*NEW* information from WPI (30th March)

[VillageLife]

NEW INFORMATION POSTED BY WPI ON FACEBOOK................


What are some of the reasons that scientists looking for XMRV would fail to detect the virus in their patient samples?

1) Use of a test on cells which don't contain XMRV
2) Use of a test which has not been clinically validated or proven that it can detect XMRV in a positive patient sample
3) Use reagents not validated to detect XMRV
5) Use of clinically validated tests on a patient sample that is truly negative for XMRV
6)Testing patients which don’t satisfy rigorous clinical definition of XMRV such as is required in the Canadian Consensus Criteria.

As illustrated above, there are many ways to produce false negative results. The failure to detect XMRV in a patient sample taken at one time, using one method, does not prove that a patient sample is negative for XMRV.

Why did WPI grant a license to a clinical laboratory (VIP Dx) to offer XMRV testing?

1) WPI felt a responsibility to offer a clinically validated test to doctors who wanted to know if their patients were positive for XMRV, but only after another lab began offering a non-clinically validated blood spot test for XMRV.
2) Because VIP Dx is a locally operated CLIA certified laboratory, WPI can better assure quality control.
3) The non-exclusive license to VIP Dx supports the work of WPI.


Questions about the Science study.


Why did scientists have to use four methods to detect XMRV in the Science study to be absolutely sure that a sample was positive or negative for XMRV?

If one carefully studies the data presented in the Science paper one would see that patients can be negative by some methods and positive by others.

Where did the patient samples used in the Science study come from?

Samples used in the study came from several medical practices and from patients who became ill while living in many different locations around the United States.

Did all of the samples come from patients who were physician-diagnosed with CFS?

Yes.

Did any of the samples used in the original study come from patients who ultimately developed cancer?

Yes, one.

How were the samples chosen?

All of the patients/samples used in the study were chosen randomly on the basis of a CFS diagnosis from more than 200 patient samples stored in the WPI repository since 2006. No one knew the status of the patients as all samples were blinded. None of the samples came from the original repository of samples owned by Dr. Peterson.

What work was done after the May 2009 submission of the Science paper?

After the study was submitted, samples from CFS patients who also developed cancer were tested and found to be positive for XMRV. These results were reported at a private meeting of cancer researchers interested in XMRV. (A positive finding was not surprising, since retroviruses are known to cause cancer.).

Similarly, samples from families with autism and CFS were tested and XMRV was detected in samples from autistic children. Research on immune defects in XMRV infected patients have also been studied and reported at scientific meetings.

Can CFS patients develop serious complications after years of being ill?

Yes, doctors have reported that CFS patients have developed serious complications after being ill for many years, but a formal epidemiological study still needs to be completed.

Why is it important to do research on patients with a chronic disease who later develop complications from that illness?

Such research is necessary to prevent disease progression and complications of having the original disease.

 

[VillageLife]

Please don't anyone be affraid about the cancer information. I'm worried but it's better we know the truth.

 

[Esther12]

Please don't anyone be affraid about the cancer information. I'm worried but it's better we know the truth.

Nah - I'm five-a-day fruit and veg. No retrovirus could beat that!!

I'm a bit worried by them announcing this autism news without having a paper published. Couldn't they get a paper rushed out if they really want to announce these results?

It seems like the Science cohort is now US only again?

Good to see the Science samples were blinded, but it would be great to get more information on this, as it's seemed a bit ambiguous in the past.

I wonder if this is what will be discussed in the new Science?

Thanks for posting this Villagelife.

 

[justinreilly]

WPI rocks hard! They just do great science and tell it like it is!

This was informative for me since I thought the 19 lymphoma patients were in the Study, but they were actually tested later (only one of the Science cohort has cancer).

Great focus on the weak European studies and how ME/CFIDS may result in very serious medical complications!

 

[justinreilly]

Please don't anyone be affraid about the cancer information. I'm worried but it's better we know the truth.

I think it's crucial that the very strong connection between cancer (glioblastomas, jaw tumors and otherwise extremely rare b-cell lymphomas) and ME are publicised! It shows how serious and frankly organic ME is.

