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)

In the early twentieth century, viruses had yet to be defined in a material way. Instead, they were known better by what they were not – not bacteria, not culturable, and not visible with a light microscope. As with the ill-defined “gene” of genetics, viruses were microbes whose nature had not been revealed. Some clarity arrived in 1929 when Francis O. Holmes, a scientist at the Boyce Thompson Institute for Plant Research reported that Tobacco mosaic virus could produce local necrotic (...) lesions on tobacco plants and that these lesions were in proportion to dilutions of the inoculum. Holmes’ method, the local lesion assay, provided the first evidence that viruses were discrete infectious particles, thus setting the stage for physicochemical studies of plant viruses. In a field where there are few eponymous methods or diseases, Holmes’ assay continues to be a useful tool for the study of plant viruses. TMV was a success because the local lesion assay “made the virus visible” and standardized the work of virology towards determining the nature of the virus. (shrink)

In a military-sponsored research project begun during the Second World War, inmates of the Stateville Penitentiary in Illinois were infected with malaria and treated with experimental drugs that sometimes had vicious side effects. They were made into reservoirs for the disease and they provided a food supply for the mosquito cultures. They acted as secretaries and technicians, recording data on one another, administering malarious mosquito bites and experimental drugs to one another, and helping decide who was admitted to the project (...) and who became eligible for early parole as a result of his participation. Thus, the prisoners were not simply research subjects; they were deeply constitutive of the research project. Because a prisoner’s time on the project was counted as part of his sentence, and because serving on the project could shorten one’s sentence, the project must be seen as simultaneously serving the functions of research and punishment. Michel Foucault wrote about such ‘mixed mechanisms’ in his Discipline and punish. His shining example of such a ‘transparent’ and subtle style of punishment was the panopticon, Jeremy Bentham’s architectural invention of prison cellblocks arrayed around a central guard tower. Stateville prison was designed on Bentham’s model; Foucault featured it in his own discussion. This paper, then, explores the power relations in this highly idiosyncratic experimental system, in which the various roles of model organism, reagent, and technician are all occupied by sentient beings who move among them fluidly. This, I argue, created an environment in the Stateville hospital wing more panoptic than that in the cellblocks. Research and punishment were completely interpenetrating, and mutually reinforcing. (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)

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)

La convicción de que los fenómenos y procesos naturales podían ser representados en un espacio físico regido por la geometría euclídea actuó en la ciencia clásica como supuesto epistemológico fundamental de la creación teórica. La posibilidad de un análisis matemático del continuo garantizaba, en efecto, una descripción intuitiva y pictórica de las trayectorias de los móviles estudiadas por la dinámica, así como una determinación precisa de los efectos producidos en el seno de las relaciones causales. Fueron convicciones y supuestos que (...) tuvieron que ser revisados en el momento en que el cuanto de acción de Planck obligó a desarrollar una nueva... física de los sistemas atómicos. Las consecuencias, no obstante, se dejarían sentir no sólo en el ámbito de la Física sino en todas aquellas regiones de la ciencia natural, como la Biología, que tenían que construirse bajo la cobertura conceptual de la naciente mecánica. El presente trabajo es una reflexión sobre los problemas filosóficos planteados en el encuentro entre la física del átomo y la química de las moléculas. The certainty that natural phenomena and processes could be represented in a physical space ruled by Euclidean geometry was a fundamental epistemological assumption of theoretical creation in classical science. The possibility of a mathematical analysis of the continuum ensured an intuitive, pictorial description of mobile trajectories as studied in dynamics, as well as a precise determination of the effects generated within causal relations. These convictions and assumptions had to be reviewed when the Plank action quantum forced the development of a new physics of atomic systems. Consequences, nevertheless, transcended the scope of Physics and... extended to all regions of natural science, including Biology, which had to be built under the conceptual coverage of the nascent mechanics. The present work is a reflection on the philosophical problems posed by the encounter of physics of atoms and chemistry of molecules. (shrink)

Ecology is usually described as the study of organisms interacting with one another and their environments. From this view of ecology, viruses – not usually considered to be organisms – would merely be part of the environment. Since the late 1980s, however, a growing stream of micrographic, experimental, molecular, and model-based (theoretical) research has been investigating how and why viruses should be understood as ecological actors of the most important sort. Viruses, especially phage, have been revealed as participants in the (...) planet's most crucial food webs, even though viruses technically consume nothing (they do not metabolize by themselves). Even more impressively, viruses have been identified as regulators of planetary biogeochemistry, in which they control cycles such as carbon, nitrogen and phosphorus – cycles on which all life depends. Although much biogeochemical research black-boxes the entities filling functional roles, it is useful to focus a little more closely to understand how viruses can be held responsible for the global processes of life. This paper will give a brief overview of the history of virus ecology and tease out the implications of large-scale ecological modelling with viruses. This analysis suggests that viruses should be conceptualized as ecological actors that are at least comparable and possibly equal to organismal actors. Ecological agency can therefore be distinguished from standard interpretations of biological agency. (shrink)