AN INTERVIEW WITH DR. RUTH KIRSCHSTEIN BY STEPHEN P. STRICKLAND, PH.D. ON THE OCCASION OF THE 100TH ANNIVERSARY IN 1987 OF THE NATIONAL INSTITUTES OF HEALTH and the 150TH YEAR IN 1986 OF THE NATIONAL LIBRARY OF MEDICINE C) APRIL 1986 Interview with Dr. Ruth Kirschstein, Director, National Institute of General Medical Sciences April 28, 1986 SS: In the case of ors. Allen and Endicott and those people who were here in the early days, we were obviously talking about the past. Before the end of my work I need to talk about the future. Particularly what I am trying to do is to identify major advances in medical science and medical treatment that~ can directly trace and credit the National Institutes of Health with. So I thought we could talk about that this morning. This may be harder for you than some of your colleagues who have given dramatic examples, as in the example of the Institute of Dental Health, which I heard was the pioneer in fluoridation. RK: It was. But finding such examples may be harder in one sense but not in another for the National Institute of General Medical Sciences. Before you leave I will give you some material regarding this. As a basic research institute, NIGMS clearly has an effect on all other things that happen. We never know when initial studies are started whether or not they will have an impact on cancer or on heart disease or on any other disease. Indeed, they may have an impact on all of than. I'll give you a beautiful example. Some years ago~ supported the work J of a man named Dr. Barnett Rosenberg from Michigan State University. He was working at the time on what he planned as a study of "The effect of electrical fields on the growth of bacteria and cells." And he found that in the systan with which he was working, the electrical fields seaned to have an inhibiting effect on the growth of bacteria. But being the good scientist that he was, he said, "Well, I'd better look at this more carefully." So he began to study the effect of the electrical fields on growth using different types of electrodes. It turned out that inhibition only occurred when he used a platinum electrode. So he realized that it was probably the platinum that had caused the inhibi­ tion. He tried platinum compounds of a variety of human cells in culture, and found that it was inhibitory to growth. He tried it on human cancer cells in culture, and out of that came the drug cis-platin, which is probably the most () important advance in cancer chanotherapy that has occurred in recent years. He was supported for this this work, as a basic study, by NIGMS. As soon as it was obvious that this was a compound that was going to be very important in relationship to cancer, his studies began to be supported by the National cancer Institute. There are a series of patented cis-platinum products now. The one marketed most is called "Platinol" and all of than can be found in the "U.S. Phannacopeia" and other sources. ss: That is definitely a good example of a significant advance. RK: There's another example of the kinds of things we support. For a number of years NIGMS supported Joe Q)ldstein and Michael Brown in their studies of the receptor for steroid chanicals on the outer membrane of the cell. The steroid chanical they chose to use was cholesterol, and they discovered the receptor for cholesterol. They also elucidated the role of the cholesterol 0 1 receptor in the genetic disease, familial hyper-cholesterolemia. That is terribly important for that disease, but it also has broader implications for atherosclerosis. NIGMS supported them for seven years. Since the time that they began to work on atherosclerosis and the role of cholesterol in that disease, the Na­ tional Heart, Lung and Blood Institute has been supporting them. So those are two examples of the kinds of things NIGMS does. And we don't know today whether what we're supporting right now is going to have implications for sanething else very quickly, but surely it will eventually. SS: In the early days the National Institute of General Medical Sciences was considered the "balance wheel", that is, taking care of things that didn't clearly fall absolutely within some specific disease category. Is that true? RK: Yes. It has two missions. If you look in the NIH book on page 94, it says the NIGMS "supports research and research training in the sciences basic to medicine that form the foundation needed to make advances in understanding disease", but furthermore the legislative history says that NIGMS also sup­ ports "those activities that have significance to two or more other institutes at NIH." In the early days of NIGMS, I guess there was a great deal of activi­ ty in the area related to the "two or more institutes". Indeed, in Dr. Stone's era, there was more activity in the applied areas: burn and trauma research, anesthesiology research, surgical research, and clinical pharmacology. As the excitement in basic biology has come about, as the "biologic revolution" has cane along, with the 1953 discovery of the helical