Journal of Psychosomatic Research: In Press: Is there a better term than “Medically unexplained symptoms”?


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The Elephant in the Room Series Three:

Journal of Psychosomatic Research In Press: Is there a better term than “Medically unexplained symptoms”?

WordPress Shortlink for this posting:

24 October 2009


An In Press version of the Editorial: Is there a better term than “Medically unexplained symptoms”?, to be published in a forthcoming issue of the Journal of Psychosomatic Research, is already available online (purchase required). The Editorial needs to be read in conjunction with a white paper from:

The European Association for Consultation-Liaison Psychiatry and Psychosomatics (EACLPP)

A white paper of the EACLPP Medically Unexplained Symptoms study group

Patients with medically unexplained symptoms and somatisation – a challenge for European health care systems  ( )

The White Paper can be downloaded from the EACLPP site here:

The document is approx 76 pages long, including tables and charts.  I had considerable difficulty opening this document, in May, due to a corrupted table and I note that the file on the EACLPP site is still glitchy. A copy of the document was therefore obtained directly from the EACLPP and can be opened by clicking the link below.  Note that there may have been revisions to the document as supplied on 19 May, but it will serve as reference for those who might also experience difficulties opening the file from the EACLPP website. If you would like a copy of the file sent to you as a Word.doc, email ME agenda with “EACLPP MUS DOC” in the subject line and I will forward a copy [600 KB].  The tables and charts are slow to load.

Draft – prepared by: Peter Henningsen and Francis Creed January 2009

EACLPP Working group on MUS version 16 Jan 2009

The current issue of the Journal of Psychosomatic Research is Volume 67, Issue 5, Pages A1-A4, 367-466 (November 2009)

Journal of Psychosomatic Research

In Press

Is there a better term than “Medically unexplained symptoms”?



References and further reading may be available for this article. To view references and further reading you must purchase this article.


Francis Creed a, Elspeth Guthrie a, Per Fink b, Peter Henningsen c, Winfried Rief d, Michael Sharpe e and Peter White f

a University of Manchester, Manchester, UK 
b University Hospital Aarhus, Denmark
c Technical University, Munich Germany
d University of Marburg, Germany
e University of Edinburgh, UK
f Queen Mary University of London, UK

Received 24 August 2009; revised 24 August 2009; accepted 7 September 2009. Available online 17 October 2009.

Article Outline


“Medically unexplained symptoms” – one advantage, but many reasons to discontinue use of the term

Criteria to judge the value of alternative terms for “medically unexplained symptoms”

Terms suggested as alternatives for “medically unexplained symptoms”

Implications for treatment

Implications for DSM-V and ICD-11




Francis Creed is Co-Editor of the Journal of Psychosomatic Research.

Francis Creed, Per Fink, Peter Henningsen and Winfried Rief were all members of the international CISSD Project, (Principal Administrators: Action for M.E.; Co-ordinator: Dr Richard Sykes. Dr Sykes is now engaged in the “London MUPSS Project” in association with the Institute of Psychiatry).

Michael Sharpe was UK Chair for the CISSD Project.

Michael Sharpe and Francis Creed have been members of the APA’s DSM-V Somatic Distress Disorders Work Group since 2007.

Francis Creed (UK), Peter Henningsen (Germany) and Per Fink (Denmark) are the co-ordinators of European EACLPP MUS Work Group.

Francis Creed and Peter Henningsen were the authors of “A white paper of the EACLPP Medically Unexplained Symptoms study group – Patients with medically unexplained symptoms and somatisation – a challenge for European health care systems”, January 2009.

Draft white paper here:

Per Fink is a member of the Danish Working Group on Chronic Fatigue Syndrome, established in August 2008 and expected to complete its work in spring 2009.


An Editorial: The proposed diagnosis of somatic symptom disorders in DSM-V to replace somatoform disorders in DSM-IV – a preliminary report by DSM-V Work Group members, Joel Dimsdale and Francis Creed on behalf of the DSM-V Workgroup on Somatic Symptom Disorders was published in the June 2009 issue of the Journal of Psychosomatic Research.

Full text of the June 2009 DSM-V SSD Work Group preliminary report can be accessed here:

See section: Psychological factor affecting general medical condition 

“…The conceptual framework that we propose will allow a diagnosis of somatic symptom disorder in addition to a general medical condition, whether the latter is a well-recognized organic disease or a functional somatic syndrome such as irritable bowel syndrome or chronic fatigue syndrome…”

No updates or reports have been published on the APA’s website by DSM-V Task Force or Work Groups since brief reports issued in April 2009. DSM-V is anticipated to be finalised in May 2012 with field trials expected to start this October. No detailed Timeline for DSM-V is available.

Previous DSM Task Force chairs, Robert L Spitzer and Allen Frances, have been two of the most vocal critics of the current Task Force’s oversight of the revision process. Read their joint letter to the APA Board of Trustees here:  Letter to APA Board of Trustees July 09. In Dr Frances Responds to Dr Carpenter: A Sharp Difference of Opinion, Psychiatric Times, 9 July, Frances called for the posting of all the suggested wordings for DSM-V criteria sets well before considering field trials.


Javier Escobar, co-author of the Special Report: Unexplained Physical Symptoms: What’s a Psychiatrist to Do? Psychiatric Times, Aug 2008, was also a member of the Work Group for the “Conceptual Issues in Somatoform and Similar Disorders (CISSD) Project.

Javier Escobar is a member of the DSM-V Task Force, serves as a Task Force liaison to the Somatic Symptom Disorders Work Group and said to work closely with this work group.

01 August 2008
Psychiatric Times. Vol. 25 No. 9
Special Report

Unexplained Physical Symptoms What’s a Psychiatrist to Do?

Humberto Marin, MD and Javier I. Escobar, MD

According to Escobar and Marin:

“The list of somatoform disorders kept expanding with the addition of vague categories, such as “undifferentiated somatoform disorder” or “somatoform disorder NOS [not otherwise specified],” which, unfortunately, are the most common diagnoses within the somatoform genre. These terms failed to transcend specialty boundaries. Perhaps as a corollary of turf issues, general medicine and medical specialties started carving these syndromes with their own tools. The resulting list of “medicalized,” specialty-driven labels that continues to expand includes fibromyalgia, chronic fatigue syndome, multiple chemical sensitivity, and many others (Table 1).

Table 1

Functional somatic syndromes

Irritable bowel syndrome
Chronic fatigue syndrome
Multiple chemical sensitivity
Nonspecific chest pain
Premenstrual disorder
Non-ulcer dyspepsia
Repetitive strain injury
Tension headache
Temporomandibular joint disorder
Atypical facial pain
Hyperventilation syndrome
Globus syndrome
Sick building syndrome
Chronic pelvic pain
Chronic whiplash syndrome
Chronic Lyme disease
Silicone breast implant effects
Candidiasis hypersensivity
Food allergy
Gulf War syndrome
Mitral valve prolapse
Chronic low back pain
Interstitial cystitis
Systemic yeast infection
Total allergy syndrome”

These labels fall under the general category of functional somatic syndromes and seem more acceptable to patients because they may be perceived as less stigmatizing than psychiatric ones. However, using DSM criteria, virtually all these functional syndromes would fall into the somatoform disorders category given their phenomenology, unknown physical causes, absence of reliable markers, and the frequent coexistence of somatic and psychiatric symptoms.”

DSM-V and ICD-11 have committed as far as possible “to facilitate the achievement of the highest possible extent of uniformity and harmonization between ICD-11 mental and behavioural disorders and DSM-V disorders and their diagnostic criteria” with the objective that “the WHO and APA should make all attempts to ensure that in their core versions, the category names, glossary descriptions and criteria are identical for ICD and DSM.”

The International Advisory Group for the Revision of ICD-10 Mental and Behavioural Disorders most recent meeting took place on 28 – 29 September. It is anticipated that a Summary Report of the meeting will be available in late November/December.

For detailed information on the proposed structure of ICD-11, the Content Model and operation of iCAT, the collaborative authoring platform through which the WHO will be revising ICD-10, please scrutinise key documents on the ICD-11 Revision Google site:

For information around the DSM and ICD revision processes see DSM-V and ICD-11 Directory page:


IACFS/ME statement, CFSAC meeting, Reeves CFS Definition Petition

Whittemore Peterson XMRV link with CFS study Media Round up: 14

WordPress Shortlink:

IACFS/ME statement: New Study finds link between XMRV retrovirus and CFS/ME

IACFS/ME’s Recommendations:
CDC’s Five Year Strategic Plan for CFS Research

Date: October 21, 2009

New Study finds link between XMRV retrovirus and CFS/ME

An article published online (10/8/09) in the journal Science reported that 68 of 101 patients with CFS, or 67 percent, were infected with an infectious virus, xenotropic murine leukemia virus-related virus, or XMRV. By contrast, only 3.7 percent of 218 healthy people were infected. XMRV is a retrovirus, a member of the same family of viruses as the AIDS virus. These viruses carry their genetic information in RNA rather than DNA, insert themselves into their hosts’ genetic material, and stay for life.

