The Race to Retract Lombardi 2009...

[bertiedog]

I think for some people belief in something becomes part of their identity / worldview. Data that questions that belief is treated as an attack on their ego - prompting an essentially emotionally motivated defense. When people are in emotional defense mode their rational side is not available to be engaged. Most human beings are not constitutionally equipped to engage in science because they subject ideas that they agree with to less critical thinking than ideas that they disagree with - i.e. they fit the data to their hypotheses not the other way around.

Judy Mikovits is the kind of person that inspires faith and support among patients. She expresses concern for patients and states that she is doing everything she can to help us. She maintains a posture of confidence, making bold assertive statements. I have not heard many statements from her admitting to any errors or mistakes on her part. Put together these are the attributes that inspire a following - a following which is emotionally disinclined to consider questions of competence. In addition Judy Mikovits possesses a powerful trump card: she can claim the reason other researchers cannot replicate her findings is because of bias against the disease. She is therefore able to place herself in a role similar to that of patients - a minority fighting a majority which is biased against it and disinclined to treat it fairly.

Folks in the scientific community understand the scientific details and can make competency judgments without this baggage. I don't see the opinions of these worlds converging. More likely the controversy will fade away due to other causes.

I think that this is an excellent description of what is going on and I also think that only time will sort out the massive divergence of opinion that has been created by the so called findings of the 2009 paper which have been proved to have been wrong.

Pam

 

[ukxmrv]

It's only an opinion Slovokia and highly insulting to patients like myself who have been reading all the research papers, talking with as many researchers from both sides of the fence as we can and coming to independant decisions and opinions about XMRV/HGRV.

If you read the book "And the band plays on" you will see lots of scientists putting themselves out on a limb, fighting, claiming contamination, cheating, trying to sabotage, denying others claims and becoming a minority over HIV/AIDS.

This is history. That's how it worked then. Some of the same players are still here now.

We need to learn from this history and see the XMRV/HGRV debate without wearing rose tinted spectacles on the other scientists involved or having romantic ideas on the players here.

This isn't a philosophy contest. Painting highly informed, educated and intelligent patients who want to see HGRV reseach continue as belonging to some sort of cult is not what this forum is about. That's unfair and biased.

I don't think that you should be so insulting to other patients who have examined the scientific evidence and just have a different opinion to yourself.

 

[jace]

Well said, ukxmrv. I note a touch of confirmation bias in bertiedog and Slovokia's posts. A touch of the pot calling the kettle black, methinks.

Lombardi 2009 can not on any stretch of the imagination be called "wrong". Silverman's VP62 sequencing was in error, perhaps. Most of that paper, as many other pieces of research can confirm, still stands.

The death of the HGRV hypothesis has been greatly exaggerated. For what reasons is a matter of conjecture. I prefer to await developments.

 

[Deatheye]

When facts don't shift the science they keep shifting the facts.

Didn't a lot of anti HGRV Scientist too? First XMRV was non existend. Then it was but not infection human cells. Then it was infecting human cells but just in laboratory not in Humans itself?
So why is this argument only usable against the Papers that find it?

Now we have what...aerosolization of hgrv causes ME/CFS.

Where does this actually come from? Not the first time I read this but I can't remember the source.

Now we have what...aerosolization of hgrv causes ME/CFS. Is that the new fact? Wow, I'm surprise that the 10% of the population that came down with this illness in Incline Village, CA as in other regions of the world, that the entire population of California have not succumb to this illness by now. It has been 30 years, you know.

Why does not everyone that has HIV get AIDS? Acording to that argument there should be noone thats immune against HIV. There also should be not one person on the world that has a genetic variation causing him to develop something other don't.

Since the majority of the scientist in field of retrovirology have categorically came out against HGRV, there can only be one other explanation. A Government conspiracy and cover-up. Well you just now join the ranks of the Wakefield/Dr. Stanislaw Burzynski/ Dr. Anjum Usman patient groups.

Did I ever say anything about conspiracy? So I assume everyone that once beliefed epilepsy is psychological is also involved in conspiracy? Everyone that once thought that AIDS does not exist is also?

So why did Mikovits put up sequencing to xmrv and VP62 when she could have put up her HGRV sequencing? She had plenty of time between the 2009 Science article and the BWG findings. I mean that is two years.

Ask Judy not me. How should I know. Thats one of those questions I would like to ask her. But I'm not going to make assumptions about this. I just don't know it.


Also why is Judy the only one det always gets the jumping on? There are other studys that found XMRV and MVLs.
If someone really thinks this is over and just bogus shoudn't it be logicall to apply this to all positiv papers?

