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Director, National Institute of General Medical

Brooklyn, New York

October 12, 1926

A. B., magna cum laude, Long Island University, 1947
M.D., Tulane University School of Medicine, 1951

Director, National Institute of General Medical
Sciences, September 1974-present

Deputy Associate Commissioner for Science, FDA,

Acting Deputy Director, Bureau of Biologics, FDA,

Assistant Director, Division of Biologics

Standards, NIH, 1971-1972

Chief, Laboratory of Pathology, DBS, NIH, 1965-1972
Acting Chief, Laboratory of Pathology, DBS, NIH,

Assistant Chief, Laboratory of Viral Immunology and
Chief, Section of Pathology, DBS, NIH, 1962-1964
Chief, Section of Pathology, Laboratory of Viral
Immunology, 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

Assistant Resident, Pathology, Veterans

Administration Hospital, Chamblee, Ga., 1952

Internship, Medicine and Surgery, Kings County
Hospital, Brooklyn, N. Y., 1951-1952

American Association of Immunologists
American Association of Pathologists
American Society of Microbiology

DHEW Superior Service Award, 1971
PHS Superior Service Award, 1978

Presidential Meritorious Executive Award, 1980

Invited member of World Health Organization Expert
Group on International Requirements for Bio-
logical Substances, Geneva, Switzerland, 1965
and 1971


MEMBERSHIPS: (continued)

Invited consultant to World Health Organization
concerning problems related to the use of Polio-
virus Vaccine, Live, Oral. Geneva, Switzerland,

Member, Board of Consultants, Journal of Medical

Member, Primate Research Centers Advisory Committee,
Division of Research Resources, NIH, 1971-1975
Member, National Commission on Diabetes, 1975

Member, National Commission on Arthritis and Related
Musculoskeletal Diseases, 1975

Member, Ad Hoc Committee on Reserpine and Breast

Cancer, 1974-1977

Chairperson, NIH Grants Peer Review Study Team,

Member, Editorial Board, Journal of Toxicology and
Environmental Health

Member, Scholars-in-Residence Advisory Committee,

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Dr. KIRSCHSTEIN. Thank you, Mr. Chairman. To my left is Mr. William Fitzsimmons, the Executive Officer of the Institute, and to his left Dr. Leo von Euler, who is the Deputy Director of the Institute.

The National Institute of General Medical Sciences has a unique place within the constellation of Institutes that comprise NIH as demonstrated in this chart. It is the role of NIGMS to support studies in biomedical sciences which are basic to and form the underpinnings of the activities of all the other-the categorical institutes.

To accomplish the objectives of NIH requires, among other things, support of fundamental untargeted investigations that generate knowledge and new concepts which, while not immediately relevant to any particular disease, will ultimately have importance to any number of human disorders. Such concepts form the foundation for subsequent research strategies developed at more disease-oriented levels.

The major share, about 70 percent, of the research supported by NIGMS comprises studies of cell structure and function and of basic genetics. studies that seek clearer insights into the molecular mechanisms that maintain human health, mechanisms which, if they go awry, can cause disease.


Sometimes the results of these basic studies find their way very quickly and very dramatically into practical application. and the best recent example of such a success story is that of the recombinant DNA technology. Fundamental research in molecular genetics and biochemistry in the 1970's has provided the basis for, and led directly to the development of this technology, and the vast part of such research was and still is-supported by NIGMS. Indeed, it was for such undifferentiated studies in genetics and biochemistry of simple organisms that Drs. Paul Berg of Stanford University and Waiter Gilbert of Harvard, both long-time NIGMS grantees, were named corecipients of

the 1980 Nobel Prize in chemistry. And Dr. Berg and three other NIGMS grantees-Drs. Herbert Boyer, Stanley Cohen, and A. Dale Kaiser-also this year won the prestigious Lasker Award for basic research.

Parenthetically, I might say that our Institute, NIGMS, has supported 42 Nobel laureates, and again this year, as for the past 6 years that I've presented before this committee, we have had Nobel laureates.

Now, scientists in this country have very quickly seen the potential of the recombinant DNA technology, and small companies, as well as large drug manufacturers, are attempting to exploit this, as I noted on the chart, for the production of rare and expensive therapeutic agents including insulin, growth hormone. and interferon, which was mentioned by Dr. KRAUSE. Just last week, the first clinical trials of synthetic insulin manufactured by use of this technology were begun, and clinical trials of interferon so produced are currently in progress.

Senator ANDREWS. Don't use the word "exploit"; use "utilize." It sounds a lot better. Otherwise, it sounds like there is some unholy alliance between those of you who discover these new breakthroughs and those who are able to pass it on to the public.

Dr. KIRSCHSTEIN. You are correct. sir. In order, though, to take full advantage of this enormous thrust made by the recombinant DNA technology, we must also continue to expand our knowledge concerning the fundamental unit of the body, the cell. a small universe which has turned out to be much more complicated than we had anticipated.

For example, the effectiveness of this new synthetic insulin is dependent on the ability of it to interact at the targeted cell. NIGMS grantees are actively studying membrane receptors which are the special areas on the cell surface which allow such interaction to take place. The detailed chemical studies of such membrane receptors hold the key to an understanding of many serious health problems such as heart disease, diabetes. and arthritis.

