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 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)

Richard Goldschmidt was one of the most controversial biologists of the mid-twentieth century. Rather than fade from view, Goldschmidt's work and reputation has persisted in the biological community long after he has. Goldschmidt's longevity is due in large part to how he was represented by Stephen J. Gould. When viewed from the perspective of the biographer, Gould's revival of Goldschmidt as an evolutionary heretic in the 1970s and 1980s represents a selective reinvention of Goldschmidt that provides a contrast to other (...) kinds of biographical commemorations by scientists. (shrink)

The importance of viruses as model organisms is well-established in molecular biology and Max Delbrück’s phage group set standards in the DNA phage field. In this paper, I argue that RNA phages, discovered in the 1960s, were also instrumental in the making of molecular biology. As part of experimental systems, RNA phages stood for messenger RNA, genes and genome. RNA was thought to mediate information transfers between DNA and proteins. Furthermore, RNA was more manageable at the bench than DNA due (...) to the availability of specific RNases, enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided scientists with a pure source of mRNA to investigate the genetic code, genes and even a genome sequence. This paper focuses on Walter Fiers’ laboratory at Ghent University and their work on the RNA phage MS2. When setting up his Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now a little-known technique, evolved gradually from a means to solve the genetic code, to a tool for completing the first genome sequence. Thus, I follow the research pathway of Fiers and his ‘RNA phage lab’ with their evolving experimental system from 1960 to the late 1970s. This study illuminates two decisive shifts in post-war biology: the emergence of molecular biology as a discipline in the 1960s in Europe and of genomics in the 1990s. (shrink)