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Molecular Embodiments the Body-Work of Modeling In MOLECULAR EMBODIMENTS ABSTRACT & Proteins, those objects of increasing interest and investment in post- genomics research, are complex, three-dimensional structures made THE BODY-WORK OF MODELING up of thousands of atoms. Protein crystallographers build atomic- IN PROTEIN CRYSTALLOGRAPHY resolution models of protein molecules using the techniques of X-ray diffraction. This ethnographic study of protein crystallography shows 1 BY NATASHA MYERS that becoming an expert crystallographer, and so making sense of such intricate objects, requires researchers to draw on their bodies as a resource to learn about, work with and communicate precise forthcoming in molecular conformations. Contemporary crystallographic modeling Social Studies of Science relies intensively on interactive computer graphics technology, and requires active and prolonged handling and manipulation of the model onscreen throughout the often-arduous process of model- building. This paper builds on both ethnographic observations of This paper has not yet been published. contemporary protein crystallographers and historical accounts of Please do not cite without permission from the author. early molecular modeling techniques to examine the body-work of crystallographic modeling, in particular the corporeal practices through which modelers learn the intricate structures of protein molecules. Ethnographic observations suggest that in the process of building and manipulating protein models, crystallographers also sculpt embodied models alongside the digital renderings they craft onscreen. Crystallographic modeling at the computer interface is thus 1 Program in History, Anthropology, and Science, Technology, and Society Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room not only a means of producing representations of proteins; it is also E51-070, Cambridge, MA 02139 Email: [email protected] means of training novice crystallographers’ bodies and imaginations. Protein crystallographers’ molecular embodiments thus offer a site The research and writing of this paper was generously supported by for posing a new range of questions for studies of the visual cultures fellowships from the Social Sciences and Humanities Research Council of and knowledge practices in the computer-mediated life sciences. Canada (Award No. 752-2002-0301) and the National Science Foundation (Grant No. 0220347). This paper has benefited immensely from many generous readers including Joseph Dumit, Stefan Helmreich, and Donna KEY WORDS Haraway. Susan Silbey also offered careful readings of the paper, as did the Scientific visualization and models, embodied practice, tacit participants in the STS Writing Workshop at MIT. I am exceptionally knowledge, expertise and training, protein crystallography, grateful to three anonymous reviewers for their generous readings and critical insights. Finally, thank you to the many protein scientists who interactive computer graphics, scientific imagination and participated in this study. This paper was awarded the Nicolas C. Mullins communication. Award by the Society for the Social Studies of Science for outstanding graduate scholarship in science and technology studies. INTRODUCTION of structure determination, making visible the forms and movements A new biological actor is taking center stage in post-genomic of a vast menagerie of proteins, the objects of molecular biology are research: the protein molecule. As journals such as Science and becoming tangible and workable in new ways. With this shift from Nature publish new protein structures almost weekly, life scientists reading and writing one-dimensional genetic codes to modeling and can be seen turning from matters of code to matters of interpreting the functions of three-dimensional and temporally substance—that is, from spelling out linear gene sequences to dynamic protein molecules come new practical and conceptual inquiring after the three-dimensional materiality, structure, and hurdles for researchers and their students. These challenges also function of the protein molecules that give body to cells. In open up a new range of questions for social studies of scientific employing new digital media, augmented computer power, and practice. innovative techniques to build atomic-resolution models of proteins, protein crystallographers and other structural biologists are Protein crystallographers use interactive computer graphics transforming the very forms of data that populate life science technologies to build three-dimensional, atomic-resolution models of laboratories and databases.2 As these life scientists ramp up the pace the intricate molecular structure of proteins, which are molecules 3 made up of thousands of atoms. I ask Diane, a professor of 2 The Protein Data Bank is an online database that stores the atomic chemistry who heads a protein crystallography lab at a large east coordinates of know protein structures, and is publicly accessible at http://www.rscb.org. When the Protein Data Bank (PDB) was first founded in 1971, fewer than a dozen protein structures had been determined and particular, structural biology has offered engineers a long-awaited entry into deposited. By 2000, 13,635 structures were available for viewers to biology, giving them quantifiable, physical objects that they can model and download onto their computers and view through interactive visualization manipulate as ‘molecular machines’ (see Myers, under review). software. As of July 2006, there were 37,658 searchable structures in the database. The PDB thus offers a growing ‘atlas of observables’ (Daston and 3 For readers unfamiliar with proteins, the following description may be Galison, 1992) for life science researchers to compare and contrast protein helpful: Proteins are ‘macromolecules,’ large, very complex organic configurations within and between species. This is an important research molecules made up of thousands of atoms. Reduced to their constituent tool in the field of what is called ‘structural genomics’ or ‘proteomics,’ parts, they are made up of smaller subunits called amino acids, linked end to which aims to determine and catalogue the structures of all proteins end to form long polypeptide chains. A protein may be made of a single produced by a given cell or organism. This work is being supported by polypeptide, or several folded in together. Amino acids themselves are corporations and government agencies, which have made huge investments small molecules made up of varying amounts of carbon, nitrogen, oxygen into the determination of protein structures from crystallographic and and hydrogen and some contain other elements such as sulfur. There are 20 nuclear magnetic resonance (NMR) techniques, as well as predictive different kinds of amino acids. While they all share a common carbon molecular modeling by computers (see Abott, 2000; Jones, 2003; Smaglik, backbone structure, each bears a different chemical side chain that confers 2000; Wadman, 1999). As a large-scale, high-throughput study of protein different chemical properties. Each species of protein has a unique sequence structures modeled on the industrial technologies and logics that organize of these twenty amino acids, and polypeptide chains can vary greatly in genomics research, proteomics and protein structure prediction is making length. For a protein to acquire biological function it must be folded major contributions to biomedical research and pharmaceutical companies correctly within the cell. Proteins fold into secondary structures, such as are using protein structures to facilitate the engineering and synthesis of alpha-helices, and these secondary structures pack together to form the drugs through rational drug design. Gathering together physicists, chemists, tertiary structures of the active form of the protein. The active forms of and computer scientists, this research fulfills long-standing desires to some proteins are made up of 2 or more polypeptides, and when these pack model, manipulate and re-make biological systems at the molecular level. In together, proteins acquire their quarternary structure. 2 coast research university, about the challenges her students face fold. With a sigh of relief she eases back into a comfortable position learning to model proteins in three-dimensions (See Figure 1).4 She in her chair. The comically anguished look on her face relaxes back tells me that it is hard to learn how to ‘think intelligently about into a warm smile. structure.’ She points to the steep learning curve her students face trying to master X-ray crystallographic techniques, and enumerates Apparently, the students in her story had not yet acquired a feeling the challenges of building molecular models and interpreting the for the proper molecular conformation. In a mode evocative of what functions of proteins from molecular forms. Acquiring the skills to Evelyn Fox Keller (1983) has described as Barbara McClintock’s ‘see what the structure is saying’ is ‘hard to do, and it takes time,’ ‘feeling for the organism,’ Diane expresses her feeling for the she tells me, but eventually ‘you do get better at it.’ She describes molecule. As her gestures and affects convey, corporeal knowledge what often happens when her graduate students show her computer appears to play a key role in her ability to ‘think intelligently’ about graphic renditions of their molecules in the early stages of the protein structure. What she demonstrates here is that structural building process. ‘Look I connected it!’ they proudly declare, biology it is
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