These new findings raise the possibility that XMRV could be a possible cause of the illness or an effect of altered immune function in CFS patients who are more susceptible to these viruses. More studies are needed to explain the occurrence of XMRV in the genetic material of CFS patients.

The research was carried out by principal investigator Judy Mikovits and colleagues from the Whittemore Peterson Institute, the National Cancer Institute, and the Cleveland Clinic in the US.

This new finding about the XMRV virus is an exciting development, although its significance has yet to be determined. First, the study needs to be replicated in well-defined CFS samples in the community and in physician’s offices. Prospective studies (following patients over time) are essential to determine if the virus is contributing to the cause, persistence, and/or severity of the illness.

The good news is that if XMRV is linked to CFS, there are many antiviral drugs that have already been safety tested in H.I.V. that may inhibit XMRV replication. Thus studies to determine the safety and efficacy of these antiviral agents for CFS/ME patients could be designed and executed in short order.

Important Meeting of the CFS Advisory Committee

on Oct. 29-30 in Washington, DC

The CFS Advisory Committee makes recommendations to the Secretary of Health and Human Services regarding government-based CFS research, funding and programs. This is a critical meeting because the future of $25 million in public funding for CFS research at the Centers for Disease Control will be discussed. IACFS/ME wants these funds to be spent on cutting edge biomedical research leading to objective diagnosis and treatment of CFS. We also want CFS to become a public health priority so that issues of stigma and the absence of good medical care are addressed.

The new CFS retroviral study on XMRV in the top tier journal Science shows what can be done to advance the medical research. But this is only a first step. Without follow-up, the momentum we now have will be lost. Only with broad based support from the professional and patient communities will we have a voice in how federal funds for CFS research are spent.

What we need is strong attendance at the CFSAC meeting. If we pack the house (we have to fill only 50 seats), that will show that we care about this illness and support all appropriate biomedical research and public policy initiatives that legitimize CFS. If you can attend for even 2 hours that would be helpful.

For an informative Q and A about the study, click on the link below:

Fred Friedberg, PhD


Tom Kindlon  21 October 2008, via Co-Cure

Reeves Criteria Petition update: Marly Silverman (Pandora) to bring petition print-out to CFSAC meeting

Marly “Marla” C. Silverman, Founder of P.A.N.D.O.R.A. (Patient Alliance for Neuroendocrineimmune Disorders Organization for Research & Advocacy, Inc has been in touch to say that she will be bringing a print-out of the “entire petition” (i.e. the visible signatures and comments) to the CFSAC meeting at the end of October.

Please use whatever resources you have access to (e.g. blogs, Twitter, Facebook, other social networking sites, newsletters, E-mail lists/discussion forums, etc) to highlight the existence of the petition. The petition also links to some critiques of the definition. Many people have also written interesting comments.

Note: I have no intention of closing the petition site until the CDC stop using this flawed definition.

I’m appending the text of the petition below with a link.

Tom Kindlon

The petition

We call on the Centers for Disease Control and Prevention (CDC) to stop using the “empirical” definition[1] (also known as the Reeves 2005 definition) to define Chronic Fatigue Syndrome (CFS) patients in CFS research.

The CDC claim it is simply a way of operationalizing the Fukuda (1994) definition[2]. However the prevalence rates suggest otherwise: the “empirical” definition gives a prevalence rate of 2.54% of the adult population[3] compared to 0.235% (95% confidence interval, 0.142%-0.327%) and 0.422% (95% confidence interval, 0.29%-0.56%) when the Fukuda definition was used in previous population studies in the US[4,5].

The definition lacks specificity. For example, one research study[6] found that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the empirical/Reeves definition.


[1] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome – a clinically empirical approach to its definition and study. BMC Med. 2005 Dec 15;3:19. Link:

[2] 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 Int Med 1994, 121:953-959.

[3] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.

[4] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.

[5] Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37.

[6] Jason, LA, Najar N, Porter N, Reh C. Evaluating the Centers for Disease Control’s empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2008, doi:10.1177/1044207308325995.

Further reading:
Problems with the New CDC CFS Prevalence Estimates Leonard Jason, Ph.D., DePaul University  i.e.



[Ed: Note: Dr David Bell will be presenting at the Thursday Session of the CFSAC (CHRONIC FATIGUE SYNDROME ADVISORY COMMITTEE) 29-20 October meeting at 3:30 p.m. and speaking on CFS and FII/MBP.  See under Lectures and presentations.]

Dr. David Bell on XMRV Research: “Now We Can Get Down to Business”
by David S Bell, MD, FAAP
October 21, 2009

This information is reproduced with kind permission from the October 2009 issue of Dr. Bell’s free Lyndonville News e-newsletter. It was published shortly after research linking the “XMRV” retrovirus and ME/CFS went live in the journal Science on October 8.

Holy smokes! Just when I want to retire this comes along. How am I going to get any peace and quiet?

Here is the Lyndonville News coming out within a week of a paper being published, and already what I have to say is old news. Probably everyone reading this newsletter has been on the edge of their seats listening to NPR, CBS, Reuters, and so on. The CDC has already said that it isn’t going to pan out. It is my guess that the media coverage will intensify because this is really big news.

First of all, congratulations…

To Drs. Judy Mikovits, Vincent Lombardi, Robert Silverman, Dan Peterson and the rest of the authors. And a special congratulations to the Whittemore Family Foundation, and the Whittemore-Peterson Institute for putting this together. For many years ME/CFS has been limping along on complex science that points to mechanisms of illness that most physicians have ignored. Limped along with skeptical specialists, medical establishments, government agencies. Limped along despite attacks by disability companies. Now we can get down to business…

Full article here


Previous ME agenda Media Round ups

Round up 14: Whittemore Peterson XMRV link with CFS study Media update: 14:  (you are here)

Revised MEA statement on retrovirus XMRV and ME/CFS (Version 2):

Round up 13: NIH $1.6 Million award for ME/CFS Research for Drs. Mikovits & Kerr: 

Round up 12: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 12:

Round up 11: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11:

Round up 10: Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal):

Round up 9: Notice from Dr David Bell, Lyndonville News; Article by Paul R. Cheney MD, PhD:

Round up 8: XMRV retrovirus study: Position statement from ME Association 14.10.09:

Round up 7: XMRV Retrovirus: Whittemore Peterson Institute: CFS: Media Round up 7:

Round up 6: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study: Videos and audios:

Round up 5: Supporting Online Material for XMRV Chronic Fatigue Syndrome study:

Round up 4: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study:

Round up 3: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome retrovirus XMRV in the media:

Round up 2: Science 9 October 2009: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 08.10.09:

Round up 1: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 09.10.09:

MEA summary of meeting of APPG on ME (21 October 2009) and APPG Legacy paper

1] MEA summary of meeting of APPG on ME (21 October 2009)

(Note this is a brief personal summary published by Dr Charles Shepherd on behalf of the ME Association and not the official meeting Minutes.  The Minutes and possibly a verbatim transcript will be issued at a later date by the  secretariat on behalf of Dr Des Turner, Chair, APPG on ME.)

2] APPG on ME launches legacy paper consultation

WordPress Shortlink:

MEA summary of meeting of APPG on ME (21 October 2009)

This is a very brief summary of key points from the APPG meeting held on Wednesday 21 October in Committee Room 21 at the House of Commons.

The meeting was Chaired by Dr Des Turner MP.

Among parliamentarians present were the Countess of Mar, Russell Brown MP, Andrew Stunell MP, Bill Wiggin MP, and Tony Wright MP..

Representatives from charities and other organisations included those from AfME, BRAME, Kent and Sussex Alternative Group for ME, The MEA, reMember, RiME, Sussex and Kent ME Society, WMMEG and the 25% Group. There were also several members of public present.

A more detailed account of the meeting will appear in the Minutes, which will be posted on the APPG website when they have been through the drafting process and agreed.


The main item was a presentation from the Rt Hon Yvette Cooper MP, Secretary of State for Work and Pensions, on benefit issues. Yvette was accompanied by Dr James Bolton, Deputy Chief Medical Adviser at the DWP.

Yvette explained that she had a strong personal interest in ME having suffered from it for a period starting in 1993 before entering parliament. During this time she was very ill for a period of roughly two years and completely off work for a year. This was followed by a period of recovery with more variable health over another two years. She has now made a full recovery and manages to combine being an MP, Minister and bringing up three children! During her early days in parliament she was actively involved with the APPG when it was chaired by Tony Wright MP. However, she did not feel it was appropriate to make general assumptions about ME/CFS based on her own experience.

