AN ABSTRACT OF THE DISSERTATION OF Barbara C. Canavan for the degree of Doctor of Philosophy in History of Science, presented on December 4, 2015 Title: Opening Pandora’s Box at the Roof of the World: The Past and Present of Avian Influenza Science Abstract approved: ______________________________________________________ Anita Guerrini By means of a case study and historical analysis, this dissertation examines the past and present of avian influenza. By integrating disconnected histories of human and animal influenza, this dissertation links historical insights with the concerns of contemporary avian flu science. It is not only a natural history of avian influenza but also a snapshot of avian flu science in progress. To understand human influenza, its path and potential, one must be aware of how avian influenza viruses came to play such a central role in human influenza ecology. Building on a history of influenza in both its human and avian forms, a contemporary case study examines the unprecedented emergence of an avian virus among wild birds on the Qinghai-Tibet Plateau (Roof of the World) beginning in 2005. Events at Qinghai stimulated an interdisciplinary and international approach among researchers, and accelerated the use of technological tools to track avian influenza. Evidence suggests that the escalation of global bird flu events is not merely a matter of chance mutations in flu viruses but is the result of antecedent conditions related to human activities. Events and science at Qinghai serve as real-world examples to understand avian influenza and to envision the unintended consequences of human and natural forces over the coming decades. This synthesis of avian influenza history and science can serve as a resource for historians of medicine, environmental historians, biologists, virologists, ecologists, and the broader public. ©Copyright by Barbara C. Canavan December 4, 2015 All Rights Reserved Opening Pandora’s Box at the Roof of the World: The Past and Present of Avian Influenza Science by Barbara C. Canavan A DISSERTATION submitted to Oregon State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Presented December 4, 2015 Commencement June 2016 Doctor of Philosophy dissertation of Barbara C. Canavan presented on December 4, 2015. APPROVED: Major Professor, representing History of Science Director of the School of History, Philosophy and Religion Dean of the Graduate School I understand that my dissertation will become part of the permanent collection of Oregon State University libraries. My signature below authorizes release of my dissertation to any reader upon request. Barbara C. Canavan, Author ACKNOWLEDGEMENTS I thank my major professor, Anita Guerrini, for her generous encouragement and guidance. She is a superb mentor who encouraged both scholarship and creativity. I am also indebted to my committee members, Michael Osborne, Steve Rubert, David Bernell, and Jake Hamblin for sharing their expertise. I had outstanding opportunities to learn from top scholars. My participation at the Hertog Global Strategy Initiative (The History and Future of Pandemic Threats) at Columbia University was an extraordinary experience. I also thank the staff at the Rockefeller Archive Center for their support and for the opportunity to conduct research there. For Doug, my gratitude for your support, encouragement, and inspiration is beyond words. I give special thanks to Lillian and Patrick for always being there, cheering me on. The wisdom and encouragement from my professors, my family, and fellow students made this goal possible. TABLE OF CONTENTS Page 1 Introduction………………………………………………………………………… 1 1.1 Overview: Avian Flu in Nature and Society……………………………... 1 1.2 Qinghai Case Study Context……………………………………………... 2 1.3 Research Goals and Questions…………………………………………… 3 1.4 Chapter Summaries………………………………………………………. 6 2 Theoretical Framework, Methods, and Literature Review…………………………. 8 2.1 Theoretical Framework…………………………………………………… 8 2.2 Qinghai Case Study Methods……………...……………………………...13 2.3 Literature Review and Primary Sources………………………………….20 3 Ecological Dimensions of Viruses………………………………………………... 44 3.1 Nature of the Virus………………………………………………………..44 3.2 Virus, Environment, and Host………………………………………….....59 3.3 Historical Perspectives: Ecological Approaches to Microbes…………… 69 4 Avian Influenza: Biography of a Cross-Species Virus………………………….... 83 4.1 Avian Influenza: Anatomy and Species Range…………………………. 84 4.2 Influenza: Origins of a Cross-Species Virus……………………………. 91 4.3 Historical Perspectives: Fowl Plague…………………………………… 96 4.4 Commodification of Poultry…………………………………………….. 104 4.5 Jumping the Species Barrier…………………………………………….. 