Interview with William Markesbery, July 7, 1986

SMOOT: Dr. Markesbery, last time we were talking you had begun a discussion on this research center, Sanders-Brown Research Center on Aging. If you would maybe start from the beginning there again--

MARKESBERY: Okay.

SMOOT: --and just kind of bring it through to the present, what this institution is all about, how it got started, uh, the origins and development of this institution over the years that you have been associated with it.

MARKESBERY: The historical perspective, you want all of that?

SMOOT: Yes sir I do, if you please.

MARKESBERY: Okay. Now I have to be consistent because you had some of this before. (laughs) There were some aging activities, uh, in the University of Kentucky in the seventies but in 1972 or '73 the John Y. and Eleanor Brown Foundation gave a million dollars to the university for the purpose of building a building to support the biologic research of aging. And, uh, the state legislature matched that with another 00:01:00million dollars and then I think there was a significant amount of money from the university to put into this to build a building, which culminated in the present Sanders-Brown Building, which was dedicated in the fall of 1979. It has about thirteen laboratories, they're well equipped, it has a barrier animal facility on the fourth floor; uh, it has a lot of support, uh, space for our secretary office, office, uh, space that is, and a, uh, conference room and library combined; so it's a very nice building for that purpose. It was dedicated, uh, uh, in the fall and the, uh, charge at that point was to get something 00:02:00started. And I took the job as director in the fall of 1979, with the hope of getting biologic age-, research in aging, uh, underway. We, uh--with funds from the dean of the College of Medicine had, uh, starter money for equipment and we had, uh, lines for about three faculty members at that point. Mind you we had a number of, a larger number of laboratories, we have like, I think there are thirteen laboratories, let me count ----------(??) write it down--(pause)-- eleven, I think that's right, twelve or thirteen laboratories. Anyway, uh, then we hired, uh, some faculty members, uh, and being a center, you don't really have, you don't have the status of a department, 00:03:00so individuals that you hire have to be in a different department. Uh, and so we hired people in the department of biochemistry and in anatomy. Uh, in addition, we brought in a number of people in the building that were interested in nervous system. Some from neurology and I happen to be from neurology, but that's not the full reason, you try to develop then, uh, aging in the nervous system, as our major prospective. And to do that we've had to unite people from--

UNIDENTIFIED WOMAN: Dr. Markesbery?

MARKESBERY: Yes.

UNIDENTIFIED WOMAN: Dr. Cushell (??) is on line one.

MARKESBERY: I'm sorry, I'm busy, uh, could you just take a message for me?

UNIDENTIFIED WOMAN: Oh, okay. Will do.

MARKESBERY: Um, anyway, we had to reach across to people in a lot of different departments. And as a matter of fact, in different parts of the university on the Lexington campus as well. So we are very pleased to have amalgamate of people from the un-, Lexington campus department 00:04:00of chemistry and department of psychology with people from the Medical Center, departments of anatomy, biochemistry, physiology, pathology, neurology, just to name a few. Uh, a number of different departments aided to the program here, say aging in the nervous system. And our first bit of luck came when we got a training grant to train pre and postdoctoral students in 1981 or '82. Uh, and that was about a half million dollar grant, that allowed us to recruit postdocs and graduate students and has been very helpful to us. Then, um, we were very fortunate to tie together a group of people and get what is called a program project grant in Alzheimer's disease, and which again was a, I think a million three or a million four or five, uh, thousand dollars, five hundred thousand dollars to, uh, study the causes of Alzheimer's disease. And then superimposed on that was a anoth-, another grant 00:05:00which became a, developed a center grant proposal and became one of the ten centers in Alzheimer's disease. And the reason we were able to get that I think was we had the program project grant as an underpinning for that, plus we had a very broad program in Alzheimer's disease. So that established us as one of the ten, um, I'd say leading centers in the country studying Alzheimer's disease, both from the clinical standpoint and research standpoint, and from a service and educational standpoint. In addition, we joined forces with Dr. Ted Kotchen in the Department of Medicine and, uh, through his initiative we have a, um, about a million pl-, a million plus grant from NIH to study systolic hypertension in the elderly. So the program we developed and the end-point of that is stroke and heart disease, so the major 00:06:00focus we have is how the brain ages and what happens to it over, over the years. And it is a very timely program to develop because of the major push now with Alzheimer's disease, it just sort of carried us along with it. In addition, the programs that have developed here are exercise physiology, that is exercising the elderly, uh, and how it can alter your physiologic response, uh, and a program in how the immune system declines with normal, with aging, as a normal cogent (??) of aging, I should say, and how this potentially relates to the diseases of the elderly. And in addition, the program here has, uh, taken in all the aging studies going on in the whole university. As the--that 00:07:00is to say, all aging activities of any type are carried on under the Multidisciplinary Center for Gerontology, which I think is, I think the name of that is going to be changed relatively soon to the University of Kentucky Center on Aging or Aging Center. I'm just about to have them get rid of Multidisciplinary, uh, Center of Gerontology and the Center of Ground Research here on Aging, which is a headache for anybody to try and say, much less remember. So the Council on Aging, which is a Donovan scholar program is a, under the social and behavioral sciences, um, are also here, as well as all those Medical Center studies, uh, in the biologic aspect of aging, so the program has developed and, uh, we have had a little luck and we've had a very good support system from the administration of the Medical Center and the university in general, which is a lot of, it's developed, you know, well.