Yvette briefly outlined the aims behind changes to the care, welfare and benefit systems that are now taking place –in particular the introduction of Employment and Support Allowance (ESA) to replace Incapacity Benefit and the role of the Work Capability Assessment (WCA) in deciding eligibility for ESA. Following on from her personal experience with ME she fully understood the concerns being expressed about assessing the fluctuating nature of ME/CFS and the need for a flexible approach regarding any possible return to work. She believed that the new WCA for ESA claimants took these problems into account. However, she was very willing to look at the problems that were raised during the meeting.

Yvette answered a series of questions from the Chair, who also read out written questions that had been submitted in advance of the meeting, along with questions from those attending the meeting. Yvette had only intended to be there for around 20 minutes but managed to stay for about an hour.

Questions relating to all the common and very familiar problems facing people with ME/CFS were discussed. In particular:

The role of the new Work Capability Assessment for ESA claimants – especially in relation to people being unable to sustain physical/mental activity and the post-exertional symptomatology experienced by people with ME/CFS. In response, Yvette pointed out that this assessment should not depend on a precise diagnosis but on what a claimant could and could not do from the point of view of physical and mental function.

The type of information and training on ME/CFS that is given to DWP decision makers and examining doctors. In response, Yvette maintained that adequate training in relation to specific illnesses such as ME/CFS was part of the DWP programme.

Difficulties in accessing assessment centres. In response, she noted these concerns, agreed that the centres must be accessible to people with disabilities, and said she is very keen to hear of specific examples.

The way in which a patient’s own GPs and specialist were progressively being removed from the opinion gathering process and replaced by doctors who knew nothing about the patient’s social and medical background. In response she noted these concerns but did not indicate that there would be any shift in the DWP position.

Providing real help for people who can and want to return to work on a flexible and/or part time basis. In response, she agreed that this was vital – citing her own experience of a gradual and flexible return to work after having quite severe ME.

Reviewing the permitted work rules – which can be very unhelpful in the case of ME/CFS. These concerns were sympathetically noted.

Des Turner raised the specific issue of problems with tribunals and the knowledge about ME/CFS of those who sat on the panels making these decisions. Examples of very unsatisfactory procedures at tribunals were mentioned by several of those present. In response, Yvette managed to somewhat duck the issue by explaining that the tribunals are classed as being ‘independent’ and their administration comes under the Ministry of Justice. This is clearly going to remain an important issue on the parliamentary agenda.

Tony Wright MP made the point that something was clearly wrong with the benefit assessment system when so many people with ME/CFS were failing on their first application but then being successful on appeal.

Charles Shepherd questioned the DWP auditing and monitoring of the success/failure rate of applications for ESA from people with specific illnesses, including ME/CFS. In response, Dr Bolton explained that no figures are available.

With regard to DLA and the government Green Paper, Yvette was asked about the mixed messages coming from ministers on the future of DLA. In reply, she acknowledged the concerns being expressed and made it clear that DLA for people of working age was not under review. She stated that a government statement on DLA would be made on Wednesday 22 October by the Rt Hon Andy Burnham.

At the end of this presentation. Charles Shepherd asked Dr James Bolton if he would be willing to meet with ME/CFS charity representatives to discuss these concerns in more detail and he agreed to do so. This meeting is now being followed up through the Forward ME group.


APPG INQUIRY INTO NHS SERVICES IN ENGLAND Des Turner explained that the report was now being written with the intention of having it ready for presentation to the APPG at the next meeting in early December. A Minister from the Department of Health will be invited to attend this meeting to respond to the report.

APPG LEGACY PAPER Des Turner explained that the APPG would have to be reformed after the general election – which will have to take place before June 2010. And with him standing down as an MP we would need to find a new Chair in 2010. To coincide with the winding up of the APPG, a Legacy Paper is being prepared which outlines the key areas of work and actions that have been taken by the APPG during the current parliament, as well as future actions. The APPG is keen to receive input on this from people with ME/CFS and a copy of the current draft will be posted on the APPG website. Comments on this draft must be received by the Secretariat by 19 November – so that further discussion on a further draft can take place at the December meeting.

STATEMENT BY WMMEG (West Midlands ME Groups Consortium): Jill Cooper read out a further statement relating to issues about patient representation, transparency and the suitability of the education and training programme provided by the ME/CFS Clinical and Research Network and Collaborative (CCRNC) This was followed by a very lively discussion on the current state of NHS services for people with ME/CFS.

XMRV: A rather informal discussion on various aspects of the new viral research findings took place.

Date of next meeting: Provisionally fixed for Wednesday 2 December

APPG website:


APPG on ME launches legacy paper consultation

A consultation on the Legacy Paper for the All Party Parliamentary Group (APPG) on M.E. was launched yesterday (October 22).

The current Chair of the APPG, Dr Des Turner, intends to stand down at the next General Election, due sometime before 3 June 2010.

Comments on the draft APPG legacy paper should be sent to the Secretariat  

This email address is being protected from spam bots, you need Javascript enabled to view it no later than 19 November 2009.

The Countess of Mar, who is Secretary of the Group, thanked people with M.E. and Action for M.E. for the work done so far in producing the draft.

The main speaker at the meeting was the Rt Hon Yvette Cooper MP, Secretary of State for Work and Pensions, who described her own personal experience of M.E. and answered a number of questions. In particular, she reassured people with M.E. that it was not the Government’s intention to change working-age Disability Living Allowance under current care reform proposals.

Other topics on the agenda included an update on the APPG Inquiry into NHS services, which is expected to produce a report before the next meeting of the APPG, which will take place on Wednesday 2 December 2009. A Minister from the Department of Health would be invited to attend.

In addition to the Chair, Dr Turner and the Secretary, the Countess of Mar, the meeting was attended by Vice Chairs Andrew Stunell MP and Tony Wright MP (Vice Chairs), plus Bill Wiggin MP and Russell Brown MP.

Minutes and a transcript of the meeting will be produced in due course.

Download Draft Legacy Paper in PDF

Revised MEA statement on retrovirus XMRV and ME/CFS

Revised MEA statement on retrovirus XMRV and ME/CFS

WordPress Shortlink:


This is a considerably extended and updated version of our first summary on XMRV research. It includes additional information relating to questions that are coming to the MEA about the research findings, in particular questions concerning possible transmission and spread of XMRV, availability of private and NHS tests for the virus here in the UK, possible treatment of XMRV with antiviral drugs, and volunteering for UK research studies. We also report on a new research study from Germany that has queried the link between XMRV and prostate cancer.

This summary is intended to be a balanced account which not only raises questions but is also very cautious when it comes to drawing any firm conclusions about the role of XMRV at this very early stage in the research.


On Friday 9 October, the front page of the UK Independent newspaper carried a major news item under the heading ‘Has science found the cause of ME?’ This referred to new research findings from America which indicate that a recently discovered retrovirus, known as XMRV (xenotropic murine leukaemia virus-related virus), could be playing an important role in causing or maintaining ME/CFS. The news item was accompanied by a very supportive editorial about the need for recognition and research into ME/CFS. These two items can be read here

The Independent story was soon followed up by the rest of the UK media, including the BBC. Most of the news reports gave a reasonably balanced and accurate account of the research. However, some reports incorrectly inferred that the cause of ME/CFS had now been conclusively discovered and that an antiviral treatment would soon be available. A selection of UK media reports can be found in the October news archive on the MEA website.

The actual research paper was published in the online edition of Science, along with a perspective written by John Coffin (Department of Molecular Microbiology, Tufts University, Boston, USA) and Jonathan Stoye (National Institute for Medical Research, London).


Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi V et al. Science October 8 2009 Abstract:

A new virus for old diseases? Coffin JM and Stoye JP. Science October 8 2009 326; p215 Abstract:

Additional online data from the study can be obtained if required.

XMRV has also been found in an American study in men who have prostate cancer. This was partly why the ME/CFS study was carried out. However, the most recent study on XMRV in prostate cancer from Germany has queried any such a link and suggested that one possible reason could be a geographically restricted incidence of XMRV infections.


Lack of evidence for xenotropic murine leukaemia virus-related virus (XMRV) in German prostate cancer patients. Retrovirology 2009, 6:92. Available on-line:


These are potentially important research findings that could help with both the diagnosis and management of ME/CFS. We congratulate all those involved in deciding to do this research study.

However, a number of questions still have to be answered before anyone can conclude that this virus plays a significant role in either the cause, transmission, clinical assessment or management of ME/CFS.

The research has demonstrated a correlation between ME/CFS and XMRV – not that it is the causative infection.

