THE ROCKEFELLER UNIVERSITY

SOME COMMENTS AND PROPOSALS

This discussion was not planned initially to be of
the nature it now turns out to be. The plan was to examine
some general trends in The University programs and suggest
some extensions which seemed important for further develop-
ment. The more medical programs were to receive particular
attention and this portion of the original plan is adhered
to.

Incidental to the preparation of the comment, an oppor-
tunity was afforded for conversations with a number of indi-
viduals of the intellectual community; some students and some
junior and some senior members of the faculty. The support
programs were also surveyed but not in detail; and several
accounts of The University and its programs were consulted.

The thrust of the general information obtained led to
the belief that it might be more reasonablé to discuss problems
of The University and its further development in a historical
and philosophical context than a coldly analytical point of
view. The presentation; which results is more useful in that
it may provoke discussion rather than propose a simple course
of action.

ee

K
he\ N

io James A, Shannon, M.D.
‘ August 9, 1970

os
Background

The transition of The Rockefeller Institute for Medical Research into
a specialized university emphasizing the life sciences appears to have reached
the end of an initial phase of organic growth. Changes which have occurred
include an increase in the number of research groups, a broadening of the
biological and behavioral base of the enterprise, the inclusion of related
programs in the chemical, physical and mathematical sciences, and the intro-
duction of predoctorate education. This growth has been accompanied by a
lessened emphasis on the more medical portions of the program. The addition
of small programs in cultural subjects appears to have been accomplished with-
out particularly influencing the hard science nature of the environment.

At this point, concern for the future of The University is commonly ex-
pressed by some of the senior staff and the institution's "alumni," but this
unease is not widespread. That which is evident seems to be stimulated by a
concern of students and faculty alike for the nged to reexamine the roles of
The University in a modern society. This is more of a national than a local
phenomenon. As best one can judge from limited discussions, there does not
appear to be a hardening of any series of simple propositions which might
serve as a guide, or, a limit, to further development.

There is general acceptance of the views that the freedom of the inde-
pendent scientist and general scientific excellence must be maintained; and
that the University is “unfinished” and should plan for continued growth.

There are differing views on how growth can best be managed. Some
would continue the operations of The University in the dominant mode of the

present; i.e, support of the individual scientific units without particular
substantive regard to the activity of other units within the environment.
Others appear to be reaching for institutional mechanisms that, continuing
the freedom of opportunity for the individual scientist, would favor programs
of an integrative nature conducive to greater interaction among a number of
the individual groups. There seems to be no particular resistance to the
concept that this might foster some coalescence of some activities around
broad conceptual statements of program purposes. All favor a flexible approach
to development, managed in a fashion that does not violate the internal sci-
entific forces of the field, If a resulting program has quite obvious societal
import, then this would be judged to be acceptable to most scientists and
desirable to many.

There is also an expressed desire to improve the opportunity for re-
search in the more complex biological systems such as can only be examined
in the total animal. Such a desire is particularly apparent in some of the
medical groups, the activities of which are generally oriented toward the
elucidation of disease phenomena. Others would couple biological studies
of the CNS with rapidly evolving opportunities jn the behavioral sciences,
and the broad extension of these to the primate including man. Without being
specific as to substantive program content, a number of scientists favor sig-
nificant involvement of The University community with problems such as "popu-
lation" and the "environment." A recurring theme that emerges from many
discussions is the role that the systematic exploration of the various as-—
pects of human development might play as an integrative force for many of
the present discrete activities.

A general characteristic of faculty views on these matters seems to be
a desire to pursue any programatic change by an expansion of the science base

of the institution rather than through a major redirection of personnel and
and resources already available. Some would also seek an increase in oppor-
tunity through affiliation with other institutions.

But one general impression comes through quite clearly, there is a
mild ferment now in process with no firm lines having been drawn on either
a conceptual or substantive level. It seems likely that a restatement of
broad University policy covering the substantive content of the University's
planning would be appropriate at this time. If the staff were assured that
the policies arrived at were to be the result of serious discussions with
both the Board of Trustees and the senior faculty, then much staff uncertainty
would be resolved in a satisfactory manner, There seems to be no thought that
this will not be done.

Extraneous factors contributing to uncertainty comprise the general
phenomena of social unrest, and its reflection in the general university
community. A triad of internal circumstances also have direct impact on the

community. These are:

e Fiscal uncertainty as the result of constraints on
federal spending and the inroads of a continuing
inflation.

e The intent of the administration to undertake a program

of further development but with a lack of understanding,
by the senior staff, of the general but substantive con-
Siderations which will underpin the plan for development.

e The change in University “leadership,” the substantive
impact of which is yet to be fully felt.

Concerning University Purpose

 

A general statement of University objectives is feasible. This should
be philosophical in nature but probably not prepared as a freestanding docu-
ment. It would be more effective if the statement were background for the

exposition of the proposed extensions of institutional program. The audience
for such a document should be students, staff, and potential sponsors as
well as the general public.

Perhaps the most important area to be examined in such a statement re-
lates to the broad purposes of the University and the development of a cen-
tral view on how its programs and operating philosophy relate to contemporary
society and some of the latter's more obvious needs. The need for such a
reasoned proposition or series of propositions is not unique to The Rockefeller
University. Rather, it is likely that the inability of many a university to
state clearly its perception of its own role in society is basic to much of
the student-faculty-administration conflict that has evolved. In the absence
of a self-definition of purpose and plan, there is much to find fault with
in any complex institution and little for the non-dissident to adhere to
firmly. The problem of Rockefeller may be particular and pressing despite
its small size because it is not a conventional university.

The Rockefeller University may thus be doubly vulnerable. It is vulnerable
to the influence of the non-thoughtful dissident that is simply a reflection
of its position as a member of the university cgmmunity. It is also prone
to criticism by a few because of its massive commitment to science, and by
others because of the fashion in which it carries out this specialized mission.
Actually, a sense of broad mission is only dimly perceived by some. Many
scientists find the University an effective locus for their own activities
but seem to lack a sense of "institution" and a set of "institutional objec-
tives" they can adhere to firmly. Then too, there may be a lack of vigorous
support of the University from those who are increasingly disenchanted with
the benevolent nature of the power and force of science as these are expressed
in the University programs; and also from those without a clear perception

of the relevance of research, particularly fundamental research, to the
satisfaction of the overt needs of a contemporary society. These attitudes
are not unique to The Rockefeller environment,

Personal security is commonly disavowed by the young scientist as a
satisfying end for which to strive and the lack of other clear and worthwhile
guides to career development lead to individual doubts and frustrations.

These are clearly evident. It is important to note that some of these con-
cerns are really quite conventional, some are derived from a heightened per-
sonal sense of social purpose which, in the individual, may or may not be
fundamental. The general scientific environment must have a reinforcing in-~-
fluence on this dissease, There is a lessening of individual career opportunity
in a contracting scientific universe, this in turn is reflected in the extension
of the period of dependency of the student and young faculty member. The net
worth of limited scientific goals and the relevance of these to a real and
brutal more general universe, pose both intellectual and emotional problems

to the developing scientist. In such a set of circumstances, short term
individual accomplishments may seem to be poor substitutes for a deeper con-
viction of the importance of, and at the same time a clear perception of
progress toward generally agreed upon important goals.

The general university environment tends to foster doubt and inquiry,
this is good; has been in the past and will be in the future. But an essential
that must be satisfied, for high institutional morale is a complete and pro-
found commitment of the young scientist to the purposes of his environment.

In the case of the general university, this has obvious social utility
without becoming committed to social programs in a direct operational mode.
This is derived from its general educational programs, its more limited pro-
grams of professional and graduate education, its innovative productivity

in the arts and sciences and its general acceptance as a center for intel-
lectual inquiry.

The general educational programs are concerned with public education,
the provision of teachers for the educational systems of the Nation, and the
basic educational experience for a number of essential professions. It may
also be deemed to be socially acceptable to many because of the cultural
function it serves in the community although, depending on how this function
is performed, it can be perceived as an institution dedicated to the perpetua-
tion of an establishment not now found to be wholly acceptable to many. It
can be argued that many universities and indeed, the university world in
general, does not perform these tasks too well. This is a healthy and quite
reasonable attitude. But it is important to note, in terms of the social
purposes of a general university, even the most disenchanted agree that the
general tasks themselves are essential.

Graduate (and professional) education in the general university pro-
vides for the definitive development of scientists, technologists and an
array of competently trained progessionals in socially essential fields.
These activities have a common characteristic, aj least in theory. Each of
the students touched by an advanced educational experience is expected in
proportion to the length and depth. of the experience, to be increasingly
capable of independent action within his field of choice. Again, there may
be disagreement on the emphasis given graduate and professional education by
field but little disagreement on the importance of this aspect of the educa-
tional process.

The third general university function is more controversial, i.e. re-
search, particularly in the sciences. This is evident when the research is
viewed with respect to its utility to society, when the benign purpose of the

ultimate product is suspect, or when its purpose is not understood. It can
also be controversial, regardless of its content, when the research is pur-
sued on a massive scale.

Distrust of sctence is not uncommon in our society. This can stem
from simple ignorance or from attitudes leading to humanistic life styles.
It may also stem from the view that much research does not have a socially
desirable objective or indeed may be anti-social in its purpose; or from the
belief that much research does not have clear relevance to the great problems
of today. In these views, research should receive a lower priority in the
allocation of the limited resources available. Simplistically stated, while
some research is good and essential, much is trivial, and some is actually
evil. In the view of others, the too vigorous pursuit of research objectives
ean detract from the competence of the educational process, and the deferral
by the university of science tasks deemed to be important and within its com-
petence. Comments such as these are not to be taken lightly by the university
world for they are not limited in their utterance to a disaffected few.

The entire array of criticism is not infrequently the main substance
of remarks of a few in our Congress and in the gtate houses across the
Nation. In the specific case of biomedical research, criticism is too fre-
quently the common currency of exchange of some deans of our medical schools
and some leaders of the medical profession. The biomedical research program
is not infrequently viewed by these as a deterrent to the needful expansion
of medical education and only a minor contributor to its excellence. In
addition, it is charged with the sequestration of an inordinate amount of
physician talent thus directly contributing to the physician shortage in the
health service delivery systems. Such views may be held to stem from ignor-
ance and to be unfair. Nonetheless, the views are current amd do influence

the attitudes of students and the general public alike. To date, they have
received far too little attention by the leadership in our universities. The
simple though valid statement that "Universities are for learning” (McGeorge
Bundy, Daedulus, vol. 99, p.555, 1970) carries little conviction when put to
the concrete test.

The broad social purposes of The Rockefeller University have not been

 

clearly stated. It must be accepted that the University makes little contri-
bution to general education or to professional education except indirectly

in its contribution to the education of faculty for other universities and
their professional schools. Further, the student body is limited in size

and substantive content. The size of the graduate student body, though sub-
stantial, constitutes only about 20 percent of the intellectual community and
is heavily concentrated in the biological, behavioral and biomedical fields.?
Given such a situation, the net worth of the University is largely determined
by the productivity of its research staff - and probably more, than less, on
this alone.

