rush to judgement, but to wait and evaluate the science impartially, and that means all of it, not only the link to ME.

Personally I think that investigating other viruses will not take our cause very far, because none of them could be shown to cause all cases of ME. We will be left with the same problem of proving that ME is a biomedical disorder, the insurance firms will be able to refuse to compensate those sick, and we will be led round the circle of psychogenic explanations all over again.

Politically it is much better for us to support the HGRV hypothesis, until we can be certain that it is mistaken. We have no idea where this science may lead. We are looking into the unknown and other unexpected causes may yet emerge from the retroviral investigations. I find it incredible, given Dr Snydermen's data that a retrovirus is not involved.


Surely we as a community are politically astute enough to realise that some interests will massively loose out should ME be accepted as it is - as a biomedical disorder. How much would it cost the insurance companies in the US to pay back all the compensation denies to sufferers for their disability over the past twenty years?

We need to be alert to attempts to divide our community, to confuse us as to where our best interests lie.

What is so wrong in allowing the science to continue? Investigation of HGRVs is in its infancy. This call for retraction makes no sense and is highly sinister.

 

[ukxmrv]

Esther,

I have been through your long reply but I still cannot see any facts to back up your assumptions about the BWG. It's just more opinion, opinion and opinion. Quoting from the paper and then interpreting any hint of an ideas to support your feeling just simply isn't going to work. All the comments you have reproduced have holes in them and could be argued any way. That what committee or group produced reports can look like.

I can't see how you would see a paper published at the last phase of the BWG to be a post-Morten of the entire event. It's obviously not true. It's a paper published by a group and doesn't contain comments from each author on what went right and wrong. That's what I would like to see.

The BEG was never designed to be a test of the Lombardi paper or the Alter/Lo paper so I am still at a loss to see why you think that it should influence any thoughts or the validity of the published work.

It may be your opinion (which is fine of course) but it is not a fact and was not the intention of the BEG.

The BEG results have a bearing on any tests used under their conditions and at that time only. It would be illogical and unscientific to argue otherwise.

Changes to a published protocol such as specifying a new condition creates a new protocol.

You don't know what was agreed, specified and laid down as an absolute requirement in any part of the process do you? Keeping an open mind (and remember I heard Dr Mikovits speak at IiME) would make this an important question and one to determine before judging a process.

These are the important questions we need answers to and it may be a wise idea to suspend any judgements until it is done.

Once again if you have any new concrete evidence to support these feelings of yours please present them here as I am interested in getting to the bottom of what happened.

 

[Esther12]

Esther - that was hysterical lol x

Oops, but thanks? I really don't mean to be too hostile on any of this. I know that there's still some uncertainty here, and I also know how difficult it is to be detached about things which affect ones own health. Even if I think that some people are really clearly wrong, I don't want to be bullying about it - I just think that we need to do more to reject some of the errors being made on this forum and the other - the 'debate' over the slide was a bit of a wake-up call to me.

I would just like to ask where retraction of Lombardi would get us? And why some here want a retraction of this paper?

Personally, I think it would be a bad mistake to retract the paper now, prior to Lipkin. Especially if the authors do not think it should be retracted, and the prostate cancer papers are not retracted. The paper explicitly links XMRV to CFS, and it seems that everyone know accepts that this is false - so there is a good reason for retraction, but I don't think doing so will bring any benefit, and could mean that some people will then be less likely to trust the Lipkin study, and ignore the results from that if they are negative.

So are Ruscetti and Mikovits just the beginning? Are all findings linking HGRVs to human disease going to be retracted?

To me, it now looks very likely that the prostate cancer studies were the result of error. They've been less controversial, have not had the sort of blinded testing we saw under the BWG, and so their may not be the same drive to retraction. I wouldn't be surprised if the authors themselves decided to retract their own work.

It seems to me that there must be powerful financial interests at play which stand to loose massively if HGRVs are confirmed. So it is all the more important not to rush to judgement, but to wait and evaluate the science impartially, and that means all of it, not only the link to ME.

Personally I think that investigating other viruses will not take our cause very far, because none of them could be shown to cause all cases of ME. We will be left with the same problem of proving that ME is a biomedical disorder, the insurance firms will be able to refuse to compensate those sick, and we will be led round the circle of psychogenic explanations all over again.

Politically it is much better for us to support the HGRV hypothesis, until we can be certain that it is mistaken. We have no idea where this science may lead. We are looking into the unknown and other unexpected causes may yet emerge from the retroviral investigations. I find it incredible, given Dr Snydermen's data that a retrovirus is not involved.

