• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Doctors Mc.Clure & Kaye respond to Annette Whittemore in "Expert-Reviews.com"

Megan

Senior Member
Messages
233
Location
Australia
Are the PCR facts right?

I'm sympathetic to McClure, and think she probably got suckered by Wessely into making unfounded comments as to her certainty that XMRV is not a factor in CFS in the UK.

I agree with the above to the extent that it sounds like McClure probably didn't understand the nature of the samples Wessely presented to her or CFS polics. She was just focussed on testing samples she was asked to test. No doubt she must also been influenced by him.

But she can no longer be so naive and she is responsible for public comments she makes. It seems to me she has been plainly inaccurate in a number of public comments, the latest of which appears in this article, as picked up earlier in this thread by Bob:

I'm not sure about the accuracy of the following quote:

One technical difference stands out from these studies. PCR was employed to amplify XMRV sequences in all four studies. Only the study from the Whittemore Peterson Institute [1] was able to detect XMRV sequences following single-round PCR, indicating that copies of the XMRV genome were not in short supply. All the others found it necessary to employ a nested PCR, a modification of the standard reaction designed to enhance sensitivity and specificity.

Additionally McClure's article says (bolding mine):

The new connection of XMRV with CFS reported from the Whittemore Peterson Institute (NV, USA), was published in Science last year [1], and claimed that, of 101 CFS patients recruited to investigate the virus etiology of the disease, 68 (67%) were XMRV positive by single-round PCR amplification of the proviral DNA from peripheral blood mononuclear cells.

Compare the above to a direct quote from the WPI Science paper second para (bolding mine):

we isolated nucleic acids from PBMCs and assayed the samples for XMRV gag sequences by nested polymerase chain reaction (PCR) (5, 6). Of the 101 CFS samples analyzed, 68 (67%) contained XMRV gag sequence.

I understand nested PCR is double round PCR, not single round PCR.

I can't see how the McClure article can be interptreted as anything other than a misrepresentation of the facts in relation to the WPI study. Much of the criticism of the WPI in the article revolves around this PCR issue. I cannot fathom how McClure, with her intimate knowledge of WPI study, could have got this point wrong accidentally, unless there has been some 3rd party journalistic or editorial intervention here that has got things mixed up. Or maybe the other person wrote it. Not that that excuses anything.

If there is anyone here that understands how the above quotes can be reconciled then please enlighten us. Otherwise I think we should be writing to the journal asking for a public correction to be made and questioning how someone of McClure's knowledge and standing could be making such errors.
 

VillageLife

Senior Member
Messages
674
Location
United Kingdom
This article seems a little out of date, this article is irrelevant.....hold on the tide is about to turn....we know the Dr Alter NIH/FDA study is coming out soon.
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
Previous comments made by McClure, Kaye & others

In considering the validity of what Prof. McClure & Dr. Kaye say about methodology in their latest article, it is useful to reflect on what has already been said publicly, both by them and by others

Quoted statements made by Prof. McClure:

In the Guardian & Independent Newspapers (6th January 2010):
http://www.guardian.co.uk/lifeandstyle/2010/jan/06/chronic-fatigue-syndrome-xmrv-virus
http://www.independent.co.uk/news/s...und-the-cause-of-me-is-premature-1859003.html

"We are confident our results show there is no link between XMRV and CFS, at least in the UK."



In her response to Annette Whittemore's letter dated 12th April http://www.wpinstitute.org/news/docs/DearDrMcClureaw4.pdf

Prof. Mc Clure says :

You should know that I am neither a clinician nor someone who has a research programme on CFS/ME. I run a retrovirology laboratory and we became interested in XMRV after the second major paper on its association with prostate cancer. We agreed to test CFS samples from a colleague because we were, at that time, the only laboratory with the means to do so.
As I explained previously, the controversy surrounding CFS and XMRV requires to be solved by national virology reference laboratories, such as the CDC and HPA.
We have published our findings. Others have published similar findings to our own. We have no further involvement in the study of CFS. It only remains for me to wish you well in your endeavours.

