The Australian scientist Frank Macfarlane Burnet—winner of the Nobel Prize in 1960 for his contributions to the understanding of immunological tolerance—is perhaps best recognized as one of the formulators of the clonal selection theory of antibody production, widely regarded as the ‘central dogma’ of modern immunology. His work in studies in animal virology, particularly the influenza virus, and rickettsial diseases is also well known. Somewhat less known and publicized is Burnet’s research on bacteriophages, which he conducted in the first decade (...) of his research career, immediately after completing medical school. For his part, Burnet made valuable contributions to the understanding of the nature of bacteriophages, a matter of considerable debate at the time he began his work. Reciprocally, it was while working on the phages that Burnet developed the scientific styles, the habits of mind and laboratory techniques and practices that characterized him for the rest of his career. Using evidence from Burnet’s published work, as well as personal papers from the period he worked on the phages, this paper demonstrates the direct impact that his experiments with phages had on the development of his characteristic scientific style and approaches, which manifested themselves in his later career and theories, and especially in his thinking regarding various immunological problems. (shrink)

In 1936, Frank Macfarlane Burnet published a paper entitled "Induced lysogenicity and the mutation of bacteriophage within lysogenic bacteria," in which he demonstrated that the introduction of a specific bacteriophage into a bacterial strain consistently and repeatedly imparted a specific property – namely the resistance to a different phage – to the bacterial strain that was originally susceptible to lysis by that second phage. Burnet's explanation for this change was that the first phage was causing a mutation in the bacterium (...) which rendered it and its successive generations of offspring resistant to lysogenicity. At the time, this idea was a novel one that needed compelling evidence to be accepted. While it is difficult for us today to conceive of mutations and genes outside the context of DNA as the physico-chemical basis of genes, in the mid 1930s, when this paper was published, DNA's role as the carrier of hereditary information had not yet been discovered and genes and mutations were yet to acquire physical and chemical forms. Also, during that time genes were considered to exist only in organisms capable of sexual modes of replication and the status of bacteria and viruses as organisms capable of containing genes and manifesting mutations was still in question. Burnet's paper counts among those pieces of work that helped dispel the notion that genes, inheritance and mutations were tied to an organism's sexual status. In this paper, I analyze the implications of Burnet's paper for the understanding of various concepts – such as "mutation," and "gene," – at the time it was published, and how those understandings shaped the development of the meanings of these terms and our modern conceptions thereof. (shrink)

In 1936, Frank Macfarlane Burnet published a paper entitled “Induced lysogenicity and the mutation of bacteriophage within lysogenic bacteria,” in which he demonstrated that the introduction of a specific bacteriophage into a bacterial strain consistently and repeatedly imparted a specific property – namely the resistance to a different phage – to the bacterial strain that was originally susceptible to lysis by that second phage. Burnet’s explanation for this change was that the first phage was causing a mutation in the bacterium (...) which rendered it and its successive generations of offspring resistant to lysogenicity. At the time, this idea was a novel one that needed compelling evidence to be accepted. While it is difficult for us today to conceive of mutations and genes outside the context of DNA as the physico-chemical basis of genes, in the mid 1930s, when this paper was published, DNA’s role as the carrier of hereditary information had not yet been discovered and genes and mutations were yet to acquire physical and chemical forms. Also, during that time genes were considered to exist only in organisms capable of sexual modes of replication and the status of bacteria and viruses as organisms capable of containing genes and manifesting mutations was still in question. Burnet’s paper counts among those pieces of work that helped dispel the notion that genes, inheritance and mutations were tied to an organism’s sexual status. In this paper, I analyze the implications of Burnet’s paper for the understanding of various concepts – such as “mutation,” and “gene,” – at the time it was published, and how those understandings shaped the development of the meanings of these terms and our modern conceptions thereof. (shrink)

Viruses have been virtually absent from philosophy of biology. In this editorial introduction, we explain why we think viruses are philosophically important. We focus on six issues, and we show how they relate to classic questions of philosophy of biology and even general philosophy.

Though viruses have generally been characterized by their pathogenic and more generally harmful effects, many examples of mutualistic viruses exist. Here I explain how the idea of mutualistic viruses has been defended in recent virology, and I explore four important conceptual and practical consequences of this idea. I ask to what extent this research modifies the way scientists might search for new viruses, our notion of how the host immune system interacts with microbes, the development of new therapeutic approaches, and, (...) finally, the role played by the criterion of autonomy in our understanding of living things. Overall, I suggest that the recognition of mutualistic viruses plays a major role in a wider ongoing revision of our conception of viruses. (shrink)

Many historical studies have been devoted to the French school of molecular biology, in particular to the work of Jacques Monod on adaptive enzymes. By focusing on Francois Jacob's studies on lysogeny between 1950 and 1960, we intend to redress the imbalance of historiography, as well as proposing a more fruitful point of view for understanding the relative importance of international contacts and local traditions in the genesis of the operon model.Elie Wollman and Jacob's work on temperate bacteriophages rendered respectable (...) a system that had been considered an artefact for more than two decades. They did this firstly by modelling their studies on those of the US phage group and secondly by basing these studies on a complex vision of the relations between bacteria and bacteriophages. The interaction between bacteria and temperate bacteriophages was considered ab initio as a biochemical process, the mechanisms of which would eventually be characterized. It was also considered as a ''normal'' phenomenon that could be used as a model to understand the process of differentiation, as well as the role of viruses in diseases and cancer. The temperate bacteriophage was a model system that was far more epistemologically open and, for this reason, in a sense more productive than the virulent phage studied by the US phage group. (shrink)

