BASIC RESEARCH Mr. Stokes. What areas of basic research do you feel are the most promising for NIGMS to support? Dr. Kirschstein. NIGMS has research programs focused on genetics, cell biology, molecular biology, biochemistry, structural biology, trauma and burn research, and pharmacology and pharmaceutical chemistry. All of these programs have made major contributions in the past and are poised to make significant advances in the future. Mr. Stokes. Could you highlight several recent findings by NIGMS-supported scientists which you feel are significant and which illustrate the importance of supporting basic research? Dr. Kirschstein. There are well-known examples of the payoffs of the basic research funded by NIGMS, such as the Nobel Prize winning work of Drs. Michael Brown and Joseph Goldstein which began as basic studies of cellular steroid receptors, moved to more focused work on a specific steroid, cholesterol, and culminated in research into the mechanisms that control cholesterol metabolism. The findings from that work have obviously been important in understanding atherosclerosis and in developing improved prevention and treatment regimens for heart disease. However, there are innumerable, perhaps less spectacular examples in many areas supported by the Institute that illustrate the importance of basic research to the progress of research on many diseases. Some of these are summarized below: Dr. James Boyd of the University of California, Davis, has Several years ago, Dr. Charles Laird of the University of Washington in Seattle developed a hypothesis about the genetic basis of the most common inherited form of mental retardation, known as the fragile-X chromosome syndrome. Dr. Laird's work in Drosophila led him to conclude that the syndrome was caused by the abnormal activation of a gene or genes. Now scientists here and abroad have found evidence in humans substantiating Dr. Laird's theory. This should permit the development of diagnostic tools and, perhaps, even treatments for this devastating disorder. Recently, Dr. Stuart Schreiber of Harvard University, a grantee whose research has focused on synthesizing molecules of immunological importance, found a series of small molecules that bind to the AIDS virus at the site where the virus would normally bind to and infect the T cells of the human immune system. Now Dr. Schreiber and others are building on this work in order to determine whether these or similar molecules could be used to disrupt the infective stages of the AIDS virus. For many years, Dr. Glenn Dryhurst of the University of Dr. Elizabeth Blackburn of the University of California, San Francisco, has worked out the mechanism by which the end portions of the chromosome, called the telomeres, protect the genetic information during cell division. Abnormalities of these telomeres may play a role in aging and cancer. Dr. David Matthews of the Agouron Institute has determined the structure of the enzyme RNase H from the AIDS virus. This should help in finding new drugs to combat AIDS. Mr. Stokes. What role does the United States biotechnology industry play in biomedical research? Do you believe that the NIH, and the NIGMS in particular, is doing enough to support the biotechnology industry? Dr. Kirschstein. The biotechnology industry is a product of the basic research supported by NIH since the Second World War, and in particular of the advances made since recombinant DNA technology was first developed in the mid-1970s. Progress in the biotechnology industry is strongly dependent on the flow of new ideas from the basic research, done primarily by academic investigators. The support of fundamental research in biology, and in chemistry as well, contributes directly to the biotechnology industry. In addition, however, funding is required for an area that could be termed "strategic research" or "generic applied research." This is basic research targeted to specific problems of importance to the industry, that lie in the area between pure research based on speculation and creative ideas and research that is applied or developmental and leads more directly to commercial products. Finally, support is needed to insure the flow of trained manpower to academia and to the industry. The NIGMS is primarily responsible for predoctoral training in the basic biomedical sciences, which produces the molecular biologists, geneticists, biochemists, pharmacologists, and chemists needed by the industry. In addition, NIGMS has a specific research training program in biotechnology which links the students' training more specifically to the needs of the industry. In particular, this program attempts to train students jointly in biology and chemical engineering, a mix which the biotechnology industry finds of real value. Although the biotechnology training programs have received adequate support in recent years, this support must be maintained and the broader training programs should be brought to a higher level of funding in order to maximize the ability of the biotechnology industry to compete worldwide. TRAINING Mr. Stokes. How does the Institute prioritize its training requirements, and thus allocate training funds between the MARC, National Research Service Awards (NRSA), Biotechnology, and MedicalScientist Training Program (MSTP)? Dr. Kirschstein. The Institute's highest priority among its NRSA training programs in FY 1992 is the Minority Access to Research Careers (MARC) Program. Both the moral and the fiscal imperatives of the 1990's mandate the enrichment of the next generation of biomedical scientists with an ever increasing number of well-trained minority individuals poised to conduct leading-edge biomedical research. Thus, the funding increase in FY 1992 for the MARC Program will expand training opportunities by 50 slots. All other NIGMS training programs receive added funds in the FY 1992 budget for stipend increases alone. Beyond this, when making allocations of training funds our next priority is the Medical Scientist Training Program, which prepares investigators having the combined M.D.