Dr. Ken Friedman on Chronic Fatigue Syndrome Part II: Research – Roadblocks and Opportunities by Cort Johnson


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?

Dr. Ken Friedman
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

Add Your Comment

{ 0 comments… add one now }

Leave a Comment