The research activities in turn, will be increasingly appraised, less
from the standpoint of the simple excellence of the units of work - general
excellence being expected on the basis of past performance, and more from
the substantive content of the research. It is inevitable that such an apprai-
sal will include considerations external to fields of science. These will
be required for a general but clear understanding of the relevance of its

programs to the great societal problems of our times. In a real way, The

 

1
For purposes of this comment, the postdoctoral fellows can be considered
to be a transient portion of the investigative staff of The University.
Rockefeller University will likely be judged by criteria which are increas-
ingly applied to an assessment of the net worth of the nation's total com-
mitment to the biomedical sciences. But the nature of the nation's commitment
in this area is undergoing change. Having established a broad program of un-
differentiated science in the past two decades, the nation's biomedical
scientists are increasingly being posed questions as to the reasonableness
of the distribution of their effort within more or less fixed resources: this
in relation to the unsolved biological and behavioral problems of medicine;
and the applicability of the newly acquired knowledge to the solution of the
social and economic burdens imposed by ignorance. A healthy reappraisal of
the distribution of our national effort is inevitable as are the program
shifts which can be anticipated. Hopefully these changes will be the result
of nature consideration of scientific opportunity and not simple expressions
of social need. Importantly, in this assessment, it is certain that note
will be taken of the maturing behavioral and social fields and the interaction
of these with the more conventional fields of biomedical activity as these
have developed during the past two decades. a

Modest amounts of research in institutions with broad educational pro~
grams are likely to be found acceptable without special regard to substantive
content. They will be assessed for their direct contribution to the excellence
of a lively educational process. But the larger research programs, such as
are conventional in research institutes and research divisions, will be sub-
ject to a more penetrating appraisal. In applying these attitudes to a con-
sideration of the further development of The Rockefeller University, some
questions become quite specific. These relate to whether or not the deploy-
ment of its resources is such as to foster a meaningful approach to a selected

number of broad problems in the fields of its concern; and whether the problems
10.

themselves are presented in a meaningful fashion. Again, the simple
excellence of a series of discrete activities may not in itself be considered
adequate.

These views do not reflect the simple view that the University should
restructure its ongoing activities in a fashion which would replace funda-
mental research with general objectives, by applied research with specific
objectives. Quite the contrary, this would be both traumatic and unproductive.
But, it may well be that such views are important in considering the further
development of the University. They may also be determinative of the ease
with which it is possible to continue the financing of the present programs
and at the same time to provide for an extension of University activity into
the future. One way or another, they will have a profound influence upon the
acceptance of the University by its sponsors, as well as by some of its
staff students.

The major problems facing the University leadership during the coming
half decade will be to sustain the excellence of the individual units; and
to select a limited number of broad program areas with acceptable general
objectives, Each of the latter must be selected with care, giving positive
consideration not only to the discrete scientific opportunity, but also to
the utility of the broad program in providing an integrative force for some
of the existing programs.

It is possible that new institutional programs deemed to be desirable
will be of a nature that they cannot be developed wholly within the labora-
tories and clinics of the University. Some no doubt can but others will only
be possible with suitable cooperative arrangements. But then, cooperative
arrangements may be desirable in themselves in the broadening influence they

can have on The University.
ll.

II

Early Developments

The University continues, as in the past, to be generally characterized
by the excellence of its scientific activities and the distinction of its
scientific staff. But, its role, within the broad sweep of science ,- has
changed during the span of its development. These changes include its func-
tional setting within the general Rockefeller interests, its institutional
purposes, and its ability to influence the contemporary science of the nation.
It is useful to review some of these occurrences, less for the details of his-
torical development than to provide some sense of history as a solid base to
view the prospects for institutional change.

The University had its beginning at the turn of the century (1901) as
a series of laboratories in chemical, biological and medical sciences aimed
generally at the provision of a science base for medicine. The then Rocke-
feller Institute was one of the nation's four or five science oriented insti-
tutions with a capability to modify American medicine. A view of contributions
to this is possible only if its activity is viewed as part of a broader, loosely
integrated set of activities supported by the Rockefeller interests.

The major elements of these programs, were The Rockefeller Institute for
Medical Research, its loosely dependent Hospital and The Rockefeller Foundation
with its subsequently developed International Health Division. The programs

supported contained a mix of domestic and overseas activities which coupled

 

1 science is used as a broad term having the dimensions of the sum of
research and education within a broad intellectual context.

“rhe General Educational Board will not be discussed.
12.

biomedical research, medical education and public health. The substance of
the work performed and supported was related to what were perceived to be
the great medical problems of the period.

Domestically, the Rockefeller Institute and Foundation were most pro-
ductive in the development of new leadership in the coupled functions of
research and education as the U.S, medical schools underwent a progressive
change from a trade school type of institution to one generally characterized
by a high degree of professionalism, These changes followed acceptance of
the general concepts of medical education propounded by Flexner. His report,
published at about the time of the 10th anniversary of The Rockefeller Insti-
tute, emphasized the need for a sound science base in the education of the
physician. The Rockefeller interests were important in part because their
individual programs expressed a similar point of view and each had well-
established mechanisms with which to exercise a determinative role on the
medical schools in the process of change. The full influence of these organi-
zations was particularly evident in the 1920's.

The modern biomedical scientist is prone to overlook the ferment in
medicine in the U.S, at the turn of the century. This reflected the develop-
ment of broad areas of relevant science in the laboratories of Western Europe
and the continuing scientific deficiencies in most American institutions.

But, a beginning of change or at the least, the opportunity for needful change,
was perceived by a number of thoughtful professionals at that time.

Bacteriology was providing an increased understanding of the nature of
infectious diseases. Organic chemistry had developed a base for the study
of metabolic phenomena. Physiology was in the process of defining the inter-
actions of components within complex organ systems and systems control. Path-

ology had made a good start in the description of the morphological expression
13.

of disease processes and provided a more rational base for the classification
of disease phenomena.

The practical utility of this new information in both the development
of sound education and in the management of disease was clearly apparent.

As a result, there were established a few modern laboratories in each of
several U.S. universities and in some of the departments of the federal es-—
tablishment, i.e. The Medical Department of the Army and the U.S. Public
Health Service. Further, the general social value of research was sharply
defined for the American public by several occurrences, Yellow Fever, in
epidemic proportions, was suppressed in Cuba; a trans Isthmus canal in

Panama was shown to be feasible providing prudent disease control was exer-
cised; and the scandals in the drug field and their correction in the creation
of the Food and Drug Administration emphasize the general need for science

and technology in the manufacture and approval for distribution of therapeutic
agents. Meanwhile, the Public Health Service was demonstrating the utility
and effectiveness of a quarantine function conducted with proper laboratory
support.

These achievements, occurring at about the time the new Rockefeller
enterprises were evolving, must have had a profound influence on the character
of the initial undertakings, The early objectives, as best one can interpret
the intellectual thrust behind the programs, were evenly divided between the
development of new knowledge and its application in the resolution of medical
or public health problems. Given the flux in education, it is not surprising
that they also included purposeful efforts to modify the form and substance
of medical and public health education in this country and abroad. The research
supported encompassed both the fundamental and the applied but eminence was

given to professionals of high competence to determine the courses of studies
14.

that they deemed to be most likely to achieve the desired end result. This

juxtaposition of general goals and freedom in the methods of pursuit of fun-
damental and applied research continues to characterize much of the overall

Rockefeller enterprises.

There can be ne doubt that these concepts together with a full appre-
ciation of the power of science led to the establishment of the laboratories
of the International Health Division of The Foundation in close association
with the Laboratories and Hospital of The Rockefeller Institute. This was
likely less a matter of convenience than to provide an increasingly important
public health enterprise with a broad science base, within an environment
committed to the use of science in the resolution of important medical problems.

The period up to the beginning of World War II was extraordinary in the
productivity of the Institute programs. A cataloguing of achievements is less
important than a sampling which can provide some sense of their major thrust.

Prominence was quickly achieved in areas of organic chemistry, (of
natural products), anatomy (cytology), cellular physiology (particularly in
relation to membrane phenomena), and physical chemistry (the formulation of
theory covering redox potentials). But the prestige of The Institute was
importantly derived from equally fundamental research which in addition had
quite specific application to disease.

The more medically oriented studies were wide ranging and quickly
achieved eminence in a number of fields. These included the study of cancer
and the relation of viruses to uninhibited cellular growth; the examination
of viral and bacterial disease including the fundamental nature of these
agents, the diseases they produce and how these latter could be prevented or
modified; the exploration of cardiovascular disease and the related problems

of hypertension and chronic renal disease: the general conceptions which
1S.

underlie the theoretical, and practical consideration of antibiotics in the
control of infectious disease.

Other productive areas of research provided precise methods for the
study of biological and biochemical phenomena in health and disease. These
were particularly important as a quantitative base for clinical science which,
beginning in the teens, developed rapidly in the U.S. during the twenties
and thirties. Related to this general type of activity was the penetrating
observations leading to the concept of fixed blood groups with its immediate
and profound influence on medical practice.

There were other important contributions but those mentioned are suf-
ficient to make an important point. The peculiar genius of the early Insti-
tute and its related Hospital was the development of broad programs of
fundamental biomedical research within a framework of disease objectives;
and to utilize the research activities as a training base for the development
of science based medical educators. Broad accomplishments by small groups
of brilliant scientists was somewhat easier during the early period than is
true today and great leaps were possible with substantially less resources.
But this does not detract from the extraordinary accomplishments of the’
early Institute scientists.

Meanwhile, the Rockefeller Foundation performed an essential role in
the developing institutions of medical education and supported selected
areas of research both at home and abroad. It is difficult to reconstruct
the details of the interacting relations among the several Rockefeller pro-
grams in sunmary form, but it is quite clear that the impact of the entrance
of gifted scientists into U.S. medicine from the Institute and Foundation
programs was profound. The programs of the International Health Division

of the Foundation and its loosely related Peking Union Medical School and

spare ee
16.

University had an equal influence on U.S, and overseas science particularly
in South America and in China, India and South East Asia.

These Foundation programs were critical in providing an international
base for the medical sciences and were particularly effective in providing
effective linkage between scientists and research activiteis in the U.S.
and Western Europe,

They also had a profound influence on public health practice in many
then called underdeveloped countries; public health practice based on an
elucidation of the mechanics of disease and its transmission. The Foundation's
overseas programs gave particular emphasis to malaria and other parasitic
diseases and to viral disease, (more particularly yellow fever).

With this general background one can examine the happenings since
World War II which produced such striking changes in the Rockefeller enter-
prises during the past quarter of a century. The Foundation activities will
be discussed first so as to provide continuity in a consideration of Univer-
sity programs in the later sections.

The Rockefeller Foundation —- Post World War II, There were a number

 

of outstanding U.S. medical schools in the late 1940's. Also, the federal
establishment was rapidly developing significant science support programs
both at home and abroad. These factors diminished the impact that could be
generated from within the private sector on medically oriented institutions
in the United States. At the same time there was obvious need for temporary
aid to institutions of Western Europe and long term needs for support of
health activities in an increasing number of “developing” nations.

In such a situation it is not surprising that the Foundation reduced
its support for medicine in the Continental U.S. rather sharply and extended

its aid in both South America and Western Europe. There was also a critical
17.

shift in program content as it became increasingly clear that poor nutrition
was an important and world wide problem, But a continuing interest of the
Foundation in medical education is apparent in the development of a model
program for the production of physicians and related medical personnel in
Cali, Columbia, and the later development of a new type of Medical institution
in Tanganyika which seemed suited to the needs of Africa. During this period,
the development of medical school staff was aided by selective research and
fellowship support to a number of medical schools in South America and in
the newly evolving nations in Africa, the Far East and Southeast Asia.

The evolution of these overseas activities as the primary programs of
the Foundation led to the abolishment of the International Health Division
and then the closure of the latters laboratories at the Institute. This was
accompanied by a curtailment of the direct research of the Foundation and a
relative expansion of grant supported activities.

But, as the last quarter of a century evolved, support of activities
in Western Europe and South America (except for Cali) was progressively with-
drawn and there was a change in program emphasis. The Foundation continued
a general interest in medical education, but increasingly emphasized agricul-
tural technology and the relation of this to the satisfaction of nutritional
deficiencies. No doubt the programs in Mexico which resulted in hardy, highly
productive hybrid strains of corn had a profound influence on this later
development. The Mexican experience was strikingly successful not only in
its impact on the immediate problems of malnutrition but also on the broader
fields of agricultural reform and food technology. These accomplishments,
in addition, had an important influence on the economy of the country.

The more recent programs in the food production area seem likely to
be equally successful. certainly in South East Asia, the Philipines and India.

