Monod, Jacques Lucien WORLD OF MICROBIOLOGY AND IMMUNOLOGY398•
importance of physiological and biochemical genetics and the
relevance of learning the chemical and molecular aspects of
living organisms, respectively.
During the autumn of 1931, Monod took up a fellowship
at the University of Strasbourg in the laboratory of Edouard
Chatton, France’s leading protistologist. In October 1932, he
won a Commercy Scholarship that called him back to Paris to
work at the Sorbonne once again. This time he was an assistant
in the Laboratory of the Evolutionof Organic Life, which was
directed by the French biologist Maurice Caullery. Moving to
the zoology department in 1934, Monod became an assistant
professor of zoology in less than a year. That summer, Monod
also embarked on a natural history expedition to Greenland
aboard the Pourquoi pas?In 1936, Monod left for the United
States with Ephrussi, where he spent time at the California
Institute of Technology on a Rockefeller grant. His research
centered on studying the fruit fly (Drosophila melanogaster)
under the direction of Thomas Hunt Morgan, an American
geneticist. Here Monod not only encountered new opinions,
but he also had his first look at a new way of studying science,
a research style based on collective effort and a free passage of
critical discussion. Returning to France, Monod completed his
studies at the Institute of Physiochemical Biology. In this time
he also worked with Georges Teissier, a scientist at the Roscoff
station who influenced Monod’s interest in the study of bacte-
rial growth. This later became the subject of Monod’s doctoral
thesis at the Sorbonne where he obtained his Ph.D. in 1941.
Monod’s work comprised four separate but interrelated
phases beginning with his practical education at the Sorbonne.
In the early years of his education, he concentrated on the
kinetic aspects of biological systems, discovering that the
growth rate of bacteriacould be described in a simple, quanti-
tative way. The size of the colonywas solely dependent on the
food supply; the more sugar Monod gave the bacteria to feed
on, the more they grew. Although there was a direct correla-
tion between the amounts of food Monod fed the bacteria and
their rate of growth, he also observed that in some colonies of
bacteria, growth spread over two phases, sometimes with a
period of slow or no growth in between. Monod termed this
phenomenon diauxy(double growth), and guessed that the
bacteria had to employ different enzymesto metabolize dif-
ferent kinds of sugars.
When Monod brought the finding to Lwoff’s attention
in the winter of 1940, Lwoff suggested that Monod investigate
the possibility that he had discovered a form of enzyme adap-
tation, in that the latency period represents a hiatus during
which the colony is switching between enzymes. In the previ-
ous decade, the Finnish scientist, Henning Karstroem, while
working with protein synthesis had recorded a similar phe-
nomenon. Although the outbreak of war and a conflict with his
director took Monod away from his lab at the Sorbonne,
Lwoff offered him a position in his laboratory at the Pasteur
Institute where Monod would remain until 1976. Here he
began working with Alice Audureau to investigate the genetic
consequences of his kinetic findings, thus beginning the sec-
ond phase of his work.
To explain his findings with bacteria, Monod shifted his
focus to the study of enzyme induction. He theorized that cer-tain colonies of bacteria spent time adapting and producing
enzymes capable of processing new kinds of sugars. Although
this slowed down the growth of the colony, Monod realized
that it was a necessary process because the bacteria needed to
adapt to varying environments and foods to survive.
Therefore, in devising a mechanism that could be used to
sense a change in the environment, and thereby enable the
colony to take advantage of the new food, a valuable evolu-
tionary step was taking place. In Darwinian terms, this colony
of bacteria would now have a very good chance of surviving,
by passing these changes on to future generations. Monod
summarized his research and views on relationship between
the roles of random chance and adaptation in evolution in his
1970 book Chance and Necessity.
Between 1943 and 1945, working with Melvin Cohn, a
specialist in immunology, Monod hit upon the theory that an
inducer acted as an internal signal of the need to produce the
required digestive enzyme. This hypothesis challenged the
German biochemist Rudolf Schoenheimer’s theory of the
dynamic state of protein production that stated it was the mix
of proteins that resulted in a large number of random combi-
nations. Monod’s theory, in contrast, projected a fairly stable
and efficient process of protein production that seemed to be
controlled by a master plan. In 1953, Monod and Cohn pub-
lished their findings on the generalized theory of induction.
That year Monod also became the director of the depart-
ment of cellular biology at the Pasteur Institute and began his
collaboration with François Jacob. In 1955, working with
Jacob, he began the third phase of his work by investigating
the relationship between the roles of heredity and environment
in enzyme synthesis, that is, how the organism creates these
vital elements in its metabolic pathway and how it knows
when to create them.
It was this research that led Monod and Jacob to formu-
late their model of protein synthesis. They identified a gene
cluster they called the operon, at the beginning of a strand of
bacterial DNA. These genes, they postulated, send out mes-
sages signaling the beginning and end of the production of a
specific protein in the cell, depending on what proteins are
needed by the cell in its current environment. Within the oper-
ons, Monod and Jacob discovered two key genes, which they
named the operator and structural genes. The scientists dis-
covered that during protein synthesis, the operator gene sends
the signal to begin building the protein. A large molecule then
attaches itself to the structural gene to form a strand of mRNA.
In addition to the operon, the regulator gene codes for a
repressor protein. The repressor protein either attaches to the
operator gene and inactivates it, in turn, halting structural gene
activity and protein synthesis; or the repressor protein binds to
the regulator gene instead of the operator gene, thereby free-
ing the operator and permitting protein synthesis to occur. As
a result of this process, the mRNA, when complete, acts as a
template for the creation of a specific protein encoded by the
DNA, carrying instructions for protein synthesis from the
DNA in the cell’s nucleus, to the ribosomes outside the
nucleus, where proteins are manufactured. With such a sys-
tem, a cell can adapt to changing environmental conditions,
and produce the proteins it needs when it needs them.womi_M 5/7/03 7:53 AM Page 398