Now usually it is the nature of this untargeted research, supported by NIGMS, to gradually evolve and become specifically focused on categorical problems. and when this occurs, the support is transferred to the more appropriate categorical Institute. Thus the NIGMS programs feed those of the other Institutes and function like a breeder of scientific concepts.


A number of examples of this come to mind. I will give you only one. Scientists at Harvard University, supported by NIGMS. have been investigating the movement of essential. but very simple chemicals across the membrane into and out of the cell. In the course of this work. they have found that the rate of transport of certain chemicals such as sodium or salt and a related element. lithium. correlates with whether or not the person whose cells are being studied has that common and very serious disease known as essential hypertension or high blood pressure of unknown cause. Upon further investigation. it was found that not only is the rate of transport increased twofold through the cells of persons with this disease, but also through cells from their close relatives. whereas transport across the membrane of cells from normal individuals is twofold lower.

The usefulness of these findings to elucidate the role of heredity in the development of essential hypertension and also as a diagnostic tool prior to the onset of the high blood pressure has been recognized by the National Heart, Lung, and Blood Institute, which is currently providing support for these investigators to continue their studies. This is but one of a number of such examples of how basic concepts developed through research funded by NIGMS can lead to information relevant to disease.


But in order to maintain the momentum of these remarkable achievements, there is need for highly skilled, creative scientists and for the availability of highly sophisticated, expensive, modern instrumentation to replace equipment which is now obsolete.

To provide these essentials. NIGMS has established a research training program, including the provision of support for medical scientist training, as well as a shared instrumentation initiative. In the shared instrumentation initiative, three or more grantees may apply for funds to purchase a major piece of equipment on the basis of a plan for optimizing its use and for sharing it, not only among themselves but also with young beginning investigators who are the future scientific leaders. of this country.

I hope I have shown you that basic undifferentiated research is absolutely essential to provide a foundation for much of the successful clinically oriented research. Our experience abundantly indicates that the basic research NIGMS supports now will form the backbone of future medical progress.

I would be pleased to answer questions, sir.


Senator ANDREWS. I appreciate your statement, Doctor. I noted with interest that you are a graduate of Tulane. My nephew is now at the Tulane Medical School. I'm surrounded by medical students in the rest of my family.

I assume that you are getting the same amount of the program that other areas in NIH are getting. In other words. the funding that you now have in the budget is sufficient to maintain your share of NIH's goal of 5000 new and competing research grants.

Dr. KIRSCHSTEIN. Yes, sir. Mr. Chairman. In President Carter's 1982 budget presentation, our share of the 5.000 competing grants is 838 grants, or 16 percent. for a total amount of $89 million.

Senator ANDREWS. Does that maintain your level?

Dr. KIRSCHSTEIN. Yes. it does.


Senator ANDREWS. Then how do we tie that in with the fact that your budget request for fiscal year 1982 proposes better than a 200-percent increase in new and competing training awards? You would go, as I understand it. from 58 to 198. or is this some other category?

Dr. KIRSCHSTEIN. No, sir: the budget of th Honal Institute of General Medical Sciences, like that of all es. is divided

into two portions-a portion to support research through the award of research grants, and a portion to support research training. The National Institute of General Medical Sciences, besides supporting basic fundamental research, is also, in a sense, the research training institute for NIH. One-third of all the research training that is done by all of the Institutes at NIH is supported by the National Institute of General Medical Sciences.

Senator ANDREWS. You are the farm club, then, supplying the heavy hitters for the other Institutes?

Dr. KIRSCHSTEIN. That is correct.

Senator ANDREWS. Why, then, again, the increase? Are we bringing on board more researchers for the future, even though the level of research seems to be maintained, as we developed earlier on in questions about the same level?

Dr. KIRSCHSTEIN. No, sir; the number of awards that you are looking at are for new individual fellowships. These are for training individuals who have received either the M.D. degree or the Ph. D. degree for a postdoctoral period which usually lasts from 1 to 3 years. These are nonrenewable. And at the end of that period of time, there would be


Senator ANDREWS. That is totally correct, but my question goes back to why the increase? You're the farm team supplying these researchers. We developed earlier on that these researchers are extremely important because it doesn't do much good to throw dollars into cancer research or stroke research or whatever else if you don't have the researchers to do the job.

We have also maintained, in the portion of the hearings that I've been privileged to chair, the concept that the budget allows us to proceed at about the same level in terms of man- and woman-hours of research that we have had in the past. Yet in yours, we run into this 200-percent increase in training the researchers. And I just kind of want to get back to why.

Dr. KIRSCHSTEIN. It is not a 200-percent increase in total numbers of trainees. The overall number of trainees for NIGMS is decreasing by approximately 60, and for NIH as a whole is also decreasing.

Senator ANDREWS. Well, the figures that I have is that these awards. go from 58 to 198.

Dr. KIRSCHSTEIN. Those are the number of individual fellowships: that is correct.

Senator ANDREWS. That's right. And the number of individual fellowships is what gives you the pool of researchers for the future. So how come quadrupling almost certainly tripling

Dr. KIRSCHSTEIN. In 1980, we supported 182 individual fellowships. The budget constraints for 1981 allow us only to have 58 fellows. and this increases to 198, therefore. would provide the return of stability to the 1980 figures.

Senator ANDREWS. In other words, you had a shortfall that you are trying to recoup?


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