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NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

STATEMENT OF DR. RUTH KIRSCHSTEIN, DIRECTOR

BUDGET REQUEST Senator HARKIN. Dr. Kirschstein, good afternoon, you're next. I understand that you have been very busy not only as Director of the National Institute of General Medical Sciences, but also as Acting Director of the Office of Women's Health.

Dr. KIRSCHSTEIN. That's correct, sir. Senator HARKIN. You are requesting $833 million for fiscal year 1992. This is 9.6 percent more than 1991.

Would you please start off with a brief overview of the programs included in your budget request? Please proceed.

Dr. KIRSCHSTEIN. Thank you, Senator Harkin. I am honored to present the achievements of the National Institute of General Medical Sciences, the Institute that stimulates scientific progress through the support of the most fundamental biomedical research.

I am also pleased to tell you that, as has been the case in almost every year in which I have testified, an NIGMS grantee once again has won the Nobel Prize this year. In 1990, the chemistry prize went to Dr. Elias J. Corey of Harvard University for his contributions to the field of synthetic chemistry. NIGMS has supported Dr. Corey's work for the past 20 years, and he is still at the pinnacle of his career.

BASIC RESEARCH

But, while NIGMS supports basic research, we also support some research that is targeted toward specific diseases. We have been supporting research using the techniques of structural biology for the design of drugs to combat AIDS. An NIGMS-supported scientist has developed a computer program that uses the three-dimensional shape of the active site of a molecule that is one of the enzymes that is essential to the growth of the AIDS virus. The computer program then found a chemical which will interfere with the growth of the virus by locking onto the enzyme. Now, he has to go further and develop a better molecule; he will then modify the chemical in order to enhance its desirable activity and decrease its toxicity. This ability to plan the structure of a drug based on the complementary structure of a related molecule is a very important phenomenon.

Among the direct beneficiaries of the basic biomedical research that NIĞMS supports is the biotechnology industry. Research by NIGMS grantees is yielding techniques that are leading to ways to inactivate viruses to make vaccines, such as Dr. Fauci talked about this morning, to insert modified genes into cells, the gene therapy that you heard about this morning, and to decipher the instructions that direct a protein to fold into the three-dimensional shapes that we have been talking about so that it will be active.

In addition, of course, to this commitment to basic research, the National Institute of General Medical Sciences supports a very large share of the biomedical research training that is funded by NĚ. This training prepares scientists to pursue research careers in a wide variety of areas. Hopefully, it will lead to further Dr. Elias J. Coreys.

In response to concerns about the need to train more scientists to do research in biotechnology, as you know, in 1989, we established a special biotechnology research training program. We expanded the program, with funds provided by the Senate, by about 60 percent in fiscal year 1991.

PREPARED STATEMENT

The Institute also sponsors the Minority Access to Research Careers Program and the Minority Biomedical Research Support Program, both of which aim to raise the number of under-represented minorities in science. The MARC program has recently extended its Honors Undergraduate Research Training Program to support students in the first 2 years of college, and plans are also being made to broaden the eligibility for MARC individual predoctoral fellowships to minorities

who are students at any of the colleges and universities throughout the United States.

The fiscal year 1992 budget request for the Institute is $833,180,000.

I would be very pleased to answer any questions you might have. [The statement follows:]

STATEMENT OF DR. RUTH KIRSCHSTEIN

I am honored once again to appear before this committee to present the

exceptional achievements of the grantees of the National Institute of General

Medical Sciences (NIGMS), which stimulates scientific progress through the

support of basic biomedical research.

As has been the case in almost every

year in which I have testified before you, in 1990 an NIGMS grantee has again

won the Nobel Prize.

The chemistry prize went to Dr. Elias J. Corey of

Harvard University for his many contributions to the field of synthetic

chemistry. According to the Nobel committee, "it is probable that no other

chemist has developed such a comprehensive and varied assortment of methods

which, often showing the simplicity of genius, have become commonplace in the

synthesizing laboratory."

NIGMS has supported Dr. Corey's work for the past 20 years, and he is

clearly at the pinnacle of his career.

But there are other scientists whose

research is supported by NIGMS -- and many more people who receive training for

research careers..who represent the Elias J. Coreys of the future.

One of these is Dr. Elizabeth Blackburn.

She has been an NIGMS grantee

since starting her independent research career 13 years ago.

In this time,

Dr. Blackburn has made major advances in understanding the structure and

function of chromosomes, the cellular components that carry each person's

genetic endowment.

Dr. Blackburn, who is a professor at the University of

California, San Francisco, studies the ends of chromosomes,

called telomeres.

These structures protect the genetic information during the chromosome

duplication that precedes cell division.

She has determined how the telomeres

function, and has recently found evidence that these structures may play a

role in the development of cancer and in aging.

Dr. Stuart Schreiber of Harvard University, an NIGMS grantee since 1982,

has made several important findings in the past year related to drugs that act

on the immune system.

To study drugs that suppress the immune system, thus

helping to prevent rejection following organ transplantation, he devised a

synthetic chemical that contains the common structural elements of two

promising new drugs.

His research is expected to lead to more effective and

less toxic immunosuppressive agents, and to provide new Insights into the

workings of the immune system.

Dr. Schreiber also discovered a series of small molecules that bind to

the human immunodeficiency virus (HIV), which causes AIDS.

These molecules

prevent HIV from infecting T cells, without disrupting normal cell function.

He believes that these molecules are promising forerunners of an effective

inhibitor of AIDS infection.

The advances in structural chemistry represented

by this work should be applicable to fighting other diseases, as well.

Another "rising star" is Dr. James Wilson of the University of Michigan

Medical School.

He led one of two teams of scientists who, in test-tube

systems, inserted normal genes into cells taken from patients with cystic

fibrosis.

Dr. Wilson showed that these inserted genes functioned correctly.

This finding, which came just one year after the cystic fibrosis gene was

discovered, may lead to treatment for this common, fatal genetic disease.

Dr. Wilson's research training, leading to the combined M.D.-Ph.D. degree, was

supported by the NIGMS Medical Scientist Training Program.

This initiative,

which currently supports 766 students in 29 different programs, has been

remarkably successful in training highly creative, dedicated, and productive

physician-scientists such as Dr. Wilson, who made this important finding just

six years after completing his research training.

At a point even earlier in her career is Dr. Lisa Matsuda, who recently

completed a postdoctoral fellowship in the intramural NIGMS Pharmacology

Research Associate Program. During her fellowship, Dr. Matsuda conducted much

of the research that recently culminated in the identification of the long

sought receptor for marijuana in brain cells.

This achievement opens many

exciting avenues for further research.

One of the first goals is to find out

why this receptor is present in the brain and what it normally does there.

The discovery of the marijuana receptor also offers hope of designing a drug,

that will have the therapeutic benefits of marijuana --which is useful against

epilepsy, nausea, asthma, pain, and high blood pressure--without its

psychoactive effects.

Preparing Scientists for Research Careers

In addition to its commitment to basic research, NIGMS supports a large

share of the research training that is funded by the National Institutes of

Health (NIH).

This training recognizes the interdisciplinary nature of

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