Accessing a copy of MRC National Archives material via PDF

Accessing a copy of MRC National Archives material via PDF

Shortlink: http://wp.me/p5foE-34g

NB: If the link isn’t working for you, try this:

Go to this URL:

http://www.nationalarchives.gov.uk/documentsonline/default.asp

which is the National Archives Documents Online page

Put this Catalogue reference code into the Search box

FD 23/4553

Select date range 1950-99

that should bring up the page. Then pick up my instructions from there.

Instructions:

Go here:

http://tinyurl.com/NationalArchivesMRC

that is:

http://www.nationalarchives.gov.uk/documentsonline/details-result.asp?queryType=1&resultcount=1&Edoc_Id=8553429

The National Archives Documents Online

Description Myalgic encephalomyelitis (ME)/postviral fatigue syndrome (PFS) : papers and journal articles; correspondence and enquiries with MRC replies

Date 1988-1997
Catalogue reference FD 23/4553
Dept Records created or inherited by the Medical Research Council
Division General Records of the Medical Research Committee and Medical Research Council
Series Medical Research Council: Registered Files, Scientific Matters (S Series)
Image contains complete documents usually loaded

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Click “Add to shopping” (there will be no charge, so don’t worry)

Click “Check out”

An email address will be requested.

Fill in a working email address.

Click “Proceed with your download”

An auto generated email will be sent to you.

The email you receive will include an order number and the date up until which the file will be available to you. (This was 28 days.)

Beneath the words:

“Your images are now available. If you have not already downloaded them, please go to the download screen at”

There is a clickable link “Download my documents now”.

Click the link which will take you to a PDF URL. The URL will be specific to your email address.

The URL will open a PDF of approximately 30 MB which you can save to your hard drive in the usual way.

The file consists of a 143 page bundle of copies of letters, responses, papers, notes of meeting and handwritten notes.

Some pages, extracts, names and addresses have been redacted and are marked:

“REDACTED UNDER
FOI EXEMPTION
SECTION 40 (2)
CLOSED UNTIL 2071”

———

(Note: This is a very large file which is why National Archives do not supply it via an email attachment. I accept no responsibility for the consequences of anyone being inconsiderate enough to forward the file as an email attachment which may cause considerable problems for some email account holders.)

Related material

28 December 2009

Response from Public Services Development Unit, National Archives

http://wp.me/p5foE-2yP 

11 December 2009

The Medical Research Council’s secret files on ME/CFS: Margaret Williams

http://wp.me/p5foE-2vm

Important statement from Imperial College, London (XMRV Detection Testing)

Important statement from Imperial College, London (XMRV Detection Testing)

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

(Please note that all the pages for the XMRV Testing were off line at 11.15am GMT)

Imperial College webpage:

Imperial College London  XMRV Testing Notification

XMRV testing

We wish to apologise for any confusion concerning the availability of this test and would like to clarify that it is only available as part of an ethically approved research project. We emphasis that our laboratory does not deal directly with patients and we are not advising people who are concerned that they might have CFS, or who have been diagnosed with CFS, to request this test.

The Prof Wessely XMRV Detection Test exchanges

The Professor Wessely XMRV Detection Test exchanges

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

This report may be reposted provided it is published in full, unedited and https://meagenda.wordpress.com is credited as the source.

Compiled by Suzy Chapman  |  7 February 2010

On 4 February, it was widely reported around the internet that the Molecular Diagnostics Unit, Imperial College, London, is now offering XMRV Detection Testing. All the available information on this £200 test, as it currently stands on Imperial College website, is published in this posting:

Complete text of Imperial College, London XMRV Detection Testing web pages (06.02.10)

In January, a study published by PLoSOne, and led by Prof Myra McClure of Imperial College, had reported that its authors found no evidence that XMRV is associated with CFS in the UK.

The study concluded:

“Based on our molecular data, we do not share the conviction that XMRV may be a contributory factor in the pathogenesis of CFS, at least in the U.K.”

and

“XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.”

On 5 February, a member of the ME community, Fiona Verity, contacted Professor Simon Wessely, one of the co- authors of the paper: 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: e8519Full paper

Prof Wessely is acknowledged in the paper as having been responsible for “providing samples and associated data from a well characterised and valuable cohort of subjects.”

[Cohort = 186 patients (62% female, age range 19-70, mean 39.6±11.3 years) from consecutive referrals to the CFS clinic at King’s College Hospital, London.]

On 5 February, the ME Association issued this position statement:

ME Association  |  05 February 2010

XMRV testing at Imperial College, London

Imperial College, the research centre in the UK that has found no evidence of XMRV infection in any of the blood samples from people with ME/CFS that they have looked at, has announced that their Molecular Diagnostics Unit is now offering their method for XMRV testing to the public: Imperial College announcement

 MEA POSITION STATEMENT

Until we have the results from more replication studies the link between XMRV and ME/CFS remains speculative and unproven. We do not therefore believe that there is any point in spending money on an expensive blood test which is not, at present, going to act as either a diagnostic marker or an aid to management. And any laboratory offering this test to the public has an ethical duty to make these points clear.

We would, however, be interested to hear from anyone in the UK who does decide to have an XMRV test.

The latest MEA summary on XMRV can be found here

A summary of the Imperial College research which looked for XMRV in ME/CFS can be found here

We hope that the situation regarding XMRV and ME/CFS will become clear once results from the other replication studies appear in the scientific journals over the coming months.

