Dr. Ken Friedman on Chronic Fatigue Syndrome Part II:
Research - Roadblocks and Opportunities by Cort Johnson
You’re researching non-invasive ways to treating pain. How is that going?
Trying to sell the federal government on underwriting the cost of studying
non-invasive methods of treating chronic pain, particularly the pain
associated with CFS, is an extremely difficult if not impossible task. To my
knowledge, not a single study on this subject has ever been funded. If we
are going to explore such methods of treating chronic pain, the CFS
community will have to mount and support such studies without the initial
involvement of the federal government. I keep looking for alternative
sources of funding or some other way of jump-starting such a research
program. Thus far, I have not found an alternative funding source but I am
hopeful that some day I will.
The chronic fatigue syndrome (ME/CFS) research program at the National
Institutes of Health (NIH) has some really good elements but it
hasn’t gotten any support from above. It actually had to scavenge funds from
its other programs to pay for its one ‘big’ initiative of the past five
years. It seems like its impossible to get significant support from the
NIH yet we have lots
of good statistics about the prevalence, disability and economic costs of
chronic fatigue syndrome. We can make a strong case about the need for
more research yet it seems like we’re talking to a wall. Why is the NIH
such a tough nut to crack?
Knowing that your future career depends upon your obtaining an
undisputable outcome of this project, which project would you choose? Hence
the reluctance of many to work on CFS.
CFS is not attractive to any institute in the NIH because it is too ill
defined. We cannot define CFS by its causative agent (because we do not know
what the causative agent is or if there is only one, single causative
agent). We cannot define CFS by the organ system it affects because it
affects multiple organ systems and we are having a tough time identifying
how CFS affects organ systems. Science is based on simplicity. In order to
prove the presence or absence of something, you want to try to find it in
the simplest system possible. If you attempt to find the presence of
something in a complex system, the task becomes much more difficult and you
may not be able to find what you are looking for amongst all the other
substances present.
The analogy I would use is the manner in which clinical trials were
conducted up to the past 20-30 years. Most clinical trials were performed
with men. Women were excluded. The reason women were excluded was because
their fluctuations in hormones were greater than those of men and those
fluctuations might produce aberrant data. The aberrant data would then make
the results more difficult to interpret if not meaningless.
Given a choice between working on a simple, clearly defined problem with an
undisputable outcome or working on a complex, constantly changing problem
with a guaranteed questionable outcome, and knowing that your future career
depends upon your obtaining an undisputable outcome of this project, which
project would you choose? Hence the reluctance of many to work on CFS.
At one of the earlier CFSAC meetings Dr Patarca stated that, “The decision to
exclusively focus on chronic fatigue syndrome (ME/CFS) might affect a
professor's chances at tenure and promotion’. You’re a professor at a major
university. Is this true? Is chronic fatigue syndrome
regarded as a kind of a dangerous career move for a young researcher? Is it the kind of topic a graduate advisor might steer his students away from?
In my own experience, I have found Dr. Patarca’s statement to be correct. In
my own case, my publications concerning CFS have been judged by my
colleagues to be inferior because they have not been published in
prestigious journals and they are not as widely read as articles in better
known, more popular areas of research. (Of course, the so-called prestigious
journals do not publish articles concerning CFS.)
Acceptance of CFS as a bone fide illness and area of
legitimate research inquiry will be a slow process
CFS is also a dangerous career move for other reasons: Funding for CFS is
uncertain and if you commit yourself to CFS research as your career, you
might not be funded and might not have a career. Advancement at academic
institutions these days is very dependent upon demonstrating a record of
continuous research funding that brings money to the school.
Not only does a faculty member need to receive research funding from an
organization, but that organization must be willing to pay the institution
“indirect costs” which give the institution an additional amount of money
for permitting the research to be done at their institution. Only large
organizations such as the federal government can afford to pay the direct
costs of a grant and approximately an additional 50 percent of the direct
costs to the institution as indirect costs. Smaller organizations would
prefer to give all of their research funds as direct costs to more
investigators than to fund 1/3 fewer investigators and give the research
funds to the institution as indirect costs.
