RESEARCHER POOL

Senator ANDREWS. Well, I remember years ago, a fellow by the name of John Rooney, who was my first committee chairman, funded the State Department, and he was a delightful guy. He was a former district attorney, and he said, "Mark, as long as you're on my committee, just remember one thing. Know the answer before you ask the question, and be sure that you know what you're trying to develop."

And what I was really inviting you to say-and I don't want to coach the witness; I wouldn't do that, because I'm not an attorney; I'm an agronomist, so I think I'm close to this other discipline-but the thing I was trying to find out was whether there had, in fact, been a shortfall or whether you had a dropout in researchers because of the pay scale or the funding for the researchers wasn't adequate to keep these people in that discipline.

Now that I've prompted you, do you have a falling out of the pool of researchers, or is this simply to make up the dropout that you had because of restraints in the fiscal year 1981 budget?

Dr. KIRSCHSTEIN. Overall, there is a decrease in the number of trainees that we have been supporting for the last 4 to 5 years. It was a particular shortfall, and there will be a particular shortfall during this current fiscal year, which we will try to make up next year if possible.

Senator ANDREWS. But is there a dropping out of the people-in other words. the career researcher? Are they staying in the field, or have they been dropping out of the field at a greater rate during the last 4 or 5 years than in the prior 5-year period? And if you don't have those figures, you could take a guess at them now and correct them for the record.

Dr. KIRSCHSTEIN. Well, we can say several things, and we may want to amplify for the record.

There are. of course, two types of individuals who are in research in the biomedical area, Ph. D. scientists and physicians. The number of physicians who are engaging in research has decreased rather markedly. And the number of physicians who are in research training has also decreased. This. for example, is one of the reasons for the NIGMS medical scientists training program, the program which strives to change that decrease by providing support for individuals who are planning to become researchers to earn the combined M.D./Ph. D. degree.

The number of Ph. D. scientists has remained approximately steady. Senator ANDREWS. Well, the concern of the committee-and I just gained the information that this has been an ongoing concern and not one that I just stumbled on this afternoon-but the concern of the Committee is maintaining a stable research pool, and you mentioned that you are seeing dropouts of trained researchers at this period of

time.

Can you give us for the record the reason for this dropping out. And can you. for the record. expand on what has happened in this to-besought-for goal. really, of a stable trained cadre of researchers who should be attracted into this subprofession of the medical profession and should be kept there? Isn't it a lot like the army? If you get them to reenlist, you can save a whale of a lot ar a much more effec

tive army on down the line than if they

out on you. So

if you could provide some of those figures, it might give the subcommittee some better insight than we would have otherwise.

[The information follows:]

MAINTENANCE OF STABLE POOL OF RESEARCH SCIENTISTS

The dominant position of American science in today's world, and the truly excellent quality of the biomedical research being conducted in this country, is nowhere more vividly demonstrated than in the yearly distribution of Nobel Prizes in the various science categories. Indeed, the NIGMS alone has, over the years, provided support to 42 investigators who have won recognition from the Nobel Prize committees. Our ability, as a nation, to maintain this level of excellence is necessarily dependent on the ability to maintain an adequate pool of talented and dedicated researchers, trained in a broad range of subject matter areas.

A number of difficulties must be overcome to achieve this goal. First and foremost is the fact that the "half-life" of a grantee is only about 5 years: i.e., only half of the scientists who received research project grants from NIH in 1980 can be expected to still be grantees in 1985: experience shows that by 1990 this figure will drop to about 35 percent. Second, between 1966 and 1977, the percentage of NIH grantees who are physicians dropped from 43 percent of the total to only 28 percent-a serious decline, Highlighted in a special article published a year ago in the New England Journal of Medicine, by Dr. James A. Wyngaarden of Duke University, entitled "The Clinical Investigator as an Endangered Species." Third. it has proven difficult to entice medically trained individuals to commit themselves to careers in certain important areas of research. For example, critical shortages of trained investigators exist in such areas as clinical pharmacology and trauma and burn research.

