ARTHUR KORNBERG, M.D.

NIH, ALMA MATER

I RECENTLY ATTENDED the first National Institutes of
Health (NIH) Alumni Reunion in Bethesda. For me,
and undoubtedly for others, it was the first alumni re-
union of any kind. Perhaps we were all rather reluctant
to repeat the experience of the college graduate who re-
turned home from a class reunion in a very depressed
mood. "My classmates" he told his wife, "have all
gotten so fat and bald they didn't even recognize me."
We did not gather from distant places primarily for
good fellowship, although we found that the warmth
and devotion of our NIH friends would have been
worth the trip. Rather we came together because the
NIH, more than any college or university, shaped our
scientific lives in the most profound way. The NIH is
an institution of such unique quality, and of such im-
portance for the training of future generations of scien-
tists and for the health and welfare of our society, that
we must do everything possible to preserve its vigor.
Institutions and nations come and they go. In worry-
ing about the longevity of the NIH we should know
something of its origins and history. It will help us as-
sess its physiological age and anticipate the problems
that might cloud its future.
The NIH started in 1887 in a small room at the Pub-
lic Health Service Marine Hospital in Staten Island. It
was a laboratory in which to practice the new science
of bacteriology. Four years later, in enlarged quarters
in Washington, it was called the Hygienic Laboratory.
Joseph Kinyoun, the first chief of the laboratory, was
sent for training under Robert Koch in Berlin and to
the Pasteur Institute in Paris.
In 1901, the Congress provided for a new and still
larger laboratory at 25th and E Streets to investigate in-
fectious and contagious diseases and other matters per-
taining to the public health. Some Public Health Ser-
vice (PHS) officers were detailed from time to time to
the laboratory in order to become familiar with bac-
teriologic diagnosis of contagious diseases and to inves-
tigate their causes and prevention.
Original and important investigations of epidemic
diseases such as cholera, plague, and yellow fever were
made at the Hygienic Laboratory.
One of my favorite microbe hunters of this era was
Joseph Goldberger. He came to this country from Eu-
rope in 1881 at the age of seven. He grew up in New
York's Lower East Side in poverty. Yet he managed to
go to City College and get medical training at Bellevue
Hospital Medical College, now New York University
Medical School. He joined the PHS in 1899, not for
money but for adventure. For the next ten years, he
made important contributions to the understanding and
control of several infectious diseases including yellow

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fever and dengue fever, each of which nearly killed
him.
In 1914 he was sent to the South to find the orga-
nism of pellagra. Each year epidemics of this disease
afflicted hundreds of thousands of people with skin le-
sions, weakness, diarrhea and mental derangements.
Many were committed to asylums. The economic ef-
fect of the disease was widespread on the cotton plan-
tations where the workers were afflicted.

Goldberger observed that in institutions with severe
epidemics, inmates were affected, but the staff people
were not. This was a remarkable disparity for a con-

Dr. Kornberg ( AnA, University of Rochester,
1940) is Emma Pfeifler Merner Professor of Bio-
chemistry at the Stanford University Medical
School. He received the Nobel Prize in Medicine
in 1959. This paper is based on a talk he deliv-
ered on the occasion of the first National Institutes
of Health Alumni Reunion, held in Bethesda,
Maryland in April, 1975.

tagious disease. He noted, too, that whereas inmates
ate corn bread, grits, molasses, and fat back, the staff
ate meat, milk, and vegetables. When he fed the in-
mates' diet to dogs, they developed blacktongue, the
canine analogue of pellagra. When he fed them meat,
milk and vegetables, they were cured. People fed a
good diet were miraculously cured; and hopelessly in-
sane people were discharged from asylums.
Goldberger proved by controlled experiments that
pellagra is a dietary deficiency disease. This landmark
discovery of a nutritional deficiency led him to inten-
sive assays of foods for their anti-pellagra value. Nu-
tritional research was a novel departure for the Hy-
gienic Laboratory, which had been oriented to infec-
tious diseases. Unfortunately, Goldberger died in 1929,
eight years before nicotinic acid was identified as the
anti-pellagra vitamin.
During World War I, the Laboratory supported basic
studies in physiological chemistry, such as those of
Baird Hastings, who attended the reunion.
The name of the Hygienic Laboratory was changed
to the National Institute of Health in 1930. Neverthe-
less, I would date the modern history of the NIH from
1938. This was the year that signalled a major increase
in size and scope. In that year the NIH moved into six
red brick buildings of Georgian design, built in Bethes-
da on a 90-acre estate donated by Mr. and Mrs. Luke
Wilson. Eventually, the campus swelled to over 300

