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number and types of institutions that seek to, and actually receive support, to participate have been relatively stable over the past five years.

Since the eligibility criteria have been clearly delineated, for some years, for the Honors Undergraduate Research Training (HURT) component of MARC, (the only institutional grant mechanism which the MARC Program uses), there has been only modest turnover in institutions participating. This turnover results from the fact that some new applicant institutions are considered more meritorious by peer review groups than some ongoing programs competing for renewed support. Since 1987, the number of institutions with HURT grants has risen from 55 to 60. Most recently, the mix of MARC institutions has been:

5 percent 15 percent 20


institutions serving Native Americans
institutions serving Hispanics
institutions serving mixed populations of
Historically Black Colleges and

60 percent

With regard to the MBRS Program, greater numbers of institu. tions have been exploring opportunities to participate in the Program. For example, because, under the Associate Investigator conponent of the Program, institutions which are relatively research intensive and which have significant enrollments of minorities are eligible to apply for MBRS grants to fund student participation on ongoing funded research projects, more such institutions are showing interest in participating in the MBRS Program. These institutions typically have experienced great increases in enrollment of minority students, which may have heightened their awareness of the need to draw minorities into the biomedical research pipeline. There has continued to be great interest in receiving MBRS support among Historically Black Colleges and Universities, two-year colleges, and others, including those that serve Hispanics and/or Native Americans. The MBRS Program traditionally has funded such institutions through its various components.

Over the past five years,

the mix of MBRS awards has typically approximated:

7 percent

20 percent
20 percent

institutions serving Native Americans and
Pacific Islanders
institutions serving Hispanics
institutions serving mixed populations of
non-HBCU institutions primarily serving Blacks
Historically Black Colleges and Universities

5 percent 48 percent


Mr. Stokes. Has the entry of new institutions resulted in increased competition for limited funds at the expense of smaller institutions, particularly HBCUs?

Dr. Kirschstein. With regard to the MARC Program, the new institutions which have participated have been similar to those funded from its beginning in 1977, including some of the Historically Black Colleges and Universities. In fact, the mix of MARC institutions has remained quite stable over recent years with

regard to the MBRS Program, the mix of institutions has been gradually changing over the past 16 years, but has remained relatively stable in recent years. When the MBRS Program began, Historically Black Colleges and Universities constituted 68 percent of the participating schools, while today they represent 48 percent. This gradual evolution in the mix of institutions participating reflects the Program's commitment to reaching minority students wherever they represent a sizeable portion of the college or university's enroll.

For example, in recent years, eligibility criteria were broadened so that today many more institutions with mixed minority student populations, such as those urban institutions with significant enrollments of Hispanic and Black students or institutions with a mix of Hispanic and Native American students, are funded by the MBRS Program. In addition, it is important to emphasize that, as the MBRS Program's budget has grown, the resources provided to HBCUs and other institutions serving predominantly minority popula. tions have increased.


Mr. Stokes. What is the Institute doing to ensure the continued funding of science at the small, less research-oriented in. stitutions, which have historically supplied minority undergraduate students into the predoctoral candidate and biomedical pools?

Dr. Kirschstein. NIGMS's MARC and MBRS Programs award the largest proportion of their funds to such small, less researchoriented institutions. The missions of these programs, in essence, establish these schools as the primary recipients of such awards. Both Programs recognize the importance of strengthening the science milieu at these institutions so that they can continue to graduate significant numbers of minorities prepared to pursue graduate de grees in the biomedical sciences. The respective mechanisms of support provided by MARC and MBRS complement each other in helping these schools in these efforts. In addition, NIGMS encourages such institutions to apply for grants under the Academic Research Enhancement Award (AREA) Program, an NIH-wide effort to stimulate research capabilities at small, less research-oriented institutions. All of these programs complement those funded by other components of NIH, the National Science Foundation, the Howard Hughes Medical Institute, and others which focus on enhancing the science base at small institutions with significant enrollments of minorities.


Mr. Stokes. To what extent does the Institute support minor. ity students attending 2-year institutions?

Dr. Kirschstein. The MBRS Program currently supports four two-year colleges. These programs, at East Los Angeles College, Bronx Community College, Navajo Community College, and Southern University, Shreveport, Louisiana, involve a total of 57 students. Two institutions in this category which had received MBRS support in the past, Selma University and Medgar Evers College, now award Bachelor of Science degrees.


Mr. Stokes. Is there a formal mechanism by which MBRS/MARC Program Directors can comment on program directions and new initia. tives?

Dr. Kirschstein. There are both formal and informal opportunities for the MARC and MBRS Program Directors to share their views with the Institute regarding the programs' activities, directions or possible initiatives. First, every year the Institute convenes separate meetings of the MARC and MBRS Program Directors. Senior Institute staff, including the Director, NICMS, attend these meet. ings and the agendas are designed to offer the Program Directors many opportunities to share views and concerns about on-going or proposed activities, as well as to offer new ideas which they would like the Institute to consider. These have been productive meetings which we intend to continue, A second avenue for Program Directors to express their views is through the review committees. MARC and MBRS Program Directors constitute about one-third of the membership of the two review committees which conduct initial peer review of these programs' grant applications and which discuss issues bearing on those programs at their meetings three times each year. Finally, through regular informal contacts by correspondence or telephone, at meetings, or in personal visits, Institute staff and MARC and MBRS Program Directors exchange views and ideas. As the Director, NIGMS, I personally feel that it is important to maintain these various avenues for interactions so that an on-going, comfortable dialogue can be facilitated.