I really disagree. I can't think of anything more likely to encourage scientists and doctors to believe that CFS is the result of abnormal illness beliefs than a bad a patients insisting that they have evidence of a virus that only Mikovits can detect.

As ever, it's best for us to try to look dispassionately at the evidence, and to allow that to guide our beliefs. It could well be that we would be treated more fairly if it was believed that CFS is caused by XMRV, but campaigning on the belief that CFS is caused by HGRV despite evidence to the contrary is going to be entirely harmful.

Surely we as a community are politically astute enough to realise that some interests will massively loose out should ME be accepted as it is - as a biomedical disorder. How much would it cost the insurance companies in the US to pay back all the compensation denies to sufferers for their disability over the past twenty years?

We need to be alert to attempts to divide our community, to confuse us as to where our best interests lie.

What is so wrong in allowing the science to continue? Investigation of HGRVs is in its infancy. This call for retraction makes no sense and is highly sinister.

There's no way that there is a cover-up of an identifiable retrovirus circulating in the blood supply.

When the first negative paper came out from Wessely, I could not have been more certain that this was not a cover-up. No-one would be stupid enough to intentionally try to hide evidence of an identified retrovirus causing CFS and circulating in the blood supply, it would be certain to come out in the long-run (this is also why I don't think it's at all likely that the positive papers were the result of intentional deception). A new retrovirus circulating in the blood supply would pose a risk to 'real people', not just mere CFS patients! Pharmaceutical companies would want to make fortunes by providing life-long ARVs. People would not want this thing to keep spreading!

CFS is usually treated badly. But retroviruses are treated seriously, and I don't see any reason to think that a political desire to hide the association between HGRVs and CFS is the cause of the growing evidence that they are not associated.

 

[Bob]

I don't think the Science paper can be rescued and expect a full retraction at some point. And fraud is not the only reason for retraction, if researchers can find alternate explanations for most or all of the findings, then they should retract the paper. That is what will probably happen in this case. Personally I think the excitement about the gels is excessive as those were not very important to the primary issue, which is whether PCR can detect the sequence of XMRV in CFS patient blood.

I am bracing myself for a full retraction, but I don't think it will be related to the gels either.

Even though I don't believe XMRV, MLV, or HGRV have a prayer of a chance of explaining ME/CFS, I think we need to leave WPI and Mikovits alone at this point, let them re-trench. We don't need to set a vindictive precedent in ME/CFS research. What will that tell future researchers?

Thanks Kurt, I think that's a helpful thing to say. Researchers and institutes should be allowed to make mistakes, if they are honest mistakes.

BTW, I think your statement about retracting all the nonsense studies, particularly the psych studies, is brilliant. We seriously should have a campaign to get those out of the literature.

I'm all for this! Let's start it here, on PR, now!

 

[Esther12]

Esther,

You posted after I started typing my last reply... which means I was typing for 30 mins! *gulp*

I have been through your long reply but I still cannot see any facts to back up your assumptions about the BWG. It's just more opinion, opinion and opinion. Quoting from the paper and then interpreting any hint of an ideas to support your feeling just simply isn't going to work. All the comments you have reproduced have holes in them and could be argued any way. That what committee or group produced reports can look like.

I don't see how you can argue away the fact that this quote supports my assertion that the BWG wanted to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility:

Studies will evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility; assess performance on specimens represented in existing blood donor repositories, and determine the prevalence of XMRV in donors.

You've not be providing any countervailing evidence for your claim that:

The BWG was never designed to see if any lab could distinguish controls from positive patients. It was designed to see if a test could be found to work under bulk conditions - it failed and the disgrace is that we do not have a test.

I don't see why this claim would be made about the BWG - particularly as the key problem I have with the study is that it looked at such a small number of samples!

I can't see how you would see a paper published at the last phase of the BWG to be a post-Morten of the entire event. It's obviously not true. It's a paper published by a group and doesn't contain comments from each author on what went right and wrong. That's what I would like to see.

I don't know what you mean by post-mortem, but the paper was an attempt to present and asses the results from the BWG.

The BEG was never designed to be a test of the Lombardi paper or the Alter/Lo paper so I am still at a loss to see why you think that it should influence any thoughts or the validity of the published work.

I don't think that anyone will ever try to recreate every exact condition of either of those papers. It would probably be impossible to do so. If the WPI had thought that a particular form of collection was necessary, they could have requested it.

You don't know what was agreed, specified and laid down as an absolute requirement in any part of the process do you? Keeping an open mind (and remember I heard Dr Mikovits speak at IiME) would make this an important question and one to determine before judging a process.