These advances are centered about laboratory support for the development of
18.

hybrid cereal grains in the Ford-Rockefeller supported International Rice
Institute in Manila, agricultural and nutritionally oriented laboratories

in India and Thailand and backup support from a limited number of U.S. labora-—
tories. Immediate application of the technological advances in agriculture
coupled with the development of indigenous sources of fertilizer and more
sensible water use have already resulted in a striking increase in food pro-
duction particularly notable in these areas. The advances now seem to be

sell along toward integration, by locally developed scientists and technologists,
into conventional agricultural practice.

The results of this shift in program emphasis by the Foundation now
seem secure. They are presented in summary form to emphasize the wisdom
of coupling fundamental research (in this case plant genetics) to a broad
activity which seeks to solve a difficult and important practical problem.

The programs also demonstrate that the concurrent development of local scien-
tists and technologists can secure long term continuing progress with in-
digenous support in foreign countries as well as in the U.S, In the light

of these successes in South East Asia and the Far East, and the development

of productive agricultural programs in Africa and the Near East it would be
surprising if the programs of the Foundation were not the subject of a further
change in emphasis.

Serious concern for the quantitative and qualitative aspects of a nation's
food supply must be matched by comparable concern for population size and
population growth and the impact of these on technological development. In
this view. it is not surprising that the establishment (in 1952) of The Popu-

1
lation Council was followed by the development of a set of scientific

 

1
This council is a separately funded activity the primary support being
derived from the Rockefeller Foundation in association with the Ford Foundation,
19.

activities within a context of the social problem. As the Rockefeller in-
volvement in this problem has increased, it has been a factor in modifying
the attitudes of both official and private agencies particularly in the U.S.
Substantial federal resources are now available and the problem is given high
priority by the Ford Foundation.

Comparable concern for the population problem has only recently become
apparent in a few U.S. universities. ‘The possible involvement of The Rocke-
feller University with such a program will be noted below at greater length.
At this point it is emphasized that little is to be gained for the University
by its entrance into the field unless a program can be evolved which is con-
genial to already existing activities, and if the program is given high
priority in the core of the University's objectives. Present University in-
volvement is minimal. The University serves as a host to some of the scien-
tists of the Population Council but the program, as now conducted, is largely

one of operational convenience,
20

Iit

Current Prospects

The Rockefeller University, Post World War II. It is clear that, as

 

with the Foundation, the role of the Institute in American science changed
with the re-establishment of the nation's programs in the biomedical sciences
after the disruption of World War II partly because its resources became in-
creasingly less distinctive.

The hard core of university science in the United States, initiated
during the thirties, was expanded rapidly with federal support in the post
war period. This was evident in the availability of more extensive resources,
the increases in pre and post doctoral education, and the increased size of
university faculties, The expansion of research opportunity was common to
both “private” and state universities, their associated professional schools
and to a number of evolving research institutes, Extensive changes in the
substance of the science enterprise parallelled the increase in research op-—
portunity, first in the physical and then in the biomedical sciences, The
full flowering of the federal influence was particularly notable in the 1955-
1965 decade as biomedical research moved from the part time avocation of a
few to a full professional occupation of many.

It is pertinent to review briefly the effect of these changes on the
volume and substance of research during the total period (1945-1965). This
period is critical in that it spans the post war decay in the influence of
the Institute, the enquiry into its future (1952), the decisions which led
to a change of institutional program (1953), and the early years of University

development.
21,

The immediate post war period (1945-1953) was profoundly influenced
by the increasing availability of antimicrobial agents and appreciation of
the increasing social and economic burden of chronic illness. These influences
resulted in a shift in research emphasis to the chronic diseases. The bio-
logical complexity of these diseases, the general disenchantment of University
scientists with the target research of World War II, and the increasing
availability of new methods for the precise quantification of biological
phenomena, were determinative influences in the evolution of a fundamental
biological approach to these problems .? As the result of an expanded in-
dustrial effort a large number of therapeutic agents which were developed em-
pirically during the fifties and early sixties which, though not preventing
or curing important acute and chronic illness, permitted the amelioration of
the acute episodic manifestations of both types of disease. Also, large
surgery with its attending drama became commonplace. During this period too,
the nature of many diseases were more clearly defined and an array of viral
vaccines were developed. Some of the latter were striking improvements on
those previously available (rabies, influence, yellow fever), others (polio,
rubella, measles, mumps) were wholly new.

These practical advances relieved the pressure for "results" and freed
the biomedical scientists to use the internal dynamics of science as a major
guide in the evolution of their research programs. These time related

phenomena are not commonly understood by many scientists.

 

line importance of so-called "basic research” was highlighted by the
evolution of the National Science Foundation and the prominence given
"basic science” by a number of Federal mission oriented agencies.
22.

As the post war research programs approached maturity, other changes in
medicine were taking place, (particularly during the 1960-1965 period), and
those were to have an important impact on the support of biomedical sciences.
There was an increasing appreciation of the need for a modification in the
methods for the delivery of health services from systems which provide for
the management of episodic illness to systems that had as their objectives
the maintenance of health. This progressive shift in objectives in the ser-
vice area is reflected in the type of continuing care provided in many spe-
cialty clinics and which can find definitive expression in the full scale
provision of health maintenance by newly evolving health care systems. But
such systems run counter to the dominant concern of most physicians for a
continuation of a fee for service system and have not as yet been fully ex-
ploited.

Nonetheless and important for present purposes, is the fact that the
changes in the health care delivery system which are in prospect make in-
creasingly possible the long term study of the emergence of chronic disease
and its natural history. These new systems will facilitate studies on the
modification and amelioration of chronic illness through the long term use
of therapeutic (and dietetic) regimens. Other studies of a quite fundamental
nature will also be feasible.

These are beneficial effects, at least in prospect, but there are others
with strikingly adverse influences. The progressive involvement of federal
agencies in providing an economic base for an increasingly high cost function
is an important factor in limiting the support of its biomedical research
enterprises. These occurrences have several consequences. Less "real dollars"
are now available to support the increasing research opportunities and an in-

creasing demand for short term results have become increasingly apparent. At
23.

the same time, medical institutions are faced with the dual responsibility

of expanding physician production and remedying defects in the service systems.
It is not unlikely that those problems will be prominent in the future deter-
mination of federal support for the coupled functions of research, education,
and research.

During the period of rapid program development (i.e, 1955-1965), there
also occurred a profound shift in the clinical investigation of disease. Ini-
tially largely limited to clinical observation, increasingly emphasis has
shifted to the active manipulation of the concerned biological systems under
highly controlled conditions. Such a shift in clinical research content is
nowhere more clear than in the increasing use of "normal volunteers" in parallel
with the patient with disease in the study of the operation of well
defined biochemical and physiological systems at rest and under quantitatively
imposed stress. Such studies provide precise information which can be utilized
in the subsequent modification of the biological systems in useful fashions
to prevent or modify serious disease. Out of these general trends, and over
the longer period under consideration (1945-1965) many clinicians have been
transformed into a clinical scientist with a full capability of operating at
all three levels of fundamental, applied and developmental research. Impor-
tantly too, the well trained clinical scientist can now approach the problems
of disease with a broad understanding of the relevant fundamental sciences
and a full capability for intimate interaction with his more biologically
based colleague.

During this same period striking changes were taking place in the more
biological portions of the biomedical sciences. The entrance of scientists
with mathematical, physical and chemical skills into these fields provided

both.the views and instruments of precise science. Biochemistry with its
24,

concern for overall phenomena of cell metabolism, simple enzymes and the
kinetics of enzyme reactions in limited systems has been extended to encom-
pass the quantitative exploration of biochemical and biophysical phenomena
on a molecular and cell organelle level.

The newly emerging field of molecular biology, drew upon, and in turn
influenced in a revolutionary fashion the disciplines of microbiology,
immunology and genetics. These, in turn, provide new insights into the molec~
ular basis of some diseases and the opportunity to explore others in a more
definitive fashion.

Perhaps even more revolutionary have been the changes in the behavioral
sciences and their potential influence on biologically oriented counterpart
areas of science. This is nowhere clearer than in experimental psychology.
The era of the "brass psychologist" is long since past. Present experimental
emphasis is on such broad areas as the development of the cognitive faculties,
perception, learning and language and on the behavioral base for a variety
of social phenomena. Direct application of some of these advances to problems
of human development are quite evident. Such studies provide the base of
others with a view that the plasticity of the central nervous system for a
substantial post natal period is a common ground for exploration both bio-
logically and behaviorally oriented scientists. Viewing the opportunities
objectively, one can only wonder if the delay in coupling of these fields
may not be largely due to our unrealistic compartmentalization of science.

Importantly, an aggregation of biological and behavioral scientific
effort could provide a new and rational base for the restructuring of our

conceptions of the proper rearing of the child and of the fundamentals of our

 

1
As early as 1962, a broad interdisciplinary discussion group was established

through NIH support within the framework of the American Academy of Arts
and Science. This continues to be a highly productive activity.
25.

general educational processes. The information for these changes is much

more likely to be provided by biologically oriented behavioral scientists
than by the more conventional students of education. Equally important, the
results of such a hard scientific exploration of these abstruse processes can
be expected to yield definitive results that are directly applicable to the
definition of, and rescuing operations possible, for the retarded child. Most
certainly they can provide a more precise definition of the role of environ-
ment (including nutritional as well as behavioral factors) in the development
of the retarded, the usual, as well as the superior child. These are truly
exciting prospects.

A large number of other areas of science are equally characterized by
broad opportunity in the fundamental sciences, some with direct applicability
to the human in distress. Included in these are:

° The further development of our understanding of viruses and

their interaction with cell information systems as a basis
for the understanding of their role in carcinogenesis, and
their likely contribution to some of the devastating diseases
of the central nervous system;

e The further exploration of the interm¢diary metabolism
of food stuffs and the directive factors leading to the
associated and interactive problems of obesity, athero-
sclerosis and diabetes;

e The provision of a rational biological base for the
understanding and further development of an array of
therapeutic agents which influence a variety of systems
including those that affect mood and influence frank dis-
turbances of behavior resulting from systematic psychiatric
disease.

but these are only a sampling.

The lessons to be learned from many of the recent advances are applicable

to the planning of future research necessary for the solution of serious prob-

lems. For any major problem it will be necessary to provide a precise under-

standing of the operation of one or more quite fundamental biological systems,
26.

to extend this to encompass a clarification of the directive influences
which modify the operations of the system within the intact animal and to
define the role of specific biological systems in the generation of disease.

Quite apart from such developments and their influence on the substance
of contemporary science, science in the process has acquired a new dimension.
This is derived from a clear capability, given time, to solve the many im-
portant problems of disease, This is more so than a decade ago and the rele-
vance of science to the many medical problems of today is more easily per-
ceived. Unfortunately, this also serves to stimulate a public whose appetite
has been whetted, but not satisfied by the advances of science.

The general character of the scientific environments out of which further
major advance will likely emerge are equally clear. The biological, and the
behavioral and medical skills required must have a braod base in the physical
sciences, mathematics, computational skills and engineering. But, studies
of this complexity will require large laboratory resources, and access to
many animal models supplemented by well organized human populations. Such
an array of talent and resources can emerge from the invisible colleges of
science which themselves provide for loosely arranged collaboration, They
can be developed through federal action in well formalized programs of col-
laborative research, Or, at times they occur within 7 individual institution
because of a general concurrance of scientific interest and an institutional
policy which fosters the belief that in the allocation of resources, some can
be utilized to foster a limited number of programs with broad purposes.

