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One of the biggest problems facing the biotechnology industry is that,

although scientists know the order of the subunits that make up a given

protein of potential commercial value, such as a new drug or a hormone, they

do

not know what directs the protein to fold into the three-dimensional shape

that is required for its activity. As a result, it is impossible to

synthesize some proteins and difficult to modify others, to improve their

effectiveness, stability, or yield. Scientists seeking to understand protein

tolding have used many approaches, including attempts to design a synthetic

protein "from scratch" to see if it can be made to fold as predicted. Now,

after many years of effort, 1 tean led by NIGMS grantees Dr. David Richardson

and Jane Richardson of Duke University has succeeded in designing just such a

synthetic protein. This accomplishment may lead Industrial scientists to new

methods to synthesize therapeutic agents on a comercial scale.

A group of researchers, working with NIGMS support at the Genex

Corporation in Maryland, recently received a patent for a new class of bloengineered proteins that they call single-chain antigen-binding proteins.

They hope that these proteins can be used to carry either radioactive or toxic

substances that could detect or kill cancer cells.

Some of these proteins

have already been targeted, and successfully attached, to cells in mouse

tumors.

The scientists say that the proteins are more effective than other

substances that seek out and attach to tumor cells, because they can penetrate

a tumor more deeply and are cleared from the body more rapidly.

Conclusion

In closing, I would like to quote Dr. Leon Rosenberg, dean of the Yale

University School of Medicine, who said in an interview with Tipe magazine

published in December 1990 that "there are more opportunities than ever to

ferret out the secrets of human biology and apply those secrets to the

reduction of human suffering....Our country has benefited enormously from the

support of much unfocused basic research because in totally unexpected ways it

has provided insights into medical problems that have been of enormous

significance." Dr. Rosenberg further said that, in a time of limited

resources, his "first priority is to create an environment in which talented

young people choose careers in health-sciences research, because without then

our future will be blighted."

This emphasis on basic research and research training mirrors that of

NIGMS

It is through the continued support of these pursuits that our country

will be able to meet some of the challenges of the next decade... and indeed,

the next century.

Mr. Chairman, the FY 1992 budget request for the Institute's research and

research training programs is $833,180,000.

I would be pleased to answer any

questions that you may have.

BIOGRAPHICAL SKETCH OF DR. RUTH KIRSCHSTEIN

October 12, 1926. Brooklyn, New York

Education: A.B., magna cum laude, Long Island University, 1947.
M.D., Tulane University School of Medicine, 1951.

Professional History: 1951-52, Internship. Medicine and Surgery.
Kings County Hospital, Brooklyn, N.Y. 1952-54, Resident, Pathology,
Providence Hospital, Detroit, MI. 1954-55, Trainee of National Heart
Institute and Instructor in Pathology, Tulane University School of
Medicine. 1957-60, Medical Officer, Pathologist, Laboratory of Viral
Products, DBS, NIH. 1960-62, Chief, Section of Pathology, Laboratory
of Viral Immunology, DBS, NIH. 1962-64, Assistant Chief, Laboratory
of Viral Immunology and Chief, Section of Pathology, DBS, NIH.
1964-65, Acting Chief, Laboratory of Pathology, DBS, NIH. 1965-72,
Chief, Laboratory of Pathology, DBS, NIH. 1971-72, Assistant Direc.
tor, Division of Biologics Standards, NIH. 1972-73, Acting Deputy
Director, Bureau of Biologics, FDA. 1973-74, Deputy Associate
Commissioner for Science, FDA. 1974-present, Director, National
Institute of General Medical Sciences, NIH. 1990-present, Acting
Associate Director for Research on Women's Health, NIH.

Professional Organizations: American Assoc. of Immunologists;
American Assoc. of Pathologists; American Society for Microbiology.

