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The Operon model and genetics in France
François Jacob Scientist
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[Q] Et quand est-ce que le modèle de l'opéron d'ailleurs est redevenu au fond... à nouveau a été reconnu? C'est à partir des gènes du développement?

Je ne sais pas exactement. Il a eu une éclipse qui a duré quelques années puis il est revenu. Mais je vous dis ce qu'il y a eu c'est que il y a eu un excès, un excès dans un sens, puis qui a induit l'excès dans l'autre. Et c'est redevenu normal au bout de quelques années. Mais pendant très longtemps, les modèles de régulation et de trucs négatifs, en particulier les gens qui faisaient de la régulation sur les organismes supérieurs, ne référaient absolument pas à nos trucs. C'était complètement...

[Q] Oui, et en particulier les embryologistes comme, je sais pas, Conrad Waddington, ou même Boris Ephrussi a été...

Non, Waddington il est venu... Il est venu à Paris exprès pour voir ce qu'on fabriquait. C'était un curieux type... Vous l'avez jamais rencontré Waddington? Très intelligent et un peu étrange. Il ressemblait un peu à Churchill, c'était le genre de type... Mais il est venu pour... Je crois qu'il faisait des conférences dont j'ai oublié le nom à Columbia, il y avait une série de conférences assez connue... Et il devait faire ça, et donc il est venu ici pour voir si on pouvait appliquer cette histoire là à sa régulation dans les supérieurs.

[Q] Et je crois qu'il l'a appliqué un petit peu au début.

Oui.

[Q] Et après, il est devenu...

Il est devenu contre. Mais c'était un peu gratuit tout ça. Mais je pense qu'il y a eu un excès de gens qui étaient pour, ce qui a entraîné un excès de gens qui étaient contre. Et il a fallu un certain temps pour remettre les choses à leur place. Mais très souvent, même maintenant, les gens ne réfèrent pas, quand ils font l'historique de ça, ils n'en parlent pas.

[Q] Non. Et même les gènes du développement, quelquefois il y a des noms, on parle de Master Gene, alors qu'on pourrait très bien parler de gène régulateur. Mais c'est une nouvelle nomenclature. Maintenant, si, en post-génomique, les gens se réfèrent énormément à votre modèle. C'est un peu devenu l'icône de la post-génomique. D'une certaine manière. Ce qui est intéressant. Mais en France, c'est votre modèle au fond qui a fait découvrir la biologie moléculaire. Oui. Ça a joué un rôle énorme.

Mais ça, c'est la connerie des Français, ça.

[Q] C'était le retard de la France.

Oui, exactement.

[Q] Qui n'avait pas du tout suivi la biochimie, la génétique.

La génétique, c'est incroyable. La première chaire de génétique a été celle d'Ephrussi. Il n'y avait pas de chaire de génétique, ni en médecine ni à la fac des sciences pendant des années. Et la première chaire de génétique a été celle d'Ephrussi. Et la première chaire de microbiologie a été celle d'André Lwoff, plus tard encore.

[Q] Et la biochimie, à part Fromageot, il y avait quand même une biochimie très traditionnelle.

Ben il y en avait un petit peu. Il y avait Gabriel Bertrand qui a été le précurseur de Monod. Gabriel Bertrand, vous ne l'avez jamais connu? Un très vieux monsieur avec la barbiche, qui marchait à petits pas, et qui occupait le bureau... alors Monod avait le... On a donné le... Trefouel a donné le service de lui là à Monod, mais pas le bureau, qui était... Alors Monod attendait qu'il soit malade pour avoir le bureau...

[Q] Et c'est Gabriel Bertrand je crois qui avait dit que dans les enzymes, c'était le métal qui était important et pas la protéine. Ce qui était un choix malheureux.

C'est quand même une grande découverte.

[Q] Pour l'évolution de la biochimie.

Et pour les enseignements des étudiants, c'était pas mal.

[Q] And when did the Operon model basically make a comeback... was once again recognised? Was it from the genes development?

I'm not exactly sure. There was an eclipse that lasted a few years and then it came back. But I'm telling you, what happened was that there had been an excess, an excess in one way which lead to an excess in the other. And it became normal again after a couple of years. But for a very long time, the regulation models and the ones of negative things, the people that were working in the regulation of superior organisms in particular were never referring to our stuff. It was completely...

[Q] Yes, and in particular embryologists like, I don't know, Conrad Waddington or even Boris Ephrussi were...

