serious disorder. He found that treatment with 2-CdA resulted Scientists studying nutrition and metabolism, particularly in patients with diabetes, are building on the work of an NIGMS grantee who conducted a series of experiments on how the uptake of nutrients by the intestine adapts to dietary changes and to other certain normal and disease states. His findings indicate that the uptake of essential amino acids, the building blocks of proteins, is higher on both low- and high-protein diets, while the uptake of sugar increases as dietary carbohydrate and protein levels increase. Question. I understand that approximately 70 percent of your basic research is characterized as molecular biology research. is such a high proportion of your work in this field? Why Answer. In the past forty years, essentially since the seminal discovery of the structure of DNA, the field of biology has been revolutionized. It has become clear that understanding both health and disease depends on discovering the fundamental molecular basis of normal development and function as well as aberrations from the norm. For example, discoveries concerning the structure-function relationships of proteins and other macromolecules such as nucleic acids are of fundamental importance for understanding all of the interactions within biological systems, from the determination of the body's ability to resist infection, to an understanding of the way a fertilized egg develops into an adult human. Since the National Institute of General Medical Sciences was given the mission of supporting research in the "general or basic medical sciences," it has always emphasized studies at the most fundamental levels--those of the cell, the subcellular organelles, the molecule, and the gene. The tools of molecular biology--recombinant DNA technology, site-directed mutagenesis, X-ray crystallography, computer-aided analysis, and many more --have so pervaded all scientific disciplines that most of the NIGMS grant portfolio could be appropriately classified as molecular biology research. MINORITY PROGRAMS Question. The Committee has been very concerned about the lack of minority representation in the sciences and the series of reports that forecast a future shortage of minority biomedical science professionals. Now that NIGMS is the lead Institute at NIH for minority science initiatives, please tell the Committee how your programs will help address this shortage. Answer. As you point out, NIGMS is now the home for both the Minority Access to Research Careers (MARC) Program and the Minority Biomedical Research Support (MBRS) Program, the two programs at NIHin the forefront of its efforts to increase the number of minority biomedical scientists. The MBRS Program takes an institutional approach to reaching this goal, awarding grants to colleges and universities with a significant minority enrollment so that the scientific milieu can be strengthened and the faculty can mount research pro jects on which students can be employed. Through this student participation, along with accompanying enrichment activities, the MBRS Program intrigues minority students into considering careers in the biomedical sciences and prepares them for the rigors of graduate school and research endeavors. A significant number of the students who have participated in the MBRS Program have gone on to graduate school to pursue advanced degrees in the sciences. The MARC Program offers a number of research training opportunities to students and faculty at institutions with significant enrollment of minorities. Most noteworthy among the efforts of the program are the Honors Undergraduate Research Training component and the predoctoral fellowship awards. These support the most promising undergraduate and graduate students as they pursue degrees that will prepare them for careers in biomedical research. The research expe riences required of these trainees and fellows provide the kind of stimulating and rigorous introduction to research that typically generates a commitment to continue toward a career and solid under pinning toward achieving that end. As with the MBRS Program participants, a significant portion of the students participating in the Honors Undergraduate Research Training component have gone on to pursue graduate degrees. During FY 1991 two new initiatives were announced. One extends eligibility to participate in the Honors Undergraduate component to freshmen and sophomores. The other opens eligibility for predoctoral fellowships to minority graduates of any college and university, not just those with MARC Honors Undergraduate programs. These initiatives, and others being planned, should strengthen the efforts of NIGMS's efforts to address the projected shortages of scientific manpower by increasing the participation of underrepresented minorities. RESEARCH TRAINING--GENERAL Question. I understand the 12,318 training slots NIH proposes to fund in 1992 are about at the level recommended by the Institute of Medicine, but the distribution is about 800 slots under the level recommended for predoctoral and 800 over the postdoctoral recommendations. Is this accurate? Answer. The 1989 National Academy of Sciences report, Biomedical and Behavioral Research Scientists: Their Training and Supply makes global recommendations to meet manpower needs in various training areas rather than providing specific training recommendations for the NIH per se. However, it does serve as a guide for the entire NIH in the prioritization of its research training needs, including the "ideal" allocation of training positions between predoctoral and postdoctoral trainees/fellows, as well as the relative weight that should be assigned to the specific training areas, i.e., biomedical versus behavioral versus clinical. Under the FY 1992 budget proposal, NIH would support an estimated 12,318 predoctoral and postdoctoral trainees and fellows, a number "in the ballpark" of the Academy's recommendations. The NIGMS predoctoral research training programs serve the special need of developing highly skilled basic biomedical research scientists whose broad interdisciplinary training give them the background to do future research in the most up-to-date areas of bio medical science. More than half of those who have received NIGMS research training support are now grantees of the other NIH institutes. It is these young people who are the "seed corn" for the continued and future prominence of the United States in biomedical research. Question. Why don't you reallocate the predoctoral and postdoctoral slots? Answer. The NIH FY 1992 budget request reflects an increase of 340 in the number of biomedical predoctoral trainees/fellows. In order to achieve this increase, the estimated number of postdoctoral trainees/fellows to be supported will decrease. The NIGMS training program has traditionally emphasized the support of predoctoral candidates, which is in keeping with their philosophy and mission of providing the undergirding in research and research training for the NIH biomedical research enterprise. RESEARCH TRAINING--BIOTECHNOLOGY In Question. Doctor Kirschstein, your Institute is also very involved with providing training opportunities in biotechnology. 