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 programs. 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! One of the biggest problems facing the biotechnology industry is that, although scientists know the order of the subunits that make up a given protein of potential commercial value, such as a new drug or a hormone, they do not know what directs the protein to fold into the three-dimensional shape that is required for its activity. As a result, it is impossible to synthesize some proteins and difficult to modify others, to improve their effectiveness, stability, or yield. Scientists seeking to understand protein folding have used many approaches, including attempts to design a synthetic protein "from scratch" to see if it can be made to fold as predicted. Now, after many years of effort, a team led by NIGMS grantees Dr. David Richardson and Jane Richardson of Duke University has succeeded in designing just such a synthetic protein. This accomplishment may lead industrial scientists to new methods to synthesize therapeutic agents on a commercial scale. A group of researchers, working with NIGMS support at the Genex Corporation in Maryland, recently received a patent for a new class of bioengineered proteins that they call single-chain antigen-binding proteins. They hope that these proteins can be used to carry either radioactive or toxic substances that could detect or kill cancer cells. Some of these proteins have already been targeted, and successfully attached, to cells in mouse tumors. The scientists say that the proteins are more effective than other substances that seek out and attach to tumor cells, because they can penetrate a tumor more deeply and are cleared from the body more rapidly. Conclusion In closing, I would like to quote Dr. Leon Rosenberg, dean of the Yale University School of Medicine, who said in an interview with Time magazine published in December 1990 that "there are more opportunities than ever to ferret out the secrets of human biology and apply those secrets to the reduction of human suffering....Our country has benefited enormously from the support of much unfocused basic research because in totally unexpected ways it has provided insights into medical problems that have been of enormous significance." Dr. Rosenberg further said that, in a time of limited resources, his "first priority is to create an environment in which talented young people choose careers in health-sciences research, because without then our future will be blighted." This emphasis on basic research and research training mirrors that of NIGMS. It is through the continued support of these pursuits that our country will be able to meet some of the challenges of the next decade... and indeed, the next century. Mr. Chairman, the FY 1992 budget request for the Institute's research and research training programs is $833,180,000. I would be pleased to answer any questions that you may have. BIOGRAPHICAL SKETCH OF DR. RUTH KIRSCHSTEIN October 12, 1926. Brooklyn, New York Education: A.B., magna cum laude, Long Island University, 1947. Professional History: 1951-52, Internship, Medicine and Surgery, Professional Organizations: American Assoc. of Immunologists; Committee Memberships: Invited member of World Health Organization Expert Group on International Requirements for Biological Substances; Geneva, Switzerland, 1965 & 1971. Chairperson, NIH Grants Peer Review Study Team, 1975-76. Chairperson, PHS Genetics Coordinating Committee, 1976-79. Member, Fogarty International Center Scholarsin-Residence Advisory Committee, 1977-82. Chairperson, PHS Task Force on Women's Health Issues, 1983-84. Chairperson, PHS Coordinating Committee on Women's Health Issues, 1984-90. Member, NIH Advisory Committee for the IOM Study of the Organizational Structure of the NIH, 1983-84. Member, NIH Peer Review Committee, 1987-88. Member, HHS Executive Development Board, 1985-present. Member, Federal Task Force on Women, Minorities and the Handicapped in Science and Technology, 1987-90. Member, Interagency Working Group on Minorities, Women and the Handicapped in Science, 1989-present. Member, Office of Technology Assessment Advisory Committee on Basic Research, 1989-present. Co-chair, Secretary's Special Emphasis Oversight Committee on Science and Technology, 1989-present. Cochair, PHS Coordinating Committee on Women's Health Issues, 1990present. ་་ Honors Awards: Elected to Institute of Medicine, National Academy FINANCIAL CONSIDERATIONS FOR ATTRACTING YOUNG SCIENTISTS Senator HARKIN. Thank you very much, Dr. Kirschstein. I am going to read a quote from your prepared statement here because it leads right into a question I have been wanting to ask you and also Dr. Raub. Dr. Leon Rosenberg, dean of the Yale University School of Medicine, said that: In a time of limited resources, his first priority is to create an environment in which talented young people choose careers in health-sciences research, because without them our future will be blighted. Well, that leads me to ask about these young people that we are trying to get involved in pursuing careers in research. I understand you have basically the lion's share of the money that goes out for stipends and pay and things like that. Right? Dr. KIRSCHSTEIN. That's correct. Senator HARKIN. And I don't know that I understand how all this works. I am learning it all the time. Let's say that you have a young person who just graduated from medical school and has been through their residency training. I think now the average age is probably what? They would be about 32, 33 years old, somewhere in there?" Dr. KIRSCHSTEIN. That's correct. Senator HARKIN. If I remember reading it correctly, the average debt now of a student getting out of medical school is $40,000 or so? Dr. KIRSCHSTEIN. I think it is pushing toward about $100,000, sir. Senator HARKIN. Average? I know private was higher than public. Dr. KIRSCHSTEIN. Well, it depends on whether the student attended a private or public medical school. You are quite correct. It would be somewhere between those two figures depending on whether it was a private or public medical school. Do you agree, Dr. Raub? Dr. RAUB. Yes. Senator HARKIN. We will find out. Let's say it's $60,000. And about that time they are probably recently married, perhaps starting a family. Let's say that they are at the top of their class. They are very bright, and they want to pursue research at NIH in Dr. Goldstein's department. Dr. KIRSCHSTEIN. Fine. Senator HARKIN. And he wants this young person. What will they start out at here? What would you start them at? What would be their salary? |