ABC Australia: McClure (ICL) "Virus linked to prostate cancer and CFS"

[Dx Revision Watch]

Is this the study to which Dr McClure is referring in the Australian interview or is she referring to an earlier, but not yet published study? This one was scheduled to start in January, this year.


From 8 March ME agenda compilation of three FOIA responses:

http://meagenda.wordpress.com/2010/...lar-diagnostics-unit-imperial-college-london/

[...]

R = Response by Imperial College, London Freedom of Information Office foi@imperial.ac.uk

[...]

[2] Request for information under FOIA by Kim LeMoon, USA:

From: foi@imperial.ac.uk
Date: 08 March 2010
Subject: RE: Request for Information – XMRV Research

R: Further to your request for information received by us on 8 February 2010, please find below the College’s response to your questions.

Request for information under FOIA in respect of all ongoing research projects or scheduled research projects relating to XMRV (Xenotropic murine leukemia virus-related virus) detection via blood samples, tissue samples or any other methods of detection

I should be pleased if receipt of this request for information could be acknowledged, together with the date by which a response will be provided.

Project Supervisors:

R: Professor Myra O McClure, Dr Steve Kaye, Professor Jonathan Weber

Project title:

R: XMRV and its association with Prostate cancer

Laboratory supervisor:

R: Dr Steve Kaye

Clinical supervisor:

R: Dr Anup Patel

1] Any Identification or Reference code assigned to Project:

R: n/a

2] Project’s Public Title; Project’s Scientific Title:

R: XMRV and its association with Prostate cancer

3] Study hypothesis/rationale (where applicable):

R: n/a

4] Ethics approval and any reference numbers attached to this approval:

R: Tissue bank ethics number 98CC141. A study to collect blood & urine specimens, prostate tissue &/bone marrow specimens to help establish methods for diagnosing and treating prostatic cancer.

5] Study design:

R: Molecular and serological methods

6] Countries of recruitment:

R: UK.

Centres of recruitment:

R: Imperial College Healthcare Trust.

Other methods of Recruitment:
R: n/a

* Through what means will prospective participants be recruited?

R: Signed consent to use biopsy tissue for retroviral analysis. Not yet underway.

7] For what diseases/conditions/study domains are patient samples to be collected?
R: Prostate cancer

* Through what means will control samples be assembled?

R: Not being assembled currently

8] Participants – inclusion criteria:

R: Participants will be restricted to those patients who are having a prostate biopsy for diagnostic purposes and have given consent for a small (10 micron) slice of their biopsy tissue to be used for research purposes.

9] Participants – exclusion criteria:

R: n/a

10] Target number of participants:

R: Open

11] Patient information material: please provide copies of any patient information material:

R: n/a

12] Anticipated start date:

R: January 2010

13] Anticipated project completion date:

R: December 2010

14] Sources of funding:

R: BRC [Ed: ICL has since clarified that “BRC” stands for Biomedical Research Centre]

15] Sponsor details:

R: None

 

[leelaplay]

Great find suzy! And thanks so for the transcript snippets and precis fred.

If McClure is now saying that she is finding xmrv, and that it is in the general population at 1% to 1.7%, will she have to retract her study with Wessely where she found nothing, or at least write an addendum that her study was flawed?

(from fred's transcript snippets) And then they move on to CFS.... which she says they got into accidentally. They were approached by "people at Kings College London who have a cohort of chronic fatigue patients" and that "this is not a disease that we have any expertise in or that we work on". The 'people at Kings' asked if they'd test some samples and so sent blood from "people who had been very sick with chronic fatigue and we tested it with our assay which was highly sensitive...and we didn't find any evidence for the infection".

Shouldn't someone discipline her for rushing into print to uphold her opinion on non-research activities by others?

(from fred's transcript snippets) The interviewer then says it looks like there's no cause and effect. In fact, the virus isn't there at all.

