Wednesday, July 15, 2015

Dear Dr. Collins: I’m Disabled. Can the N.I.H. Spare a Few Dimes?

Dear Dr. Collins: I'm Disabled. Can the N.I.H. Spare a Few Dimes?
By: Brian Vastag | July 14, 2015

Three years ago, a sudden fever struck veteran science writer Brian
Vastag on a blue-sky Wisconsin morning. He's been sick ever since. Now
cognitively and physically disabled, he lives on the island of Kauai.
On Brian's third "illiversary," he presents an opportunity to National
Institutes of Health Director Francis Collins.

Dear Dr. Collins,

You might recall the last time we spoke. It was January 2013, and I
was working as a science reporter at The Washington Post. Your people
arranged an early call for you to announce that the N.I.H. had decided
to retire most of its research chimpanzees. We spoke for about 20
minutes, and I typed up a 600-word story. It wasn't very good.

I was working from home that gray day because I had little choice. I
was mostly bedbound then, seven months after a sudden fever had
knocked me prostrate. My legs were so weak that climbing the stairs to
my home office required pulling myself up the railing hand-over-hand.
My brain was so sluggish I asked few questions of you. The ones I
managed to croak out were poor, no doubt.

Too sick to work, I did anyway. I loved my job at the Post – not an
easy gig to come by – and I was desperate to keep it. I had been
following the research chimp story for a while, and I liked that the
N.I.H. chose me to break your news.

I've long appreciated how the N.I.H. helps the world. My career began
there in 1998, when Paul van Nevel hired me for a science writing
fellowship at the National Cancer Institute. I count your
communications director John Burklow among my mentors, and I was
honored to write Paul's obituary. That first boost of professional
success propelled me to an exciting career.

Lately, though, my love for your august institution has been strained.
You see, I've been felled by the most forlorn of orphan illnesses. The
most accurate name for it is myalgic encephalomyelitis, which means
"painful inflammation of the brain and spine." (Yes, it is painful,
and yes, there's strong evidence of neuroinflammation.) At the N.I.H.
and elsewhere, it is instead called chronic fatigue syndrome. That's a
terribly vague and dismissive moniker for so serious an illness, and
one that needs to be retired. Fatigue is not the primary or most
troubling symptom for most people with M.E.

In the past, you've shown a soft spot for certain orphan diseases. Well, the history of M.E. is akin to locking an entire orphanage in a cellar and bulldozing the house.

On the list of illnesses the N.I.H. studies, M.E. (listed as "M.E./C.F.S.") is near the bottom in funding, ranked 231 out of 244. It received $5 million in 2014, less than hay fever, which cripples no one.
That's not enough money to equip a laboratory and run it for a
year. This abject neglect – or sustained prejudice, or maybe both –
stretches back a full three decades at the N.I.H. (For a detailed
history of how this sad state came to be, read Hillary Johnson's
deeply-reported book Osler's Web.)

No one has a good count of M.E. patients in the U.S. – the C.D.C. misspent funds earmarked for this purpose – but there's plausible evidence that several hundred thousand people are disabled by it. That's comparable to the burden of multiple sclerosis – the illness M.E. most closely resembles. N.I.H. funds $110 million in M.S. research each year, and a sustained government investment has been crucial in the development of a dozen F.D.A.-approved M.S. drugs. M.E.
patients have no approved treatments.

But M.E. is finally emerging from the basement. Brand name
institutions and big-time researchers now recognize the huge burden
M.E. places on society – tens of billions in medical expenses, lost
productivity, and missing tax revenue each year. Columbia University's
Ian Lipkin is searching for infectious triggers, and has reported
severe immune problems in patients. Columbia received $150 million in N.I.H. grants in 2015; Lipkin's operation gets a big chunk of that. But when the famous virus hunter applied for a trifling $1 million for M.E. research, the N.I.H. turned him down, twice. So spurned, Lipkin and colleague Mady Hornig recently resorted to eating habanero peppers to raise money.

