Biology, Computing, and the History of Molecular Sequencing: From Proteins to DNA, 1945-2000 (Anglais) Relié – 11 mai 2012
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For historians of the life sciences in the 20th century, Biology, Computing and the History of Molecular Sequencing represents a big leap in bringing together histories from molecular biology, computer science, mathematics and even evolutionary biology. Supported by an impressive archival and oral research, and by a thorough revision of the secondary literature of the field, García-Sancho's book is a celebration of what the history of recent and contemporary science can achieve, and for years to come it will remain as an obliged reference not only for historians of science, but for sociologists and all those interested in the detailed development of the industrialized-information society.
The book's virtues are many. As mentioned before, bridging the gap between the history of biology and the history of computing (but also, the history of technology and the history of science) is perhaps the most notable one for the general reader. No less important is Garcia-Sancho's narrative, written in a fluid, clear and reader-friendly style, and supported by appropriate historical photographs and excellent explanatory figures elaborated by the author. The general structure of the book certainly contributes to the narrative’s clarity, each of the three parts being devoted to each of the major developments in the long history of sequencing: part one, on the emergence of protein (chapter 1) and nucleic acid (chapter 2) sequencing in the work of Frederick Sanger between 1943 and 1977; part two, on the automation of assemblage of data and the creation of the first sequencing software (chapter 3) and databases (chapter 4) between the 1960s and 1980s; and finally, part three devoted to the development (chapter 5) and commercialization (chapter 6) of the first automatic sequencers between 1980 and 1998. As can be inferred by this description alone, the book covers the main events in the trajectory that has resulted in the current symbiosis between biological research, automation and computers.
However, for the historian of science, and in particular for the historian of recent biological sciences, an equally important contribution of García-Sancho's work stems from its sophisticated historiographical perspective. This is reflected in three major ways. First, García-Sancho's convincing and thorough argumentation of sequencing as “the result of the confluence of a variety of practices in a form of work”. Following the influential categories of John Pickstone of ways of “knowing” and “working” in the history of science, and his more recent proposal of “working knowledge”, as a way to “analyze the proliferation of analytical and rationalized working knowledges after the 1970s” (p. 12), García-Sancho embarks on a long-term convincing narrative of sequencing as a form of work. He refuses to interpret sequencing in the way molecular biologists and genomicists do: as a tool subordinated to their disciplinary practices. In doing so, his account is able “to link sequencing with a multiplicity of actors –molecular biologists or not- who, in finding responses to practical problems, crossed disciplinary boundaries “ (p. 12). His choice allows the author to narrate a coherent history of practices, tools, actors and disciplinary cross-overs around sequencing, that extend along half a century of research, from Frederick Sanger's protein sequencing techniques in the 1940s and 1950s, to the automated DNA sequencers of the late 1980s and 1990s. In a highly specialized field, like today’s history of science, this is a notable achievement, given the fact that the author provides a thick reconstruction and not a general account. As a historian of science, I must acknowledge that García-Sancho's narrative may be one of the most fruitful applications of Pickstone's categories to date.
Second, García-Sancho's historiography reflects his solid awareness of the dangers of writing history of recent and contemporary science, and in particular writing the history of genomics, a field empowered by the notable characters of its main actors (Craig Venter, James Watson, among others), and by the salient place it has cultivated within contemporary science and society at large. Having myself warned of the risks faced by historians in legitimating the genomicists' narrative of their own field, I cannot but appreciate the fact that García-Sancho has incorporated previous findings on the connection between evolutionary biology and the development of the first computer tools for sequence analysis. As García –Sancho convincingly argues, and I have argued before, some of the first analytical and comparative tools of today's bioinformatics originated in the field of evolutionary biology. This genealogy, however, is totally erased in the genomicists' accounts, who tend to see themselves as heirs of the molecular biology revolution. Among other undesirable consequences of these accounts it is important to mention how disciplinary hierarchies and science policy priorities have been shaped –and continue to be- by the attribution of every major development in 20th century life sciences to the iconic developments surrounding Watson and Crick's double helix model of DNA. By selectively eliminating actors in their personal narratives (in this case evolutionary oriented scientists), the genomicists not only deliver a monophonic history, but influence the present and future trajectories of science.
Third, García-Sancho's historiography is an important reminder of the benefits of using new and diverse resources in the writing of recent and contemporary science. He does so in particular in chapter 6, by recurring to the history of business and corporate culture of Caltech, and by appealing to a comparative account of the different cultures of scientific institutions to account for the divergent trajectories of sequencing automation and the further commercialization of sequencers. Again, the author's historiographical decisions have further implications, since he demonstrates that institutional cultures are more important that supposed national styles in explaining the development of commercialized automatic sequencers and the different approaches in the private and public attempts to sequence the entire human genome in the late 1990s.
Making use of those historiographical tools, Garcia-Sancho puts together a lot of previous scattered historical research, done by historians of biological sciences and of computing science in the last 15 years. The research culture at Cambridge’s Laboratory of Molecular Biology and the career of Frederick Sanger being, for instance, one of the best documented episodes in the field. Nevertheless, the book offers refreshing interpretations and new historical research, in particular in parts two and three. Among those that I profited the most are the historical account of the automation of sequence assemblage and the different paths of the introduction of computers to biological research at Cambridge (which opens a door to analyze the resistance of biologists to full automation), the detailed historical reconstruction of the first DNA database in 1980 at the European Molecular Biology Laboratory in Heidelberg (including a thorough discussion of the role of “information engineers” and the evolving disciplinary hierarchies between computer scientists and biologists), and the development and commercialization of automatic sequencers at Caltech (in which the corporate and marketing culture of science at Silicon Valley enters the history of science).