SMOOT: What is different about what this center is doing versus other centers studying these various, uh, problems across the country?

MARKESBERY: You mean others that are Alzheimer's disease centers or other centers, aging centers?

SMOOT: Aging centers, generally. Of course, Alzheimer's is one specific then to deal with, uh--

MARKESBERY: Right. Well, the difference in this aging center and I'm not exactly sure how it got, I guess the money called the tune, that's how it got its start, but this center developed first the research base. Now other centers have developed the social and behavioral science descriptive aspect of aging first, or the clinical care and geriatrics part of it. Well, what has happened here, we developed the, the biologic research aspect first and then the social and behavioral aspect and then the clinical and geriatrics part, which is under-, underway now, it's d-, it's undergoing development and has a major 00:09:00push from the College of Medicine. The Medical Center, in general, has developed, uh, a teaching program and a clinical care program for the elderly. And the importance of all of that is, there's several important factors. It's very difficult to get a physician to go into a nursing home in this day and age. I mean our nursing home care is abysmal, not only in Kentucky, but in this country. In Central Kentucky we do as well as any place, I think, and it is still not very good. We really have to upgrade the care of our elderly and, uh, we have to get physicians interested and to do that you have to, you can't go to a fifty or sixty year old physician and, and reacquaint him with how you practice medicine, he is already fixed in his routine, his beliefs. What you have to do, you have to influence medical students and house officers. So our plan is to get more geriatrics into the 00:10:00medical school curriculum and, uh, to have a rotation for medical students involved with the clinical side of this, this program. And in addition, to establish links with, uh, nursing homes and develop teaching nursing homes that will have the goal as strong as you can give, uh, ideal optimum care with cost containment and, and really establish these, this nursing home as we are trying to develop the teaching nursing home, as one that is, uh, an exemplary standard of excellence for teaching not only physicians, but nurses and pharmacists and all your health care professionals. Anyway, so this center has developed a little differently than most aging centers. And I don't know whether has given us a leg up or whether it is good, but so far we've had, we've had pretty good luck, and I think it's probably an 00:11:00ideal way to do it. We get some other folks coming in from outside that say it is a pretty good way of doing it. Establishing your building and your basic science research program and then adding on to that the social and behavioral and the clinical aspects of.

SMOOT: Demographics would seem to dictate that a lot of people would be going into care for the elderly, uh, considering that the population is generally aging, you have a baby boom generation that just turned forty and in a few more years, of course, you're going to have those people entering into their sixties and so on, and hopefully well beyond that because of the advances made in longevity and these types of things. Uh, what is keeping more people from going into, uh, care for the elderly? It is not as lucrative as some of the other areas?

MARKESBERY: It's partially that. Uh, it is not as romantic and dramatic and as exciting. There are a lot of chronic diseases there that you can't cure, you know we, we all go into medicine thinking we are going to cure man's ills, and, uh, it's just not as exciting to get chronic 00:12:00diseases that you, and, uh, people that, uh, are older and you probably don't relate to as well. And, uh, who have multiple diseases in most, uh, people over sixty-five or seventy on; multiple different medications and multiple problems associated with aging. So it's just the lack of excitement and I, I, it's a little less lucrative, I suspect, but, uh, not much more well, not much less lucrative than other, other fields. I, I think it's more the view that you are caring for older people in a nursing home and that's all there is to it, which it really not what geriatrics is. It's a continuing of care from the home to the hospital to the chronic care facility and back home, hopefully. And it encompasses physical medicine and rehabilitation and preventive 00:13:00medicine just as well as any other; and I think we need to become more aware of that in geriatrics. And I think you are going to see a, a development of more aging programs and I think eventually we'll find that--you'll find, uh, more physicians going into studying, uh, the problems of the elderly and caring from them a little bit better; but it's really not happening right now, and it would probably have to be legislated on us before we really get carefully serious about it.

SMOOT: Um-hm. You mentioned earlier that in fact the state, and it has, there's been general expose as being abysmal, that is to say nursing home care throughout the United States.

MARKESBERY: Um-hm.

SMOOT: What do you think may be the major causes for this? It is because of the, uh, people that go into geriatric care? Is it because of the, uh, social, uh, factors involved with the, dealing with across the generations? Or is it just a broad range of things that you would sight 00:14:00as being the major causes for, uh, problems in that particular area?