the PHAROS, July 1975

acres and 50 buildings housing 12,000 staff. Beyond
growth in size, the move to Bethesda also led to a
broadening of research directions, most notably crea-
tion of the National Cancer Institute.
I find it hard to believe that my own acquaintance
with the NIH goes back almost that far. [If I include
some personal narrative, it is because I believe that my
experiences at the NIH were reasonabIy typical of its
many hundreds or even thousands of alumni, who, over
time, have formed the essence of the institution.]
I came to the NIH in the fall of 1942 as a commis-
sioned PHS officer. I had been transferred from sea
duty at the suggestion of a ship captain exasperated by
my inattention to naval etiquette. I was assigned to
work on rat nutrition in a section directed by William
H. Sebrell. He had succeeded Joseph Goldberger and
had been trained by him; so had some of the labora-
tory aides who prepared the synthetic animal diets we
used. I had intended to practice medicine. But after a
year, I found full-time laboratory investigation even
more challenging and exciting. Thomas Parran, who
was then Surgeon-General, told a group of us that he
wanted PHS officers not so well-rounded but sharper
at the edges. So an assignment to the NIH might be
more than a two-year rotation.
Rat nutrition and a search for the vitamin, folic acid,
were interesting until I saw greener pastures. I was en-
thralled by a seminar in which Edward Tatum present-
ed the one gene-one enzyme concept based on his neu-
rospora work with George Beadle. Seminars were held
then in the quaint room of a rustic cottage, called Top
Cottage, later moved by the Clinical Center and erased
by Building 3 1. An even greater revelation for me was
the enzyme work of Fritz Lipmann, Herman Kalckar,
Carl Cori and Severo Ochoa. Here was a window on
another world of science: enzymes of astonishing speci-
ficity and catalytic potency linked the combustion of
foodstuffs to the generation of ATP which made the
cell grow and the muscle move. What fantastic natural
poetry! But there was no one at the NIH doing such en-
zymology or biochemistry.
I will be forever grateful to the NIH for sponsoring
me as a PHS officer to train with Severo Ochoa in New
York in 1946 and then with Carl Cori in St. Louis in
1947. I was convinced that the vitamin hunters had ex-
hausted their prey, as had the microbe hunters a gen-
eration before them, and that the next era would be-
long to the enzyme hunters.
The NIH to which I returned in 1947 had not
changed much in the war years, but seeds had been
planted and were beginning to sprout. The next year
an S was added after Institute on the lettering of the
Building 1 architrave, signifying the creation of Dental,
Heart, and other categorical institutes. The Research
Grants Division was established. Planning for the Clin-
ical Center was started.
I regard the five years between 1947 and 1952, dur-
ing which I worked at the NIH, as the most productive
and gratifying in my scientific life. I recall a visit in
1950 from Gerty Cori. She lamented my being in a