Mr. Stokes. Doctor, can you explain to the Committee the net effects which coordinating the MARC and MBRS Programs will have on those institutions which have both programs? How will this affect the number of students supported?

Dr. Kirschstain. I believe that the institutions participating in the MARC and MBRS Programs will benefit from the establishment by NIGMS of the Minority Opportunities in Research (MORE) Programs Branch, which will oversee the full range of NIGMS programs to attract more underrepresented minorities into research. The staff leading the MORE Programs Branch will strive to coordinate the administrative aspects of the MARC and MBRS Programs while recogniz. ing the unique features of each Program. Such administrative oversight will assure that the participating institutions receive information and advice which are consistent and constructive in building complementarity between the Programs. For example, program guide. lines that delineate program goals, eligibility, review criteria, and other parameters will be written to minimize uncertainties about each Program, as well as to address common grants management concerns. We anticipate that the number of students supported by the two programs will increase, as additional resources are allocated to these well-coordinated programs.


Mr. Early. Doctor, I see in your opening statement that an NIGMS grantee has again won the Nobel Prize. Can you tell us how the work of Dr. Corey, and of other NIGMS grantees, helps to make "smart" drugs?

Dr. Kirschstein. Dr. Elias Corey at Harvard University was awarded the Nobel Prize for developing the theory and methodology of organic synthesis, specifically relating to the creation of "smart" drugs. Dr. Corey developed a model of how a complicated molecular structure might be taken apart, piece by piece, to determine its original, fundamental chemical composition. He then uses the model to put the pieces back together through a logical set of reactions, until the final product, which is functionally equivalent to the initial compound, is synthesized. The beauty of Dr. Corey's work is that these final compounds have the desired therapeutic action, while the undesirable, and sometimes toxic properties can be eliminated.

While Dr. Corey's approach stems from the field of chemical synthesis, another NIGMS grantee, Dr. Irwin Kuntz of the University of California, San Francisco, has used the tools of structural biol. ogy to develop a computer program that uses the three-dimensional shape of a molecule, instead of its chemical structure, to identify compounds that might bind to the target molecule. This approach has already enabled him to identify a compound that blocks the action of an enzyme essential to the replication and survival of the virus that causes AIDS. While the compound is not active against the virus unless it is used in doses that greatly exceed the lethal limit for humans, the approach provides yet another highly promising Bethod that can be used to search for new drugs. Dr. Kuntz is working to modify the chemical to minimize its toxicity while retaining its antiviral activity.


Mr. Early. According to your justification and opening statement, your rather small AIDS research program is having a significant impact and coming up with some promising findings. summarize those for us please?

Can you

Dr. Kirschstein. The AIDS program has generated a number of useful and important results. of these, two stand out. First, a group at the University of California at San Francisco has used the published structure of the Human Immunodeficiency Virus (HIV) protease as a starting point for drug design. As described above, using a novel approach, developed by Dr. Kuntz, they were able to screen a computer database for compounds that could fit onto the surface of the HIV protease and thus inactivate the virus. They identified a material that has long been used in the treatment of depression, and that proved experimentally to be, as predicted, an active inhibitor of the protease. The chemical structure of this compound did not look at all like a molecule that would be an inhibitor, and almost certainly would not have been found by the usual routes for drug discovery. Dr. Kuntz and his colleagues are now trying to modify his compound so that will be usefu as an antiAIDS drug.

The second major achievement was just announced in the past few weeks. This was the determination of the structure of the HIV RNase H, a component of a viral protein that is essential for replication of the AIDS virus. Knowledge of this structure will also allow a rational approach to drug design, targeting a different portion of the AIDS virus. It is essential that a diverse set of antiviral agents be developed to combat this dread disease.


Mr. Early. What is the average increase for noncompeting research project grants under the budget proposal? For new and competing grants?

Dr. Kirschstein. The FY 1992 budget request provides a 7 per. cent increase for noncompeting research project grants and an 8.6 percent increase for new and competing grants. This proposal provides approximately 3 percent growth, after adjusting for inflation, using the 1992 Biomedical Research and Development Price Index of 5.8 percent.

Mr. Early. What was the downward negotiation rate for competing grants in FY 89 and FY 90?

Dr. Kirschstein. In FY 1989 and FY 1990, the downward negotiations for competing research project grants were 10.6 percent and 13.9 percent, respectively.

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Dr. Kirschstein. Our FY 1991 funding strategy is to determine appropriate funding levels using FY 1990 levels as a baseline upon which to build. Thus, in order to establish the appropriate support level for all competing and noncompeting grants, the Institute staff is examining each research project award on an individual basis. In doing this and in making prudent budget adjustments, we are guided by principles that were recommended by our National Advisory Council as well as by the principles outlined in the NIH cost-management plan.

For new competing awards, we are carefully analyzing the budget levels recommended after review by the study sections and Council. Using such analyses, we establish grant budgets so that the average cost of these awards will be equal to an increase of ap. proximately six percent over the average cost of such awards in FY 1990. This is appropriate based on the increase in the Biomedi. cal Research and Development Price Index.

We are sensitive to special needs, however. For example, many awards to first-time investigators are being made without adjustment, in order to give these new scientists a good start on their first independent research projects. These investigators are supported by special FIRST awards, which are limited to approximately $70,000 direct costs per year.

For competing continuations, grants are awarded at a level of ten percent over the amount awarded in FY 1990 plus additional funds

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