structure of DNA and then ) the subsequent expansion of all the nucleic acid research, this basic molecu­ lar biology has been supported by NIGMS. We have gradually emphasized more of the basic sciences and a little bit less of the activities in applied research. That doesn't mean we are doing none; it's just a matter of anphasis. I see that as something that probably will continue. We are expanding our horizons (I mean the world when I say "we") so rapidly in these areas: molecular biology, structural biology (the relationship of the structure to the function of proteins, nucleic acids); the use of nuclear magnetic resonance spectro­ scopy, and X-ray chrystallography, in such a way that we can't keep up with all of it. NIGMS thinks that these areas are important; that's why we're supporting than. C) SS: vbat about the immunologic function? RK: There are a number of Institutes that support immunology at NIH. I would say the ma.jor one is the National Institute of Allergy and Infectious Diseases; however, I think there is a role for NIGMS, and we have begun to take advantage of it by pursuing research in basic cell biology using the immune system as a model. So what we are doing is supporting basic immunobiology. The Cancer Institute and what was Arthritis and Metabolic Diseases Institute (which has been split into two) are also involved in those activities because much of arthritis has an immune basis. But NIGMS does have a role in immunology. SS: Are you able to state an anphasis for the future that scientists then respond to? You sit in a very crucial position; you know what's going on, you know what particular medical needs are as well as what's going on in basic medical science. Do you sometimes suggest to the scientific comnunity that there is a need for more work in an area? 0 2 RK: I tend not to do that very much. We firmly believe that the scientific canmuni ty itself knows where the anphasis areas are. We do sponsor meetings such as those on receptors on cell surfaces, on membranes, or on structure­ function of nucleic acids and proteins. But basically the scientific commu­ nity knows where the leading edges, the cutting edges, are. We tend to let it lead the science we support. I wrote an article this year for "U.S. Medicine" which discusses some of that. We have a brochure that expresses some of that. SS: It seans that specialization increases even in basic bianedical science, and scientists are so busy going to their own particular meetings and keeping up with their own particular fields, while you sit at a sort of pinnacle watching a number of basic fields, and you probably go to more meetings than you like. I just wondered if that gave you a little broader view. j RK: My staff goes to many meetings also, and it does give us a broader view. What I think is most amazing is that a basic scientist who at one time would have been considered a biochenist or a geneticist or a cell biologist is in fact all of these today. All these fields are blending together now. These scientists are picking up the new areas and reading the new literature. As you know, NIGMS has had traditionally, from its inception, another very important role; the role of research training. Since 1974-75 we have e:npha­ sized multidisciplinary research training. So someone who is taking a Ph.D. degree in biochenistry will be broadly trained in cellular and molecular biology or genetics. Hopefully he or she will, at least at the course level, know what's going on, and even if he or she specializes and does a particular biochenical project for the Eh.D. thesis, he will nevertheless be very broadly trained when he finishes. We have done that in a number of areas in order to assure a real breadth as well as depth of training. SS: That is particularly important right now, I would think, with the pushing back of boundaries on several biological fronts. RK: Absolutely. And what we find is that young people switch fields very quickly. They generally take their doctorates in, say, a department of genetics, and end up working in a department of bioche:nistry as a post­ doctoral, and then on to a department of biophysics as the place where they finally work. SS: Training programs do not seen particularly in vogue these days in political circles, but you still have a strong training program. RK: We still support about one-third of all the research training that NIH provides, and about two-thirds of the pre-doctoral, pre-Ph.D. training that NIH supports. Training programs are not "in vogue". They haven't been for quite some time, and indeed the dollars that have floW=d to research training D have been essentially flat for ten years or so. The only increases in funds that have been available for research training since about 1973-74 have come from the need to provide increases in stipends. But the authorities are becaning more aware of this, and we are hoping to see some changes in that regard, because, frankly, for the dollars that are available,~ are training many fewer students. Do you know