When the advances in the life sciences, particularly those related to
the nature of man and his problems, are viewed in this manner it is not
surprising that the newly developed University Medical Centers have been

and hopefully will continue to be particularly well suited to take advantage
27,

of these opportunities. Such institutions may be faulted for their over
concern for science and their less than adequate performance in the educa-
tional and service areas. But, it is to be devoutly hoped that in remedying
these latter deficiencies, they will not destroy an otherwise superb organi-
zation for the biomedical sciences of the future. They are particularly

well suited to support the evolution of broad programs of fundamental research
and at the same time foster the interaction of scientists operating at the
extremes of fundamental and quite practical endeavor. These new science
organizations have no need to adhere to any particular organizational pattern.
They have a capability to evolve without concern for the scientific character
of their professional staff, or the substance of their research undertakings.
They need not adhere to any particular predetermined size or number of scien-
tific groups that may be required for the prosecution of a given set of prob-
lems. Then too, dealing as they must with the application of the leading
edge of science to the practical problems of medical care and the education
of physicians their social purposes are both secure and evident.

And yet they operate at a serious disadvantage. This is derived from
the fact that they are not primarily research institutions and increasingly
they must respond to a need for a greater abundance of physicians and to
needed modification of the health care systems of the nation. Then too,
their role in the production of medical specialists frequently tends toward
undue fractionation of programs.

But to return to the evolution of the Rockefeller Institute -

 

Some of these phenomena which relate to the evolution of science in
the 1955 to 1965 decade, were becoming evident in the early fifties. The
deficiencies in the organization and programs of the Institute were clear

even in the face of the continuing productivity of the Institute staff. But,
28.

the progressive effects of these influences on the character and quality of

the Institute programs were evident in the operational limitations on the
ability of the Institute staff scientists to participate in the rapidly pro-
gressive revolution in American science which was beginning to take place.

Of particular notw was the fairly rigid functional structure of the Institute,
and a limitation on the size of research groups and the resources that could

be made available. Conventions concerning the source of support imposed strict
limitations on the ability of Institute scientists to participate with their
university colleagues in the broad increasing support provided from federal
sources.

It was within such a frame of reference (1952-1953) that a searching
enquiry was made into the operations and future prospects of the Institute
and the continuing need for the replacement of its senior leadership group.
This set of inquiries led to several general decisions. These involved a
modification of the basic bylaws of the institution, permitted the initiation
of formal graduate education, looked to external sources for funds to expand
the physical plant, the support of an increasingly large group of scientists,
the ultimate creation of The Rockefeller University and influenced the program
content of the new University.

The program of the Institute expanded rapidly thereafter, the Univer-
sity's primary purpose being, to emphasize the broad reaches of the rapidly
developing biomedical sciences and at the same time to provide a broader
science and cultural base for the expanding environment.

New opportunities were developed in fields of chemistry, physics and
mathematics and biology on a reasonable scale. History and logic were in-
troduced on a more limited scale. The biomedical fields were substantially

broadened by these changes and the activities of many groups enhanced by an
29.

increase in group size and the provision of new resources. This expansion
of activity was particularly evident in the biological area with emphasis
being given to the many aspects of science emerging in the fields generally
grouped within "molecular biology." Other expansion encompassed studies on
the development and operations of the central nervous system. Also, a good
beginning was made in programs within the behavioral sciences. But the more
medical aspects of the University's program did not flourish in a comparable
fashion although continued support was provided in the infectious disease
area, in studies concerned with lipid metabolism and atherosclerosis, in
liver disease, and in problems associated with drug dependence.

The bulk of the new activities and the expansion of already existing
activities followed the conventional pattern of the earlier Institute in
that each group was established within a fairly well defined area in science,
As with the “older” activities, collaboration of groups was encouraged but
general "goals" that might encompass major joint enterprises of several groups
were eschewed. In all these changes, excellence in scientific effort was
sought for and achieved. In many ways the program evolution was quite similar
to comparable developments taking place concurrently in many first class
general universities.

One cannot quarrel with the purposes set forth by the review committee
in its report to the Board of Trustees (1953). This reflected the rugged
individual views and life styles of many if not most of the leaders in the
biological sciences at that time. A pertinent passage in this report is as
follows:

"The Institute should be continued, developed and strenghtened,

with its research emphasis at the long-range fundamental level

in areas of medical research which its independence, resources

in men and material, and lack of departmentalization make it
uniquely qualified to explore, with the double function of pro-
30.

ducing trained investigators as well as research publications.

To the extent that resources permit, it should support additional

selected activities outside the central establishment which will

further contribute to the accomplishment of its objectives.

"The present policy of freedom from all programmatic, or project

research should be continued. Each individual scientist should

be free to shift the direction of his research in accordance with

his own best judgment."

Nonetheless, some would comment along somewhat different lines today.
Research can be pursued as an essential part of a lively program of
general and graduate education and this must be done in the general University
which requires a sound science base for the primary educational purpose of

the institution. However, when research is supported and performed on a
massive scale, the requirements for an adequate program have additional
obligations. These relate to the general purposes of the research and its
broad relevance to societal needs. To decide otherwise is to conclude that
science, supported directly or indirectly by society is a thing apart from
society and connot thrive in close association with the latter's problems.

It is particularly true that the development of any broad area of the
biomedical science, even when it has "its research emphasis at the long-range
fundamental level in areas of medical research," must have some general pur-
pose in mind. It is also clear that such a purpose for its accomplishment
to be complete, most generally will involve a mix of activities; some pursued
on quite a fundamental level and some on a more applied level; and depending
on the area of study there may be a component on a developmental level.
Further, such a general purpose will rarely find healthy expression within
a scientific environment except in the case of small discrete groups of
scientists in the absence of one or more integrative forces. These can be

generated so as to have a substantive influence on the direction of the many

components that necessarily will be involved in the solution of any broad
31.

problem but need not stifle individual initiative. Finally, it is quite

clear that many of the diverse problems of medicine can provide a variety of
integrative forces for such general purposes. The acceptance of one or more

of such general purposes has the dual advantages of providing both a scientific
guide to the evolution of the program and a social value to the overall enter-
prises.

It is to be emphasized, that such science organization as is necessary
to provide for the achievement of one or more general purposes of a complex
nature, can heighten the scientific excitement of an evironment rather than
depress it. But this requires sensitive “management.”

Such a view does not envisage the compression of all of an institution's
activities into a series of stereotyped scientific organizational forms.
Rather, the view expresses the conviction that many areas of the biomedical
and behavioral sciences can only find full and definitive expression if the
science organization is such that several discrete science objectives can be
encompassed within a broader general purpose. Such a general purpose must
inherently have great importance, and must be able to encompass the narrower
scientific objectives of individual groups involved. When such a task is
well performed, it does indeed make the whole greater and more satisfying
than the sum of its component parts. Bluntly stated, the achievement of such
a goal in any area of science requires enlightened scientific leadership and
not direction in the ordinary sense of the word.

Contrary to these convictions, the application of the philosophical
design for the developing University (p.29) and the rapid advances and changing
nature of biomedical problems and biomedical capability have both resulted
in a progressive movement away from the fundamental character of the programs

that characterized the Rockefeller Institute before World War II, and which
32.

continue to characterize the activities of the Rockefeller Foundation today.
Both of the latter adhered to general purposes as a set of concerns in the
allocation of resources and in program development. The positive moves of
the University as it sought to provide for "research emphasis at the long
range fundamental level in areas of medical research" wrought changes of
considerable importance. The broad base was indeed acquired but the expan-
sion of the base was accompanied by a progressive withdrawal of the University
from medical problems of broad significance, and the lack of development of
other integrative forces which might be useful in the provision of effective
interaction of discrete groups of scientists.

In consequence of this, major contact and continued involvement with
the great problems of medicine by The University's scientists have become
attenuated, The successful prosecution of such problems requires broad re-
sources which are neither provided the medical groups in being nor the environ-
ment of the University. The long term survival of effective "medical" acti-
vities in such a set of circumstances, is highly dubious, thus throwing into
sharp relief a set of problems that must be solved by the University, its
executive group and its senior faculty. Furhtermore, the changes in the
University programs coupled with the program changes of the Foundation, i.e.
their more or less total commitment to the international field and the closing
of the I.H.D. laboratories at the University, have interacted to provide a
radical change in basic operating relationships of these two Rockefeller
organizations,

Contrary to the continued prominence of social relevance in program
formulation by the Foundation, the major thrust of the Institute's extension
to a University has been toward scientific excellence of discrete research

units in lively areas of biological and behavioral science as ends in themselves.
33.

The elements of program that have emerged tend to increase the penetration
of our understanding of many areas within these sciences but some obvious
connections with many pressing problems of the real world have not been
developed.

It is important to note and indeed to emphasize that the addition of
graduate education to the programs of the new University does not appear to
have been determinative of the source of evolution of the institution. Rather,
the determinative circumstances relate to the changes of research content of
the institution and the broad development of biomedical research in other
settings as the biomedical sciences have come of age during the past two
decades. It is not unlikely though that graduate education suffers, as does
the research itself, from overfractionation of the fields of endeavor.

These views on the development of the University's programs in the past
and their present opportunities can be briefly summarized in a simple series
of statements and a simple series of propositions.

1, Against a rich background of achievement in the biomedical sciences
and medicine, the Rockefeller Institute has evolved along lines that are a
simple extension into practice of the recommendations of the advisory group
in 1953.

2. Rapid growth has since taken place. This has involved a broad
expansion of staff, the provision of more adequate resources and the formal
introduction of pre-doctorate education; all of this was accomplished within
the concept of a specialized university emphasizing the broad reaches of
science with general relevance to medicine, broadly defined.

3. As a result of this development, the present University is composed
of talented professionals with multiple discrete scientific objectives in the

physical, biological, behavioral and medical sciences.
34,

4, The thrust of science in general during the past decade has re-
sulted in the definition of many problem areas in both biology and medicine,
the social importance of which is only matched by their complexity. This in
turn has created opportunities which are beyond the capability of small to
moderate sized individual research groups, and poses questions as to the
reasonableness of extending into the future some of the operating conventions
of the past. An alternative, is to determine whether there are broad pur-
poses which, if accepted by a number of new and old groups, might serve as
healthy integrative forces for a portion of the University's program.

5. A search for such program purposes should be undertaken with
several objectives and several principles in mind. Relative to objectives:

e These should be considered within a scientific context
that gives particular emphasis to ongoing activities.

e But other opportunities should also be examined looking
less to short term (0-5 year) developments than to middle
range (5-10 year) and long range possibilities.

e These considerations should be modulated by an indepen-
dent appraisal of the relevance of the programs considered
to societal need.

e Advantages should be taken, in any redirection of a
portion of the University's program, of the opportunity
this may provide in reacquiring real and continuing con-
tact with the programs of the Rockefeller Foundation.

Relative to the principles:

e Research of excellence such as is conceived requires
scientific leadership of a high order and broad com-
mitment of a number of cooperating units of work to
some common purposes. This cannot be directed in the
ordinary sense of the word nor be effectively imposed
upon a scientific environment.

e Further, the development of research programs around
several general purposes should not be undertaken with
the view of encompassing all or indeed the majority of
scientists within the present intellectual community.
Much of the present activities of the University should
be supported for itself and because of the significance
of the activity on the national scene,
35.

6. Concluding this section one can say that the University faces
the general decisions noted above and the very specific decision which follows.
The increasing complexity of the more medical sciences is quite obvious,
Applying such considerations to the present medical activities of the Univer-
sity one can only conclude that the resources now available to these groups
are generally non-competitive with their counterpart in the University. Nor
are the resources adequate to satisfy the medical portions of most of the
large programs that would appear particularly suited to the environment. If
it is not possible to expand the scope of these more medically related ac~
tivities and improve the resources available to groups involved, they should
be closed out as the result of definitive executive action. They should not
be permitted to decay through processes of attrition. Some of the medical
areas do not now possess the critical mass of scientists or the resources
necessary for the continuation of an effective program even with limited
objectives. Alternatively a salvage operation might consider the remedy of
some of the major deficiencies through collaborative arrangements with other
institutions. But , while this might solve the immediate resource problem,

it should not be considered to be a permanent solution to the problem.
36.

