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ANNUAL REPORT
FY 1975



NATIONAL INSTITUTE

OF

GENERAL MEDICAL SCIENCES



NATIONAL INSTITUTES OF HEALTH
BETHESDA, MARYLAND



e<#, tof-^l-7^



NIGMS ANNUAL REPORT

FISCAL YEAR 1975

CONTENTS



Page



THE DIRECTOR'S REPORT

NIGMS Research Training 1

Center Grants 2

Staff Changes 2

National Advisory General Medical Sciences Council 3
Institute Fiscal Data

Table 1 - By Budget Mechanism 3a

Table 2 - By Program : . ; _..,-, 3b
Appendix: NIGMS Research Training ... ;

National Research Service Awards

Predoctoral Institutional 5

Postdoctoral Institutional ,, , - ;; ,- .. 6

Individual (Postdoctoral) 6

Research Training Support 9



PROGRAM REVIEWS

Biomedical Engineering

Scope _,. h : , - ? ■ 12

Objectives ,.,, ... -, : .-. : s [ . . 12

Research 13

Research and Development 13

Automation of Clinical Laboratories 14

Research Training 16

Research Highlights 17

Contracts 21

Appendix: Support of Research on 26

Ultrasound by NIGMS



Cellular and Molecular Basis of Disease

Scope 30

Objectives 30

Research 31

Pathobiology 31

Cell Structure and Dynamics 31

Membrane Structure and Function 31

Enzyme Catalysis and Regulation 31

Proteins and Macromolecules 32

Biomolecular Models anc Mechanisms 32

Manpower - 32

Research Highlights 34



CONTENTS Page

Clinical and Physiological Sciences

Scope 44

Objectives 44

Research and Manpower 45

Anesthesiology 45

Trauma and Burns 45

Behavioral Sciences and Adaptation 46

General Medicine 47

Research Highlights 47



Genetics

Objectives, Scope, and Role 51

Overview of Program Activities 52

Specific Issues 53

Recombinant DNA Molecules 53

The Evaluation of Genetic Counseling 54

Research Highlights 55

Contracts 63



Pharmacology-Toxicology

Introduction 67

Manpower 68

Pharmacology Research Associate Program 69

Research Career Development Awards 69

Program Administration 69

Organization and Management 69

Support 69

Communication 70

Research Highlights (Clinical) 70

Research Highlights (Basic) 76

Contracts 80



THE DIRECTOR'S REPORT

The Institute has completed its first year with a new Director. This has
been a year during which no major organizational changes have taken place,
while the Director and her immediate staff have reviewed in detail each
program area as well as the totality of mechanisms that each has been using
to fund research and research training. As was discussed in last year's
annual report, each program director has full responsibility within his
given area. Above and beyond this, as seems appropriate, based partially
on mandated areas of emphases but even more on the preceptions of program
scientific staff, growth is encouraged in areas in which innovative research
seems likely. Furthermore, since there is considerable overlap between
program areas such as "pharmacogenetics," "cellular and subcellular changes
induced by trauma," "behavioral genetics," and "application of engineering
at the cellular level," emphasis has been and will continue to be placed
on interactions, cooperation and exchanges between programs.

Although the budget for this Institute, as for all others, remained quite
uncertain for much of the year, the final appropriation enabled NIGMS to
fund quality research projects adequately. Furthermore, restoration of
previous cuts in noncompeting research grants was possible in most instances.

NIGMS RESEARCH TRAINING

A major activity of the Institute staff during fiscal '75 was the development
and implementation of the new National Research Service Award Program, which
was authorized by Congress on July 12, 1974, through Public Law 93-348.
This law replaced the earlier, more general authority for support of research
training under which the Institute had been operating. A grandfather clause
gives the Institute authority to phase out existing programs, including
the so-called "Weinberger Program," in an orderly manner. This means that,
for an interim period, the Institute is operating three different training
programs .