Much more epidemiology and laboratory work now needs to be done to answer the essential points set out below:

◦ Carrying out further and larger studies using different populations of people in different countries with ME/CFS. This work should include people at different stages of the illness (to see if the virus is present in the same percentages in both early and late cases) and in all degrees of severity. Research in different countries is vital in view of the conflicting geographical findings relating to XMRV in prostate cancer.

◦ Using different international laboratories to test for evidence of the virus.

◦ Assessing what, if any, correlation there is between the presence of this virus and (a) severity of symptoms, (b) a clear infectious onset with a known infection, (c) immune system abnormalities, CD4 abnormalities in particular, and (d) various other factors involved in sub-grouping of people under the ME/CFS umbrella.

◦ Assessing to what extent this particular retrovirus virus is also present in other chronic conditions, especially those such as multiple sclerosis and lymphoma where viral infections have been implicated as a causative factor.

◦ Assessing whether this virus is acting as a benign marker of disease or immune dysfunction, or is a ‘passenger virus’, or whether it has a role in the actual disease process and development of symptoms.

◦ Investigating whether the presence of the virus in healthy people acts as a predisposing factor in the development of ME/CFS (possibly when another infective trigger appears) and/or prostate cancer – rather than being involved in the actual disease process.

◦ Investigating what effect, if any, the virus has in healthy people who carry it over a period of time.

◦ Assessing whether people with evidence of the virus should be treated with antiretroviral medication, and if so developing a suitable antiviral drug or combination of antiviral drugs.

◦ Assessing whether animal model studies would help to increase our understanding of the way in which this virus may infects cells and possibly cause disease.


Until these research findings have been robustly replicated, and we have the answers to some of the above questions, there is no point in asking your doctor to be tested for XMRV. This is because the NHS does not currently have the facilities to do so and the testing procedures are only being used in a research capacity at present. But if it does turn out that there is a consistent and strong association with ME/CFS then testing for XMRV would almost certainly have to be made available.

We are not aware of any private pathology laboratories here in the UK that are able to test for XMRV, or are intending to start offering this test. Private testing is available in some countries outside the UK.


We know that some people with ME/CFS are now very concerned about the possibility of transmission of XMRV through what are termed body fluids (ie blood, saliva, semen). However, until we know more about what this virus does in the body it would be premature to start arriving at firm conclusions and recommending all kinds of restrictions to normal daily living. Remember: we still do not know for certain whether this is a disease-causing virus in humans and whether it plays a role in causing or maintaining ME/CFS.

And if this virus was behaving as an ‘ME virus’ in the way that HIV, another retrovirus, causes and transmits HIV infection, often leading to AIDS, there would be a significant number of sexual partners of people with ME/CFS developing ME/CFS – but this is clearly not the case.

One simple way of obtaining some early clues about viral transmission of XMRV would be to test for the presence of the virus in healthy partners and offspring of people who have the infection and comparing the findings to a control group of people that have no such link.


If this virus is also present in up to 4% of the normal healthy population here in the UK (ie around 2.4 million, or ten times the number of people who have ME/CFS), as appears to be the case in America, and it does play a significant role in diseases such as ME/CFS and prostate cancer, there will be widespread and very serious implications for public health, blood donation etc. This could also include vaccination against the virus and treating people who are XMRV positive. But these are complex decisions which can only be made in the light of further research studies.

In relation to blood donation in the UK, current advice is that people with ME/CFS who have symptoms, or are receiving treatment, should not donate blood. It would seem sensible in the short term, until we know more about transmission and pathogenicity of XMRV, to consider extending this restriction to people who have recovered from ME/CFS. It seems strange that many overseas countries have not followed the UK lead on blood donation and ME/CFS.


It should be noted that unlike the retroviral infection HIV, ME/CFS is an illness that occurs both sporadically and in highly localised acute geographical outbreaks, often involving closed communities such as schools and hospitals, where there is no obvious evidence of bodily fluid transission. This fact would obviously question the role of XMRV as a precipitating infection in the onset of the illness.

In the pivotal Royal Free Hospital outbreak of ME, far more than 4% of a previously healthy population of doctors and nurses contracted an unknown infection at roughly the same time (the hospital had to close due to lack of staff). This fact would question the role of XMRV as a key predisposing factor if it only occurs in 4% of the population.


Until we know more about the possible role of XMRV in ME/CFS there is no point in asking your doctor about antiviral drug treatment. If it turns out that the virus does play a role in causing or maintaining ME/CFS then antiviral drug treatment will need to be investigated. This will involve clinical trials to test possible drug treatments for both safety and efficacy – a process that normally takes a comsiderable amount of time and money.

The 2007 NICE Guideline on ME/CFS specifically states that doctors should not use antiviral medication to treat ME/CFS. This dogmatic position is unlikely to change without clear evidence of benefit in good quality randomised clinical trials.


The ME Association is keen to progress this research here in the UK through any way we can help. We have already made contact with virologists who are interested in this virus here in the UK and funding from the Ramsay Research Fund (RRF) could be made available very quickly if we receive a good quality research proposal.

More information on the work of the RRF can be found here

Since publication of these results it has become apparent that a number of international research groups are intending to try and confirm or refute the findings. The MEA has been contacted in relation to four such groups already – two from overseas. This is obviously good news and should help to clear up some of the immediate uncertainties.

If volunteers are required for any research taking place in the UK we will place an annoucement on the MEA website.


◦ An American group from the Whittemore Peterson Institute, in collaboration with the National Cancer Institute and the Cleveland Clinic, have reported finding evidence of a human retrovirus known as XMRV in blood samples taken from people with ME/CFS.

◦ Using peripheral blood mononuclear cells, DNA (viral genetic material) from the virus was found in 67% of patients (68/101) compared to 3.7% in healthy controls (8/218).

◦ The XMRV virus was shown to grow in cell culture in the laboratory.

◦ Further studies have found that 95% of people with ME/CFS have antibodies to the virus – indicating an immune response to a recent or past infection.

◦ Blood samples were collected from people with what is referred to in the paper as CFS who live in different parts of the United States, as well as from healthy controls.

◦ A more detailed, but easy to understand, summary of the XMRV research has been prepared by Dr Suzanne Vernon for the CFIDS Association of America. This can be read on their website:

◦ The paper in Science does not provide any detailed information about the patient group (ie age, gender, illness characteristics) or control group. However, a report on the research published in The Wall Street Journal states that 20/101 people in the CFS group also had a lymphoma, a type of cancer affecting the lymph nodes. Questions have therefore been raised about the inclusion of these patients in the CFS group, as well as the make up of the control group and how these patients were selected. See commentary from Professor Andrew Lloyd published on the website of the ME/CFS of NSW, Australia:


◦ Retroviruses are a small group of human viruses that consist of HIV (causing AIDS) , HTLV-1 (causing T-cell leukaemias and lymphomas) and HTLV-2 (often asymptomatic not yet clearly linked to any specific disease).

◦ They were discovered in the 1980s when it became possible to culture T-cells in vitro.

◦ They infect CD4 bearing lymphocytes – a special type of immune system cell that is derived from the thymus gland.

◦ Endogenous retroviruses (ERVs) are also found in humans and usually cause no ill effects.

◦ XMRV is retrovirus that was first described about three years ago in some men who have prostate cancer.

◦ It may also be linked to other medical conditions, including fibromyalgia.

◦ XMRV is related to a group of viruses that can infect mice.

◦ This type of virus is thought to be transmitted through body fluids such as blood, semen and breast milk. It is not thought to be transmitted through the air – like a flu virus.

◦ Testing for evidence of the XMRV virus in blood is currently only available at a few specialised laboratories here in the UK.

◦ Demonstrating a link between a retrovirus and ME/CFS does not, by itself, resolve the physical vs psychological debate. Research studies have demonstrated links between retroviruses and diseases as diverse as autoimmune disorders (which could be relevant to ME/CFS), immunodeficiency diseases, multiple sclerosis, tumours, anaemias and schizophrenia.


The bottom line to this interesting research is that it currently raises more questions than answers.

◦ Does the presence of XMRV in healthy people make them more likely to develop ME/CFS when another infection appears?
◦ Does XMRV cause ME/CFS in some cases?
◦ Does XMRV become active as a result of having ME/CFS?
◦ Or is it simply an innocent bystander with no role in the illness?
◦ Should XMRV be treated?

When we have accurate answers to at least some of these questions we can move forward, if necessary, with testing and treatment.

We will update this summary as further information becomes available.

If you want to comment on it please do so via

Dr Charles Shepherd
Hon Medical Adviser, ME Association

Summary 2 dated 22 October 2009

Professor Peter D White document to CNCCs re XMRV and CFS

Professor Peter D White document to CNCCs re XMRV and CFS

22 October 2009

A copy of the document below was passed anonymously to ME agenda, yesterday, together with evidence that it originates from Professor Peter White (Barts and The London NHS Trust).