MARKESBERY: That's really a very good question, because you know you look at it historically, most of our grandparents, uh, and their grandparents were cared for in the home. We didn't have institutions like we have now. Uh, there were a few state institutions where if people became severely demented or weren't able to be cared for in their home, they were placed in state institutions. But for the most part, families pulled up their bootstraps and cared for their loved ones in their home. Now this had some--adds historical perspective and I think of an interesting thing that happened to me one time. I mentioned to you, we had a joint meeting with, uh, sort of Russian physicians and scientists that came over and for an exchange, they came out of university. I asked them the question, through multiple interpreters, "What were their nursing homes like?" And they gave me a very flat answer, "We don't have much more nursing homes." "Well, 00:15:00who cares for your, your chronic care elderly patients?" Said, "Well, they're cared for in their homes or loved ones." "Well, what if they can't do that?" "Well, they're cared for by the next door neighbor." "Well, what if they can't do that?" "Well, they are cared for by someone in that community and if not in that community, then an adjoining community." And they made it sound, now you have to, to put this in context; it was through multiple interpreters in the Russians, like you have nothing but good news. And certainly have great respect for their elderly and, uh, perhaps that may be a very, very important factor. Anyway, they, they seemed to truly have more respect and more interest in caring for their elderly. And our, uh, yuppie generation and our present, uh, younger generations aren't terribly interested in caring for their loved ones in their own home; so now we have lots of nursing homes developing. And it's a proper motive in most instances 00:16:00and it's not done with the loving care that you get in a home, therefore, it's done, it's done, and the care is ten-, given by people who are there because they are working an eight-hour shift, and they are there because they are making dollars to put food on their table; and they really don't have the missionary zeal and the deep-rooted interest in giving the kind of care that's really needed. So there's that factor, factor of, of not being very exciting for physicians; and you end up then with, uh, less than ideal care because there is no commitment on the part of American medicine or in those really running the nursing home to really give the best of care. Plus you are dealing with diseases that we can't, there's no cure in many instances. 00:17:00Um, osteoarthritis, for an example, incontinence, variety of causes, dementing diseases, uh, severe heart disease, cancer, uh, these are the things that are in nursing homes and, uh, they are harder to do much with and we are just not giving the best care, but we can't go on like we are. We are really going to have to improve our care in that. I don't think I really can answer your question well. There are a lot of factors that go into this, uh, something has to be done to improve it.

SMOOT: Do you see something along the lines of, of trying to educate people into the importance of trying to take care of their elderly within the home, or perhaps within, at least within the community in which they are from and then maybe some kind of like outpatient arrangement with them to get the specialized treatment that they are going to need. Because after all, you can't get those kind of treatments outside of a established medical facility.

MARKESBERY: You are absolutely right. Uh, in the background for that, there are, there is a great push by our administration that is our state and federal administrators, to keep people in the home. And, uh, more dollars are being spent trying to determine ways that people can care for them in their home and not in nursing homes, because nursing homes are eating up large segment of our health care budget. But your question is a very interesting one in that our center has just received from the state legislature through the center of excellence, we were one of the ----------(??) of excellence at university, to deliver the programs that were funded in our center of excellence, are to give, to go to the outreach areas of the state of Kentucky, in a number of different settings. It's a team of, a health care team 00:19:00of physicians in both the workers and nurses; and improve the care of demented individuals, primarily those with Alzheimer's disease, but any dementing disease. But also in the Department of Medicine, to care for individuals, to educate, uh, caregivers on the how to improve the care of their loved ones in the home; and I think it is very important. So it's a role that the major medical centers are going to have take. Being a small state like this with a large rural segment, we have to, uh, we are in an ideal position to establish programs that could be national models for this, as a matter of fact, on how to do good outreach care and keep people in their homes as long as possible and keep them out of nursing homes. But I truly believe, in the--I'll get myself in hot water putting this on tape, I'm sure--but I truly believe that the care in the home by someone who loves you, um, with, uh, a loving physician as well, and a caring physician, is much better than 00:20:00you will get in a nursing home. Because there are people there that care about you twenty-four hours a day and in a nursing home you get three eight-hour shifts. You're there because, they, they may be well- intentioned and good-hearted, but they are still not your relatives and, don't, you know, not a husband or a wife or a son or a daughter, and will not just give the intimate care that someone would give if they are a loved one. So I think we ought to do everything we can to keep people in their home. There is a limit on what families can do and what caregivers can stand, and they eventually will in many instances, uh, give up, put up their hands, I can't give this person anymore and at that point then we need chronic care facilities. But that system of chronic medical care system has improved considerably and that is one of the things we would like to help do here at this center.

SMOOT: Let me draw back on another thing that you mentioned in 00:21:00describing the center. Uh, you mentioned that you had animal, animals here for experimentation.

MARKESBERY: Um-hm.

SMOOT: Is that correct? Have you ever had any problems with that in terms of outside factors like the, uh, Society for the Prevention of Cruelty to Animals--

MARKESBERY: Um-hm.

SMOOT: --or any of these people that have, uh, raised questions or complaints about your use of animals for experimental purposes?