IV

Great Problems

The truly great problems of today do not derive from science. Some
follow success, such as population growth incidental to control of disease
and temporarily at least, a more adequate food supply; or, the uncontrolled
use of science based technologies and a consequent despoilment of the en-
vironment. Still others derive from the affluence of some nations which
accompanies technological excellence, and the lack of an ability of other
nations to achieve an acceptable level of self-sufficiency.

Only portions of these problems can be stated in terms of the oppor-
tunities for scientific advance. Contained within the life sciences is the
opportunity for fundamental changes in our comprehension of biological and
behavioral phenomena such as may result from the development of clarifying
generalizations useful in unifying what now are quite diverse areas of effort.
The central role of cell information systems in our understanding of many
problems is certainly one of these of recent orjgin. The infectious origin
of much disease is another; this evolving in the final quarter of the last
century.

When viewed in this light, it is possible to list some important areas
of ignorance in the life sciences, Some samples with particular biomedical
parameters can be stated in terms of disease;

Mental health and mental retardation,
Cardiovascular diseases,

Cancer and,
Debilitating diseases of the Central Nervous System.
37.

In terms of biological or behavioral phenomena;
Human development,
Environmental degradation and,
Population growth and its consequences,

Or, in terms of the inadequate operation of particularly relevant systems;

Medical education and the
Delivery of health services.

Several features are apparent in such a partial listing. The items are
simply translatable into a set of very broad purposes which can be utilized
in the development of research programs. With such broad purposes, the de-
rived programs will be comparable broad and obviously complex and only suited
for analysis in terms of national needs and their satisfaction. They are less
useful as a guide to the specific development of institutions. Nonetheless,

a broad comprehension of national needs and the roles science may play in
their satisfaction must be well understood by scientists generally if science
is not to be considered a thing apart from society, and lacking in relevance
to societal need. Relevance when used in this context is not a "tired" and
meaningless term, Rather, when properly used, it can be a conceptual strength
in providing a rational base for a broad effort and in the design of institu-
tional programs contained within the larger national effort.

For, though a set of national needs may have little consequence to the
day to day activities of the individual scientist, and the satisfactions he
derives, they can have meaning to institutions within which science is pur-
sued on a massive scale, In this view, the institutional setting for science,
can be characterized by randomness or by serious purpose; and the personality
of the institution will be largely determined by the extent to which either

of these views is dominant. Generally speaking, though the excellence of an

individual scientific activity may bear no relation to the presence or absence
38,

of explicit institutional purposes, the latter may be important in deter-
mining the sense of institution within the intellectual community.

Despite these caveats on utility; the simple listing of major problems
with medical dimensions is useful. Particularly when expanded to encompass
more specific items within a general problem. An examination of these can
provide some interconnections of narrow areas of endeavor which are useful
in the consideration of broader programs which may be suitable for a single
institutional setting. As examples of opportunity, cardiovascular disease
and human development will be briefly discussed, Then brief consideration
will be given to some non-categorical areas of science.

Cardiovascular Diseases —- Atherosclerosis. Problems posed by the car-

 

diovascular diseases can be accommodated within a consideration of a small
number of specific disease conditions; atherosclerosis, hypertension and a
C-V disability due to infection. These diseases are the direct cause of
approximately 1.0 million deaths a year, atherosclerosis alone accounting
for about half the total, and are said to produce disability in about 30
million people in the United States,

But there is little purity in such an analysis. For example, disability
due to atherosclerosis is commonly attended by the concurrent problems of
the retina, the heart and the kidney. Further, diabetes, a metabolic disease,
is prominant in the causation of atherosclerosis and together these two
make substantial contributions to the overall toll of disability and death,
To complicate the matter further, there is no doubt that obesity contributes
to the incidence of atherosclerosis and hypertension as well as to that of

diabetes.
39.

Nonetheless, out of this complex of related diseases, certain unifying
concepts have emerged in the past twenty years which provide a solid base
for systematic exploration, There can be no doubt that the atherosclerotic
process has as a basic biological underpinning, disturbances in metabolism
with spin offs in the interconversion of food stuffs on the one hand and de-
parture from the normal in the transport of lipid on the other. It is equally
evident that this complex of diseases are modifiable by diet, drugs and hor-
mones. Undoubtedly the "disease" atherosclerosis represents a "final common
path" which has its origin in diverse biological phenomena. Included in
these diverse biological phenomena there seems to be certain biological sus-
ceptibilities which are transferred from parent to child by poorly understood
genetic information systems. The most striking examples of this are to be
found in familial lipid diseases and in diabetes,

There is no doubt that the systems involved in these diseases are
quite complex but not such as can be expected to defy their ultimate eluci-
dation. Indeed, the very complexity of the systems underlying these disease
manifestations, their coupling with other biological phenomena that result
from specific disturbances in metabolism provide an array of biological models
amenable to searching biological and chemical manipulation,

The ultimate solution of the problems of atherosclerosis may well be
the development of information which permits their rational management by a
combination of reasonable diet and the specific addition of accessory food
factors comparable in general conception to vitamins. But these latter sub-
stances, not being essential for normal development, would be directed toward

the modification of either metabolic or lipid transport mechanisms or both.
40.

A characteristic of contemporary research in this area is the general
lack of comprehensive programs that can provide a realistic approach to an
obviously complex biological problem, This is understandable but makes
little sense when the broad opportunity is considered,

Human Development, similarly, is a problem which is inclusive of many
and diverse activities. Nonetheless, it can provide a philosophical center
around which a variety of problems undertaken within indivividual institu-
tions can be given broad meaning.

One such set of related activities might be grouped around the phenomena

associated with the initial phases of human development, In this case, con-

 

cern might be evidenced for fertility, fertility control and the associated
phenomena of implantation and early pregnancy. Programs of this general type
would necessarily find expression in the study of the physiological circum-
stances of conception and early development as well as the examination of
agents and devices which are candidates for the limitation of offspring.
Logically these latter studies would include the systematic study of the ac-
ceptability, the effectiveness and the hazards of procedures utilized less

as a statistical exercise than in terms of the biological and physiclogical
systems involved. Such an approach would not envisage the establishment of
the massive studies. These are not suited for a single institution and though
they have both practical and scientific interest are more suitably conducted

within a national frame of reference.

 

It may be of practical importance to note that the National Heart and Lung
Institute has recently formed a committee to enquire into the problem with

a view to the development of a ten year program. This committee, which
first met on July 9, 1970 will be operational for about one year. A certain
consequence of this action will be a diversion of funds, even in the face

of a general shortage, to the support of well conceived programs in the
area,
41.

The later stages of development are equally exciting. Although our

 

ignorance of these happenings are greater than our knowledge, it is quite
clear that mammalian development is a continuum which encompasses both the
fetal and early childhood periods. This latter type of development has in-
creasingly occupied the interest of the biologist and behavioral scientists
alike. However, joint undertakings by these two groups of scientists are
few.

Biologists, in their increasing concern with the sequential phenomena
attendant on development, have grouped their activities about a number of
discrete nodes. Some of these are concerned with:

e The development of immunological competence, both humoral

and cellular, and the separate and combined relation of these
to the susceptibility of the developing mammal to infectious
disease.

e The development of primary and secondary sex characteristics,
the interaction of these to the details of the development of
the CNS in utero and the plasticity of postnatal growth as this
is influenced by early manipulation of the endocrinological en-
vironment of the developing mammal.

e The postnatal development of the CNS, an obviously unfinished
organ at birth, and the effect of envjronmental influences on
both the architecture and functional capabilities of the brain
and the reflection of these in behavioral phenomena.

e The development of new animal model systems which permit earlier
access to the developing mammal for a wide variety of biological
purposes, During the past several years, working colonies of
marsupials (usually the oppossum) have been developed and are
just being introduced into biological studies as a standardized
biological form,

The behavioral scientists have recently found the processes of early

development even more intriguing in studies which include a variety of model
systems, (birds, rodents, primates, humans). It is clear that the behavioral

characteristics of the adult and indeed his intellectual capacity is largely

influenced by events happening in the early days, months and years of life.
42,

But again, the phenomena examined to date serve more to define the importance
of this period of development and its suitability for a wide array of behavioral
studies than to clarify the underlying mechanisms involved. Land marks in
this area are important though few in number. The most striking involve the
phenomenon of “behavioral imprinting," the sequential determination of sex
characteristics, and the demonstration of the early and definitive influence
of early social experience on intellectual development.

These general aspects of human development (i.e. the study of the early
period) are available for profitable exploration by both biologists and be-
havioral sciences particularly as joint enterprises. The opportunities
in these areas are great and the information to be derived so important to
concepts of child development and the structuring of the child's early edu-
cational experiences that much more serious consideration must be given to
the field. This type of emphasis most generally requires the declaration
of institutional purposes since the resources required for definitive pro-
grams are both extensive and costly. (See also Section 111),)

There are other areas of equal importance that are particularly notable
in the circumstances surrounding human development, two of which relate to
nutrition; one the genesis of chronic obesity, another the association of
poor early nutrition and a limitation on intellectual development, Both of
these have high scientific content and at the same time the information derived

from studies will have very practical consequences.

 

1 such a broad series of studies having as their ultimate purpose a more
rational understanding of the educational process would be of direct
concern to the Office of Education, the newly developing National Insti-
tutes of Education, and the Ford Foundation.
43 |

In a very general way, it can be shown that poorly nutured offspring
develop to small size at maturity and, at least in the case of the human,
are thought to suffer intellectual handicaps not remediable at a later age.
The obvious impact of such a set of circumstances on the inadequately nur-
tured minorities in this country and citizens of whole nations abroad is
clear and of first order importance; that is, of course if it can be shown
to be indubitably true.

But considering human development from a mechanistic point of view,
an intriguing problem emerges. It is likely, in the progressive unfolding
of the information system in sequential development, certain stages of CNS
development are particularly vulnerable to biochemical insult, and quite
likely the insult by one or more quite specific nutritional deficiencies.
This can take place either in utero or postnatal development. Viewed as a
parasite, it may be that the fetus is less susceptible if it can draw upon
maternal tissue to satisfy its essential needs even in the presence of
moderate maternal deprivation. This is a reasonable hypothesis and at least
has the virtue of being amenable to examination, in experimental animal
model systems and in the human.

During the postnatal period however, when the plastic nervous system
can be influenced by a variety of environmental influences, the situation
is quite different. The reservoir of essential nutriment is limited to the
dietary intake. Again, as a working hypothesis, it seems unlikely that the
total caloric intake of the developing child is as important in CNS (and
behavioral) development as the availability of quite specific nutrients
during quite specific times in the development process. Alternatively, it
is quite certain that a severe limitation on total caloric intake will divert

otherwise essential nutrients to simple energy producing processes,
44,

Importantly, these possibilities are amenable to fairly precise explora-
tion in well organized biological and behavioral studies of child development.

But, it is possible to expand almost endlessly the major problems
attendent on early human development, Actually the term, though commonly
used, has so broad a connotation as to be useless except for general conceptual
purposes.

One must pause at this point in the general presentation and remark:
"But , what has all this to do with fundamental research." Such a remark
might stem from those biologists who are quite right in believing that much
of the growing edge of the biological sciences is concerned with the study
of phenomena at a molecular level. And this is more than a fashionable comment
to make. But here too, there are areas of science which can profit by a suitable
selection of groups and scientific personnel with the view to utilize a broad
problem as a loosely contrived integrative force.

And as an aside and before exploring this point further, it may be
said that the exploration of molecular phenomena will be essential for the
ultimate understanding of many problems of human genetics, the definitive
examination of agents which influence fertility, the elucidation of the se-
quential phenomena of the determinative forces involved in cell growth and
diffentiation and in organ development, as well as the details of the deter-
minative forces that provide the biological base for intermediary metabolism
and more particularly for lipid transport mechanisms. In these latter in-
stances the techniques of the molecular biologists and his insight into
biological processes become portions of a broader program with program pur-

poses directed toward the elucidation of more complex systems,
45,

But, to return to molecular biology as such, one can touch briefly on
the operations of the systems concerned with DNA ----- > RNA ---~-— > protein
replication systems. The operations of these systems are sufficiently in-
triguing , important and complex to occupy the total intellectual capability
of large numbers of scientists. And, there is no doubt that deeper insights
into the fundamental characteristics of many important and vital biological
systems will emerge.