 

[George]

XMRV Testing Facts - from WPI facebook page

From the WPI facebook page

http://www.facebook.com/notes/whittemore-peterson-institute/xmrv-testing-facts/377139018025

What are some of the reasons that scientists looking for XMRV would fail to detect the virus in their patient samples?

1) Use of a test on cells which don't contain XMRV
2) Use of a test which has not been clinically validated or proven that it can detect XMRV in a positive patient sample
3) Use reagents not validated to detect XMRV
5) Use of clinically validated tests on a patient sample that is truly negative for XMRV
6)Testing patients which dont satisfy rigorous clinical definition of XMRV such as is required in the Canadian Consensus Criteria.

As illustrated above, there are many ways to produce false negative results. The failure to detect XMRV in a patient sample taken at one time, using one method, does not prove that a patient sample is negative for XMRV.

Why did WPI grant a license to a clinical laboratory (VIP Dx) to offer XMRV testing?

1) WPI felt a responsibility to offer a clinically validated test to doctors who wanted to know if their patients were positive for XMRV, but only after another lab began offering a non-clinically validated blood spot test for XMRV.
2) Because VIP Dx is a locally operated CLIA certified laboratory, WPI can better assure quality control.
3) The non-exclusive license to VIP Dx supports the work of WPI.


Questions about the Science study.


Why did scientists have to use four methods to detect XMRV in the Science study to be absolutely sure that a sample was positive or negative for XMRV?

If one carefully studies the data presented in the Science paper one would see that patients can be negative by some methods and positive by others.

Where did the patient samples used in the Science study come from?

Samples used in the study came from several medical practices and from patients who became ill while living in many different locations around the United States.

Did all of the samples come from patients who were physician-diagnosed with CFS?

Yes.

Did any of the samples used in the original study come from patients who ultimately developed cancer?

Yes, one.

How were the samples chosen?

All of the patients/samples used in the study were chosen randomly on the basis of a CFS diagnosis from more than 200 patient samples stored in the WPI repository since 2006. No one knew the status of the patients as all samples were blinded. None of the samples came from the original repository of samples owned by Dr. Peterson.

What work was done after the May 2009 submission of the Science paper?

After the study was submitted, samples from CFS patients who also developed cancer were tested and found to be positive for XMRV. These results were reported at a private meeting of cancer researchers interested in XMRV. (A positive finding was not surprising, since retroviruses are known to cause cancer.).

Similarly, samples from families with autism and CFS were tested and XMRV was detected in samples from autistic children. Research on immune defects in XMRV infected patients have also been studied and reported at scientific meetings.

Can CFS patients develop serious complications after years of being ill?

Yes, doctors have reported that CFS patients have developed serious complications after being ill for many years, but a formal epidemiological study still needs to be completed.

Why is it important to do research on patients with a chronic disease who later develop complications from that illness?

Such research is necessary to prevent disease progression and complications of having the original disease.

I am particularly interested in study's of long term CFS/ME patients. Of the original 202 patients cared for by Dr. Peterson in Incline Village 77 went on to develop B cell Lymphoma which is what my mom died of after years of illness.

 

[Gerwyn]

Nah - I'm five-a-day fruit and veg. No retrovirus could beat that!!

I'm a bit worried by them announcing this autism news without having a paper published. Couldn't they get a paper rushed out if they really want to announce these results?

It seems like the Science cohort is now US only again?

Good to see the Science samples were blinded, but it would be great to get more information on this, as it's seemed a bit ambiguous in the past.

I wonder if this is what will be discussed in the new Science?

Thanks for posting this Villagelife.

rushing a paper results in the english fiasos the science cohort was only us to start with there is no ambiguity about the patient cohort now and there never really was to start with

 

[parvofighter]

Nice to have some fog cleared away

1. Now are these the same responses that will be published in Science? I'm not sure. Anyone?
2. So.... about those allegations of masses of cancer patients in the Science study....
   

For those needing a reminder:

Where did the patient samples used in the Science study come from? Samples used in the study came from several medical practices and from patients who became ill while living in many different locations around the United States.

Consistent with the WPI's previous assertions, some of the patients that were seen in "several medical practices" were international patients who had travelled to these US clinics for care.

 

[Gerwyn]

1. Now are these the same responses that will be published in Science? I'm not sure. Anyone?
2. So.... about those allegations of masses of cancer patients in the Science study....
   