MARKESBERY: We haven't had direct complaints to us that I am aware of at this--up until now. Uh, there is quite an outcry from the National -- --------(??) group, but, um, using experimental animals is not correct. We use rats and people are less likely to be concerned about the rat than they are with a cat and a dog and a monkey, and, uh, so in a sense there is not as many rat lovers out there as there are dog, cat and monkey lovers and I can, can identify that and understand that. So, 00:22:00but use primarily using rats; there are a few guinea pigs, uh, and, uh, but primarily rats. Very interesting that an old rat will cost, uh, I guess now about a hundred and fifty dollars. You think about a rat itself costing a hundred and fifty dollars is quite amazing. Um.

SMOOT: Can't use some of the, uh, local rats that are running around here? (laughs)

MARKESBERY: Well, it's kind of hard to, kind of hard to find. These are rats that have been raised under lovely controlled conditions.

SMOOT: Um-hm.

MARKESBERY: One of the things we are doing here is, uh, our barrier animal facility allows us to raise animals under completely controlled conditions. And, uh, we can raise a rat from day one through, uh, twenty-four to thirty months here and have our own colonies, and know the exact environment in which they have been raised and the humidity level, the noise level, the temperature level, what they've eaten, what their bacterial flora is throughout their life. Therefore, you know the life history of that animal and have a better chance 00:23:00of understanding his response to normal aging, which is very, very important. The National Institute of Aging established a policy that, that supported and, uh, pushed for individual medical centers to have barrier facilities so that true aging studies could be done, um, with the right kind of animals, and, uh, we were fortunate enough to have funding for that when the place opened and it's taken a long time, but we now have our barrier animals, um.

SMOOT: I know that other parts of the Medical Center uses cadavers for experimental purposes. Does this center use them as well?

MARKESBERY: No, we don't. Don't have any.

SMOOT: Don't have any use for that sort of experimentation?

MARKESBERY: No, we do, we get brains from all over the country as a part of a national autopsy network and as part of our Alzheimer's disease research center, but it, it's the brain only.

SMOOT: Um-hm. What is the, uh, policy on use of those types of, uh--

MARKESBERY: Well, obviously, the family has to give their permission and we send them a report on what, uh, we find, uh, in their loved one's brain. And, uh, then we can utilize that part of the brain that-- you take part of it and freeze it and part of it -------------(??)--and we utilize that for all our studies, and that's, that's inherent in the permission that we get from the family. And it's very interesting that most families of loved ones with Alzheimer's disease want an autopsy and want to prove that's what it is, because that's the only way in the world to prove that diagnosis. And, two, to try and do something about this disease by, uh, offering the brain for research uh, it's been a very supportive system of families and it's been done through very careful education of these families. It, it's very difficult to go out and say we, you know, "We want to take care of your loved one," and we 00:25:00eventually we'll ask, may I ask you--we don't do this ahead of time--we ask, ask them for autopsies. Uh, and you know some people have very strong feelings about autopsies. Obviously, it is a very sensitive issue and we just ask and if they don't want it, that's just fine. But a number of families--I think Dr. Wilson will tell you that--there are over forty or so now that have pre-arranged for autopsies to be done on their loved ones while they are still alive. So this is a, a nice, a nice feature of the eighties where people are having an, an informed view of what the disease is about and how in the world we can ever get through a position where we can understand it, by allowing us to tell you that the only species that develops it is man. It doesn't happen in lower animals, you can't see the disease in animals at all, and there's no experimental model for it; therefore, you have to study it in human beings. So very, very, very helpful to us to be able to be an autopsy center, one of the three autopsy centers in the country, as 00:26:00well as, uh, have our own ----------(??) autopsy network here in the Medical Center.

SMOOT: What's the method of disposal of these organs once they have, once the experimentation has been terminated?

MARKESBERY: They are cremated. They are cremated.

SMOOT: Um, I heard recently, I suppose it was on the news or perhaps it was in the newspaper. I really can't recall, that, uh, they had some sort of significant breakthrough in, uh, with the diagnosis of Alzheimer's or is this perhaps something that has come out a little bit too soon. You, you recall?

MARKESBERY: No ----------(??).

SMOOT: Could you tell me a little bit about that, uh?

MARKESBERY: Sure. One of the major problems that we had in Alzheimer's disease is about once every two months the National Enquirer gets a hold of some piece of research and sensationalizes it. The last one was a protein that's in the brain of patients with Alzheimer's disease, called alz-, A-l-z50, Alz50, and it was done by a very good laboratory 00:27:00at Albert Einstein College of Medicine in New York, a man named Peter Davies, that I know. And, uh, it was overplayed in the, in the press as a magic breakthrough and what happens every time this happens, uh, something comes up, the families all say, gee, here, here's the big breakthrough, through we're looking for. In point of fact, it really isn't. It's a nice piece of research that was in Science and it may help considerably down the road, but it doesn't give rise to a diagnostic laboratory test at all, and it hasn't improved our, our position in terms of treatment or anything else at that point. It has some promise in the future, but it just got played way out of proportion. It was on nightly, national nightly news--

SMOOT: Right.

