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National Institutes of Health.

Division of Research Resources



Annual Report.
July 1, 1975- j™ e 30, 1976



United, States. ,a/ Trut//ete* of fea+tf, , 2)f/&s<3+J



'/ rfessssrc/? Resources.



ANNUAL REPORT 4cffvi

FISCAL YEAR 1976
(July 1, 19 75- June 30, 1976)

DIVISION OF RESEARCH RESOURCES



National Institutes of Health
Bethesda, Maryland 20014



TABLE OF CONTENTS

Report of the Director 1

Report of the Deputy Director 5

Animal Resources Program 13

Biotechnology Resources Program .' 31

Chemical/Biological Information-Handling Program 53

General Clinical Research Centers Program 87

Biomedical Research Support Program 99

Minority Biomedical Support Program. 109

Office Grants and Contracts Management 115

Office of Program Analysis 117

Office of Science and Health Reports 119



iii



REPORT OF THE DIRECTOR
Dr. Thomas G. Bowery



Report of the Division Director

related - " ^ ^^ ° f the DireCt ° r ' NIH ^ -gage in a study

" . . .to the administrative structure of DRR and how
thxs mxght be modified to better utilize management
resources and assure coordination of programs?"

t^°I 8ani ! at , i0n Pl3n Wh±Ch WaS the result °£ studies conducted by DRR
program and administrative staff was dpvpinno^ t- ", y UKK
that would achieve better uti^^ de 7 loped - ^ Proposed improvements
among the Divitwc utilization of personnel, greater cohesion
among the Division s programs, and enhanced effectiveness in realizing
the Division's contemporary primary goal and basic objective: §

• To identify and meet the research resource needs and
opportunities of the NIH

• To conceive, create, develop, and assure the availability
of those resources that are essential for the effective
conduct of biomedical research.

The internal reorganization of the Division is based on the establishment
Sl2ri° f f ^ ^tefirative Division-wide functional sy^tems^ha
will enhance the unique strengths of our five highly differentiated

SinorT'*:' 8 ';.^ 1 ReSOurces p r°g~m, Biotechnolo gy ^sources Pr ogram
Minority Biomedical Support Program, Biomedical Research Support Program

Pro^a"^ neral R6SearCh SUPP ° rt) ' Gen « al Clinical ResearTcenters

^Zt, SVS TT 3re Pr ° 8ram Directio *. Scientific and Technical Merit Review
Grants and Contracts Management, Integrated Information Management S
Scientific and Health Communications. 8 ' a

^." Ve Pr ° gram Dir ^tors aftd the five heads of each system constitute a
Divisional Resource Directorate to assure that the programs and the
functional systems are well formulated, understood/and executed to meet

to b^HH 10 ,T te u P ° rary g ° al and o^ctive. Areas of mai or emphasis
to be addressed by the Resource Directorate are Division-level program

llt:Ztt a ttr StTati °^ and eValUatl ° n; and P ° liCy ^rmulation Pr : n 8 d ram

The strength of this mixed mode organizational concept of five differentiated
tHense" « ™ integrative functional systems lies in its capability
tinlT ? serve the changing research resource needs of the nationwide
biomedical research community and the NIH. nationwide

With the official acceptance and implementation of plan by the Director
NIH i„ October 1975, the Resource Directorate has turned Its coUective'



attention to the identification, prioritization, and establishment of even
more effective processes for dealing with two broad areas:

Management Action Issues

• Development of a Five-Year Plan to include specific objectives,
steps to reach those objectives, including the development of
new programs and/or modif ication of existing programs.

• Development of a process to followup DRR/Institute Interfacing
with tangible working agreements between DRR programs and
various Institute components.

• The identification of a process to provide complete research
highlight information from programs. The availability of this
information would be geared to specific management/administrative
milestones during the years.

Management Development Objectives

• Better problem-solving strategies and decision-making techniques.

• Improved decision-making consistent with role change in organization.

• Develop capability for non-hierarchical, functional operations.

• Evoking more points of view and risk taking.