How do you change an ingrained mind set like that?
Acceptance of CFS as a bone fide illness and area of legitimate research
inquiry will be a slow process. It will require the availability of research
funds, and a sufficient number of published, undisputed research papers in
well-respected journals to convince the medical community that CFS is a real
illness with a known cause.
More importantly the medical community must be educated. We need to educate
both physicians and medical students. In my own, modest way, I am attempting
to do both. The CDC has a healthcare provider continuing education course
and has trained a cadre of individuals (mostly physicians) to deliver this
course. The course provides continuing medical education for physicians,
continuing nursing education for nurses and continuing education units
(CEU’s) for other healthcare providers. There is no charge for taking the
course.
“Which came first, the chicken or the egg?” Were NIH to have
a large, well-funded, extra-mural, CFS research program, new researchers would apply
The instructors, such as myself, volunteer their time and quite often absorb
the expenses associated with giving the course. I try to give at least one
course per year. This year, I flew to Michigan to give the course to
approximately 40 healthcare providers in that state. This May, 2007 course
was the first CFS healthcare provider continuing education course ever given
in the state.
Providing education to medical students may be a bit more promising. Several
medical schools are introducing courses that discuss chronic illness. The
faculty responsible for teaching such courses should consider CFS a chronic
illness and may be willing to devote curriculum time to CFS. Patients should
contact their local medical schools and determine if a course discussing the
management of chronic illness is being offered. If it is, they could
volunteer to be interviewed by students who are taking that course.
In addition, in New Jersey, we have just established the first medical
student scholarship for CFS. Medical students between their first and second
years of medical school may write an essay on an assigned CFS-related topic.
The medical student who writes the best essay wins a $3,000 tuition payment
for the second year of medical school. The scholarship contest is available
to medical students in all three of New Jersey’s medical schools. I hope to
establish similar scholarship programs in other states.
Once CFS is accepted and treated by the medical community, it will begin to
receive adequate funding.
There are a lot of issues at the NIH but one of the problems holding up the
pace of the CFS research program there appears to be a lack of researcher
interest – they don’t get all that many grant applications for CFS research.
Is attracting new researchers to the field a big problem in CFS?
The question you ask is a bit like, “Which came first, the chicken or the
egg?” Were NIH to have a large, well-funded, extra-mural, CFS research
program, new researchers would apply. Unfortunately, the funding of CFS
research has been extremely modest and the level of funding on a
year-to-year basis has fluctuated wildly. Moreover, in the past, the NIH has
funded CFS Centers of Excellence whose funding was abruptly terminated.
Under these circumstances, researchers are reluctant to apply to the NIH for
the scant CFS research funds that remain.
Unfortunately, the funding of CFS research has been extremely
modest and the level of funding on a year-to-year basis has fluctuated wildly.
I recently participated in a workshop on CFS research funding held by the
NIH in Rockville, MD. This September 17th, 2007 discussed grantsmanship and
which institutes at NIH have an interest in CFS research. All CFS grants are
treated like all other grants and sent out to study sections for peer
review. The peer reviewers “score” the applications on the basis of
scientific excellence, feasibility and significance. Such scoring is subject
to the frailties of human behavior and prejudice.
While several representatives of NIH institutes in attendance at that
meeting professed interest in CFS research, those representatives have to
rank other illnesses or topics in the research “portfolio” and make
judgments as to which grants to fund based upon their perceptions of which
grants are of the highest importance and, therefore, should be funded. While
NIH is encouraging researchers to submit CFS applications, there are no
guarantees as to how these applications will fare.
The Idea that chronic fatigue syndrome (ME/CFS) is a multi-systemic disorder has been around
for at least 10 years yet for the most part we still have one researcher
looking at the brain, one looking at the immune system, one at the endocrine
system. Is this kind of fragmented system by system approach to CFS the way
to research this disorder?