For those needing a reminder: Consistent with the WPI's previous assertions, some of the patients that were seen in "several medical practices" were international patients who had travelled to these US clinics for care.

Where on earth did those allegations come from in the first place.it was crystal clear that those patients were tested after the science data in the First place.It was also clear that they did not comefrom peterson.Why Did Vernon raise the issue at all

her silence on the cohort issue is even more puzzling considering the CAA s attitude to patient selection for the bloodbank clearly at odds with Oxford. Oxford does not use post exhertional malaise fatigue at all.

 

[Mark]

This has surely got to be a taster for the Science clarification, information they put together in order to answer those questions. Seems to me they have recently taken some time out from busily doing really important science, to sort out some of these spurious loose ends. I reckon they have their priorities right, and it looks to me like they have now cleared up all my niggling little areas of confusion (I couldn't really call them doubts).

Nah - I'm five-a-day fruit and veg. No retrovirus could beat that!!

I admire your good cheer on this news Esther, and such positive thinking has to be the best approach to strive for given that we accept that in all illness there's a good chance that positive thinking may be helpful - but my own initial reaction is more like :worried:. I'm trying to remind myself that loads of things cause cancer and we don't know how strong this association/likelihood is, but I'm also thinking about the recent discovery of retroviruses living in telomeres and thinking that this is not good news at all.

I'm a bit worried by them announcing this autism news without having a paper published. Couldn't they get a paper rushed out if they really want to announce these results?

It's not like the autism news wasn't out already, in fact I can't see any autism news there at all, we already knew about this. Here, they are just clairfying issues that have been challenged and clearing up confusions that have arisen.

On the question of how they release information, I understand that there's a scientific 'ethic' that you don't do this and you wait for publication before saying anything, and I think I understand the reasoning behind this ethical principle. I have never bought it though, I have always thought it is actually a deeply unethical position that one mustn't do this, and I'm not really interested in debating why. The fact that they have taken the approach they have to communicating information fills me with confidence in them actually, yes it sometimes comes across that they're a bit unprepared and small-time about these things but again, that also makes me trust them more. People are really funny to me if they trust scientists on the basis that (a) they are super-big corporations and have great glossy PR, and (b) they don't tell the public anything until they've waited for somebody else to give them the OK, but instead keep all the latest knowledge to themselves for a year or two and only share it backchannel within the scientific priesthood.

It seems like the Science cohort is now US only again?

EDIT: My answer on this was rendered redundant by Parvofighter and Gerwyn while I was posting, so I've edited it out, but I'll leave the next para in even though it isn't relevant to this specific point after all.

Much of the apparent confusion about what they said, and the complaints about the lack of detailed patient cohort information etc, seem to have been because the blinding procedures in their methodology were so rigorous that they didn't know all this stuff for sure themselves until months later. Which only goes to make the study all the more credible. Paraphrasing from memory: "Exemplary. As good a first study as I have seen" (John Coffin) - this perhaps is the sort of thing he was talking about.

Good to see the Science samples were blinded, but it would be great to get more information on this, as it's seemed a bit ambiguous in the past.

Guess that particular ambiguity is because they were blinded to their own blinding procedures.

- "How were the samples blinded?"

- "How the hell would I know? I hope you understand that I didn't blind them myself!"

Of all the information I'm hungry for, the details of how the samples were blinded isn't high on my list.

We are talking ultimately about matters of trust here, are we not? What I don't get with these sorts of questions about the methodological detail is why people - I'm thinking of lots of people here, not Esther specifically, who is IMO performing a valuable scrutineering function here - imagine that by having this information, or by seeing this sort of stuff in the publication, will tell you anything whatsoever. They could have written up all kinds of details about how they did every little detailed step, and it still wouldn't have any bearing on whether a rational person should trust their findings or not, because if you're going to doubt their integrity, then what they wrote about their methodology could still hide whatever trickery they wanted. If you're going to doubt their integrity, then no amount of information they give you should change that one iota, if you are rational. Whereas if you doubt the quality of their methodology and the quality of their scientific method, then I refer you once again to Mr Coffin and the journal Science, and I suggest to you that a team that is capable of convincing those people that they are the first in the world to prove the infectivity in humans of a gammaretrovirus, is a team that is good enough at science to be able to blind a study properly.