McClure says "I can't say that because all we have done is to test 186 chronic fatigue patients. I mean, we could be in the same position as the Americans are with their prostate cancer - they're the only ones who can find an association so far, until we publish anything that we might find, so we can't say that - because, as the American group, Lombardi's group, has pointed out ad nauseum to people, we are not testing the same patients as they have so.... "

SO now she CAN'T say that the virus is not there? Hasn't she already said that she has proven that it is not there? Again - can we get a retraction or make more of this somehow?

Also, love that she seems to have difficulty saying that 3 letter acronym W P I. She says "the American group" Lombardi's group"

And I guess parvo WPI etc proving that they didn't use the same criteria for the patients is getting to her a touch. Love her use of "ad nauseum". Again though, if she admits that she was testing a different cohort, is that not reason for a retraction or addendum?

I'm so naive in these things - it seems to me she's given lots of quotes that can be used with the BMJ to force a retraction or addendum. Is this possible or am I just engaging in wishful thinking?

 

[Dx Revision Watch]

Also, from Julius's FOI response:

Shortlink: http://wp.me/p5foE-2Pr

[...]

[4] Request for information under FOIA by Julius, Canada

To: Imperial College London, Freedom of Information Office
Date: 09 February 2010
Subject: Request for information under FOIA in respect of Molecular Diagnostic Unit XMRV Test

Please acknowledge receipt of this request along with a Reference Number, and the date by which a response will be provided.

From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for 200 by the Molecular Diagnostic Unit via the Imperial College London website.

Please provide information regarding the exact testing methods employed in the test offered including, but not limited to the following:

1) blood sample volumes and processing

2) does the test use a molecular plasmid control in water or a positive blood sample

3) primer sequences and amplification protocol used

R: Further to your request for information dated 9 February 2010 regarding the exact testing methods employed in XMRV testing carried out at the College (below) technical details associated with testing CFS tissue for the presence of XMRV are published in PLoS 1 January 6th 2010.

Modifications of the assay for prostate cancer are not yet published and are not available to the public. The College hopes to publish this information before the end of the year.

 

[Robin]

I kind of feel bad for her. She's probably like, "WTF did I get myself into???? F*$&!"

 

[ukxmrv]

What deos she mean by "no one has isolated the virus"?

 

[bullybeef]

(from fred's transcript snippets) And then they move on to CFS.... which she says they got into accidentally. They were approached by "people at Kings College London who have a cohort of chronic fatigue patients" and that "this is not a disease that we have any expertise in or that we work on". The 'people at Kings' asked if they'd test some samples and so sent blood from "people who had been very sick with chronic fatigue and we tested it with our assay which was highly sensitive...and we didn't find any evidence for the infection".

I think the highlighted comment says everything. Chronic Fatigue isn't ME!! There is plenty of evidence to suggest what they really mean is neurasthenia. Even the definition suggests chronic fatigue.

Neurasthenia: chronic fatigue: a condition marked by chronic mental and physical fatigue and depression

 

[garcia]

I kind of feel bad for her. She's probably like, "WTF did I get myself into???? F*$&!"

Robin, save your sympathy for the innocent victims. McClure made some pretty strong statements earlier, which will come back to haunt her at some point. I hope she has the good sense to apologise for the harm she has caused to CFS patients, but I strongly suspect she won't.

Did anyone listen to what she said re: prostate cancer? Paraphrasing: "We know it's not a contaminant because its been sequenced in (8?) patients. It differs slightly from patient to patient, which it wouldn't do if it was a contaminant. Also it is different from any known murine virus."

Take those same arguments and apply them to the WPI Science paper and CFS! McClure is validating the WPI's methodology (without necessarily meaning to).

The story re: wanting to stop patients being prescribed anti-retrovirals to protect them is absolutely riddled with inconsistencies. It would be pretty much impossible to be prescribed anti-retrovirals on the nhs. What Wessely wanted was to stop any momentum gathering for the XMRV hypothesis. He wanted to kill it. Only the little man isn't big enough to do that. Nobody is.