It is being circulated by Professor White to the Clinical Network Co-ordinating Centres (CNCCs).

Professor White is also a co-PI (Principal Investigator) of the MRC funded PACE Trials.

Caveat: Amongst other issues, there have been expressions of concern over Professor Lloyd’s use of the term “‘endogenous retroviruses’ (ERVs)” in his original commentary, a term reproduced in the document being circulated by Professor Peter White to CNCCs.

Note: The original commentary by Professor Andrew Lloyd is published here  on the website of The ME/CFS Society of NSW Inc.


Document Properties:

MS Word Document file name: xenotropic murine leukemia virus-related virus XMRV and CFS.doc

Document Created: 15 October 2009

Document Title: Dear ME/CFS Society,

Author: Andrew LLoyd

Company: Barts and The London NHS Trust


Document text:

Dear colleagues,

In light of the recent publication in Science regarding a new retrovirus discovered in patients with CFS and the attendant widespread publicity, the following is a scientific appraisal of this publication and the evidence so far. It has been adapted almost in full with permission from an article by Professor Andrew Lloyd, Director, Centre for Infection and Inflammation Research, University of New South Wales.

The first comment is that the findings are potentially important to our understanding of the illness. The paper describes the detection of genetic material of a virus known as xenotropic murine leukemia virus-related virus (XMRV) in 68 of 101 (67%) patients in the US, described as having illness “fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome and the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) and presenting with severe disability”, compared to 8 of 218 (3.7%) healthy individuals. The significance of this finding was further supported by detection of XMRV proteins in the blood of 19 0f 30 patients, but none of 5 healthy subjects. Antibodies against XMRV were found in the blood of 9 of 18 patients and none of 9 healthy individuals. The XMRV was shown to grow in cell culture in the laboratory. As the retrovirus family also includes HIV, on face value this finding raises the suggestion that CFS may be caused in some cases by infection with XMRV which may affect both the immune system and the brain.

However, several strong notes of caution need to be applied:

1) Research into CFS has been plagued over several decades by studies using sophisticated molecular laboratory techniques to examine poorly characterised subjects and samples. In the recent study, the 101 patients are reported to have met diagnostic criteria for CFS, but perplexingly no details of their age, gender, or illness characteristics were provided – except the indication that the illness in these patients was causing “severe disability”. This information is critical to allow the reader to understand how comparable the patients in the study were to ‘typical’ patients with CFS in the USA and worldwide. Disconcertingly, one of the authors of the study, Judy Mikovits has suggested during interviews with the Amy Dockser Marcus in the Wall Street Journal, that “20 patients of the 101 in the study have lymphoma” – if this statement is accurate the reliability of the designation of the 101 patients must be cast into serious doubt (as diagnosis of lymphoma precludes a diagnosis of CFS). Perplexingly, the paper also does not describe how the healthy control subjects were selected – for instance if the controls were family members of the cases, or individuals working in the laboratory where the studies were performed this would be inappropriate as they may have altered rates of contact with the XMRV.

2) the finding of a retrovirus in the blood would seem to be highly significant, however so called ‘endogenous retroviruses’ (ERVs) are actually found commonly in humans and generally cause no ill effects. These retroviruses are derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; and so are passed on through generations and now remain in the genome. Some research suggests that human ERVs may cause certain  autoimmune diseases and cancers. XMRV has previously been associated with prostate cancer. Accordingly, the finding of XMRV in the recent study raises the possibility that infection with this virus may cause CFS in some patients – alternatively it may become active as a result of CFS – or it may have no role whatsoever in the illness (i.e it may be an epiphenomenon).

3) those of us who have been undertaking research into CFS for a long period will remember the remarkably comparable “discovery” of a retrovirus in patients with CFS made by Elaine Defreitas which was published in the similarly prestigious journal, Proceedings of the National Academy of Sciences in 1991. In brief, the initial report was of a retrovirus with both genetic material and viral proteins, as well as antibodies against the virus, identified in a significant proportion of patients and not in healthy individuals. A series of subsequent studies failed to confirm the findings – or find evidence for any known retroviral infection. This outcome is an important reminder that biomedical research is highly complex process and often uses new technologies to make discoveries – some are confirmed and found to have lasting significance – many are not. This process is a necessary element in the pathway to improved understanding of disease.

There can be no doubt that CFS is one of the most challenging on the list of unsolved medical conditions, hence the last two decades have witnessed many such ‘discoveries’ – time will tell whether this one stands the key test of independent replication, which is verification of the same finding in other laboratories and using other patient samples. A number of research groups will be undertaking this task over the next several months – until these results are in – there is no likelihood of a meaningful “diagnostic test”. If the findings were confirmed the likelihood of an effective treatment would be several years away at the earliest.


NIH $1.6 Million award for ME/CFS Research for Drs. Mikovits & Kerr

XMRV Retrovirus Whittemore Peterson CFS study Media Round up: 13

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Source: Prohealth

NIH Bets $1.6 Million on Continued ME/CFS Research by Drs. Mikovits & Kerr*

October 21, 2009

Dr. Judy Mikovits (principle investigator) and the Whittemore-Peterson Institute, with collaborator Dr. Jonathan Kerr, have been awarded a 5-year, $1.6 million grant from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to support ongoing research into the disease mechanisms of chronic fatigue syndrome. Dr. Kerr is associated with St. George’s College in London.

The award was announced Sep 24 on the WPI website, before news of the CFS-associated XMRV retrovirus was published Oct 8 by the journal Science. A description of the project (# 1R01AI078234-01A2) is now included in the NIH’s Research Portfolio Online.

( )

Key Details from the NIH’s Project Description

• Title: “New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome.”

• Objective: “To provide significant insight into the disease mechanisms of Chronic Fatigue Syndrome so accurate testing and specific treatments can be developed with a goal of curing the disease and preventing life-threatening complications.”

• Timing: start date Sep 28, 2009; projected end date, Aug 31, 2014.

• Funding: First fiscal year funding $335,600; total funding $1.6 million.

• Project Description provided by applicant: (excerpt formatted for greater legibility, as follows).


“Chronic Fatigue Syndrome (CFS) is a complex disease estimated to affect between 0.5%-2% of the population in the Western world.

Its pathogenesis is thought to involve both inherited and environmental (including viral) components, as with other chronic inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, and atherosclerosis.

Consistent with this chronic inflammatory context, CFS patients are known to have a shortened life-span and are at risk for developing lymphoma. We hypothesize that chronic inflammatory stimulation from active and recurrent infections of multiple viruses on a susceptible host genetic background leads to the pathogenesis characterized by CFS.

The overall goal of this research project is to define these viral and host parameters in European and American cohorts of CFS patients that correlate with distinct disease phenotypes, including the development of mantle cell lymphoma (MCL) in a subgroup of the American cohort.

In Aim 1) we will identify and confirm novel viral infections in European and American CFS patient cohorts.

1.1) We will use two complementary methods for detection of novel virus mRNA: massive parallel signature sequencing (MPSS) and a custom DNA microarray.

1.2) Quantitative polymerase chain reaction Q-PCR will be used for confirmation of virus gene expression.

1.3) Immortalized cell lines will be developed to isolate virus and elucidate links between virus and host cell gene expression.

In Aim 2), we will elucidate genetic factors of susceptibility and the dysregulation of the host defense system. Specifically, we will determine:

2.1) PBMC gene expression of 88 human genes previously confirmed as being differentially expressed in CFS

2.2) Serum chemokine and cytokine profiles using multiplex suspension antibody arrays on a Luminex platform

2.3) HLA, KIR genotypes and whole genome SNP profiles

2.4) Defects in the type I Interferon signaling pathway.

In each subaim both cohorts will be compared to normal and disease controls using specimens of serum and PBMC taken at multiple time-points from individual patients and taken from our unique and extensive sample repository.

This study:

• Will provide information necessary for development of treatment and diagnostic strategies for distinct subgroups of CFS patients,

• And may identify novel virus associations, genetic signatures, and biomarkers, which can predict the development of MCL, thus enabling use of preventive therapeutics.”….


[*Ed: Dr. Jonathan Kerr is a member of the Research Committee for the UK CFS Research Foundation; Dr Kerr is also a member of the MRC’s CFS/ME Expert Group  which is chaired by Professor Stephen Holgate.  Professor Holgate is also a member of the CFS Research Foundation’s Research Committee. ]


Patient community websites, blogs, commentaries

Previous material in the XMRV series of Media updates has referred to “Koch’s postulates”

Jean Harrison, via Co-Cure, 22 October 2008:

From Wikipedia (admittedly not always the best source, but in this case pretty sound)

“1.The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.