These are the important questions we need answers to and it may be a wise idea to suspend any judgements until it is done.

Sure - there are things we don't know. From what I've seen though, it seems like the study was well done, and designed to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. Just because some things are unknown does not mean that we should avoid making any judgement - some things will always be unknown, but we still need to try to decide what is most likely to be true.

Once again if you have any new concrete evidence to support these feelings of yours please present them here as I am interested in getting to the bottom of what happened.

There is no more evidence than the paper. I do not know why you think they were only examining bulk testing methods.

 

[Firestormm]

Hi Jace,

To respond to one particular point in your post, I'm fairly sure the WPI/NCI did have VP62 in their labs. It's actually documented in the supporting online material for Lombardi:

p7

"""""""""""""""
Lysates were prepared from XMRV-VP62-infected Raji (lane 1), LNCaP (lane 2) or Sup-T1 (lane 3).
"""""""""""""""

Hi Sam,

I hadn't actually noticed that mentioned in Lombardi et al. Wonder why it hasn't been mentioned before now? How very strange. I thought they were denying ever to have had the stuff. Or maybe that was the supporters? I don't know. I did see it in Cohen's article of course - think I posted his comments re-confirming it also - somewhere on here

Lombardi Supplementary Online Material: http://www.sciencemag.org/content/suppl/2009/10/08/1179052.DC1/Lombardi.SOM.rev.pdf

It refers to Figure S3. Not that I understand what it means or can ascertain if this was done at the WPI. I assume it was from what you said.

Thanks

 

[Bob]

I disagree, there is no trouble for the 0/0 studies in the Silverman sequence problem. If everyone had just run gag and env sequences, as WPI did,then maybe this would cause some issues. Fortunately, most of the 0/0 studies used broader, and more sensitive tests, including the pol gene, which MUST be present in a viable virus, even if it is integrated in the host DNA. And the pol gene is stable in the entire MLV family (it is the 'conserved portion' of the viral genome that is required for replication and can not mutate or the virus loses viabillity). Therefore, the specific VP-62 MLV sequence that was retracted is not changing the general conclusions. The 0/0 studies overwhelmingly demonstrated that there is no MLV family in ME/CFS patient samples, contradicting the WPI hypothesis.

Interesting info thank you Kurt.

One thing that hasn't been focused on much is the WPI's serological results.
The anti-body research is worth following up, whether HGRV's are involved or not.
It has the potential to lead to further insight into ME, and to be used as a biomarker, whether HGRV's are inolved or not.
And as far as I can recollect (which doesn't mean much) the negative studies haven't addressed the serological results.
(Does anyone know if I'm right about that?)

 

[Sam Carter]

Interesting info thank you Kurt.

One thing that hasn't been focused on much is the WPI's serological results.
The anti-body research is worth following up, whether HGRV's are involved or not.
It has the potential to lead to further insight into ME, and to be used as a biomarker, whether HGRV's are inolved or not.
And as far as I can recollect (which doesn't mean much) the negative studies haven't addressed the serological results.
(Does anyone know if I'm right about that?)

Hi Bob,

Multiple groups, including the WPI itself and NCI/Ruscetti, have been unable to replicate the serology findings presented in Lombardi.

 

[ukxmrv]

I'm not really sure why you posted that reply Esther.

You didn't respond to any of my points. For example I stated what I would like to see as a post mortem but you typed words but didn't address it. You then stated as a reply to a further point that it appeared like a well designed study. Once again demonstrating that you are basing your judgements on your opinion and cannot provide a scientific argument.

Once again you admitted that you did not know what restrictions that the WPI was under but unlike me you don't seem interested in knowing what they were or importantly with-holding judgement until you know.

As far as I can tell you are unable to provide any data or specifics on why the BWG should have any bearing on the Lombardi Science paper or the Alter Lo paper.

You seem to be arguing that because there was no enough data in the BWG to make this distinction clear for you in providing an argument, then you are still happy to hold the opinion that the BWG could be used to judge these two different papers.

Once again I would state that you are entitled to your opinions but that you cannot provide a basis for this. For me there are too many unknowns and I will be following further data and information as it develops to fill in the holes.

 

[Bob]

Hi Bob,

Multiple groups, including the WPI itself and NCI/Ruscetti, have been unable to replicate the serology findings presented in Lombardi.

Yes, I think that Dr Singh looked for antibodies, didn't she?
And did they do serology work in the BWG?
(Sorry, brain like a sieve as usual!)