On 6 February, the ME Association published this notice: http://tinyurl.com/MEAonICLXMRVtest

“Late last night The ME Association was informed that this announcement about XMRV testing does not apply to people with ME/CFS, or suspected ME/CFS. It only relates to the availability of the Imperial College XMRV test to referring doctors who are dealing with cases of prostate cancer. A full clarification will appear on the Imperial College website on Monday. It will appear here once we have it.”

The ME Association does not specify the provenance of this information.

When Imperial College does publish a clarification I will post an update at the top of this posting.

There has been much confusion about the purpose of this test and the patient population(s) that might be referred for it.

Questions have also been raised around the specific testing methods being used in relation to XMRV and its possible association with prostate cancer or suspected prostate cancer. Other laboratories have found XMRV in prostate tumour and tumour-associated tissues only, not in whole blood samples as specified by Imperial College. (References [1], [2] and [6], Imperial College website text.)

Ms Verity has very kindly given permission to publish in full the email exchange between herself and Professor Wessely.

From: Fiona Verity
Sent: 05 February 2010 16:57
To: Zielona, Olga
Subject: F.A.O Prof Wessley please forward

Dear Professor Wessley,

I am aware that the XMRV test is to be made available for purchase. I am concerned about this and would be grateful if you would read the following email that I have sent to ME agenda (below). I hope you will understand that there are many very vulnerable people aware of the research into an illness that is crippling their lives. Whilst you and your colleagues I am sure have their best interests at heart I fail to see why you are now offering this test to CF/ME sufferers and furthermore they will be charged.

Your own research failed to detect the XMRV virus yet you are going to sell this test for £200 to the very people that your research results concluded will not have this virus. I feel I must have misunderstood the thread of all this somewhere and I hope you will take the time to reply; my main question at this point is, do you expect the XMRV virus to now be detected in these tests perhaps through a different approach, if so what will you be doing with the findings and if not is there a benefit to be had by those paying and having the test?

Your advice is keenly awaited.

Thank you

Fiona Verity MSc

5th February 2010

To Whom It May Concern,

As I understand it the research for the connection between CF and XMRV virus tests according to Kings College were inconclusive. Furthermore, it appears questionable that this UK study can be compared with the major research and findings carried out in the US, as the exact conditions were not replicated and therefore one would expect different outcome measures. From what I understand it the very approach offered by Kings College for the process/testing of XMRV is flawed in-as-much as their controls do not replicate the procedures and protocols applied in the US therefore suggesting that King’s College research would fail to detect the XMRV virus.

Needless-to-say I am concerned that you are now making this same XMRV test available to ME/CF patients because it appears that this will be wasting their money – unless of course the testing approach has been altered to replicate US study and test? Secondly if the test is the same as that used in Kings College’s initial research then these results from the new tests paid for by CF/ME sufferers will go further to ‘falsely’ supporting inconclusive outcome result of Kings College’s own research.

I urge you therefore to look further into the matter so as not to afford a disservice to those you wish to assist i.e. ME/CF sufferers not to mention the devastating consequences of supporting research that could indeed be harmful to further much needed research in the field.

However, if I have misunderstood any element of this I look forward to an explanation at your earliest convenience.

Your faithfully

F. Verity MSc

 

From: Wessely, Simon
Date: 5 February 2010 18:26
Subject: RE: F.A.O Prof Wessley please forward
To: Fiona Verity

Thank you for your inquiry re the announcement from Imperial College that they are offering a diagnostic test for XMRV

I understand that this is not intended for people who know they have CFS or are concerned they might have CFS

I can see that this is not clear from the announcement though, but it seems this was an oversight which is going to be speedily corrected

I hope this clarifies matters

Simon Wessely

Professor Simon Wessely
Vice Dean, Institute of Psychiatry,
Head, Department of Psychological Medicine,
Director, King’s Centre for Military Health Research,
King’s College London

Imperial College website content as it stood at 6 February 10

Complete text of Imperial College, London XMRV Detection Testing web pages

Shortlink: http://wp.me/p5foE-2K1

ME Association position statement: XMRV testing at Imperial College, London

ME Association position statement: XMRV testing at Imperial College, London

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

Following an extraordinary move by Imperial College, London to offer testing for XMRV infection at £200 a pop (ICL must be very confident their test will return no positives), the ME Association issues a position statement:

ME Association  |  05 February 2010

XMRV testing at Imperial College, London

Imperial College, the research centre in the UK that has found no evidence of XMRV infection in any of the blood samples from people with ME/CFS that they have looked at, has announced that their Molecular Diagnostics Unit is now offering their method for XMRV testing to the public: Imperial College announcement

MEA POSITION STATEMENT

Until we have the results from more replication studies the link between XMRV and ME/CFS remains speculative and unproven. We do not therefore believe that there is any point in spending money on an expensive blood test which is not, at present, going to act as either a diagnostic marker or an aid to management. And any laboratory offering this test to the public has an ethical duty to make these points clear.

We would, however, be interested to hear from anyone in the UK who does decide to have an XMRV test.

The latest MEA summary on XMRV can be found here

A summary of the Imperial College research which looked for XMRV in ME/CFS can be found here

We hope that the situation regarding XMRV and ME/CFS will become clear once results from the other replication studies appear in the scientific journals over the coming months.

