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 NIH. 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 stu̟dents 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 longsought 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 NIGMS 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 biomedical 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, a 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 liposomes, to deliver drugs to cancer cells, was selected as the outstanding graduate student at her school for the 1988-89 academic year.

In an effort to extend its impact, the MARC Program recently began accepting supplemental applications from schools with existing honors undergraduate research training prograns. These supplements will enable the schools to expand their programs, which are now limited 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 locate 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.

The

In late 1990, two groups of NIGMS-supported scientists at Harvard and Columbia Universities made another important advance in AIDS research. 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!