Humanising and dehumanising pigs in genomic and transplantation research.

Biologists who work on the pig (Sus scrofa) take advantage of its similarity to humans by constructing the inferential and material means to traffic data, information and knowledge across the species barrier. Their research has been funded due to its perceived value for agriculture and medicine. Improving selective breeding practices, for instance, has been a driver of genomics research. The pig is also an animal model for biomedical research and practice, and is proposed as a source of organs for cross-species transplantation: xenotransplantation. Genomics research has informed transplantation biology, which has itself motivated developments in genomics. Both have generated models of correspondences between the genomes of pigs and humans. Concerning genomics, I detail how researchers traverse species boundaries to develop representations of the pig genome, alongside ensuring that such representations are sufficiently porcine. In transplantation biology, the representations of the genomes of humans and pigs are used to detect and investigate immunologically-pertinent differences between the two species. These key differences can then be removed, to 'humanise' donor pigs so that they can become a safe and effective source of organs. In both of these endeavours, there is a tension between practices that 'humanise' the pig (or representations thereof) through using resources from human genomics, and the need to 'dehumanise' the pig to maintain distinctions for legal, ethical and scientific reasons. This paper assesses the ways in which this tension has been managed, observing the differences between its realisations across comparative pig genomics and transplantation biology, and considering the consequences of this.

Adjusting to precarity: how and why the Roslin Institute forged a leading role for itself in international networks of pig genomics research.

From the 1980s onwards, the Roslin Institute and its predecessor organizations faced budget cuts, organizational upheaval and considerable insecurity. Over the next few decades, it was transformed by the introduction of molecular biology and transgenic research, but remained a hub of animal geneticists conducting research aimed at the livestock-breeding industry. This paper explores how these animal geneticists embraced genomics in response to the many-faceted precarity that the Roslin Institute faced, establishing it as a global centre for pig genomics research through forging and leading the Pig Gene Mapping Project (PiGMaP); developing and hosting resources, such as a database for genetic linkage data; and producing associated statistical and software tools to analyse the data. The Roslin Institute leveraged these resources to play a key role in further international collaborations as a hedge against precarity. This adoption of genomics was strategically useful, as it took advantage of policy shifts at the national and European levels towards funding research with biotechnological potential. As genomics constitutes a set of infrastructures and resources with manifold uses, the development of capabilities in this domain also helped Roslin to diversify as a response to precarity.

Genetics without genes? The centrality of genetic markers in livestock genetics and genomics.

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a (usually material) element existing in different forms in the genome, that can be identified and mapped using a variety (and often combination) of quantitative, classical and molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align (but never fully integrate) in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden.

Sequencing through thick and thin: Historiographical and philosophical implications.

DNA sequencing has been characterised by scholars and life scientists as an example of 'big', 'fast' and 'automated' science in biology. This paper argues, however, that these characterisations are a product of a particular interpretation of what sequencing is, what I call 'thin sequencing'. The 'thin sequencing' perspective focuses on the determination of the order of bases in a particular stretch of DNA. Based upon my research on the pig genome mapping and sequencing projects, I provide an alternative 'thick sequencing' perspective, which also includes a number of practices that enable the sequence to travel across and be used in wider communities. If we take sequencing in the thin manner to be an event demarcated by the determination of sequences in automated sequencing machines and computers, this has consequences for the historical analysis of sequencing projects, as it focuses attention on those parts of the work of sequencing that are more centralised, fast (and accelerating) and automated. I argue instead that sequencing can be interpreted as a more open-ended process including activities such as the generation of a minimum tile path or annotation, and detail the historiographical and philosophical consequences of this move.

Normal development and experimental embryology: Edmund Beecher Wilson and Amphioxus.

This paper concerns the concept of normal development, and how it is enacted in experimental procedures. To that end, I use an historical case study to assess the three ways in which normal development is and has been produced, used, and interpreted in the practice of experimental biology. I argue that each of these approaches involves different processes of abstraction, which manage biological variation differently. I then document the way in which Edmund Beecher Wilson, a key contributor to late-nineteenth century experimental embryology, approached the study of normal development and show that his work does not fit any of the three established categories in the taxonomy. On the basis of this new case study, I present a new interpretation of normal development as a methodological norm which operates as a technical condition in various experimental systems. I close by suggesting the questions, and ways of investigating developmental biology, that are opened up by this perspective.

Managing variation in the investigation of organismal development: problems and opportunities.

This paper aims to clarify the consequences of new scientific and philosophical approaches for the practical-theoretical framework of modern developmental biology. I highlight normal development, and the instructive-permissive distinction, as key parts of this framework which shape how variation is conceptualised and managed. Furthermore, I establish the different dimensions of biological variation: the units, temporality and mode of variation. Using the analytical frame established by this, I interpret a selection of examples as challenges to the instructive-permissive distinction. These examples include the phenomena of developmental plasticity and transdifferentiation, the role of the microbiome in development, and new methodological approaches to standardisation and the assessment of causes. Furthermore, I argue that investigations into organismal development should investigate the effects of a wider range of kinds of variation including variation in the units, modes and temporalities of development. I close by examining various possible opportunities for producing and using normal development free of the assumptions of the instructive-permissive distinction. These opportunities are afforded by recent developments, which include new ways of producing standards incorporating more natural variation and being based on function rather than structure, and the ability to produce, store, and process large quantities of data.