Working with Laboratory Automation in Synthetic Biology

This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Amphibious Researchers: working with laboratory automation in synthetic biology Chris Mellingwood PhD University of Edinburgh October 2018 ii I declare that this thesis has been composed solely by myself and that it has not been submitted, in whole or in part, in any previous application for a degree. Except where stated otherwise by reference or acknowledgment, the work presented is entirely my own. Signature: 5 June 2019 iii Acknowledgements I have been fortunate to have incredibly insightful and patient academic mentors willing to share their knowledge and experiences. I am very grateful to my supervisors Jane Calvert, Pablo Schyfter, and Alistair Elfick for their time, generosity, and thoughtful advice. Special thanks also go to Dominic Berry, Emma Frow, Julie and David Morroll for their invaluable support and guidance. I am also grateful to Naomi Chambers, Jane Gregory, and James Sumner for giving me the opportunity and confidence to start and to Alistair Brown, Miguel Garcia-Sancho, Robert Meckin, Lasse Meiner Nykjær, and Niki Vermeulen for their encouragement throughout. I am especially indebted to Sue Llewellyn for her kindness and mentorship over many years. Valuable feedback was also provided by Karen Kastenhofer, Susan Molyneux- Hodgson, Deborah Scott, Robert Smith and all the participants of the Society for the study of New and Emerging Technologies (S.NET) conference at the University of Bergen in October 2016, and the Community and identity in contemporary technosciences workshop at the University of Vienna in February 2017. A huge thank you to Katie and Al Mellingwood (who is two weeks younger than this thesis but far more advanced), Jack Melling, Joan Melling, Lynsey Moys, Michael Moys, Andrew Nardone, Keith Robertson, Lyndsey Watson, Tom Watson, Jim Wood and Sheila Wood for their practical and moral support. I am also grateful to the Engineering and Physical Sciences Research Council for funding this PhD research. Finally, I would like to express my thanks to the engineers, scientists and academic researchers and technicians I observed and interviewed for generously giving their time and contributing to this project. iv To Katie and Alexander Jack Mellingwood “such riches …” v Abstract This thesis analyses the use of robots and automation in academic biosciences laboratories in the UK. Both system vendors and policymakers argue that robots, specifically liquid-handlers and robotic arms, offer more efficient, precise and reliable methods for experimental work. These arguments for the potential of automation systems for the biosciences form a cadre of promissory narratives about the future value of such technologies. One reason vendors promote the use of robots is to remove error-prone humans, with their need for sustenance and sleep, offering instead the mechanical reliability of a robot system unencumbered by such bodily limitations. Somewhat paradoxically, I argue that to negotiate the hybrid disciplinary space of laboratory automation and the biosciences, researchers need significant embodied skills. Furthermore, they must forge relationships among multiple knowledge communities, and engage in boundary-work to manage ambivalences and deal with competing demands. Laboratory-based automation system users learn how to be skilled in embodied ‘fingertip-feeling,’ and how to be adept at relationship management and boundary-work. To do this, they need to understand both ‘wet’ cell behaviour and ‘dry’ robot behaviour; they must become amphibious researchers. My study identifies five promissory narratives found in policy documents and system vendor descriptions of laboratory automation and the biosciences, particularly in automation-driven synthetic biology. These promissory narratives describe potential future benefits of increasing automation in biosciences laboratories. The five narratives are that automation will: result in more time for researchers because robots are more efficient and more precise; increase parameters and the ability to tackle problems with very large numbers of variables; enhance the reproducibility of experimental results; provide increased technological capacity for laboratories, making them more competitive in international funding arenas; and result in further opportunities for commercialisation of products and services. Through an analysis of documents, interviews and laboratory practices, I show that these promissory narratives for automation and the biosciences are reconfigured by the lived experiences of laboratory users. I establish that researchers’ lived experiences can both challenge and support promissory narratives in this area, and argue that developing understanding of users’ practices is essential to an assessment of the future value of automation-driven synthetic biology. My thesis further demonstrates that the ways that researchers make automation systems work in the biosciences involve an attentive engagement between users’ bodies, their competences, and their belonging and identity as part of particular groups. Researchers using laboratory automation technologies engage their bodies and manage their relationships to generate trust and confidence in robot functioning. These researchers have to mobilise the ‘wet’ and the ‘dry’ simultaneously to maintain a proper functioning system. In short, they must be amphibious researchers. vi Lay summary When scientists conduct experiments in laboratories, they use a range of tools. Research scientists learn how to use their tools and how to work in laboratories in a variety of ways, including through formal training and education programmes and through informal learning. One of the differences between formal and informal learning is that formal learning involves written instructions and informal learning involves learning by doing. In biological science laboratories, researchers use pipettes to mix different liquids and, often, experienced researchers develop their skill in pipetting through practice, and they develop that skill by learning from other researchers and by pipetting themselves. A group of researchers in the field of synthetic biology, and others, have argued that one of the problems of pipetting manually is that human scientists make mistakes and humans cannot pipette accurately and quickly over long periods. One of the solutions that some technology vendors are proposing to this problem is to use more automation in laboratories. Vendors of liquid- handling robots argue that more bioscience laboratories should use automation. Both vendors and policymakers further argue that increasing the use of automation in this field will result in more scientists being able to reproduce results in different laboratories, and to share and collaborate on projects more easily. My research has analysed these vendor and policymaker arguments and compared them to how current researchers are using automation and robots in their daily work. My findings suggest that current users of automation systems in this area have experiences that help further understanding of what it takes to build a successful automated system in a bioscience laboratory. The time I spent observing and talking to current system-users helped challenge some of the vendor and policymaker arguments and promises about automation technologies. My research demonstrated that there are many different technological solutions currently available for bioscience researchers; however, one of the most important considerations for system builders is not technological in nature. System builders and operators in my study needed to understand computer and biological sciences, and at least some of those researchers needed to feel comfortable working with groups in different academic disciplines. I have called researchers that can work comfortably across academic areas ‘amphibious researchers.’ These researchers are amphibious because they can understand and integrate ‘dry’ computer science laboratory techniques with ‘wet’ biological sciences laboratory techniques. Perhaps most crucially, these researchers are also able to ensure the results they produce using integrated laboratories are acceptable in their respective academic communities. My study therefore recognises that there are different opinions about the usefulness of automation in the laboratory, and that current laboratory users are well placed to judge that usefulness for their particular needs. vii Summary of contents Acknowledgements ..................................................................................................... iii Abstract ........................................................................................................................ v Lay summary

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