about the report that the National Acadany of Sciences Committee on ManpoW=r submits every two or three years? That report comes up with a recorrmendation regarding how many trainees there should be. 3 Based on its recomnendation regarding the number of pre-doctoral trainees in the basic sciences, when you take the overall number and consider the share that would ordinarily be supported by NIGMS, we are currently supporting about 800 fewer than what is suggested because we don't have the funds to do more. SS: Has the report for 1985 teen published? RK: Yes. SS: And that is the kind of report that the Congress does pay attention to, even if the Administration generally does not make proposals in accordance with it? RK: We hope so. Not only do we give the Congress copies, but I testified to that effect at the hearing this past year. So I'm hoping for change, and that the funds will become available. SS: I am glad you brought up training because, given the key role of this institute in training and given the advances and flourishing field of basic science, I want you to say a word about training and the role here. RK: The NIH asked the Acadany to do a study, and what it showed was that individuals trained under NIH support did better when compared to those who had received their research training in the same acadanic institutions without NIH support. More of then finished their doctorates than others, more of than went on to prestigious institutions to get post-doctoral training, more of than got good acadanic positions and were more successful in obtaining research grant support than those who had not been so supported. This is not of enormous statistical significance, but it is good enough to say that this support is important. Back in the 1960s, the Institute's support of research training was much more discipline-oriented, so we had training grants in departments of micro­ biology, biochanistry, anatomy, pathology, genetics, and physiology. You must remember the crisis when Nixon impounded the funds and research training went completely down the drain. We lost the old authority to do training under the Public Health Service Act and something new was substituted for it, which was the National Research Service Act. I think that's all outlined in the Alma­ nac. It was that act that said that there should be a periodic study of the need for and supply of research manpower. vhen Dr. Stetten was the Di rector the impoundment of the funds and the loss of the authority to train occurred. The National Research Service Act was passed a few months before I took the Directorship, and I have been here since September 1974. This Institute has never had a director who has stayed as long! Stone was here about five years. Hunt and Powell were here for very short times. Dr. Hunt had another 0 job at NIH and he was just here as an interim director when the Institute started. Dr. Powell stayed a couple of years, as I recall, then came Stone, then Stetten for 3 1/2 or 4 years. Then the the other Dr. Stone, Dr. Robert Stone, who was the Director of NIH, asked Dr. Stetten to be the Scientific Director of the entire NIH. And that's when I came. SS: Had you been in the Institute before?. 0 4 RK: No, I had not been in the National Institute of G=neral Medical Sciences, but I had been at NIH for many years with one year's sabbatical at the FDA. I spent the early part of my career in the intramural program. I was with an organization called the Division of Biologics Standards, which was the group that did the regulatory activity regarding vaccines. I worked on the polio vaccine and did research on polio and other viral diseases. That Division did not give research grants; they were incorporated into the Food and Drug Administration in 1972-73 and I moved up to FDA for a year and a half as the Deputy Associate Commissioner for Science. I missed NIH terribly and when this job became available I applied for it and was selected. SS: I am going to ask your secretary to give me your curriculum vitae so I have that. I knew you had been here quite a long time with NIH. RK: And I had the distinction to be the first woman to be appointed as Director. SS: I want to ask you about this Institute and NIH, given your long perspec­ tive. One thing that's going to be difficult, but I think in the centennial year of the NIH it's very important to do, is to get public attention focused on the "informal" purposes, the payoff of this continuous investment of public dollars in NIH from the the '30s on. You've given us two very iinportant examples. Have you got some more? RK: We wrote a document about this called, "The Unexpected Payoffs of Basic Biomedical Research" and I'll give you a copy. I think probably the most important thing recently was the discovery of recanbinant DNA technology. The payoffs from that are absolutely incredible. It's going to be interesting because, whereas people thought in the initial phases that the payoffs were going to be primarily in the medical arena, and indeed important rredical