MARKESBERY: --it made, uh, New York Times, as usual and, uh--

SMOOT: Well, I assure you, I didn't see it in the National Enquirer. (laughs)

MARKESBERY: Well, no, no, there are a lot of things that come out in the National

Enquirer that are really very hokey. This is real, but you have to realize that this group of

families and patients sitting out there with no hope whatsoever, and anything we give them in the

way of hope they latch onto, and, and naturally play it up and, uh, and the press and the media in general just sitting there waiting for a big breakthrough. It's probably not going to come for a long time. Small little steps like this one is going to add to our knowledge. I was c-, I was on a NIH study section, uh, up until the last year, and one of the study section meetings--which we worked our heads off for three days in Washington reviewing a grant. Um, I got a call from the associate director of a NINCDS, which is the National Institute for Neurologic Disease and one, and there was a new drug that came out potentially, uh, curing Alzheimer's disease. Would I get busy and learn everything I could about this and, uh, perhaps be ready to 00:29:00testify before a congressional committee. And, uh, the bottom line was that this wasn't any more of a breakthrough than anything else, but someone had treated five patients and said they had improve-, or, you know, five patients said they improved. Something got into, uh, I think it was Time or Newsweek not too long ago, as a major breakthrough, where they had studied five patients by putting ------ ----(??) down the brain, drifting in, uh, an old-fashioned drug called uracolene (??) in the brain for, uh, a longer period of time, and the families said they improved, although neuro site testing said they did not. This got into, into the lay press and was heralded as a new way of treating Alzheimer's disease. And we have to guard against those things, they are very, gets the hope of the families up falsely and, uh, then they come crashing down when they find out there is really not a cure and there's really nothing new to diagnosis the disease yet and we have to very patient. So your question is a very good one, but we're-- those sort of things do happen--but, um, those of us who are 00:30:00in the ten centers have to fend off the questions of the, of the care giving families and the early patients and when you know, this what we've been waiting for? When in fact it isn't, so you have to give bad news all the time.

SMOOT: Um-hm. How much information does someone in your position, doing research on something specific like Alzheimer's disease, you compare the areas of research such as, uh, something that springs to mind to me would be genetic research or any neurological research that might be going on and would somehow relate to, uh, your own research?

MARKESBERY: Well, what, what you try and do in this business is to find out what new probes are being, new research tools are being used in whatever field and immunology has developed very rapidly. It is sort of a field of the eighties. Molecular genetics is going to be the field of the late eighties and the nineties, I think perhaps I may have misstated, maybe immunology is the field of the seventies and molecular 00:31:00genetics is a field of the eighties, but just developing now; so it should develop even into the nineties. But what you try and do is use those techniques and apply them to the disease you are studying. So you do try and keep up with other areas and hire good people in those areas if you can to try and enhance your program. And to have them apply their tools or in learning what new tools you can use from allied fields and biochemistry and mo-, um, molecular biology and genetics and things like that, and apply them to your field so it is important to keep up. If you go to the meetings you will see that in the area of Alzheimer's disease that very specific new molecular genetic probes are being used to study Alzheimer's disease. It is about somewhere in the range of 20 to perhaps 30 and maybe even more percent of Alzheimer's 00:32:00disease that is inherited that we know of and you need to study that group of patients intensely as sort of a window into the disease overall. So, you comment about genetics and immunology is really a very good one, especially about molecular genetics.

SMOOT: Let me ask you something similar, along similar lines. Uh, perhaps this is something that is a bit faddish but springing forth from the youth cult that we seem, uh, to, uh, keep going very strong in the United States, but, uh, for a long time you'd hear people, not necessarily in the medical professions, but futurist and these types of people talking about the benefits of exercise, benefits of nutrition and taking mega doses of, uh, vitamins and so forth to keep you young longer, make you stronger, increase your longevity, et cetera. Have you been doing any research along these lines, uh?

MARKESBERY: No, we really haven't. There--the, uh, I guess you'd look upon the research we are doing here as trying to improve the quality 00:33:00of life to the other end of the spectrum, rather than extending the life to the other end of the spectrum. So we really haven't done that. The exercise physiology person here, Dan Richardson, has just gotten a grant to study, uh, how the, uh, capillaries have changed with aging and how they change with exercise in the elderly; which will give some good basic information, but we're not doing any directly with, uh, nutrition or exercise. In the, should say, uh, in the Don-, in the Donovan program there are exercise fitness programs for, for them, which are utilized, uh, considerably by the people in the Donovan program. And I have a feeling we should be doing more with exercise, you probably saw an article in the last month, or maybe the last couple of weeks, that shows that exercise can increase the, uh, mobility and 00:34:00perhaps the length of life, uh, if you exercise regularly. And we probably should be doing more with that, but we're not. It's a good area to expand into.