In response to comments made about the original paper published in "Science" magazine, Dr Judy Mikovits & Dr Francis Rusceti had the following to say (Published 14th May 2010 in "Science"):
http://www.sciencemag.org/cgi/conte...al&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Of the technologies used to identify and isolate XMRV in patients with CFS, PCR from DNA or cDNA from unstimulated peripheral blood mononuclear cells is the least sensitive method. We contend that the three recently published negative PCR studies (1315) do not qualify as being studies that fail to replicate our study, as neither the same PCR methodologies were used nor did these studies draw on the additional cell culture and immunological methods that we employed to observe XMRV nucleic acids and proteins. Although we offer to send samples in which we have detected XMRV, the groups that published these results neither requested nor analyzed any samples we had found positive for XMRV in our laboratories.

In a press release (June 1st 2010) WPI stated the following:

http://www.wpinstitute.org/news/docs/WPI_Erlwein_010610.pdf

The scientific methods used by WPI are very exact and require specific techniques to ensure accuracy. Differences in techniques employed by Erlwein et al. not only explain their failure to replicate the WPI study, but also render the conclusions meaningless. These differences include, but are not limited to the following:
1) blood sample volumes and processing;
2) patient criteria/population differences;
3) number and type of tests done to assure accurate results, including white blood cell
culture;
4) use of a molecular plasmid control in water versus a positive blood sample; and
5) different primer sequences and amplification protocol used to find the virus, which
were not validated by a clinical control
.

I note that Prof. McClure & Dr. Kaye have conspicuously avoided addressing the "differences" notified to them by the WPI (particularly the issue of culturing) in their latest article and will be shocked to learn that the WPI have already found XMRV (high % of participants) in UK patients.

TGOP
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
It's in the July 2010 edition

This article seems a little out of date, this article is irrelevant.....hold on the tide is about to turn....we know the Dr Alter NIH/FDA study is coming out soon.

Yes Villagelife, it does seem to be out of date and yet it's published in the July issue of Expert Review ....... that's partly my point !!! :eek:

Regards,

TGOP ;)
 

Mithriel

Senior Member
Messages
690
Location
Scotland
XMRV is found in prostate tissue, not blood. We do not know which tissue is best to detect XMRV in ME/CFS and having the correct tissue is vital in PCR.

The nay sayers of XMRV are very inaccurate about what they say about the WPI, the Science paper and the cohorts. It does not inspire any confidence.

It is also very unprofessional to not reveal that they did one of the studies. This is the second time she has done that.

I have found over the years that you can tell whether a researcher stands with is or against us by how much integrity they have.

Mithriel
 
Messages
59
Location
Bognor UK
I note that Prof. McClure & Dr. Kaye have conspicuously avoided addressing the "differences" notified to them by the WPI (particularly the issue of culturing) in their latest article and will be shocked to learn that the WPI have already found XMRV (high % of participants) in UK patients.

TGOP

How many UK patients have the WPI tested to date and what sort of positive % are holding up TGOP?
 

parvofighter

Senior Member
Messages
440
Location
Canada
The banality of evil

Protecting patients from robust differential diagnosis?
A comment was made earlier about protecting patients from a proper differential diagnosis:
I think it's likely that the speed of their (McClure's) work, and the forthright manner is which it was promoted were a result of Wessely's belief that the XMRV news will cause psychological damage to his patients which he wants to mitigate.
Let me get this straight. McClure's haste in producing a botched failed study - together with lousy cohorts, unstimulated blood, and sweeping, "forthright" unsubstantiated generalizations ("We are confident our results show there is no link between XMRV and CFS, at least in the UK.") ... followed by unsubstantiated allegations of contamination... were done to "protect" ME/CFS patients from the dangers of a robust differential diagnosis process.