ICL/KCL XMRV study: Responses to Authors’ Response on PLoS

ICL/KCL McClure/Wessely XMRV study: Responses to Authors’ Response on PLoS One

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

Related material:

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Abstract and links for full paper: http://wp.me/p5foE-2Bd
Media coverage Round up 1: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2: http://wp.me/p5foE-2BA

Imperial College London News Release PDF: Imperial College London News Release XMRV

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Otto Erlwein¹, Steve Kaye¹, Myra O. McClure¹*, Jonathan Weber¹, Gillian Wills¹, David Collier², Simon Wessely³, Anthony Cleare³

1 Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom, 2 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King’s College London) De Crespigny Park, Denmark Hill, London, United Kingdom, 3 Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Camberwell, London, United Kingdom

The website of PLoS One, online publishers of the Imperial College London study “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome” (5 January 2010), maintains a Comments Section here

In response to criticism around subject selection procedures and methodology, study authors from the Institute of Psychiatry, King’s College London, have published the following response:

Original Article
Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Authors Response
Posted by Anthony_Cleare on 12 Jan 2010 at 19:55 GMT  

on behalf of

Professor Simon Wessely, Professor of Psychological Medicine
Professor David Collier, Professor of Psychiatric Genetics
Dr Anthony Cleare, Reader in Neuroendocrinology

On 13 January, a version of the commentary below was published on the PLoS One site in response to Wessely, Collier and Cleare, by sociologist, Angela Kennedy:

Angela Kennedy

The authors’ reply to the concerns about patients selection for research for this paper raises more problems in addition to those of the original paper. My comments here should be read in addition to other problems raised by authors on this forum.

Firstly, the authors express some resentment towards those who have legitimately questioned this research cohort and the criteria over the years, which is rather surprising. Contrary to insinuation by the authors, no person on the PloSOne Responses Forum has insinuated that the research cohort they use are somehow ‘ess deserving’ than say, the WPI cohort, purely that they are a different type of patient, using different criteria that select a different population, and that this may cause problems with the findings, and claims made based on those findings, with regard to the British ‘CFS’ population.

This is a reasonable concern to express, and such a deduction can be made based on the evidence the authors provide themselves in their paper, citations, and their response. For example, their paper states:

“Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness.”

In the authors’ response here, they also write:

“Thus patients in our service have also co-operated in studies of PET and fMRI neuroimaging, autonomic dysfunction, neurochemistry, respiratory function, vitamin status, anti nuclear antibodies, immune function, neuroendocrine function and genetics “

While patients being processed for a research cohort may well, indeed are likely, to have co-operated and had such tests done, this does not necessarily mean that patients with positive results are part of the research cohort.

Indeed, positive results, which would indicate organic abnormality, would surely be likely to prevent a patient being selected for a cohort, by the very logic described in the author’s paper here, by their own response (the additional tests are considered ‘not clinically necessary’?) and in at least one of their citations (Quarmby et al)?

In the Quarmby et al paper, the cohort is described, in which the criteria used (in addition to ‘Fukuda/CDC’) is ‘Oxford’. The Oxford criteria (Sharpe et al 1991), in particular, actually do allow for patients who fulfil organic abnormality to be selected out of a research cohort. Indeed, Anthony David, referring to these, commented at the time:

“British Investigators have put forward an alternative, less strict, operational definition which is essentially chronic (6 months or more) severe disabling fatigue in the absence of neurological signs with myalgia, psychiatric symptoms and previous viral infections as common associated features.”

Here, special attention needs to be paid to the term ‘previous viral infections’ and ‘absence of neurological signs’, in order to contextualise the cohort selection process applied using the Oxford Criteria.

It is therefore quite reasonable to presume that patients in the cohort described in the Erlwein et al paper are less likely to be suffering from organic abnormalities associated with ‘CFS’ populations than in other research cohorts.

It is also rational to be concerned that the cohort described here may not be representative of many people diagnosed with ‘CFS’ in Britain.

NICE guidelines for example, acknowledge that very little research has been done on ‘severely affected’ patients, who comprise, possibly, at least 25% of the population of people given a ‘CFS’ diagnosis (though so little research has been done on ‘severely affected’ in Britain, the true number is not yet clear).

While patients potentially destined for a research cohort which weeds out ‘detectable organic abnormality’ may be subjected to a rigorous amount of investigations, those not undergoing this process do not undergo such testing – at least not in the NHS. Indeed, such investigations of clinical patients are severely proscribed in the majority of ‘guidelines’: NICE, and the RCPCH guidelines as just two examples.

Ironically, Fukuda guidelines also make the following comment:

“The use of tests to diagnose the chronic fatigue syndrome should be done only in the setting of protocol-based research.

“In clinical practice, no additional tests, including laboratory tests and neuro-imaging studies, can be recommended. Examples of specific tests (which should not be done) include serologic tests for enteroviruses; tests of immunologic function, and imaging studies, including magnetic resonance imaging scans and radionuclide scans (such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) of the head.

“We consider a mental status examination to be the minimal acceptable level of assessment.” (1994)

That clinical populations are not to be afforded the types of investigations given to research populations makes the whole idea of ‘medically unexplained’ or ‘unexplained by disease’, or ‘functional’ (as synonymous with ‘non-organic’ or not discernibly ‘organic’) as common characterisations of CFS (including by at least one of the authors themselves in previous publications –  for just one example, Page et al, 2003), highly problematic at best.

It is also significant that ‘CFS’ is so often described as a ‘diagnosis of exclusion’ (see, for example, the Centre for Disease Control CFS information website.

(Footnote: http://www.cdc.gov/cfs/cfsdiagnosis.htm )

Certain research case definitions comply with this assumption, such as the Oxford Criteria (Sharpe et al, 1991) and CDC Criteria (Fukuda et al, 1994). Here, ‘diagnosis of exclusion’ also functions as a euphemism of ‘medically unexplained’. The key problem within this recurring theme in the literature, which most frequently remains un-addressed, is how a clinical patient’s condition can all too easily become ‘medically unexplained’ because of the practice of encouraging doctors to severely limit investigations in the first place: except, it would appear, ironically, in research populations in which ‘organic’ illness is being weeded out to provide the type of cohort that might fulfil ‘not organically ill’ definitions.