substances have been made: human insulin, human growth hormone (there will be a whole series of others), one of the areas where this technology is going to have the greatest impact of all is in agriculture, and the whole area of botany. They can now do things with nitrogen-fixation and the supply of nitrogen to plants that will change the way one can grow plants. You won't have to worry whether the soil has nitrogen in it or not. ¼hat you have been reading in the papers recently about the protection of plants against frost is going to be enormously significant. The other thing that came out of recanbinant DNA technology was the ability to genetically engineer bacteria to do certain things like clear up oil spills! or. Chakrabarty designed bacteria that could actually eat oil. I'm not sure anybody has used that corrmercially yet, though I'm sure they're working on it because it's quite iinportant. SS: I heard something about that and thought it was quite fascinating. RK: Some of these biotechnology companies are developing other things. Cne of than that I know about, which was written up in the Washington Post awhile ago, is the developnent of a product using recombinant DNA technology to dissolve hair. You can see how that would be valuable in the plumbing field! These are important and practical things that all came out of this same basic technology along the way. 5 SS: I remember at one point, back in the '50s when there was finally a pro­ posal to create the National Science Foundation, there was sort of a bid to have all basic sciences at the National Science Foundation and minimize that element here. One of the arguments against it was that it's very imfX)rtant to keep basic sciences as closely as possible related to those things that you want it to specifically affect. Not that you can predict it absolutely. RK: You can't. And as a result there is no question that the activities particularly of NIGMS, not so much the other institutes, interdigitate with those of the National Science Foundation; particularly in basic genetics, basic molecular biology, and in chemistry. The National Academy of Sciences just did a study on opportunities in chemistry. It describes not only what goes on in support of chemistry at the National Science Foundation, but also here at NIGMS. NIH plays a very large role in studies of chemistry, almost all of which come fran support by the NIGMS. We have a portfolio of about $68 million worth of research grants in chemistry. They are related or can be related in one way or another to something to do with the people's health. Thus, if a project is designed for the organic synthesis of something that was not related at all to health, like for the dry cleaning industry, for example, it would not be supported by NIGMS. If it has a relationship to drugs or something that could be seen to be generally health-related, we may consider it. Now it may turn out just as in the developnent of cis-platinum; that somebody who is thinking about something related to, say, the dry cleaning industry, may find something that is related to the develo:pnent of a chemotherapeutic agent, or to a diagnostic agent, or something of the sort. The Division of Research Grants is responsible for reviewing the grant applications for relevance to the NIH mission. If a research grant application is submitted, which, in the view of the scientists at DRG does not have health relevance, it gets sent back. SS: And then I suppose whoever proposed it can send it to the National Science Foundation. RK: That's right. Many of them send the applications both places, and we work very closely with the NSF staff to be assured that neither do any duplicate funding. Science cannot be precisely targeted, but applications to NIH must be health related, and our staff looks at things like that. SS: There was a period of time back in the early '60s, especially when NIH was still growing, when its outside friends, the medical research lobbyists, seemed to be pushing for answers for specific diseases because they thought that too much attention was being spent on basic research. I think the DNA breakthrough changed all that and caused everybody to see its relevance. I wonder, does that tension fran earlier on still exist at NIH? Are you as able to easily carry your banner for basic general science as those advances in cancer and heart disease? RK: There was a period when it was difficult, but I do think it has changed. The banner can be carried very easily now, and I think a number of things have 0 6 caused that. The biologic revolution has been very specifically responsible for that, because it has allov;ed the public to become aware of the irnfX)rtance of basic research, and the scientists themselves, many of whom probably felt in the early days that they didn't want to get involved in the "political arena" realized that they might suffer if they didn't. So they have begun to talk about their science, and make it much more interesting, and now hardly a day goes by that there isn't