When (if ever) is it OK to halt the differential diagnosis process?
If there is any lesson to be learned from this XMRV/ME/CFS debacle, it is the danger of allowing incompetent psychiatrists to entirely derail the legitimate and essential process of differential diagnosis, with their morally bankrupt argument of "protecting the patient". If anything, a differential diagnosis should be an organic, continuing process, that allows for new research to revolutionize treatment prospects. Any clinician - no matter how "esteemed" - robs themselves of any iota of credibility when they profess to know the answers to a scientific question - without the benefit of robust scientific enquiry. (Think Reeves, on his published expectation that no link between XMRV and ME/CFS would be found). Shame on McClure if she allowed herself to also be hoodwinked into rushing through her XMRV study, with the intent to shut up ME/CFS patients.

When a potential new avenue of scientific enquiry unfolds to a hitherto misunderstood disease, WHEN is it OK to snuff out this research with the argument that one is "protecting" patients? When is it OK for science to come to a screeching halt - because we know "everything" there is to know about a given disease? This colossally arrogant attitude ensures that no scientific progress will be made in our understanding of Medically Unexplained Diseases. And it is an arrogance that the medical profession has been a bystander to in the past, allowing it to flourish unchecked.

Ignorance might be McClure's early excuse - she has none now
McClure may have been hoodwinked due to her own ignorance and lack of due diligence on the Wessely cohort issue. However she continued to throw up smoke and mirrors with gay abandon, after publication of this dreck - at a time when clarity (and funding for XMRV research) were desperately needed. She shows a complete lack of insight on the need for a sense of urgency with many desperately ill patients.

Lead, follow, or get out of the way!

I have one thing to say about McClure's sordid, grasping attempts to position herself as a credible scientist - even as the horse is already out of the barn:

Lead, follow, or (better yet), get out of the way!

McClure has abundantly proven herself incompetent and undeservedly arrogant, and has shown no indication that she can lead XMRV/ME/CFS research with competence nor follow the likes of Alter and Ruscettis with grace. I say, "Get out of the way", so that credible international scientists can advance the science. And as so many posters have rightly pointed out - McClure's latest feeble attempt at a riposte is laughably out-of-date, given what we know of the imminent NIH/FDA publications. McClure is easy for anyone who has followed the science, to dismiss as laughable. If one hasn't been following the science though, McClure offers a dangerously enticing vision of someone who actually cares about science, yet who is merely creating distracting white noise.

For heaven's sake McClure - follow your earlier promise:

"We have no further involvement in the study of CFS"

Pleaaaase!!!
 
Messages
41
Lead, follow, or get out of the way!
I have one thing to say about McClure's sordid, grasping attempts to position herself as a credible scientist - even as the horse is already out of the barn:


Lead, follow, or (better yet), get out of the way!


McClure has abundantly proven herself incompetent and undeservedly arrogant, and has shown no indication that she can lead XMRV/ME/CFS research with competence nor follow the likes of Alter and Ruscettis with grace. I say, "Get out of the way", so that credible international scientists can advance the science. And as so many posters have rightly pointed out - McClure's latest feeble attempt at a riposte is laughably out-of-date, given what we know of the imminent NIH/FDA publications. McClure is easy for anyone who has followed the science, to dismiss as laughable. If one hasn't been following the science though, McClure offers a dangerously enticing vision of someone who actually cares about science, yet who is merely creating distracting white noise.

For heaven's sake McClure - follow your earlier promise:


"We have no further involvement in the study of CFS"

My sentiments exactly.
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
For good advocacy, ask Parvo


Lead, follow, or get out of the way!

I have one thing to say about McClure's sordid, grasping attempts to position herself as a credible scientist - even as the horse is already out of the barn:

Lead, follow, or (better yet), get out of the way!

McClure's latest feeble attempt at a riposte is laughably out-of-date, given what we know of the imminent NIH/FDA publications. McClure is easy for anyone who has followed the science, to dismiss as laughable. If one hasn't been following the science though, McClure offers a dangerously enticing vision of someone who actually cares about science, yet who is merely creating distracting white noise.
For heaven's sake McClure - follow your earlier promise:

"We have no further involvement in the study of CFS"

Pleaaaase!!!