This problem of the growing shortage of physician-researchers is perhaps the most acute and has been the subject of considerable study and debate. Some important reasons for the decline, according to Dr. Wyngaarden, include the instability of Federal support to biomedical research and research training, curriculum revisions in the medicai schools, and the disincentives contained in the payback provisions of the National Research Service Act awards. One impact of the payback provision. Dr. Wyngaarden argues. is to help ** make a tentative research training decision a very difficult step to take-making it impossible to sample the research life without incurring, what he calls. "unwarranted economic or professional penalties."

At the request of the Congress. the National Academy of Sciences has been carefully studying these and other issues related to the role of the Federal Government in the training of biomedical research scientists. Three recommendations emanating from the Academy's studies are particularly significant: (1) that the NIH should provide funding support for a total of 4.250 predoctoral trainees each year: (2) that, through its medical scientist training program. the NIGMS should specifically provide support each year for 725 individuals enrolled in combined M.D.-Ph. D. degree granting programs: and (3) that an attempt should be made to encourage research training of a broad, multidisciplinary nature.

As the principal source of support for research training at NIH. the NIGMS has played a vital role in the maintenance of the Nation's pool of high-quality biomedical research scientists-providing support for two-thirds of the predoctoral trainees funded by NIH and roughly 40 percent of all the NIH-funded trainees. Coordinating its efforts with those of other components of the NIH. the NIGMS has followed the NAS guidelines regarding the number of predoctoral trainees to be supported and has strongly emphasized broad. multidisciplinary training. In addition. the Institute has provided support for the full number of M.D-Ph. D. trainees recommended by the Academy Through its minority access to research careers program. the NIGMS has also expanced opportunities for minority group members-long underrepresented in the field of biomedical research-to enter careers in scientific research..

Roughly 10 percent of the trainees supported by the NIGMS are the recipients of individual NRSA fellowship awards. The remainder receive support for research training under institutional fellowship awards provided by the Institute to various university training programs throughout the country. Typically, these awards are made for a 5year period. during which the programs are gradually brought up to full strength in terms of the number of classes and number of trainees permitted on the award. At the end of this period. the schools must recompete if they wish continued support, on the

basis of the quality of their programs. Because NRSA awards were started in fiscal year 1975, a large part of the research training budget has a 5-year cycle. This was reflected in the Institute's training budget for fiscal year 1980, with its large proportion of competing awards, and can be expected again in fiscal year 1985.

It is the hope of the NIGMS, and the NIH generally, that efforts to stabilize the yearly funding of competing research projects will encourage physicians and scientists to enter research, and thus maintain an adequate national pool of highly qualified researchers. But, as the Director of NIH has indicated in a recent article, scientific research is a profession with a naturally "high metabolic rate," and as many as 2,000 principal investigators are lost every year. Because of the critical importance of attracting. and retraining. the best young minds available to biomedical research, the NIGMS is committed, through such mechanisms as the medical scientist training program, to do what is possible to overcome the obstacles which may prevent maintenance of a stable pool of highly qualified research scientists.

SUBMITTED QUESTIONS

Senator ANDREWS. I have, as I'm sure you know, a whole host of questions, but in the interest of time, we will let you answer them for the record and go on to our next witness.

[The following questions were not asked at the hearing but were submitted for response for the record:]

Question:

QUESTIONS SUBMITTED BY THE SUBCOMMITTEE

PHARMACOLOGICAL SCIENCES

Last year you described for us investigations involving prostaglandins that were part of a research program being supported by your Institute through the Pharmacology Research Center at Vanderbilt University.

Have these investigations shed further light on our knowledge of these substances and their involvement in certain diseases?

Answer: Prostaglandins are naturally occurring substances found in almost every cell in the body. Researchers are still only beginning to discover the various roles that these substances play in the normal and abnormal functioning of body tissues; but, it is already clear that a knowledge of how prostaglandins are formed and released within the body is critical to an understanding of a variety of diseases and disorders.