Jarred Younger, at the University of Alabama-Birmingham, has a list of
off-the-shelf drugs and supplements that can reduce neuroinflammation.
They urgently need to be tested in patients. In Norway, a phase three
clinical trial of the cancer drug Rituximab in M.E. holds great
promise. In early trials, nearly two-thirds of patients improved after
repeated doses of Rituximab, and a quarter went into full remission.
Such promising results, if reported in cancer patients, would be
trumpeted as a breakthrough.
Additional studies to sort out which
patients might benefit from this drug are urgently needed; the N.I.H
Clinical Center would be a fantastic home for such trials. It's
unseemly to let a tiny Scandinavian country overtake the enormous U.S.
of A. in this, or any, realm of medical research.

At Stanford University, prominent geneticist Ron Davis is searching
for genetic risk factors. His investment is deeply personal, as his
adult son – formerly a world-traveling photographer – is severely ill
with M.E., and can no longer walk or talk.

When you peruse the recent M.E. literature, you'll see a mix of young
researchers and experienced lab leaders producing a string of insights
into how the illness damages the immune system and the brain.
Mutations in the gene MTHFR have been identified by the Open Medicine
Foundation as a risk factor. Diagnostic biomarkers await validation.
Promising treatments need to be tested in patients. And all of this
has happened with little support from the N.I.H.

Patient advocates have called for $250 million in M.E. research
funding, a figure commensurate with the burden of disease. This is a
huge ask, and in all likelihood politically infeasible, so let me make
a smaller one. A new N.I.H. program funded with as little as $10 million to $20 million per year would be absolutely transformative for the field – and for patients. Such a program would affirm the N.I.H.'s commitment to understanding the illness. It would draw more young researchers to studying M.E., and it would encourage further private funding. Such a commitment would also give patients – many housebound or bedbound for decades – hope that they'll be healthy again. I challenge you to find another illness where such a small investment could make such a huge difference.

You now have broad support from the medical community to make this
happen. Earlier this year, the Institute of Medicine made a strong
call for a robust M.E. research program. And just last month, an
N.I.H.-appointed panel urgently made the same recommendation. With the
bipartisan 21st Century Cures Act poised to pass Congress – giving
N.I.H. an extra $8.75 billion over five years – you could do so
without pulling money from existing programs. At the same time, you
could help things along by moving responsibility for M.E. from its
long-term parking spot at the Office of Research on Women's Health to
one of the institutes that, you know, funds disease research.

A year before I fell ill, I backpacked Rocky Mountain National Park.
My legs carried me up to the continental divide, where I sat on the
edge of a precipice marveling at the peaks around me. At nearly 13,000
feet above sea level, the thin air addled my thinking – a feeling I
now live with every moment, as if someone poured molasses into my ear,
gumming up all trillion synapses. It's a terrible way to go through
life, especially so for someone who not so long ago made a good living
with his brain.

Here in Hawaii, there's a smaller mountain behind my yard. It's called
Sleeping Giant, and the giant's forehead juts less than 500 feet above
my back patio. A well-trod trail carries people up there for sweeping
views down the volcanic slope and across the endless Pacific. Oh how I
would love to drink in that view. But I may as well be gazing up at
K2; a summit attempt would be supremely unwise, as a sophisticated
exercise test found that I suffer from severe metabolic, cardiac, and
pulmonary dysfunction. Exercise for M.E. patients is more damaging
than sugar is to a person with diabetes.

At 43, my productive life may well be over. There's a good chance I
have hiked my last trail. The nation's coffers lose some $25,000 in
tax revenue each year I remain disabled, and I will soon know if
Social Security Disability Insurance will start coming my way. I don't enjoy being a drain on society, and neither do any of the other M.E.
patients I know.
And yet, with the ever-growing research interest in
M.E., I have hope that someday I'll be able to stand for more than a
few minutes, walk for more than a block or two, maybe even resume my
career. (It took me four days, with frequent breaks, to write this
letter…that's a bit slow for newspaper work.)

