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)

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)

It has long been taken for granted that the immune system’s capacity to protect an individual from infection and disease depends on the power of the system to distinguish between self and nonself. However, accumulating data have undermined this fundamental concept. Evidence against the self/nonself discrimination model left researchers in need of a new overarching framework able to capture the immune system’s reactivity. Here, I highlight that along with the self/nonself model, another powerful representation of the immune system’s reactivity has (...) been developed in the twentieth century immunology. According to this alternative view, the immune system is not a killer of nonself strangers but a peace-maker helping to establish harmony with the environment. The balance view of the system has never become part of the dominant paradigm. However, it is gaining more and more currency as new research develops. Advances in mucosal immunology confirm that instead of distinguishing between self and foreign the immune system reacts to microbial, chemical and self-induced alterations to produce responses that counterbalance effects of these changes. (shrink)

This paper considers the foundational role of the contagium vivum fluidum—first proposed by the Dutch microbiologist Martinus Beijerinck in 1898—in the history of virology, particularly in shaping the modern virus concept, defined in the 1950s. Investigating the cause of mosaic disease of tobacco, previously shown to be an invisible and filterable entity, Beijerinck concluded that it was neither particulate like the bacteria implicated in certain infectious diseases, nor soluble like the toxins and enzymes responsible for symptoms in others. He offered (...) a completely new explanation, proposing that the agent was a “living infectious fluid” whose reproduction was intimately linked to that of its host cell. Difficult to test at the time, the contagium vivum fluidum languished in obscurity for more than three decades. Subsequent advances in technologies prompted virus researchers of the 1930s and 1940s—the first to separate themselves from bacteriologists—to revive the idea. They found in it both the seeds for their emerging virus concept and a way to bring hitherto opposing thought styles about the nature of viruses and life together in consensus. Thus, they resurrected Beijerinck as the founding father, and contagium vivum fluidum as the core concept of their discipline. (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)