- Ph.D. degree, who can bridge the gap between basic and clinical research. This highly successful program attracts some of our most motivated and dedicated young people with the promise of a career which includes both the excitement of solving problems in fundamental biomedicine with the satisfaction of applying these solutions to clinical practice. Within the context of a need for predoctoral research training across a broad array of disciplines, our third priority would be for biotechnology research training. Young men and women trained in biotechnology will fill newly developed niches in both academic and corporate research laboratories as we move toward the year 2000 and beyond. Their discoveries will both illuminate the fundamental processes of basic biology, chemistry, physical sciences, and medicine and form the foundation of the technological and commercial underpinnings of American industry. Mr. Stokes. How do NIH predoctoral stipends compare to those offered by other science-oriented Federal agencies? Dr. Kirschstein. The following is a list of predoctoral stipend levels at different agencies for FY 1991. These figures are for the first year of graduate education and include only the sti pend paid to the student. Mr. Stokes. Does the payback requirement for National Research Service Awards affect the willingness of young people to pursue federally supported graduate training in biomedical sciences? Dr. Kirschstein. The payback obligation for National Research Service Awards concerns most students when they consider acceptance of the NIH-supported traineeships and fellowships. Many students decide that their likely career employment will fulfill the NRSA service obligation and accept such awards. Others, especially those with economically depressed backgrounds, are more cautious and do not accept them. A particular problem has arisen with the payback requirement for trainees in the new NIGMS biotechnology training grants program. This Congressionally-mandated program is clearly broader in the scientific fields it covers than are other NIH training programs, and prospective trainees and fellows (as well as program directors) are concerned that the likely employment fields, such as chemical engineering, would not qualify as creditable for payback purposes. We are currently trying to broaden the definition of creditable payback service in order to remedy this problem. Mr. Stokes. It is my understanding that the Institute is conducting an examination of its minority programs. Please describe the process being used. Dr. Kirschstein. The Institute is conducting several assessments of its minority programs, one of which is a formal evaluation and the others, more informal but nevertheless serious examinations. The formal evaluation is of the Minority Access to Research Careers (MARC) Honors Undergraduate Research Training Program. This evaluation involves a process of designing a study, gathering and analyzing data, and preparing a report presenting results and any recommendations. We are presently in the early phases of this evaluation project, and the design phase should be completed within the coming six months. This evaluation will be done under contract, with the Institute's Office of Program Analysis overseeing the work. Less formal reexaminations of the Minority Access to Research Careers Program and the Minority Biomedical Research Support Program (MBRS) have begun, as well. About six months ago, I asked a working group of senior staff and program staff to begin looking at these programs and formulating issues that should be discussed as we look to the future. Since NIGMS is now responsible for both the MARC and MBRS Programs, it is important for us to examine the goals of both programs, the mechanisms used to achieve these goals, options for maximizing the complementarity between the two programs, and opportunities for enhancing their efforts to address the demographic imperative of drawing greater numbers of underrepresented minorities into research careers. The staff working group formulated a set of issues which are being considered, along with others, by a group of distinguished advisors drawn largely from institutions with significant enrollments of minorities (both MARC and MBRS schools). A representative of the Institute's Council and several representatives of professional societies and research-intensive institutions are also participating. These advisors will draw up some suggestions and raise questions for my attention, which I will then discuss with the Council, program staff, other members of the minority community, the Associate Director for Minority Programs, NIH, and other interested parties, including members of Congress. We hope that these assessments will all prove helpful to us as we continually strive to adapt our programs to take advantage of new opportunities and meet new challenges. Mr. Stokes. When do you expect recommendations to be complete? Dr. Kirschstein. In the case of the formal evaluation of the MARC Honors Undergraduate Research Training Program, the study is likely to be complete late in 1992 or early in 1993. The reexaminations of the MARC and MBRS Programs, which I just described, should be complete later this year. MARC Mr. Stokes. The fiscal year 1992 budget request for the MARC Program shows an 11 percent increase. Will you tell us please what the increased support will allow the Program to accomplish? Dr. Kirschstein. The 11 percent increase in support provided to the MARC program in FY 1992 will be used to provide a four percent increase in the stipend level for all students supported under this program. It will also allow modest increases in two new initi atives begun in FY 1991. The first initiative is the extension to freshman and sophomore students, on a pilot basis, of the traditional Honors Undergraduate Research Training Program, which previously supported only juniors and seniors. The second initiative, portable MARC predoctoral fellowships, extends eligibility for minority predoctoral individual fellowships to all minority individuals, regardless of the institution (MARC, MBRS, or other) of their baccalaureate degree. Mr. Stokes. Last year, the Committee urged the Institute to explore portable MARC predoctoral fellowships to enable all eligible minority honor students to apply. What action has been taken? Dr. Kirschstein. The program of portable MARC predoctoral fellowships was announced early this year. Applications will be received by a deadline of May 10, 1991. The applications will be |