2.The microorganism must be isolated from a diseased organism and grown in pure culture.

3.The cultured microorganism should cause disease when introduced into a healthy organism.

4.The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Koch’s postulates were developed in the 19th century as general guidelines to identify pathogens that could be isolated with the techniques of the day.[3] Even in Koch’s time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates.[2][4] Attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of virology.[5][6] Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch’s postulates.[7] Therefore, while Koch’s postulates retain historical importance and continue to inform the approach to microbiologic diagnosis, fulfillment of all four postulates is not required to demonstrate causality.”



Previous ME agenda Media Round ups

Round up 13: NIH $1.6 Million award for ME/CFS Research for Drs. Mikovits & Kerr: (you are here)

Round up 12: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 12:

Round up 11: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11:

Round up 10: Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal):

Round up 9: Notice from Dr David Bell, Lyndonville News; Article by Paul R. Cheney MD, PhD:

Round up 8: XMRV retrovirus study: Position statement from ME Association 14.10.09:

Round up 7: XMRV Retrovirus: Whittemore Peterson Institute: CFS: Media Round up 7:

Round up 6: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study: Videos and audios:

Round up 5: Supporting Online Material for XMRV Chronic Fatigue Syndrome study:

Round up 4: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study:

Round up 3: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome retrovirus XMRV in the media:

Round up 2: Science 9 October 2009: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 08.10.09:

Round up 1: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 09.10.09:

XMRV Retrovirus Whittemore Peterson CFS study Media Round up 12

XMRV Retrovirus Whittemore Peterson CFS study Media Round up: 12

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ABC News

Good Morning America [ABC] -XMRV


Click here for interview with Dr. Donnica Moore about the link between the XMRV and ME/CFS


New York Times

October 21, 2009

Op-Ed Contributor
A Case of Chronic Denial

EARLIER this month, a study published in the journal Science answered a question that medical scientists had been asking since 2006, when they learned of a novel virus found in prostate tumors called xenotropic murine leukemia virus-related virus, or XMRV: Was it a human infection?

XMRV is a gammaretrovirus, one of a family of viruses long-studied in animals but not known to infect people. In animals, these retroviruses can cause horrendous neurological problems, immune deficiency, lymphoma and leukemia. The new study provided overwhelming evidence that XMRV is a human gammaretrovirus – the third human retrovirus (after H.I.V. and human lymphotropic viruses, which cause leukemia and lymphoma). Infection is permanent and, yes, it can spread from person to person (though it is not yet known how the virus is transmitted).

That would have been news enough, but there was more…

Read full commentary by Hillary Johnson, author of Osler’s Web here

While you’re on the NYT site, email Hillary’s commentary to family, friends and contacts!

Hillary Johnson’s website here:
Hillary Johnson blogs at:


From Martin L. (Marty) Pall, via Co-Cure

21 October 2009

Mikovits and her colleagues published a paper and accessory materials in the journal Science, a highly respected journal and have also provided additional and in some cases more recent information elsewhere. In the Science publication they report that the XMRV retrovirus occurs in about 2/3rds of CFS/ME patients but only in 3.7% of normal controls. They also report that subsequently, using a more sensitive assay, XMRV occurs in over 90% of CFS/ME patients – we don’t know what the percentage is for normal controls using that more sensitive assay.

The virus was originally isolated from some aggressive prostate cancer cells. In addition, in unpublished data, it is also apparently shows high prevalence in fibromyagia patients and in atypical multiple sclerosis (MS) patients.

Comment: These data apparently show that XMRV is not specific for CFS/ME but rather occurs in other disease states, as well as in some normals. My own view is that this makes it much more likely to be an opportunistic disease, caused by the changes in immune function and other properties of these diseases, rather than a primary cause. Specifically, the retrovirus, based on its DNA sequence, has its replication stimulated by NF-kappaB activity, an activity that is elevated as part of the NO/ONOO- cycle and has been reported to be elevated in CFS/ME. Furthermore, the low NK cell activity and other types of immune dysfunction, that occurs in these various diseases,  may also be expected to stimulate the ability of the virus to maintain itself in disease sufferers.

In order to show that it is the primary cause of CFS/ME, it is necessary to show that XMRV follows Koch’s postulates, but so far it does not apparently follow Koch’s first postulate, which requires that it always occurs in people with the disease but does not occur in normals. The other three Koch’s postulates have not been tested.

In contrast to that, we have a good fit to the five principles underlying the NO/ONOO- cycle for both CFS/ME and fibromyalgia. Because one can argue that the fit to these five principles serve very much like Koch’s postulates for NO/ONOO- cycle disease, I will argue that we have a substantially more compelling case for a NO/ONOO- cycle etiology than we do for an XMRV infectious etiology for either CFS/ME or fibromyalgia.

That does not mean that XMRV is unimportant, however. Even if it turns out to be an opportunistic infection, like mycoplasma and HHV-6 are, it still may contribute to the etiology of the disease. And it still raises the question of whether we can cure cases of CFS/ME and fibromyalgia simply by normalizing the NO/ONOO- cycle as opposed to normalizing it and also using antivirals to depress XMRV and/or HHV-6. This is a question and I don’t claim to have the answer to it, although my hope is that normalizing the cycle will also cure at least some of these infections, that may not be true.

There have been comments in the media to the effect that this finally shows that CFS/ME is physiological, not psychological. This is true, but this should have been obviously true anyway, at least six or seven years ago. Nevertheless the media coverage of CFS/ME obtained by Mikovits and her colleagues must be viewed as a true gift to those interested in extending public knowledge of this disease.

Martin L. (Marty) Pall

Dr. Martin Pall’s NO/ONOO- Theory/Treatment Discussion Group:

The Tenth Paradigm – Dr. Martin Pall’s Website for CFS/MCS/FM/ETC:



October 19, 2009

Virus Linked to Chronic Fatigue Syndrome

Scientists have detected the DNA of a retrovirus in the blood of patients with chronic fatigue syndrome. The discovery raises the possibility that the virus may be a contributing factor in chronic fatigue syndrome.

Transmission electron micrograph of round virus particles.

XMRV virus particles seen by transmission electron microscopy. Image courtesy of University of Utah Health Sciences Public Affairs.

Chronic fatigue syndrome, or CFS, is a debilitating disease that affects millions of people in the United States. It’s characterized by profound fatigue that doesn’t improve with bed rest and can be exacerbated or re-kindled by physical or mental activity. A number of other symptoms are also associated with CFS, including cognitive deficits, impaired sleep, myalgia, arthralgia, headache, gastrointestinal symptoms and tender lymph nodes.

No specific cause for CFS has yet been identified. However, patients with CFS are known to have some abnormalities in their immune system. Recently, scientists found evidence of a virus called xenotropic murine leukemia virus-related virus, or XMRV, in the tumors of patients with prostate cancer. Some patients with XMRV-positive prostate cancer were reported to have a specific immune system defect that was also seen in CFS patients. Suspecting a link between the virus and CFS, a team of scientists from the Whittemore Peterson Institute at the University of Nevada, NIH’s National Cancer Institute (NCI) and the Cleveland Clinic set out to look for the virus in blood samples.

The scientists identified DNA from XMRV in the blood cells of 68 of 101 (67%) CFS patients, as reported in the online edition of Science on October 8, 2009. In contrast, the blood of only 8 out of 218 healthy people (3.7%) contained XMRV. Blood cells not only contained XMRV DNA, but also expressed XMRV proteins and produced infectious viral particles.

The researchers also found that XMRV stimulates immune responses in people with CFS. Plasma from 9 out of 18 CFS patients infected with XMRV reacted with a viral protein, whereas none of the plasma from 7 healthy donors showed a reaction.

“These compelling data allow the development of a hypothesis concerning a cause of this complex and misunderstood disease, since retroviruses are a known cause of neurodegenerative diseases and cancer in man,” says Dr. Francis Ruscetti of NCI, who worked on the project.

Retroviruses like XMRV have also been shown to activate a number of other latent viruses. This could explain why so many different viruses, such as Epstein-Barr virus, have been associated with CFS.

The researchers cautioned, however, that while this study found an association between XMRV and CFS, further work will be needed to determine whether XMRV truly contributes to the development of CFS.

“The discovery of XMRV in 2 major diseases, prostate cancer and now chronic fatigue syndrome, is very exciting,” says Dr. Robert H. Silverman, a co-author at the Cleveland Clinic. If a role for XMRV is established, there could be new opportunities for prevention and treatment of these diseases.

