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Coversheet for Thesis in Sussex Research Online A University of Sussex DPhil thesis Available online via Sussex Research Online: http://eprints.sussex.ac.uk/ This thesis is protected by copyright which belongs to the author. 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 Please visit Sussex Research Online for more information and further details Knowledge Accumulation and Vaccine Innovation: Lessons from Polio and HIV/AIDS Ohid Yaqub Doctor of Philosophy University of Sussex Submitted in September 2008 ii I hereby declare that this thesis has not been submitted, either in the same or different form, to this or any other university for a degree. Ohid Yaqub iii To my parents and Corinne, Two worlds that should not be separate. iv ACKNOWLEDGEMENTS This thesis was funded by the Economic and Social Research Council and supervised by Paul Nightingale. Paul is a supervisor who is extremely generous with his time, ideas and encouragement; and who manages to make academia look extremely fun. His energy and enthusiasm were most important to me when I really thought the ship was sinking. I cannot thank him enough and feel privileged to have worked with him. My first opportunity to pursue some of the ideas in this thesis was under the supervision of Ed Steinmueller and Aldo Geuna. I thank them for their help in that year, in which they worked with me to find a research topic I was happy with. I am indebted to Erik Millstone for being the first to patiently show me the importance of science and technology policy when I was a smug science undergraduate. His commitment to teaching still astounds me today. I am also appreciative of all the advice shared with me by Virginia Acha, Daniele Archibugi, Stuart Blume, Jo Chataway, Keith Pavitt, Ammon Salter and Andy Stirling. I thank Janet French and Carmen Long for helping me to address my administrative incompetence through ever more ingenious methods. I owe a large debt to Maureen Winder and staff at the Pavitt library for always offering me a helping hand. It is the staff - not the books - which make the Pavitt library so invaluable. I have made many new friends, who have not only helped me develop my ideas but have also helped me to take refuge from them. I thank Abdullah, ‘Betta, Dagmara, Dajana, Elyse, Florian, Georgina, Kai, Katie, Maria, Molly, Oliver, Osvaldo, Rob, Roberto, Rocio, Ruud, Vanessa, Yari, Yun, and Zeeda – fellow students who have made up such a large part of ‘Team Spru’. I reserve special thanks for Josh, whose organisation of weekly socials has been so central to the friendly atmosphere, and Basak, whose afternoon breaks have kept me sane, grounded and motivated. Mauricio, who sits opposite me, has had to endure the peculiarities of my working habits, as well as my ‘quick’ vaccine questions. I thank him for his illuminating answers. I have also been fortunate to grow up amongst a clever group of friends. I found an unexpected bounty of comments from Corinne, Boodie, Sandeep and Clyde. They were subjected to my most tenuous and incomplete ideas; I am grateful to them for receiving them sympathetically and constructively. I am sorry that my acknowledgement to Corinne must be limited to this. I am grateful to the many who have offered to read large portions of drafts. They provided both editorial and substantive suggestions, particularly in identifying the more soporific parts of the manuscript. They tried to set me straight but any remaining errors are down to my own shortcomings and stubbornness. My final thanks are for my family who have encouraged me to study and pursue the things I care most about. In particular, Shahin’s support during the thesis-writing really showed that he has been there before. I really have no way of acknowledging just how much they have helped because it extends far beyond my understanding. I recognise that together they have provided me with inspiration, hope and ambition for a healthier, more equitable world. v UNIVERSITY OF SUSSEX OHID YAQUB SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Knowledge Accumulation and Vaccine Innovation: Lessons from Polio and HIV/AIDS ABSTRACT This thesis contrasts vaccine innovation efforts in the cases of poliomyelitis and HIV/AIDS. It addresses the question of why some fields of human endeavour can be seen to yield positive change more quickly than others. The thesis develops a perspective that views innovation as a cumulative learning process. It employs the notion of a ‘testing regime’ to draw attention to the role of testing in driving this carefully managed learning process during the development of vaccines. Repeated testing, under conditions that are varied using instruments and skill, generates knowledge that is reliable and robust for technological purposes. Governance is needed to co-ordinate this process of testing to ensure the resulting knowledge growth is shared and cumulative. This lens is used to explore the creation of intermediate conditions, the development of instrumentalities, and the role of governance in vaccine innovation processes. The thesis uses the notion of ‘social visions’ to explore how attention directed to poliomyelitis contrasted with neglect and apathy afforded to AIDS in its early manifestations. Shared, rather than competing, visions are found to play a significant role in setting the vaccine innovation process in motion. However, the thesis finds that key pathogenic features of the virus and certain ethical and safety stances make learning and the accumulation of technological knowledge inherently difficult. Importantly, the thesis finds policy measures can mitigate or exacerbate these learning challenges considerably. Whilst greater market support and increased research funding tend to be positive contributions to vaccine development, this research shows they are only part of what is needed to take ideas through to innovation. The empirical evidence gathered in this thesis, when viewed through the testing regime lens, suggests that science and innovation are distinct activities but their inter-relationships can be enhanced with the development of an infrastructure focussed on nurturing skills, fostering the use of new techniques, encouraging the development of new instruments, and implementing governance measures to co-ordinate testing efforts and resources. vi LIST OF CHAPTERS 1 Introduction 2 Evolutionary Theories of Technical Change: A review 3 Testing Regimes: A lens to explore vaccine innovation 4 Appreciative Synthesis: Methods and methodology 5 Conetxtual Analysis of Vaccines: Economic and technical dynamics 6 Knowledge Accumulation in the Road to Poliomyelitis Vaccines 7 Dead-ends and Detours in the Road to HIV Vaccines 8 Which HIV Vaccine? Competing directions of technical change 9 Testing Times for an AIDS Vaccine: Testing regimes in clinical development 10 Conclusions vii TABLE OF CONTENTS Chapter 1 ................................................................................................................................ 1 Introduction............................................................................................................................ 1 1.1 The need for vaccines................................................................................................... 3 1.2 Funding for vaccine innovation ................................................................................... 5 1.3 Uncertainties of the early innovation process .............................................................. 7 1.4 Focus of thesis: Technological knowledge accumulation.......................................... 10 1.5 Broader implications of the testing regime for science policy................................... 11 1.6 Outline of the thesis ................................................................................................... 14 Chapter 2 .............................................................................................................................. 17 Evolutionary Theories of Technical Change: A review....................................................... 17 2.1 ‘Science-push’ or ‘Demand-pull’?............................................................................. 17 2.2 Evolutionary theories: Moving beyond push-pull debates......................................... 20 2.3 Constraints and structure in the growth of technical knowledge ............................... 21 2.4 Knowledge flows between science and technology................................................... 23 2.4.1 Learning from outside the firm ........................................................................... 24 2.4.2 Learning inside the firm...................................................................................... 25 2.4.3 Learning through instrumentation....................................................................... 27 2.5 From bounded to blinded-rationality: fertile ground for new theory......................... 30 Chapter 3 .............................................................................................................................. 34 Testing Regimes: A lens to explore vaccine innovation...................................................... 34 3.1 Operational principles in technology ........................................................................
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