something in the newspapers about their work. Journals are now published like Discover, Science 80 - 86 (the original editor of Science 80 is the man who is going to do the television series for the centennial -- Allen Hammond is the current one). Scientists have begun to realize this, and they are talking about the irnfX)rtance of their work, so that it has been easier to provide the documentation. Secondly, because of the great lobbying by the other groups, there have been several basic science organizations that put together very good lobbying efforts. The American Society for Microbiology is extrememly sophisticated at this. The American Society for Cell Biology has done more and the Federated Societies have done more. Then there is an organization which is very interesting and very good that began to get itself organized in 1975 called the Delegation for Basic Biomedical Research. Mahlon Hoagland, who was the director of the Worcester Foundation for Experimental Biology was the first director or president of that group. He organized a group of primarily Nobel laureates: George Palade, Arthur Kornberg, Jim Watson, and a couple of others, to work in this area. The other people who were very active in it, interes­ tingly enough, v;ere the people at the Retina Foundation, because they realized that, although they were working on research on the eye, there was a lot of basic research that needed to be done. They put together this group, and hired a full-time person to work with them named Bradie Metheny and their headquarters is, I believe, in Boston. Mahlon is retired now. I saw him yesterday at the National Academy of Science's meeting. He is living in Vermont. The man who works with him is Federico Welsch, who was also with the Worcester Foundation. It's a good group, and they have worked very hard. Indeed, each time that there has been some effort to decrease the budget by the administrations in all areas, particularly in basic research, that group has come down and arranged hearings on the Hill, in front of the Appropriations Committee. Mr. Natcher has had them down twice, I think. A number of them came to testify in front of Senator Weicker not more than three weeks ago. So I think there is a real groundswell, and we have encouraged it in every way. SS: How difficult is it to decide when the time has come to make public an advance that you believe is terribly important? On the one hand, the need to build the support of public officials, particularly those sitting on the appropriations corrmittees, is very strong. You have to keep selling in a certain way; you have to keep people up to date by giving them evidence of progress. en the other hand, you can't be premature about such announcements. How do you do that, and who does it? Is it up to the scientists? RK: It's basically up to the scientist and his organization. We feel very keenly that we are providing support. We are very pleased to provide it, but 0 we really can't take pride of authorship in it. I think the scientists under- 7 stand, much more so than they ever did before, that they must acknowledge the federal funding or it's likely not to be there in the future. The people on ) the other side of this room are in my information office; that's the one group we have here who keep contact with the information offices at the various uni­ versities. We do some things, like writing "NIGMS Research Reports" at 3-month intervals, and we pick out the imfX)rtant things that the various scientists we support have done. One of the reasons that it 1 s so irnfX)rtant to have a highly sophisticated scientific staff in an institute that does nothing but give ) grants is because we have to be able to recognize what is imfX)rtant; they're not performing as just a bunch of technical people who plug in the money and do whatever administrative tasks are needed -- they read those grant applications; they read the progress reports; they read the literature and go to scientific meetings. They set up meetings and we develop a series of lectures that we give each year in which we hear imfX)rtant people talk. As a result, we know what seans to be imfX)rtant. The one thing that I think is crucial is that none of us over-pranise. We can, when something looks exciting, talk about it, but I think we need to be absolutely sure that we don't say, "The cure for X will be available tomorrow" when it will not. Then the public has every right to become disillusioned the next time you say it. So we are extraordinarily careful about that. SS: In your tenure of twelve years or more as Director, what other exciting advances can you think of that we should pay special attention to? RK: I think the whole area of the relationship of structure to function of various comfX)nents of the cell at both the cellular organelle level, and the molecular level. One of the things is.the developnent of the nuclear magnetic resonance spectroscopy. It has two prongs to it. The technology is the same, but it has moved in two directions. First, as an adjunct