SMOOT: Is this something that you would need direction from the, uh, federal or state governments, uh, in order to do or?

MARKESBERY: No, I think it can be local internal decision if we wanted to develop in that direction and probably is one that we should, but our walls are sort of bulging right now, we don't have enough space for everyone. So we're, you know, we're, we're a little bit hesitant about adding new programs until--we don't have the space ----------(??). We are trying to make the ones we have, uh, sort, of, uh, standards of excellence and do our best to make them, uh, productive.

SMOOT: You already mentioned that the center receives a considerable amount of, of funding from outside sources.

MARKESBERY: Um-hm.

SMOOT: Uh, could you give me a ratio of basic research to applied 00:35:00research in this particular center?

MARKESBERY: Define what applied is, I guess I could do it, maybe you better tell me what you mean.

SMOOT: Well, my understanding of applied research is, is you are given a specific task, okay, versus just generally expanding knowledge in something like basic research where you are really given a free hand to do whatever sorts of research you might want to do within the general framework of the institution versus giving an assignment from a government, almost on a contractual basis, to perform, uh, certain, uh, tasks, to, uh, expand knowledge in a specific way, or to, uh, actually produce something specifically.

MARKESBERY: Well, the reason I ask you to clarify that is because, uh, the research in Alzheimer's disease is, is very specific. We have, we told them what we wanted to do and now they expect us to do it. In that sense, we're doing specifically what they have viewed us to do. So in a sense, that's applied, but we have the latitude to freelance 00:36:00within the framework of what we said we'd do, and in that sense it's basic. And I think probably if you look at what we do here, it's about seventy, thirty basic, uh, seventy, thirty basic to applied that is seventy basic to about thirty applied, okay. Our large grant, uh, in systolic versus chronic hypertension studying systolic hypertension in the elderly is a contract, uh, that, uh, has us treating patients with this systolic hypertension with medication and not treating some other people and, uh, applying the outcome of the treatment to see if treating systolic hypertension really has an effect on stroke or heart disease, so in a sense, that's, uh, that's pretty applied I think.

SMOOT: Um-hm. Is that the way you would define those, those two terms?

MARKESBERY: I think that's, that's probably ----------(??).

SMOOT: Okay. Um, you mentioned earlier, uh, that perhaps there would be a need for government intervention, in terms of upgrading, uh, the level of health care as provided by nursing home care facilities. Uh, what is your general opinion and perspective on government regulation generally in the framework that you work, uh, in, uh, the Center on Aging, uh, or I can try to rephrase that a little bit, how would you characterize the regulations imposed upon you, and that may be too strong a word also, but imposed upon you by the government? Do you think they are adequate? Do you think that they are inadequate? Do you think there should be more or less government intervention and regulation? What are your general views on that topic?

MARKESBERY: No, I think in what we do here, with, uh, more of an eye 00:38:00toward research, uh, we are very tightly regulated by, uh, the federal government, because they, they pay us to do this research--

SMOOT: Um-hm.

MARKESBERY: --and I think it is probably appropriate the amount of, there's a lot of red tape, and you can see my desk is full of papers that relate to the grants that, that we are dealing with. And it's a headache in many ways, but it's about the only system that will work. And I think the regulation of the research component of the federal spending is done rather well and I think it's not, uh, under regulated, maybe a little over regulated. But, uh, as someone who works in that system and who has been a peer reviewer of the work that goes on there and I'm on that congressional advisory committee. Uh, I think the system works. Now as it relates to clinical care, uh, government control is becoming much more vice-like in making, uh, 00:39:00the paperwork more, making it harder to care for individuals; and I'm not very excited about that. Although, the other side of the coin is when you have to send someone for a CAT scan of the head, that's maybe three to five hundred dollars, I don't believe that anyone should ever have to pay three to five hundred dollars for an X-ray study of their head, no matter how fancy it is and how much the machine costs, and I think part of the government control of that sort of thing. So I have this ambivalent feeling about it. I, I think we have too many people, and again I'm getting myself in hot water, too many people making too much money out of medicine, and if I could control it, now that I'm, have children and married, I would make the rules such that it would be almost a monastic sort of existence. You go into medicine, you live in the hospital, you care for the people because you 00:40:00are dedicated in doing it, and, uh, you don't have much else to do in your life. Now, that's very constraining and generally unreasonable and, and sort of a right wing view, but I think we have a situation now with money--medicine being exploited by folks making too much money and I know I'm overpaid, I'd be the first to admit that. But I truly believe that we ought to go into medicine for the pure reason of wanting to take care of sick people. And you have to realize that it's really an amazing opportunity, because people put their trust in you, put their lives in your hands, and you have a chance to, to help them and we get paid for doing that. I, the system isn't right, it really isn't right. And I, I think, I, I don't think the government control of it will put what I would like to see into it and I think those countries that have government control in medicine have an awful 00:41:00lot of unhappy physicians and I don't have a lot of experience with the English system, but probably not ideal. But I think our system has to be changed eventually. And, if I could be the architect, there would probably be very few people applying to medical school--(laughs)--I guess, but there's a guy that really would do what needed to be done, that is dedicate ourselves to taking care of sick people. Because, I think we don't look back enough and say, gee, you know, what was, what were our ideal-, our ideals when we started this? We've become flooded by this overwhelming avalanche of information that you have to learn. You become a little bit burned out early on because there is so much that you have to do and you have to work so hard, and you start thinking selfishly. And, uh, once that happens, you lose your, your idealism and I think medicine needs to retain, those in medicine, really need to retain their idealism. And I guess I'm up on a soap-box 00:42:00again, I didn't mean to, that wasn't your question at all, but I think it is very important that we maintain our idealism in medicine.