One of those papers came from Dr. Bierger germany. First paper was negativ. Then he sad he's looking into it together with judy to find out what he is doing wrong. Then he comes up with a second paper positiv. Saying that Judys explanation made it able to find it. So she actually helps other people if they really try and ask her.

So he for example is one of those I'm really awaiting a statment.

Maybe it turns out XMV or MLV are not a problem after all. If so fine, let's celebrate it. But in my opinion theres still too much contradicting information out there. To much questions not answered. And to much papers still on the way that ask questions about XMRV / MLV / HGRV or however you wanan call it. If this topic is over there are a lot of scientists waisting there time. If it's so obivious that this is over I wonder how so many scientists still seem to e interested in such nonsence.

 

[Bob]

I think for some people belief in something becomes part of their identity / worldview. Data that questions that belief is treated as an attack on their ego - prompting an essentially emotionally motivated defense. When people are in emotional defense mode their rational side is not available to be engaged. Most human beings are not constitutionally equipped to engage in science because they subject ideas that they agree with to less critical thinking than ideas that they disagree with - i.e. they fit the data to their hypotheses not the other way around.

Just out of interest, who are you directing those comments at slovokia? Members of this forum?

 

[Bob]

I do not know if XMRV, or other retroviruses, are associated with ME or not, but there is still some evidence that suggests they might be, despite all of the negative research papers, the BWG study and the partial retraction.
There is antibody research that cannot be explained by contamination, and there is ongoing unpublished research, and so it is not surprising that some patients wish to see the research continue until it is fully resolved.
There is also evidence that XMRV is associated with prostate cancer, and Dr Singh's prostate cancer research is not easily explained by contamination.
XMRV definitely exists anyway, as a novel retrovirus that has an affinity for human tissue.
So I feel that I am entitled to take an interest in this field of research, and to discuss it as much as I wish to.

 

[slovokia]

Hi Bob,

Yes I think some posters on these forums display characteristics that I describe above. There is little point to naming names - it would just elicit yet more ego defenses and arguments. If we cannot agree on the implications of studies like the BWG we are not likely to agree about how to classify posters behavior patterns either.

One thing I wonder about the folks still supporting the 2009 Lombardi paper - what kind of evidence would have to be produced for you to change your minds about whether the only virus sequenced so far by Mikovits or her coauthors (i.e. XMRV) is associated with CFS/ME? I guess some folks think that Mikovits found some other virus which she has not yet sequenced? Does the 2009 Lombardi paper present any evidence for this other virus?

Everyone is free to believe whatever they wish and post their opinions in these forums. I am not out to censor anybody.

 

[Deatheye]

@slovokia
Did you actually read anything I wrote above? You fokusing again on only one study (mikovits)? You choose to take the BWG as the end of all overtrowing every positiv paper out there cause of what?

Hi Bob,
One thing I wonder about the folks still supporting the 2009 Lombardi paper - what kind of evidence would have to be produced for you to change your minds about whether the only virus sequenced so far by Mikovits or her coauthors (i.e. XMRV) is associated with CFS/ME?

Are we discussing about HGRV XMRV MLV all together? Just one of them? And beeing associated with CFS me or the generell ability of those to infect humans?
And how do you define association of the virus with cfs/me? I don't remember judy saying that they cause CFS / ME.

To really belief that this virus family is no health risk to humans I personally would need more questions answered.

How sure are we to be able to find it in blood under what circumstances? There are different papers that show it is hard to find in blood. For example the macaque study found the virus in blood for a certain time after infecting them. After that they coudn't find it in the blood anymore only in the organs. Searching in organs would also be a good idea.

There is also this paper:
http://forums.phoenixrising.me/show...gative-results-from-using-common-PCR-reagents

It shows that it's possible to have false negativs. It also says that a lot of the negativ papers had the variables neeeded to get false negeativs, and a lot of papers didn't even state the information in such a detail to know if they had those variables or not.

In generell there are a lot of other people that published positiv papers. I'd like to hear from them an explanation what went wrong if they where wrong.

I kinda don't see why I just should beliefe they where all wrong. I don't see the more weighting proof on the negativ side that trows away all the positiv findings. It propably would be something else if the 2009 Paper was the only one saying they could isolate the virus.

For me it just seems like trowing a cube with the number 1 or 2 depending on the number you decide which "side" your on.

Hi Bob,
I guess some folks think that Mikovits found some other virus which she has not yet sequenced? Does the 2009 Lombardi paper present any evidence for this other virus?