to the use of X-rays, it has essentially become a diagnostic imaging tool that is being used by many of the other institutes in research to look at various organs (the brain, in particular) in order to find lesions. The other one is the ability to study, in vivo (in the body, not in vitro - outside), the metabolism of various important chanicals within~rta1n tissues and certain structures. By being able to do that, one can figure out the structure of a protein or a nucleic acid, what its particular function is relative to that structure; why it folds the way it does and why it's able to do what it can do. The great mystery of the world is that the DNA molecule is enormously long when you stretch it out, and yet it has been folded and put into a space that gets it into those tiny microscopic chranosomes in the nucleus. That's what the structure-function relationships are all about. That, I think, is one of the most exciting things. The other thing is the whole molecular basis of developnent. We've learned what developnent is; for example: every cell in the body has a full complanent of the genes. But only c-ertain ones are expressed, so that the genes for car­ diac muscle developnent are not expressed in the liver. Some are turned on and sane are turned off, and that's what we're learning about. We set up two lecture series over the past several years. One was in cele­ bration of the twentieth anniversary of NIGMS, which was in 1982-83. The legislation was passed in Cctober 1962 and.the Institute started in January of 1963. This is the ~Witt Stetten, Jr. lecture and we give it annually now. We pick the outstanding scientists for that. 0 8 The second one is in conjuction with the Neurological Diseases Institute. When I first came here, Dr. Stetten had appointed to this Advisory Council Marjorie Guthrie, and she served three years during my term. Marjorie Guthrie is now dead. She was Woody Guthrie's widow, and she devoted her life, subse­ quent to his death, to trying to improve knowledge regarding genetic diseases in general, and in particular, Huntington's Disease. That's what Woody died of. Marjorie was quite a remarkable wanan. She was one of the lobbying forces recently, so when she died, we set up a lecture series with the Neurology Institute in her name. These have been lectures more related to the genetics of central nervous system diseases in particular. There has been an im_EX>rtant advance in this area that has allowed geneticists and molecular biologists, through the use of recombinant DNA technology, to home in on a series of markers, on specific chromosomes. These markers are related to specific diseases, which cannot be defined because we do not know where the genes are on the chromosomes. Thus we do not know what the specific cause of the disease is. The first disease to which this new technique has been applied is Huntington's Disease. By taking pieces of DNA that are called "restriction fragment-length polymorphisms", we have learned a great deal. Let me explain. While you and I are both humans, and we each have the same complement of chromosomes, the differences being that you have a Y and I ) have two X's, our genetic material is not exactly similar. There are vari­ ations between all sorts of humans. Those are what are called polymorphisms. By taking various pieces of DNA, (one can cut it with the restriction enzymes that have been developed with recombinant DNA technology) and by studying those pieces along with studying large populations of people that have a particular disease, scientists can find a particular genetic marker that may be associated with that disease. The Huntington's Disease marker is localized to chromosome #4. This has allowed people to begin to focus on where the genetic defect is. In fact, we have not yet found the genetic defect, but it is going to even­ tually enable one to develop a diagnostic test. 1.) The second genetic disease that this has been used on is probably the most canmon significant genetic disease, and that's cystic fibrosis. They have just found a series of four markers on chromosome #7 that are beginning to get closer and closer to the gene for cystic fibrosis. For a long time people have worked on it and been unable to crack it, but it looks like they're getting very close. That's probably one of the most exciting things that's going on: finding markers for various diseases. They just found one for one of the muscular dystrophies and also for manic depressive disease. The ability to understand the chemistry of a number of compounds, and therefore to tailor-make drugs is another thing that I think is enormously important. We have, over the years, found chemicals that have some activity as therapeutic agents, but are mixtures of mirror images, so-called stereo­ isomers, where one of the two had a left-hand fold, and one of them had a right-hand fold, for example, and only one of those two was active. Therefore, the drug was either less powerful or, sometimes actually toxic. By sophisticated chemistry