The studies can be wholly contained within their own physical and chemical
context, and the interaction of such scientists is commonly with others work-
ing at an even more fundamental level. The latter are concerned with the
refinement of spectroscopy, crystalography, microscopy, nuclear magnetic
resonance and complex organic synthesis so as to be able to define the physi-
cal and chemical characteristics of individual system components, They may
do this simply to understand the detailed structure of interesting biologi-
cally active compounds or to learn the nature of the structure which permits
it to perform some unique operation in the system from which it is derived.

Such information is obviously important and essential if one is to under-
stand the physical arrangements of the components of a system, These will,
in turn, influence both the reaction kinetics, and the energetics of the
system and the products that can be derived. The opportunities for progress
in such endeavors are exciting and most certainly should be pursued.

But provision for other studies in the field can also be made, These
might deal with problems at much the same level of biological complexity but
would be more concerned with the operation of these primary systems in the
related fields of immunology, virology, genetics and the genetic basis of

disease and disease susceptibility, Other studies could be undertaken
46,

which relate to the implications of these systems to information processes.
concerned with sequential phenomenon determining cell development, the phe-
nomena of growth and its disturbances.

Continuing this thought, and moving from the general and fundamental
to more specific studies in the applied area, it is apparent that the results
of such studies have application in the clarification of very abstruse prob-
lems the solution of which is important for the prevention or management of
serious disease. Likely condidates for such studies include the examination
of these phenomena in relation to:

e Metabolic disturbances which underlie a variety of molecular

diseases generally characterized by mental retardation, by

disturbances of lipid metabolism and its association with athero-
sclerosis, diabetes and a number of other disease entities.

e Immunological disturbances resulting in a number of autoimmune
diseases.
e Disturbances of growth, perhaps with a view to understand the

process of carcinogenesis.

With this brief background, a general point can be made. The normal
mechanics of the evolution of new knowledge of a fundamental nature can be

of several types.

It may be restrictive, as in Model A :
Model A

Level 1 Application Application Application
A B Cc

Level 2 Paralell pindoheliey/ Paralell
area Vahl Vi ! area
a ns
e { - @
Level 3 Component Component Component
Study A Study B Study C
47.

Or, it may be more general, reflecting the developments in the restrictive
field but also providing for interconnections with other activities that

reflect a broad purpose as in Model B:

Model B

Level 1 bprelis <—— > Application Application
Level 2 u abil <—— 1

 

   

Level 3 Component Component =>. Component
A B Cc

Model B portrays a typical biomedical research program B pursued at the
fundamental level 2, as an element in a more complex interactive series of
related studies with logical bridges of activity laterally with adjacent
fields, with more fundamental inquiry of the components of the system (level
3) and with the array of activities having interaction with one or more con-
plex systems perhaps associated with human biology in health or in disease,
(level 1).

In such a situation..the decision that must be made by an institution
is quite clear. It may conclude that the associated fields are progressing
as rapidly as can be expected through the normal interplay of scientific
forces. Alternatively, the institution may conclude that it can, through the
judicial selection of purposes and the meaningful allocation of resources
provide for substantial increase of the effectiveness of a fundamental field
and at the same time, subserve one or more general purpose. The quality
of the science may be excellent in either case. However, if the latter de-

cision is made the institution has acquired a general purpose beyond the
48,

Simple exploration of the biologically unknown. Importantly too, it can
provide broader resources for a set of related activities which share some
common purposes than when each activity is carried on in isolation one from
another,

Few scientists doubt the ability to plan a move from a specific obser-
vation to a more fundamental level of enquiry in order to explore the general
phenomena involved in an initial discovery. However, scientists are too fre-
quently skeptical about the effectiveness of planned development of broadly
associated fields. It must be admitted that the latter is a harder end to
achieve, and also that attempts in this direction are speculative.

It is nonetheless clear that spectacular insights to quite fundamental
problems are not infrequently derived from very complex systems when these
are readily available. Recent observations within the DNA -—---- => RNA -->
-—> protein system make this quite clear.

The key to this system, the ramifications of which have dominated bio-
logical thought during the past quarter of a century, was derived from a
qualitative observation on a complex system, i.e. the conversion of one strain
of pneumococcus to another which bred true, through the use of a specific
nucleic acid.

The unravelling of the structure of DNA, the concept of a system with
RNA having a template relationship both to DNA and the derived proteins, the
relation of all these to structural elements within the cell, and the complex
of specific enzymes essential for the catalysis of these reactions, were all
high adventure and required an extraordinary biochemical and biophysical effort.
The effort literally involved hundreds of scientists, both in competition and

in collaboration with one another. Yet, there were other contributions which
49,

were essential and which were derived from a study of more complex systems.
Some of these were concerned with metabolic phenomena of bacteria and their
dependent viruses, and the demonstration of the biological characteristics
of naked DNA and the modification of DNA viruses in the cancer field with a
controlled exchange of protein coats. These were indeed very complicated
phenomena to arrange for and to interpret but they gave much point to the
studies that were limited to the isolated systems themselves.

Other equally important data of a qualitative nature have been derived
from the applied fields. One was the introduction into the cell information
system the genome of a virus that itself otherwise disappears, A more recent
occurrence is demonstration of the reverse of the DNA -~~-- > RNA process,
with the availability of RNA dependent DNA polymerase, and the finding that
this is the property of a number of cancer producing RNA viruses.

Demonstrated first for the virus of Rous sarcoma, then for the virus
of Rausher mouse leukemia, it is now known to characterize the RNA of at
least six RNA tumor viruses. It would appear that the core of each of these
contains an RNA-dependent DNA polymerase capable of constructing DNA. This
reverse channel of information permits the derived DNA to serve as a pro
virus or intermediate in the replication of the RNA virus. This is an extra-
ordinary finding which has broad implications in several reaches of biology,
particularly in immunology, quite apart from its impact on problems contained
within the cancer field.

There is no doubt that major and striking advances at a fundamental
level are attributable more to individual insight (or to serendipity) than
to the details of a planned scientific environment, But this need not be

taken as the exclusive principle for the design of scientific organizations,
50,

It is equally true that providing resources are broad, and this is important,
many fundamental advances can be anticipated to derive from the persistent
pursuit of a general purpose in systems that may be quite complex, In many
cases the signal changes have come from laboratories with broad purposes,
with many and diverse biological models and an interesting mix of scientific
personnel, Most of these characteristics can be developed in large groups
or in intimately interacting groups of smaller size. In either case, the
resources required for an effective effort are quite broad.

There is probably no single lesson to be learned from these exciting
developments that has relevance to the administration of scientific organi-
zations other than the importance of providing for such intimate interaction
within the operation of the institution when this is possible. The effec-
tiveness of an individual scientist and the quality of his endeavor at a
fundamental level may have little dependence on the arrangements within the
institution, The effectiveness of his work is frequently due to the opera-
tion of a number of "invisible colleges." In such a situation the develop-
ment of parallel activities and those in the more applied fields are not
then the particular responsibility of any one institution, they are more
the result of the random operation of a set of forces within the mechanics
of science itself,

But the problems for the institutional management are still quite clear.
In the case of a biomedical research enterprise, broad problems in medicine
can be supported as a collection of discrete scientific activities pursued
as ends in themselves; or resources can be allocated in a fashion that provides
a more purposeful setting for the interaction of some of these scientific

forces within a limited number of selected program areas.
Sl.

Which is the wiser view. [It is likely that the wisdom of an institu-
tion will be most manifest in its ability to select the areas which will
benefit most by each method. Most certainly, many require some organization
is only to provide the biological resource; some of these will benefit by
a joining together of several groups in a common effort; other areas may not
profit by such arrangements.

This section probably does not warrant any summary treatment - at. least
not of a substantive nature. The material discussed reflects more of a point
of view concerning the varied opportunities in the biomedical field than a
simple statement of what it is important to do. Then also, it reflects the
view that the major problems suited for medicine and its related institutions
are complex, and that most would profit by some consideration of order and
organization in the allocation of resources with a clear understanding of
the purposes to be subserved., It states that some of these should be stated
in social as well as scientific terms; but there are other types of activity
which should be viewed as parts of broader programs, the individual pieces
of which acquire purpose only when the whole is,viewed within the far reaches
of science. Finally, it reflects the view that the excellence of an effort
and its importance is not derived from the level (i.e. fundamental, applied
or developmental) at which it is pursued. Fundamental research can be trivial;
applied and developmental work revolutionary in its impact on science.

An institution should have a mix of programs when viewed in this general
manner; it will profit by few programs with broad resources, than many which
are inadequately supported; its reputation and its character will reflect
both its purposes and the intelligence with which these purposes are pursued;
but purposes it must possess if it is to have character and these must be

well understood,
52,

Vv

Some Program Proposals

This section includes a brief discussion of several considerations
pertinent to the planning of further University development. Then a series
of program proposals are made and each briefly discussed. Each proposal has
fundamental science as its base but includes the application of new knowledge
to a broad human problem, Taken as a group, they are examples of the type
of program development that is both possible and desirable. The proposals
may have as their major utility the presentation of a point of view that can
serve as the basis for general discussions. Nonetheless, each proposal is
believed to be reasonable, to have a sound base in existing science and if

implemented, would benefit the University.

General Considerations

Institutional planning is a process, which to be effective, must include
the development of proposals which are quite explicit. However, the process
of planning is complex and complicated. Proposals which suggest new dimen-
sions for The University should be made with the view to evoke discussion of
basic institutional purposes; not as a series of propositions easily conver-
ted into a blueprint to guide executive action. The process of change can
be exciting or dull; and resented or accepted by the intellectual community
depending, perhaps, less on the substance of change than on how this is effected,

and the resulting influence on the scientific environment of the institution.
53.

In the planning for institutional development there is obviously an

 

overriding consideration. This relates to how major program innovation is
likely to influence the character of the institution over the middle and
long range period. Generally speaking, it is difficult, and usually not de-
sirable to "turn an institution around” except in the case of institutions
that have run out of a mission or when its program content is judged to be
inadequate. Such circumstances may be particularly important in the review
of mission oriented agencies of an official or an industrial nature. They
do not usually obtain for educational institutions except where senior ap-
pointments over a decade or so have been unfortunate, whose resources for
modern science are inadequate or when it is clear that a new dimension of
science would be advantageous to the institution. The first two of these
three characteristics do not obtain for the programs of The Rockefeller Uni-
versity.

The prospect of further program evolution for the University, can be
in the light of changes in the nature of its programs and changes in the
prospects of science since the last systematic studies in 1952. The review
should examine the basic program and the propositions which were held to be
determining for institutional development at that time. Were the same type
of review undertaken today, would these same propositions be given equal
weight as a basis for change as in the earlier period. Viewed in this light,
most of the principles were obviously sound, though the details of others
would probably be stated differently today.