While researching the effects of a multi-system illness by determining the
proper or improper function of each physiological system may seem to be, and
actually is, a fragmented approach to determining the cause of that illness,
it is the traditional way biomedical research is done. Science, and
therefore biomedical research, is based upon a model of simplicity. To find
the cause of a pathological response in a complex or complicated system, a
researcher would try to exclude all those factors (and possibly systems)
that are not involved. Moreover, the human body is so complex and there is
so much knowledge about the various organ systems, that it is difficult for
an investigator to be an expert on all organ systems.
At this point in time, so many abnormalities have been found in so many organ systems, that one wonders how one illness can be so disruptive to so many systems? The findings of so many abnormalities
in so many organ systems, coupled with the unusualness of the abnormalities,
works to discredit the illness.
Traditionally, the
investigation into the workings of the human body has been divided into
organ systems. Thus, a cardiovascular physiologist traditionally studies the
cardiovascular system. Were his/her research to lead into the area of lung
(or pulmonary) physiology, another researcher with expertise in lung
physiology would be consulted or asked to join the project.
No physiological researcher is naïve enough to believe that the organ
systems function independently of each other. The ability of one organ
system to affect another is defined as physiological integration. In a
traditional human physiology course, one learns the basic functions of each
of the organ systems, and subsequently studies the interactions or
integration of these organ systems.
While the organ system approach may appear to be a fragmented way of
learning about CFS, the organ system approach to CFS has led to many
significant findings that might have gone undetected were researchers, who
were unfamiliar with the normal functioning of organ systems, to attempt to
perform CFS research. In the development of our children, most would agree
that a child needs to learn to crawl before he/she can walk. So too in
human, biomedical research, the functioning of organ systems must be
evaluated before organ system integration can be studied.
You’ve mentioned that you think low blood volume in CFS probably leads to
poor oxygenation in the tissues and that this may play a major role in CFS.
We’ve known about low blood volume for about 10 years now and it’s
astonishing to me how little progress the research community has made on
this. It’s only this year to my knowledge that anyone’s even started trying
to find a cause for it. Wouldn’t most diseases have teams of researchers
working on findings like this?
The low blood volume finding in patients with CFS is unusual. Not only does
it add to the mystery of CFS, but It adds to the non-acceptance of CFS as an
illness. At this point in time, so many abnormalities have been found in so
many organ systems, that one wonders how one illness can be so disruptive to
so many systems? The findings of so many abnormalities in so many organ
systems, coupled with the unusualness of the abnormalities, works to
discredit the illness. The question is not why so many researchers would shy
away from CFS research, the question is why do the few remain loyal to CFS
research? It takes a very dedicated, self-assured, and either a financially
secure researcher or a researcher oblivious to the need for financial
security to dedicate him or herself to CFS research.
The question is not why so many researchers would shy
away from CFS research, the question is why do the few remain loyal to CFS
research? It takes a very dedicated, self-assured, and either a financially
secure researcher or a researcher oblivious to the need for financial security
to dedicate him or herself to CFS research.
The finding of a low blood volume in some CFS patients, raises some very
interesting questions for both cardiovascular and renal (kidney)
physiologists: What is the cause of the low blood volume? What are the
effects of the low blood volume? How should we go about restoring the low
blood volume? What are the consequences of restoring the “normal” blood
volume?
These are very basic physiological questions of a kind that had been
explored in the 1930’s and 1940’s. Those kinds of studies were certainly
thought to have been completed by or in the 1960’s. The basic, physiological
concepts of human, blood volume regulation were thought to be understood.
Cardiovascular research has moved beyond that kind of research. Now, CFS
research, suggests that we do not know and we do not understand all that
there is to know about blood volume regulation.