now, scientists have been able to separate those two, produce only the active one, and discard the one with toxic side effects. That's a very im_EX>rtant advance. SS: In all of these advances we talked about how you currently keep up with who is doing what, particularly your own grantees. As a general proposition, 9 would you say that the National Institute of General Medical Sciences has been consistently, periodically, generally, or what word would you use? -- involved in these major advances? RK: Pretty consistently. Even with the rare exceptions that come from seren­ dipity, the basic knowledge about the cell and its constituents, about the genes and the chemistry of nucleic acids, about the chemistry of proteins, carbohydrates, and so forth, has to come from basic studies. There is this ) l:>elief by some people that scientists like to live in ivory toW=rs and study scientific phenomena for the sake of phenomena. That's not true. Scientists want to make discoveries that will help mankind. They are always looking for ways in which whatever they have found will have important significance. It's a characteristic of human nature to do that. So they do look for ways to apply things, or to have other people apply them. I think this has l:>een very consistent along the way. I will give you some pamphlets on this. SS: I have a special interest that I have l:>een looking into and sort of pushing for a long time, and I wanted to ask you about that. I'm not sure it falls within your purview especially, but it is work on the connection l:>etween the biological,. psychological and physiological; that is, the phenomenon of the placebo, and how placebos somehow can trigger physiological phenomenon. We don't know a whole lot about that nexus, do YJe? RK: No, and that's not in NIGMS. We do some l:>ehavioral sciences, very little. But I think the Mental Health Institute probably would have more ability to talk about that. SS: What I found the last time I really looked at the NIH enterprise as a whole, which was eight years ago, was that there was very little in this. RK: True, hoW=ver, what I think you'll find is that there is not a lot of activity on that in general, but a great deal of it in specifics involving particular clinical trials where clearly those effects are something that they have to count on along the way. Of course, in some of the peculiar histories of certain "possible cancer chemotherapeutic drugs" -- in some of the frauds - I think there is very specific evidence of the po~r of suggestion. And that's a very dangerous phenomenon l:>ecause what happens is that people seek uproven "cures" in lieu of getting the treatment they should get. SS: On the other hand you have those happier examples like Nonnan Cousins' ••• RK: Oh, that one is a l:>eauty, I agree. There's no question about that kind of thing. I have seen enough patients in the little bit of clinical work I did, and I've seen enough people I know whose attitudes about licking disease cannot help but have importance. If one doesn't care, then one gives up. Under certain circumstances there certainly must l:>e excretion or secretion of important chemicals, perhaps related to immunologic response, that provide the ability to combat various problems. SS: What have YJe left out of central importance that YJe need to get on record? RK: There are two other research training.programs that I think YJe ought to mention. One is unique; NIGMS is the only Institute that does it, and that's the support of an M.D.-Ph.D. research training program, called, "Medical 10 Scientist Training Program". This was actually a creation of Dr. Shannon. I've simply continued it. It stemmed fran the realization that medical students in the normal curriculum of a medical school do not learn how to do research and really don't learn to understand what research is all about, and that a cadre of future clinical researchers would be needed. Starting in 1965, this program trained people who could really do research and make advances; who could take the basic knowledge of genetics and recombinant DNA technology, for example, and apply it in gene therapy. These individuals get an integrated course through medical school and graduate school, earning not the M.D. and Fh.D. degree, but a canbined M.D.-Ph.D. degree. They are the brightest, most wonderful students, at the finest schools, and they have made significant contributions and the vast majority of them are doing research now. The second program stemmed from a realization at NIH as a whole that there are far too few minority bianedical researchers. So a program was set up in this institute, since we are a pranier training institute, called MARC, Minority Access to Research Careers, in which we provide research training to individuals who are associated with schools that have significant numbers of the minority students - both the traditional black colleges as well as the urban colleges and universities which these days have large nt.nnbers of minority students. City University of New York