Guilty!…. By Association? Taking Our Measure

February 25, 2011

Posted by Cort Johnson

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5107-judge-with-gavel.jpgGuilty!

Dr. Klimas was raked over the coals recently for being a co-author of a study on stress management that brought symptomatic relief to some people with CFS. In the upset of the moment the rest of Dr. Klimas’s work – her uncovering of the central immune dysfunction in ME/CFS (NK cell dysfunction), her numerous research papers, her advocacy work as President of the IACFS/ME, IACFS/ME Board member, CFSAC member, Fair Name Committee Member and her decades of work as a physician specializing in ME/CFS, was mostly forgotten.

Now it’s Dr. Vernon’s turn to be at the end of a ‘guilt by association’ charge.

The Clinical Director of the WPI, Dr. Deckoff-Jones recently wrote
http://treatingxmrv.blogspot.com/

Quote:
I’ve had a lot of mail lately about the CAA. The recent comments, and absence of meaningful commentary, by Kim McCleary, the president of the CAA, on CNN, are a disgrace: The fact that Suzanne Vernon, the Director of research, has 30 papers on PubMed coauthored by William Reeves, most recently in 2009, pretty much puts the nail in the coffin for me.

I love the transparency and commitment to objectivity Dr. Deckoff-Jones has shown in her blogs regarding the WPI’s objectives and to her antiretroviral treatments. She’s dealt with often emotional topics in admirable fashion and I look forward to watching her help create a vibrant and creative clinical environment at the WPI. (. See From the Patient Side: Dr. Deckoff-Jones Talks.) In this case, however, I think she’s wrong.

Guilt by association does often work, it’s true, and it’s easy to see how it would in this case. Dr. Reeves, is after all, greatly disliked in the CFS community and Dr. Vernon did co-author a substantial number of papers with him. On the face of it you might think that the 30 papers she co-authored with Dr. Reeves would be more than enough to put ‘the nail in the coffin’ for her and the CFIDS Association of America.

The Evidence

A quick look at the papers Dr. Vernon co-authored with Dr. Reeves suggests, however, the picture is far more complex. A PubMed search using “SD Vernon” and “WC Reeves” does pull up 30 papers but most of those papers (17) are not on CFS at all but on Papillomavirus work Dr. Vernon did with Dr. Reeves outside of the program. Over the ten years or so Dr. Vernon was with the CFS research team she co-authored only 13 papers with Dr. Reeves – a surprisingly small number suggesting, in fact, that hers and Dr. Reeves research interests in CFS diverged and their paths intersected only occasionally. …

A look at the papers themselves (see the list below) indicates that they are almost all on CFS pathophysiology.. They included studies on immune (complement) activation during exercise, gene expression levels in people who came down with CFS after an infection, genetic differences in HPA axis receptors, mitochondrial dysfunction after infection with Epstein Barr Virus, auto-antibodies in CFS, mycoplasma, sRNA gene sequences, gene expression and biomarkers, economic impact, etc. molelcular profiling, etc.

These papers, however, don’t begin to tell the story of her time with the CDC or with CFS. While working with other CDC and outside researchers she published papers on cytokine networks, a theory of HPA axis bistability suggesting a novel way to return the axis to proper functioning, gene expression network analysis, inflammatory immune signaling, neuroendocrine and immune network remodeling, genetic evaluation of the serotonergic system, gene expression and exercise. Some of these are on subjects the WPI is researching right now.

‘Dr. Vernon’s Studies’ - It’s important as well to draw the distinction between studies which she initiated (was the chief author) and which she was a part of (see the last list). These studies indicate an unfailingly interest and curiosity in the pathophysiological side of ME/CFS with a particular interest in viruses. (In the Empirical Definition study which is referred to so frequently referred she is the second to last author note which is the least significant place to be; the most significant being the first author (study initiator) and last author (senior author overseeing the project)

In fact, based on her record at the CDC and the CDC’s turn to more psychological matters since she left, perhaps the most logical conclusion to make about Dr. Vernon’s departure from the group, is that she pressed for more physiological research and left the CDC after the program took a more psychological bent. (Shortly after she joined them the CAA began the investigation into the CDC’s finances that lead the CAA to call for Dr. Reeves ouster in late 2008.)

