Answer: The NIDCD has identified five areas of research for study that are particularly relevant to women's health:

Meniere's disease is a very difficult disease characterized by periods of dizziness, nausea, vomiting and loss of hearing. Scientists in one NIDCD research program have demonstrated an inner ear response to a particular virus, cytomegalovirus (CMV). CMV is a well-established cause of disorders of the auditory, visual and central nervous systems. Some surveys have established the presence of the virus in 50 percent of upper middle income white females and 83 percent of lower income minority women. "Quiescent" CMV may play a role in the development of Meniere's disease.

Otosclerosis is the most common cause of progressive conductive hearing loss in the adult with a normal eardrum, and it is more common in women than men. An NIDCD-supported physician-scientist has found that a class of drugs, biphosphonates, acts effectively to inhibit bone remodeling. If shown to be effective, these drugs could be used to prevent the onset of otosclerosis in families known to be prone to the disease or to arrest the progression of the disease in persons already affected.

A predominant problem in the elderly is the natural decline in smelling ability that typically occurs after age 60. NIDCD grantees developed a smell identification test that made it possible to test the sense of smell throughout the age span. With this useful clinical tool, when patients complain of a loss of the sense of smell, their sense of smell can be measured and compared to what is normal for their age and gender. Throughout the life span, women have been known to have a more acute sense of smell than men.

Voice tremor affects women primarily and makes speech difficult to understand. For example, because of the high frequency response of the telephone, voice tremor renders use of the telephone a difficult task. This disorder has a dramatic effect in limiting one's ability to communicate in professional and personal situations. In a definitive study, scientists in the NIDCD's Voice and Speech Section have developed a new treatment, injecting botulinum toxin into throat muscles in patients with this disorder. These injections were very successful in eliminating tremor entirely in some and almost completely in others. Grantees are continuing work on diagnostic methods with voice tremor.

While the ear is the organ of hearing and receives sounds from the environment, the ear also produces sounds itself, called otoacoustic emissions. These sounds emanating from the ear may be useful in identifying the type of hearing loss. They represent one of the specific functions of the sensory cells in the inner ear. In most cases, emissions remain extremely stable over time but females evidence measurable changes with monthly hormonal cycles. These findings are revealing new understanding of the biochemistry of the inner ear and its interactions with noise exposure, aging and drugs such as aspirin.

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 NIGMS 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 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 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.