With the Divisional internal realignment of resources essentially completed,
we are focusing our attention on program development through the preparation
of a Divisional Five-Year Plan that is proactive to NIH and grantee
institutional needs. We seek to produce a plan that will lead and shape
the budgetary allocation process rather than a plan dictated by the
budgetary mechanics of the current "Forward Plans . "

i
Thus, we look forward to the challenges and opportunities we anticipate
from the report of the Scientific Mission Study currently being
conducted by a distinguished outside panel of 15 specialists through a
coordination contract with Bolt Beranek and Newman, Inc. of Boston,
Massachusetts .



REPORT OF THE DEPUTY DIRECTOR
Dr. James F. O'Donnell



Report of the Deputy Director

A significant portion of the Deputy Director's efforts during Fiscal Year 1976
was directed to the establishment and development of a Divisional Scientific
and Technical Merit Review System. The rationale for initiating a change in
the DRR review system was based on the traditional but recently restated
policy of the NIH that there should be a rational separation of scientific and
technical merit review from program operations. Such a system has as its
stated goals:

• increasing the mutuality of program knowledge and a sharing
utilization of health scientist administrator personnel among
the five DRR programs , and

• decreasing the subtle but inherent conflict of interest involved
in having the four roles of program planning, program development,
application review, and program evaluation under the direct leader-
ship of an individual program director.

The major features of the newly implemented review system are as follows:

1. Overall responsibility for the initial, scientific, and technical
merit review of research (resource) and training grant applications
assigned to the DRR for initial review rests with the Deputy Director,
DRR. The Deputy Director also has the responsibility for overseeing
review functions of the National Advisory Research Resources Council
(NARRC) .

2. Health scientist administrators, who are not the directors of DRR
programs, have been selected as executive secretaries of the DRR
Initial Review Committees.

3. Executive secretaries have responsibilities relating to the review
functions of the committees; Program Directors have responsibilities
relating to the program advisory functions of the committees.

It is the intent of the Division to seek authority to establish a program
advisory committee for the Biotechnology Resources Program. Although the
Program has no review activities, the lack of an established program committee
results in a serious deficiency of high quality advice for the Program staff.

Program staffing problems of a year ago have been significantly ameliorated by
the selection of Dr. Suzanne Stimler as the Director of the Biotechnology
Resources Program, Dr. Francis Kendrick as Director of the Biomedical Research
Support Program, and Dr. Leo Whitehair as Director of the Primate Research
Centers Section of the Animal Resources Program. Several additional health
scientist administrators have been added to the various Program Branches.

The Deputy Director has served as the project officer on the contract with
Bolt Beranek and Newman, Inc., of Boston. Bolt Beranek and Newman has the
responsibility to coordinate the evaluation of the scientific mission of the
Division. The contract was let on July 15, 1975, and is scheduled to



terminate on October 1, 1976. The initial efforts of the contractor dealt
with the selection, following the concurrence of the Deputy Director, NIH, of
a 15-member evaluation panel. The panelists are:

Dr. Irwin W. Sizer

Co-Chairperson

Massachusetts Institute of Technology

Dr. Linda S. Wilson

Co-Chairperson

Associate Vice Chancellor for Research

The Graduate College

University of Illinois

Dr. Carleton B. Chapman

President

The Commonwealth Fund

Dr. Clifton 0. Dummett

Associate Dean for Extramural Affairs

School of Dentistry

University of Southern California

Dr. Marvin A. Jackson

Chairman

Department of Pathology

Howard University College of Medicine

Mr. Jonathan Leff

Director of Special Publications

Consumers ' Union

Dr. Robert R. Marshak

Chairman

Department of Medicine

School of Veterinary Medicine

University of Pennsylvania

Dr. Bruce H. McCormick

Professor

Department of Information Engineering

University of Illinois at Chicago Circle

Dr. William D. McElroy

Chancellor

University of California at San Diego

Dr. Joseph L. Melnick

Chairman

Department of Virology and Epidemiology

Baylor College of Medicine



Dr. Frederick Hosteller

Chairtwn

Department of Statistics

Harvard University

Dr. Richard M. Restak

(M.D. -Private Practice in Neurology)

Dr. Henry W. Riecken'

Professor

Department of Behavioral Medicine

University of Pennsylvania School of Medicine

Dr. Elizabeth S. Russell
Senior Staff Scientist
Jackson Laboratories

Dr. James B. Wyngaarden

Chairman

Department of Medicine

Duke University Medical Center

The first meeting of the Panel, held in October 1975, was devoted to present
tions by DRR staff concerning the Division's programs and organization. The
Director and Deputy Director of NIH also met with the panel and discussed th
purposes of the evaluation study. Several expert consultants for each of th
programs were selected to supplement the subsequent tasks of the panelists.

