What history tells us XXXX. The success story of the expression “genome editing”

International audienceThe expression « genome editing » designates the possibilities opened by the CRISPR-Cas9 enzyme to cut and modify genemes at precise positions. This expression has been rapidly adopted by biologists, but also journalists and laymen. I descibe steps in the recent emergence of this expression, as well as the reasons of its success.L’expression « édition du génome » désigne la possibilité ouverte par l’enzyme CRISPR-Cas9 de couper et de modifier le génome à des sites précis. Cette expression est utilisée aussi bien par les biologistes que par les journalistes et le grand public. Nous montrons dans cet article que cet usage est récent, nous décrivons les étapes qui ont conduit à sa diffusion et les raisons de son succès

Changer les gènes ? Un projet qui n'est plus prioritaire

International audienceModification of the human germ line has remained a distant but valuable objective for most biologists since the emergence of genetics (and even before). To study the historical transformations of this project, I have selected three periods—the 1930s, at the pinnacle of eugenics, around 1974 when molecular biology triumphed, and today—and have adopted three criteria to estimate the feasibility of this project: the state of scientific knowledge, the existence of suitable tools, and societal demands. Although the long-awaited techniques to modify the germ line are now available, I will show that most of the expectations behind this project have disappeared, or are considered as being reachable by highly different strategies.La modification ciblée de la lignée germinale (et donc de l'espèce humaine) est restée un objectif distant mais raisonnable, depuis l'émergence de la génétique (et même avant) jusqu'à ces dernières années. J'ai choisi trois temps pour étudier les évolutions historiques de ce projet – dans les années 1930, au sommet du mouvement eugéniste, autour de 1974 quand la biologie moléculaire triomphait, et aujourd'hui – et j'ai sélectionné trois critères pour estimer la faisabilité d'un tel projet – l'état des connaissances scientifiques, l'existence de techniques adaptées, et les demandes de la société. Bien que les techniques longtemps espérées pour modifier la lignée germinale soient aujourd'hui disponibles, je montrerai que la plupart des attentes qui soutenaient ce projet ont disparu, ou sont considérées comme pouvant être atteintes par des stratégies totalement différentes

Monod and the spirit of molecular biology

International audienceThe founders of molecular biology shared views on the place of biology within science, as well as on the relations of molecular biology to Darwinism. Jacques Monod was no exception, but the study of his writings is particularly interesting because he expressed his point of view very clearly and pushed the implications of some of his choices further than most of his contemporaries. The spirit of molecular biology is no longer the same as in the 1960s but, interestingly, Monod anticipated some recent evolutions of this discipline

Pseudoalleles and gene complexes: the search for the elusive link between genome structure and gene function

International audienceAfter their discovery in the first decades of the XX th century, pseudoalleles generated much interest among geneticists: they apparently violated the conception of the genome as a collection of independent genes elaborated by Thomas Morgan's group. Their history is rich, complex, and deserves more than one short contribution. I will focus on two issues: the way the phenomenon of pseudoallelism suggested that the genome was more than a simple addition of independent genes, and the connection established between the formation of pseudoalleles during evolution and their functional roles. I will successively consider the first explanations for the origin of pseudoalleles elaborated in the mid-1930s, the metabolic/developmental sequential model proposed by Ed Lewis in the 1950s, the disappointments encountered with the T-complex in the 1970s, and the fading of the previous models after the molecular characterization of the pseudoallelic gene complexes in the 1980s. Genomes are more than collections of genes, but their structures are the result of a complex evolutionary history that leaves no place for simplistic models

What history tells us XXXIX.CRISPR-Cas: From a prokaryotic immune system to a universal genome editing tool

International audienceCRISPR-Cas9 is an enzyme that allows to cut (and modify) genomes at precise sites . This new technology, simple and cheap, opens new paths to fundamental research as well immense opportunities for applications. I show that this new tool finds its origin in the study of a bacterial system of immunity against bacteriophages. I will emphasize the importance of three articles published in 2005. These contributions have not been properly cited by followers. This case study is an excellent example of the extensive rewriting of history done by scientists.CRISPR-Cas est une enzyme qui permet de couper (et de modifier) les génomes aux sites précis choisis par l’expérimentateur. De nombreux travaux ont été effectués avec ce système, et les perspectives de recherche fondamentale et d’applications que ce nouvel outil ouvre ont suscité ces dernières années un vaste débat. Dans cet article, nous décrivons comment cet outil universel trouve son origine dans l’étude d’un système d’immunité bactérienne contre les virus. Nous montrons en particulier l’importance de trois articles publiés en 2005, dont le rôle a été minimisé dans les publications ultérieures. Il s’agit d’un magnifique exemple de réécriture de l'histoire par ses acteurs

What history tells us XXXXI. Ubiquitin and proteolysis

International audienceThe importance of the discovery, at the beginning of the 1980s, of a complex mechanism pf protein degradation involving multiple additions of a small protein called ubiquitin, and the use of energy (ATP), is unanimously acknowledged. I describe the multiple obstacles that the quality of the experimental work permitted to overcome. The idea that protein degradation could be an important step of cellular control was not obvious for molecular biologists. The use of ATP for such a process seemed unnecessary. And the complexity of the system was unexpected. This discovery deeply transformed molecular biology

Rebels? No, Simply Scientists

Michel Morange reviews Rebels, Mavericks, and Heretics in Biology, an alternative history of modern biological thought

Il était une fois, les sciences de la vie

La question de l’orientation de la recherche vers des objectifs ciblés est aujourd’hui directement posée. Quelle place laisser à la recherche fondamentale, « libre » ? Le débat s’enlise souvent dans des positions de principe. L’histoire montre que la recherche scientifique a toujours été orientée, plus ou moins directement, par la société dans laquelle elle était faite. La politique scientifique du CNRS n’a échappé, à aucun moment, à ce conditionnement. Mais l’histoire nous révèle aussi les c..