Friday, March 4, 2016

An Open Letter to Dr. Collins and Dr. Nath on the NIH internal ME/CFS study

Note: As of Sunday, March 6, NIH has dropped the somatoform comparison group.  Thank heavens!  But they are still looking for "the underlying physiology of fatigue."  So I still wish they would spend as much time learning about M.E. as they have spent deciding on the [admittedly admirable] lineup of tests.

Dear Dr. Collins and Dr. Nath:
I echo the sentiments of many ME/CFS patients in expressing concerns about the way the in-house NIH study on ME/CFS is proceeding.
The stated hypothesis of this new study is that: post-infectious ME/CFS is triggered by a viral illness that results in immune-mediated brain dysfunction."  Is that really all there is to the hypothesis?  Dr. Wallit's participation raises troubling questions as to whether that is so.  The comparison groups chosen for this study also suggest there is more to the hypothesis than we have been told.  
I beg you, Drs. Collins and Nath, please rethink the hypothesis - and Dr. Walitt's role in this study. I also ask you to rethink the comparison groups. This disease has been a serious problem in the US for 30 years, and for 30 years both NIH and CDC have obstructed the creation of a strong biomedical research community – nevertheless, it has existed. 
What has happened here?  A hypothesis created by people who know next to nothing about this disease is being plonked on top of us. If I may say so, yet again.  Why?
Make no mistake about it, fellow patients: Dr. Walitt is playing with somatoform diseases here – he just thinks there’s a biological cause for them. 
He seems insulted that we might be unhappy about his inclusion.  All I can say is that anybody who uses the words "chronic fatigue syndrome," "fibromyalgia," and "somatoform illnesses" in the same sentence is unacceptable in a preliminary study of my disease sponsored by NIH.  
Last March Dr. Walitt published an article containing the following sentence:  "The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome. " (Chemobrain: a critical review and causal hypothesis )
I really do not care if Dr. Wallit is looking for a physiological cause for what are called "somatoform" illnesses.  The problem is that he thinks ME/CFS is a somatoform illness.
Then there are the comparison groups.  Where did these come from?  Two comparison groups:  post-symptomatic Lyme Disease patients, and patients with physical somatic disorders.  The choices of comparison groups themselves suggest that the research hypothesis for this project has not been fully revealed to patients.
With only enough money to put 40 ME/CFS patients in the study, may I ask why we are bothering with comparison groups at all?  Does it not make more sense to do this first study with ME/CFS patients v. controls - and then use more ME/CFS patients?  
Since 1998 I have known that i had the defective 37kDa Rnase-L and a severe case of HHV-6A. Later testing showed natural killer cell dysfunction (in my case, a natural killer cell function of 2-3%) and abnormal cytokine patterns. In 2009, Dr. Dan Peterson found active HHV-6A and CMV in my spinal fluid. Do you think that my serious encephalitic and neurological symptoms could have had something to do with that evidence? The immune defects and viruses go away on Ampligen and come back 7-12 months off it. I am a sample of 1, but there are more like me. Many more. We have patients improving on the antiviral Vistide at Dr. Peterson's (I cannot take Vistide; my liver markers shoot up).  The late Martin Lerner had patients on both Vistide and another antiviral, Valcyte;  Dr. Jose Montoya at Stanford has had success with Valcyte as well.  
Please pay attention to this evidence.  Talk to clinician/researchers.  
If not – then please run that hypothesis past some non-psychiatric specialists in our field before running with it in the first NIH internal study on our disease since Straus discovered (to his dismay) that we have abnormally LOW levels of adrenaline (patients with major mood disorders tend to have abnormally HIGH levels of adrenaline) 20 years ago.  Dr. Straus had planned to be able to say we really had depression; hence his disappointment. (Psychiatists in the UK - and CDC's CFS group - finally found a use for Straus's adrenaline study in the unsupported hypothesis that patients had too many stressors earlier in life and had, in effect, run out of mechanisms to cope with them.  If that were true, wouldn't one expect to find this disease much more common in Kosovo, parts of Africa, and in the embattled mid-east?  Why hasn't it popped up in refugee communities internationally?)
Perhaps you could put this off until you can hold a workshop with recognized ME/CFS experts. I am confident we could pull one together quickly.
The well-respected British organization, Invest in ME , is holding a research conference May 3 in London.  I am certain they would include you if asked.  Another international research organization for this disease, IACFS/ME (International Association for CFS/ME) is meeting in Miami in October. Put this on a workshop there, or let them help you set up an earlier one. Or ask the public members of CFSAC to help you create a workshop. Ask any of us to help you create a workshop. You need to discuss the hypothesis and comparison groups with the longstanding biomedical ME/CFS community before committing to them. 
In the beginning of 2000, ignoring the existence of CFSCC, the late Stephen Straus of NIAID and CAM at NIH ran a "state of the science" meeting about "CFS" with the usual suspects (if you forgive my saying so) – the psychiatrists from the UK who have had an inordinate amount of influence on perceptions of this disease both abroad and within HHS. After pressure from Congress he relented to having ONE public member from CFSCC attend (Nancy Klimas). But Congress continued to ask for a more objective  conference. Donna Dean had just been placed as head of CFSCC, and she ran a conference the next fall that was fantastic – full of science and discussions with researchers who had previously known nothing about the disease. Unfortunately, there was a presidential shift in 2001 and CFSCC was shut down (to emerge, weakened, as CFSAC almost three years later). Dr. Dean left, and nothing happened again until 2011, when Dennis Mangan ran another excellent State of the Knowledge conference at NIH, which then came to naught. 
When researchers do not know the very long history of this disease (technically going back to atypical polio in 1934, but practically speaking, back 60 years to the Royal College outbreak and creation of the terms myalgic encephalomyelitis in the UK and epidemic neuromyesthenia in the US), they make blunders. They can be perfectly well-meaning, but this topic is a mine field and requires someone who knows the history to navigate it. I am discouraged that once again NIH is going off on its own, as if we were never here at all.
One last way to salvage this study.  Simply ditch the hypothesis and comparison groups and run it as a study of potential biomarkers in ME/CFS, without prejudging their meaning.
This is a very raw hypothesis. I love the scientific evidence you want to bring to bear, but I wish you were working on biomarkers for ME/CFS – not the physiological basis for "somatoform" illnesses.

