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Annual report : National Institutes of Health (Volume 1952) online

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herds, native herds, and problem herds has just started and no results are
available yet. A capillary tube agglutination test, employing stained anti-
/gens, has been devised for the diagnosis of Q fever in cattle. Simple and
specific, the test can be employed as a field tool.


Biophysical Characteristics of Bacteria and Viruses. The objective of
this unit, headed by Dr. C. C. Shepard, is the study of the morphology of in-
tact bacteria and viruses and their component parts. The work centers around
the electron microscope, but corroboration and clarification is constantly
sought with other technics such as electrophoresis, ultracentrif ligation, and
immunological and chemical methods . During the past year a study of B.
tularense was begun, and as soon as this is finished other organisms will be
investigated. Because much time thus far has been spent on investigation of
technical aspects, it is hoped that the study of other organisms will move
somewhat faster.

Biochemical, Physiological and Immunologic Aspects of Gram-Negative
Pathogens. In a study of the metabolism of Coxiella burnetti , employing liv-
ing organisms from infected yolk sacs and measuring the enzymatic activity by
conventional methods. Dr. Richard A. Ormsbee has shown that the major part of
the classical carbohydrate oxidation system is present. A study of the mech-
anism of antibiosis active against Q fever has shown that in descending order
of effectiveness, terramycin, aiireomycin, and Chloromycetin are effective in
the treatment of Q fever. It was also shown that there is a constant relation
between the size of the infectious dose and the therapeutic dose, and that the
action of aureomycin and terramycin is rickettsiostatic. In connection with
tularemia vaccine, purification and fractionization of antigen has resulted in
isolation of a highly active antigen which is now being characterized.

Bacterial and Mycotic Diseases Section

Immunologic Studies of Organisms. The objectives of these studies,
conducted by Dr. Carl L. Larson, are to investigate antigens capable of pro-
ducing immunity toward Gram-negative orgeinlsms. Major findings include the
following. A booster dose of soJ-uble antigen from B. t\ilarense given three
montns after primary vaccination produces greaxer immunity than does a com-
parable amount of antigen given at intervals of two to three weeks. Antigens
from P. pestis grown at 30° C. or 37° C. are capable of Immunizing guinea pigs
against infection when incorporated into Freund's adjuvant. The toxic effect

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of killed Brucella for mice is enhanced when killed tubercle bacilli are added.
Volunteers vaccinated with soluble antigen from B. tularense develop antibodies
against this organism, with no unfavorable response noted. Among vaccinated
individuals, four cases of tularemia occurred; these were very mild ajid not
typical of laboratory infections.

Studies of Gram-Negative Pathogenic Bacteria. In these investigations,
by Dr. B. H. Hoyer, three main groups of organisms have been studied:
Brucella , Pasteurella pestis , and Leptospira . The objectives are to achieve
better understanding of nutritional, enzymatic, and immunologic properties of
these organisms by developing suitable growth media, by fractionation and
purification of antigens, by testing enzymatic activities, and by animal pro-
tection tests. Studies of antigenic cross reactions of Brucella ureases in
vitro reveal cross reactions among urease-containing preparations from Br.
abortus, Br. sxiis , and Br. melitensis . By a simple precipitation procedure in-
volving lowering the pH of soluble antigens prepared from P. pestis , it is
possible to separate the ajitigen mixture into toxic and nontoxic fractions.
A defined medium for the growth of the free-living Le'ptosplra biflexa has also
been developed. Organisms grown in this medixjm are being used to study some
of the growth characteristics of leptospirae. Application of this knowledge
to pathogenic leptospirae is planned.

Immunologic and Physiologic Aspects of the Pulmonary Mycoses. Dr.
Samuel B. Salvin's studies concern the epidemiologic, diagnostic, and thera-
peutic aspects of various diseases caused by fungi, with special reference to
histoplasmosis. In cooperation with certain investigators, serums are being
examined for precipitins, complement -fixing antibodies, and neutralizing anti-
bodies. It appears that a combination of these tests not only establishes the
diagnosis of histoplasmosis but aids in prognosis. White mice may be actively
immunized against infections with H. capsulatum with acetone-dried cells, and
studies are under way to test whether or not other fungi can be employed to
produce specific immunity.