Since the late 1950' s, the NIGMS had gradually developed a major program for
research training at both the predoctoral and postdoctoral levels covering
some 20 major discipline areas and serving future needs for trained investi-
gators not only in the NIGMS research programs, but for all of the Institutes
at NIH. In January 1973, the Government began a phase-out of these grants
which was interrupted a year later, but, in effect, reinstated in July 1974
when the old authority was replaced by Public Law 93-348. In the summer of
1973, a postdoctoral research training program, the so-called "Weinberger
Program," had been begun, offering support in a limited number of research
areas judged to be in particular need of additional manpower. A similar
feature of P.L. 93-348 required the Secretary, DHEW, to limit support of
research training to areas for which a shortage of research manpower had been
shown to exist. The National Academy of Sciences was requested to provide
the analysis and to make recommendations in this regard. Because of the
time requirements for such an analysis, the Institutes, including NIGMS, were
allowed to announce support in areas which, in their best judgment, were in
particular need for research manpower. In the opinion of the Institute
staff, and supported broadly by the academic community, this purpose would



be served by encouraging the development of increased breadth in graduate
science education. Five multidisciplinary predoctoral training programs
were announced to the public in December 1974. In order to meet more speci-
alized objectives, four institutional and 10 individual postdoctoral programs
were announced. In addition, the Institute was able to re-start the MARC
Faculty Fellowship Program and further formulate plans for a prebaccalaureate
program, although no awards have been made yet. Descriptions of the areas
of support which were announced are in the appendix.

Because of unavoidable delays in formulating guidelines for the institutional
awards, the final announcements were not made until December 1974, with a
deadline for receipt of applications in February, and final study section
review in April 1975. With the short time for preparing applications, it
is probable that not all potential applicants were able to submit proposals.
In spite of this, the Institute received 312 applications for institutional
awards, which represented a major review task for the Division of Research
Grants. Although project site visits are often helpful in the review of
grants of this kind, time and staff were not sufficient to allow any to be
made. Tables showing the institutional and individual awards made in
FY 1975 by program as well as the phase-out awards in the old program are
included in the appendix.

CENTER GRANTS

The Institute extended its experimental procedure for review of center grant
applications from the review of the Molecular Pathology Center Grants to
that of Burn and Trauma Research Centers and will be extending it to the
review of Anesthesiology Centers as well. In this procedure, the Division
of Research Grants first reviews each individual project using an appropriate
initial review group; and the total project, along with the request for core
support, is then reviewed by a special study section which determines whether
the proposals, considered together, form an integrated whole. The procedure
is still evolving, and a number of problems which have arisen are being
solved in order to improve it.

An alternate method was used by the Biomedical Engineering Research Program,
in which several applications for research centers were reviewed at the same
time by a single special review committee — a method which provided for
excellent review.

STAFF CHANGES

A new Director, Dr. Ruth L. Kirschstein, was appointed. Previous appoint-
ments were reconfirmed as follows:

Dr. Leo von Euler - Deputy Director

Dr. Arthur Heming - Associate Director for Program Activities

Dr. Charles Miller - Special Assistant for Manpower

Dr. Vincent Price - Special Assistant



A number of new professional members joined the staff:

Dr. Sara Gardner - Pharmacology-Toxicology Program

Dr. Sue Badman - Cellular and Molecular Basis of Disease Program

Dr. Americo Rivera - Biomedical Engineering Program

Dr. George Cosmides and Dr. Dorothy Brodie transferred to other Institutes,
and Dr. Matti Al-Aish transferred from the Cellular and Molecular Basis of
Disease Program to the Biomedical Engineering Program.

NATIONAL ADVISORY GENERAL MEDICAL SCIENCES COUNCIL

During FY 1975, one of the new and highly valued members of the NAGMS Council,
Dr. James H. Birnie, died unexpectedly; and three other members — Miss Susan
Norton, Dr. Clifford Gurney, and Dr. Robert Murray — completed their terms of
office. Their contributions to the Council were significant and they will
be missed. Three new members, Dr. Louis Levin, Dr. Dean Warren, and Ms. Helen
Chang, joined the Council in March. The Council agreed to continue to review
the activities, programs, and problems of each of the five program areas by
forming into subgroups which will study the programs in detail during the
coming year.