Mary M. Schweitzer, Ph.D.


  1. Wonderful open letter Mary. Thank you for taking the time to write it. I hope they will listen.

  2. Thank you for explaining where this study falls short. I too was surprised by the small number of ME patients to be used, and the inclusion of two comparison groups of questionable merit.

  3. An excellent summary of the shortcomings of the proposed NIH study and the personnel involved.
    Thank you.
    Please note that the Invest in ME conference is to be held on the 3rd of June 2016 - not early May as you have said.

  4. I am going to SSDI hearing for ME/CFS but I have been saddled with a somataform diagnosis which I am very concerned about. I have very low adrenal output. Therefore, could you post a link to the study or studies on adrenal function and ME/CFS? Thanks!

  5. Please reply to this comment as I for got to check notify me on the one above. Otherwise, I'll never keep track! Thanks again for your excellent letter.

    1. The original was in 1991! Demitrack MA1, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW. "Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome." J Clin Endocrinol Metab. 1991 Dec;73(6):1224-34.

      Here is a discussion by Cort Johnson on Phoenix Rising when he still ran it:

      And you can also try googling "CFS cortisol levels".

  6. Please reply to this comment as I for got to check notify me on the one above. Otherwise, I'll never keep track! Thanks again for your excellent letter.

  7. Thanks, Mary! I really appreciate it. Best of luck!

  8. Excellent blog post. Thank you Mary!

  9. Thank you Mary. I'm in Europe and really value your knowledge of the history. Another puzzle for me is the terminology - post-infectious 'myalgic encephalomyelopathy' - hypothesising immune-mediated brain dysfunction - hasn't the World Health Organisation recognised that since 1969 - given that 'itis' means inflammation, which is an immune response (albeit that USA has only recently adopted WHO ICD-10 codes)? I realise that inflammation in the brain and spinal cord has been disputed, but some recent research validates this. I may have missed some information, or very likely be confused. By the way, I noticed that Invest in ME invited Drs. Collins and Nath to their June 2016 Biomedical Researchers Colloquium. It would be a valuable opportunity for NIH to meet and discuss with the world's leading researchers into this disease, so I do hope they can send a representative -

    1. Hi Jo! I've been to two of the Invest in ME conferences. I only get to go to the second day - but a researcher from NIH would go both days (the first day is for researchers and clinicians only). It is a great crash course in what ME is, and how research is proceeding internationally. So I will continue to suggest that they pick SOMEBODY to be the ME expert on the team and send that person to London.