Are the studies suggesting low blood volume in CFS sufficient and
sufficiently convincing to alter the direction of cardiovascular research,
and reopen research into areas long concluded? With cardiovascular research
now at the molecular level, who will reverse the tide of “modern” research,
and restart the now “classic” kinds of studies needed to determine and
document changes in blood volume and to determine the mechanism(s) behind
them?
What scientist or group of scientists would risk their future capabilities
of being productive scientists as well as the ability to earn an income to
explore the possibility of low blood volume? Why would a scientist or group
of scientists depart from mainstream cardiovascular research on the basis of
a few preliminary studies in an ill-defined group of patients who have an
illness that many believe does not exist?
Are there any particular areas in ME/CFS that excite you right now?
The whole area of CFS research is exciting to me. I have long believed that
a lot of physiology can be learned by studying pathophysiology. CFS presents
significant pathophysiology in multiple organ systems. Hence there is an
opportunity to learn a lot of physiology from CFS.
To my mind, CFS is one of several related complex illnesses. Other related
illnesses include fibromyalgia, multiple chemical sensitivity, Gulf War
Illness, and Lyme Disease. Understanding the physiology and/or
pathophysiology of one of these illnesses will aid in understanding the
pathophysiology of the others.
To my mind, the majority of the symptoms of CFS are the result
of an initial disturbance of one of the body systems that triggers a response in many others.
I call the response that occurs in the many other organ systems, “the final, common pathway.”
To my mind, the majority of the symptoms of CFS are the result of an initial
disturbance of one of the body systems that triggers a response in many
others. I call the response that occurs in the many other organ systems,
“the final, common pathway.”
It is my speculation that the similarity of symptoms exhibited in the final,
common pathway, despite the different triggers of CFS, suggest that CFS is
not one illness and that eventually we will be researching a group of
related illnesses. I would argue that the current stage of CFS knowledge, is
like the early stages of knowledge for cancer. Today, no one believes that
all cancers are the same and that the variation in symptoms seen in patients
is confounding, unexplainable variation of one illness.
The lack of understanding of CFS and its related illnesses despite
scientific investigation suggests that CFS is different from traditional,
known illnesses. CFS represents a new kind of illness. When the day comes
that CFS is understood, it will be the day when we have defined a new group
of illnesses with unique pathophysiological mechanisms that have not been
described to date.
Clearly there is a cascade of events that lead to CFS. When we identify the
steps in this cascade, and understand the relationships between them, we
will understand not only CFS, but the group of related illnesses as well. To
me, that is the challenge, and that is the excitement of CFS research.
Given the NIH's unwillingness to fund an active ME/CFS research program
we’ve hoped the Roadmap Initiative will provide a breakthrough for us. At
first glance the Roadmap Initiative looks perfectly suited to this disease; it's designed to address the kind of multi-systemic research
we need but
that the NIH has difficulty providing. You are not, however,
high on the ability of the Roadmap Initiative to deliver for ME/CFS patients.
What are your concerns about it?
I would argue that the current stage of CFS knowledge, is
like the early stages of knowledge for cancer
As I understand it,
the Roadmap Initiative is not disease specific, but
process specific. Let’s say that an award is made to study inflammatory
processes in humans. A great deal of data will be obtained. How much of this
data is relevant to the inflammatory processes associated with CFS? How will
we determine if the inflammatory processes characterized in these studies
are similar to, or differ from, the inflammatory processes that occur in
CFS? Who will pay for these latter studies? Under the roadmap initiative,
there will be no funds for the specific CFS studies needed to cure or treat
CFS.
Under the Roadmap Initiative, tracking of the dollars expended on CFS
research will become difficult if not impossible. If federal agencies took
funds dedicated to CFS research and shifted those funds to research in other
areas before the Roadmap Initiative, think of how easy it will be for them
to shift the funds from CFS research to other research projects when there
is no mandate for CFS-specific research, and no way to track the actual
dollars spent on CFS research.
To Dr. Ken
Friedman on Chronic Fatigue Syndrome (ME/CFS) Part I