Diarrheal and Dysenteric Diseases. These studies by Dr. K. C. Milner
concern the pathogenesis, immunity, chemotherapy, and epidemiology of infec-
tions with bacteria of the Salmonella group. It was found that administration
of certain antibiotics, even at non-toxic levels, appears to increase the sus-
ceptibility of chicks to infection with Salmonella typhimuriijm . Traditionally
prepared vaccines confer on mice a very low order of protection when chal-
lenged with S. enteritidis and S. typhimurium . The implications of this find-
ing are being explored, particuJ.arly with regard to their bearing on typhoid
immunization. Another project concerned improvement of methods for establish-
ing the specific etiology of rat-bite fever. A stable soluble antigen has
been prepared from disintegrated cells which, within limits of present experi-
ence, reacts specifically in complement -fixation and precipitation tests.
Its practical utility is to be tested as suitable materials become available.
The unit has also shown that cultures of the Streptobacillus may be preserved
by lyophilization.

Serology of Diseases Caused by Infectious Agents. The objective of
this -unit, directed by Dr. David B. Lackman, is to support the research pro-
gram of units in the laboratory by performing serologic tests for the dis-
eases under investigation. This includes a diagnostic service for clinical
specimens. The study of the antigenic structure of members of the spotted
fever group of rickettsiae and the psittacosis group of viruses represents

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an important continuing project of the unit. Findings in the past year in-
clude detection of human cases of psittacosis in Twin Falls, Idaho. The
presence of this disease had not "been suspected. A procedure is \inder study-
in which complement fixation is utilized in the assay of tularemia soluble
antigens. Good results have been obtained in the early stages of this work.
The agent isolated elsewhere as the cause of bovine encephalitis has been
shown to be a member of the psittacosis group of viruses. Thus far no rela-
tionship between bovine encephalitis and human disease has been shown.

Culture Studies of Infectious Agents.. In addition to its research
objectives, this unit, in charge of R. K. Gerloff, is responsible for main-
taining strains of rickettsiae and viruses in embryonated eggs, to supply
mass inoculation procedures for other units, and to prepare antigens for
experimental use. The unit has isolated a virus from Haemaphysalis leporis -
palustris ticks by direct inoculation into embryonated eggs; it Is believed
to be an insect virus with pathogenicity only for the developing chick embryo.
Other findings include the demonstration that Ornithodoros moubata ticks can
be infected with Q fever by direct feeding on the membranes of iiS^ected
embryonated eggs. The virus of Colorado tick fever was also shown to be
neurotropic and, when cultivated in the embryonated egg, the central nervous
system tissue of the embryo is the only rich source of the virus.

Pathology of Infectious Diseases. To support the- various research
projects of the laboratory, this unit, headed by Dr. W. J. Hadlow, provides
pathologic examinations of animal material from both natural and experimental
disease conditions. entails a detailed microscopic study of a wide
variety of tissues from many species of animals. Dui-ing the past year the
unit reported an extensive interstitial myocarditis had been found associated
with experimental Spirillum minus infections in several wild and laboratory
animals. The agent of bovine encephalitis was shown to cause a fibrinoiis
peritonitis, similar to the serositis foimd in the natural disease, but no
encephalitis in experimentally infected guinea pigs.


In preparation for the opening of the Clinical Center, this laboratory
(Norman B. McCullough, Chief) has completed its plans for the Microbiological
Institute's clinical research program to be conducted in the new facility.
The program will concentrate on infectious and parasitic diseases of public
health importance.

Based on a coordinated laboratory- -clinical approach, this program
will seek to improve existing, or to develop new, methods and techniques for
the diagnosis and prevention of infectious diseases, and to develop new or
more effective methods of treatment, control, or cure. Specific approaches
will be employed on selected diseases along such lines as the early recovery,
isolation, and classification of etiological agents; the development of de-
tectable antibodies; and therapeutic trials of certain drugs and antisera.

