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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.



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.


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 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.



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.

Established by the NIGMS in 1972, the Minority Access to
Research Careers (MARC) Program provides special research train-
ing opportunities and incentives in the biomedical sciences in
order to attract and retain minority students with the potential
for research careers. The backbone of the MARC Program is the
Honors Undergraduate Research Training (HURT) Program, which em-
phasizes the value and importance of a biomedical research
career and provides support at the undergraduate level. It is
rewarding to note that at a time when the percentage of students
(minority and nonminority) earning biological science degrees
has decreased nationwide, the number of students earning science
degrees at MARC supported institutions has increased. An esti-
mated 589 students will receive support in FY 1992.

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
was transferred to the NIGMS from the National Center for
Research Resources, NIH. The goals of the MBRS Program, estab-
lished in 1972, are to increase the number and quality of minor-
ity health scientists, and to strengthen the capability of eli-
gible minority institutions research in the biomedical sciences.
Two major grant mechanisms are used to respond to the diverse
needs of applicant institutions. The MBRS Traditional Program,
supports faculty research projects and/or student participation
in biomedical research, while the MBRS Program for Undergraduate
Colleges, established in 1985, supports enrichment activities,
as well as pilot studies or regular research projects. An esti-
mated 98 institutions will receive MBRS support in FY 1992.

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,

each geared to the point in career progress of the recipient.
The variety includes High School Summer Student Research Appren-
ticeships; Supplements for Undergraduate Students; Supplements
for Graduate Research Assistants; and, Supplements for Investi-
gators. NIGMS awarded a total of 80 minority supplements in
FY 1990.

Question. Are you undertaking any new initiatives? Answer. NIGMS is undertaking several new initiatives to increase the number of minorities in biomedical research.

In response to Congressional interest, in FY 1991 the MARC
Honors Undergraduate Program will be expanded, on a pilot basis,
to extend support to promising freshmen and sophomore students;
(until this time, support has been available only to juniors and
seniors). By identifying students earlier, and getting them
"hooked on science,” it is hoped that the number of eligible
students entering the biomedical research pipeline will be

MARC predoctoral fellowships have historically been awarded only
to graduates of the MARC Honors Undergraduate Program. In
FY 1991, in recognition of the fact that many, if not most
minority students attend universities whose enrollment is heter-
ogeneous, the NIGMS will expand eligibility to include qualified
applicants from non-MARC institutions. Again, it is hoped that
extending the eligibility of fellowships to all minority stu-
dents will increase the applicant pool entering the research



Question. Getting new scientists started in their careers is particularly important to maintaining the vitality of the country' s research enterprise. What programs does NIGMS support to encourage new scientists early in their biomedical research careers?

Answer. Recruiting talented young men and women into biomedical research careers, and providing support for them during the requisite years of specialized training has always been a vital part of the Institute's mission. In all of its research training programs, the Institute stresses the importance of laying the basic foundation both for disease-oriented research and for further fundamental studies. The Institute has a number of training programs to meet the variety of training needs that exist.

Through the traditional institutional and individual National
Research Service Award (NRSA) the Institute provides for the
broad, multidisciplinary training that the Institute believes is
necessary in preparing trainees to pursue research careers in a
wide variety of areas, many of which reflect the scientific
goals of other NIH components.

The Medical-Scientist Training Program (MSTP) addresses the spe-
cialized need for scientists who can bridge the gap between
basic and clinical research. This program, which supports re-
search training leading to the combined M.D.- Ph.D., has been
remarkably successful in training creative and productive

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ted 788 trainees.

The 1992 budget will support an estima

The Biotechnology Training Program is another specialized training area developed by the NIGMS in response to Congressional concern that the United States must produce greater number of scientists with expertise in biotechnology if it is to maintain its position as a world leader in this field. An estimated 307 trainees and fellows will be supported in FY 1992.

Recognizing the need for an increase in the number of minority researchers, the Institute initiated the Minority Access to Research Careers (MARC) Program, which has been described above, in detail.

Agreeing that the early support of young scientists is critical to their continued involvement in and commitment to research as a career, the NIGMS offers First Independent Research Support and Transition (FIRST) Awards to provide a sufficient period of research support for newly independent biomedical investigators to initiate their own research. The grants are intended to underwrite the first independent investigative efforts of an individual; to provide a reasonable opportunity for an investigator to demonstrate creativity, productivity, and further promise; and to help in the transition to traditional types of NIH research project grants.

NIGMS also gives special consideration for funding to firsttime applicants whenever the appropriate combination of circumstances permits.


Question. What are the payoffs, such as in research on cancer or heart disease, of the basic research which the National Institute of General Medical Sciences supports? How long does it usually take to achieve that "payoff" in more disease-targeted research or practice?

Answer. 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 treatment regimens. However, there are innumerable, perhaps less spectacular examples from 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 been investigating how DNA is repaired in Drosophila flies. In the process, he has identified a Drosophila model for the human disorder known as Fanconi Anemia, a genetic defect that affects all types of blood cells and is associated with malformations of the heart, kidney, and limbs and a predisposition to leukemia and other cancers. He discovered that a particular mitochondrial enzyme, nuclease, which is altered in a mutant strain of Droso

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