The issue of ‘disability’ also needs to be clarified. The references cited in the Erlwein paper to support the statement that the patient cohort was of ‘high levels of disability’ refer only to ‘disability’ in psycho-social terms or feelings of ‘fatigue’, and not in terms of physical impairment, a key omission.

Mundt et al’s paper, in particular, focuses on specific mental health problems and the social exclusionary effects of living with these. While in no way invalidating or trivialising the disability caused by mental health problems, it must be pointed out that both Mundt et al and Chalder Scales nevertheless fail to elucidate a high level of physical or physiological (say, for example, neurological, mitochondrial and/or cardiovascular) impairment – key problems present in people given a clinical diagnosis of ‘CFS’, usually related to specific organic abnormalities that can be found, if they are tested for in the first place.

With regard to the Canadian criteria (Carruthers et al), in fact they have undergone some ‘validation’. Jason et al found:

“…Canadian criteria selecting cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurologic symptoms. The overall findings suggest that the Canadian clinical criteria appear to select a more symptomatic group of individuals than the CFS criteria, and these individuals do demonstrate less current and lifetime psychiatric impairment than those selected according to the CFS criteria. In contrast, the CFS group was not significantly different from the Chronic fatigue-psychiatric group in psychiatric impairment.

“Predictably, the Chronic fatigue-psychiatric group evidenced the highest frequency of current and lifetime psychiatric disorders… Overall, there were 17 significant symptom differences between the Canadian and Chronic fatigue-psychiatric group, but only 7 significant symptom differences between the CFS and Chronic fatigue-psychiatric group. Findings suggest that the Canadian criteria select a group of patients with more symptoms, and the Canadian criteria identify a group with higher levels of physical functional impairment and less psychiatric comorbidity.

“Findings from the present study indicate that the Canadian criteria does capture many of these cardiopulmonary and neurological abnormalities, which are not currently assessed by the current CFS case definition (Fukuda et al., 1994).

“However, it is worth noting that when the Fukuda et al. (1994) CFS case definition was conceived, the research had not yet been done investigating these abnormalities. In combination with symptom patterns, it is possible to conclude that the Canadian group does select individuals with greater impairment, particularly given the physical composite score, fatigue/weakness, neurologic and neuropsychiatric symptoms, as these symptoms can interfere with daily living and occupational performance. Results from this present investigation highlight the importance of contrasting different diagnostic criteria in order to gain a greater understanding of the syndrome now known as CFS. The findings do suggest that the Canadian criteria point to the potential utility in designating post-exertional malaise and fatigue, sleep dysfunction, pain, clinical neurocognitive, and clinical autonomic/ neuroimmunoendocrine symptoms as major criteria for future attempts to define this syndrome…”  (Comparing Definitions )

In addition to using the Carruthers et al criteria (or ‘Canadian Criteria’), the WPI give this information about their patient cohort in their supporting online material:

“Their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to peturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assyas) and elevated cytokines particularly interleukin-6 and interleukin-8. In addition to these immunological abnormalities, the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing…”

(http://www.sciencemag.org/cgi/content/full/117905/DC1 )

It is therefore highly unlikely, as the authors indeed acknowledge in their reply here, that Erlwein et al were testing the same type of patient as those tested by the WPI, which inevitably makes the Erlwein et al findings – and perhaps some of the wilder claims that they have ‘cast serious doubt’ on the WPI’s findings, unfortunately made in some of the lay media – not scientifically tenable. The failure of Erlwein et al to include such type of patient in their cohort, does not mean that such patients do not exist in Britain. Copious patient anecdotal experience, research reports, and charity surveys indicate that they do exist. Whether XMRV is present or not is another matter, but there are enough identifiable problems around patient selection alone with the Erlwein et al paper to indicate this is not a definitive disproving of the existence of the virus in Britain.

Ongoing neglect of the importance of establishing a possible ‘CFS’ patient population in Britain, clinically and in research settings, using the Canadian Guidelines, is preventing the development of knowledge that might help extremely ill and disabled people here in Britain.

The problems I have briefly outlined here do not fully express the range and depths of problems with regard to: the identity of an accurate ‘CFS’ population; the instabilities of ‘CFS’ criteria per se; the faulty concepts of ‘medically unexplained’ or ‘functional’ and relation to ‘psychogenic’ explanations for somatic illness; the vagaries of criteria that claim to facilitate a ‘diagnosis of exclusion’; and the psychogenic dismissal of serious organic dysfunction of patients given a ‘CFS’ diagnosis, problems that have happened for many years. These problems are relevant to the Erlwein et al paper. Furthermore, they are highly relevant to all research that claim a psychological and/or behavioural aetiology to the condition or conditions that get deemed as ‘CFS’.

REFERENCES

Carruthers, B. et al (2003): Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, Vol. 11(1), pp 7-115.

Chalder, T. Berelowitz, G. Pawlikowska, T. Watts, L. Wessely, S. Wright, D. Wallace, E. P.:Development of a fatigue scale. Journal of Psychosomatic Research Vol 37: Issue 2: Feb 1993: 147-153.

David, A.S.:Postviral syndrome and psychiatry.  British Medical Bulletin: 1991: 47: 4: 966-988.

Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.:The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994 Dec 15;121(12):953-9.