Committee Memberships: Invited member of World Health Organization
Expert Group on International Requirements for Biological Substances;
Geneva, Switzerland, 1965 & 1971. Chairperson, NIH Grants Peer
Review Study Team, 1975-76. Chairperson, PHS Genetics Coordinating
Committee, 1976-79. Member, Fogarty International Center Scholars.
in-Residence Advisory Committee, 1977-82. Chairperson, PHS Task
Force on Women's Health Issues, 1983-84. Chairperson, PHS Coor.
dinating Committee on Women's Health Issues, 1984-90. Member, NIH
Advisory Committee for the IOM Study of the Organizational Structure
of the NIH, 1983-84. Member, NIH Peer Review Committee, 1987-88.
Member, HHS Executive Development Board, 1985-present. Member,
Federal Task Force on Women, Minorities and the Handicapped in
Science and Technology, 1987-90. Member, Interagency Working Group
on Minorities, Women and the Handicapped in Science, 1989-present.
Member, Office of Technology Assessment Advisory Committee on Basic
Research, 1989-present. Co-chair, Secretary's Special Emphasis
Oversight Committee on Science and Technology, 1989.present. Co-
chair, PHS Coordinating Committee on Women's Health Issues, 1990-
present.

Honors. Awards: Elected to Institute of Medicine, National Academy
of Sciences, 1982. Doctor of Science, Honoris Causa. The Mount Sinai
School of Medicine, 1984. Honorary Doctor of Laws, Atlanta Univer:
sity. 1985. PHS Special Recognition Award.-group award to PHS Task
Force on Women's Health Issues (Chairperson), 1985. Distinguished
Executive Service Award of the Senior Executive Association, 1985.
Presidential Distinguished Executive Rank Award, 1985. Honorary
Doctor of Science, Medical College of Ohio, 1986. Office of Person-
nel Management Profiles in Excellence, 1989. Dr. Nathan Davis Award
(American Medical Association), 1990.

FINANCIAL CONSIDERATIONS FOR ATTRACTING YOUNG SCIENTISTS

Senator HARKIN. Thank you very much, Dr. Kirschstein. I am going to read a quote from your prepared statement here because it leads right into a question I have been wanting to ask you and also Dr. Raub.

Dr. Leon Rosenberg, dean of the Yale University School of Medicine, said that:

In a time of limited resources, his first priority is to create an environment in which talented young people choose careers in health-sciences research, because without them our future will be blighted.

Well, that leads me to ask about these young people that we are trying to get involved in pursuing careers in research. I understand you have basically the lion's share of the money that goes out for stipends and pay and things like that. Right? Dr. KIRSCHSTEIN. That's

correct. Senator HARKIN. And I don't know that I understand how all this works. I am learning it all the time.

Let's say that you have a young person who just graduated from medical school and has been through their residency training. I think now the average age is probably what? They would be about 32, 33 years old, somewhere in there?

Dr. KIRSCHSTEIN. That's correct.

Senator HARKIN. If I remember reading it correctly, the average debt now of a student getting out of medical school is $40,000 or so?

Dr. KIRSCHSTEIN. I think it is pushing toward about $100,000, sir.

Senator HARKIN. Average? I know private was higher than public.

Dr. KIRSCHSTEIN. Well, it depends on whether the student attended a private or public medical school. You are quite correct. It would be somewhere between those two figures depending on whether it was a private or public medical school. Do you agree, Dr. Raub?

Dr. RAUB. Yes.
Senator HARKIN. We will find out. Let's say it's $60,000.

And about that time they are probably recently married, perhaps starting a family. Let's say that they are at the top of their class. They are very bright, and they want to pursue research at NIH in Dr. Goldstein's department.

Dr. KIRSCHSTEIN. Fine.

Senator HARKIN. And he wants this young person. What will they start out at here? What would you start them at? What would be their salary?

Dr. KIRSCHSTEIN. Well, I think Dr. Goldstein can answer that question better than I can, because I do not have an intramural program to support such individuals. But, depending on how many years the person is out of a residency, the salary at NIH would probably be somewhere around $29,000 or $30,000.

Senator HARKIN. They are just out. I'm saying they are just out of school.

Dr. KIRSCHSTEIN. It's about $28,000 or $29,000.

Senator HARKIN. And you want to get them young and you want to get them in a career of research.

Ďr. KIRSCHSTEIN. It's approximately $28,000 or $29,000.
Senator HARKIN. That is here at NÍH.
Dr. KIRSCHSTEIN. Yes.

Senator HARKIN. Can you tell me how you can live on $28,000 or $29,000 a year with a family and pay off debts from medical school? You get my point.

