SummaryIn the 1940s a controversy developed between John H. Northrop (Nobel Laureate, 1946) and Max Delbrück (Nobel Laureate, 1969) on the formation of bacteriophage. From the historiography of molecular biology there emerges a picture of an obstinate Northrop who repudiated the ‘correct’ insights revealed by the experiments of Delbrück. The established reputation of Northrop confronts one with the question of why Delbrück's epoch-making experiments were not convincing for Northrop. It will be argued that this was a consequence of local incommensurability (...) between Northrop's physiological/chemical research style and Delbrück's bacteriological/genetic research style. The analysis of this controversy reveals the elements that made up these two research styles. (shrink)

The classical view of the gene prevailing during the 1910s and 1930s comprehended the gene as the indivisible unit of genetic transmission, genetic recombination, gene mutation and gene function. The discovery of intragenic recombination in the early 1940s led to the neoclassical concept of the gene, which prevailed until the 1970s. In this view the gene or cistron, as it was now called, was divided into its constituent parts, the mutons and recons, materially identified as nucleotides. Each cistron was believed (...) to be responsible for the synthesis of one single mRNA and concurrently for one single polypeptide. The discoveries of DNA technology, beginning in the early 1970s, have led to the second revolution in the concept of the gene in which none of the classical or neoclassical criteria for the definition of the gene hold strictly true. These are the discoveries concerning gene repetition and overlapping, movable genes, complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary transcript, pseudogenes and gene nesting. Thus, despite the fact that our comprehension of the structure and organization of the genetic material has greatly increased, we are left with a rather , open and general concept of the gene. This article discusses past and present contemplations of genes, genomes, genotypes and phenotypes as well as the most recent advances of the study of the organization of genomes. (shrink)

The 1940s and 1950s were marked by intense debates over the origin of drug resistance in microbes. Bacteriologists had traditionally invoked the notions of ‘training’ and ‘adaptation’ to account for the ability of microbes to acquire new traits. As the field of bacterial genetics emerged, however, its participants rejected ‘Lamarckian’ views of microbial heredity, and offered statistical evidence that drug resistance resulted from the selection of random resistant mutants. Antibiotic resistance became a key issue among those disputing physiological vs. genetic (...) explanations of variation in bacteria. Postwar developments connected with the Lysenko affair gave this debate a new political valence.Proponents of the neo-Darwinian synthesis weighed in with support for the genetic theory. However, certain features of drug resistance seemed inexplicable by mutation and selection, particularly the phenomenon of ‘multiple resistance’—the emergence of resistance in a single strain against several unrelated antibiotics. In the late 1950s, Tsutomu Watanabe and his collaborators solved this puzzle by determining that resistance could be conferred by cytoplasmic resistance factors rather than chromosomal mutation. These R factors could carry resistance to many antibiotics and seemed able to promote their own dissemination in bacterial populations. In the end, the vindication of the genetic view of drug resistance was accompanied by a recasting of the ‘gene’ to include extrachromosomal hereditary units carried on viruses and plasmids. (shrink)

'Lysogeny is the hereditary power to produce bacteriophage'. This definition, coined by André Lwoff in 1953, seems simple enough. However, it summarizes a very complex history, which began with the discovery of bacteriophages. How was the novel relationship between a virus and a bacterial cell conceived? In what way did this relationship renew the question of the nature of viruses? How did it generate a theory of hereditary factors? It was soon shown that bacteria can produce a lysogenic agent without (...) exogenic phages. That was in 1925 with the discovery of lysogeny. In an attempt to throw light on the history of lysogeny, I have traced the work of Eugène Wollman from 1919 to 1943, and have examined the work of J. Bordet, O. Bail and F.M. Burnet. The second part of this paper is devoted to the experiments that led to the elucidation of lysogeny. Of particular importance was the shaping of the concept of 'prophage'. Lysogeny was studied anew and clarified at the Institut Pasteur in Paris under the guidance of André Lwoff. How was genetic determinism of lysogeny brought to light? What new models and new concepts then formed the basis of genetic analysis of the relationship between the virus and its bacterial host? These aspects are seen in the light of the work of André Lwoff, François Jacob, Joshua Lederberg and Elie Wollman. (shrink)