Research Grants
Training Grants
Special Programs (Centers)
Fellowships

Research Career Awards
Management and Services
R&D Contracts
Scientific Evaluation
TOTAL



BUDGET MECHANISM






Table 1






(FY 1975)


Total Costs




Number


(thousands)
$ 99,574


Percent


1,522


53


409


35,123


19


34


20,257


11


520


16,525


9


290


7,007


4


-


6,142


3


16


2,195


1


_


406
$187,229


_


2,791


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APPENDIX

NIGMS RESEARCH TRAINING

NATIONAL RESEARCH SERVICE AWARDS



c



Areas of Support
Predoctoral Institutional National Research Service Awards

1. Cellular and Molecular Biology

Programs should be of a cross-discipline nature in cellular and molecular
sciences, involving cooperation between two or more Ph.D. degree programs or
departments (such as anatomical sciences, biochemistry, biophysics, genetics,
microbiology, and pathology), with representative faculty members capable of
providing integrated training and offering thesis research opportunities at
the cellular and molecular level.

2. Genetic Mechanisms and Regulation

Training should focus on the principles and mechanisms of genetics, drawing
upon a number of disciplines and research areas such as chemistry, bio-
chemistry, cell regulatory processes, and developmental biology. The goal
of the program is further understanding of molecular and physiological
mechanisms as well as population and behavioral aspects of heredity and of
genetic disease.

3. Pharmacological Sciences

Training should emphasize the acquisition of competence in the broad fields
of pharmacology and toxicology to conduct research on drug actions and effects
in living cells, in' animals, and in man — ranging from the chemical to the
clinical level, with thesis opportunities also included in such areas as bio-
chemistry, physiology, medicinal chemistry, pharmacogenetics and behavioral
pharmacology and other cognate fields, via collaborating departments.

4. Systems and Integrative Biology

Research training should center around cross-field graduate programs involving
such disciplines and departments as physiology, bioengineering and biomathe-
matics; or physiology, nutrition and behavioral science; or other combinations
of disciplines for building research competence, usually toward investigating
organ systems and/or integrative functions of animals and man.

5. Medical Scientist

Special programs of integrated medical and graduate research training required
to investigate problems of diseases in man. These interdisciplinary programs
assure the highly selected trainees access to the full range of pertinent
biological, chemical, physical and social sciences as well as medicine.
Graduates may be expected to enter medical school faculties in either basic
science or clinical departments to conduct research and to translate new
knowledge directly to clinical teaching, practice, and other aspects of
health care.



Postdoctoral Institutional National Research Service Awards |

1. Basic Pathobiology

Advanced training in a research environment affording interdisciplinary
opportunities for post-Ph.D.'s from basic biological sciences and biophysical-
biochemical fields to participate in fundamental biomedical research problems
including research on, or applicable to, an understanding of pathologic and
disease systems; and to provide post-M.D.'s with an in-depth working knowledge (
of the principles and tools of basic science for research at the cellular and
molecular levels in both normal and diseased states.

2. Genetics (with emphasis on Medical Genetics)

Advanced and special research training in genetics, utilizing and applying the
principles and fundamental mechanisms of genetics toward the understanding of
human genetic disease. Postdoctoral trainees to be drawn from diverse basic
biological and medical backgrounds for research study with faculty represent-
ing various approaches to genetic research — ranging from biochemical genetics
to human population genetics. Preference will be given to applications
presenting training opportunities in medical genetics.

3. Clinical Pharmacology

Advanced research training in basic and clinical pharmacology and planned
studies to acquire fundamental scientific knowledge and research techniques ^
in areas such as chemistry, biochemistry, physiology, genetics, certain
behavioral science subdisciplines and clinical research specialties, to make
individuals holding the M.D. or Ph.D. degree competent to investigate, in
depth, the effects and the mechanisms of drug actions in humans.

4. Trauma and Burn Research

Special multidisicplinary, research-based program to train postdoctoral
scientists to become capable of advancing our knowledge of the body's complex
reaction to trauma and burn injuries. The supervisory staff should include
trauma surgeons and/or burn specialists as well as basic scientists, and the
program director is expected to emphasize research training in related fields
such as physiology, biochemistry, and microbiology.



Individual (Postdoctoral) National Research Service Awards

1. Anesthesiology

Research training support is offered to individuals with the M.D. degree^/
and special interest in anesthesiology who seek to acquire fundamental
knowledge and competence in an appropriate basic science field that will
provide an investigative background needed to strengthen the fellow's
capability for contributing significantly to research in anesthesiology.



(



1/ Where the M.D. degree is mentioned or implied, it refers also to
other medical, professional degrees such as D.D.S., D.O., D.V.M.