Dr. KIRSCHSTEIN. I get your point, and it is a very serious one And I think we all have to address it because we need to have this pool of talent that you mentioned. It is absolutely essential.

Senator HARKIN. I agree. I think it may be the most serious problem that faces us right now because we can talk about all these wonderful research things we are doing, but if we do not get these young people and get them into research, you are right. We have an old expression out in Iowa. You eat your seed corn. You do not want to do that. And you can put everything you want into growing the crops and everything, but if you don't have the seed corn for next year, you're out.

MEDICAL SCIENTIST TRAINING PROGRAM Dr. KIRSCHSTEIN. We do have one program that I think can help this situation along. It is the program sponsored by the National Institute of General Medical Sciences to train a young medical student, while he is in medical school for a career as a research scientist. This is the Medical Scientist Training Program (MSTP), the combined M.D./Ph.D. program. We are very pleased—I have mentioned this to you before_to have such a program at the University of Iowa Medical School. These young people get their tuition and a stipend while they are going through what is approximately a 6 to 7 year course of study. They graduate with a dual degree, and have learned the disciplines of research. Graduates of these programs are among the most successful individuals who apply for research grants.

PAYBACK REQUIREMENTS Senator HARKIN. What is their responsibility? What do they have to pay back for all of this?

Dr. KIRSCHSTEIN. The payback is that which the National Research Service Act requires. For every year after the first year of training, they have to pay back 1 year either doing research or teaching. These MSTP graduates are on the road to research careers, and we have not had any difficulty in them fulfilling this payback obligation.

Senator HARKIN. This is the National Research Service Act.

Dr. KIRSCHSTEIN. The National Research Service Act is the authorizing legislation under which the research training activities of NIH at the universities and medical schools for Ph.D. students, M.D./Ph.D. students, and post-doctorals is undertaken.

Senator HARKIN. And under that you have this scholarship pro-
gram or stipend program.
Dr. KIRSCHSTEIN. Yes, sir; through my Institute. That's correct.
HISTORY AND DESCRIPTION OF MEDICAL SCIENTIST TRAINING

PROGRAM
Senator HARKIN. And how long has that been in existence?
Dr. KIRSCHSTEIN. It has been in existence since 1975.

Senator HARKIN. Is it increasing, decreasing, staying the same? How much money? This costs money. Right?

Dr. KIRSCHSTEIN. Yes; the program's size has actually been increasing. I am really very pleased to tell you that we have been able to gradually increase the support so that now we support 788 such students in 29 medical schools throughout the country. The program started 27 years ago with three schools. We gradually increased to about 25 medical schools and then over the last few years we have been able to add four more schools.

Senator HARKIN. That's 788 students. Now, at what point do you get these students? They are through with their undergraduate programs?

Dr. KIRSCHSTEIN. Yes; they start as freshmen or first year medical students. Senator HARKIN. Or Ph.D., you say.

Dr. KIRSCHSTEIN. They receive a combined M.D./Ph.D. degree. By the time they graduate, they have been trained in the disciplines of biomedical research, which is what the Ph.D. degree imparts, as well as in the disciplines and the activities required to be a physician. So, they are beautifully prepared to do biomedical research, primarily clinical research.

INCREASE IN RESEARCH TRAINEE STIPENDS

Senator HARKIN. I am going to have to take another really close look at it. Mr. Hall just informed me that we put $15 million additional in there for each of the institutes for increasing the stipends.

Dr. KIRSCHSTEIN. Yes.

Senator HARKIN. But when you spread that all out over however many you have, it probably doesn't add up to very much.

Dr. KIRSCHSTEIN. These funds are being used to increase the stipends by 3.5 percent in 1991. Another stipend increase, 4 percent above the 1991 level, is proposed for fiscal year 1992.

SALARY AND STIPEND PROFILES FOR RESEARCH CAREERS

Senator HARKIN. Dr. Raub, I probably should ask Mr. Hall this. Do we have here a good outline of the salary structure at NIH from director on down and what the career path might look like for someone who wanted to be involved in research as a career?

Dr. RAUB. We could certainly lay that out for you. I don't believe that information is contained in the budget materials; but we can provide the salary structure from entry level scientists earning

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