7/28/2019 Obituario Francois Jacob 1920-2013
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DOI: 10.1126/science.1239975, 939 (2013);340Science
Lucy Shapiro and Richard Losick2013)Franois Jacob (1920
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7/28/2019 Obituario Francois Jacob 1920-2013
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PERSPECTIV
Franois Jacob (19202013)
RETROSPECTIVE
Lucy Shapiro1 and Richard Losick2
The French Nobel laureate ushered in the field
of molecular genetics by defining the regulate
cellular pathway that translates DNA into
proteins.
Franois Jacob died on 19 April in Parisat the age of 92. We have
lost one ofthe great architects of modern biology,
whose legacy touches all aspects of gene regu-lation from
viruses and bacteria to humans, aswell as in human diseases such as
cancer. Toan astonishing degree, his insights and
elegantexperiments established the framework forunderstanding the
mechanismsthat underpin gene control inevery decision a cell
makeson its journey through the celldivision cycle, in
embryogen-esis, in tissue differentiation,and in the formation of a
mul-
ticellular organism. He wasnot only a visionary scien-tist but
also a humanist withextraordinary perception ofthe workings of the
scientificmind and the literary ability toconvey his insights with
graceand compassion.
Jacob wrote and talkedabout day science and night science.
Hedescribed day science as how we present ourdiscoveries in
seminars and papers, as a lin-ear progression of observations and
scientific
design to a voil conclusion. Night scienceis how the discovery
process really happens,in its messy, intuitive, questioning
progres-sion, where we construct and then demol-ish hopeful
hypotheses, fighting a lot withyourself. Most important to this
process ishow one formulates questions that then drivethe design of
the experiment. He spoke elo-quently of the tool box of life, like
engineersparts on a shelf, which through evolutionundergo
arrangements and rearrangements toconstruct complex genetic
regulatory circuitsthat result in the myriad of Earths life
forms.
Franois Jacob was born in 1920 in Nancy,
France. His journey from a bourgeois Pari-sian life as a medical
student to his immer-sion in phage genetics with Andr Lwoff atthe
Institut Pasteur included a hiatus imposedby the invasion of France
by Nazi Germany.Jacob managed to get out of Paris and even-tually
join Charles de Gaulle in England. He
fought with the Free French Army in Europeand North Africa until
1944 when he wasseriously injured, spending many monthsrecovering
from wounds that would end hischosen career as a surgeon and that
wouldplague him for the rest of his life. At looseends, he tried
journalism and acting, butcompleted his medical degree in 1947
while
looking for other ways of con-structing a new life. He
even-tually learned of the researchgoing on in the attic at
theInstitut Pasteur and decidedthat he would join the worldof phage
and bacteria. Every
month he would apply to workwith Lwoff but was summar-ily
rejected. Finally, Lwoffrelented, telling him excit-edly about his
discovery ofprophage induction and thathe needed someone to workon
it. Jacob responded, Imdying to work on induction,
without a clue about what it meant. In 1950,Jacob joined the
attic, with Lwoff at oneend of a long corridor and Jacques Monod
atthe other. Just 15 years later, Jacob, Monod,
and Lwoff would be awarded the 1965 NobelPrize in Physiology or
Medicine for theirdiscoveries concerning genetic control ofenzyme
and virus synthesis.
Jacob earned a doctorate in science in 1954at the Sorbonne,
focusing on the concept of aprovirus. He observed that
bacteriophageavirus that infects bacteriacould integrate itsgenome
into that of a host bacterium, remaindormant as a provirus
(prophage), and haveits genome passed on to bacterial
offspring.When the provirus becomes active again, thevirus enters a
lytic cycle in which its genomeis expressed and new virus is
produced to
infect other bacteria.Experimental results from lie Wollman,
Jacob, and Lwoff on lysogeny and immu-nity, and from Monod on
lactose inductionof-galactosidase synthesis in bacteria weremerged
in the Big Synthesis, which postu-lated that the two seemingly
unrelated sys-tems were controlled by a common mecha-nism involving
repressors that inhibit geneactivity. That is, genes are controlled
by dedi-cated macromolecules (initially thought to beRNA, but later
shown to be protein, although
we now know that both control genes) tharegulate their activity.
Monod held that alregulation must be mediated by repressorswhereas
Jacob believed that activators coulalso be part of gene-control
pathways, an idethat later proved to be correct.
The work with -galactosidase resultein the identification of the
lactose operon (acluster of three adjacent genes that controlthe
transport and metabolism of lactose inbacteria) and led the Pasteur
team to postulatthe existence of factor X as an intermediatbetween
the gene and the ribosome to producprotein. These ideas, as well as
experiments bElliot Volkin and Lazarus Astrachan, pointe
to factor X being messenger RNA, which wademonstrated by Sydney
Brenner, MatthewMeselson, and Jacob during a 1-month visito Max
Delbruck at the California Institute oTechnology in 1960.
Studying conjugation (the transfer ogenetic material by direct
cell-to-cell contactinEscherichia coli, Wollman and Jacob
demonstrated that the order of genes on the chromosome is linear
and that this order undergoes a circular permutation during
chromosome transfer between strains. This led to thsurprising but
correct conclusion that theEcoli
chromosome must be circular.Every discovery by this remarkable
manhas its imprint on the logic and reasoning thaare used to this
day to understand life. Fromearly on in his time at the Pasteur,
Jacob wafixated on understanding how a pair of cellwith the same
DNA could be programmed tturn into two different kinds of cells.
This quesultimately led him to switch fromE. coli anphage lambda to
an organism with eyes, soul and plenty of sexthe mouse.
Thcombination of genetics and the possibility oa cell culture
system led him to propose aninterdisciplinary Institute of the
Mouse a
the Pasteur to study developmental regulationof a complex being.
Although the institutnever materialized, Jacob went on to use
themouse as a model system to explore the relationship between
embryonic developmenand cancer, clearly a disease of
regulation.
Throughout his life in science, Jacobknew that he was involved
in the greaadventure of the century, and his eloquenbooks about
this adventure are a living testimony to his legacy.
CREDIT:HENRIBUREAU/APIS/SYGMA/CORBIS
10.1126/science.123997
1Developmental Biology, Stanford University, Stanford, CA94305,
USA. 2Molecular and Cellular Biology, Biological
Laboratories, Harvard University, 16 Divinity Avenue,
Cam-bridge, MA 02138, USA. E-mail: [email protected];
[email protected]
Published by AAAS
