Copyright  2004 by the Genetics Society of America
DOI: 10.1534/genetics.104.030320
Perspectives
Anecdotal, Historical and Critical Commentaries on Genetics
Edited by James F. Crow and William F. Dove
Leo Szilard: A Personal Remembrance
Werner Maas1
Department of Microbiology, New York University School of Medicine, New York, New York 10016-6402
S INCE retiring as a full-time faculty member about
10 years ago, I have occupied myself with writing
chronicles of past experiences. The first was an account
of the advances made in the elucidation of gene expres-
sion and its regulation during the twentieth century
(Maas 2001). The second was an account of the history
of a Jewish family in the Palatinate region of Germany,
based on a memoir written by my father after World War
I (Maas 2003). Now, in looking for another chronicle to
write, I was very pleased to be asked to write a Perspectives
essay about Leo Szilard. I could think of no better topic
and I accepted enthusiastically.
I first met Szilard in 1951 and had many contacts with
him until the time of his death in 1964. During this
period I developed an unreserved admiration for him
as a scientist and as a human being. I consider it a
privilege that I now have an opportunity to describe this
unusual man as I remember him.
Szilard started a new career in biology in 1947 after
having made significant contributions to physics and
having been instrumental in the development of the
atomic bomb. At that time he asked Aaron Novick, a
young physical organic chemist, to join him in his new
venture. Novick accepted enthusiastically, and this was
the beginning of an association that lasted over many
years. They began their entry into biology by taking the
phage course at Cold Spring Harbor in 1947, which at
that time was taught by Max Delbrück (see Susman
1995).
Novick and Szilard set up their own laboratory at the
University of Chicago in 1948, where Szilard had been
appointed a professor of biology and sociology. They
became members of the new Institute of Radiobiology
and Biophysics, which was located in a former synagogue
of a Jewish orphanage. Their laboratory was in the base-
1
Address for correspondence: Department of Microbiology, New York
University School of Medicine, 550 First Ave., New York, NY 10016-
6402. E-mail: maaswo1@endeavor.med.nyu.edu
Genetics 167: 555–558 ( June 2004)
ment of this building. Their plan was to study mutation
in bacteria, and they looked for methods to measure
mutation rates.
At Cold Spring Harbor they had encountered Jacques
Monod, who had told them about his diauxie experi-
ments in which, in the presence of the two carbon
sources glucose and lactose, glucose is used preferen-
tially. Szilard was intrigued by this finding, and to ana-
lyze it he and Novick designed an apparatus for the
continuous culture of bacteria, which they called a
chemostat (Novick and Szilard 1950). Subsequently,
this device turned out to be very useful for the study of
mutation rates, as well as for physiological studies on
bacteria. Aaron Novick has given a vivid account of his
association with Szilard during this period (Novick
1966).
In 1951 I was working in the laboratory of Bernard
Davis at Cornell Medical College in New York City. We
were studying various biosynthetic pathways of Esche-
richia coli with the use of mutants isolated in our labora-
tory. Szilard was a frequent visitor and liked to discuss
our work with us. My own problem concerned the man-
ner in which genes control the production of enzymes,
as postulated in Beadle’s one gene–one enzyme hypoth-
esis. Do they determine the structure of enzymes or
merely the rate at which the enzymes are produced?
To study this question, I used a temperature-sensitive
mutant requiring pantothenic acid for growth in which
the enzyme affected by the mutation could be measured
in extracts. I found that the extracted enzyme was much
more heat labile than the corresponding enzyme from
the wild-type strain. It seemed likely that the enzyme
molecule itself was affected by the mutation, but there
was the possibility that the observed difference was due
to an extrinsic factor produced in the mutant. I posed
this question to Szilard, and he immediately suggested
that I could get an answer by studying heat inactivation
in mixtures of mutant and wild-type enzymes. I carried
out the experiments Szilard suggested, and the results
showed clearly that the difference in thermal stability
556 W. Maas
was due to a difference in the enzyme molecules them-
selves.
I am ashamed to say that I did not mention Szilard’s
crucial suggestion in the acknowledgment at the end
of my published paper (Maas and Davis 1952). I can
say only that, as far as I know, there are other people
who received similar crucial suggestions or advice from
Szilard without acknowledging his contribution. I think
that Szilard was not bothered by these omissions, be-
cause his passion was to solve scientific questions, and
he was not concerned about receiving personal credit
for his contributions.
