Miguel García-Sancho

Bidirectional Shaping and Spaces of Convergence: Interactions Between Biology and Computing from the First DNA Sequencers to Global Genome Databases

This article proposes a new bi-directional way of understanding the convergence of biology and computing. It argues for a reciprocal interaction in which biology and computing have shaped and are currently reshaping each other. In so doing, we qualify both the view of a natural marriage and of a digital shaping of biology, which are common in the literature written by scientists, STS, and communication scholars. The DNA database is at the center of this interaction. We argue that DNA databases are spaces of convergence for computing and biology that change in form, meaning, and function from the 1960s to the 2000s. The first part of the article shows how, in the 1980s, DNA sequencing shifted from passively incorporating computers to be increasingly modeled in digital coding and decoding. Information retrieval algorithms, reciprocally, were altered according to the peculiarities of DNA in the first sequence-storage databases. The second part of the article investigates the impact of these reciprocal interactions and globalization on the organization of research centers, ways of conducting big science, and scientific values. Through convergence and new technologies such as data mining, biology and computing were transformed technologically, institutionally, and culturally into a new bio-data enterprise called genomics.

A new insight into Sanger's development of sequencing: from proteins to DNA, 1943-1977.

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger’s sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger’s papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine.

Animal breeding in the age of biotechnology: the investigative pathway behind the cloning of Dolly the sheep

This paper addresses the 1996 cloning of Dolly the sheep, locating it within a long-standing tradition of animal breeding research in Edinburgh. Far from being an end in itself, the cell-nuclear transfer experiment from which Dolly was born should be seen as a step in an investigative pathway that sought the production of medically relevant transgenic animals. By historicising Dolly, I illustrate how the birth of this sheep captures a dramatic redefinition of the life sciences, when in the 1970s and 1980s the rise of neo-liberal governments and the emergence of the biotechnology market pushed research institutions to show tangible applications of their work. Through this broader interpretative framework, the Dolly story emerges as a case study of the deep transformations of agricultural experimentation during the last third of the twentieth century. The reorganisation of laboratory practice, human resources and institutional settings required by the production of transgenic animals had unanticipated consequences. One of these unanticipated effects was that the boundaries between animal and human health became blurred. As a result of this, new professional spaces emerged and the identity of Dolly the sheep was reconfigured, from an instrument for livestock improvement in the farm to a more universal symbol of the new cloning age.

Genetic Information in the Age of DNA Sequencing

The claim that genes encode and transmit information is a central conceptual tenet in biomedicine. Historians have placed the origins of this claim in the rise of molecular biology after World War II, and philosophers still debate the utility of understanding genes as information for biomedical research. In this article, I will investigate how “genetic information” as both a concept and a model for experimental practice was affected by the emergence in the mid-1970s of technologies that enabled scientists to determine the sequence of chemical units of DNA, the molecule that constitutes genetic material. I argue that DNA sequencing, rather than changing the meaning of genetic information, transformed the possibilities of what could be achieved with this concept and directed it to large-scale enterprises such as the Human Genome Project. Thus, my argument suggests that scientific concepts should be regarded as entities that, beyond abstract thinking, enable researchers to do things—in this case, embarking on a multi-million-dollar project aimed at sequencing the information encoded in the human genome.

Academic and molecular matrices: A study of the transformations of connective tissue research at the University of Manchester (1947–1996)

This paper explores the different identities adopted by connective tissue research at the University of Manchester during the second half of the 20th century. By looking at the long-term redefinition of a research programme, it sheds new light on the interactions between different and conflicting levels in the study of biomedicine, such as the local and the global, or the medical and the biological. It also addresses the gap in the literature between the first biomedical complexes after World War II and the emergence of biotechnology. Connective tissue research in Manchester emerged as a field focused on new treatments for rheumatic diseases. During the 1950s and 60s, it absorbed a number of laboratory techniques from biology, namely cell culture and electron microscopy. The transformations in scientific policy during the late 70s and the migration of Manchester researchers to the US led them to adopt recombinant DNA methods, which were borrowed from human genetics. This resulted in the emergence of cell matrix biology, a new field which had one of its reference centres in Manchester. The Manchester story shows the potential of detailed and chronologically wide local studies of patterns of work to understand the mechanisms by which new biomedical tools and institutions interact with long-standing problems and existing affiliations.

