Jacob, François WORLD OF MICROBIOLOGY AND IMMUNOLOGY318•
could be transferred to a female cell which was not carrying
the prophage, but not vice versa. Zygotic induction showed
that both the expression of the prophage and immunity was
blocked in the latter instance by a variable present in the cyto-
plasmthat surrounds the cell’s nucleus.
In another experiment, he and Wollman mated male and
female bacterial cells, separating them before they could com-
plete conjugation. This also clipped the chromosome as it was
moving from the male to the female. They found that the
female accepted the chromosome bit by bit, in a certain order
and at a constant speed, rather similar to sucking up a piece of
spaghetti. Their study became known as the “spaghetti exper-
iment,” much to Wollman’s annoyance.
In the book Phage and the Origins of Molecular
Biology, Wollman explained that by following different
genetic markers in the male, they could determine each gene’s
time of entry into the zygote and correctly infer its position on
the DNA. Jacob and Wollman also used an electron micro-
scopeto photograph the conjugating bacteria and time the
transmission of the genes. “With Élie Wollman, we had devel-
oped a tool that made possible genetic analysis of any func-
tion, any “system,” Jacob said in his autobiography. The two
scientists also discovered and defined episomes, genetic
strains which automatically replicate as part of the develop-
ment of chromosomes.
Jacob and Wollman also demonstrated that bacteria
could mutate and adapt in response to drugs or bacteriophages.
Evolution and natural selection worked in bacteria as well as
in higher life forms. Jacob and Wollman summarized theirresearch in the July, 1956, issue of Scientific American:
“There is little doubt that the basic features of genetic recom-
binationmust be similar whether they occur in bacteria or in
man. It would be rather surprising if the study of sexual repro-
duction in bacteria did not lead to deeper understanding of the
process of genetic recombination, which is so vital to the sur-
vival and evolution of higher organisms.”
In 1956 Jacob accepted the title of laboratory director at
the Pasteur Institute. Within two years Jacob began to work
with Jacques Monod, who had left Lwoff’s lab several years
earlier to direct the department of cellular biochemistryat the
Pasteur Institute. Arthur Pardée also often joined in the
research. Jacob and Monod studied how an intestinal enzyme
called galactosidase is activated to digest lactose, or milk
sugar. Galactosidase is an inducible enzyme, that is, it is not
formed unless a certain substrate—in this case lactose—is
present. Inducible enzymesdiffer from constitutive enzymes
which are continuously produced, whether or not the inducer
is present. By pairing a normal inducible male bacteria with a
constitutive female, they showed that inducible enzyme
processes take precedence over constitutive enzyme synthesis.
In the experiments conducted by Jacob and Monod, the
inducer, lactose, served to inhibit the genethat was regulating
the synthesis of galactosidase.
Afterward, Jacob realized that his work with Monod
and his earlier work with Wollman on zygotic induction were
related. In The Statue Within,he said, “In both cases, a gene
governs the formation of a cytoplasmic product, of a repressor
blocking the expression of other genes and so preventing
either the synthesis of the galactosidase or the multiplication
of the virus.” Their chore then was to determine the location
of the repressor, which appeared to be on the DNA.
By the end of the decade, Jacob and Monod had dis-
covered messenger RNA, one of the three types of ribonucleic
acid. (The other two are ribosomal RNA and transfer RNA.)
Each type of RNA has a specific function. MRNA is the medi-
ator between the DNA and ribosomes, passing along informa-
tion about the correct sequence of amino acids needed to make
up proteins. While their work continued, Jacob accepted a
position as head of the Department of Cell Genetics at the
Pasteur Institute.
In 1961, they explained the results of their research
involving the mRNA and the now-famous Jacob-Monod
operon model in the paper, “Genetic Regulatory Mechanisms
in the Synthesis of Proteins,” which appeared in the Journal of
Molecular BiologyMolecular biologist Gunther S. Stent in
Sciencedescribed the paper “one of the monuments in the lit-
erature of molecular biology.”
According to the Jacob-Monod operon model, a set of
structural genes on the DNA carry the code that the messenger
RNA delivers to the ribosomes, which make proteins. Each set
of structural genes has its own operator gene lying next to it.
This operator gene is the switch that turns on or turns off its
set of structural genes, and thus oversees the synthesis of their
proteins. Jacob and Monod called each grouping of an opera-
tor and its structural genes an operon. Besides the operator
gene, a regulator gene is located on the same chromosome as
the structural genes. In an inducible system, like the lactoseFrançois Jacob, whose research on the operon culminated in a Nobel
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