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)

This paper examines the vital role played by electron microscopy toward the modern definition of viruses, as formulated in the late 1950s. Before the 1930s viruses could neither be visualized by available technologies nor grown in artificial media. As such they were usually identified by their ability to cause diseases in their hosts and defined in such negative terms as “ultramicroscopic” or invisible infectious agents that could not be cultivated outside living cells. The invention of the electron microscope, with magnification (...) and resolution powers several orders of magnitude better than that of optical instruments, opened up possibilities for biological applications. The hitherto invisible viruses lent themselves especially well to investigation with this new instrument. We first offer a historical consideration of the development of the instrument and, more significantly, advances in techniques for preparing and observing specimens that turned the electron microscope into a routine biological tool. We then describe the ways in which the electron microscopic images, or micrographs, functioned as forms of new knowledge about viruses and resulted in a paradigm shift in the very definition of these entities. Micrographs were not mere illustrations since they did the work for the electron microscopists. Drawing extensively on primary publications, we adduce the role of the new instrument in understanding the so-called eclipse phase in virus multiplication and the unexpected spinoffs of data from electron microscopy in naming and classifying viruses. Thus, we show that electron microscopy functioned not only to provide evidence, but also arguments in facilitating a reordering of the world that it brought into the visual realm. (shrink)

It is argued that the major interpretations of tobacco mosaic virus which were suggested in the first half of the 20th century can be ordered into two conflicting approaches. It is shown that explaining the existence of these different approaches as views from different perspectives, is a mistaken metaphor. The different approaches resulted in the "construction" of different research objects as answers to the questions "What is a virus"? Although these different conceptions did exclude each other, they co-existed because of (...) the consensus concerning the existence of tobacco mosaic "disease". (shrink)

Scholars have argued that the beginning of virology can be dated from the end of the 19th century: the discovery that some infectious agents could pass through ultrafilters produced a criterium to distinguish ultrafilterable viruses from infectious agents that are not filterable, e.g. bacteria. A filterable agent, claimed to be the cause of human influenza, was isolated in 1933. It will be argued in this paper, however, that the influence of a bacteriological paradigm on influenza research in the first half (...) of the twentieth century was very powerful. Until the late 1940s influenza viruses were studied as infectious entities which, although filterable, were conceived of as analogous to bacteria. It was assumed that filterable viruses which infected animals were a kind of ultrabacteria. According to the bacteriological paradigm the assumed dependence of the filterable viruses on living cells was easy to account for. The second half of the 1940s saw the 'modern concept of virus' begin to be applied to the influenza viruses. Influenza vaccinations in 1946 did not appear to provide protection, from which it was concluded that the influenza virus is very variable. Furthermore, in 1946 and 1947 experimental studies were published, which indicated that the influenza virus may go through an eclipse during its multiplication: it disappears as an infectious agent. Viewed from this perspective, it was only by the second half of the 1940s that research on the influenza virus became emancipated from the bacteriological paradigm. (shrink)

Contemporary oncological research is predominantly characterised by genetic explanations, a situation which may be briefly denoted as the oncogene paradigm. This essay discusses why the new paradigm was perceived so attractive that it could take over the whole field of oncology within a time-span of less than two decades. It is argued that the revolutionary character of the oncogene paradigm stems from the fact that it transcends a dichotomy which has kept experimental cancer research divided for more than three quarters (...) of a century. This concerns the dichotomy between so-called exogenous and endogenous explanations of cancer causation. This essay mainly focuses on the role of the exogenous/endogenous dichotomy in the reception of research on oncogenic viruses, especially discussing the work of Nobel laureate Peyton Rous on cancer viruses at the Rockefeller Institute. Rous was severely criticised by James Ewing, director of the Memorial Hospital for Cancer and Allied Diseases in New York, who held the idea that the origin of cancer was based in the cell. The twentieth century controversy over oncogenic viruses is placed in the context of the intense discussion over causality in medicine during the first decades of the twentieth century in Germany. It is argued that the oncogene paradigm may be seen as revolutionary because it succeeded in uniting the exogenous and endogenous explanations of cancer in a single paradigm. (shrink)