Szilard spent a great deal of his time visiting other
scientists in the quest for obtaining information about
questions that interested him. He was very purposeful
during his visits. As an example, during a party in Ber-
nard Davis’ apartment in New York City, in which Monod,
François Jacob, Novick, and other researchers were pres-
ent, Szilard suddenly appeared. However, he did not
join the group in the living room, but instead took over
a bedroom and invited each guest, in turn, in for a
private chat, quizzing them on their latest work and
findings, suggesting new experiments and novel inter-
pretations, and reporting how these might relate to the
work of others.
Szilard was a very private man. He never talked about
personal problems and even did not talk about scientific
problems, unless he could formulate them in precise
questions. I experienced these aspects of his personality
when I visited him in the mid-1950s in Denver, where
he was spending the summer carrying out experiments
at the University of Colorado Medical School. He asked
me to join him for lunch and to first meet him at his
laboratory at the Medical School. When I arrived, he
was working with a column, apparently carrying out a
separation. When I asked him what the experiment was,
he would not tell me. I found out only later that he was
trying to separate male-producing sperm from female-
producing sperm to be able to control the sex ratio.
One of his vital concerns was human reproduction and
its consequences for the welfare of society.
In retrospect it was perhaps just as well that he did
not tell me about the nature of his experiment. In a
recent article in The New York Times Magazine (Novem-
ber 1, 2003) there was a story about a woman who, after
having had three boys, wanted very much to have a girl.
She had been told that a method for being fertilized
with female-producing sperm from her husband was
available. The couple decided to undergo this proce-
dure and the woman became pregnant, but the preg-
nancy resulted in the birth of male twins. After 50 years,
Szilard’s reticence was vindicated.
His sense of privacy was also revealed to me in Denver.
I had been wondering why Szilard spent his summers
in Denver in the first place. I learned only much later
that he had a wife who taught public health at the
University of Colorado Medical School. Her maiden
name was Trude Weiss and he had married her in 1951.
Nobody I knew, including Szilard himself, ever men-
tioned this relationship to me.
Our subsequent lunch engagement had an amusing
aspect. We ate at a rooftop restaurant of what seemed
to be Denver’s only skyscraper. When we sat down I
noticed that all the other tables in the restaurant were
occupied by women. Szilard seemed not to notice this
and we carried on our discussion. After a while some
well-dressed women were walking slowly among the ta-
bles and I then realized that we were at a fashion show.
One of these ladies came to our table and after looking
at us said, “I guess you guys are not interested.” The
remark did not bother Szilard and we continued our
discussion.
My next encounter with Szilard occurred in 1956 at
New York University School of Medicine where I was
studying the control of enzyme synthesis in the pathway
of arginine biosynthesis in E. coli. I had discovered that
the addition of arginine to a growing culture inhibited
the formation of the enzyme ornithine transcarbamylase
(OTCase) that catalyzes the conversion of ornithine to
citrulline, an intermediary step in arginine biosynthesis.
A former colleague from the Davis Laboratory, Henry
Vogel, had found inhibition by arginine of the forma-
tion of another enzyme of the arginine pathway and had
coined the term “enzyme repression” for this feedback
control.
While studying the rate (kinetics) of OTCase forma-
tion following the removal of arginine from a growing
culture of E. coli, I found an unexpected result. At that
time Monod was studying the kinetics of enzyme forma-
tion for the formation of the inducible enzyme ␤-galac-
tosidase after addition of lactose. He had found that
the enzyme is produced at a constant rate for several
hours. In contrast, I found that OTCase was produced
at a fast rate for only 20 min after the removal of argi-
nine, after which there was a sharp drop in the rate of
enzyme synthesis. To explain this unexpected result, I
postulated that during the initial 20 min arginine would
be made rapidly in the cells and the accumulated argi-
nine would inhibit further OTCase synthesis.
At that time I was joined by a visiting investigator from
Italy, Luigi Gorini. To test the idea that the decrease of
OTCase synthesis was due to accumulated arginine, we
had to find conditions of growth under which arginine
could not accumulate. We discussed this problem with
Szilard and Novick, who happened to be visiting our
laboratory, and they suggested that such conditions
could be obtained by growing an arginine-requiring
mutant in a chemostat, with arginine being the rate-
limiting growth factor. They had carried out chemostat
experiments on the effect of added tryptophan on tryp-
tophan synthesis and were in a good position to give us
precise directions. When we carried out the experiment
as they had suggested, we found that OTCase was pro-
duced at a high and constant rate, as expected from
 Perspectives
“Monod kinetics.” We concluded from these experi-
ments that the bacteria have a very high capacity for
making OTCase, but that the formation of the enzyme
is slowed down by internally produced arginine to a low
level that is still sufficient for normal growth. Later this
kind of regulation was demonstrated in many metabolic
pathways.