This article shows how Lamarckism was essential in the birth of the French school of molecular biology. We argue that the concept of inheritance of acquired characters positively shaped debates surrounding bacteriophagy and lysogeny in the Pasteurian tradition during the interwar period. During this period the typical Lamarckian account of heredity treated it as the continuation of protoplasmic physiology in daughter cells. Félix d’Hérelle applied this conception to argue that there was only one species of bacteriophage and Jules Bordet applied (...) it to develop an account of bacteriophagy as a transmissible form of autolysis and to analyze the new phenomenon of lysogeny. In a long-standing controversy with Bordet, Eugène Wollman deployed a more morphological understanding of the inheritance of acquired characters, yielding a particulate, but still Lamarckian, account of lysogeny. We then turn to André Lwoff who, with several colleagues, completed Wollman’s research program from 1949 to 1953. We examine how he gradually set aside the Lamarckian background, finally removing inheritance of acquired characters from the resulting account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex dual role of Lamarckism as it moved from an assumed explanatory framework to a challenge that the nascent molecular biology had to overcome. (shrink)

Although it has not been much noticed, reproduction is the central theme of François Jacob’s important history of biology, La logique du vivant (The Logic of Life). In a book ostensibly devoted to heredity, this molecular biologist had reproduction integrate levels of organization from organisms to molecules and play a major role in each historical transition between them, not just in the influential argument for a shift “from generation to reproduction.” Moreover, I claim, La logique was the first general history (...) of (research on) reproduction. Earlier histories had tackled only aspects of generation and reproduction; none historicized the latter. Jacob’s innovation came out of the rising prominence of reproduction in neo-Darwinist studies of populations and in his own field, the cellular genetics of bacteria and their viruses, and engagement with history and philosophy of science. The discovery of bacterial “sex” enabled microbial genetics but, ironically, led Jacob to a sexless concept of reproduction. This approach molded a history that reached across the living world but slighted sex and the complexities of reproduction in multicellular organisms. Readers can learn from its strength and limitations. (shrink)

During the 1960s, Howard M. Temin (1934-1994), dared to advocate a "heretical" hypothesis that appeared to be at variance with the central dogma of molecular biology, understood by many to imply that information transfer in nature occurred only from DNA to RNA. Temin's provirus hypothesis offered a simple explanation of both virus replication and viral-induced cancer and stated that Rous sarcoma virus, an RNA virus, is replicated via a DNA intermediate. Popular accounts of this scientific episode, written after the discovery (...) of an RNA-directed DNA polymerase in 1970, tend to describe the reaction to his proposition as ardent opposition. Typically these accounts use a 'molecular biology' standpoint emphasizing the central dogma's part in its rejection. In this article, however, this episode will be examined from a joint perspective of virology and experimental cancer research. From this perspective it is clear that Temin's work was well within the epistemological and methodological boundaries of virology and cancer research. Still, scientists did have reasons to doubt the provirus hypothesis, but these do not seem to be good enough to either justify an account that portrays Temin as a renegade or his ideas as heretical. (shrink)

This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the “degenerative” or the “retrograde (...) evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)

This article concerns itself with the reception of Rous' 1911 discovery of what later came to be known as the Rous Sarcoma Virus (RSV). Rous made his discovery at the Rockefeller Institute for Medical Research which had been primarily established to conduct research into infectious diseases. Rous' chance discovery of a chicken tumor led him to a series of conjectures about cancer causation and about whether cancer could have an extrinsic cause. Rous' finding was received with some scepticism by the (...) scientific community that held that cancer was not infectious and favored explanations which located the origins of cancer in the inner mechanism of the cell. After 4 years of unsuccessful effort to isolate and further determine the virus Rous felt compelled to discontinue his work on cancer viruses. When 55 years later, the significance of Rous's discovery was attested by the award of the Nobel Prize, it opened up debates about the issues of delayed recognition and scientific reputation. This article also considers why Rous' hypothesis of a viral origin of cancer could not be incorporated into the existing body of knowledge about cancer before the 1950s. (shrink)

This article concerns itself with the reception of Rous’ 1911 discovery of what later came to be known as the Rous Sarcoma Virus. Rous made his discovery at the Rockefeller Institute for Medical Research which had been primarily established to conduct research into infectious diseases. Rous’ chance discovery of a chicken tumor led him to a series of conjectures about cancer causation and about whether cancer could have an extrinsic cause. Rous’ finding was received with some scepticism by the scientific (...) community that held that cancer was not infectious and favored explanations which located the origins of cancer in the inner mechanism of the cell. After 4 years of unsuccessful effort to isolate and further determine the virus Rous felt compelled to discontinue his work on cancer viruses. When 55 years later, the significance of Rous’s discovery was attested by the award of the Nobel Prize, it opened up debates about the issues of delayed recognition and scientific reputation. This article also considers why Rous’ hypothesis of a viral origin of cancer could not be incorporated into the existing body of knowledge about cancer before the 1950s. (shrink)