 

[fred]

Isolating the virus and the virus in control groups

Ref not being able to isolate the virus in blood, I think the nuance here is that Prof McClure is discussing XMRV in prostate cancer.

Silverman found XMRV in prostate cancer but Dr Mikovits was the first to isolate it in the blood of ME patients. So, technically, McClure is right in what she is saying (although she does give the impression that ICL has managed to do this but she can't say more until the results are published later in the year).

The same applies to the control group figures (1% and 1.7%): this is for prostate cancer XMRV. What is not clear, however, is which XMRV Prof McClure was trying to find in the Kings samples. If it was prostate XMRV, that could explain why she didn't find it. And if she was looking for ME XMRV with prostate cancer assays, that could also explain why she didn't find it.

 

[Dx Revision Watch]

Ref not being able to isolate the virus in blood, I think the nuance here is that Prof McClure is discussing XMRV in prostate cancer.

Silverman found XMRV in prostate cancer but Dr Mikovits was the first to isolate it in the blood of ME patients. So, technically, McClure is right in what she is saying (although she does give the impression that ICL has managed to do this but she can't say more until the results are published later in the year).

The same applies to the control group figures (1% and 1.7%): this is for prostate cancer XMRV. What is not clear, however, is which XMRV Prof McClure was trying to find in the Kings samples. If it was prostate XMRV, that could explain why she didn't find it. And if she was looking for ME XMRV with prostate cancer assays, that could also explain why she didn't find it.

From the FOI response:

"From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for 200 by the Molecular Diagnostic Unit via the Imperial College London website.

Please provide information regarding the exact testing methods employed in the test offered including, but not limited to the following:

1) blood sample volumes and processing

2) does the test use a molecular plasmid control in water or a positive blood sample

3) primer sequences and amplification protocol used

R: Further to your request for information dated 9 February 2010 regarding the exact testing methods employed in XMRV testing carried out at the College (below) technical details associated with testing CFS tissue for the presence of XMRV are published in PLoS 1 January 6th 2010.

Modifications of the assay for prostate cancer are not yet published and are not available to the public. The College hopes to publish this information before the end of the year."

 

[julius]

What is not clear, however, is which XMRV Prof McClure was trying to find in the Kings samples. If it was prostate XMRV, that could explain why she didn't find it. And if she was looking for ME XMRV with prostate cancer assays, that could also explain why she didn't find it.

She said very clearly at one point, (she even emphasized it by repeating it twice) that the prostate and CFS strains are 'exactly the same'. She left no doubt that this is what she believes.

I wondered the same. Could looking for the prostate virus have made enough difference to cause the negative results?

 

[Bob]

You make some great points islandfinn...

If McClure is now saying that she is finding xmrv, and that it is in the general population at 1% to 1.7%, will she have to retract her study with Wessely where she found nothing, or at least write an addendum that her study was flawed?

Exactly!

Shouldn't someone discipline her for rushing into print to uphold her opinion on non-research activities by others?

Yes, she does seem to have been unnaturally keen to rush through this research on the presumption that there is no XMRV in ME patients... and she seems to be very keen to deny anti-retrovirals to ME patients... was she possibly under the influence of someone very influential, beginning with 'W'?

The interviewer then says it looks like there's no cause and effect. In fact, the virus isn't there at all.

McClure says "I can't say that because all we have done is to test 186 chronic fatigue patients. I mean, we could be in the same position as the Americans are with their prostate cancer - they're the only ones who can find an association so far, until we publish anything that we might find, so we can't say that - because, as the American group, Lombardi's group, has pointed out ad nauseum to people, we are not testing the same patients as they have so.... "

So now she CAN'T say that the virus is not there? Hasn't she already said that she has proven that it is not there? Again - can we get a retraction or make more of this somehow?

This is a very different attitude to what she was quoted as saying in the BBC news article i.e. that there is no XMRV in ME patients in the UK.

Also, love that she seems to have difficulty saying that 3 letter acronym W P I. She says "the American group" Lombardi's group"

I noticed this too... I think it must be professional pride and ego at work here!