In collaboration with the Research Foundation of Children's Hospital,
Washington, D. C, clinical studies of respiratory viral diseases were con-
ducted in the past year by a scientist of the Laboratory of Clinical Investi-
gation. The viral isolation and other laboratory work were carried out by
the Laboratory of Infectious Diseases. This project will be transferred to
the Clinical Center after the facility is opened. The results of the past

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year's study Include recovery and identification of Coxsackie group viruses
new to the Washington area; evaluation of the use of the suckling mouse for
diagnosis of herpes simplex infection and refinement of the technique using
early passage neutralization tests; and further clarification of the diagnosis
of herpangina and differentiation from gingivo - stomatitis.

Diseases which will "be studied when the Clinical Center begins opera-
tions include brucellosis^ rheumatic fever^ histoplasmosis, hepatitis, trichi-
nosis, amebiasis, schistosomiasis, and filariasis.


The Extramural Programs Branch of the National Microbiological Insti-
tute is responsible for the administration of research grants and research
fellowships in the broad field of microbiology. This program is coordinated
with the Institute's own research activities, and a continuous review is
maintained of disciplines and fields covered.

The present extramural program covers such fields as viral, rickettsial,
spirochetal, and protozoal diseases, and investigations dealing with fungi.
The program also includes the sponsoring of fellowships to provide training
for scientific personnel interested in microbiological research. In addition,
research grant support is implementing a nation-wide sectional research pro-
gram for biological warfare defense, the objectives of which are to expaxid and
to strengthen the existing civilian facilities for the specific diagnosis of
outbreaks of diseases not ordinarily included in routine laboratory tech-
niques, and to encourage original research by independent investigators on
diseases which may be of importance to biological warfare defense.

A total of 2i<-4 research grants amounting to $2,177^813 is currently
being supported by the National Microbiological Institute. Forty- two fellow-
ship awards were also made in fiscal year 1952.

A survey completed in the past year indicated that a considerable
amount of research in microbiology is being supported by the grants programs
of other Institutes at NIE. This reflects the fact that many chronic diseases
have their origin in infectious diseases. The survey showed that 172 research
projects amounting to $1,738^769 were being supported by other Institutes, of
which the microbiological component was computed at $1,337^903- Examples of
projects in this category include those dealing with septic shock, endocardi-
tis, rheumatic fever, oral microbiology, genetic studies, joint inflammations,
and certain central nervous system diseases .

During the past year the Tropical Medicine Study Section of the Divi-
sion of Research Grants sponsored several conferences on toxoplasmosis, a
parasitic disease in which medical science has shown increasing interest in
recent years. As a result of the conferences, diagnostic facilities for toxo-
plasmosis have been established at the Communicable Disease Center of the Pub-
lic Health Service in Atlanta. These facilities are available to health
departments throughout the nation.

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R. H. Felix, Director


Introduction 127

Research Grants and Fellowships Branch 128

Training and Standards Branch 132

Community Services Branch 13^

Professional Services Branch 139

Biometrics Branch , , . 1^1

Publications and Reports Section l42

Intramural Research: National Institute of Mental Health and National

Institute of Neurological Diseases and Blindness 1^3

Section on Developmental Neurology lij-ij-

Section on Physical Chemistry lij-5

Section on Neiirophysiology l46

Section on the Spinal Cord ikj

Section on Technical Development l48

Section on Aging 1^9

Section on Drug Addiction 1^9

Section on Endocrinology I5I

Laboratory of Socio -Environmental Studies 15I

Clinical Psychiatric Research 153

Studies at Clinical Center 153

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July 1, 1951 - December 31, 1952


Mental illness continued to present one of the Nation's most serious
public health problems - with estimates indicating that there are some
650,000 persons in mental hospitals, and several million others with severe
emotional disturbances. Under the provisions of the National Mental Health
Act of 19^6, the National Institute of Mental Health has continued its efforts
toward reducing the toll of mental and emotional disorders through its pro-
grams of intramural research, research grants and fellowship awards, training
grants, and technical assistance and grants-in-aid to the States to develop
community mental health programs .