Well said Parvo - as always.
You are very astute in your observations and right on the money with this one. :victory:

Thanks

TGOP :D
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
UK XMRV study - please donate to help WPI do this research

How many UK patients have the WPI tested to date and what sort of positive % are holding up TGOP?

Hi Bananaman,

I don't know the numbers at this stage, but be assured that of the 50 people sampled so far, the percentage of positives seems to be overwhelmingly supportive of what Dr. Mikovits has consistently said, i.e. that XMRV is found in the UK population and therefore not geographically confined to certain hotspots in the U.S.

The remaining 200 or so participants in the UK XMRV study, are scheduled to have their blood draws within the next month and Mr. Ed Cutler and his wife (Phlebotemy Services International - who are working with the WPI in order to make sure that the blood samples are handled & preserved correctly) have flown over here from the States to start that process next week.

Please note that this study has been funded by the Whittemore Peterson Institute and Invest in ME, but because NHS hospitals have not co-operated with the blood drawing process (as was hoped), the cost of drawing the blood samples has risen substantially. Hence I would urge anyone who can afford to (and wishes to help to fund this research effort), give generously to the WPI at : http://www.wpinstitute.org/help/help_donation.html

It is utterly infuriating that far from helping this research, those who might be expected to assist with facilitating this type of study have actually been unhelpful and even obstructive.

Regards,

TGOP
 

biophile

Places I'd rather be.
Messages
8,977
No doubt Wessely filled McClure in on how CFS is a "functional" illness so the retrovirus would either not be found or would play no significant role in the perpetuation of symptoms. I wonder if McClure will still be "1000% sure" of her position after the NIH/FDA study is published?

For heaven's sake McClure - follow your earlier promise:"We have no further involvement in the study of CFS" Pleaaaase!!!

Like Wessely's "retirement" from CFS all those years ago! ;)
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
XMRV is found in prostate tissue, not blood. We do not know which tissue is best to detect XMRV in ME/CFS and having the correct tissue is vital in PCR.

The nay sayers of XMRV are very inaccurate about what they say about the WPI, the Science paper and the cohorts. It does not inspire any confidence.

It is also very unprofessional to not reveal that they did one of the studies. This is the second time she has done that.

I have found over the years that you can tell whether a researcher stands with is or against us by how much integrity they have.

Mithriel

My thoughts exactly. Well said.
 

Cort

Phoenix Rising Founder
I agree with the above to the extent that it sounds like McClure probably didn't understand the nature of the samples Wessely presented to her or CFS polics. She was just focussed on testing samples she was asked to test. No doubt she must also been influenced by him.

But she can no longer be so naive and she is responsible for public comments she makes. It seems to me she has been plainly inaccurate in a number of public comments, the latest of which appears in this article, as picked up earlier in this thread by Bob:



Additionally McClure's article says (bolding mine):



Compare the above to a direct quote from the WPI Science paper second para (bolding mine):



I understand nested PCR is double round PCR, not single round PCR.

I can't see how the McClure article can be interptreted as anything other than a misrepresentation of the facts in relation to the WPI study. Much of the criticism of the WPI in the article revolves around this PCR issue. I cannot fathom how McClure, with her intimate knowledge of WPI study, could have got this point wrong accidentally, unless there has been some 3rd party journalistic or editorial intervention here that has got things mixed up. Or maybe the other person wrote it. Not that that excuses anything.

If there is anyone here that understands how the above quotes can be reconciled then please enlighten us. Otherwise I think we should be writing to the journal asking for a public correction to be made and questioning how someone of McClure's knowledge and standing could be making such errors.

I actually thought it was a pretty good article until Megan pointed out the relevant section of the Science paper- which just flabbergasted me. Either McClure's made a error of immense proportions or we're missing something; the problem is I can't imagine what we're missing - the statement seems so clear; they're both talking about PBMC's and PCR and gag sequences....It doesn't get any weirder than this, really.
 

