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around $28,000 to $30,000 through senior positions in the laboratories, clinics, or senior administrative positions.

Senator HARKIN. I would also like to know about, if I am using the word properly, trainee grants that go out to universities.

Dr. RAUB. Yes.

[The information follows:]



Director, National Institutes of Health:

Executive Level IV

Commissioned Corps

Senior biomedical research service

Senior executive service (M.D.'s): Includes physicians comparability allowance

Senior executive service (Ph.D.'s)

Tenured scientist (M.D.): Includes physicians comparability allowance

Tenured scientist (Ph.D.)

Nontenured clinical physician: Generally serve up to 3 years

Nontenured research physician: Appointment up to 7 years before considered for tenure
Nontenured research scientist (Ph.D.): Appointment up to 7 years before considered for tenure
'Actual pay in Commissioned Corps depends on years of creditable service and medical specialty.











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Senator HARKIN. I would like to see what that looks like for the last few years also.

Well, some of these people-you have just mentioned a couplehave been 18 years; Dr. Corey, 20 years.

Dr. KIRSCHSTEIN. Yes; we have about seven grantees of NIGMS who have been supported in excess of 30 years for the superb work they are doing.

Senator HARKIN. I would like to see what goes on year after year. How are these people paid, and what kind of pay do they receive? What kind of incentives are there for them to continue on to do that? Young people entering these professions and entering a career in research have to think about their future too.

I would like to be involved with you, Dr. Raub, and whoever your successor is as head of NIH, to really look at this and see if we can't address this problem over the next couple of years by really setting up a new system or better system of both stipends in-house and the trainees grant program that would put it on a better scale, on a more accelerated scale perhaps.


Dr. RAUB. May I add two footnotes to Dr. Kirschstein's comments without belaboring the points?

Each year's budget development is a delicate balance between opportunities now and long-term investments. While a critical part of that issue of attracting and keeping people in science is the training grant programs, as we have talked about, an equally critical part, if not more so in the short run, is the perception of whether one could ever get a grant if one were a scientist.

Many young people are guided when deciding to stay in science or not by the anxiety levels of their mentors concerning the ability to continue getting the kind of support that Dr. Kirschstein's examples highlight. We do not believe there is any magic answer to this, but a major part of the budget strategy is to make an impact now as well as a future investment.

The other footnote has to do with the intramural program. In one area, we are authorized by law to participate in a trial loan repayment system. The HOPE legislation, as it is called, is related to AIDS research and gave us a program-specific authority for loan repayment for physicians who are working for us in an AIDS research setting. We initiated loan repayment for about 20 of those AIDS researchers in the first year. We expect that number to double this year. Depending on the size of their debt and the length of their commitment to us, we are able to help them, by direct payment, to retire some of that debt. This is envisioned as a trial to determine whether this kind of additional incentive will have a material difference on both recruitment and retention. We are developing that data and we will be analyzing it very carefully for its implications.

Senator HARKIN. It is pretty ingenious. I like that idea. That's good. You are doing that right now.

Dr. RAUB. Yes; in one area, in intramural research related to AIDS.

Senator HARKIN. I understand.


Dr. KIRSCHSTEIN. If I may, in addition, Senator Harkin, many of the institutes do make every attempt to give new, young investigators an opportunity to start their first research grant, using a particular mechanism called the FIRST grant. In addition, we have new investigators who apply for the regular research grant for their first award. And we look at those applications very carefully and particularly try to help such young people to get started.


Senator HARKIN. Well, I look forward to working with you both and other directors on this problem. And we have other questions. I'll submit them to you in writing, Dr. Kirschstein.

[The following questions were not asked at the hearing, but were submitted to the Department for response subsequent to the hearing:]



Question. Doctor, we hear a lot about the relevance of basic research to disease treatment and prevention and how, eventually, these fundamental scientific advances evolve into critical "spin offs" for other institutes at NIH.

Could you give the Committee a few recent examples of basic research initiated by your institute which was later "spun off” to other institutes?

Answer. NIGMS is pleased that so much of the basic research supported by the Institute is paying off through advances in the more targeted studies being funded by other components of the National Institutes of Health and that this progress is often occurring far more rapidly than in the past. Among recent examples of this phenomenon are the following:

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Scientists trying to develop improved vaccines against influenza
are using a method, called "antisense RNA technology," which was
discovered about five years ago by NIGMS grantees. This "anti-
sense RNA" approach involves synthesizing a strand of RNA which
is complementary to and will lock onto the RNA of the flu virus,
thus blocking the ability of the virus to proliferate. This
type of vaccine would represent a vast improvement over past in-
fluenza vaccines since it would strike at the heart of the
virus, rather than the changeable outer coating, thus minimizing
the need for yearly variants of the influenza vaccine. Anti-
sense technology is also being applied to a host of other bio-
medical problems, as well as to some agricultural ones.

Cancer researchers are taking advantage of a new class of bio-
engineered proteins called single-chain antigen-binding pro-
teins, which were developed by an NIGMS-supported grantee.
These proteins will be attached to radioactive or toxic sub-
stances and targeted to detect or kill cancer cells. These bio-
engir.eered proteins hold great promise for cancer therapy since
they can penetrate tumors to a greater degree than regular anti-
bodies and can be cleared more quickly from the body than most
conventional chemotherapeutic agents.

Mapping the approximately 100,000 genes in the human genome is a
pain-staking and daunting process. Scientists trying to pin-
point the chromosomal location of disease-causing genes are,
therefore, pleased to now have at their command a new technique
to quickly identify where a probe for a specific gene is lo-
cated. The technique, developed several years ago by an NIGMS
grantee, applies a fluorescent tag to the probe, which immedi-
ately glows and affords more precise resolution of the probe' s
chromosomal location. Heretofore, radioactive tags had been
used, a procedure that took far longer and was less precise.

Promising preliminary results have emerged from studies regarding the potential of a compound called 2-CdA in the treatment of a white blood cell malignancy called hairy cell leukemia. This compound was discovered several years ago by an NIGMS grantee who was trying to uncover the molecular basis of another

serious disorder. He found that treatment with 2-CdA resulted
in complete remission in virtually all patients with hairy cell
leukemia. The compound has also proven beneficial in treating a
number of other malignancies of the lymphatic system.

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. Why is such a high proportion of your work in this field?

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.


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 pro


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 NIH in 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 underpinning 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.


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

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