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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 NIX. 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 an 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

biomedical research today, and stresses approaches to biological problems that

cut across departmental lines.

Such experience prepares trainees to pursue

research careers in a wide variety of areas, including those within the

missions of virtually all the other NIH Institutes.

In fact, over half of the

trainees supported by NIGHS obtain research funding from other parts of NIH.

It is especially critical to train scientists who are qualified to do

research in biotechnology if..as pointed out by Congress and the National

Academy of Sciences--the United States is to maintain its position as a world

leader in this field.

In response to this concern, in 1989, NIGMS established

a special program to support biotechnology research training. The Institute

expanded this program substantially in fiscal year 1991, increasing the number

of individuals to be supported by about 60 percent.

NIGMS also sponsors two programs aimed at increasing the number of

underrepresented minorities in science.

These programs make the Institute the

primary focal point at NIH for minority bionedical research and research

training

In an August 1990 article in Science magazine, the Institute's

Minority Access to Research Careers (MARC) and Minority Biomedical Research

Support (MBRS) Programs were called "a major factor in stimulating the

research Interest" of minority students. Among these students are Robert

Turner, I MARC honors undergraduate research trainee at Lehman College of the

City University of New York, and Maria Elena Hernandez, a graduate student in

chemistry at the University of Texas at El Paso who is working with MBRS

support. Mr. Turner is studying hemoglobin structure, and plans to

concentrate on sickle cell research in graduate school.

Ms. Hernandez, whose

research focuses on the use of microscopic bubbles of fat, called liposones,

to dellver drugs to cancer cells, was selected as the outstanding graduate

student at her school for the 1988-89 acadeaic yoar.

In an effort to extend its impact, the MARC Program recently began

accepting supplemental applications from schools with existing honors

undergraduate research training programs.

These supplements will enable the

schools to expand their programs, which are now llaited to the support of

college juniors and seniors, to also support promising students in the first two years of college. Other plans are being made to broaden eligibility for

MARC individual predoctoral fellowships, which are currently available only to

students who graduate from the MARC honors undergraduate program.

Structural Biology and AIDS

While most NIGMS - supported basic research is not targeted to any specific

disease, the Institute does have a program in which the techniques of

structural biology are used to design drugs against AIDS.

Structural biology

is a flourishing field in which a molecule's physical structure is related to

its function.

An NIGMS - supported scientist working in this area, Dr. Irwin

Kuntz, Jr., of the University of California, San Francisco, recently developed

a computer program that uses the three-dimensional shape of a molecule, rather

than its chemical structure, to identify compounds that might bind to it.

This approach, a form of rational drug design, enabled Dr. Kuntz to locute a

compound that blocks the action of an enzyme essential to the survival of the

AIDS virus, HIV.

The compound, which is the common antipsychotic drug

haloperidol (sold under the trade name Haldol), is only effective against HIV

when used in doses that greatly exceed its lethal limit.

For this reason,

discovering the potential therapeutic advantages of haloperidol can only be

considered a starting point. Dr. Kuntz and his colleagues are now making

changes in the drug's structure that, hopefully, will preserve the desired

antiviral activity while lessening its toxicity.

In late 1990, two groups of NIGMS - supported scientists at Harvard and

Columbia Universities made another important advance in AIDS research.

The

Investigators determined the three-dimensional structure of the part of the

receptor protein of human cells through which HIV enters the body.

This work

should greatly increase our understanding of how the virus works, as well as,

help to design new drugs to block AIDS infection.

Basic Research Advances Biotechnology

Among the direct beneficiaries of the basic biomedical research supported

by NIGMS is the biotechnology industry.

Such research has yielded genetic

techniques that could lead to new ways to inactivate viruses; insert modified

genes into cells; and even produce tomatoes that ripen slowly and can

*

withstand mechanical handling, while still retaining their flavor and color!

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