My next encounter with Szilard occurred in 1957
when I attended the Federation Meetings in Chicago
and stayed at the Quadrangle Club where Szilard was
also staying. I met him during breakfast and told him
about a conclusion I had reached on the control of
enzyme formation on the basis of my experiments. It
contradicted a widely accepted hypothesis proposed by
Monod.
Monod had proposed that for inducible enzymes,
such as ␤-galactosidase, the gene coding for this enzyme
would make an inactive enzyme protein, which would
then become activated by interaction with its substrate
lactose. Monod was a strong believer in a unitary hypoth-
esis for the control of enzyme formation. Thus, for re-
pressible enzymes, such as OTCase, he would postulate
that arginine prevented the interaction of inactive OT-
Case protein with ornithine, the substrate for OTCase.
In our chemostat experiments we used a mutant
blocked in ornithine formation, and yet this strain pro-
duced OTCase at high levels in the absence of its sub-
strate. The conclusion I presented to Szilard was that
for a unitary hypothesis one had to assume that, in the
case of inducible enzymes, there was a repressor present
and that the inducer prevented the action of the repres-
sor. Szilard was impressed with my hypothesis and said
that it could explain recent results they had obtained
in their own laboratory. He wanted to publish my hy-
pothesis right away, but I refused, because I had no
direct experimental evidence for it. He did publish an
article on the subject subsequently in 1960 (Szilard
1960).
Early in 1958 Szilard presented my alternative unitary
hypothesis at a seminar at the Pasteur Institute in Paris.
At that time Arthur Pardee, Jacob, and Monod had
begun an experiment designed to distinguish between
the two hypotheses. A lively discussion followed the semi-
nar, with the thinking of Monod clearly favoring his
internal inducer hypothesis. When the experiment was
finished and the results were analyzed, it was clear that
the alternative hypothesis presented by Szilard was cor-
rect for the induction of ␤-galactosidase. Enzyme induc-
tion was shown to involve the removal of repression.
Later in 1958 Szilard spent some time at the National
Institutes of Health in Bethesda, staying at the nearby
Kenwood Country Club. I visited him there and we had
an animated discussion about the latest developments
in the regulation of enzyme synthesis while sitting in
the relaxing atmosphere of the swimming pool.
After 1960 I had only a few contacts with Szilard.
He was heavily engaged in political activities concerned
557
mainly with nuclear arms control and peaceful coexis-
tence. At one time he invited me and my wife to his
debate with Edward Teller on NBC on the topic, “Is
Disarmament Possible and Desirable?”
In 1964, I visited Szilard in La Jolla, where he had
moved to work at the Salk Institute. For several years
he had been instrumental in creating this institute. He
was living there with his wife Trude at the beautiful La
Valencia Hotel. He met me at the San Diego airport
and asked me immediately what was new in my work.
“Nothing,” I said. He looked at me, disappointed. “You
think I am lazy,” I said. “That is right,” was his reply.
Szilard died in his sleep in La Jolla on May 30, 1964.
To me it was a great loss and I shall always miss him. He
had an extraordinary gift for rational thinking, which he
used tirelessly and altruistically not only for the solution
of scientific problems, but also for generating ideas and
schemes for improving the social and political condi-
tions of humankind. A detailed account of his life can
be found in the biography by William Lanouette, Genius
in the Shadows (Lanouette 1992).
ADDENDUM: LEO SZILARD, 1898–1964
Werner Maas has given an insightful, personalized
account of Szilard as a biologist. Yet, many readers of
Genetics, especially the younger ones, may not be fa-
miliar with Szilard’s remarkable life and achievements
outside biology. Despite his great contributions, he
never received major awards or high positions, and elec-
tion to the National Academy of Sciences came only 3
years before his death. He lived a nomadic life and
usually had no permanent job. But to those who knew
him, his probing intellect, unorthodox personal behav-
ior, and supreme self-confidence are the stuff of legend.