Jason LA, Torres-Harding SR, Jurgens A, Helgerson J.:Comparing the Fukuda et al. Criteria and the Canadian Case Definition for chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome 12(1):37-52, 2004.

Mundt, J.C. Marks, I.MShear, K. Griest, J.H.:The work and social adjustment scale: a simple measurement of impairment in functioning. British Journal of Psychiatry (2002) 180: 461-443.

Page, L.A. Wessely, S.:Medically unexplained symptoms: exacerbating factors in the doctor–patient encounter. J R Soc Med 2003;96:223-227.

Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al: Chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.

Competing interests declared: Social scientist critically evaluating ‘psychogenic’ explanations for somatic illnesses. Parent of adult who given a ‘CFS’ diagnosis as a child.

Documented involvement of viruses in ME/CFS: M Williams 30 December 09

Documented involvement of viruses in ME/CFS by Margaret Williams

One of a series – see notice below

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

Full text here in MS Word format: Documented involvement of viruses in ME 30.12.09

and at:

http://www.meactionuk.org.uk/Documented-involvement-of-viruses-in-ME.htm

http://www.meactionuk.org.uk/Documented-involvement-of-viruses-in-ME.pdf

Documented involvement of viruses in ME/CFS

by Margaret Williams

30 December 2009

For decades it has been known and shown that viruses play a role in ME/CFS. Now there is evidence of a direct association with a gamma retrovirus – XMRV – that disables the immune system in ME/CFS, thus allowing numerous latent viruses to re-activate, which could result in the protean symptomatology…

NOTICE

Magical Medicine: How to make a disease disappear – Hooper and Williams – Spring 2010

Prior to the publication of the MRC PACE Trial results in the Spring of 2010, Professor Malcolm Hooper and Margaret Williams will be releasing a series of linked documents addressing central flaws in the PACE Trial.

These documents form part of a more substantial document that has the provisional title

Magical Medicine: How to make a disease disappear

This document has a dedicated web page at:

http://www.meactionuk.org.uk/Magical-Medicine.htm

This web page will contain an easily accessible Contents page so that people can surf and then select whatever section (or part of a section) they may wish to look at.

Although he and Margaret Williams have previously addressed some of the issues contained in the substantial document, Professor Hooper thinks it essential for there to be a single, comprehensive narrative of events and information leading up to and involving the PACE Trial.

Magical Medicine: How to make a disease disappear

Professor Malcolm Hooper and Margaret Williams

Spring 2010

http://www.meactionuk.org.uk/Magical-Medicine.htm

Documents already published that form part of the larger PACE Response document:-

1. Interstitial cystitis and CFS (26th August 2009)

http://www.meactionuk.org.uk/Interstitial_cystitis_and_Chronic_Fatigue_Syndrome.htm

2. More evidence of inflammation in ME/CFS (14th November 2009)

http://www.meactionuk.org.uk/More-evidence-of-inflammation-in-(ME)CFS.htm

3. The role of viruses in ME/CFS // XMRV (21st November 2009)

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm

4. The MRC’s secret files on ME/CFS (10th December 2009)

http://www.meactionuk.org.uk/The-MRC-secret-files-on-ME.htm

5. Statements of concern about CBT/GET for the Judicial Review (12th December 2009)

http://www.meactionuk.org.uk/Statements-of-Concern-for-High-Court.htm

6. Can the MRC PACE Trial be justified? (17th December 2009)

http://www.meactionuk.org.uk/Can-the-MRC-PACE-Trial-be-justified.htm

and now this latest one:

7. Documented involvement of viruses in ME/CFS (30th December 2009)

http://www.meactionuk.org.uk/Documented-involvement-of-viruses-in-ME.htm

XMRV retrovirus replication: Round up 4

XMRV retrovirus replication: Round up 4:

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA
Round up 3 here: http://wp.me/p5foE-2Ci

Shortlink for this posting: http://wp.me/p5foE-2CG

Additional material, on 8 January, will be added to the top of this posting.

Wall Street Journal  |  Jacob Goldstein  |  7  January 2010

Or maybe that virus isn’t linked to Chronic Fatigue Syndrome

—————-

The Economist  print edition  |  7 January 2010

Science and Technology: Chronic fatigue syndrome

A fight over the cause of a mysterious disease

—————-

PLoS ONE Discussion Board

Topic: Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

On the discussion board for PLoS ONE (who published the Imperial College study) Dr M McClure, a co-author of the study, has been responding to queries and comments.

—————-

Media coverage

Evening Herald  |  John Von Radowitz  |  6 January 2010

New drugs for chronic fatigue ‘do not work’

—————-

Discover Magazine  |  6 January 2010

Scientist smackdown: Is a virus really the cause of Chronic Fatigue Syndrome?

—————-

ScienceNOW Daily News  |  Sam Kean  |  6 January 2010 

Chronic Fatigue Syndrome Attacked Again

Related content:

Science Magazine
NEWS OF THE WEEK
Virology
Chronic Fatigue and Prostate Cancer: A Retroviral Connection?
Sam Kean (9 October 2009) Science 326 (5950), 215-a. [DOI: 10.1126/science.326_215a]

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Questions to Dr McClure

Cort Johnson, Creator of Phoenix Rising: An ME/CFS Website and ‘Bringing the Heat’: An ME/CFS Blog raised the following questions with Dr McClure, co-author of the Imperial College London paper. Dr McClure’s responses are interspersed. Cort has given permission for these to be republished.

Forums.aboutmecfs.org

Dr. McClure’s Response To Questions

I emailed Dr. McClure some questions and she responded.