Dr. John Oates, director of an NIGMS funded research team working at Vanderbilt University, has been among the leaders in prostaglandin-related research. His most recent report, in the December 11, 1980, issue of the New England Journal of Medicine, describes a newly discovered prostaglandin and indicates that there is a marked overproduction of this prostaglandin-D2 in patients with a rare, often fatal disorder called systemic mastocytosis. This is a condition characterized by episodic attacks of flushing, the precipitous lowering of blood pressure, and rapid heartbeat--all of which can result in life threatening shock.

Analyzing the urine from one patient suffering from systemic mastocytosis, Dr. Oates noted this overproduction of the prostaglandin-D2, and decided to treat another such patient with aspirin, which acts to inhibit prostaglandin production. This second patient has now fully recovered, and has been disease-free for over eight (8) months.

While it has been known that a prostaglandin of one type or another is involved in many clinical conditions, this is one situation in which a specific prostaglandin has been associated with a specific disorder. As a result, not only did Dr. Oates save at least one life, he and his colleagues have opened up studies aimed at one day using pharmacologic agents aimed at inhibiting the production of or antagonizing the action of only a specific prostaglandin, without disturbing other bodily functions. Aspirin and other nonsteroidal anti-inflammatory agents which are used today are not selective in terms of their action.

Other aspects of prostaglandin pharmacology and physiology are being studied at the Medical University of South Carolina. In studies in which endotoxic shock is produced in rats, NIGMS grantees have discovered that administration of certain nonsteroidal, anti-inflammatory drugs can significantly improve survival by inhibiting the synthesis or activity of thromboxane, another prostaglandin. (Thromboxane has been implicated in the aggregation of platelets, a contributing factor to endotoxic shock.) These observations are consistent with the hypothesis that thromboxanes play an important pathophysiological role in endotoxic shock and provide a basis for the design of therapeutic agents which may be useful in treating endotoxic

shock in man. These findings are also significant because of their potential value in understanding various toxic shock syndromes.

These two examples are indicative of the types of research in the prostaglandin area supported by the NIGMS Pharmacological Sciences Program.

Question: How might these findings be applied to our understanding of the disease processes involved in arthritis?

Answer: It is already known that inflammation, in a joint or elsewhere, results in increased prostaglandin production in the affected tissues, and that prostaglandins, in turn, tend to contribute to the inflammatory process and increase pain. But, additional basic research focused on the structure, synthesis, and release of the various prostaglandins (as well as their metabolites or byproducts) is necessary before we can understand their role in a specific disease like arthritis.

Question: Do you support any research to investigate the possible role of these substances in producing menstrual cramps?

Answer: The NIGMS does not support investigations related to the possible role of prostaglandins in producing menstrual cramps, since such research would be supported by the National Institute of Child Health and Human Development. However, the work of Dr. Oates and other NIGMS grantees on prostaglandins will have importance for and influence studies of individual disorders, such as menstrual cramps.

GENETIC SCREENING AND COUNSELING

Question: Do you support research in genetic screening and counseling?

Answer: The NIGMS is not directly involved in the areas of screening and counseling. Research on the development of screening methodologies for particular genetic diseases is the responsibility of the various categorical institutes at NIH--the NHLBI, for example, has a sickle cell disease program. Research on the delivery of genetic services, including studies of the effects or effectiveness of genetic screening and counseling, on the other hand, is a responsibility of the Health Services Administration.

Nevertheless, screening and counseling programs are necessarily dependent upon an understanding of fundamental genetic structures and processes, as well as on techniques, developed through basic, untargeted genetic research; and support of such research is one of the primary functions of the NIGMS. Indeed, it should be noted that one of the newest techniques now being used to screen individuals for sickle cell disease grew out of recombinant DNA technology developed, in large measure, by NIGMS grantees.

Question: Have any new diagnostic techniques been developed to detect the presence of genetic disease, either prenatally or in other affected individuals?