With the opening of the Public Health Service Clinical Center plahned
for the near future, the Institute began preparations to make the best use of
the expemded facilities for laboratory and clinical research • Dr. Seymour S.
Kety was named Associate Director in Charge of Research for the combined basic
research programs of the National Institute of Mental Health and the National
Institute of Neurological Diseases and Blindness, and Dr. Robert A. Cohen was
appointed Director of Clinical Research for the National Institute of Mental
Health. New sections are being organized in intermediary metabolism, enzym-
ology, cerebral metabolism, cellular physiology, functional neuroanatomy,
cytoarchitecture, animal and human behavior, special sense physiology, and

Research studies at the Institute during the past 18 months have pro-
duced new information on the physiological activities of cellular nucleic
acids, the physiolo©r of the cerebral cortex, the basic neural mechanisms op-
erating in the spinal cord, the relation between aging and changes in the
nervous system, and the meaning of spontaneous verbal behavior in psychiatric
interviews. The Section on Addicting Drugs, at Lexington, Ky., made important
gains in its studies of the addictive properties of narcotic drugs and the
personality of addicts. A cooperative project with the Worcester (Mass.) Foun-
dation for Experimental Biology has produced methods of analyzing urinary and
blood steroids of a reliability previously unobtainable.

The 1^5 independent projects which received support through research
grants covered a wide range: anatomy, biochemistry, and physiology of the
nervous system; normal child development; distribution, frequency, and genetics
of mental illness; psychological processes; cause and diagnosis of various
mental and emotional disorders; evaluation of methods of prevention and treat-
ment, ajid relationships between social stress and mental illness. Special
grants were made to support projects concerned with specific program needs of
the Institute. Seventy -two new research fellowships were also awarded.

In supporting training programs, the Institute followed the principle
that quality of teaching was of first importajice. During the past 18 months,
383 grants were made to support graduate teaching in the psychiatric disci-
plines; 1,3^3 stipends were awarded to individual trainees, and kO medical
schools received grants for the psychiatric education of some l4,000 students.

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Evidence of the growth of State and community mental health programs is
found in the increase of funds contributed from State auid local sources to
match Federal gremts-in-aid. The ratio is now three dollars for each Federal
dollar. States and communities put increased emphasis on providing psychiatric
orientation for persons in related professions, such as teachers, social
workers, and public health nurses. States sought assistance from the Institute
and its regional consultants in making their community mental health programs
more effective. The Institute's demonstration clinic in Prince Georges County,
Md., showed results indicating the Importance of offering a community a variety
of consultative and educational services in addition to clinical services for
individuals .

The proposed draft act for the hospitalization of the mentally ill,
which has served as a guide to State legislatures and has resulted in improve-
ments in State laws concerning the mentally ill, was brought up to date in line
with experience, and reissued. At the request of five States, comprehensive
surveys were made of ik mental hospitals and schools for mental defectives.

In determining the best use which might be made of the Institute's facil-
ities and professional services, particular attention was given to rehabilita-
tion of the mentally ill, drug addiction among minors, aging, juvenile de-
linquency, industrial mental health, and mental deficiency. Efforts were con-
tinued to help the States develop meaningful systems of reporting statistical
data concerning the mentally ill. The Institute also prepared informational
material in response to the interest of the public in mental health problems,
and helped the States develop their informational services.


The Research Grants and Fellowships Bramch is responsible for administer-
ing the extramural grant and fellowship program of the National Institute of
Mental Health, including administration of the Mental Health Study Section. As
in the past, this program receives assistance from and coordinates its activi-
ties with the Division of Research Grants.

It is now five years since the first research gi'ants were awarded under
the National Mental Health Act. Feeling that this was an appropriate time to
review the accomplishments of the research grant program and the direction in
which it might move in the future, a comprehensive analysis was made of the
grants awarded to date, for consideration by the Mental Health Study Section
and the National Advisory Mental Health Council.