Recent Work

Even if her work at the CDC had been questionable – and which, aside from being the co-author of one paper (Empirical definition), it isn’t – shouldn’t Dr. Vernon be most judged on her work after she left the confines of the CDC? As Research Director of the CFIDS Association she has been able to put lead a program for the first time. What does her work at the CAA suggest about her priorities. Should that put the ‘put the nail’ in the CAA’s coffin’ for CFS patients (or for the Clinical Director’s of WPI? :))

Since Dr. Vernon left the CDC the CFIDS Association has

  • created a Research Network and BioBank (currently being used to assess XMRV)
  • Put on the 3 day Banbury Conference (with another one scheduled for this year) which brought many new faces to the field
  • funded six studies on abnormal pain (and other) receptor levels, neuroendocrine-immune system functioning as people come down with ME/CFS after an infection, the cause of inadequate blood flows to the brain, the effects of exercise on gut microflora and immune activation, mitochondrial dysfunction in the brain and developing software program to make makes sense of 20 years of CFS research – that will be provided to other researchers after it is complete.
  • Teamed with new researchers from eight institutions that have not studied CFS before to submit two grant proposals on autoimmune aspects of CFS
  • Got chronic fatigue syndrome researchers the opportunity to compete for a 50 million dollar Congressional medical defense fund
  • Was awarded the OFFER Researcher Excellence Award at the Reno 2008 IACFS/ME Conference
  • Published papers on Immune Network Remodeling in GWS, cytokine networks in CFS, Immune functioning in GWS and periperhal blood gene expression after stress.

It doesn’t – at least for me. Dr. Vernon has been effective in enrolling new researchers in the field, in getting researchers to work together, in creating new resources for CFS research (Biobank) and in getting CAA researchers federal grants. A closer look at her record suggest that instead of being ‘the nail in the coffin’ for the CFIDS Association, she’s a considerable asset to the field.

Many Tricky Subjects

There are many tricky subjects in CFS. Dr. Vernon, with her history with the CDC, is clearly one. Dr. Klimas co-authorship of a stress reduction was another. The President of the IACFS/ME, Dr. Friedberg, is another. Dr. Friedberg is a psychologist (with ME/CFS) who has studied the use of behavioral therapies in CFS and argues vociferously for more pathophysiological research and less behavioral research. This is not because he believes behavioral therapies don’t help; he finds they do help with him and with his patients but he does not believe they help enough; ie they are not the answer – something both he and Dr. Klimas are in agreement on.

What about Dr. Jason? He has a record of unparalleled record of advocacy for CFS. The most probing and outspoken member of the CFSAC committee he was also a Board of Director for the IACFS/ME. He’s produced seminal studies indicating how prevalent and costly CFS is, demonstrated that the Empirical Definition brings in increased rates of people with depression, co-authored review papers highlighting the high rates of oxidative stress in the disorder, and publically blasted the CDC for conducting personality studies. Yet Dr. Jason is also a psychologist who has studied ‘coping’ and behavioral therapies and was a co-author of the paper that argued that an ‘empirical-like definition consisting of a series of questionnaires was the next step for ME/CFS? (It did not set the criteria).

Dr. Deckoff-Jones is very new to this field and Dr. Vernon is a somewhat problematic figure given her history with the CDC, but I think she’s proved herself -both at the CDC and afterwards – to be a friend, a very good friend to ME/CFS. Dr. Deckoff-Jones has been a very good friend to ME/CFS as well. I hope Dr. Deckoff-Jones will reconsider that ‘nail’ and these two very good friends to ME/CFS can work together at some point.

Papers Co-authored by Dr. Vernon and Dr. Reeves

Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. Review.

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome. Rajeevan MS, Smith AK, Dimulescu I, Unger ER, Vernon SD, Heim C, Reeves WC.Genes Brain Behav. 2007 Mar;6(2):167-76.

The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Vernon SD, Reeves WC. Pharmacogenomics. 2006 Apr;7(3):345-54.

Challenges for molecular profiling of chronic fatigue syndrome. Vernon SD, Whistler T, Aslakson E, Rajeevan M, Reeves WC. Pharmacogenomics. 2006 Mar;7(2):211-8. Review.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A. BMC Infect Dis. 2006 Jan 31;6:15.

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

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome. Vernon SD, Reeves WC. J Autoimmune Dis. 2005 May 25;2:5.

The economic impact of chronic fatigue syndrome. Reynolds KJ, Vernon SD, Bouchery E, Reeves WC. Cost Eff Resour Alloc. 2004 Jun 21;2(1):4.

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER; International Chronic Fatigue Syndrome Study Group. BMC Health Serv Res. 2003 Dec 31;3(1):25. Review.

Absence of Mycoplasma species DNA in chronic fatigue syndrome. Vernon SD, Shukla SK, Reeves WC. J Med Microbiol. 2003 Nov;52(Pt 11):1027-8. No abstract available.

Bioelectronic DNA detection of human papillomaviruses using eSensor: a model system for detection of multiple pathogens. Vernon SD, Farkas DH, Unger ER, Chan V, Miller DL, Chen YP, Blackburn GF, Reeves WC. BMC Infect Dis. 2003 Jun 19;3:12.

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC. Dis Markers. 2002;18(4):193-9.

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC. BMC Microbiol. 2002 Dec 23;2:39. Epub 2002 Dec 23.