RustyJ

Contaminated Cell Line 'RustyJ'
Messages
1,200
Location
Mackay, Aust
There is a possible explanation for the disparity between McClure's assertion concerning the Science paper methodology on the issue of PCR tests. It could be that WPI & co isolated sequences in both single round and nested PCR testing. Whereas McClure is saying no one else could find it in single round, only in nested. I haven't gone through enough of the Science paper to find out if this is true. If it is true then the confusion is created by how McClure made her statement. It is not a discrepancy.
 

Eric Johnson from I&I

Senior Member
Messages
337
As I understand it, McClure, Kaye and the rest of the lab crew do know how to find XMRV. They find it in prostate cancer samples. I think questioning their technical ability may not be in order.

I still suspect that Wesseley took them for a ride -- fed them some "poor psychiatric patients being taken advantage of" story, and then gave them bum samples.

Prostate samples, ok. But blood? Allegedly, in the macaques, the urogenital tissues and lymph nodes had the goods, the blood not much of it.


I also suspect that McClure, and others in her lab apparently, have pretty big egos. McClure, and maybe others, are probably having a very, very hard time accepting that they screwed up royally. They're trying to find a way to preserve their high opinion of their abilities

Yeah, hard to know but certainly not unlikely. One thing I can't remember ever hearing of is a scientist conceding a dispute. The losing side just kind of fades away. I've never thought about it before but I guess it is kind of pathetic that you rarely hear of that.
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
One thing I can't remember ever hearing of is a scientist conceding a dispute. The losing side just kind of fades away. I've never thought about it before but I guess it is kind of pathetic that you rarely hear of that.

Stephen Hawking, 2004, regarding black holes. He had a bet with John Preskill about the origin of thermal radiation from black holes, and publicly announced that he was conceding the bet, that he was convinced that Preskill was right and he was wrong. Hawking has class and self-assurance.

You're right that it's rare, and that's why I remember hearing Hawking on the radio about it. But it may be that it's actually more common, and just not carried out in the public eye. Generally, outside of their specialized circles, no one cares if a scientist concedes s/he's wrong.
 

SOC

Senior Member
Messages
7,849
Me, previously:
As I understand it, McClure, Kaye and the rest of the lab crew do know how to find XMRV. They find it in prostate cancer samples. I think questioning their technical ability may not be in order.

Prostate samples, ok. But blood? Allegedly, in the macaques, the urogenital tissues and lymph nodes had the goods, the blood not much of it.

Good point, I wasn't on top of that issue. They may know next to nothing about finding XMRV in blood. Or worse, they think they know more than they do. "A little knowledge is a dangerous thing."

So if there's a lot more XMRV in prostate tissue than there is in blood, they wouldn't necessarily be using amplification techniques that might be needed for blood samples.

If all this is true, then it gets even harder (not that it was easy) to have any sympathy for them whatsoever -- were they really quick-testing in a way that is NOT usual for their lab and then being "1000% certain" they were right? Sounds scientifically irresponsible to me....

This sounds more and more like a B movie.... or a nightmare....
 

thegodofpleasure

Player in a Greek Tragedy
Messages
207
Location
Matlock, Derbyshire, Uk
Otherwise I think we should be writing to the journal asking for a public correction to be made and questioning how someone of McClure's knowledge and standing could be making such errors.

I also think that this is an important thing to do.
Has anyone got any thoughts about the wording for such a letter of correction ?

TGOP
 

Mithriel

Senior Member
Messages
690
Location
Scotland
It takes time and experimentation to get a reliable diagnostic test. The NHS has a lab in charge of working out PCR tests for various organisms. When thye get one to be repeatable it becomes part of diagnostic routine.

They have not managed it for all organisms.

A single negative test is meaningless, much more so than finding something. You have to go back and look at your collection set up, your primers, your technique, the tissues used, even without tthinking of the problem with cohorts.

If a positive finding needs validation, a negative one needs to be repeated many times and even then it could be some flaw you hadn't thought about.

They are totally unscientific.

I have also discovered that it is well known in studies of MULVs that culture is often required, it is not unique to XMRV, so it looks as if they did not do even the most basic literature search before they started. That is what you get when you rush things!

Mithriel