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)

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)

Philosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy (...) of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations. (shrink)

Upon entering clinical medicine in the 1940s, antibiotic therapy seemed to complete a transformation of hospitals that originated in the late nineteenth century. Former death sinks had become harbingers of therapeutic progress. Yet this triumph was short-lived. The arrival of pathologies caused by resistant bacteria, and of nosocomial infections whose spread was helped by antibiotic therapies, seemed to be intimately related to modern anti-infective therapy. The place where such problems culminated were hospitals, which increasingly appeared as dangerous environments where attempts (...) to combat infectious diseases had instead created hothouses of disease evolution. This paper will focus on one aspect of that history. It caused clinical medicine and hospital hygiene in particular to pay attention to a dimension of infectious disease it had previously paid little attention to thus far: The evolution of infectious disease—previously a matter of mostly theoretical interest—came to be useful in explaining many phenomena observed. This did not turn hospital hygienists into geneticists, though it did give them an awareness that the evolution of infectious disease in a broad sense was something that did matter to them. The paper advances its argument by looking at three phases: The growing awareness of the hospital as a dangerous environment in the 1950s, comprehensive attempts at improving antibiotic therapy and hospital hygiene that followed from the 1960s and lastly the framing of such challenges as risk factors from the 1970s. In conclusion, I will argue that hospital hygiene, being inspired in particular by epidemiology and risk factor analysis, discussed its own specific version of disease emergence and therefore contributed to the 1980s debates around such topics. Being loosely connected to more specialized studies, it consisted of a re-interpretation of infectious disease centred around the temporality of such phenomena as they were encountered in day-to-day dealings of clinical wards. (shrink)

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their (...) own previous concepts. Archival work with stored soil and clinical samples produces a record described here as ‘the biology of history’: the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today. (shrink)

Since the 1940s, microbiologists, biochemists and population geneticists have experimented with the genetic mechanisms of microorganisms in order to investigate evolutionary processes. These evolutionary studies of bacteria and other microorganisms gained some recognition from the standard-bearers of the modern synthesis of evolutionary biology, especially Theodosius Dobzhansky and Ledyard Stebbins. A further period of post-synthesis bacterial evolutionary research occurred between the 1950s and 1980s. These experimental analyses focused on the evolution of population and genetic structure, the adaptive gain of new functions, (...) and the evolutionary consequences of competition dynamics. This large body of research aimed to make evolutionary theory testable and predictive, by giving it mechanistic underpinnings. Although evolutionary microbiologists promoted bacterial experiments as methodologically advantageous and a source of general insight into evolution, they also acknowledged the biological differences of bacteria. My historical overview concludes with reflections on what bacterial evolutionary research achieved in this period, and its implications for the still-developing modern synthesis. (shrink)

A notion of experimental series is developed, in which experiments or experimental sets are connected through experimental suggestions arising from previous experimental outcomes. To that end, the justification of Howard Temin's DNA provirus hypothesis is examined. The hypothesis originated with evidence from two exploratory experimental sets on an oncogenic virus and was substantiated by including evidence from three additional experimental sets. Collectively these sets comprise an experimental series and the accumulative evidence from the series was adequate to justify the hypothesis (...) by persuading the virology community of its veracity. The notion of crucial experiment is also discussed in terms of experimental series. (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)

Frederick Griffith was an English bacteriologist at the Pathological Laboratory of the Ministry of Health in London who believed that progress in the epidemiology and control of infectious diseases would come only with more precise knowledge of the identity of the causative microorganisms. Over the years, Griffith developed and expanded a serological technique for identifying pathogenic microorganisms, which allowed the tracing of the sources of infectious disease outbreaks: slide agglutination. Yet Griffith is not remembered for his contributions to the biology (...) and epidemiology of infectious diseases so much as for discovering the phenomenon known as ‘transformation’. Griffith’s discovery, for many, was a pure case of serendipity whose biological relevance had also largely escaped him. In this paper, I argue that the key to understanding the significance of bacterial transformation – and the scientific legacy of Fred Griffith – rests not only on it initiating a cascade of events leading to molecular genetics but also on its implications for epidemiology based on the biology of host–parasite interactions. Looking at Griffith’s entire career, instead of focusing only on the transformation study, we can better appreciate the place of the latter within Griffith’s overall contributions. Presented in this way, Griffith’s experiment on bacterial transformation also ceases to appear as an anomaly, which in turn leads us to rethink some of the most prevalent historical conceptions about his work. (shrink)