2. Cellular and Molecular Biology

Awards are intended to assist individuals holding the Ph.D. degree in the
biological or physical sciences in acquiring special advanced research
training toward developing necessary cross-field knowledge for a research
career in cell sciences — in areas such as membrane structure and function,
cell motility, differentiation, enzyme catalysis and regulation, and pro-
teins and other macromolecules, which are essential for an understanding of
living systems at the cellular-molecular level. The program also would
provide individuals holding the M.D. degree with the requisite background
and skills in basic research to bring new knowledge at the subcellular and
molecular level into medicine.

3. Genetics

Awards are made for advanced research training, developing and utilizing the
principles and fundamental mechanisms of genetics and related fields toward
further understanding of genetic regulatory processes in general and of
human genetic disease. Applicants may seek research study with investigators
representing various approaches to genetic research — ranging from biochemical
genetics to human population genetics.

4. Basic Pathobiology

Advanced training in a research environment affording interdisciplinary
opportunities for post-Ph.D.'s from basic biological sciences and biophysical-
biochemical fields to participate in fundamental biomedical research leading
to an understanding of pathologic processes; and to provide post-M.D.'s with
an in-depth working knowledge of the principles and tools of basic science
for research at the cellular and molecular levels in both normal and diseased
states.

5. Systems and Integrative Biology (Bioengineering and Physiology)

Research training support is offered to individuals holding the M.D. or Ph.D.
degree who seek to apply engineering, physical and/or mathematical principles
to biological and medical problems. Support is also available to individuals
seeking competence in the in-depth and quantitative study of organs and
systems involved in integrated physiological functions of animals and man.

6. Pharmacological Sciences

Training should emphasize the acquisition of competence in the broad fields
of pharmacology and toxicology to conduct research on drug actions and effects
in cells, in animals, and in man. Proposals may range from the chemical to
the clinical level of study and include training opportunities in such areas
as biochemistry, physiology, medicinal chemistry, genetics, and other cognate
fields.



7. Behavioral Science Related to Medicine

Research training support is offered to individuals holding the Ph.D. degree
who seek competence to apply the knowledge and methods of such behavioral
science disciplines as psychology and sociology to medical/clinical problems,
or to individuals with backgrounds in medicine or the fundamental biomedical
sciences who seek appropriate training in behavioral sciences. The training
should prepare individuals tc conduct research in such developing fields as
behavioral genetics, the behavioral aspects of trauma and its treatment, and
pain research.

8. Clinical Laboratory Sciences

Research training for individuals holding the Ph.D. degree in a basic bio-
medical science who seek to apply this knowledge to the development of
clinical laboratory science. Individuals with a medical background who seek
research training in depth in a basic biomedical science with the goal of
applying this knowledge to clinical laboratory medicine are also eligible.

9. Trauma Research

The goal of this program is to educate individuals capable of advancing our
knowledge of the body's complex reactions to trauma and burns. Candidates
are expected to emphasize research training in such fields as physiology or
biochemistry and should be under the supervision of a staff that includes
both trauma surgeons or burn specialists and basic scientists.

10. Epidemiology

Research training for individuals holding the M.D. degree who seek broad
competence to study epidemiological problems. The range of problems in
epidemiology has now become so wide that increased specialization and rigorous
preparation are required to advance this field.



FY 1975 Awards in Research Training



Table I

Institutional NRS Awards in FY 75

(Dollars in thousands)



Institute


Program Area


Appl


ications


No.


Trainees


Total


Program


of Support


Rev'd


Appvd .


Awards


Pre


Post


Costs


Cellular &


Cellular &














Molecular


Molecular Biol.


78


58


33


365





$3,457


Basis of


Pathobiology


36


29


17





67


1,213


Disease


Medical Scientist


24


17


11


80





874


Genetics


Genetic Mech-
anisms and
















Regulation


34


29


22


155





1,360




Genetics
















(Medical)


24


14


12





40


699


Pharmacology-


Pharmacological














Toxicology


Sciences


52


38


32


137





1,263




Clinical Pharm.


14


7


7





14


266


Biomedical


Systems &














Engineering


Integrative
















Biology


12


7


4


22





239


Clinical &


Systems &














Physiological


Integrative



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Online LibraryNational Institute of General Medical Sciences (U.Report of program activities : National Institute of General Medical Sciences (Volume 1975) → online text (page 1 of 9)