112 5 Qinghai Case Study: Opening Pandora’s Box at the Roof of the World………......119 5.1 Introduction………………………………………………………………119 5.2 Riding the Permafrost Rooster…………………………………………...121 5.3 Natural History of an H5N1 Virus……………………………………….133 5.4 Chronology: Events at Qinghai…………………………………………..137 5.5 Wild Goose Chase………………………………………………………..142 5.6 Ecological Pathways for H5N1 viruses at Qinghai………………………156 5.7 Qinghai: a Black Swan Event?…………………………………………...164 5.8 Systematic mapping analysis……………………………………………..167 TABLE OF CONTENTS (Continued) Page 6 High Politics and Pandemic Predictions…………………………………………… 178 6.1 Early Influenza Research and Vaccine Trials……………………………. 179 6.2 Historical Perspectives: Predictive Theories for Pandemics…………….. 196 6.3 Swine Flu 1976: Predictive Theories Applied…………………………... 203 7.4 Avian Flu Research Controversies………………………………………..220 7 Conclusions and Broader Impacts………………………………………………… 225 Archives and Bibliography…………………………………………………………... 230 Appendices…………………………………………………………………………… 276 LIST OF FIGURES Figure Page 1. Qinghai case study logo……………………………………………………………. 7 2. Systematic Mapping Example……………………………………………………. 18 3. Theoretical Framework – Conceptual Diagram…………………………………... 19 4. Icosahedron……………………………………………………………………….. 50 5. Phage………………...……………………………………………………………. 54 6. Influenza Virus Structure………………………………………………………… 84 7. Influ-Venn-Za……………………………………………………………………. 85 8. Influenza A Virus Host Range………………………………………………….... 86 9. Natural History of HPAI H5N1………………………………………………….. .90 10. Transmission Cycle for Bird Flu………………………………………………... 95 11. Qinghai-Tibet Railway Map……………………………………………………..121 12. Qinghai-Tibet Railway Tourist…………………………………………………. 123 13. Woman with yak at Qinghai Lake………………………………………………. 124 14. Qinghai-Tibet Railway Embankments………………………………………….. 126 15. Qinghai-Tibet Railway Bridge………………………………………………….. 127 16. Bar-headed Goose in Munich…………………………………………………… 131 17. Flyways for Waterbirds…………………………………………………………. 139 18. Bar-headed Goose Portrait……………………………………………………… 143 19. Qinghai-Tibet Plateau Research Categories…………………………………….. 169 20. Distribution of H5N1 Literature by Year……………………………………….. 170 21. H5N1 Research Categories……………………………………………………....171 LIST OF FIGURES (Continued) Figure Page 22. Funding for H5N1 research……………………………………………...............172 23. Qinghai-H5N1 Research by Category…………………………………………... 173 24. Funding for Qinghai-H5N1……………………………………………………... 174 25. Countries publishing research about Qinghai-H5N1…………………………… 175 26. Influenza Recycling Theory…………………………………………………….. 201 LIST OF TABLES Table Page 1. Viral Disease Reservoirs……………………………………………………... 63 2. Viral Zoonoses: Environmental Pathways…………………………………. ...66 3. Major HPAI Outbreaks 1959-2015………………………………………… .103 LIST OF APPENDICES Appendix Page Appendix 1 Phylogenetic Tree of Qinghai-H5N1………………………..276 Appendix 2 Results of Qinghai-H5N1 systematic mapping……………..277 1 Chapter One: Introduction 1.1 Overview: Avian Influenza in Nature and Society From a broad perspective, much of what is familiar about the history of human civilization is the direct result of a stable interglacial period suitable for agriculture and prolonged human settlement over the past millennia. It is challenging to comprehend the scale of changes in our human-constructed and natural worlds. In particular, there is no historical analog for understanding the impact of such changes on the microbial world. This dissertation seeks to examine changes for one familiar and recurring aspect of that microbial world: the influenza virus. The volume of avian influenza (bird flu) outbreaks in the first few years of the twenty-first century has already exceeded the total number of outbreaks recorded for the entire twentieth century.1 In poultry, bird flu has gone from being an exceedingly rare disease to one that emerges continuously, seemingly an evolution in fast forward. The World Health Organization characterized the continued presence of the influenza virus in wild birds and poultry farms as a global health crisis and one of the most extensive animal diseases ever recorded.2 There is fear that if an avian influenza virus were to become transmissible among humans (currently, it is not) it would herald a pandemic worse than the one of 1918. Even absent a catastrophic pandemic, some experts see bird flu as a “dress rehearsal” for future zoonotic disease, one in which the pathogen originates in the animal world.3 1 Ruth Cromie et al., “Responding to Emerging Challenges: Multilateral Environmental Agreements and Highly Pathogenic Avian Influenza H5N1,” International Wildlife Law and Policy 14, no. 3–4 (2011): 206–42. 2 Anthony J McMichael, Maria Neira, and David L Heymann, “World Health Assembly 2008: Climate Change and Health,” Lancet 371, no. 9628 (June 7, 2008): 1895–96. 3 Ian Scoones,