Following XMRV since the beginning has been my first real direct foray into the world of professional science, I don't claim any experience or background knowledge about science beyond what I learned at school, so in that sense I admit that I am a total layman. It was initially something of a surprise to me to find that, at this level, publishing a logbook full of longwinded stuff like "A test tube was filled with ordinary tap water using a 5ml pipette and placed inside a beaker of jelly" ain't quite the level of detail they bother with. But I quickly figured out how and why things are the way they are, and I'm perfectly comfortable that there's absolutely no point talking about certain types of methdological details. Any retrovirologist who wants to replicate these results can reasonably be expected to figure out how to blind their study for themselves.

I know what you mean about it seeming ambiguous Esther, but my reading is that there has been little information in response to questions that have led in that direction because they felt that information about such matters was only potentially relevant to their own integrity, not to the scientific issues at hand. That's why I've posted previously that, if I were them, I would probably find some of the questions that have been raised pretty insulting.

One direct hit there, Esther, the Science cohort being US only after all does rather cry out for yet more clarification, but I suspect the answer will either lie in our misinterpretation of something they said, or in some mistakes they made in their early public pronouncements. I'm sure they've realised they made some mistakes along the way in their public pronouncements, and frankly saying their results were worldwide when they weren't would be a pretty big one (if indeed we check back and that actually is what they said), but I doubt this implies anything about the quality of their science.

It all still looks solid to me, and the only thing that is changing for me is that I'm starting to face the fact that this wonderful breakthrough has a lot of stings in its tail.

 

[Gerwyn]

From the WPI facebook page

http://www.facebook.com/notes/whittemore-peterson-institute/xmrv-testing-facts/377139018025

What are some of the reasons that scientists looking for XMRV would fail to detect the virus in their patient samples?

1) Use of a test on cells which don't contain XMRV
2) Use of a test which has not been clinically validated or proven that it can detect XMRV in a positive patient sample
3) Use reagents not validated to detect XMRV
5) Use of clinically validated tests on a patient sample that is truly negative for XMRV
6)Testing patients which don’t satisfy rigorous clinical definition of XMRV such as is required in the Canadian Consensus Criteria.

As illustrated above, there are many ways to produce false negative results. The failure to detect XMRV in a patient sample taken at one time, using one method, does not prove that a patient sample is negative for XMRV.

Why did WPI grant a license to a clinical laboratory (VIP Dx) to offer XMRV testing?

1) WPI felt a responsibility to offer a clinically validated test to doctors who wanted to know if their patients were positive for XMRV, but only after another lab began offering a non-clinically validated blood spot test for XMRV.
2) Because VIP Dx is a locally operated CLIA certified laboratory, WPI can better assure quality control.
3) The non-exclusive license to VIP Dx supports the work of WPI.


Questions about the Science study.


Why did scientists have to use four methods to detect XMRV in the Science study to be absolutely sure that a sample was positive or negative for XMRV?

If one carefully studies the data presented in the Science paper one would see that patients can be negative by some methods and positive by others.

Where did the patient samples used in the Science study come from?

Samples used in the study came from several medical practices and from patients who became ill while living in many different locations around the United States.

Did all of the samples come from patients who were physician-diagnosed with CFS?

Yes.

Did any of the samples used in the original study come from patients who ultimately developed cancer?

Yes, one.

How were the samples chosen?

All of the patients/samples used in the study were chosen randomly on the basis of a CFS diagnosis from more than 200 patient samples stored in the WPI repository since 2006. No one knew the status of the patients as all samples were blinded. None of the samples came from the original repository of samples owned by Dr. Peterson.

What work was done after the May 2009 submission of the Science paper?

After the study was submitted, samples from CFS patients who also developed cancer were tested and found to be positive for XMRV. These results were reported at a private meeting of cancer researchers interested in XMRV. (A positive finding was not surprising, since retroviruses are known to cause cancer.).

Similarly, samples from families with autism and CFS were tested and XMRV was detected in samples from autistic children. Research on immune defects in XMRV infected patients have also been studied and reported at scientific meetings.

Can CFS patients develop serious complications after years of being ill?

Yes, doctors have reported that CFS patients have developed serious complications after being ill for many years, but a formal epidemiological study still needs to be completed.