In this view, program change and the modification of institutional ob-
jectives are viewed within a continuum of program evolution subject to periodic
study bty administration and faculty alike. Such an institutional review re-

quired no formal mechanisms in the earlier times. Programs were smaller, less
54,

complicated, and fewer in number. The program resources were largely derived
from endowment and support of the entire enterprise was at a much more modest
level, Systematic program review was both possible and effective incidental
to the annual consideration of budgets, and the turnover of institutional
staff was quite low. It was possible, under those circumstances, for the
objectives and programs of the institution to be easily comprehended, without
recourse to formal reporting techniques, by an interested senior group of the
faculty, the Director and The Board of Trustees. It was further possible for
programs to be modified almost imperceptibly and progressively within a body
of a slowly changing science,

But those circumstances no longer obtain in the University: nor do they
in other settings where research is pursued as a primary institutional objec-
tive. Also, contrary to common comment, changes that are increasingly apparent
in research organizations relate less to the origin of research support than
to the size, complexity and substance of the programs, to the pace of present
scientific discovery, and in the magnitude of the resources now necessary
for a productive enterprise. In the case of The Rockefeller University, these
changes have had a particular impact due to the rapid evolution of the bio-
logical and clinical sciences during the past two decades, and the disappearance
of the hard barriers that heretofore separated the biological from the beha~
vioral sciences. These changes are fundamental and have largely occurred
since the last major review.

Considering these happenings, it is appropriate to pose questions, the
answers to which will have immediate impact on the direction of program

development.
55.

The first relates to the general purposes of The University. Should
The University continue to consider itself a specialized university, the pro-
grams of which will continue to emphasize those aspects of science which have
particular relevance to the human in both health and disease. One must be
quite explicit in developing an answer to this question since in the final
analysis all science has relevance to the human species, the betterment of
his existence, an improvement in the circumstances of living and his under-
standing of both himself and the world about him, The question is more simple
and more blunt. Its major thrust concerns whether the University will continue
to emphasize objectives with a medical connotation in the forefront of its
Planning; and whether it will develop its more fundamental programs in a
fashion that provides a sound science base and a lively scientific environment
for the pursuit of other acticities of a more applied nature; and whether
ample provision will be made for the latter programs that have direct rele-
vance to an understanding of human development and the maintenance of health
as well as the understanding of disease, its prevention, amelioration and
cure,

In arriving at an answer to this quite fundamental question it must be
understood that concepts of medicine have been considerably broadened, since
the establishment of the Institute at the turn of the century, and importantly,
since the examination of the Institute in the early fifties. The biomedical
sciences now encompass the broad application of information from the behav-—
ioral as well as the biological sciences for the betterment of man, the phe-~
nomenon of human development, and the impact of an increasingly hostile
environment on the human within broad ecological considerations. The major

question relates to the extent that “health" and "medicine" are a major
56,

directive force which will continue to be dominant in institutioanl planning -

o

av
an answer to this question cannot be satisfied by disucssions more characterized

by sophistry= than clarity.

The second question relates to some of the procedures The University may
find useful in the fulfillment of its purposes. As indicated earlier, the
development of any broad field is largely dependent upon the random forces
within the dynamics of a lively science. However, it is frequently possible,
as a matter of institutional policy, to facilitate the interaction of discrete
groups within a broader program with general but quite explicit purposes.

An informational system; importantly, and in either case, it is likely

 

that a more formal system of program examination is needed by The University
for the provident expenditure of the funds available. It is likely that The
University is of a size and complexity that requires an informational system
that minimally will provide for the submission of relatively simple annual
scientific reports by each of the senior faculty members. Each such report
could reasonably contain in summary form:

e A brief account of activities during the preceding year,

® A projection of the direction of program during the coming
year within middle range (perhaps 5 years) expectations,

e The current distribution of personnel and resources
together with an estimate of their adequacy in relation
to further program development,

° A brief discussion of collaboration with other scientific
groups (within and external to The University) which may
have influenced the course of development and the desira-
bility of undertaking collaborative activity in the future.

 

1
Sophistry - deceptively subtle reasoning or argumentation ~ Webster.
57.

The report might also contain the statistics of the operation relative
to dollars expended, sources of support, and personnel changes. The bulk of
this information can be supplied from a central source,

Such a reporting system would have many uses for the administration.

It would provide a firm factual base for a consideration of the operation

by the senior faculty, the executive officers of The University and its

Board of Trustees. In that the assembled reports would be highly substantive
in nature, they would be useful for planning purposes and in the allocation
of resources. Such a set of reports are an essential for any reasonable ex-
pansion of the activities of The University. Quite apart from the utility

of such information for internal use, The University must have a more factual
account of the ongoing activity if serious consideration is to be given The
University by prospective donors,

Actually, an informational system such as is proposed, is an essential
for the prudent management of the resources available quite apart from the
utilization or resource allocation as an instrument of policy in the evolu-
tion of new institutional programs. An informational base is always both
essential and important for the allocation of resources in any situation not
characterized by unlimited funds. The point to be emphasized is that the
informational base must be sound if the intellectual community as a whole is
to reap the greatest benefit from the resources available, The fact that
The University receives approximately 40 percent of its support from sources
other than endowment makes such a factual basis for programming all the more
important, if the overall enterprise is to achieve the long term stability

essential for a productive program.
58.

Program Proposals

Several programs are proposed for initial consideration. Each would
add a new dimension to the intellectual community; each would require new
physical resources; each would result in new operating relations within the
metropolitan community; and each has as its end purpose the solution of a set
of human problems. Consideration of these problems may be helpful in the
broad definition of institutional purposes,

Research in reproduction. <A significant program in this area can only
be proposed in a document such as this in general terms; the specific ele-
ments deemed to be feasible for a single institution will be determined
largely by the resource ultimately developed, its location and the relations
which may evolve with collaborating institutions.

A comprehensive program would entail both basic and applied investiga-
tions in the behavioral, biological and clinical aspects of the entire range
of reproductive phenomena including: (a) developmental aspects of puberty,
including, for example, such problems as precocity, delayed puberty, abnor-
malities of gonadal differentiation and psychological aspects of adolescence;
(b) adult sexual phenomena including, for example, mating, conception, con
traception, fecundity, infertility, the climacteric, and psycho-sexual phe~
nomenon generally; (c) pregnancy and such related aspects as spontaneous and
induced abortion, complications of pregnancy such as toxemia and extopic
pregnancies, and maternal mortality and morbidity; (d) perinatal and early
post-natal phenomena with emphasis, for example, on fetal loss, prematurity,
congenital abnormalities and the tetralogical problems related to prior ex-

posure to physical and chemical agents.
59.

Needless to say, an institutional program would be more modest in
coverage and could conveniently cover the period of family planning, preg~
nancy and early development of offspring. Such studies should be integrated
with subsequent observations on the psychological and somatic development of
the offspring. However, these latter efforts would be more feasible out-
side of a reproduction research program proper, but could be included in
related programs such as have been proposed below for the behavioral sciences,

Basic investigations in reproduction would entail work with a number
of animal species as well as with the human subject. There is a growing
skepticism as to the clinical significance of reproductive phenomena observed
in the rodent and in other lower forms. Accordingly , there is greater need
for emphasis. on primate studies. This shift to a major emphasis on the use
of primates in animal studies imposes logistical and budgetary problems of
major administrative importance, These are especially burdensome in a
crowded urban setting. Otherwise, the usual facilities and resources for
biomedical animal studies would prove adequate.

The clinical studies outlined above would qntail many special arrange-
ments in order to blend the complex service requirements with the research
function, Experience has shown that primary clinical control is essential
to sound investigation on the human subject. No existing care facility now
catering to a broad range of problems in human reproduction provides sufficient
clinical control to serve as an ideal focus for the proposed research program,
There would be needed a new type of community-based facility with suitable
related in-patient resources. Both would require proper full time clinical
and research personnel. The administrative arrangements would be such as to

provide optimal clinical care as an adjunct to the primary research function,
60.

A favorable setting for such a facility might be in a newly developing
community health care program which services a mixed socioeconomic popula-
tion. Two such programs are now in planning; one by the Roosevelt Hospital,
the other by the French-Polyclinic group. A model laboratory clinical re-
search center can probably be incorporated within the broad planning for these
enterprises, It would then be quite feasible to provide for both long term
and short term studies as a cooperative extension of either of these programs.

In theory at least, such a research function could be grafted on to a
well planned and properly organized pre-paid comprehensive medical care sys-
tem, including both in-patient and out-patient resources, together with a
staffing and administrative pattern which would allow for a high degree of
clinical control. However, the prospects for such a program are not good
in the metropolitan area.

Admittedly, many acceptable studies are presently conducted in various
centers providing obstetrical, gynecological and family planning services.
For the most part these are short term, highly specific investigations with
relatively poor follow-up and somewhat dubious records. For the most part,
such research yields highly circumscribed data and provides little over-all
comprehension of human reproductive processee. With a rapidly changing
moral and legal basis for human conduct in this area, even the most rigidly
devised and carefully executed studies are fraught with difficulty. The de-
velopment of resources and programs in these broad areas which will yield
comprehensive and reliable data under conditions of optimal clinical care

on a sound community basis presents an enormous challenge.

 

Jan exception to this may develop in newly planned studies at the Columbia
Presbyterian Hospital Center. As best one can gather from informal enquiry,
a new center will emphasize the family planning process and there already
exists an activity in the area of child development. These are not planned
as a single enterprise.
61.

For example, most of the antifertility agents in current use are attended
by a variety of biological phenomena which can be grouped under the heading of
continuing pseudopregnancy and originate in a modification of the operations
of the endocrine system. These agents directly influence ovulation and im-
plantation, but the actions are also reflected in modifications of water and
electrolyte balance, in changes of mood, and in modification of clotting
mechanisms of the blood. They also produce cellular change in tissues that
are common target areas for carcinogenesis. Despite their practical impor-
tance and general use, these agents have not been studied either in animal
model systems or in man in a definitive fashion. Qualities of safety and
effectiveness have rather been assessed by the net results of massive field
trials. It is unlikely that wholly new agents will be as easily introduced
in the future as in the past. Equally important, the bulk of the commonly
used antifertility agents group around a single type of biological activity
(i.e. progestational) leaving the many other phenomena of fertility, fertili-
zation and implantation more or less unexplored. In consequence, the field
continues to be open to innovative exploration,*an essential of which is a
more definitive understanding of normal processes.

Importantly, the study of the physiology of fertility and its control
is only possible within a setting that encompasses the entire gamut of ser-
vices that are essential for family planning; including genetic counselling
and the optional termination of pregnancy. But the associated services them-

selves provide broad investigational opportunity.

 

linis area of early human development is one of those selected for
extensive development by several units of the federal establishment.
62.

Genetic counselling is in the early stages of its development, Even
so it now requires resources for chromosonal analysis and metabolic study of
cell clones derived from the developing fetus. There is thus available rather
unique biological material for the exploration of many aspects of human genetics
and their reflection in metabolic phenomena. The manipulation of the genetic
substance, including a repair of genetic "defects" will continue to be a
speculative though interesting enterprise. Meanwhile, developmental work
is required to convert a series of research procedures into routines available
for more general use.

Then too, since the termination of pregnancy is now optional, the oppor-
tunity for systematic study of the biochemical and biological phenomena which
attend early pregnancy are open for reexamination within a context of timed
human pregnancies,

The complex problems associated with fetal development are equally
obvious. The simple morphology of development has been the primary concern
of anatomists and embryologists since time immemorial. More recently, it is
possible to consider development from a substantially broader point of view,
The extraordinary changes in the biological systems which attend early de-
velopment when viewed as the result of the sequential operation of the cell
information systems bog the imagination, but an exploration of these phenomena
must be begun,

Research in the development of human behavior. Studies in this area

 

can be most rewarding in the immediate and middle range future. This is in
part because of the deep insights that have been developed on the consequences
that attend the early environmental experiences of the new born, in part be-
cause of the demonstrated influence of the early years on the characteristics

of later intellectual development, and in part because of an increased capa-
63.

bility to provide bridges between the biological and behavioral phenomena
that attend human development,

These features of human development with their broad base in comparative
studies are particularly suited for consideration by The University because
of already existing excellence in several related fields, But it is doubt-
ful whether these scientists can take advantage of the general opportunities
unless there is an expansion of staff in several critical areas and unless
more suitable clinical and animal resources can be made available,

Some indication of the specific nature of work that can be undertaken
as an extension of ongoing programs are contained in recent proposals for
studies of "Human Development and Learning" and "Primate and Animal Studies
of Behavioral Development.” These proposed studies are quite specific and
merit favorable consideration in their own right. However, they would bene-
fit from a broader statement of purpose directed toward the understanding of
the biological and behavioral determinants of human development,

For such a group of related studies to be effective, small groups of
children alone and in association with elements,of the family group would
have to be available under highly controlled environments during major pore
tions of the early development period. These observations are not easily made
in the conventional experimental school; novel arrangements are necessary;
and it is necessary to include the study of special groups of children in
settings different from those obtaining in a metropolitan environment.

