Abstract
Following the completion of the Human Genome Project (HGP), a critical challenge has been how to make biological sense of the amassed sequence data and translate this into clinical applications. A range of large biological research projects, as well as more distributed experimental collaborations, are seeking to realise this through translational research initiatives and postgenomic approaches. Drawing on interviews with key participants, this article explores the biological assumptions, sociological challenges and spatial imaginaries at play in arguments around one of these developments, which is using genetically altered mice to understand gene function. The knockout mouse project (KOMP) is a large-scale initiative in functional genomics, seeking to produce a ‘knockout mouse’ for each gene in the mouse’s genome, which can then be used to answer questions about gene function in mammals. KOMP is frequently framed as one successor to the HGP, emblematic of the ambitions of internationally coordinated biological research. However, the development of new technologies for generating and managing genetically altered mice, alongside the challenge of asking biologically meaningful questions of vast numbers of animals, is creating new frictions in this extension and intensification of biological research practices. This article introduces two separate approaches to the future of international research using mutant mice as stakeholders to negotiate the biological, sociological and spatial challenges of collaboration. The first centres on the directed research practices and sociological assumptions of KOMP, as individual researchers are reorganised around shared animals, databases and infrastructures. The second highlights an alternative vision of the future of biomedical research, using distributed management to enhance the sensitivities and efficiencies of existing experimental practices over space. These exemplify two different tactics in the organisation of an ‘arguably’ big biology. They also critically embody different sociological and spatial imaginaries for the collaborative practices of international translational research.
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Notes
‘Knockout mice’ are mice that have had their genome manipulated to eliminate a single gene. This allows researcher to explore the effect this gene has on animal development and phenotype to help decipher gene function. Knockout mice are only one of the many genetically altered animals now being produced. They differ from transgenic mice, which have had DNA from another species introduced into their genome. Most knockout animals are produced through first generating targeted knockout mutations in mouse embryonic stem (ES) cells. Embryos are extracted from mice 4 days after fertilisation and an inserted sequence of artificial DNA is used to switch off the specified gene. ES cells are used because the gene will then be knocked out of all the adult tissues. The altered ES cells are injected back into a mouse embryo, which is then implanted in an adult mouse uterus and allowed to develop. The National Human Genome Research Institute has a fact sheet on Knockout mice (http://www.genome.gov/12514551, accessed 27 November 2012).
For further information, see http://www.knockoutmouse.org/, accessed 30 May 2013.
This article is based on research carried out for the ESRC fellowship ‘Biogeography and Transgenic Life’. This traced the different ways mice are ‘on the move’ in contemporary biomedical research: internationally, in the establishment of large-scale mutant mouse resource centres; corporeally, in the development of further mouse models of human disease; and affectively, in the changing ways these animals are figured in different scientific, regulatory and ethical cultures. This article is based on ethnographic research, literature review and in-depth interviews with key scientists involved in and critiquing the development of KOMP, carried out in the United Kingdom, the United States and Singapore from 2008 to 2009. It is further informed by over 80 interviews with research scientists, animal welfare scientists, regulators, patient groups and others involved in the changing use of mouse models, as well as participation in research meetings and conferences. All research participants were offered anonymity.
There is an overlapping area of debate on establishing protocols for mouse sharing (Einhorn & Heimes, 2009). This is an important component to the realisation of KOMP, but full consideration of changing property regimes for research animals exceeds the scope of this short paper.
Much of this ubiquity comes from the simple fact they were the animal favoured by Elisabeth Russell in the 1930s, who backcrossed many early genetic experiments onto this background strain (Scientist 7, USA 2009). For further information on the history of making laboratory mice in the United States, see Rader (2004).
For updates, see http://www.knockoutmouse.org/about/geneprogresssummary, last accessed 30 May 2013.
The European Commission has provided Sixth Framework Programme funds to integrate data emerging from the variety of mouse projects in CASIMIR (Coordination and Sustainability of International Mouse Informatics Resources). Although KOMP is a trans-NIH initiative, the larger amount of funding for the integration of gene and phenotype data for mutant mice has come through Europe.
Developments in personalised medicine are changing the way model organisms are being used in experimental and translational research. Whereas conventional biological research using model organisms relies on statistical models to make judgements about the safety and efficacy of new therapeutic interventions at the level of populations, personalised medicine seeks to examine the wide range of data relevant to the genetic profile of individuals being treated. See for example Davies (2012a).
Association for Assessment and Accreditation of Laboratory Animal Care International, http://www.aaalac.org/, last accessed 30 May 2013.
There are emerging discussions about how RFID technologies might be used to train animal caretakers to work with animals in standardised ways, by training bodily movements, rather than disseminating written instruction. Attach sensors and transmitters to the room, cage-racks and sleeves of staff, set the standard operating procedures for a given task, for example handling micro-isolator cages, and each person can then be evaluated, for efficiency and precision, against the programmed sequence of movements. This development is still nascent but has the potential to transform discussions about the value of tacit knowledge in relation to both the geographies of scientific knowledge and embodied practices of animal care.
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Acknowledgements
My thanks to the ESRC and research respondents for making this research possible, to Emma Frow and Sabina Leonelli for comparative and generative conversations about the emerging contours of ‘big’ biological research, to all the participants of the ESRC Genomic Forum workshop ‘Making it Big? Tracing Collaboration in the Life Sciences’ (University of Exeter, March 2011) which formed the basis of this special issue, and to Sarah Franklin and Carrie Friese for additional input. I am grateful for the perceptive and generous comments from the three reviewers.
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Davies, G. Arguably big biology: Sociology, spatiality and the knockout mouse project. BioSocieties 8, 417–431 (2013). https://doi.org/10.1057/biosoc.2013.25
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DOI: https://doi.org/10.1057/biosoc.2013.25