Primary and secondary data have been provided the panelists, which in additio:
to the information they have obtained through a considerable number of
institutional visits and interviews with NIH officials, will form the basis i
the panel's report.

We anticipate that the Mission Study Report will serve as a very useful
document for staff and Council dialogue in the development of a Five-Year PI
for the Division.



DRR BRANCH REPORTS



11



Fiscal Year 1976 Annual Report

Animal Resources Program
Division of Research Resources

INTRODUCTION

The overall objective of the Animal Resources Branch (ARB) is to
support resource projects that provide, or enable biomedical scientists
to effectively use, animals in human health related research. Special
attention is given to those animal resource activities that are broadly
supportive of the missions of the various NIH components. The Branch
objectives are accomplished through a Primate Research Centers Program
a Laboratory Animal Sciences Program, and Research Contracts.

PRIMATE RESEARCH CENTERS PROGRAM

The seven Primate Research Centers were established with Federal funds
in the early 1960 's to provide unique research environments for the use
of nonhuman primates in many important areas of biomedical research.
The core operations of the Centers are funded by grants from the Animal
Resources Branch. The Centers have continued to make many significant
contributions in the forefront of biomedical primatology. During the
past year, many important contributions were made in areas including
reproductive biology, neural control of the cardiovascular system, lung
diseases induced by environmental agents, infectious diseases,
nutritional and metaboloic diseases, and behavioral sciences.

Core financial support provided for the Centers by this program has
permitted the 132 core staff scientists to conduct biomedical
research on a total of 98 grants and contracts with total funding
of $5,214 million. In addition, the 253 collaborative and affiliated
scientists from a number of universities utilized the facilities and
other resources of the primate Research Centers to conduct investi-
gative research on 120 grants and contracts with total funding of
$7,092 million. The Centers also provided the research environment for
163 graduate students to pursue their thesis research. The program
provided salary support for 164 doctoral level staff and technical
and administrative personnel.

During the past year, problems associated with obtaining sufficient
numbers of nonhuman primates for biomedical research use have remained
at a critical stage. Therefore, domestic breeding of the various
primate species most useful to the Centers ' research program has
continued to receive special emphasis. Approximately 1,100 infant
primates and fetuses were produced by the Centers during the year,
representing approximately 50 percent of their annual requirements. Small
nuclear breeding colonies of approximately 24 less commonly used primate
species were also maintained to assure their survival for future research
purposes .

The missions of the seven Centers and selected examples of their
research activities are as follows:

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OREGON PRIMATE RESEARCH CENTER

The missions of this Center are in the areas of reproductive biology,
and cardiovascular, metabolic and immune disease. An example of
their research accomplishments is as follows :

Cholesterol Gallstones in Squirrel Monkeys:

Investigations have shown that squirrel monkeys ( Saimiri sciureus )
develop cholesterol gallstones when fed several different types of
semipurified diets. Studies have been made to determine the factors
that are associated with gallstone formation and of the mechanisms
involved in their formation. Diets containing cholesterol and
safflower oil (unsaturated fat) were found to consistently cause
gallstone formation. Male castrates were noted to be particularly
susceptible to gallstone formation, although no difference was detected
in gallstone prevalence between normal, intact male and female animals.
Studies also revealed that the highest rates of cholesterol absorption
were consistently found in animals fed a combination of safflower oil
and cholesterol.

