Dr. Komaroff Transcription
I: So, according to CDC, in the United States in 2007, it is reported to have 1 million patients of
CFS. And do you consider this to be trustable data?
K: I do.
I: Is it still increasing?
K: I don't think we have any good evidence that it is increasing. I mean, have such evidence, youwould need to make that measurement at two points in time, and see a growth. And, the studies
that have been done have only been done in the last fifteen or twenty years, and never before
that. So, I think we don't know if it’s increasing.
I: And so, WHO categorized CFS as a neurological disease, including encephalomyelitis, and is it
an appropriate categorization of the disease?
K: I think it is. I think there is evidence from brain imaging studies, from brain hormone studies,
neuro-endocrine studies, and from studies of the autonomic nervous system, which begin
obviously in the brain, many studies in those areas show abnormalities in patients with CFS
compared with healthy control subjects or compared with depression control subjects or other.
So, I think it is an illness that affects the central nervous system, and the autonomic nervoussystem in many patients.
I: So, this is something specific to the patients.
K: Yeah. I am not saying that the abnormalities are unique to these patients, I am not saying that
there is a diagnostic test of the brain that is unique to CFS, but what I am saying, is that there aremany measurable abnormalities in these patients compared with healthy people or comparedwith depressed people.
I: And um, in Japan, there are some people who say obsessive characters or perfectionists can bea risk factor or more susceptible to the disease. Do you think...?
K: I don't think there is a lot of evidence for that. I would say that my impression as a doctor fromcaring for many patients, is that most of them, but not all of them, were very ambitious andsuccessful and very physically active people before they became ill. But, whether that means they
were perfectionistic, I don't know. And not all of the patients would appear to me to be
perfectionistic or very hard working before they got ill.
I: And, in terms of the cause of the disease, do you think somehow according to the articles that I
read, do you consider viral infections is the major or sole cause of the disease?
K: I think that the cause of the disease is not proven. That is, I have said that there is muchevidence that there are abnormalities in the central nervous system. Those abnormalities could
be caused by an infection and the immune response to the infection, but that has not been
proved.

I: And then, actually in Japan, or probably in the United States as well, but worsened chronic
fatigue could be the potential cause of the syndrome. What do you think? Do you understand?
K: I am not sure what you mean by worsened chronic fatigue.
I: Accumulated chronic fatigue or stress.
K: Very hard work and excessive stress.
I: Right.
K: I think very hard work and excessive stress adds to the vulnerability for many diseases. So, I
think it is perfectly logical that it could add to making someone get Chronic Fatigue Syndrome,
but I doubt that it is THE exclusive cause of Chronic Fatigue Syndrome. So many of the patients
become ill very suddenly. Last week, they were very active physically, very busy and all of asudden they no longer have the energy to do...it is very hard for me to see how stress could
cause such a sudden change.
I: Understood. So, to be honest, I was not so familiar with this disease or disorder. So, eventhough it is called Chronic Fatigue Syndrome, but like the onset is not necessarily chronicallyinitiated, right?
K: Often, it is very sudden, and often it is sudden with an illness that is like an infection, withfevers, and swollen glands, and sore throats, and aching muscles. People say, 'I have a flu, I havea cold,' but they never get better from that. So in many patients, it surely seems as if an infection
causes it, and there are some cases that are very well documented, where people get adocumented infection, and don't get better, and go on to Chronic Fatigue Syndrome. CDC did a
study that was published in 2006, that showed several kinds of infections can be followed by CFS.
I: In that case, there is no more inflammation or evidence of fever?
K: Fever is gone in most people, but in some people, they keep coming back with periodic fever.
I: In Japan, there is another report that 40% of patients spontaneously recovered over time, sothey claimed that patients do not need to be so pessimistic.
K: I think 40% seems high to me. The CDC published one study in which over 10 years, about 40%of people did improve very considerably. In our experience, it is more like 10 or 15%.
I: So once diagnosed as CFS, it is very...
K: In most of my patients, it is remained for many years.
I: I see. How do you think we can make Japanese people more recognize CFS as a serious illness?
As you mentioned it is hard to recover. What is a way to make them recognize or appreciate theseriousness of the illness.
K: I think the best way, all over the world, not just in Japan, will be more research that shows that
this is an underlying illness, with a physical or biological basis. The problem I think is that theillness is defined only, at least the CDC definition, only by symptoms. So, anyone can say they
have a symptom, and it is very hard to prove that someone has a symptom, and that I thinkcauses the illness to be, causes some people not to take the illness seriously. Once there is adiagnostic test, or a cause identified, then I think people will take the illness much more seriously.
I: Do you think someone can develop such a biomarkers and effective treatments...?
K: There are a lot of groups that are working to do that. And, as I said earlier, there are many
biomarkers that are abnormal more often in patients with the illness, than in healthy people. But,they are not abnormal in 100% of the people. Very poor sensitivity for a diagnostic test.
I: To my understanding, a variety of virus can cause these kinds of symptoms, not a single one.
K: Right. I have always thought that this is an illness that can be triggered and probablyperpetuated by a number of different infectious agents. My prediction has been that those
infectious agents will be the type that cannot be completely eradicated from the body by theimmune system. Once you are infected, you remain infected for the rest of your life, and if thatkind of infectious agent, mostly viruses, can infect the brain, that makes them even more likely tocause this illness. And the two kinds of viruses that we have focused our attention on, are herpes
viruses, and retroviruses, because both of those viruses produce life-long infection, and both can
infect the central nervous system. So I have always thought they were the most likely kinds ofinfectious agents to cause this illness, but I don't think that has been proven, yet.
I: And later in life they could be re-activated.
K: Yes, exactly.
I: Regarding complications or the symptoms of the patients, how seriously in general does CFS
effect muscle weakness or physical activity of the patients?
K: Not much demonstrated effect on muscle strength. I think most studies of muscle strength do
not show significant weakness of the muscles, but people lack the energy to continue any
physical activity for very long.
I: So this is consistent with infections. I mean...
K: Could be. I mean, some infections you keep getting worse and worse and worse.
I: Understood. And also do you think CFS patients are most susceptible for cancer?
K: I don't think there's any proof of that. It’s a risk theoretically, but I don't think there's any
evidence for that.
I: And related to that question, do you think there is a regional difference, like in terms of thecause of the virus?
K: I think that it’s possible, but unlikely.
I: OK. So these are kind of possibilities--transmission from one person to another?