Towards future archives and historiographies of 'big biology'.

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Recasting the Local and the Global: The Three Lives of Protein Sequencing in Spanish Biomedical Research (1967–1995)

This chapter explores how protein sequencing – a technique enabling the determination of the fine structure of protein chains – circulated across different biomedical fields in Spain during the last third of the twentieth century. By focusing on three individual scientists, I argue that protein sequencing had three distinct Spanish lives and was inextricably linked to the biographies of its users. Between 1967 and 1995, protein sequencing shifted from an aid to prevent agrarian plagues in Franco’s dictatorship to a promising diagnostic tool in the transition towards democracy and, finally, an out-of-fashion technique overshadowed by the emergence of recombinant DNA methods. My proposed three lives challenge over-simplistic comparative frameworks and suggest that the local configuration of a new scientific technique should not be sought in its similarities or idiosyncratic differences with a given ‘global’. Protein sequencing in Spain was rather shaped by the researchers’ will of constructing a professional space of their own and achieving a complex equilibrium between the fulfilment of local demands and the engagement with what was considered international and cutting-edge at each historical time.

The Recombinant University: Genetic Engineering and the Emergence of Stanford Biotechnology

continuities and intersections. Although written under the Cambridge influence of Jim Secord’s “knowledge in transit” paradigm, perhaps more could have been said about the kind of circulation between writers, publishers, and readers that featured in those science-themed fairy tales, and in particular about the specific role of women and children as active audiences for science. A more refined analysis of present scholarship on science and literature would have been valuable. Take for instance Barbara Naumann’s guest contribution to a special issue of Science in Context (2005), in which several papers explore different “contact zones” and aspects of self-reflection and self-representation. A certain comparative approach using other cases from outside Victorian Britain might also have been informative and relevant for a complete analysis of that particular genre. Perhaps Lord Byron was right when he said, as Keene quotes: “Truth is stranger than fiction” (p. 187). The truth here is that the book is a remarkable piece of historical research that might interest several audiences beyond the specialized area of history of science and chemistry. This is another sign of the dynamism of present scholarship on the intersections between science and literature, and also of the vitality of the British Society for Literature and Science and the Cambridge Children’s Literature Seminar. Keene helps us to pursue the idea that “reasoned scientific books are not easily distinguished from more imaginative or fantastical writings” (p. 8). Her research confirms that literary devices were indeed used in the past, in particular in Victorian Britain, as a metaphor for scientific understanding.

From Chemical Degradation to Biological Replication (1962–1977)

The impact of Sanger’s determination of insulin (1955) and his subsequent Nobel Prize (1958) led to the uptake of his technique not only by biochemists, but by other biological researchers. Especially active were the members of an emerging group in the Cavendish Laboratory, close by in the University of Cambridge. The Cavendish Laboratory had been a leading centre in physics since its foundation in the late-nineteenth century, with James Clerk Maxwell, J.J. Thompson and Ernest Rutherford all producing important contributions to the structure of the atom and its electromagnetic properties (Warwick, 2003; Buchwald and Warwick, 2001; Hendry, 1984). From the early 1930s onwards, a group of Cavendish investigators were among the pioneers in the application of X-ray crystallography to proteins.

The Sequence of Insulin and the Configuration of a New Biochemical Form of Work (1943–1962)

The Department of Biochemistry at Cambridge, where Sanger began his career, was the creation of its first director, Frederick G. Hopkins. Hopkins had arrived at Cambridge when medical sciences were dominated by the physiologist Michael Foster and, during the first decades of the twentieth century, had struggled to establish biochemistry as a new discipline at the University. Hopkins was awarded the first Chair in Biochemistry in 1914, and in 1923 given his own building, the Dunn Institute of Biochemistry. His research agenda, as in physiology, was concerned with the functional processes of the body. Hopkins, however, focused on their molecular basis through a ‘dynamic’ study of metabolism (Geison, 1978; Weatherall and Kamminga, 1992).