The WPI and Mikovits sad they are sequenzing other viruses they noticed after the publication of the 2009 paper. I don't think that the 2009 paper shows anything in that regard. They noticed afterwards more variation and sad they woul sequenz them. Why they haven't till know? Ask them I'd like to know too.

 

[alex3619]

Who believes in HGRVs?

I have had a really good chuckle at times at some of the anti-HGRV posts here on this thread. At times I have laughed out loud. Its highly amusing.

Let me address some central themes. I am writing about my position, not others, they can speak for themselves.

1. Do I believe HGRVs cause ME or CFS? No.
2. Do I believe that HGRVs are associated with ME or CFS? No.
3. Do I believe that HGRVs exist? No.

I have no belief in any of these things.

Now the other side:

4. Do I believe that XMRV is dead? Yes, the King is dead, long live the King - we are no longer discussing the Silverman artifact in connection with future research.
5. Do I believe that HGRVs might exist? Yes.
6. Do I believe that HGRVs might be associated with CFS or ME? Yes.
7. Do I believe that HGRVs might cause CFS or ME? Yes.

I think that the classic definition of XMRV is dead in CFS and ME research, but only the anti-XMRV advocates are pushing it. Nobody else is. So argue against something we are not even discussing if you want, we can just ignore you.

So what are we doing? We are examining possibilities! We will continue to examine possibilities until we are cured. If you want it to stop, give us a cure, or face the reality it wont stop, ever. There is no belief in HGRVs, at least for most of us, though I grant a few seem to have such a belief or argue from that position. Go argue with them if you want - but you wont get very far I think.

I continue to examine all theories and evidence within my limitations. I will continue to do so. HGRVs may not be relevant, but so far the evidence is not HGRVs don't exist, nor that HGRVs are irrelevant to CFS or ME. A logically defensible version of your argument, unlike the ones you actually use, is:

"In our view the evidence is sufficiently strong that it is improbable that HGRVs have been found in CFS (CCC) patients." This would be accurate.

The claim is often made to authority, experienced retrovirologists. How many decades of experienced virologists, doctors, and medical specialists being wrong do we have to listen to before we are distrustful of claims based on maybes? We want evidence - one way or another.

I for one eagerly await the Lipkin study. That will give us a probability estimate that the HGRV research is wrong. Its worth stating again: a probability estimate. That will tell us exactly how much of our attention should be on HGRVs. No guess, no voting, no politics, but hard math. Until now we don't have math of that quality supporting the anti-HGRV view.

So the only ones who have an unjustified belief system are those arguing that we all believe in HGRVs if we discuss them. Really? How many of us have said we believe in them? How many like me have said, explicitly, repeatedly, that they don't believe in them?

What I think is that every avenue must be researched. We are still in the dark as to causation. If someone wants to continue researching issues others have abandoned I have no problem with that. My suggestion to those who think this is wrong is do research into something else that might be causal or curative. A definitive cause or an effective cure will stop HGRV research dead ... unless the HGRV research is what leads to it of course.

Back to my own hypotheses: I have been wondering if lympocytic death might be a cause of low NK cell activation via high sIL2r release. Their has been a lot of evidence on sIL2r published recently. Most of it points to deliberate cleavage of IL2r to produce the soluble version, usually from activated T cells. Unless something different is happening in ME or CFS then it is unlikely to be due to lymphocyte death. Also, surely someone would have looked at ME severity and correlated it with sIL2r. They have in rheumatoid arthritis and found it is only weakly correlated. However, while I know this was looked at a decade ago, it could be another area where the research has halted due to lack of funding and political will.

So I am looking at many theories, from the likely causes to the unlikely, and discuss them all. HGRVs are one of these.

In discussing these issues we are looking at possibilities, and will continue to do so. In arguing against any discussion, except maybe against a few individuals, the anti-HGRV argument is tilting at windmills. You are arguing against something that doesn't exist. So its irrelevant.

As for believing in scientist, experts, doctors, they have had 77 years since the first major hospital epidemic and the majority are still clueless. I should believe in them - why? I read their papers. I have no problems with the considered claims made in them. The hyperbolic claims made to the media is however another issue. How come scientists can be so considered in their papers, and so unscientific when talking to media? Thats politics, not science, and when they are occasionally faced with an angry patient email or whatever, its usually because of the politics. They don't get that. They think if a scientist acts politically they should still be treated as scientists and not face political backlash. They are repeatedly surprised, or at least act surprised and outraged for the media, that they are attacked when they make hyperbolic claims. I don't approve of such attacks, but I am not surprised by them, at all.