[Pause in recording.]

SMOOT: Well, there are some people that would argue it seems that, uh, that was the way medicine was, uh, approached by most physicians in the early days, there was a bit more idealistic tinge to it--

MARKESBERY: Um-hm.

SMOOT: --uh, of course, in the twentieth century and especially since World War II, there has been a massive growth in the economic opportunities--

MARKESBERY: Right.

SMOOT: --provided to physicians, uh, a real, uh, entrepreneur in medicine can do very well indeed, and many have done so on a variety of levels. Uh, you mentioned the English system as, as one model. Of course, now there was Germany and the Scandinavian nations and lots of other countries, in fact, I would think most other countries have some sort of social system, uh, of course, I could say, socialized system.

MARKESBERY: Right.

SMOOT: Uh, and we have some of that, too. We usually just don't call it that.

MARKESBERY: That's right.

SMOOT: Uh, and at least on a ----------(??) pay basis, there's nothing wron-, directly wrong with that, but it is a matter of, uh, how you structure it, I suppose. And, uh, of course, the organized medicine in the United States has not been overly receptive to that kind of thinking--

MARKESBERY: Right.

SMOOT: --even though such programs as Medicare and Medicaid has made a lot of physicians very wealthy.

MARKESBERY: Yeah, and as I, as I think back to my younger days when a town physician was extremely well respected. And as physicians increase their wealth, the curve of their respect in the community goes down--(laughs)--it, it seems to me. In spite of all of this, I may be sounding negative, the medical care given in this country is much superior to any other than I know about. And I guess the system 00:44:00works in that regard, but it sure is eating up a mountain of money to do it right now. The technical advances are kind of exciting, we're able to do things we couldn't do before and, um, make diagnosis we couldn't make before, so the free enterprise system works in improving our diagnostic ability and perhaps our treatment ability, but where we really get stuck is in diseases such as malignant cancers and Alzheimer's disease and things like that, we can't do, we can't treat them, we can't prevent them, we can't arrest them, uh, and it's where we need to make strides, and that's why you need more people going into, into academic medicine to do research. And that's a major problem in that we are not getting as many throughout the country, not only here in Kentucky, but throughout the country good, young, bright minds are not going into the research areas.

SMOOT: Um-hm.

MARKESBERY: I think we talked about that before.

SMOOT: We've touched on that. That is a big problem. A lot, a lot of other people have mentioned that to me. Well, how long does it take to become an academic physician?

MARKESBERY: According to your drive, I, uh, it, you know, it took an internship in four years after internship, uh, if it took nine years of, uh, medical school and specialty training. And that, in all candor probably had another year or two of fellowship training, but my drive was such that I could go out and, uh, do research as well as service work when I finished my training. I'd been much better off if I had had a year or two of neurochemistry to top that off, but, uh, it's a, and it doesn't, you know, it doesn't pay as well as well as if you were going to go out and go into neurosurgery on Fifth Avenue, I mean you can make a bundle doing that. So that our system is not rewar-, it's rewarding guys like me, I mean, I'm overpaid as I said, but for 00:46:00the young person starting out, it's not as rewarding financially. But you got to have that burning zeal to want to get involved or be a megalomaniac or have an outrageously large ego to think that you can tackle some of these problems, anyway. And you have to have the role model of someone that sort of struck you early in your training as a, gee, this is, I would like to follow someone like this and, and learn about how to cure disease or how to approach a disease from a research standpoint. I don't think we are doing a very good job of that right now. At least that's one excuse for why people are not going into academic medicine as much.

SMOOT: What do you see as some of the, of course, I'm asking you now to go into something very speculative, but what do you see as some of the possible, uh, benefits to be procured in the future from the research 00:47:00that is being done here? Aside from the direct benefits of, uh, improving care and perhaps even curing Alzheimer's disease. Uh, can you see other areas that we're goin-, that are going to be benefitting in a major way or perhaps in an indirect important way, uh, from the research that is being conducted here?