Why is it important to do research on patients with a chronic disease who later develop complications from that illness?

Such research is necessary to prevent disease progression and complications of having the original disease.

I am particularly interested in study's of long term CFS/ME patients. Of the original 202 patients cared for by Dr. Peterson in Incline Village 77 went on to develop B cell Lymphoma which is what my mom died of after years of illness.

i am very sorry to hear that

our analysis of the english studies were pretty much spot on

 

[Mark]

Consistent with the WPI's previous assertions, some of the patients that were seen in "several medical practices" were international patients who had travelled to these US clinics for care.

Hmm. OK, I get it, after quite a bit of re-reading, comparison and thought, this all looks fine and everything indeed is, was and always has been consistent. But it's a bit of a shame they didn't mention that point again here themselves in the statement that finishes "around the United States". The question was "where did the patient samples come from?" but obviously we are also interested in where the patients themselves came from as well! When one reads the sentence there's a strong tendency to assume they were alll just US patients. The WPI said they themselves were surprised to realise that they had some international patients in the study, I believe, so in a way they made the same assumption themselves - it would have been better if they'd have clarified that point also in this answer.

Also, I don't recall whether the confirmation that there were international-origin patients in the study actually stated that some of those international-origin patients tested positive. Exactlly where those patients were from, and of course the details of those test results (percentages etc) might be interesting if there are enough of them. All important questions for us outside the US.

 

[George]

Yeah, they were weren't they! (big grins) I need to dig out that paper by Dr. Peterson and post it.

I missed it that this had already been posted in "XMRV research" section, so I guess we need to merge or just take the conversation over their.

I really think long term study of patients is going to be a vital part of filling in the picture.

 

[parvofighter]

Answer for @Ladybugmandy

once we stop the infection, we have about the same cancer risk as the general population...even if we have some virus in reservoirs, right?

Hi ladybugmandy, Dr Mikovits gave a very helpful example when talking about Karposi's Sarcoma, common manifestation of AIDS. You may recall hearing about this deadly, virally-caused cancer from the Tom Hanks movie, The Philadelphia Story. Karposi's Sarcoma is caused by the Human Herpesvirus 8 (HHV-8).

In her ProHealth talk Dr Mikovits talked about this.
From: http://forums.aboutmecfs.org/content.php?36-Section-4

I led a drug development program about a decade ago just before I came to California and we were going to make drugs to target AIDS associated malignancies and we found as soon as we got the highly active anti-retroviral therapy and got rid of the HIV and silenced that the Kaposi's Sarcoma went away as did the HHV8 so they cut the budget for that drug program and rightfully because there's no need to develop these drugs because they learned that at that point all you have to do is control the retrovirus, get the immune system back to functioning, and also the good news is most of those men their immune systems are functioning well.
​

Hope this helps. Now as for that buzzing noise...

 

[parvofighter]

That is really promising news and hopefully the same will hold true for XMRV.

I agree CFS-since-1998: it is promising, isn't it. I think it was Dr Bell that talked about XMRV as the Puppet Master? I kind of think of XMRV as a cheerleading team, rooting for the opportunistic viruses (HHV-6, Epstein-Barr, PVB19 etc) to get off their butts.

Because I'm getting antibody treatment for my persistent parvovirus B19 infection, we see this clinically too. And it's behaving exactly as if there were a "cheerleader" rooting for this opportunistic infection. There's tons of research to show that Ig therapy works wonders for persistent PVB19 infections. But it would appear that not all PVB19 infections are persistent because of a retrovirus.

We've been able to dramatically improve both my PVB19 and ME/CFS symptoms with Ig therapy - but not indefinitely and not completely. I keep relapsing - exactly as if a little retrovirus XMRV in the background were giving mouth-to-mouth to my remaining PVB19 fellas, each time we hit them with a higher dose of Ig. The fact that I'm positive for the RNase-L antiviral defect fits this picture too. So maybe the folks who need long-term Ig therapy for persistent PVB19 are the ones who have an antiviral pathway defect - which makes them susceptible to the XMRV - and which makes the PVB19 hang in there indefinitely? Until antiretrovirals and/or immune modulators (?Ampligen) come in.