Here is a very brief account, mostly taken from the much
fuller one by Lanouette (1992).
Szilard was born in Budapest on September 11, 1898.
He was precocious in both scientific aptitude and social
concerns, foreshadowing the two dominant features of
his later life. He also displayed early the originality, free-
wheeling imagination, and uninhibited determination
for which he was both admired and castigated.
In 1920 he joined the physics department at the Uni-
versity of Berlin, where he met Albert Einstein, who
became his life-long friend. His graduate thesis was on
the statistical interpretation of thermodynamics. In this
thesis, he applied the concept of entropy to information,
thus foreshadowing by a quarter century Shannon’s de-
velopment of modern information theory (Crow 2001).
He also developed a statistical concept, comparable to
R. A. Fisher’s “sufficiency.”
Szilard had a penchant for patenting his ideas. These
included a refrigerator with no moving parts (with Ein-
stein), a cyclotron, and the chain reaction concept. The
latter, the basis for a future atomic bomb, was developed
as early as 1933. Along with Eugene Wigner and John
558
von Neumann, Szilard joined a seminar given by Ein-
stein. Quite a teacher, quite a class!
In the 1930s, Szilard became increasingly concerned
about the rise of Hitler. Realizing that a nuclear bomb
might be possible, he was fearful that this would be
developed in Germany. Szilard’s most widely known ac-
complishment was persuading Einstein to lend his name
to urging President Roosevelt to develop nuclear en-
ergy. For the next few years Szilard persistently pushed
this and came up with one idea after another. Eventu-
ally, as the world learned in August 1945, the project
was horribly successful.
Szilard was responsible for three efforts to demon-
strate against the bombing of Japanese cities. The first
petition came close to receiving the President’s atten-
tion, but Roosevelt died at about this time. The next
two never got past the bureaucracy of the nuclear estab-
lishment.
After the war, he again devoted his creative imagina-
tion, his boundless energy, and his dogged persistence
to social causes, especially attempts to assure that nu-
clear bombs would not be used. He concocted various
schemes, scientific and political, to this end. He was
instrumental in putting the development of nuclear en-
ergy into civilian rather than military hands at the Pug-
wash Conferences, in founding the Bulletin of the Atomic
Scientists, the Federation of American Scientists, and,
later, the Council for a Livable World.
I particularly enjoyed his book, The Voice of the Dolphins
(Szilard 1961). Aware of the presumed high intelli-
gence of dolphins, Szilard used this as the basis of a
clever work of science fiction. The dolphins were asked
to solve problems too difficult for human minds, espe-
W. Maas
cially those involving international relations. Not sur-
prisingly, the ideas the dolphins came up with bore
considerable resemblance to what Szilard had been ad-
vocating.
In 1959, Szilard developed bladder cancer. With char-
acteristic confidence and scientific insight, he overruled
medical advice and took charge of his own radiation
treatment. It worked, at least for a time, for when his
death came on May 30, 1964, it was from another cause.
James F. Crow, Ed.
LITERATURE CITED
Crow, J. F., 2001 Shannon’s brief foray into genetics. Genetics 159:
915–917.
Lanouette, W., 1992 Genius in the Shadows. Charles Scribner’s Sons,
New York.
Maas, W., 2001 Gene Action—A Historical Account. Oxford University
Press, New York.
Maas, W., 2003 Das Leben meines Vaters 1888–1936. Evangelischer
Presseverlag Pfalz, Speyer, Germany (English translation can be
obtained from Werner Maas).
Maas, W., and B. Davis, 1952 Production of an altered pantothe-
nate-synthesizing enzyme by a temperature-sensitive mutant of
Escherichia coli. Proc. Natl. Acad. Sci. USA 38: 785–797.
Novick, A., 1966 Phenotypic Mixing: Phage and the Origins of Molecular
Biology, pp. 133–141. Cold Spring Harbor Laboratory Press, Cold
Spring Harbor, NY.
Novick, A., and L. Szilard, 1950 Description of the chemostat.
Science 112: 715–716.
Susman, M., 1995 The Cold Spring Harbor Phage Course (1945–
1970): a 50th anniversary remembrance. Genetics 139: 1101–
1106.
Szilard, L., 1960 The control of the formation of specific proteins
in bacteria and in animal cells. Proc. Natl. Acad. Sci. USA 46:
277–292.
Szilard, L., 1961 The Voice of the Dolphins. Simon & Schuster, New
York.