    2. My edit function isn't working so well on this page, for some reason - I forgot your other question.

      I did not see encephalopathy in the notice - perhaps I missed something. The US only adopted ICD-10-CM (the US version of ICD-10) last October! NCHS originally placed CDC (postviral) in G93.3 and CDC (NOS, or not otherwise specified) in the old garbage category. One reason I think they are emphasizing postviral is they are signaling they mean G93.3, which as you probably know puts the disease in neurology.

      Yes, the main reason NIH and CDC has objected to using the patient-preferred name, "myalgic encephalomyelitis," for the disease (which would, I hope, also require using definitions for ME) is the absence of signs of "inflammation." In my own case, I think the symptoms I have off Ampligen, plus having two viruses known to be neurotropic active in my spinal fluid at the same time, is a strong argument there is an infection and (again using my symptoms) inflammation. I think they will eventually see that as they study more patients.

      Of course, there are many diseases whose name does not precisely reflect what they are. So they are being a little priggish to quarrel about "evidence of inflammation" when the name has been in continuous use for 60 years.

      The main reason I would be surprise if they used encephalopathy is that the term is suddenly being used a lot to describe the physical damage to the brain that happens to veterans of the second Iraq War who had close encounters with IEDs, and football players who had close encounters with each other.

    3. Argh - won't edit. That would be CFS (postviral) in G93.3 and CFS (NOS) in R53.83. Technically, NCHS took CFS out of G93.3 entirely - but both the IOM report and this study are using CFS (postviral) - so I suspect it's going to end up back there.

  10. Mary, as the mother of an adult daughter who has been suffering with ME for many years (and it's progressing where she can't work anymore), I so appreciate your wise and informative posts. Thank you from the bottom of my heart.

  11. That you for articulating my concern much better than I could have, Prof. Mary Schweitzer.

    It would be great to ditch the control groups, or use control groups of other illnesses which have received more study, such as MS.

    More ME patients mean more statistical power.

    Also, why in the world when many blood volume, circulatory, and immunological abnormalities are found in ME is the NIH using researchers, such as Walitt and Gill, who view this as a somatoform disorder, and apparently have not heard of ( or "dismiss" all this evidence)...

    Reminds me of:
    Not theirs to reason why
    All the world wonder'd

  12. Thank you Mary for being our advocate. My wife killed herself February 20th, 2015, after 20 years with M.E.,and she had lost all hope in our CDC and NIH.
    I contracted it in 2009 but it was not caused by a virus or flu. My immune system was crushed by severe stress and trauma. Like you, I have reactivated HHV6, Coxsackie, and EBV. I also have Human Parvo

    1. I am so very sorry for your loss. I lost my husband of 40 years to cancer in 2013. I am hopeful that all the attention in the US to viruses, immune defects, and other biological abnormalities in ME and CFS (G93.3) will soon hit a point where medical researchers nationwide realize how badly they need to figure out this disease. As for your case - depending on the history of it, it's possible that you got sick when your wife did, but it did not pop out until later, which happens. Or that you had slow onset. Or that, as you say, you were under so much stress and trauma that your immune system just crashed. Without CDC tracking this disease, without biomarkers, it can be very difficult to figure out what causes it. The late (and much missed) Tom Hennessy used to say, different insult/same result. He meant that we came into the disease through different doors.

      I do think that one of the better ideas NIH has had about this data set is that with only 40 patients in it, one way they can reduce the heterogeneity is to only take those who had a sudden onset after a viral illness. This is only a preliminary study - hopefully with what they find out, when they expand to larger studies, they will be able to use a biomarker to define the study sample.

  13. Thank you Mary for being our advocate. My wife killed herself February 20th, 2015, after 20 years with M.E.,and she had lost all hope in our CDC and NIH.
    I contracted it in 2009 but it was not caused by a virus or flu. My immune system was crushed by severe stress and trauma. Like you, I have reactivated HHV6, Coxsackie, and EBV. I also have Human Parvo

  14. Walt, my heart breaks for you. Hang in, there is hope!

    1. Thank you :)
      It's been tough but I celebrate her life every day. I am surrounded by joyful memories

  15. Thank you, Mary, and I'm sorry for loss too. Char had M.E. before we married in 2002. I contracted M.E. in 2009 so she believed she gave it to me, which is understandable, because it's it's viral based, in my opinion.

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