Interesting stuff. As you can probably tell, I love science-based hope.:Retro smile:

 

[Mark]

our analysis of the english studies were pretty much spot on

Of course! Was that ever in doubt? Thank you so much Gerwyn for all the incredible work you've done on this.

There's another thread discussing this news from the WPI here:

http://www.forums.aboutmecfs.org/showthread.php?4035

 

[Gerwyn]

I agree CFS-since-1998: it is promising, isn't it. I think it was Dr Bell that talked about XMRV as the Puppet Master? I kind of think of XMRV as a cheerleading team, rooting for the opportunistic viruses (HHV-6, Epstein-Barr, PVB19 etc) to get off their butts.

Because I'm getting antibody treatment for my persistent parvovirus B19 infection, we see this clinically too. And it's behaving exactly as if there were a "cheerleader" rooting for this opportunistic infection. There's tons of research to show that Ig therapy works wonders for persistent PVB19 infections. But it would appear that not all PVB19 infections are persistent because of a retrovirus.

We've been able to dramatically improve both my PVB19 and ME/CFS symptoms with Ig therapy - but not indefinitely and not completely. I keep relapsing - exactly as if a little retrovirus XMRV in the background were giving mouth-to-mouth to my remaining PVB19 fellas, each time we hit them with a higher dose of Ig. The fact that I'm positive for the RNase-L antiviral defect fits this picture too. So maybe the folks who need long-term Ig therapy for persistent PVB19 are the ones who have an antiviral pathway defect - which makes them susceptible to the XMRV - and which makes the PVB19 hang in there indefinitely? Until antiretrovirals and/or immune modulators (?Ampligen) come in.

Interesting stuff. As you can probably tell, I love science-based hope.:Retro smile:

it appears that XMRV acts as a psudogene, and indeed, can be described as a puppet master is the same sense as HIV because of its ability to bind within CREB CRE genes which are transcriptonal regulators sometimes commonly known as gene switches ,usually in conjunction with other regulatory molecules

 

[Bob]

It seems like the Science cohort is now US only again?

I have definitely seen Judy Mikovits quoted as saying that she has tested a number of UK patients for XMRV, and that the same percentages were holding up. (I can't remember if she said how many samples were tested.)
I'm certain that I've seen this quoted more than once, although I haven't seen it followed up since with any solid statements about it.

 

[Mark]

Where on earth did those allegations come from in the first place.it was crystal clear that those patients were tested after the science data in the First place.It was also clear that they did not comefrom peterson.Why Did Vernon raise the issue at all

I just checked back on that to see what the origins of the cancer patient allegation were and it seems that the basis was that 4 or 5 patient numbers appeared both in the Science study and also in a presentation by Dr Peterson which listed cancer patients.

"Assuming no error in the patient numbers provided, there does appear to be a cancer overlap," Anika noted.

Seems to me the only way to reconcile everything is to say there must indeed have been an error, in which case surely far more likely to be in Dr Peterson's slides than in the Science study? I haven't seen that point of detail clarified yet.

Apologies if I'm hopelessly out of date on this, I wasn't online much when this particular issue was unfolding and I haven't really followed this issue too closely, and don't have time to trawl through the threads at the moment, so I'm writing from a considerable distance from the issue and giving an impression on how it looks. Based purely on the basis given for the "allegation", it looks to me like somebody trawled through all the WPI material they could get their hands on, spotted this issue with the patient numbers, and took it from there. How the issue was raised I don't know, but I would have expected that the way to do it would be to email the WPI and ask.

It seems like it should be simple enough to check such matters, but I also get the impression that, for whatever reason, doing so required a lot of poring over pages of numbers and cross-checking data; there's also perhaps the added complication of whatever was going on with the blinding process. I suppose I can see how the WPI may have felt that checking this particular detail wasn't top of their job list - maybe Vernon got fed up waiting and raised the question publicly in hope of getting it answered? But I'm just speculating on one possible type of explanation there.

Impression I'm left with therefore is: it is now confirmed that this issue was a red herring, but we still don't know the exact source of the error or misunderstanding that led to the alllegation, and without that, we can't tell how the whole misconception about cancer patients in the initial study arose.

 

[Gerwyn]

i think the problem for me is that the trial population did not contain any of dr petersons patients and that had been made abundantly clear before the sais slide show