MARKESBERY: Well, I guess I'll have to be very self-serving to think we are going to have a major impact on any of the diseases that we are looking at or anything that we are studying, but since there have been thousands and probably tens of thousands of people studying cancer for over thirty years and we're still no further along in that area, probably not even when you think that we're going to have a lucky break here and find a cause or a cure for any diseases, but we might add small little building block increments to the overall effort to 00:48:00understand some diseases or how the body ages. I think that is part of what we are going to do here. The, the dramatic breakthrough is probably, there are not many dramatic breakthroughs in science as you're probably are well aware. And, uh, we're probably are not going to have major breakthroughs, uh, during my lifetime here in, in curing diseases, but perhaps we'll add some building blocks to understanding about, uh, how to approach Alzheimer's disease and perhaps how the immune system does age and how that might allow, uh, diseases to affect the elderly that won't affect the younger person whose immune response is intact. And it's true these small little incremental building blocks that we'll be making, uh, having a major impact and perhaps helping mankind. I guess the programs we have that, uh, give direct 00:49:00care to people can be weighed into this in some way, even though we might not cure diseases, we help families care for them and we help diagnose them and we have our programs for the elderly, uh, be it exercise fitness or classes for them or workshops or whatever; I guess there's some direct benefit there, but, uh, primarily looking at the research effort, it's gonna be only through adding small increments to our knowledge base that will probably have an impact.

SMOOT: Let me ask a real cynical devil's advocate sort of question. Uh, you mentioned the years of research that has been spent on cancer. Some people would say, well, they don't really want to find the answer to cancer too soon. After all, those institutions that have been built 00:50:00up are worth millions and millions of dollars, it provides them with lots of jobs, it gives them something to do, gives an enormously, uh, wonderful lifestyle, et cetera, et cetera. Let's, let's get off in some minute detail over here and not really go after the big question and, and looking at the big picture and find the answer too soon. Something along the same lines as you might hear from somebody who found, uh, that water would run an automobile and the automobile and oil industries would not be very happy about that. Uh, what's your response to that sort of a type of question?

MARKESBERY: Well, in my idealism I believe that people working in these areas would truly love to find a cure instantaneously and take all the research money that's being poured into cancer and poured into atherosclerosis, hypertension, diabetes, or some other area until that's found out as well. Because, I think, we, we all are, uh, well-meaning in, in research and although each one of us would like 00:51:00to find the breakthrough for cancer or any other disease and say that hey, I've done this and my life is, uh, now has more meaning because I have made a major contribution. So, I really, I really don't think that, uh, there's any slowness in the research simply because of economical reasons. I, I haven't, I think the most, everybody in this field, uh, although very pragmatic, uh, really would like to find a breakthrough and you hope it would be tomorrow. And you only have to see one suffering person either as a physician or a lay person and know what a horrible problem cancer is and, uh, I think the good in all of us would like to see it, see the answer today, and if it's, if it's a form of vaccine or some magic drug that keeps cells, abnormal cells from dividing, uh, we'd be excited about it and, and, uh, wouldn't 00:52:00mind giving up our research dollars. I mean if somebody could come in tomorrow and say, hey, we've got a way of stopping Alzheimer's disease and, uh, it's in a form of a pill that costs, uh, two cents each, I'd be the most excited guy in the world and we'd close up our Alzheimer's shop and jump into something else, uh, very, very quickly, I was going to say jump into other problems of the elderly, and I, there's so many of them it is like a big smorgasbord table. Right now you can just pick and grab what, what you want, what you want to study. And I think that's the wonderful part about, uh, academic medicine, you have the freedom to do what you want and study what you want and, uh, give it your best shot, and, uh, hope that you can come out and maybe help someone. And I, that's why I think it's the most exciting, uh, opportunity in the world and I would do it all over again, uh, the, the same way, just to be a part of it. I, I really have an immense respect 00:53:00for the field.

SMOOT: Is there anything else you would like to add, uh, to what we have talked about over the past three sessions, uh, or anything in specific that you would like to point to regarding a, the development of the history of the Medical Center, that you think I have not discussed with you?

MARKESBERY: No, I think you have done very well. I, I think it's a, it got off to a very unique start, uh, as far as a state institution. Uh, now it's, uh, it's doing very well, although we're not, you know, we have areas that we are developing, uh, that make us, uh, set us apart from other state institutions and I think we're, state and medical centers, and I think we're doing fairly well. I, I happen to be grateful for my opportunity here and I, I try to be positive about the place and I, I don't think that's inappropriate because I, both my 00:54:00brother and I were given the opportunity to go to school here and, uh, he was in the class behind me here, and I know we're both very grateful for all that opportunity and having the state provide us with that opportunity and giving us both the opportunity to practice medicine in our different ways, uh, and to learn from it and to have a lifestyle that's very exciting. I really don't have, I'm delighted to see somebody putting this all together. I'm afraid I've given you too much of my personal philosophy rather than historical part of this, but, uh, I sort of answered them as they came. (laughs)

SMOOT: Well, there is a lot that can be learned from that as well. And I appreciate your time and your comments very much. On behalf of the Medical Center, the library and myself, thank you.

MARKESBERY: You're very welcome.

[End of Interview.]