Our understanding of what microbes are and how they evolve has undergone many radical shifts since the late nineteenth century, when many still believed that bacteria could be spontaneously generated and most thought microbial “species” (if any) to be unstable and interchangeable in form and function (pleomorphic). By the late twentieth century, an ontology based on single cells and definable species with predictable properties, evolving like species of animals or plants, was widely accepted. Now, however, genomic and metagenomic data show (...) that lateral gene transfer compromises this picture of stability and predictability, and refocuses our attention on multilineage communities. Treating such communities as unstable but identifiable evolving “individuals” makes us again pleomorphists, of a sort. (shrink)

A notion of experimental series is developed, in which experiments or experimental sets are connected through experimental suggestions arising from previous experimental outcomes. To that end, the justification of Howard Temin’s DNA provirus hypothesis is examined. The hypothesis originated with evidence from two exploratory experimental sets on an oncogenic virus and was substantiated by including evidence from three additional experimental sets. Collectively these sets comprise an experimental series and the accumulative evidence from the series was adequate to justify the hypothesis (...) by persuading the virology community of its veracity. The notion of crucial experiment is also discussed in terms of experimental series. (shrink)

The first part of this paper has shown that the development of regulatory genetics and the lactose operon model stemmed from laboratory cultures rooted in local traditions. A "physiological" culture may be recognized in the Pasteurian context. The institutional continuity provided the basis for a tenuous link between Pasteur, Lwoff, and Monod. My claim is that the "national" value of regulatory and physiological genetics is an artifact produced in the course of the legitimization process accompanying the institutionalisation of the discipline. (...) In the 1960s, the lactose operon model was turned into a "flag-object," a symbol of the new culture. The work done by the Pasteurian group became therefore the most important, if not the only, exemplar of molecular biology in France.The second part o f the paper described the origins of general patterns that dominated the building of molecular biology in France. The study of the relationships between molecular biologists and biochemists or immunologists revealed the existence of alternatives to the development of operon research, or to the convergence with molecular biology. Both examples uncover specific paths leading to achievements that might be viewed as international trends: the expansion of RNA and translation studies, and the development of cellular immunology. They illustrate two possible patterns of linking local settings and disciplinary traditions: an oligopolistic situation where a few groups or one institution dominate an entire field, and the emergence of "collective" trends through collaboration networks or schools. (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)

Between 1946 and 1960, a new phenomenon emerged in the field of bacteriology. "Bacterial sex," as it was called, revolutionized the study of genetics, largely by making available a whole new class of cheap, fast-growing, and easily manipulated organisms. But what was "bacterial sex?" How could single-celled organisms have "sex" or even be sexually differentiated? The technical language used in the scientific press -- the public and inalienable face of 20th century science -- to describe this apparently neuter organism was (...) explicit: the cells "copulated," had "intimate contract," "conjugal unions," and engaged in "ménage à trois" relationships. And yet, to describe bacteria as sexually reproducing organisms, the definition of sex itself had to change. Despite manifold contradictions and the availability of alternative language, the notion of sexually active (even promiscuous) single-celled organisms has persisted, even into contemporary textbooks on cell biology and genetics. In this paper I examine the ways in which bacteria were brought into the genetic fold, sexualized, and given gender; I also consider the issues underlying the durability of "bacterial sex.". (shrink)

Upon entering clinical medicine in the 1940s, antibiotic therapy seemed to complete a transformation of hospitals that originated in the late nineteenth century. Former death sinks had become harbingers of therapeutic progress. Yet this triumph was short-lived. The arrival of pathologies caused by resistant bacteria, and of nosocomial infections whose spread was helped by antibiotic therapies, seemed to be intimately related to modern anti-infective therapy. The place where such problems culminated were hospitals, which increasingly appeared as dangerous environments where attempts (...) to combat infectious diseases had instead created hothouses of disease evolution. This paper will focus on one aspect of that history. It caused clinical medicine and hospital hygiene in particular to pay attention to a dimension of infectious disease it had previously paid little attention to thus far: The evolution of infectious disease—previously a matter of mostly theoretical interest—came to be useful in explaining many phenomena observed. This did not turn hospital hygienists into geneticists, though it did give them an awareness that the evolution of infectious disease in a broad sense was something that did matter to them. The paper advances its argument by looking at three phases: The growing awareness of the hospital as a dangerous environment in the 1950s, comprehensive attempts at improving antibiotic therapy and hospital hygiene that followed from the 1960s and lastly the framing of such challenges as risk factors from the 1970s. In conclusion, I will argue that hospital hygiene, being inspired in particular by epidemiology and risk factor analysis, discussed its own specific version of disease emergence and therefore contributed to the 1980s debates around such topics. Being loosely connected to more specialized studies, it consisted of a re-interpretation of infectious disease centred around the temporality of such phenomena as they were encountered in day-to-day dealings of clinical wards. (shrink)