HIV and human papillomavirus as independent risk factors for cervical neoplasia in women with high or low numbers of sex partners. Vernon SD, Unger ER, Piper MA, Severin ST, Wiktor SZ, Ghys PD, Miller DL, Horowitz IR, Greenberg AE, Reeves WC. Sex Transm Infect. 1999 Aug;75(4):258-60.

Association of human papillomavirus with HIV and CD4 cell count in women with high or low numbers of sex partners. Piper MA, Severin ST, Wiktor SZ, Unger ER, Ghys PD, Miller DL, Horowitz IR, Greenberg AE, Reeves WC, Vernon SD.
Sex Transm Infect. 1999 Aug;75(4):253-7. 17.

An unusual cervical carcinoma showing exception to epitheliotropism of human papillomavirus. Unger ER, Vernon SD, Hewan-Lowe KO, Lee DR, Thoms WW, Reeves WC. Hum Pathol. 1999 Apr;30(4):483-5.

Characterization of RNA in Cytologic Samples Preserved in a Methanol-Based Collection Solution. Dimulescu I I, Unger ER, Lee DR, Reeves WC, Vernon SD.
Mol Diagn. 1998 Jun;3(2):67-71. 19.

Detection of human papillomavirus in archival tissues. Comparison of in situ hybridization and polymerase chain reaction. Unger ER, Vernon SD, Lee DR, Miller DL, Reeves WC. J Histochem Cytochem. 1998 Apr;46(4):535-40.

Human papillomaviruses and anogenital cancer. Vernon SD, Unger ER, Reeves WC.N Engl J Med. 1998 Mar 26;338(13):921-2. No abstract available.

Human papillomavirus and disease status following therapy for cervical cancer.
Unger ER, Vernon SD, Nisenbaum R, Thoms WW, Spann C, Miller DL, Lee DR, Horowitz IR, Icenogle JP, Reeves WC. Clin Infect Dis. 1998 Feb;26(2):373-8.

Human papillomavirus type in anal epithelial lesions is influenced by human immunodeficiency virus. Unger ER, Vernon SD, Lee DR, Miller DL, Sharma S, Clancy KA, Hart CE, Reeves WC. Arch Pathol Lab Med. 1997 Aug;121(8):820-4

Association of human papillomavirus type 16 integration in the E2 gene with poor disease-free survival from cervical cancer. Vernon SD, Unger ER, Miller DL, Lee DR, Reeves WC. Int J Cancer. 1997 Feb 20;74(1):50-6.

Cervical cancer survival in a high risk urban population.Thoms WW, Unger ER, Johnson PR, Spann CO, Hunter SH, Smith R, Horowitz IR, Icenogle JP, Vernon SD, Reeves WC. Cancer. 1995 Dec 15;76(12):2518-23. Review.

Human papillomavirus and disease-free survival in FIGO stage Ib cervical cancer. Unger ER, Vernon SD, Thoms WW, Nisenbaum R, Spann CO, Horowitz IR, Icenogle JP, Reeves WC. J Infect Dis. 1995 Nov;172(5):1184-90.

Human papillomavirus infection and associated disease in persons infected with human immunodeficiency virus.Vernon SD, Holmes KK, Reeves WC.
Clin Infect Dis. 1995 Aug;21 Suppl 1:S121-4. Review.

Localisation of HIV-1 to human papillomavirus associated cervical lesions.
Vernon SD, Zaki SR, Reeves WC. Lancet. 1994 Oct 1;344(8927):954-5. No abstract available.

A longitudinal study of human papillomavirus DNA detection in human immunodeficiency virus type 1-seropositive and -seronegative women.
Vernon SD, Reeves WC, Clancy KA, Laga M, St Louis M, Gary HE Jr, Ryder RW, Manoka AT, Icenogle JP.J Infect Dis. 1994 May;169(5):1108-12.

The HIV-1 tat protein enhances E2-dependent human papillomavirus 16 transcription. Vernon SD, Hart CE, Reeves WC, Icenogle JP. Virus Res. 1993 Feb;27(2):133-45.

Human papillomavirus, human immunodeficiency virus, and cervical cancer: newly recognized associations? Vernon SD, Icenogle JP, Johnson PR, Reeves WC. Infect Agents Dis. 1992 Dec;1(6):319-24. Review.

Dr. Vernon Initiated CFS Studies At the CDC (Lead Author)

The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Vernon SD, Reeves WC. Pharmacogenomics. 2006 Apr;7(3):345-54.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A. BMC Infect Dis. 2006 Jan 31;6:15.

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome.Vernon SD, Reeves WC. J Autoimmune Dis. 2005 May 25;2:5.

Absence of Mycoplasma species DNA in chronic fatigue syndrome.
Vernon SD, Shukla SK, Reeves WC.

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC.

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC.

The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Vernon SD, Reeves WC.

Challenges for molecular profiling of chronic fatigue syndrome.
Vernon SD, Whistler T, Aslakson E, Rajeevan M, Reeves WC.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus.
Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A.

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