K: Sure. If it is a retro-virus, or a family of retro-viruses, it would be passed by close contact withthe body fluids of another person. And it might be very hard, to catch it from some other person,
because most of my patients do not have a spouse or a child or a family member who has thisdisease, but some do. And, I have seen what appeared to be an epidemic of this illness innorthern California and northern Nevada, where many people, including many members of thesame family, became ill in a close window of time. But I think that would be unlikely that aretrovirus was causing something where 5 members of a family come down with something.
That's not the way retroviruses behave. It would be a more easily transmitted infection, like aaerosol spread infectious agent. So, I think we just don't know.
I: Is there any animal model of the disease?
K: I think, in a disease which is defined only by symptoms, and since the only species that can talkis our species, I am dubious about animal models. There are some animals whose physical activity
level can be measured, and who are used as animal models of chronic fatigue when their physicalactivity slows down, but I don't know if that is a very good model.
I: I'd like to go back to the previous question. Is there, especially in your experience, patients whoget disease after blood transfusion?
K: We have not seen that. We ask patients if they have ever had blood transfusions, and ofcourse some of them have, but most have not. So.
I: So there is this meeting of the CFS Association in Japan, will be held in January 29th, 2011...
I2: I'd like you to give them some message...and if possible, I'd like to record it on separate
memory. And before we go on to that, I'd like to ask you about your clinical experience. How
many patients have you been seeing?
K: I have seen about 450 patients over 25 years. Right now I remain in contact with about 200 ofthem.
I2: I see. What is a major treatment for them?
K: There are no proven treatments, but many of the patients have a sleep disorder, that
contributes to their fatigue, and very low doses of medicine called tricyclic drugs cause them tohave more hours of deep sleep every night, and make them feel better, never a cure, but makethem feel better. Very low doses of tricyclics.
I: So, anti-depressants?
K: Well, in high doses it’s an old-fashioned anti-depressant, but normal doses for depression are
200 or 300 milligrams a day, and we use 10 milligrams at bed time. It couldn't effect depression,
but you can measure the effect on the brainwave sleep activity.
I2: Actually Mieko, she used to live in the United States in the 1990s, and then she got ... so it had
been for two years until she was diagnosed by CFS so maybe I am wondering if many patients

here or even in Japan, have a long way to get diagnosed. So, your 450 patients, do they comedirectly to your clinic, or they search…
K: They are all referred by their doctors.
I2: Around the Massachusetts area?
K: All over. Mostly the New England area, but they come from all over the country, even othercountries.
I2: And also, in terms of the research findings, I searched NIH funding sources, and I found for theCFS research, they gave 5 million dollars, and instead for HIV research, they gave more than3,000 million. I found the newspaper advertisement in Washington Post, December 6th, theygave a big ad to promote research. Do you think in the future the research will be increased?
K: I think it depends on the results of the studies to try to understand this work.
I2: So it is kind of a problem with the science community, and how do you think about thesurrounding situation in the science community? Do you think the advocacy movement would
develop into one like HIV/AIDs?
K: Yes, and also the, you know, there is only so much money to spend on research. And if you
have just this much money, what you want to do is spend it on the problems where it looks most
likely that you will make an important discovery. There has to be a really exciting opportunity tomake new discoveries to spend the precious money, because otherwise, that money could bespent on HIV. Or diabetes, or heart disease. Where everyone knows this is a problem and weknow enough about the biology of the problem that you can see how important research could
be done to further understand the biology.
I2: I think this is exactly the problem in the Japanese science community. Because in terms of CFS
research, there are no such kind of biological research.
K: Well, there is a lot of research in Japan on fatigue in general, and you know, fatigue is a hugeproblem for most societies, even in people who do not meet the criteria for Chronic Fatigue
Syndrome. Fatigue and cancer, fatigue and auto-immune diseases. I was at a dinner last nightwith a dermatologist whose expertise is in psoriasis which is an immunologically mediateddisease, and she said fatigue is a terrible part of the skin disease, psoriasis, so there is a lot of
fatigue studies in Japan, maybe even more than in the United States.
I2: And also they have a fund for this research, but the CFS Association, the patients themselves
feel it’s not a right direction to solve their problems, so they expected the research like yours to
be done in Japan. Also, to improve their understanding of what it is. So, the meeting in January
next year, they expect you to send a message to improve or promote that kind of biologicalresearch related with the virus, so you give some message to promote that...
K: You know, maybe the best way of doing that, because I am very busy right now with this andother related issues, I wrote an article on the biological abnormalities in Chronic Fatigue
Syndrome that is published on the website of the CFIDS Association, the main patient advocacy

group. Ah! that's it. With the permission of the association, this could be translated and used.
Well, it was a pleasure meeting you both.
I2: Thank you so much. Can I take a picture of you?