The basic requirements for most of these studies is a physical resource
and a program that maintains a systematically ordered population group

covering the period of development to be studied, assorted biologists and
64.

behavioral scientists with suitable motivation who are grouped around one
or more of the major areas of exploration to be undertaken and the broad
back up of a number of animal model systems, these to include primates.

The clinical expression of these resources are now conventionally found
in well baby clinics, pediatric departments of medical centers as well as in
experimental educational settings. Most of these resources are organized
quite separately one from another and are primarily suited for the delivery
of specialized medical or educational services. The opportunistic super-
imposition of investigative activities upon such service activities are too
frequently ad hoc in nature. As such, the services do not provide an ade-
quate central resource for really critical research.

But, it is possible to provide for a more suitable clinical setting and such
an organization could provide quite adequate health services. A suitable popu-
lation group, when properly organized, would require a mix of clinical care
personnel and an adequate investigative staff and suitable back up resources.
However, an important point must be made. It is unlikely that any population
group desired for study can be held together for an adequate length of time
unless a set of related health services of high quality are provided as an
essential core for the program,

An inordinate amount of space, in this discussion, has not been given
to these aspects of early human development. There is no doubt that the en-
vironmental circumstances attendant on this early period are as important
in the determination of adult capability as is the inherited genetic capa-
bility. The initial years largely complete most of the biological and much
of the fundamental behavioral characteristics upon which subsequent develop-
ment into adulthood will depend. It is true that this obtains for the more

general biological functions such as body size, etc. More important though,
65.

is the conditioning of the quality of the cognitive faculties, the patterns
of perception, learning, speech and language which may be difficult to modify
during subsequent development. Our present systems of child rearing now

pays particular and detailed attention to the biological needs of the devel-
oping infant and the young child, with little attention to behavioral and
intellectual development prior to the child's entrance into the formal
educational process. By this time, much that is not reversible has already
taken place. Present information does not provide firm guides to action,
only an appreciation of the importance of this period of growth,

Substantial benefit would derive from an association of these programs
with some of those considered under the heading of Research in Human Repro-
duction. Both types of study require access to a general population with a
mixed cultural background, the ability to select small samples for special
study, and service arrangements which would tie family group to a study
program for long periods of time.

All these could be arranged within the operations of a comprehensive
community health program, particularly one that encompasses the study of
human reproduction from a broad point of view. It is further pertinent to
point out that the animal resources for the two general types of study have
much in common, These would require fairly extensive control of the environ-
ment of a number of animal species including primates. Both sets of studies
would require varying degrees of control over both the behavioral and bio~
logical characteristics of the environment.

The suggestion emerges from these considerations that The University
might well consider the possibility of establishing a subdivision of its
activities directed in a purposeful way to the phenomena attendant on

Human Development. This would be a major university enterprise important
66.

in itself but with broad interaction both with the metropolitan community
and some of its institutions of higher learning.

Research in Atherosclerosis is another area that might be considered

 

for emphasis as part of the further development of The University. The
general nature of the opportunities for research in atherosclerosis was
briefly discussed in Section IV. Advantage could be taken in such a develop-
ment, of the existing commitments of University scientists to a number of
associated problems that relate generally to the disease, But the scale of
these activities is too small for them to be considered a major university
program,

The importance of medical problems associated with atherosclerosis is
reflective of the fact that the major problems in "medicine" today are in
the chronic disease area. Many important studies of chronic diseases can
be conducted in the conventional hospital setting, particularly when the
studies are directed toward acute phenomena which appear intercurrently
within the longer term progress of the basic illness, But the study of the
disease process itself requires the long term study of individuals with dis-
ease against a backdrop of a developing understanding of the normal operation
of the systems particularly involved in the disease process. Furthermore,
when the special disease under study is due to an underlying disturbance
which can be caused by more than a single cause and the morphology of a sys-
tem limits the nature of the phenomena attendant upon the development of overt
disease, then the disease models which can contribute to an understanding of
the pathogenesis of disease are numerous. This set of complex requirements
has tended to limit the effectiveness of programs in many areas of chronic
illness in the conventional University Hospital and this is even more true

for atherosclerosis than for many other disease conditions.
67.

Problems of this order of complexity should serve as a special challenge
to medical research organizations because of the selectivity they can exercise
in the subject material undertaken and their ability to provide for the back
up research that is essential. Contrary to the University Medical Centers,
the research oriented institution does not have the need imposed upon it, to
provide for a complete array of specialty groups fro both medical education
and specialty training. Furthermore, the urgencies of these needs in the con-
ventional medical center setting tends to occupy so much of the faculty time
that their activities are generally hospital centered. To date, medical
school faculties have been quite unable to participate in the development of
broadly based community programs, a primary purpose of which is the conduct
of research, These institutions are under such heavy pressure to provide
for medical service programs as ends in themselves and for the progressive
modification of medical service systems, that they have little opportunity
to utilize the new arrangements for research purpose. Research oriented in-
stitutions need not suffer such distractions.

Apart from these organization considerations, the undertaking of a major
program in the field of atherosclerosis has much to recommend it as one of
several in the chromic disease area that might be given high priority by The
University. Program development can be based on an extensive body of infor-
mation that relates to lipid metabolism and lipid transport. The study of
these systems in diabetes, in obesity and in what would appear to be uncompli-
cated atherosclerosis would provide information on the interconnections of
a series of important disease entities, and the consequences of these dis-
eases to the target organs such as the retina, the heart, the kidney and

the Central Nervous System,
68.

Such a centrally important disease process warrants attention in its
own right, Additionally, as the result of recent decisions made at a national
level, more than ordinary financial support will llkely be available despite
an almost certain continuation of constraints on the federal support of re-
search,

Looking to the middle range future (5-10 years) it is likely that our
knowledge of this disease will develop rapidly. This estimate poses a serious
problem for the individual investigator. For a productive program it is
likely that he must associate himself with a national program that provides
tight coupling of his own activities with others in a collaborative effort.
Alternatively, an institution may elect to emphasize research in atherosclero-
sis as an institutional effort of major magnitude, Such an effort would
represent a substantial challenge. The challenge derives from the fact that
the exploration of the disease with suitable leadership at both the labora-
tory and clinical level can be guided in a fashion that has a high prospect
of success and the achievement of a leadership role in a program of obvious
national importance, .

Should this area be considered in the further development of The Uni-
versity's programs, then it should be considered in relation to the studies
on human reproduction and human behavior discusses above,

A comprehensive program in atherosclerosis has as an essential, the
availability of several controlled population groups. One must be of sub-
stantial size for random sampling and for control biological studies. Then
there must be smaller groups such as are contained in specialty clinics with

well documented patients manifesting systematic disorders of a metabolic

nature. Particular attention in these groups can be given to the phenomena
69,

attending diabetes, heart disease, obesity and other groups at high risk,
including patients with familial metabolic defects. Such patient populations
can be grouped around any one of several clinical settings which have as their
purpose the provision of comprehensive health care, a common requirement
for the study of human development noted above.

Supporting these clinical resources, well instrumented biochemical
and biophysical laboratory facilities of more than ordinary volume capability
must be available. These would be needed for the repetitive study of the
biological systems believed to be important in the genesis of the metabolic
disturbance and to monitor changes purposely induced. It is obvious from
this brief consideration that for such studies to have the opportunity for
success, there must be a broad institutional commitment to pursue the problem
of this disease in depth, in breadth and for a long period of time.

Within such a view the present Rockefeller Hospital would continue to
be a critical resource for the performance of the detailed studies not
generally suited for the conventional clinical setting. But, as with the
studies on human development, the primary clinieal resource would be the
community population for the study to have reasonable prospects for success,

Other areas of science will not be explored in this presentation.

 

Those given summary treatment can be taken as typical examples of probelms
that would profit by expansion of resources, that couple laboratory and
clinical resources such as might be possible in association with one or
more health care systems,

But a limited examination of a number of other areas of University
activity show many to have a feature in common, This is an ability to

make the present activity more significant through an ordered expansion,
70,

As another general characteristic of a number of activities reviewed, many
would profit if expansion is provided in a fashion that would facilitate
contact of the activity with other ongoing activities with parallel objec-
tives. These observations do not derive from a comprehensive survey of the
variety of programs now contained within The University. Such an examina-
tion, to be undertaken, would have as a requirement a more effective central
information system than is now current.

Further, the present study has been limited to some activities that
are medically oriented, more so than is generally true of many of the bio-
logically oriented programs of The University. Nonetheless, the study should
not be taken simply as special pleading for a broader orientation of Uni-
versity activity toward programs of medical and consequently of social in-
terest. Rather they reflect four general and separable points of view.

The proposals in the field of human development have the possibility
of achieving two scientific and one organizational objectives.

e The time is particularly ripe for the biological and behavioral
sciences to join in common cause with the view qf clarifying our understand-
ing of the influence of genetic as well as pre and postnatal environmental
factors on the ultimate potential for biological, emotional and intellectual
development. Studies in these fields can have critically important impact
on very general concepts of child development and the relation of these to
the conventions governing the rearing of the child and the early stages of
the educational process.

e The studies on human reproduction proposed for consideration can
give prominence within the programs of The University to many scientific
activities that are equally critical to the problems of population and popu-

lation control, a general problem of substantial social import.
71.

e From the standpoint of organizational considerations, the complex
of study program proposals in these general fields of human development pro-
vide a natural bridge for redeveloping more intimate working relations of
The University with the Rockefeller and other major foundations with long
term interests in these areas, They would also provide a productive working
link with a population segment and with some of the intellectual elements
of the metropolitan area,

The proposals covering the field of atherosclerosis reflects the view
that the state of knowledge of this process permits the statement of some
general working hypotheses that warrant definitive exploration. The complex
of disturbances which lead to the evolution of the disease are important, as
are their expression in overt disease of vital target organs,

But, more importantly, each study emphasizes the view that the oppor-
tunity for striking advances in medicine has shifted from phenomena that
can be observed over short periods, to phenomena that can only be productively
examined over long periods. The medical community has found it difficult to
adapt to the new situation even though both eduaational and research oppor-
tunities are influenced equally. In such a situation, the hospital and its
laboratory resources become ancillary to the study of population groups over
long periods of time. Consequently, most chronic illness is not suitably
studied within the confines of the usual specialty clinics of The University
hospital. Other arrangements are essential and these will be most effectively
developed in association with the comprehensive health care systems which
are now beginning to develop. But, if these are to be useful for both research
and educational purposes, then wholly new concepts in their organization must

emerge, It is believed that the clinical needs for sound studies on human
72.

development and on atherosclerosis would be helpful as guides to the overall
design of such a resource, The scientific opportunities are obvious.

Not related to the specific studies proposed, but more to the general
area of concern for The University is yet quite another consideration, It
is believed that the present Hospital of The Rockefeller University is impor-
tant but only suited for a limited type of study, Further, to provide a more
general facility, such as could produce a capability for intimate coupling
of clinically and biologically oriented scientists within a common environ-
ment, is prohibitively expensive even at the current program level of medical
research, Were this done, it would still not provide a suitable environment
for the comprehensive study of most chronic disease, Other arrangements are
required. But perhaps of fundamental importance is the conviction that the
present medically oriented groups and the resources available to them are
inadequate for a vigorous program of medical research such as would provide
both balance and opportunity to the more biologically and behaviorally oriented

scientists of The University.