My statement that I have no problem with the papers does not apply to a minority of biopsychosocial papers, nearly all from the UK, which do not address the evidence, use misleading definitions of so many things, and for which studies are designed carefully so they will not produce results which refute them, which is the opposite of good science in my opinion.

For example, I have really enjoyed and appreciate some of the anti-XMRV papers. One I wrote a glowing review of. I have no problems with those authors because their statements in public match their science. I respect them. That is not my universal regard for many other authors, who make rediculous comments to the media. You can figure out who I mean yourself, I think we all have a list but its up to you to make up your own mind based on the evidence.

Stop tilting at windmills. The vast majority of us don't believe in HGRVs, so arguing that we should stop believing in them ... well, you win, we don't, we never have, lets continue the HGRV discussion ...

Bye
Alex

 

[kurt]

Alex, you speak of evidence. What evidence is there that HGRVs exist and are present in the ME/CFS population? Then, what evidence is there that HGRVs are NOT present in the ME/CFS population? How would you compare the two batches of evidence?

 

[alex3619]

Hi Kurt, I capture it as incomplete, and controversial, and contradictory. We have evidence of something, but are still not sure what it is. It might or might not be an HGRV. It might be another retrovirus entirely, or none at all. Thats the problem, its all might bes. One of the issues we face is that every study is too small and too limited to do justice to the questions, almost entirely due to limited funds.

I have put most of my speculation on hold until after Lipkin - unlike some I think its a good idea to do such a large blinded test using suspected optimal methods. Then we will know.

However, there is NO doubt that the viruses or simlar virii exist, none at all. There is NO doubt that these viruses can infect human tissue. There is CONSIDERABLE evidence that we are resistant, not immune, to such viruses, which will make transmission rates very low. The question as to causation in CFS is much more problematic - we don't know even near enough to have a good model. There is not much point in examining it either until after the Lipkin study is in, and that of course presumes its in favour of such viral presence in CFS or ME.

On the other hand, there is still reason to research factors which are known to be important in MLVs and which are also seen in CFS and ME patients, such as cytokine storms and cytokine shfits (to Th2 bias for example). More specific MLLV research awaits confirmation which is still pending.

I am still concerned about blood safety. If a virus is present at very low amounts, undetected, then it might not pose a problem for most, but might still be a problem for those ill enough to need a transfusion. This is even more problematic for those who are receiving organ transplantsw, due to immunosuppressive drugs. What the BWG showed though is there is no point in testing for MLLVs as yet, as no test is reliable. This is about possibilities, not probabilities at this point, barring further evidence. I am open to such evidence however, for or against.

However its entirely justified for the WPI to continue MLLV research if they think they have a case. We do not know all that they know inside the institute, which even under normal circumstances would be a lot more than is published ... and these are not normal circumstances.

Bye
Alex

 

[citybug]

So here is new information today which shows a PCR chemical (uracil, UNG) can create false negatives. Also agrees the studies were iffy about stating the levels of spiked virus in controls. They were spiking with mouse dna and could not find the dna they knew was there.

http://www.biomedcentral.com/1756-0500/4/457/abstract
False negative results from using common PCR reagents

From the pdf regarding the XMRV in CFS studies

Of concern, despite the importance of the actual PCR methods used to amplify these potentially novel viruses, we were unable to determine the type of Taq or master-mix used in 11 of 38 publications. Of the remaining 27 publications, 13 studies used Taq or master-mixes likely containing UNG (it was present in 8 studies and possibly used in the remaining 5 studies that we examined)....
In the majority of studies commented on in this manuscript, the positive control used was an XMRV plasmid, and most papers were not clear about the amount of plasmid used for control amplification. Therefore, amplification of the high copy number positive control could occur while samples positive for a low copy number virus could be inhibited by carry-over PCR contamination.

 

[Bob]

One thing I wonder about the folks still supporting the 2009 Lombardi paper - what kind of evidence would have to be produced for you to change your minds about whether the only virus sequenced so far by Mikovits or her coauthors (i.e. XMRV) is associated with CFS/ME? I guess some folks think that Mikovits found some other virus which she has not yet sequenced? Does the 2009 Lombardi paper present any evidence for this other virus?

Well, I can only speak for myself...
But I'm not just looking at the Lombardi paper... I have been studying a great deal of other (published and unpublished) XMRV research over the past couple of years.

There now seems to be a scientific consensus that XMRV is a real virus that has an affinity for human tissue. It took a long time for this consensus to be reached. Originally, many scientists were saying that XMRV was not a real virus. So this has been an interesting field of research to follow, whether or not there is an association with ME.