is an example. It is a very different place now from ) when I lived in ~w York and went to high school and college. The schools of Puerto Rico and the southwest, which have significant numbers of Hispanic students participate. What we have done is support not only the faculty manbers of those schools to become better researchers, but also set up a program of starting the kids early in an honors undergraduate research training program which supports than through the junior and senior years at college. The idea is that this is just the start of a continuum to go on to research careers. The IOM-NAS recently did a study of this program and reported that it is working rather well. So those are the two other things I think are important. SS: That's fine. And would you like to say anything about the role of the National Institute of General Medical Sciences with respect to the future? RK: The research in basic biomedical science that NIGMS supports now is going to have significance in the application of medical advances for future gener­ ations. It will very often take ten to twenty-five years before. one knows the () significance of some of those activities. But it can happen much more quickly. I think the practical significance of recombinant DNA technology was apparent within six or seven years. Actually the first products came out within less than ten. SS: Very good. You've given me a great deal of information. 11 l-UKKJ.LULUM V .l lAt. ") RUTH L. KIRSCHSTEIN, M.D. POSITION: Director, National Institute of General Medical Sciences BIRTHPLACE Brooklyn, New York and DATE: October 12, 1926 EDUCATION: A.8., magna cum laude, Long Island University, 1947 M.D., Tulane University School of Medicine, 1951 EXPERIENCE: Director, National Institute of General Medical Sciences, NIH, 1974-present Deputy Associate Commissioner for Science, FDA, 1973-1974 Acting Deputy Director, Bureau of Biologics, FDA, 1972-1973 Assistant Director, Division of Biologics Standards, NIH, 1971-1972 Chief, Laboratory of Pathology, DBS. NIH, 1965-1 972 Acting Chief, laborato~y of Pathology, DBS, NIH, 1964-1965 Assistant Chief, Laboratory of Viral I!Tlllunology and Chief, Section of Pathology, DBS, NIH, 1962-1964 Chief, Section of Pathology, Laboratory of Viral Inrnunology, DBS, NIH, 1960-1962 Medical Officer, Pathologist, Laboratory of Viral Products, DBS, NIH, 1957-1960 ) Medical Officer, Resident in Pathology, Clinical Pathology, Clinical Center, NIH, 1956-1957 Trainee of National Heart Institute and Instructor in Pathology, Tulane University School of Medicine, 1954-1955 Resident, Pathology, Providence Hospital, Detroit, Mich., 1952-1954 Assj stant Resident, Pathology, Veterans Admi ni strafion - Hospital, Chamblee, Ga., 1952 · Internship, Medicine a.nd-Surge-ry, Kings County Hospital, Brookly-n, N.-Y:, 1951-1952 - - CERTIFICATION: Medical Specialty Board Certification, -Pathology (anatomic and clinical pathology}, 1957 I I ASSOCIATION I MEMBERSHIPS: American Association of I1m1unologists American Association of Pathologists American Society for Microbial og_y SPECIAL AWARDS or CITATIONS: Presidential Distinguished Executive Rank Award, 1985 Distinguished Executive Service Award of the Senior Executive Association, December 1985 Elected to Institute of Medicine, National Academy of Sciences, 1982 Honorary Doctor of Science, Medical College of Ohio, 1986 Honorary Doctor of Laws, Atlanta University, 1985 Doctor of Science, Honoris Causa, The Mount- Sinai School of Medicine, 1984 ) DHEW Superior Service Award, 1971 PHS Superior Service Award, 1978 Presidential Meritorious Executive Rank Award, 1980 PHS Eaual Opportunity Achievement Award, 1983 PHS Special Recognition Award--group award to PHS Task Force on Women's Health Issues (Or. Kirschstein, Chairperson), 1985 2 COMMITTEE . MEMBERSHIPS: Invited member of World Health Organization Expert Group on International Reauirements for Biological Suhstances; Geneva. Switzerland, 1965 and 1971 Invited consultant to World Health Organization concerning problems related to the use of Poliovirus Vaccine, Live, Oral; Geneva, Switzerland, 1967 Member, Primate Research Centers Advisory Committee, Division of Research Resources. NIH .. 1971-1975 Member, Editorial Board. Journal of Toxicology and Environ­ mental Health. 1973-19 Member. Ad Hoc Committee on Reserpine and Breast Cancer, 1974-197, Member, National Commission on Diabetes, 1975 Member, National Commission on Arthritis and Related Musculo- skeletal Diseases, 1975 Chairperson, NIH Grants Peer Review Study Team, 1975-1976 Chairperson, PHS Genetics Coordinating Committee, 1976-1979 Memher, Fogarty International Center Scholars-in-Residence Advisory Committee. 1977-1982 Member. NIH Coordinating Committee on Manpower, 1978-1983 Chairperson, PHS Task Force on Women's Health Issues, 1983-1984 Memher. NIH Advisory Committee for the IOM Study of the Organizational Structure of the NIH, 1983-1984 HHS Executive Development Board, 1985-present PHS _Coordinating Committee on Women's Health _Issues, -1985-present - ) J