No, Waddington came over... he came over to Paris especially to see what we were doing. He was an odd guy... did you ever meet Waddington? Very intelligent and a little strange. He sort of looked like Churchill, he was the type of guy... but he came over to... I think he was giving conferences, of which I've forgotten the name, at Columbia, there was a series of quite famous conferences... and he was supposed to do that, so he came over to see if what we were doing could be applied to his regulation in the superiors.

[Q] And I think he applied it a little at the start.

Yes.

[Q] And afterwards, he became...

He became against it. But that was a little too easy. I think that there was an excess of people who were in favour of it, which lead to an excess of people who were against it. And it took a long time to put the record straight. But very often, even now, when people do the history of it all they don't refer to it, they don't talk about it.

[Q] No. And even the development genes, they sometimes have names, we speak of master gene, when we could very well be speaking of regulator genes. But it's a new nomenclature. Nowadays, in post-genomics people do refer to themselves very often to your model. It has became a sort of icon of post-genomics, in some ways. Which is interesting. But in France, it's your model that basically helped to discover molecular biology. Yes. It played a key role.

But that's... that's the French stupidity.

[Q] It was the backwardness of France.

Yes, exactly.

[Q] Who hadn't followed biochemistry or genetics at all.

Genetics, that's incredible. The first genetics chair was Ephrussi's. There was no genetic chair for years, not in Medicine or at the Science Faculty. And the first genetics chair was Ephrussi's. And the first microbiology was André Lwoff's but even later.

[Q] As for biochemistry, apart from Fromageot, it was still quite traditional.

Well, there were some. There was Gabriel Bertrand who was Monod's precursor. Did you ever meet Gabriel Bertrand? A very old man with a goatee, who took very small steps and who had the office... Monod had the... he was given the... Trefouel had given his department to Monod, but not the office, which was... So Monod was waiting for him to get sick to get the office...

[Q] And it was Gabriel Bertrand, I believe, who said that in enzymes, it was the metal that was important and not the protein. Which was an unfortunate choice.

It's quite an unbelievable discovery.

[Q] For the evolution of biochemistry.

And for student's education.

François Jacob (1920-2013) was a French biochemist whose work has led to advances in the understanding of the ways in which genes are controlled. In 1965 he was awarded the Nobel Prize in Physiology or Medicine, together with Jacque Monod and André Lwoff, for his contribution to the field of biochemistry. His later work included studies on gene control and on embryogenesis. Besides the Nobel Prize, he also received the Lewis Thomas Prize for Writing about Science for 1996 and was elected a member of the French Academy in 1996.

Listeners: Michel Morange

Michel Morange is a professor of Biology and Director of the Centre Cavaillès of History and Philosophy of Science at the Ecole Normale Supérieure. After having obtained a Bachelor in biochemistry and two PhDs, one in Biochemistry, the other in History and Philosophy of Science, he went on to join the research unit of Molecular Genetics headed by François Jacob, in the Department of Molecular Biology at the Pasteur Institute, Paris. Together with Olivier Bensaude, he discovered that Heat Shock Proteins are specifically expressed on the onset of the mouse zygotic genome activation. Since then he has been working on the properties of Heat Shock Proteins, their role in aggregation and on the regulation of expression of these proteins during mouse embryogenesis. He is the author of 'A History of Molecular Biology' and 'The Misunderstood Gene'.

Michel Morange est généticien et professeur à L'Université Paris VI ainsi qu'à l'Ecole Normale Supérieure où il dirige le Centre Cavaillès d'Histoire et de Philosophie des Sciences. Après l'obtention d'une license en Biochimie ainsi que de deux Doctorats, l'un en Biochimie, l'autre en Histoire et Philosophie des Sciences, il rejoint le laboratoire de Génétique Moléculaire dirigé par le Professeur François Jacob à l'Institut Pasteur. Ses principaux travaux de recherche se sont portés sur l'Histoire de la Biologie au XXème siècle, la naissance et le développement de la Biologie Moléculaire, ses transformations récentes et ses interactions avec les autres disciplines biologiques. Auteur de "La Part des Gènes" ainsi que de "Histoire de la Biologie Moléculaire", il est spécialiste de la structure, de la fonction et de l'ingénerie des protéines.

Tags: Quand Monod, André Lwoff, Gabriel Bertrand, Conrad Waddington, Boris Ephrussi

Duration: 4 minutes, 10 seconds

Date story recorded: October 2004

Date story went live: 24 January 2008