But also, there is some evidence that XMRV is associated with prostate cancer. Some of Dr Singh's evidence cannot be explained by contamination. So this suggests that XMRV may indeed by a human retrovirus.

As for the Lombardi study, the serology results still stand, and have apparently been confirmed by Maureen Hanson (presented at the Ottowa conference but unpublished).
The question of specificity or cross-reaction has been raised, but Mikovits has reported that these antibodies are specific for MLVs.
(As far as I understand, much of the PCR, nested PCR and culturing work, in the Lombardi study, still officially stands as well... I believe that the partial retraction only relates to the 11(?) samples that were tested in Silverman's lab.)

Now there is a new paper that raises questions about all of the negative studies in relation to using PCR to detect low copy numbers.
This has been a big question for many of us for a long time...
When looking for a novel virus at extremelly low copy numbers, can the standard procedures for PCR be relied upon?
Very few of the negative studies, if any, have devoted time to studying the behaviour of XMRV in human blood and tissue, but they have just carried out a standard investigation using existing PCR procedures using blood only. So for me personally, I cannot be certain about the adequacy of the negative studies, however many there are, and however esteemed the researchers are. I don't dismiss them outright, but I cannot be certain that they have conclusively ruled out the possibility of HGRVs.
Even Dr Singh, who, people say, carried out a thorough study, did not test human tissue for her ME study, and her results for healthy controls do not match up in the ME blood study and the prostate tissue study. (Tissue = ~4%, Blood = 0%).

On the surface, I agree that the BWG study seems strong in many ways, but it is not definitive.
There has always been a question about using EDTA instead of Heparin, for example... This is not a new issue.
And there are so many variables in relation to a potentially novel human retrovirus.
And only 15 samples (is that correct?) were tested - that is a very small number.

So, yes, the VP62 contamination threw a spanner in the works, and, yes, there have been discrepancies in the research results...
But that doesn't mean that we are not interested in seeing the research continue...
There might even be a similar undetected retrovirus associated with ME, that has not yet been detected... It's a possibility... And the XMRV research might lead us to new discoveries.

The reason that many ME patients are so interested in the retrovirus research, is that they see a good fit for their disease.
It would explain so much.
Yes, there are plenty of questions, and some people think that a retrovirus would not explain some of the clusters or epidemics, or the general epidemiology of ME... But, for me, I think that the epidemiology issues raise questions, but do not give answers...

So, many of us think that this is definitely an interesting field that should be fully explored, and it does not entirely rely on the Lombardi paper.

But I do accept that other people might not be interested in this research, and don't see it as a likely explanation for ME.
I also accept that the current retrovirus research in relation to ME looks weak, especially to people who are only aware of the Lombardi study, and have not been following all of the other research closely.
But continued general research into XMRV-like viruses will not be fruitless (as it hasn't been so far), and there are many questions left to answer in relation to an ME-retrovirus association, such as the antibodies. Also, this field of research might also lead us to unexpected answers that are not currently on the radar, in relation to the immune system, for example. I don't see why it should not continue in parallel to other research.

While I continue to see possibilities and questions, then I will continue to take an interest in, and explore and support this field of research.


And there is one other important aspect of this research that is not just related to ME...
XMRV is infective, and infects human tissue, and exists in many labs as contamination...
If it hasn't already infected the human population, it is only a matter of time before it (or a mutation) goes wild...
So this does seem like a crucial field of research in relation to the safety of the human population.
I think they need to urgently pump many multiple millions of funding into it, and at least some of the US health agencies seem to realise this.
Some studies suggest that the virus can evade the human immune system, can disappear from the blood, can sometimes only be detected in certain specific tissues, can become latent and can hide from detection, so it seems that simple PCR blood tests will not be good enough to protect the population.

 

[RustyJ]

Well, I can only speak for myself...
But I'm not just looking at the Lombardi paper, but I have been studying a lot of the other (published and unpublished) XMRV research over the past couple of years.

There now seems to be a scientific consensus that XMRV is a real virus that has an affinity for human tissue. It took a long time for this consensus to be reached. Originally many people were saying that XMRV was not a real virus. So this has been an interesting field of research to follow, whether or not there is an association with ME.

But also, there is some evidence that XMRV is associated with prostate cancer. Some of Dr Singh's evidence cannot be explained by contamination. So this suggests that XMRV may indeed by a human retrovirus.

As for the Lombardi study, the serology results still stand, and have apparently been confirmed by Maureen Hanson (presented at the Ottowa conference but unpublished).
The question of specificity or cross-reaction has been raised, but Mikovits has reported that these antibodies are specific for MLVs.