The causes of M.E. will eventually be discovered, treatments will be
found, and patients will enjoy long-term remissions. As the leader of
our nation's medical research enterprise, you have a decision to make
– do you want the N.I.H. to be part of these solutions, or will the
nation's medical research agency continue to be part of the problem?
At the very least, you could ensure Dr. Lipkin doesn't have to scorch
his intestinal tract again just to drum up a few research dollars.


Brian Vastag

Monday, July 13, 2015

ME and CFS By Mary Schweitzer

ME and CFS

By Mary Schweitzer

This disease was first documented in a cluster
outbreak in Los Angeles in 1934, in the middle of a
polio outbreak.

It was given the name Atypical Polio, and through
other cluster outbreaks it either was called that, or
sometimes Icelandic Disease for an outbreak there.

In 1955, when the Polio vaccine supposedly
eliminated polio (not quite), there were three major
cluster outbreaks in the UK.

The most famous was an outbreak among medical
personnel at Royal Free Hospital in London. That
ended up being given the name Myalgic
Encephalomyelitis (actually, originally benign
Myalgic Encephalomyelitis because it didn't
immediately kill you - and WHO still includes the
word benign, tho it was soon dropped by
physicians because, as Ramsay said:

"There's nothing benign about ME"

In 1969, ME was added to the ICD codes under

ME is coded at 323.9 in the chapter on neurology
in ICD-9-CM, which the US is still using (until
October 1), though it has been known to disappear
for a while ...

Ramsay and Richardson and several other British
clinicians continued to work on ME for a while, and
Ramsay published a textbook on it in 1986, revised
in 1988. You can find his definition of ME from his
1986 textbook (reformatted with more white
spaces to be easier to read) here:

In the US, the term ME was simply not used.

Instead, the US adopted "Epidemic

The term had fallen pretty much out of use by the
mid-1980s cluster outbreaks, unfortunately. But
because of that, we in the US do not have a history
of ME diagnoses, and most doctors have never
heard of it.

Up through the 1960s, Multiple Sclerosis had been
diagnosed as "Hysterical Paralysis" - but the proof
of the deterioration of the myelin sheath ended

I include this because - what a coincidence -
suddenly in 1970 and 1971 there were two articles
asserting that ME was really "Hysterical Paralysis" -
solely on the evidence that some of the outbreaks
had occurred in women's or girls' dorms.

I've always thought they were looking for
somebody to take the place of the MS patients in
their clinics ...

"Hysterical" never caught on - but its flip side,
"Neurasthenia" (a nervous condition, the vapors)
became the favorite diagnosis of British

       It was not generally used in the US. But
       when British psychiatrists USED this
       diagnosis, they were violating the rules of
       WHO's ICD, because it was supposed to
       be coded under neurology, not psychiatry.

Then in the mid 1980s there were cluster outbreaks
of the disease all over the place - the United States,
Canada, the UK, Australia.
At first, the late Stephen Straus of NIAID (the
National Institute for Allergies and Infectious
Diseases at NIH) insisted it was Chronic
Epstein-Barr, because the trigger in many of these
outbreaks was a cluster outbreak of Epstein-Barr
(Mono, Glandular Fever).

THEN, Straus found it was not clearly due to EBV,
and for reasons that still escape me, he became
furious at the patients. Really....

Straus began using the phrase "the Chronic Fatigue
Syndrome" in 1986 in his funding requests. In
1988, there was a conference headed by Straus
and by Holmes of CDC to name and define this
"new" entity.

There were at least four researchers or clinicians
who knew what ME was at the conference, and
they strongly urged that the committee recognize
the outbreaks as ME.

They were ignored.

Holmes published a definition for the newly named
"Chronic Fatigue Syndrome" after the committee
met, and that became known as Holmes Criteria
(1988). The article never mentioned ME. 

Then the British shrinks came up with their own
definition for "CFS", where they did not exclude
psychiatric symptoms and any physical explanation
for the symptoms DID get the patient excluded.