DELTA PRIMATE RESEARCH CENTER

This Center's primary mission is in the area of infectious diseases
research. An example of their accomplishments during the past year is
as follows:

Filariae of Man in Primates :

Studies have been made to determine the relationship of certain types
of filariae (nematode endoparasites) of several nonhuman primate
species (chimpanzee, rhesus monkey, patas monkey) to several types of
human filariae. Comparative morphological studies of these human and
nonhuman primate endoparasites were made. The " per s tans - like" filaria
of the chimpanzee was shown to be virtually identical to Dipetalonema
perstans (filaria) of man in the same geographical area (Cameroon, West
Africa) . The parasite in the chimpanzee offers an excellent model for
the study of the behavior and other biological aspects of the human
parasite. It also provides an opportunity to investigate the patholo-
gical changes which may be produced by the parasite in its definitive
host. Other studies involved the successful experimental transfer of
a human strain of Loa loa (threadlike filarial roundworm of West Africa)
via infected vectors ( Chrysops , a tropical tabanid fly) to produce
patent infections in three species of monkeys . Work is now focused on
the development and onset and course of patency, as well as the involve-
ment of the spleen in suppression of peripheral microfilaremia.



14



YERKES PRIMATE RESEARCH CENTER

The major missions of the Yerkes Center are in the areas of neural
and behavioral research, immunology, Great Ape reproductive physiology
and the study of neoplastic diseases. The following is an example of

these research activities:

Physiological Concomitants of Drug Abuse:

Investigations were focused on the diverse and varied effects which
pharmacologic agents (drugs) can have on behavior of intact, conscious
animals due to their actions on the central nervous system. This work
demonstrates that several drugs (including d_ - amphetamine and
chlorpromazine) can have marked effects on operant behavior in nonhuman
primates (squirrel monkey and chimpanzee) when administered at doses
comparable to those used in humans. The data indicated that the
behavioral effect of the drugs was determined by the rate at which
the behavior was ongoing prior to drug administration. The drugs,
d_ - amphetamine and chlorpromazine increased the rate of behavior
when it was low in rate prior to drug administration and decreased
behavior rates that were high prior to drug administration. The effects
of cocaine and morphine (alone or in combination with other drugs) were
also studied in the squirrel monkey and chimpanzee. These drugs increased
low rates and decreased high rates of behavior. Studies are in progress
to determine the effects of cocaine on heart rate, mean systemic
arterial blood pressure and body temperature.

WASHINGTON PRIMATE RESEARCH CENTER

The mission of this Center is neurophysiological research with particular
relationship to control mechanisms of the cardiovascular system. In
•addition, the collaborative research program involves a large number
of scientists of many biomedical research disciplines. An example of
the research activities at this Center is as follows:

Central Nervous System and Endocrine Control of Temperature and
Metabolism:

Studies were made to determine the response of chair-adapted male
baboons to acute and sub-acute cold exposure. Measurements were made
of various serum plasma and urinary hormone levels to assess the
increase of thyroidal activity and activation of the hypothalamic-
pituitary-thyroid axis by cold stress. Arterial blood pressure and
heart rate (cardiovascular parameters) were also monitored during cold
exposure and were noted to rise as core temperature fell. These latter
findings suggested inhibition of the baroreceptor reflex due to the
developing core hypothermia. In contrast to results found in other
experimental animals (e.g., rat, goat), the nonhuman primate does not
exhibit a prompt activation of the thyroid gland via hypothalamic



15



thyrotrophin-releasing-hormone (TRH) and pituitary thyrotrophin-secreting
hormone (TSH) . Rather, the first indication of hypothalamic stimulation
of the pituitary-thyroid axis did not appear in the baboons until the
third day of cold stress and moderate hypothermia.

WISCONSIN PRIMATE RESEARCH CENTER

The basic research missions of the Wisconsin Center are in the areas
of primate behavior, reproduction, and neuroscience. An example of
research activities at this Center is as follows:

Prenatal Androgens and the Development of Behavioral Sex Differences :

Studies were made with rhesus monkeys to assess the relative effectiveness
of two different androgens (male sex hormones); namely, testosterone and
dihydrotestosterone, on the development of behavioral sex differences.
Since both hormones are active in the display of adult sexual behavior,
efforts were made to determine whether dihydrotestosterone is active
in the prenatal organization of sexually dimorphic behaviors . Twelve
pseudohermaphrodites were studied. Some of these animals were produced
by exposure prenatally to varied doses of testosterone propionate (TP)
over different time periods, while other animals were exposed prenatally
to varied doses and time treatments with dihydrotestosterone propionate
(DHTP) . The findings clearly indicate that prenatal treatment with
DHTP is effective in altering morphological and behavioral traits
toward the masculine form. However, external genitalia of the animals
were not well masculinized. Another finding from this study is that the
mother-peer rearing condition does allow early and full development of
mounting behavior in both male rhesus and rhesus pseudohermaphrodites.