(1) You (apparently) looked at different gene sequences than in the original report. Why look at different sequences?

We chose sequences we considered to be specific for XMRV and generic to MLV for the reasons given in the paper.

(2) You stated that you felt Lombardi et. al. should held off a bit with their findings. What do you they should have done differently?

I gave my opinion in response to a question at a press conference, but it is not for me to advise or lecture Lombardi et al.

(3) Some questions have been raised by Dr. Vernon regarding techniques that were slightly different from the original paper. Could those effected your results?

No. Provided controls have been included to a) confirm the integrity of the DNA b) ensure that human DNA is being amplified c) to ensure that no inhibition of the PCR is taking place and d) the assay is sufficiently sensitive to detect the virus, then a diifference in protocol does not matter. We controlled for all of this. The one major difference we could not control for, of course, was that the patient cohort is different.

(4) You noted your rigorous attempts to preclude contamination. Does this suggest that contamination from a murine leukemia virus could have effected Lomdardi’s results?

It is far from clear that this was a problem in the Lombardi paper. Indeed, their sequencing data (given in the supplementary data to the Science paper) would argue against it. We highlighted our own conditions because it was right to give a clear insight into how the experiments were carried out.

(5) If the Lombardi et. al. are not finding XMRV what might they finding and culturing in their lab?

They would argue that they are detecting XMRV in their patients. We have not tested those patients, so we cannot dispute this point. Our data simply says that we cannot find this virus in a UK cohort.

Official Statement from the Whittemore Peterson Institute Regarding UK Study

Official Statement from the Whittemore Peterson Institute Regarding UK Study [Imperial College London PloS ONE XMRV paper]

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

Released: 6 January 2010    

PDF: WPI Official Statement 06.01.10

Whittemore Peterson Institute for Neuro-Immune Disease

FOR IMMEDIATE RELEASE
Frankie Vigil
R&R Partners for
Whittemore Peterson Institute
775-336-4555
frankie.vigil@rrpartners.com 

Official Statement from the Whittemore Peterson Institute Regarding UK Study

The Whittemore Peterson Institute (WPI) has reviewed the paper entitled “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome.” This study did not duplicate the rigorous scientific techniques used by WPI, the National Cancer Institute and the Cleveland Clinic, therefore it cannot be considered a replication study nor can the results claim to be anything other than a failure not just to detect XMRV, but also a failure to suggest meaningful results.

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.

The WPI study was published after six months of rigorous review and three independent lab confirmations, proving that contamination had not taken place and that infectious XMRV was present in 67 percent of CFS patients diagnosed according to the Canadian and Fukuda criteria.

In contrast, this latest study was published online after only three days of review. Significant and critical questions remain as to the status of patient samples used in the UK study as those samples may have been confused with fatigued psychiatric patients, since the UK has relegated “CFS” patients to psychiatric care and not traditional medical practices.

“Little is known about the prevalence of XMRV world-wide, much less the incidence of XMRV in ME/CFS or prostate cancer” emphasizes Dr. Judy Mikovits. “WPI and its NCI collaborators are actively engaged with international research teams to investigate these important questions.”

WPI does not recommend the use of anti-retroviral drugs that have yet to be proven to be effective in treating XMRV infection. However, several large pharmaceutical companies have expressed interest in developing anti-retroviral and immune modulating drugs that will effectively treat XMRV associated diseases.

WPI looks forward to the results of other scientific groups around the world, serious about replicating its scientific results, by using the same techniques as WPI and its collaborators. The fact that XMRV was detected in 67 percent of the CFS samples in the U.S. study determined a significant association between XMRV and CFS, demanding a much more serious inquiry by responsible health agencies around the world as to the cause of this debilitating disease

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Whittemore Peterson Institute
The Whittemore Peterson Institute for Neuro-Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of the immune system and the nervous system, often results in lifelong disease and disability. The WPI is the first institute in the world dedicated to X associated neuro-immune disease (XAND), and other X associated diseases, integrating patient treatment, basic and clinical research and medical education.

XMRV retrovirus replication: Round up 3

XMRV retrovirus replication: Round up 3: NHS Choices; CFIDS news release; Neuroskeptic blog

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2Ci

Media coverage

NHS Choices  |  6 January 2010

UK NHS Choices site

Virus link to CFS ‘in doubt’

“Serious doubt has been cast on the theory that…chronic fatigue syndrome is caused by a new retrovirus,” The Guardian reported. The newspaper said researchers from London have failed to replicate findings from the US that suggested a possible role for a virus called XMRV in causing CFS, also known as ME (myalgic encephalomyelitis).

In the new study none of the 186 UK CFS patients tested carried the XMRV virus, in contrast to the US study in 2009, which found that about two-thirds of 101 CFS patients tested had the virus. Why the two studies have different findings is not clear, but the results of the UK study do not support an association between XMRV infection and CFS in UK patients. This highlights the importance of different research groups repeating experiments in different populations.

CFS is a complex disease, and its causes are not well understood. Although an association with XMRV has not been established, this does not rule out the possibility that viral infection is involved. Much more research will be needed in this area.

Where did the story come from?

The research was carried out by Dr Otto Erlwein and colleagues from Imperial College London and King’s College London. The researchers were funded by the South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry and the National Institute for Health Research Biomedical Research Centre. The study was published in the peer-reviewed open access journal PLoS ONE.

The Guardian, Daily Mail and The Independent reported the story. In general, the coverage is balanced and accurate. The headline of the Daily Mail story that “British experts say ME virus is a myth” might be taken to mean that this research excludes any role for viral infection in CFS/ME, but this research only looked at one virus (XMRV).