Now there is a new paper that raises questions about all of the negative studies in relation to using PCR to detect low copy numbers.
This has been a big question for many of us for a long time...
When looking for a novel virus at extremelly low copy numbers, can the standard procedures for PCR be relied upon?
Very few of the negative studies, if any, have devoted time to studying the behaviour of XMRV in human blood and tissue, but they have just carried out a standard investigation using existing PCR procedures using blood only.
Even Dr Singh, who, people say, carried out a thorough study, did not test human tissue for her ME study, and her results for healthy controls do not match up in the ME blood study and the prostate tissue study. (Tissue = ~4%, Blood = 0%).

On the surface, I agree that the BWG study seems strong in many ways, but it is not definitive.
There has always been a question about using EDTA instead of Heparin, for example... This is not a new issue.
And there are so many variables in relation to a potentially novel human retrovirus.
And only 15 samples (is that correct?) were tested - that is a very small number.

So, yes, the VP62 contamination threw a spanner in the works, and, yes, there have been discrepancies in the research results...
But that doesn't mean that we are not interested in seeing the research continue...
There might even be a similar undetected retrovirus associated with ME, that has not yet been detected... It's a possibility... And the XMRV research might lead us to new discoveries.

The reason that many ME patients are so interested in the retrovirus research, is that they see a good fit for their disease.
It would explain so much.
Yes, there are plenty of questions, and some people think that a retrovirus would not explain some of the clusters or epidemics, or the general epidemiology of ME...
But I think that these are questions, rather than answers...

So, many of us think that this is definitely an interesting field that should be fully explored, and it does not entirely rely on the Lombardi paper.

But I do accept that other people might not be interested in this research, and don't see it as a likely explanation for ME.
I also accept that the current research in relation to ME looks weak, especially to people who are only aware of the Lombardi study, and have not been following all of the other research closely.
But continued general research into XMRV-like viruses will not be fruitless (as it hasn't been so far), and there are many questions left to answer in relation to an ME-XMRV association, such as the antibodies. Also, this field of research might also lead us to unexpected answers that are not currently on the radar, in relation to the immune system, for example. I don't see why it should not continue in parallel to other research.


And there is one other important aspect of this research that is not just related to ME...
XMRV infects human tissue, and exists in many labs as contamination...
If it hasn't already infected the human population, it is only a matter of time before it (or a mutation) goes wild...
So this does seem like a crucial field of research in relation to the safety of the human population.
I think they need to urgently pump many multiple millions of funding into it, and at least some of the US health agencies seem to realise this.
Some studies suggest that the virus can evade the human immune system, can disappear from the blood, can sometimes only be detected in certain specific tissues, can become latent and can hide from detection, so it seems that simple PCR blood tests will not be good enough to protect the population.

Not a bad summary Bob. The only addition I have is that the issues of PCR negatives will also call into question the BWG results which was not clear in your comment. Secondly, Lo is uncontested atm and is a validation of Lombardi. Since Lo found multiple variants and not a single contaminant his work is preeminent and must take on the major role now. So we have 1 and two-thirds positive studies still unchallenged (I have removed Silverman's contribution to Lombardi.) And the negative studies under a very big cloud.

 

[Bob]

Not a bad summary Bob.

Well, it's only my own perspective... Like I said, I can only speak for myself.

The only addition I have is that the issues of PCR negatives will also call into question the BWG results which was not clear in your comment.

Yes, that's a good point Rusty... It is another reason, amongst many, that the BWG results are not definitive.

Secondly, Lo is uncontested atm and is a validation of Lombardi. Since Lo found multiple variants and not a single contaminant his work is preeminent and must take on the major role now. So we have 1 and two-thirds positive studies still unchallenged (I have removed Silverman's contribution to Lombardi.) And the negative studies under a very big cloud.

Yes, I don't tend to focus on Lo's work because he hasn't followed it up, and it hasn't been replicated by anyone else.
Lo has had about a year now to do further research, and we haven't heard much from him recently... I'd really like to know if he is continuing with the research, and how it's developing. At least he will be fully involved in the Lipkin study, and so he will be able to replicate his own work.

 

[alex3619]

a little more philosophical ...