 

[fred]

Different XMRV types

She said very clearly at one point, (she even emphasized it by repeating it twice) that the prostate and CFS strains are 'exactly the same'. She left no doubt that this is what she believes.

I wondered the same. Could looking for the prostate virus have made enough difference to cause the negative results?

Following on this theme.....

Isn't the difference between prostate XMRV and ME XMRV that the former has been found in tumour tissue whilst the latter has been isolated in blood? And didn't Prof McClure mention that Kings sent her DNA samples (and someone posted here before that this could mean tissue not blood)?

Hasn't Dr Mikovits also said that XMRV differs between prostate cancer and ME?

And where's that thread on 'Six different types of XMRV'? EDIT: here it is. http://www.forums.aboutmecfs.org/showthread.php?4285-Six-strains-of-XMRV-so-far!

Seems like ICL could have been looking for apples in a pie with a fork when they should have been looking for carrots in a stew with a spoon.

 

[julius]

Isn't the difference between prostate XMRV and ME XMRV that the former has been found in tumour tissue whilst the latter has been isolated in blood?

It's actually a genetic difference.

 

[vdt33]

All of you have done a great analysis! It's about time that these doctors and researchers are held accountable for their willful ignorance and incompetence that has done so much damage to so many people. It's tragic that it is taking so long for the truth to come out.

Best to all,

vdt

 

[Dx Revision Watch]

From the PLoS ICL paper:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008519

Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, Cleare A. (2010) Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS One. 2010; 5: e8519

PCR detection of XMRV and MLV sequences.DNA was extracted from EDTA whole blood using a standard phenol-based organic deproteinisation procedure [19]. DNA concentrations were determined by absorbance at 260 nm (A260). Each sample was amplified in three nested PCRs using primers targeted to an XMRV-specific sequence, to a sequence conserved amongst most MLV and, as a control for sample addition and PCR-inhibition, to a human beta-globin (hBG) sequence (Table 1). Each first-round reaction was performed in a 25 l volume containing 0.5 units TaqGold (Applied BioSystems, Warrington, UK), 1 x TaqGold reaction buffer (Applied BioSystems), 1.5 mM Mg2+, 200 mM each dNTP, 2.5 pmol each primer to which 5 l DNA extract or control was added. Reaction conditions were one cycle of 94C, 8 minutes, 35 cycles of 94C 30 seconds, 55C 30 seconds, 72C 30 seconds and one cycle 0f 72C, 7 minutes. Second round reaction mixes were identical to the first round and the sample was a 1 l transfer from the first round reactions. Second round reaction conditions were as for the first round over 30 cycles. PCR amplicons were visualised on a 1% agarose gel stained with ethidium bromide. Each PCR run consisted of test samples, six negative (water) and two positive controls. The positive control was a dilution of a plasmid with a full-length XMRV (isolate VP62) insert, generously gifted by Dr R. Silverman. To validate the sensitivity of the PCR, an end-point dilution of the plasmid was performed. To determine specificity of the PCR, a sample of human DNA from the LNCaP prostate cancer cell line (American Type Culture Collection, code CRL-1740) was amplified with the XMRV and MLV primer sets. To ensure integrity of the DNA extracts, three randomly selected samples were titrated to end-point using the hBG PCR to determine if the PCR copy number equated with the A260. To determine if the DNA extracts exhibited low level non-specific inhibition of PCR, 10 samples were subjected to 30 cycles of the first round hBG PCR (reaction mix and conditions as above) followed by 40 cycles of a nested real-time SYBR-green PCR using the SYBR-green Fast PCR kit (Roche, Lewes UK) according to the manufacturer's instructions.

 

[fred]

It's actually a genetic difference.

Sorry, I didn't word that first part too well. I meant to say that there are differences between the two XMRVs in where and how they've been found.

 

[fred]

DNA was extracted from EDTA whole blood.....

