This paperback edition of Miguel García-Sancho’s 2012 monograph remains a highly informative piece of scholarship. It provides a history of the British Sanger Institute, established in bucolic Hinxton by the Medical Research Council and the Wellcome Trust under the inaugural directorship of (now Sir) John Sulston in 1993. With the European Bioinformatics Institute, an outgrowth of the Biocomputing Unit of the European Molecular Biology Laboratory (EMBL), the Sanger Centre, as it was initially named, housed the core of the British contribution to the Human Genome Project (HGP). Yet more than just an institutional history of DNA sequencing, this book provides a history of the sequencing of biological macromolecules writ large. In demonstrating that this practice actually began with proteins, not genes, in the 1940s, García-Sancho has two overarching goals. The first is to complicate arguments, made by participants in the “golden age” of molecular biology and the HGP, that DNA sequencing was a product of the molecular biology of the 1950s and 1960s, and especially of the 1970s commercialization of recombinant DNA technologies. The second is to reassess a stance he believes some ethical, legal, and social implications (ELSI) and science and technology studies (STS) literature has perpetuated: that the convergence of biology and computing, too, began only in the 1970s.
The book has three parts. The first centers on the British biochemist Frederick Sanger, and chronicles how his methods for sequencing amino acids in proteins slowly incorporated problems and practices from molecular biology. This was stimulated both by his 1958 Nobel Prize for the sequence of insulin, and by his subsequent move from the Department of Biochemistry at Cambridge to the new Laboratory of Molecular Biology (LMB) there in 1962. In this new environment, Sanger transitioned from a focus on chemical degradation to biological replication in the 1960s and 1970s. In Sanger’s sequencing of protein and RNA, molecules were cleaved at specific sites with acids and enzymes and separated by chromatography. But for DNA, Sanger developed a new method whereby the molecules to be sequenced were replicated with an enzyme (polymerase) in the presence of nucleotides that could be identified on the ends of newly made molecules with radiolabeling, gel electrophoresis, and autoradiography. This echoed the natural processes of DNA replication in cells, and was soon incorporated into the toolkits of the molecular biologists Sydney Brenner, François Jacob, and others.
The second and third parts of the book focus on the mechanization of DNA sequencing. Throughout the late 1970s and 1980s, the author notes, “molecular biologists were increasingly inclined to determine the information contained in … DNA sequences by applying Sanger’s techniques, rather than by computing it from behavioural or developmental mutations” (67). Sequencing, in other words, wrought a transformation in the idea of genetic information, whereby the language of genes came to be understood in terms of linear information that could be directly determined, rather than as a message to be indirectly decoded from morphological or behavioral outputs. Yet computers were rarely used in Sanger’s DNA sequencing. This was not the case outside the LMB – the American Margaret Dayhoff’s phylogenetic work with protein sequences was a case in point – and by the early 1980s, the situation had changed around the LMB as well. With the EMBL and business and civil service professionals, LMB biologists helped build a database (still extant as EMBL Bank, alongside GenBank and the DNA Databank of Japan) for storing and analyzing known DNA sequences. Tenuous relationships between the database’s “information engineers”(91–92) and its affiliated biologists, however, led to the foundation of the Biocomputing Unit at EMBL in 1987 (113–114).
The third part shifts the center of gravity to the USA. Even as a competing method for DNA sequencing had been published by Walter Gilbert and Allan Maxam at Harvard in 1977, just two years after the earliest paper was published by Sanger and Alan Coulson, beginning in the 1980s a group led by Leroy Hood at the California Institute of Technology automated and improved upon Sanger’s technique. Autoradiographs previously generated from four gel lanes, read by eye or with the help of computer programs, were replaced with a linear pattern of fluorescent colors in only one gel lane read by computer. This concept, based on technical rather than biological elegance, formed the core of the DNA “sequenators” developed and sold by Applied Biosystems in the 1990s (Ch. 6). These powered both the HGP and Celera Genomics’ rival sequencing effort, even as they removed considerable control from human actors.
García-Sancho’s book has many strengths. The central procedural thrust is a productive application of sociologist John Pickstone’s famous “working knowledges,” in which sequencing is treated as a “form of work” absorbing practices and problems from divergent fields (13). The author assiduously documents his sources in two Appendices, which include short and valuable biographies of all individuals interviewed. Moreover, the book ties together the complex and disparate pieces of the history of sequencing into a single coherent narrative. Finally, García-Sancho offers a welcome critical reassessment of the HGP, which joins those of historians Bruno Strasser, Hallam Stevens, and Joseph November in situating the Project within broader histories, while questioning its status as the inevitable result of elucidating the double helix. In so doing, he also makes astute connections to science policy, wondering whether the oversold promises of the HGP may have resulted from the misconception that linear genetic information, directly read, would also be directly useful.
Yet the book has its pitfalls. First, many pieces of this story have been told elsewhere, even as the author does offer a much-appreciated longue-durée synthesis. Second, the author’s self-conscious references to his own methodologies, such as in his comparisons of historical reconstructions by interviewees, are sometimes distracting in the main text of the book. Lastly, the book’s analysis sometimes relies too heavily on the concept of disciplines, given that in all but as actors’ categories, the author purports to transcend them. All of this being said, however, this solid monograph will be consulted by specialists for years to come.