This all reminds me a llittle of the Schrodinger's cat experiment. An XMRV related virus either is or is not involved in ME or CFS. Its one or the other. On the basis of some evidence, some want to call it definitively - yes or no. This wishful thinking at best, and little more than a guess - and educated guess, but still a guess. I don't like guessing, I am with Einstein in one sense - I don't want to rely on a roll of the dice, I want it to be demonstrated or refuted with strong evidence either way. Is the XMRV related research challenged? Yes. So is the anti-XMRV research. This is cutting edge research, the old answers may be very different from what is discovered, until we find the answers we wont know. I downloaded the PCR contamination paper a while ago but don't have the time to read it maybe for several days, so can't comment any further.

Some may argue I am being hard on the anti-XMRV research. Not so. Lets turn it around and see what the story would be like if the roles were reversed with regard to some of the commentary.

If the XMRV proponents said they have definitively proven XMRV was not only associated with CFS but caused CFS, and were stating so to the media, most of my posts would be against the WPI and the XMRV hypothesis. I regard this as an open question, one which needs an answer. It is the overblown claims that keep being made, based on social issues or misjudgement, not reason, that I have a problem with. This could still go either way, and one new discovery could change everything - for or against. For example, and this is speculation that has been raised elsewhere, if the Rituximab researchers have found the cause of CFS, and just not released it yet due to the need to publish, and that was incompatable with the HGRV hypotheses, it would rapidly dominate once we were aware of it. Another major breakthrough could come any time, and that could send us in a whole new direction.

My best guess, and its only a guess, is that the final answer will be a surprrise, some twist that should have been obvious as it is obvious in hindsight. Of course thats mostly my sense of irony playing out, so don't take it too seriously.

HGRVs as a cause of ME or CFS are unproven. Ditto for association. The claim that the hypothesis is wrong is also unproven.

Please note that in this sense I am not talking about absolute proof, but I want sufficiently strong evidence that any alternative looks remote. We don't have that yet. Until we do it is my contention that the XMRV related research should continue. A strong result from Lipkin would be such evidence, and if against the HGRV hypotheses it would take an extraordinary new discovery to put it back on the table ... not that it would be impossible, but again such a thing cannot be predicted. I have said before that the one thing from the Lipkin XMRV study I would not like to see is an equivocal result, something that can be interpreted either way. A strong result, for or against the hypothesis, is what I hope for.

It is also quite appropriate to say that the research into XMRV must continue anyway, aside from ME or CFS, because its a new virus that is out there, and its infective, as several people have noted. In all of this I have repeatedly looked at the risk assessment. The claim that our defences stop XMRV cold is much like the French claim that the Maginot line would stop the Germans ... its only correct if there is no other issue that has not been taken into account (like a land route around the line), and even then it doesnt make it impossible, only very difficult. The downside risk is so high that I will keep supporting research until there is good evidence we don't need it. That does not mean we need a global panic, nor that it should be the number one research priority, only that it should not be ignored.

The WPI is not wrong to continue this research, nor are any of the other researchers looking to understand XMRV and related viruses in humans.

Its been two years - how many ME or CFS patients have had histological examination of a range of tissues, including lymph nodes? None? Its time that tissue testing was involved, as I have been saying all along. If our tissues stain like the prostate cells in Singh's work, then we will know there is something there, although that wont tell us definitively by itself what that something is due to the risk of cross reactivity.

One thing that has been obvious in ME and CFS research, a major problem that has surfaced again and again, if you don't konw what to look for you probably wont find it. Its not what we know that is the problem, its what we don't know. We have a lot of questions, and very few hard answers. I don't like guesswork on something this important.

One a personal note I would prefer not to have a retrovirus - but I either do or don't, my wishes will not change reality.

Bye
Alex

 

[Bob]

It is also quite appropriate to say that the research into XMRV must continue anyway, aside from ME or CFS, because its a new virus that is out there, and its infective, as several people have noted. In all of this I have repeatedly looked at the risk assessment. The claim that our defences stop XMRV cold is much like the French claim that the Maginot line would stop the Germans ... its only correct if there is no other issue that has not been taken into account (like a land route around the line), and even then it doesnt make it impossible, only very difficult.

Yes, I've heard people saying that our defenses stop XMRV, but this is not based on conclusive evidence.
Yes, APOBEC3 has shown to be effective at stopping XMRV in vitro, but that only tells us exactly that...
It doesn't tell us that XMRV cannot infect humans.
I think that there's been other research that shows that XMRV can bypass APOBEC3 to infect cells via another route. (Can't remember details.)
And XMRV can definitely infect human tissue.