1989 NIH prepared a report on the training needs in the field of biotechnology and, based on your 1992 request, we are 943 training slots below your 5-year plan. Do you feel the estimates you made in 1989 are still accurate? Answer. The NIGMS biotechnology training program was initiated in 1989 in response to both the urging of the Senate Appropriations Committee and the recommendations made by a panel of experts convened by NIH in 1988. The panel recommendation that the new program expand to up to 1,500 trainees/year by 1993 was an accurate reflection of the demands for trainees that existed, and could be predicted in this specialized research field. However, the availability of funding for research training, the training needs that exist in other research areas, and the pace at which universities are able to mount new biotechnology training initiatives dictate that the rate of increase in this program be less than originally envisioned. GENETIC RESEARCH Question. How does your Institute's work in the fundamental problems of genetics and the transfer of genetic information relate to the research being conducted by the Human Genome Research Project? Answer. NIGMS supports untargeted, investigator-initiated research in genetics. The results of this research in the past 20 years, and especially in the 1980s, provided the foundation for the current efforts, supported by the National Center for Human Genome Research (NCHGR), to map and sequence the human genome and the genomes of model organisms. For example, NIGMS-supported scientists developed the basic procedures for both physical and genetic mapping of chromosomes. The Genetics Program of NIGMS continues to support research on model systems that is designed to lead to a better understanding, and eventually prevention and treatment, of human genetic diseases. In the process, this research generates information that is essential to the performance of the more focused goals of the NCHGR. In the past year, for example, NIGMS supported several research projects whose results will have an impact on the interpretation of mapping and sequencing information. In fact these findings are the latest in a series that contradict the "central dogma” that all genetic information resides in the nucleotide base sequence of DNA.. In one case, an NIGMS grantee showed that the formation of telomeres--the ends of chromosomes--occurs in a different way from the rest of the DNA. In another case, NIGMS grantees are unraveling a newly discovered process called RNA editing, in which nucleotide bases are added to or deleted from the RNA transcript to make it a functional template for protein synthesis. These new findings indicate that the processing of genetic information is more complex than previously thought, and will need to be taken into consideration as the genome project progresses. NIGMS grantees are also developing tools, often as byproducts of their research on fundamental genetic problems, that are likely to aid in the genome project. For example, an NIGMS grantee showed that ribozymes can be designed to cleave specific DNA sequences (in addition to RNA sequences). Such ribozymes could be useful in chromosome mapping. NIGMS also supports two resources, GenBank, the nucleic acid sequence database, and the Human Genetic Mutant Cell Repository, that are playing essential roles in the genome project. As an indication of the importance of these resources to the genome project, the Repository recently made available to the scientific community a panel of highly characterized somatic cell hybrid cell lines for use by laboratories conducting mapping studies. Conversely, NIGMS expects that as chromosomes are mapped and their sequences determined, new questions will be raised, opening up new opportunities for basic genetic research that will fall within the mission of NIGMS. Question. How has your genetics program been affected by the creation of the Human Genome Center? Answer. As you know, until the creation of the National Center for Human Genome Research, the Genetics Program was responsible for the administration of grants related to the genome project. In fiscal year 1990, those projects that were directly targeted to the acquisition of mapping and sequence data and the development and implementation of technologies for genome analysis were transferred to the Center. This has enabled the Genetics Program to concentrate its efforts in the areas of its traditional strengths--investigations designed to better understand basic genetic processes in model systems whose results can be applied to a better understanding of genetic diseases. The Genetics Program continues to interact closely with the NCHGR to coordinate research and training activities and to assure that knowledge stemming from both components will be fully exploited. QUESTIONS SUBMITTTED BY SENATOR DALE BUMPERS RESEARCH TRAINING OF MINORITIES Question. The National Institute of General Medical Sciences seems to play a lead role in the National Institutes of Health in supporting programs aimed at increasing the number of minorities engaged in biomedical research. What efforts are you making that hold the most promise for achieving this goal? Answer. In addition to the traditional biomedical research training program of the National Institute of General Medical Sciences (NIGMS), which strongly encourages the support of minority students, the Institute sponsors several specialized research training and research grant programs specifically designed to increase the number of minorities engaged in biomedical research. う Established by the NIGMS in 1972, the Minority Access to In addition to the HURT Program, the MARC Program also awards individual Predoctoral Fellowships Awards to outstanding graduates who choose to pursue a doctoral degree in the biological sciences; Faculty Fellowships, to provide opportunities for advanced research training to faculty drawn from institutions with primarily minority enrollment; and Visiting Scientist Awards to entice scientist-teachers to serve in the capacity of visiting scientists at institutions with substantial minority enrollments. The primary intent of the latter two awards is to strengthen research and teaching programs in the biomedical sciences for the benefit of the students and faculty at these institutions. An estimated 193 awards will be made in these three areas in FY 1992, with the majority of support going to individual predoctoral fellows. In 1989, the Minority Biomedical Research Support (MBRS) Program The NIGMS also participates in the NIH-wide Minority Supplements Program, in which principal investigators holding NIGMS research grants may request supplemental funds to support minority scientists and students. The aim of these supplements is to attract and encourage minority individuals to pursue biomedical research careers. A wide range of minority supplements are available, |