Related Links:
Chronic fatigue syndrome:


Patient community websites and blogs

Cort Johnson’s Phoenix Rising website

Cort Johnson’s Blog and comments

“A supernova (pl. supernovae) is a stellar explosion. Supernovae are extremely luminous and cause a burst of radiation that often briefly outshines an entire galaxy”. This discovery has the potential for being a world changing event in every way for chronic fatigue syndrome patients. If it really works out – still an if – one almost has to think in inter-galactic terms to find an appropriate analogy of how different things could be five years from now…”

Check out “The Potential of XMRV” in the latest edition of ‘Bringing the Heat’ from Phoenix Rising.


This is ME – rutts tankespinn


Previous ME agenda Media Round ups

Round up 12: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 12:

Round up 11: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11:

Round up 10: Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal):

Round up 9: Notice from Dr David Bell, Lyndonville News; Article by Paul R. Cheney MD, PhD:

Round up 8: XMRV retrovirus study: Position statement from ME Association 14.10.09:

Round up 7: XMRV Retrovirus: Whittemore Peterson Institute: CFS: Media Round up 7: 

Round up 6: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study: Videos and audios: 

Round up 5: Supporting Online Material for XMRV Chronic Fatigue Syndrome study:

Round up 4: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study:

Round up 3: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome retrovirus XMRV in the media:

Round up 2: Science 9 October 2009: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 08.10.09:

Round up 1: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 09.10.09:

MRC Two day Research Workshop 19 and 20 November 2009

MRC Two day Research Workshop 19 and 20 November 2009

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May be reposted

Research into CFS and ME has been designated a UK Medical Research Council “high priority” area. The MRC convened a Research Advisory Group in 2003 and did a lot of talking. Six years down the line, with a Bill Reeves (CDC) chaired joint MRC/Action for M.E. Research Summit, a new multidisciplinary panel and a lot more talk, we are still waiting for the MRC to put its money where its mouth is. The new MRC Expert Group on CFS/ME Research meets in November for a two day research workshop. For how many more years is the MRC going to be talking about its objective to encourage and conduct high-quality research into CFS and ME?  

The MRC CFS/ME Expert Group, chaired by Professor Stephen Holgate, has scheduled a two day research workshop for 19 and 20 November.

Since no details of this Research Workshop have been published by the MRC or by Action for M.E. or the ME Association (who attend meetings of the group), I have, today, submitted a request to the MRC for information under the Freedom of Information Act.

I have requested:

A copy of the Agenda for the two day research workshop scheduled for 19 and 20 November.

A copy of the list of participants for the research workshop.

Clarification of whether the MRC CFS/ME Expert Group intends to continue to hold meetings beyond the two day research workshop.

The MRC are obliged to provide a response within 20 working days.  I anticipate a response on or before Friday, 13 November and will update you then.


For Minutes of the December meeting of the MRC CFS/ME Expert Group see previous posting:

The list of members and the Panel’s Terms of Reference were previously obtained by me under FOIA and published here on ME agenda.

The Agenda and Minutes of the meeting on 15 December can be downloaded here or opened in PDF format here:

PDF: Minutes CFS/ME Expert Group Meeting 15 December 2008

Document Library
CFS/ME Expert Group meeting – 15 December 2008
Issued: 15 Dec 2008
Primary audience: Researchers
Document Summary

Agenda and minutes from the 1st meeting held on 15 December 2008


The list of members can be opened in PDF format here:

PDF: CFS/ME Expert group membership

Term of Reference can be opened in PDF format here:

PDF: Finalised Terms of Reference for CFS/ME expert group

or go to MRC site for full article and files:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis 

( )

XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11

XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11

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XMRV researchers to speak on campus

University of the Pacific  15 October 2009

Fatigue syndrome researchers to speak on campus

“Two of the researchers who recently announced that a retrovirus may be linked to Chronic Fatigue Syndrome will be on campus Oct. 26 to discuss their findings. The event will have limited seating and is open to the first 50 people who reserve a space…”

Full announcement here


Philadelphia Business Journal

John George Staff Writer   16 October 2009

Hemispherx drug for chronic fatigue held up by additional FDA demands

“A decision on Hemispherx BioPharma’s new drug application for Ampligen, twice delayed by the FDA earlier this year, is still in limbo.

“William A. Carter, CEO of the Center City biotech company, said last week the company is responding to issues raised by the Food and Drug Administration during its review of Ampligen, an experimental treatment for chronic fatigue syndrome…”

Article here



Follow the Whittemore Peterson Institute on Facebook at: Whittemore Peterson on Facebook


CFSAC October Meeting

In a post on 16 October

CFSAC Agenda Presentation: XMRV Association with CFS Dr D Peterson  WordPress Shortlink:


For Supplementary Information see PDF:  or html:


CFSAC Agenda – October 29-30, 2009

U.S. Department of Health and Human Services



Both days of this meeting will be videocast (Realplayer required)

Go to the NIH website at:

Scroll down to October 29th Chronic Fatigue Syndrome link for:

Air date: Thursday, October 29, 2009, 9:00:00 AM
Time displayed is Eastern Time, Washington DC Local

You will be able to view the event at:  when the event is live.

FAQ on video streaming at:

The videocast will be archived for a few weeks after the meeting.  Mintutes of the meeting will be posted on the CFSAC website with archived copies of the testimonies provided for the meeting.

CFSAC webpage:


Videocasts of Days One and Two of the previous meeting (27 – 28 May 09) can still be viewed at: 

Day One: Wed 27 May:  (Realplayer required)

Day Two: Thurs 28 May:  (Realplayer required)


Patient community websites and blogs

Cort Johnson’s Phoenix Rising website

Cort Johnson’s Blog and comments  

XMRV – Hope and Caution
by cort on October 16, 2009  

XMRV – Puppet Master?
by cort on October 15, 2009


Previous ME agenda Media Round ups

Round up 11: XMRV Retrovirus Whittemore Peterson CFS study Media Round up 11:

Round up 10: Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal):

Round up 9: Notice from Dr David Bell, Lyndonville News; Article by Paul R. Cheney MD, PhD:

Round up 8: XMRV retrovirus study: Position statement from ME Association 14.10.09:

Round up 7: XMRV Retrovirus: Whittemore Peterson Institute: CFS: Media Round up 7: 

Round up 6: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study: Videos and audios: 

Round up 5: Supporting Online Material for XMRV Chronic Fatigue Syndrome study:

Round up 4: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study:

Round up 3: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome retrovirus XMRV in the media:

Round up 2: Science 9 October 2009: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 08.10.09:

Round up 1: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 09.10.09:

Whittemore Peterson Institute XMRV retrovirus study link with CFS: Media Round up 10

Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal): Media Round up 10

WordPress Shortlink:

This is the tenth Round up of media coverage of the Whittemore Peterson Institute XMRV study published, last week (08.10.09), in Science journal.  Round ups also include commentary from patient organisations, patient community websites and bloggers and links for related material.


Press Release:

The European ME Alliance 

Eight-Country European ME Alliance Issues Kudos to WP Institute, Pledges Cooperation
October 16, 2009

The European ME Alliance  is a group of European organizations formed less than a year ago to encourage more ME/CFS biomedical research funding – Belgium, Denmark, Ireland, Germany, Norway, Sweden & UK.

ME Alliance Press Release Oct 16:

The European ME Alliance (EMEA) wish to congratulate the Whittemore- Peterson Institute for the painstaking, professional and groundbreaking work which its staff have performed, along with the National Cancer Institute and the Cleveland Clinic, which has resulted in the publication of the findings of a novel virus XMRV in causing or influencing ME.

The members of EMEA recognize that the staff at WPI are performing research of the highest quality.

The publication of this research in Science magazine is itself an amazing achievement.

This work has been achieved in an amazingly short period of time and the tenacity, dedication and sheer excellence of the WPI has brought hope to millions of people, patients, carers and friends, in Europe and further afield.

EMEA announces its continued full support for WPI and hopes to be able to become a stronger partner in the future.

Signed by all members of the European ME Alliance:

Belgium – ME/CFS Association (Nieuwrode, Belgium)
Denmark – ME-NetDK
Ireland – Irish ME Trust
Germany – Fatigatio e.V.
Norway – Norges ME-forening
Spain – Liga SFC
Sweden – Riksföreningen för ME-patienter
UK – Invest in ME

The European ME Alliance


Tate Mitchell reports via Co-Cure mailing list    16 October 2009

The CFIDS Assoc. just posted some updates on their Facebook page, including a link to an interview with Laura Hillebrand, author of Seabiscuit, by The New Yorker, the Oct. 29-30 CFSAC meeting agenda is published, which is to include a presentation by Dr. Daniel Peterson entitled ‘XMRV Association with CFS’, and CFIDS Assoc. Scientific Director Suzanne Vernon writes about the new XMRV findings”

Oct. 29-30 CFSAC agenda

Interview with Laura Hillebrand




By Suzanne D. Vernon, PhD
Scientific Director, The CFIDS Association of America

The announcement on October 8, 2009, that an infectious retrovirus called XMRV (xenotropic murine-related retrovirus) was linked to CFS, could be the game-changing scientific event we have been waiting for. Whether XMRV provides the long-awaited causal link will depend on the findings described in the Science paper being replicated by another laboratory in another group of CFS patients. To help clarify what we know, let’s review the findings.