 

[SilverbladeTE]

Alex
gawd luv ya mate, a ray of sanity in an insane world

Very often, answers to such questions end up being HUGE pains in the bunghole, because they open up a can of Loch Ness Monster-sized worms
Like "How the hell did we miss that?!"
or
"ugh, that's lots of standard models down the drain chaps! now we've got to build new ones...put the kettle on, Harry, this is a three-pipe problem!"
etc

Why is everyone so adamant, so sure? Two of my passions are history and science, and do you know how often the "accepted view" or "duel, irreconcilable views" got blown out of the water and shown wrong (sometimes BOTH wrong), sparked fights etc?

As I keep saying, such things usually take 5+ years to work out, no matter how damn smart/advanced things are. So starting from 2009, that gives us, oh another two years at least to *DEBATE* these issues before the facts are sieved out of the dross
yes DEBATE cause that's all this is. Enjoy it, seriously, "the game IS the candle" for us. We cannot change the outcome in anyway, for it is either...MLV/XMRV/whatevah, or it is not. The Universe doesn't care if we understand binary or 01
We've all got our biases, we're all Human, always remember that
Science is really chipping away at ignorance with toothpicks and we're ALL ignorant, admit it but don't revel in it!

me, personally, a retrovirus coming from rodents makes a lot of sense...I like the idea of it, but my likes have bugger all to do with the reality of it and I know it.
Mice have had an enormously long relationship with Humans, we've eaten them, had them in our granaries for millienia, heck our distant ancestors have ate them for millions of years, plenty of time for such a virus to "jump ship", for to ot become resistant, for it to become better at evading/modulating our immune systems.
would explain difficulty in determining causative agent of ME
and I'd like to have SOMETHING to understand and cuss at for this horrible damn ailment, ya know! "Take that you pesky virii!" *boot up the jacksey!* (1)
MLV, virulently toxic pesticides, hell, even Emperor Ming! Long as it's supported by the evidence knowing WHAT did this to me would help me rest at peace


Revealed! the true cause of ME!

(and in case folk haven't get it yet, I use humour, irony/sarcasm and lot of very multi-layered meanings in stuff: you get more with a parable and a joke, than with a big stick alone! )

(1) No virii were actually harmed in the making of this post, they were not threatened with death, either, though I think the majority of us believe the virii/amoeba/mycolpaasma/toxins/mutantsfromspace that cause ME may, just may, deserve the death of the dreaded CactiChiliSauceBungholio!! :victory:

 

[alex3619]

When some patients in their discussion move away from a hypotheses analysis to a factual analysis without any scientific validation within their comments, this is when it becomes a problem. When the comments within a thread moves from hypothesis to factual that is a concern. XMRV causes ME/CFS, HGRV causes ME/CFS, Aerosolization HGRV can cause ME/CFS. You can see the leap of illogical conclusions.
Eco

Hi Ecoclimber, agreed.

The debate serves three very useful purposes in my view.

1. We have very little capacity to engage in advocacy. With so little capacity its important to put our energy where its most needed. Of course if most of that energy is spent arguing or tearing others down, we are just wasting it. If you disagree with someone, irreconcilably, then start an alternative. if you don't like the CAA then advocate for someone or something else, elevate that choice to a position where it can do more for us than the CAA can. If necessary, start a new organization. The debate is to a large degree about understanding and setting priorities. We have to know which direction to head or we will be eternally lost.

2. We suffer from dreadful confusion and a long history of medical and scientific ignorance. We are looking for certainty - not that there is any such thing for the most part, but reducing uncertainly helps with stress. If debate helps us this way its a good thing - but if it adds to uncertainty I think most will just turn away from the debate.

3. We need hope. Hope is the difference between getting by and sinking into despair. Rituximab is the current Great White Hope (reference to whales, not people, Moby was an obsessive figure to Ahab). Such hopes have failed us in the past, repeatedly, but here is the thing. Eventually one will turn out to be the solution - we don't know which, we don't know when, but it will happen.

Bye,
Alex

PS I just read the link you posted Ecoclimber. I have been frustrated with the lack of publishing from WPI too. I have also wondered why they just don't release a series of reports on their website ... traditional journal publishing is flawed, if you have something important and its hard to publish, just put it on the web. I agree with Johan on that. The web is faster, and reaches a wider audience, including scientists. Sure its not peer reviewed, but I am sure than many also post reviews on line - whether anonymously or not, and I prefer not.

 

[markmc20001]

(1) No virii were actually harmed in the making of this post, they were not threatened with death, either, though I think the majority of us believe the virii/amoeba/mycolpaasma/toxins/mutantsfromspace that cause ME may, just may, deserve the death of the dreaded CactiChiliSauceBungholio!! :victory:

funny! got to love the silverblade CactiChiliSauceBungholio treatment imagery during a moment like this.