What kind of research was this?

This cross-sectional study investigated whether people in the UK with chronic fatigue syndrome (CFS) were infected with the xenotropic murine leukaemia virus-related virus (XMRV). In 2009, a case control study from the US found that more people with CFS carried the virus than people without the condition. The researchers in this study wanted to see if XMRV was similarly common in people from the UK with CFS.

A cross-sectional study design is appropriate for determining how common a particular trait is among a certain group of people. However, neither this study, not the original case-control study could prove whether XMRV potentially caused CFS, as neither would be able to establish whether people with XMRV had been infected before they developed CFS or after. The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than in those without it, as it did not include a control group of people without the disease.

What did the research involve?

The researchers enrolled 186 people with CFS who were living in the UK. These people had been medically examined and diagnosed with CFS according to standard criteria, and other potential causes of their symptoms had been ruled out. Blood samples were taken and tested for the presence of DNA from XMRV or a related virus called murine leukaemia virus (MLV). A number of control tests were also carried out to show that the DNA in these samples was intact, that any positive findings were not a result of contamination of their experiment and that their test would identify XMRV if it was present. The inclusion of these controls is important for ensuring that the experiments were working well and were reliable. The researcher who carried out the DNA tests did not know which of the samples came from people with CFS.

The participants, all of whom had been referred to a CFS clinic, were mainly female (62%) with an average age of 39.6 years. They had been unwell for an average (median) of four years (range one to 28 years), and had high levels of fatigue. Few participants were working and about a fifth (19%) belonged to CFS/ME support groups. Just under half of the participants (45%) said that their CFS definitely related to a viral infection and 45% said that it might relate to a viral infection. The researchers suggested that the characteristics of their sample were typical of those seen in CFS patients attending specialist clinical services in the UK.

What were the basic results?

The researchers did not identify XMRV or MLV in the blood from any of the 186 CFS patients tested. Their control tests showed that the DNA being tested was intact, that there was no contamination in their experiments and that when XMRV was present (in a positive control sample containing XMRV DNA) their test detected it.

How did the researchers interpret the results?

The researchers concluded that they “found no evidence that XMRV is associated with CFS in the UK”. They suggested that the reason for the differences between their findings and those from the US might be due to differences in how common XMRV infection is in the different countries.

Conclusion

This study suggests that the XMRV infection is not common in CFS patients in the UK. A previous case-control study from the US found that about two-thirds of the 101 CFS patients tested carried XMRV, compared to about 4% of 218 healthy controls. This led the researchers from the US study to suggest that XMRV might be the cause of CFS in these patients. The reason for the differences between the US and UK studies is not clear, but the authors of the UK study suggest that it could be due to XMRV infection being more common in the US than in Europe.

The findings of this current study highlight the importance of different research groups repeating experiments in different populations. The study does have some limitations in that it was relatively small and all participants came from one CFS centre in London. Further studies in more participants from different centres in the UK would be useful in determining whether these findings are typical of the UK as a whole.

Even if this study had found significant levels of XMRV in CFS patients, it would not have been able to prove the virus actually caused the condition. This is because, like the original US case-control study, it could not establish whether people with XMRV had been infected before they developed CFS or after.

The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than those without, as it did not include a control group of people without the disease.

The results of this UK study do not support an association between the XMRV virus and CFS in UK patients. The researchers do not rule out a role for all viruses in CFS, and say that “prospective epidemiological studies have confirmed that certain infective agents, for example Epstein Barr virus, are unequivocally associated with subsequent CFS, even if the mechanisms are unclear and almost certainly multi factorial”. CFS is a complex disease, and its causes are not well understood. Much more research will be needed in this area.

Links to the headlines

Research casts doubt over US chronic fatigue virus claim. The Guardian, January 06 2010
British experts dash ME breakthrough hopes following American promise of new treatment. Daily Mail, January 06 2010
Scientists’ claim to have found the cause of ME is ‘premature’. The Independent, January 06 2010

Links to the science

Erlwein O, Kaye S, McClure MO, et al. Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. PLoS ONE, 2010; 5/

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Patient advocacy organisations

CFIDS Association of America   |  6 January 2010

CFIDS Association of America Expresses Concerns About UK XMRV Replication Study

Additional and More Rigorous Research Needed

CHARLOTTE, N.C. (January 6, 2009) – The CFIDS Association of America issued the following statement in response to a study published in today’s edition of PLoS ONE that failed to detect the XMRV virus in banked samples drawn from 186 CFS patients in the United Kingdom. A study published Oct. 8, 2009 in Science reported that 68 of 101 CFS patients from clinics in the U.S. tested positive for XMRV.

“The CFIDS Association of America reviewed the study published in today’s edition of PLoS ONE. We are concerned about many elements of this study including differences between the patients selected by the two groups, different processes used to collect and test the blood samples, and the rapid nature of the new publication, as evidenced by the three days that separated the dates of submission and acceptance,” stated K. Kimberly McCleary, president and CEO of the CFIDS Association of America. “We urge the media and the research and patient communities to view these findings in the context of evolving understanding and to insist upon more rigorous and standardized replication studies before drawing conclusions about the role of XMRV in the pathophysiology of CFS.”