Dr. Judy Mikovits and her team at the Whittemore Peterson Institute for Neuro-immune Disorders (WPI) made a very insightful connection three years ago. XMRV was first described in prostate cancer in 2007 by investigators at the Cleveland Clinic, who also reported that XMRV-positive prostate cancer patients have alterations in RNase L, an antiviral immune system pathway. The WPI investigators knew that RNase L activity is also altered in blood cells from CFS patients and they made the decision to look for XMRV in CFS patients with this immune defect.

When scientists want to find a virus, we look for it in the sickest individuals because often this is where there is likely to be the highest levels of a virus, if present. Dr. Dan Peterson has been caring for and researching CFS patients since the 1984 Incline Village outbreak, so he identified CFS patients with prolonged disabling fatigue, cognitive impairment, and documented laboratory immunological abnormalities (including altered RNase L activity) to hunt for XMRV.

The WPI laboratory team detected XMRV sequences in 68 of 101 (67%) CFS patients tested and in 8 of 218 (3.7%) healthy control subjects. The Cleveland Clinic confirmed the presence of XMRV in a subset of these same CFS cases, 7 of the 11 (64%) samples from WPI. The Cleveland Clinic researchers found that the CFS XMRV was similar to prostate cancer XMRV, and not a mouse virus (murine leukemia virus) that could have been a contaminant explaining the discovery.

The investigators designed several new assays to understand XMRV. They looked to see if XMRV was expressed in peripheral blood mononuclear cells (PBMCs) of CFS patients. PBMCs from 19 of 30 CFS patients expressed XMRV proteins compared to 0 of 16 PBMC samples from healthy controls. They also wanted to know which cells harbored XMRV; they found it in T and B cells in the blood of one CFS patient. The investigators looked to see if the XMRV from CFS patients was infectious. Both blood cells and plasma (the cell-free fraction of blood) from XMRV-positive CFS patients were able to transmit this virus to a susceptible cell line, indicating infectiousness in laboratory culture. Finally, they wanted to know if XMRV stimulated the immune system to produce antibodies. Plasma from 9 of 18 CFS patients had antibodies that reacted with a virus protein similar to that found in XMRV, compared to no reaction from plasma of 7 healthy controls.

This Science paper tells us that XMRV plays a possible role in CFS pathogenesis in these CFS patients. How much we can generalize these findings to other CFS patient populations? That answer will depend on the results of replication studies.

The design of replication studies should include CFS patients who are similar to those selected by Dr. Peterson and reported in the Science study. Unfortunately, the details about the CFS patients were not sufficient to enable independent investigators to select similar CFS patients. For example, we need to know the age, sex, duration of illness, medical history, and medication use, to name a few characteristics, of the studied patients to select CFS patients who as similar as possible to the original group. We also need to know something about the healthy control subjects, since there is nothing in the paper or supplementary materials that describes how they were selected. Independent replication studies should also include patients with mild and moderate CFS, at least one chronic disease control group (e.g., multiple sclerosis, lupus) and sex and age-matched healthy controls. We are actively working with several independent research groups to expedite these studies.

While these exciting studies of XMRV continue, the CFIDS Association continues its support of our funded investigators. It’s important to remember that HIV was discovered to be the cause of AIDS 26 years ago, but worldwide research on AIDS treatment, cure and prevention continues today. Our funded investigators’ research on why EBV triggers CFS, whether ion-channel receptors are markers of fatigue, why CFS patients have higher rates of leaky gut, why CFS patients have slow blood flow to the brain, why CFS patients have metabolic disturbances in the brain, and how we can bring this information, as well as XMRV, together using powerful computational tools are all important as we work together to solve CFS.

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. 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. Science 8 October 2009. 1179052.

Supporting online material for Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. 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. Science 8 October 2009.

A new virus for old diseases? Coffin JM and Stoye JP. Science 8 October 8 2009.

Information about the Association’s research program:



Professor Andrew Lloyd AM
Director, Centre for Infection and Inflammation Research University of New South Wales

New Retrovirus – Comments by Professor Andrew Lloyd

©2002 – 2009 ME/CFS Society of NSW Inc. 



RESCIND would like to emphasize what we feel are probably the two most powerful quotes on record in M.E. (C.F.S.) history…

Dr. Nancy Klimas as quoted from the Q & A New York Times article “Is a Virus the Cause of Fatigue Syndrome?” – posted online Oct 15, 2009

“But I hope you are not saying that C.F.S. patients are not as ill as H.I.V. patients. My H.I.V. patients for the most part are hale and hearty thanks to three decades of intense and excellent research and billions of dollars invested. Many of my C.F.S. patients, on the other hand, are terribly ill and unable to work or participate in the care of their families. I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses (in 2009) I would rather have H.I.V.”

Dr. Marc Loveless as quoted by Tom Hennessy from A Brief History of the Name Change Movement

Dr. Shelekov looked puzzled and maybe a little skeptical. But Dr. Marc Loveless, sitting next time to him said, “Dr. Shelekov, this man (meaning me) is telling you the truth. I have treated more than 2500 AIDS and CFS patients over the past 12 years. and my CFS patients are MORE sick and MORE disabled, every single day, than my AIDS patients are, except in the last two weeks of life!”

I immediately said to Dr. Loveless that “YOU have to use that line in every speech you give on this illness for the rest of your life!” (in 1994, Dr. Loveless gave this same testimony under oath to the US Congress).


Radio broadcasts

Science Friday on NPR

“Science Friday is a weekly science talk show, broadcast live over public radio stations nationwide from 2-4pm Eastern time as part of NPR’s ‘Talk of the Nation’ programming.”

Podcast:  Virus Tied to Chronic Fatigue Syndrome

Clicking on this link will start download of mp3 Podcast from Science Friday site: 


Patient community websites and blogs

Cort Johnson’s Phoenix Rising website

The news on XMRV is breaking fast and items are being added regularly to the XMRV Resource Center on Phoenix Rising. The Resource Center has links to scientific articles, analyses by chronic fatigue syndrome specialists (check out the video by Dr. Klimas on CFSKnowledge Center), media reports, Q&A’s, blogs and more.

Hillary Johnson (journalist and author of Osler’s Web)




Related links

Science and Technology News

Hemispherx Biopharma Finds New Retrovirus in Chronic Fatigue Syndrome

Rochester, New York 10/16/2009 08:55 PM GMT (TransWorldNews)

Hemispherx Biopharma, Inc. (AMEX: HEB) has announced a discovery of a novel retrovirus in Chronic Fatigue Syndrome (CFS). The retrovirus may shed light on the potential mechanism of action of Ampligen, an experimental therapeutic, in CFS. CFS is a debilitating disease of unknown etiology that affects 17 million worldwide…


Fibromyalgia & CFS Blog

UPDATE: Ampligen for Chronic Fatigue Syndrome
Friday October 16, 2009

NEWSBRIEF: We now have an update on the FDA’s much-delayed decision on Ampligen for chronic fatigue syndrome that explains why we’ve been kept waiting for so long….


Links to scientific coverage

Whittemore Peterson Institute Q and A
Whittemore Peterson Institute Press Release
Science News: Retrovirus might be culprit in chronic fatigue syndrome
New Scientist: Chronic fatigue syndrome linked to ‘cancer virus’
Scientific American: Retrovirus Linked to Chronic Fatigue Syndrome, Could Aid in Diagnosis
Nature: Virus linked to chronic fatigue syndrome
NIH News: Consortium of Researchers Discover Retroviral Link to Chronic Fatigue Syndrome


Previous ME agenda Media Round ups

Round up 10: Whittemore Peterson Institute XMRV retrovirus study link with CFS (Science journal):

Round up 9: Notice from Dr David Bell, Lyndonville News; Article by Paul R. Cheney MD, PhD:

Round up 8: XMRV retrovirus study: Position statement from ME Association 14.10.09:

Round up 7: XMRV Retrovirus: Whittemore Peterson Institute: CFS: Media Round up 7: 

Round up 6: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study: Videos and audios: 

Round up 5: Supporting Online Material for XMRV Chronic Fatigue Syndrome study:

Round up 4: XMRV Retrovirus: Whittemore Peterson Institute Chronic Fatigue Syndrome study:

Round up 3: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome retrovirus XMRV in the media:

Round up 2: Science 9 October 2009: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 08.10.09:

Round up 1: Whittemore Peterson Institute (WPI) Chronic Fatigue Syndrome link to retrovirus: 09.10.09: