Monod, Jacob, Lwolf: Nobel Prize Lectures

Date:
1966-1970
Reference:
PP/CRI/H/3/5/4
Catalogue details

Licence: In copyright

Credit: Monod, Jacob, Lwolf: Nobel Prize Lectures. Source: Wellcome Collection.

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    From Enzymatic Adaptation to Allosteric Transitions One day, almost exactly 25 years ago—it was at the beginning of the bleak winter of 1940—I entered André Lwoff's office at the Pasteur Institute. I wanted to discuss with him some of the rather surprising observations I had recently made. I was working then at the old Sor bonne, in an ancient laboratory that opened on a gallery full of stuffed monkeys. Demobilized in August in the Free Zone after the disaster of 1940, I had succeeded in locating my family living in the Northern Zone and had resumed my work with desperate eager ness. I interrupted work from time to time only to help circulate the first clandestine tracts. I wanted to complete as quickly as possible my doctoral dissertation, which, under the strongly biometrie influence of Georges Teissier, I had devoted to the study of the kinetics of bacterial growth. Having determined the constants of growth in the presence of different carbohydrates, it occurred to me that it would be interesting to determine the same con stants in paired mixtures of carbohy drates. From the first experiment on, I noticed that, whereas the growth was kinetically normal in the presence of certain mixtures (that is, it exhibited a single exponential phase), two com plete growth cycles could be observed in other carbohydrate mixtures, these Jacques Monod cycles consisting of two exponential phases separated by a complete cessa tion of growth (Fig. 1). Lwoff, after considering this strange result for a moment, said to me, That could have something to do with enzyme adaptation. Enzyme adaptation? Never heard of it! I said. Lwoff's only reply was to give me a copy of the then recent work of Marjorie Stephenson, in which a chap ter summarized with great insight the still few studies concerning this phe nomenon, which had been discovered by Duclaux at the end of the last cen tury. Studied by Dienert and by Went as early as 1901 and then by Euler and Josephson, it was more or less redis covered by Karström, who should be credited with giving it a name and attracting attention to its existence. Marjorie Stephenson and her students Yudkin and Gale had published several papers on this subject before 1940. [See (I) for a bibliography of papers published prior to 1940.] Lwoff's intuition was correct. The phenomenon of diauxy that I had discovered was indeed closely related to enzyme adaptation, as my experi ments, included in the second part of my doctoral dissertation, soon con vinced me. It was actually a case of the glucose effect discovered by Dienert as early as 1900, today better known as catabolic repression from the studies of Magasanik (2). The die was cast. Since that day in December 1940, all my scientific ac tivity has been devoted to the study of this phenomenon. During the Occupa tion, working, at times secretly, in Lwoff's laboratory, where I was warmly received, I succeeded in carrying out some experiments that were very sig nificant for me. I proved, for example, that agents that uncouple oxidative phosphorylation, such as 2,4-dinitro- phenol, completely inhibit adaptation to lactose or other carbohydrates (J). This suggested that adaptation im plied an expenditure of chemical po tential and therefore probably involved the true synthesis of an enzyme. With Alice Andureau, I sought to discover the still quite obscure relations be tween this phenomenon and the one Massini, Lewis, and others had dis covered: the appearance and selection of spontaneous mutants (see 1). Using a strain of Escherichia coli mutabile (to which we had given the initials ML because it had been isolated from André Lwoff's intestinal tract), we showed that an apparently spontaneous mutation was allowing these originally lactose-negative bacteria to become lactose-positive. However, we proved that the original strain (Lac-) and the mutant strain (Lac*) did not differ from each other by the presence of a specific enzyme system, but rather by the ability to produce this system in the presence of lactose. In other Copyright © 1966 by the Nobel Foundation. The author is head of the Department of Biochemistry of the Pasteur Institute, Paris, France. This article is the lecture he delivered in Stockholm, Sweden, 11 December 1965, when he received the Nobel Prize in Physiology or Medicine, which he shared with François Jacob and André Lwoff. It is published here with the a lso ' be ° 1 n c ! it d e d in the complete volumes of Nobel Lectures in English published by the Elsevier Publishing Company, Amsterdam and New York. It was translated from French by François Kertesz.