CFIDS Association scientific director Suzanne D. Vernon, PhD, made the following assessment: “The new report from the U.K. should not be considered a valid attempt to replicate the findings described by Lombardi, et al., in the Science article. This paper heavily underscores the need for expedient, yet robust, XMRV-focused research to build upon the results reported this past fall, studies like the one being conducted by the Department of Health and Human Services Blood XMRV Scientific Research Working Group.” Vernon holds her doctorate in virology from the University of Wisconsin and had 17 years experience in public health research on infectious diseases before joining the Association’s staff in 2007 to lead its research program. She added, “Without a standardized method of detecting XMRV, millions of dollars might be wasted on independent attempts to determine the prevalence of XMRV in different populations.”

“Every person whose life has been impacted by CFS wants urgently to identify the cause of and a cure for this devastating condition that affects millions of people worldwide. While time is of the essence, we must insist upon rigorously conducted and reviewed science that provides absolute validation, definitive answers and unbridled hope,” said McCleary.

The CFIDS Association of America is the nation’s largest charitable organization dedicated to making CFS widely understood, diagnosable, curable and preventable. It is the greatest source of funding for CFS research outside the federal government. To view Dr. Vernon’s detailed analysis of the U.K. study, please visit

http://www.cfids.org/cfidslink/2010/010603.asp

Citations:
Erlwein O, Kaye S, McClure MO, Weber J, Willis G, Collier D, Wessley S, Cleare A. (2010) Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS ONE 5(1):e8519. doi:10.1371/journal.pone.0008519

Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 8 October 2009. 1179052.

Science Bloggers

Neuroskeptic  | 6 January

Chronic Fatigue Syndrome in “not caused by single virus” shock!

Imperial College London News Release 06.01.10

Imperial College London NEWS RELEASE 06.01.10

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2BT

Imperial College London News Release

On the ICL website

Open PDF: Imperial College London News Release XMRV

Wednesday 6 January 2010

New virus is not linked to Chronic Fatigue Syndrome, suggests UK research

New UK research, published today in PLoS ONE, has not reproduced previous findings that suggested Chronic Fatigue Syndrome may be linked to a recently discovered virus. The authors of the study, from Imperial College London and King’s College London, say this means that anti-retroviral drugs may not be an effective treatment for people with the illness.

An estimated three in 1000 people have Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis (ME), experiencing severe physical and mental fatigue that is not alleviated by rest, together with other symptoms such as muscle pain, headache, joint pain and depression. Diagnosing CFS is difficult, as symptoms vary and there is no standard test. The fundamental cause of CFS is unknown and it is usually treated using rehabilitation techniques such as cognitive behavioural therapy or graded exercise therapy.

In October 2009, a group of US scientists published research in the journal Science that suggested that a recently discovered virus called XMRV could be linked to CFS. In their study, 68 out of 101 patients with the illness and 8 out of 218 healthy controls appeared to be infected with the virus.

However, in today’s study, researchers found no evidence that patients with CFS had the XMRV virus, after analysing tissue samples from 186 patients with CFS using sensitive molecular testing techniques.

This more recent analysis showed no molecular evidence for XMRV in any of the samples from CFS patients. The researchers say this means that anti-retrovirals should not be used to treat CFS, as they would be unlikely to have an effect on the symptoms. However, several labs in the US now offer CFS  patients treatments based on the earlier findings that linked the condition with XMRV.

Professor Myra McClure, one of the authors of the study from the Division of Medicine at Imperial College London, said: “Our research was carried out under rigorous conditions – we looked at samples from well-studied patients, and we used very sensitive testing methods to look for the virus. If it had been there, we would have found it. The lab in which we carried out the analysis had never housed any of the murine leukaemia viruses related to XMRV, and we took great care to ensure there was no contamination.

“We are confident that our results show there is no link between XMRV and Chronic Fatigue Syndrome, at least in the UK. The US study had some dramatic results that implied people with the illness could be treated with anti-retrovirals. Our recommendation to people with Chronic Fatigue Syndrome would be not to change their treatment regime, because our results suggest that anti-retrovirals would not be an effective treatment for the condition,” added Professor McClure.

After reading the US study, clinical researchers from King’s College London sent blood samples from 186 CFS patients to the Imperial Retrovirology Laboratory team. King’s has been running an NHS service for CFS patients for nearly twenty years, and the previously stored samples came from patients had been fully investigated and examined, meaning that CFS was the correct diagnosis.

The Imperial scientists extracted the DNA from the samples and analysed it using a sensitive technique, called Polymerase Chain Reaction (PCR), which can locate tiny fragments of virus DNA. The scientists analysed control samples of water at the same time to ensure there was no contamination. They also looked for a specific marker fragment of human DNA in the sample to make sure the technique was working.

The water controls contained no DNA, showing that the samples were not contaminated. All the test samples, from patients and healthy controls, contained the human DNA they looked for, suggesting the technique was working well.

Dr Anthony Cleare, Reader in Psychiatric Neuroendocrinology, one of the authors of the study from the Chronic Fatigue Syndrome Clinic at King’s College London, said: “Chronic Fatigue Syndrome is a serious and debilitating condition. It can also be extremely frustrating for people with the illness, as we have yet to identify its  fundamental cause, or come up with any definitive treatments. The recent US study generated real excitement among doctors and patients alike as it seemed to open up a new line of research. Unfortunately, we have not been able to replicate those findings.”

“It is important to emphasise that today’s findings do not invalidate all previous research, some of which has shown that CFS can be triggered by other infective agents, such as Epstein Barr Virus or Giardia parasites. As ever in science, no single study is conclusive and there are lots of other research groups working on this at the moment. We await their results with interest,” added Professor Simon Wessely, another author of the study from the Chronic Fatigue Syndrome Clinic at King’s College London.
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Notes to Editors:
1. “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome” PLoS ONE, Wednesday 6 January 2010.