the PHAROS, July 1975

government laboratory. How could I convince her that
with my close colleagues Bernard Horecker, Leon Hep-
pel and Herbert Tabor I was enjoying an ideal academ-
ic environment.
When I moved in 1953 to be a professor and chair-
man of a department in a medical school, I made two
errors in judgment. I believed that the advent of the
Clinical Center and the disease-oriented institutes
would stifle basic research at the NIH. And, I believed
that administrative life in a university would be unob-
trusive. As we all know, research at the NIH flourished,
and I learned that university administration can indeed
be burdensome.
The greatness of the NIH rests on achievements in
three areas: first, research at the NIH, second, guid-
ance of the extramural grants and training programs,
and third, training of scientists at the NIH. Each has
been successful beyond my most optimistic expecta-
tions.
As for research achievements: first, in the past 25
years, no single institution has so dominated the jour-
nals of basic medical science, and some of these con-
tributions have been of stellar magnitude. I could
easily use the rest of this essay to recite them.
Second, the extramural grants and training pro-
grams have been the single most important foun-
dation for the biological revolution of the postwar
period. Let me expand on this.
Guided initially by NIH scientists, the peer review
system for awarding grants and fellowships has admin-
istered tens of billions of dollars with a scrupulous re-
gard for quality and without a hint of chicanery. I know
of no government program of this magnitude with such
a magnificent record.
The results of the massive support of biomedical sci-
ence training and research during the past 20 years
have been extraordinary. No one imagined that we
would acquire so quickly the firm grasp we have today
of the basic designs of cellular chemistry and its regula-
tion. The nature of heredity, clouded in formal genetic
language only 20 years ago, can now be described in
explicit chemical terms. If the first half of this century
belonged to physics and chemistry, then the second
half belongs to biology.
Knowledge of the structure of genetic material and
the way in which cells regulate their expression prom-
ises great benefits in medicine and agriculture. Vigor-
ously applied, this new knowledge could transform the
image of health and disease as drastically as any ad-
vance in history. Beyond these practical benefits, the
new knowledge of gene and cellular structure gives us
deep esthetic pleasure. We have new insights into the
origin of life on earth and a basic appreciation of how
man is related to his earthly ancestors and neighbors.
I have cited two facets of the NIB: intramural re-
search and the extramural support programs. The third
facet, the training of scientists at the NIH, is less recog-
nized but of equal rank with the other two. In the un-
trammeled atmosphere of well-equipped, well-directed
laboratories, hundreds upon hundreds of young M.D.s

99

and Ph.D.s were introduced to professional science.
Some remained at the NIH. But the majority left to
staff research, clinical, and administrative departments
throughout the world. Today they populate and, as
professors, chairmen, and deans, direct the finest uni-
versity departments of basic medical science and clin-
ical science. Today they are the clinicians in the lead-
ing hospitals. Today they are the research directors of
the foremost pharmaceutical companies. They bring a
novel outlook from their training in basic biological
and chemical sciences to the lecture hall, laboratory,
bedside, and to industry. The NIH is truly a National
University of Health.
I am not now part of the NIH nor do I have senti-
mental attachments to institutions. I therefore can state
with minimal bias that the NIH has been and is today
an integral part of the machinery of basic and applied
research in the country, and so it must remain. The
NIH is absolutely essential for the future health and
well being of our nation and all of mankind.
Why then was there an NIH Alumni Reunion? The
alumni gathered, not only to recall the past and pres-
ent achievements of the NIH, but to express their con-
cern for its future. Despite its superb record, and its
dedication to science and conquest of human disease,
the NIH is being subjected to severe criticism. Unfor-
tunately, the NIH has grown to a size that makes it vul-
nerable, although much of this growth was due to pub-
lic health programs imposed upon it. The enlarged
budget is an obvious target for budget cutting and for
anti-science forces. As with all worthwhile things the
struggle for survival is never won. This is even more
true for support of science than for other institutions
in society. Let me explain by contrasting the nature of
science progress with the support of science by society.
The goals and attitudes in research have not changed
in any fundamental way for hundreds of years.
Achievement in science depends on the same human
qualities required in other professions, in art, and in
business. We find among scientists the same variety of
abilities and styles, of strengths and weaknesses, that
are found among lawyers, doctors, politicians and busi-
nessmen. What is different is science itself. Science dif-
fers from other human activities in the way it is prac-
ticed and the way it progresses. The pattern of science
is a stepwise extension of what was done before.
The steps are small and usually do not follow a path
or seek a goal. Rather they develop as in Walpole's
story of three princes of Serendip, who in their travels
were always discovering by chance or by sagacity things
they did not seek.
Whether serendipitous or planned, scientific activity,
seen with perspective, always moves forward. Science
is thus unique among human endeavors in the polarity
of its movements. We call it progress. I must repeat
that it is science that is extraordinary, not the scientist.
Because science enables ordinary people to express
their creative talents in a purposeful way, their hum-
ble probings, picayune individually, combine to exert