As you can imagine, this definition has really
muddied the waters by producing very different
data sets, pulling in a lot of patients with primary
depression or anxiety.  It is called the "Oxford
In 1994 there was an attempt to reconcile the
international definitions, and the result was what is
called Fukuda (1994).

Most good biomedical research has been done
using Fukuda - but I personally think they started
out using a tighter-defined group of patients, often
from a cluster outbreak.

The Fukuda definition requires 6 months of
"debilitating fatigue," and then 4 of 8 symptoms
(substantial impairment in short-term memory or
concentration; sore throat; tender lymph nodes;
muscle pain; multi-joint pain without swelling or
redness; headaches of a new type, pattern, or
severity; unrefreshing sleep; and post-exertional
malaise lasting more than 24 hours).

       The biggest problem with Fukuda is that
       patients could have four symptoms that really
       aren't indicative of ME or cluster-outbreak

CFS was never put into WHO's ICD-9 codes
because WHO was getting ready to roll out

So the US put it under "vague signs and symptoms"
in ICD-9-CM, which will be in use in the US until
October 1.

In ICD-9-CM (which is what your doctor currently
uses in the US), CFS is coded at 780.71 and ME
is coded at 323.9.

The UK adopted ICD-10 in the mid 1990s;
Canada adopted its own version, ICD-10-CA in

Both ME and CFS are coded to G93.3 along with
Postviral Fatigue Syndrome in the WHO's ICD-10.
However, CFS was only in the index, not in the
more formal tabular version.

In 2003, Canada added CFS to the tabular version
to their ICD-10-CA, and put them all at G93.3 -
under Neurology.

The National ME/FM Action Network of Canada
created a very good definition to go with the new
Canadian category, calling the disease  ME/CFS.

So there IS a legitimate definition for ME/CFS - it
is the Canadian Consensus Criteria (CCC) for
Canada's ICD-10-CA classification of ME and
CFS at G93.3 (Actually, that is the "International
Consensus Criteria" (2003) - but since there are
two other sets of definitions called the International
Consensus Criteria, most of us use CCC.)

Meanwhile, in the US, in anticipation of moving to
ICD-10, CFSAC recommended in 2004 that the
US adopt the Canadian definition. It repeated that
recommendation several times over the next
decade, and finally, in 2014, CFSAC asked for an
open workshop of professionals to update the
Canadian Consensus Criteria, or CCC, as it is
often called, and then to adopt it.

The result was a flurry of activity, but not as
CFSAC had requested. And it may have been due
to other factors as well.

There was the IOM, which suggested renaming the
disease SEID (Systemic Exertion Intolerance
Disease), and the P2P. 

Both were very rushed and it is unclear how much
impact they will have on the government health
agencies they were supposedly advising.

However, both stressed that this is not a psychiatric
disorder. (The biggest problem with SEID is that it
omitted the exclusions that were in Fukuda and the
CCC, and that can result in a very strange data set,
a mess for both researchers and clinicians.

In the meantime, in 2011 a group of clinicians and
researchers met in Calgary in Canada to create a
new research definition for Myalgic
Encephalomyelitis, which they then published in the
Journal of Internal Medicine.

It REQUIRES post-exertional exacerbation of

As the US moves into ICD-10-CM in October,
CFS will not be put in G93.3 with ME.

It will be coded at R53.82 - back in vague signs
and symptoms.

Changing the chapter is a SERIOUS departure
from WHO's rules for using ICD (and your nation's
own version of it). I know of no other disease or
disorder where the US has done that, frankly.

NCHS (which is within CDC), who is in charge of
the various US ICD-CM codes, insists that the
R53.82 code means they are "not changing" how
CFS is coded - but they have definitely changed
how it is coded in WHO's ICD-10.

I think they are being deliberately misleading. I
heard them testify back in 2003 that CFS and ME
were both going to be in G93.3 in ICD-10-CM -
then they came back in 2005 and all that had
changed, after Bill Reeves of CDC had insisted
vociferously that they not "change" where CFS is
(from the US standpoint, but obviously not from the
international standpoint).