In brief, I cannot do other than praise the publication of Miguel García-Sancho’s book, as an important contribution that summarizes not only the empirical results of previous historians and his own research results, but the conceptual and theoretical advances of recent history of science as a mature field of research.
Anyone who either worked in a research laboratory during the 1970s, 1980s or 1990s, or followed
the vicissitudes of biology during that time, can look forward to a trip down memory lane when
they read this book. Make that four lanes, if you were involved with DNA sequencing in any way.
Do you remember pouring polyacrylamide gels between those tall sheets of glass held together
with clamps? (Mine, I have to admit sheepishly, leaked and wound up as often in the sink as
between those sheets). How about melting agarose in order to pour those smaller gels (much
easier) for RFLP analyses? Or wicking solutions through sheets of filter paper to produce
chromatograms with different-coloured spots? The furore over PCR and its eccentric inventor,
Kary Mullis? Miguel García-Sancho brings all these memories - which were in turns exciting,
exhilarating, embarrassing or often just downright exhausting - vividly back to life in his new
book recounting the history of molecular sequencing in the second half of the twentieth century.
Sequencing today is inextricably linked with, indeed entirely subsumed within, molecular
biology, a fact that, the author laments, has also caused its history to be conflated with that of
DNA and genomics. In the process, he says, the history of research into protein sequencing which
did not merely precede DNA research, but also continued to develop alongside it, has been
marginalized, if not completely ignored. Furthermore, the understanding and portrayal of
sequencing itself, he argues, has been reduced to that of a `technique devised to solve a particular
experimental problem' within the `pathway of a particular scientific discipline, molecular biology'
(p. 11). Among his explicit aims in this book, therefore, are to provide a bigger, more complete
history of sequencing, encompassing its many genealogies in different disciplines, and to treat
sequencing as a `particular form of work', a result of the confluence of multiple scientific practices
`unrestricted by disciplinary frameworks' (p. 12).
García-Sancho's goal in producing such a history is laudable and the meat of his book provides a
thorough survey of the various practices that played their part in both the invention of molecular
sequencing techniques and their applications. I am a little sceptical, however, about the framing
device for his account of this history. For one, I am not sure that his charge of a narrowness of vision,
especially on the part of various historians of science, is entirely accurate. His own
account is, in fact, rich in references to eminent historians - Soraya de Chadarevian, John
Pickstone, Bruno Strasser and Edna Suárez-Díaz, to name but a few of the most prominent - whose
work has pushed and expanded boundaries of the type that he criticizes. While the book has done
well to draw attention to this scholarship, the references to the approaches and methods these
authors have described are entirely appropriate as they stand and do not need the additional
justification. García-Sancho is slightly more persuasive in his criticisms of the understanding of the
scientists who participated in the molecular revolution in biology. It may well be true that the
perceived success of the Human Genome Project and its promise for the future of biomedicine
instigated scientists to recollect their research experiences in a way that implies a conflation of the
history of sequencing with DNA. But it seems to me that he is overlooking the possibility that such
narratives were constructed more in keeping with the specific rhetorical aims of these researchers
and less because they did not understand importance of proteins in sequencing or, more broadly, in
So intent seems García-Sancho on freeing the history of sequencing from its confines within
molecular biology that he overlooks his own insights about academic disciplines being `strategic
constructions of researchers' (p. 62), instead of strict areas of study with sharply delineated
boundaries. This fuzziness in disciplinary boundaries is especially true of molecular biology, which
can be considered more appropriately as a discipline born of techniques and approaches than as
one stemming from a particular subject of inquiry, and which is utilized by many of the older
subdisciplines of biology, including biochemistry and genetics. García-Sancho might have done
better to treat molecular biology also as yet another `form of work' in biology, whose practices
were among those whose confluence influenced the development of sequencing, and whose own
progress was significantly influenced by advances in protein research in addition to nucleic acid
None of the criticisms above, however, detract from the wealth of information that García-
Sancho has to impart in the body of his narrative, and these facts and stories give this book its
greatest value. Biology and chemistry form only part of the story, as he makes clear here in
devoting nearly two-thirds of the book to the other major player in this history, the computer in its
multiple roles. In today's world of high-speed Internet, hand-held devices and terabyte memory
chips, most of us take our computers and their capabilities for granted. While we would certainly
acknowledge their vital role in the development of the biological sciences, I would venture to say
that few, if any, of the historians of science who use them have anything more than a superficial
understanding of how these technologies have shaped scientific practices and understanding. The
author has done a masterful job of integrating information about the way in which different
aspects of computer science - from something as mundane as word processing to the processing of
millions, if not billions, of base-pairs' worth of DNA sequence data - have contributed to the
development of sequencing as it is practised today. And for that reason alone Biology, Computing,
and the History of Molecular Sequencing is an invaluable, possibly even essential, addition to the
bookshelf of anyone wishing to understand modern biology in all its facets.
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