100

irresistible forces in exposing the grand designs of
nature.
The flow of science to me resembles the movement
of rivers. Rivers have a fixed direction and continuity
as they flow down to the sea. Like rivers, the pace and
dimensions of scientific movement vary enormously.
But shallow or deep, broad or narrow, sluggish or
swift, the movement is inexorably forward.
There may be eddies in sciences as in rivers; and
there may even be apparent reversals of direction. In
recent memory, Profim Lysenko and his followers in
the Soviet Union stifled genetics and molecular biology
there for a whole generation, and Soviet medical sci-
ence and agriculture still carry the deep scars of that
period.
In contrast to the forward movement of science, the
support of science by society has no direction. The at-
titude of society toward its social problems has been
likened to the swing of the pendulum. And so also the
support of science, rising and falling as it has through-
out history, does not resemble a river, but rather the
movement of tides.
In the support of NIH and science in this country,
we saw a very low tide during the 193Os, before the
War. Then there followed a strong high tide for twenty
years after the War. For the past ten years, the support
of science has been visibly ebbing away. Funds for ba-
sic research by excellent scientists at the NIH and else-
where have been cut at a time when inflation and ad-
vanced technology call for increases. And the support
for the training of our best young scientists has been
drastically curtailed. This support for research and
training cannot be finely regulated. When the flow of
science support is turned down, the stream of progress
dries up and cannot be restored for years. Why are we
reversing the tide of science support?
It cannot be for reasons of sound economy. We in-
vest in medical research only about 3% of the gross
product of a 100 billion dollar health industry. There
is no industry based on technology today that spends
less than 5% of its product on research and develop-
ment.
The lifeline of medicine has been and will remain
science and technology. When medicine grapples with
the unknown, the art of witchcraft eventually super-
venes. In the future, medicine must become more re-
liant on science and technology, not less so.

The difficulty with research support in our society,
I have come to realize, is the failure to understand the
nature and importance of basic research. This is true
of the lay public and physicians, of legislators and po-
litical leaders. They do not realize the long time scale
of basic research, and that its utility, its applicability,
is not obvious. If it were, it would be developmental
rather than basic research. They do not realize the
quantitative scale of basic research, the need for a crit-
ical mass of research effort. Fragments of knowledge
unwelcomed and unexploited are lost as were Gregor
Mendel's basic genetic discoveries. They also do not

th? PHAROS, July 1975

realize that the scientists who do basic research are the
least articulate, least organized and least able to justify
what they are doing, and this is in a society where sell-
ing is so important, where the medium is the message.
If there were a record of research grants in the Stone
Age, I believe it would show that the major grants were
awarded for proposals to build better stone axes and
that the critics of the time would have ridiculed a tiny
grant to someone fooling around with metals. The rec-
ord clearly shows that X rays were not developed for
their value in medicine and surgery but because physi-
cists were curious about some utterly esoteric questions
about electricity in a vacuum. The record also shows
that antibiotics were discovered and brought to the
point of clinical trial not by pharmacologists searching
for therapeutic drugs, but by a bacteriologist and a bio-
chemist who were curious about how enzymes dissolved
bacterial walls.
In our more recent experience who among us can
forget the scourge of polio? It was basic research in
virology, immunology, and cell culture that gave us the
polio vaccine. Otherwise we would be spending billions
on more elegant iron lungs and on Sister Kenny physio-
therapy centers.
In concluding, I want to emphasize the fact that no
one person, or committee, planned the extraordinary

development of the NIH today. It is a serendipitous dis-
covery. By chance and sagacity we have an institution
of the greatest value for the health of our society. In the
Bicentennial Year spirit let us celebrate and preserve it
as we do our Constitution. Had we had the good sense
to develop national institutes of comparable stature in
agriculture and energy resources, many of our present
problems would be less serious.
There are two compelling reasons why society must
support the NIH and science. One is substantial: the
obscure science of yesterday is curing diseases today
and will do more tomorrow. The other reason is cul-
tural. The essence of our civilization is to explore and
analyze the nature of man and his surroundings. As
proclaimed in the Bible in the Book of Proverbs:
"Where there is no vision, the people perish."
Despite the current emphasis on food and fuel,
America's greatest strength is not in mineral resources,
nor in hydroelectric power, fossil fuels, nor in its soil.
It is not in the accumulation of a huge weapons arsenal
either. America's strength is in the moral and intellec-
tual resources of the people.

Address reprint requests to the author at the following ad-
dress:

Department of Biochemistry
Stanford University Medical School
Stanford, California 94305

the PHAROS, July 1975

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