From July 1, 19^1, through September 1, 1952, slightly over $5,000,000
was awarded in support of 165 projects. Analysis by problem area showed that
heaviest support had been given to research into (a) the etiology, symptoma-
tology and pathology of mental illness, (b) development or evaluation of treat-
ment methods, (c) normal child development, (d) studies of the nervous system,
and (e) the relation of environmental stress to mental health and illness.
Forty-four percent of the applications for "basic" research were approved,"
compared to 27^ of "clinical" applications. However, clinical applications re-
ceived 58^ of the funds, compared to 33^ for basic research.

Analysis by disorder showed that 42^ of the funds were spent on projects
dealing more or less directly with a psychiatric disorder, 22^ on "adjustment
problems" of various kinds, and 20^ on basic research with no immediate or

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direct application to any disorder. The remaining l6^ was spent on neurologi-
cal and miscellaneous other disorders.

Analysis by methodology showed that a minimum of 50 categories had to be
used in classifying the projects. The largest number of approved projects em-
ployed psychological methods (62). Projects utilizing social science methods
(i|-2), and those utilizing biological, chemical or pharmacological methods (36)
were next in frequency. Twenty-two projects were essentially studies in psy-
chiatric treatment methods. Relatively few projects (I8) were supported in
interdisciplinary research, which may be an indication of the difficulty of
this type of approach.

This analysis was used by the Mental Health Study Section and the Na-
tional Advisory Mental Health Council in considering the problem of priorities
in mental health research. Lengthy discussions by both groups, and a study of
suggestions on priority areas by present and former members of both groups,
indicated considerable similarity between these suggestions and the actual dis-
tribution of funds in the past 5 years . It was also the consensus that it
would probably be harmful to progress in mental health research and to the in-
vestigators working in this field to establish a formal list of priority areas.
The present system of reviewing individual applications on their merit was
felt to be preferable. It was agreed, however, that more attention could be
paid to "gap" areas and to encouraging investigators from other than strictly
psychiatric or psychological disciplines to concern themselves with problems of
mental health and illness.

One way of accomplishing this is through the activities of the Study
Section and Council. During the period covered by this report, a committee of
the Mental Health Study Section was established, on the suggestion of the
Council, to explore the contributions which might be made to the problems of
mental health and illness by the biological and biochemical sciences. This
committee has held a first meeting sjid has arranged a second one to consider
various approaches to the problem of regional localization of function in the
brain, with plans for future meetings on other specific topics.

Another committee of the Study Section which has become active in this
period is the committee to evaluate completed projects. This is an expression
of the continuing concern of the staff and its advisory bodies to evaluate the
research grant program and to determine ways in which it might be strengthened
or reoriented to meet the changing needs and emphases in the field.

The furtherance of research is aided not only by support of direct re-
search activities but also by the support of research conferences, at which
investigators are given the opportunity of exchanging ideas and information
and obtaining new insights and leads from other disciplines and investigators.
Three such conferences were held in 1952, supported by the National Institute
of Mental Health. The first of these was the final conference on psycho-
surgery, chaired by Dr. Fred A. Mettler, and attended by psychiatrists, neurol-
ogists, surgeons, axid others actively working in this field. The second was a
conference on the effect of early experience on mental health, held at the
Jackson Memorial Laboratory in Bar Harbor, Maine, under the chairmanship of
Dr. J. P. Scott. The third conference consisted of a series of meetings held
in conjunction with the annual meetings of the major professional societies
concerned with problems of mental health, to discuss the problems which arise
in carrying out interdisciplinary research in the mental health field, to

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compare methods and techniques which have been evolved, and to point the way
toward more effective research in which the utilization of teams of workers
from various disciplines is required.

In the past l8 months, IU5 separate research projects have received
support through research grants. These projects, as in the past, cover a wide
range of problems concerned with the field of mental health and illness: basic
studies on the anatomy, biochemistry, and physiology of the nervous system,

Online LibraryNational Institutes of Health (U.S.)Annual report : National Institutes of Health (Volume 1952) → online text (page 16 of 29)