The positive control was a dilution of a plasmid with a full-length XMRV (isolate VP62) insert, generously gifted by Dr R. Silverman.

Does this mean they looked for the virus in blood using Silverman's prostate XMRV sequence?

 

[Dx Revision Watch]

ME Association on XMRV

The ME Association (the personal fiefdom of Dr Charles Shepherd) has issued this, today:


MAY BE REPOSTED

XMRV TESTING IN THE UK

The ME Association is receiving questions from people with ME/CFS and from health professionals about various aspects of XMRV blood testing here in the UK.

We have therefore summarised all the relevant information that is available at present.

General Advice on XMRV blood testing:

Our general advice regarding XMRV blood testing remains as follows:

Until it has been firmly established that there is a definite link between XMRV and ME/CFS, and an accurate method of testing for the virus in blood samples has been agreed by international retrovirologists (virologists who specialise in this type of infection), there is no point in people with ME/CFS spending a large sum of money on private laboratory testing for XMRV.

This is because:

1 With only one research study so far supporting a link to ME/CFS, and 3 validation studies not finding any evidence of XMRV in people from Europe with ME/CFS, the link between XMRV and ME/CFS remains uncertain.

2 There is no evidence at present to show that XMRV is a disease causing virus in relation to ME/CFS, or that it causes ME/CFS.

3 Being XMRV +ve does not confirm that someone has ME/CFS - the presence of XMRV cannot therefore, in our present state of knowledge, be used as a diagnostic marker for ME/CFS.

4 Being XMRV+ve is not, at present, an indication for treatment with antiviral medication, or any other speculative prescription- only medication. Antiviral drugs such as AZT can have serious side-effects (including development of myopathy and neuropathy - muscle and nerve damage) and given the fact that the NICE guideline on ME/CFS states that antiviral medication should not be prescribed in ME/CFS, doctors in the UK are unlikely to be willing to prescribe antiviral medication in the current state of uncertainty.

5 The current methods for testing for XMRV may be producing either false positive results or false negative results. The accuracy of commercial testing has not been properly validated.

6 Individual counselling and medical advice should be available to people who take an XMRV test - in exactly the same way that it is given to people before and after taking an HIV test. In the case of commercial XMRV testing, this sort of advice does not appear to be available in the private sector. From the ethical point of view, the availability of informed medical input also apply to research studies if the XMRV result is going to be given to the people involved.

There are further XMRV research studies in progress in Australia, Europe and the USA, and the results will be gradually appearing over the coming months. Hopefully, a clearer picture will have emerged by the end of the year as to whether XMRV is linked to ME/CFS. If this is the case then further research will then need to examine whether the virus is actually involved in causing symptoms in ME/CFS (it may just be a harmless passenger) and whether appropriate antiviral medication needs to be assessed in clinical trials.

XMRV testing: NHS and Private

Testing for XMRV is not available on the NHS and we are not aware of any private UK pathology labs who are testing for this virus, or have the expertise to do so. So the only way to get an XMRV test is to send a blood sample to an overseas laboratory. Further information on the availability of overseas XMRV testing can be found here: http://www.xmrvtesting.co.uk/

One of the commercial laboratories in the US that has been offering XMRV blood tests has now withdrawn this facility until the scientific controversy surrounding XMRV and ME/CFS has been resolved >> http://www.codiagnostics.com/XMRV/diseases.php

Extract from the codiagnostics statement on XMRV:

While XMRV is an infectious retrovirus and will certainly impact the medical community, people with CFS may be better served by waiting for further studies connecting XMRV to CFS prior to investing in a diagnostic. Those who choose to be tested anyway should understand that any testing at this point is research only in aiding to establish the actual prevalence of the virus in the CFS community. Until the scientific controversy surrounding XMRV is resolved, Cooperative Diagnostics has removed its test from the market and will participate in research only.

What should people in the UK do if a blood test shows that they are XMRV +ve?