NEW ENGLAND PRIMATE RESEARCH CENTER

The major core program mission of this Center is in the areas of
infectious diseases and primate pathology. In addition, a large number
of collaborating scientists conduct a major portion of their research
activities at the Center. An example of the research projects is as
follows:

Effect of Herpesvirus saimiri in Human Cell Cultures:

Human cell cultures were successfully infected with Herpesvirus saimiri .
The virus was found to multiply in these cell cultures but did not induce
a complete cytolytic infection. The infectious virus was recovered up to
187 days after initial infection. Cell fusion techniques resulted in the
recovery of infectious virus from the latently infected human cell
cultures 347 days after initial infection. Therefore, it was fully
demonstrated that this primate oncogenic virus was capable of infecting
human cell cultures, first as a persistent infection and later as a
latent infection.



16



CALIFORNIA PRIMATE RESEARCH CENTER

The mission of this Center is in the areas of environmental health
sciences and infectious diseases. An example of their research
activities is as follows:

Influence of Acid Aerosols on Production of Chronic Lung Disease:

Because of the prospects of greater use of sulfur-containing fossil
fuels for energy needs in the future, comparative studies were made with
three species (rhesus monkey, guinea pigs and rats) to assess the
biological effects of sulfuric acid (H2SO4) . The animals were
continuously exposed to acid aerosols generated from vaporized sulfate
(SO3) entering a humidified airstream. Pathological studies on lung
tissue from the animals following exposure revealed striking differences
in species susceptibility to acid aerosol induced pulmonary damage.
The respiratory tract of the rhesus monkey and rat were found to
have a remarkable resistance to sulfuric acid induced morphological
damage, in contrast to the extreme sensitivity of the respiratory
airways of the guinea pig to acid aerosols.

LABORATORY ANIMAL SCIENCES PROGRAM

The Laboratory Animal Sciences Program (LASP) assists institutions in
developing and improving animal resources for biomedical research and
training through the award of research and resource grants and contracts.
Currently special program areas include support for animal colonies of
unusual and special value for research; studies directed at finding
animal models which are needed for research on human diseases; projects
to assist institutions to comply with the legal and policy requirements
for care of laboratory animals; laboratories for the diagnosis and
control of disease of laboratory animals ; research related to improving
health care and determining environmental requirements of animals used
in research; reference and information centers dealing with selected
problems ; and research training of specialists in the field of laboratory
animal medicine. The Program awarded funds totaling $8,044 million in
fiscal year 1976, which supported 73 discrete animal research and
resources projects, 5 institutional fellowship programs, 4 individual
fellowship awards, and 16 contracts.

ANIMAL MODELS AND SPECIAL COLONIES

The major objectives of this program area are (1) to define,
characterize, and exploit the relevant biological attributes of
selected animals which display potential for use in several areas
of biomedical research; (2) to establish, improve, or expand special
colonies of well characterized animals which are of proven value for
specialized areas of biomedical research, but which are not generally
available from other sources; and (3) to preserve unique and valuable
stocks and strains of animals which may otherwise be lost due to particular
circumstances .



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Support for projects related to the establishment of special animal
colonies and animal model development increased slightly from FY 1975
to $1,459,306, but the number of projects was decreased by 2 to a total
of 19. During FY 1976, 13 of these resources provided support for 55 NIH
funded research projects having a total funded value of $4,690,808. Support
was provided to an additional 42 research projects which received funding
from other sources in the amount of $1,115,901.

The majority of the currently active projects are related to vertebrate
species such as rats, mice, guinea pigs, hamsters, dogs, cats, rabbits,
nonhuman primates, armadillos, and amphibian species. However, interest
in the development of models is not limited to vertebrates. For
example, the research potential of several marine invertebrate species
has led to support for their development as research resources. A
contract is supporting the development of methods for rearing the sea
hare in the laboratory. The sea hare is a marine mollusk with large


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