If you have been informed that as a result of a blood test you are XMRV +ve, this result should be discussed with your GP and/or ME/CFS specialist. The ME Association cannot provide individual advice on lifestyle or drug management in this situation. This has to be a decision for you and your medical adviser.

Retesting XMRV status in the UK

The MEA believes that a small but important part of further research into a possible link between XMRV and ME/CFS is to retest anyone who has sent blood to the US. This process would involve retesting at one of the retroviriology laboratories here in the UK that has been unable to find any evidence of XMRV in the blood samples they have analysed so far. We know that the UK research groups would be willing to do this retesting but this research can only move forward if people are willing to volunteer. The MEA Ramsay Research Fund is willing to assist with the funding of this research.

We have also indicated that all the research groups that have published positive and negative findings on XMRV so far should now test a new cohort of mutually agreed ME/CFS patients. We will then know whether there is agreement or disagreement when blood samples from the same cohort of people with ME/CFS are simultaneously tested. The MEA Ramsay Research Fund would again be willing to help fund a well designed study.

Blood donation and XMRV status

The ME Association has written to Sir Liam Donaldson, the Chief Medical Officer, to ask him to reconsider the current advice on blood donation and ME/CFS so that people with a past history of ME/CFS are also excluded from donating blood. The position, at present, remains unchanged in that people with ME/CFS should not donate blood until they have fully recovered. This official advice goes back some time and is not related to XMRV.

Summary of current advice regarding blood donation can be found here:

http://www.meassociation.org.uk/ind...ion-canada-uk-andusa&catid=30:news&Itemid=161

Most recent statement on the blood donation situation in Canada:

http://www.transfusionmedicine.ca/a...ces-responds-possible-new-blood-safety-threat

Possible consequences of being XMRV +ve

We have been asked whether insurance companies and others will be placing restrictions on people who are XMRV +ve in the way that this sort of discrimination can take place with people who are HIV+ve. At present, we are not aware of any insurance companies that have introduced any such restrictions, or are intending to do so in the near future. But this is clearly something that people will need to think about if they are considering having an XMRV blood test. Remember the relevant question may be whether you have been tested for HIV (or XMRV) and not whether the result is in your medical notes.

It should also be noted that the exact mode of transmission of this retrovirus remains uncertain. If XMRV does turn out to be a disease causing virus similar to HIV, and can be transmitted in a similar way through body fluids, then people who turn out to be XMRV+ will obviously have to take the same precautions in relation to lifestyle, sexual relations etc that apply to HIV. They will also have to cope with some of the restrictions that may occur as a result.

MEA website poll on XMRV

The April MEA website poll is assessing public opinion on XMRV >>

http://www.meassociation.org.uk

Dr Charles Shepherd
Hon Medical Adviser, ME Association

ENDS

 

[fred]

Suzy, I've started a separate thread on the MEA statement :Retro tongue:

http://www.forums.aboutmecfs.org/sh...g-in-the-UK-statement-from-The-ME-Association

 

[Bob]

Following on this theme.....

Isn't the difference between prostate XMRV and ME XMRV that the former has been found in tumour tissue whilst the latter has been isolated in blood? And didn't Prof McClure mention that Kings sent her DNA samples (and someone posted here before that this could mean tissue not blood)?

Hasn't Dr Mikovits also said that XMRV differs between prostate cancer and ME?

And where's that thread on 'Six different types of XMRV'? EDIT: here it is. http://www.forums.aboutmecfs.org/showthread.php?4285-Six-strains-of-XMRV-so-far!

Seems like ICL could have been looking for apples in a pie with a fork when they should have been looking for carrots in a stew with a spoon.

She also said that XMRV has only been isolated from tissue and not from the blood... so obviously she didn't read the Science paper then!

Does anyone know exactly what DNA she used for her ME research study?
And why was she studying DNA anyway? XMRV is an exogenous virus, not an endogenous virus, so she' should have been looking for retro-viral RNA in the blood, not at any DNA, surely?

hmm... I think maybe we just shouldn't waste any more time, effort or energy on this failed and discredited study!