Fatal Flu: History, Science, and Politics of the 1918 Influenza Pandemic
In 1918 an influenza pandemic killed over 50 million people world wide including 675,000 in the United States alone. This Capstone Thesis asks the question: what caused the 1918 pandemic to become so fatal? In order to understand how the influenza outbreak of 1918 turned into one of the world’s deadliest pandemics, I took a unique approach to tackling the mystery of the “Spanish Influenza,” by interpreting the high fatality rate from both a social and natural scientific approach. This project is broken into two parts.
The first part of this paper gives a historical analysis of the 1918 influenza pandemic. The first four chapters answer the questions: (1) what caused the 1918 pandemic to become so fatal? (2)What was the social response to the disease and how did the United States cope with the crisis of the war and outbreak of influenza simultaneously? (3) What were the non-pharmaceutical interventions that were implemented and how effective were these measures in thwarting the spread of the pandemic? (4) Finally, within the last century how have virologists and medical historians remembered and portrayed the 1918 pandemic?
The historical analysis focused on the significance of the United States Public Health Service and the communication between different levels of public health agencies. To do this I drew from a number of primary sources found in The Journal of American Public Health as well as local newspaper archives. A case study of non-pharmaceutical interventions in Syracuse, NY, Princeton, NJ, and New York, NY was also conducted using newspaper archives and local pamphlets. This study found that early implementation of specific interventions held throughout the duration of the second wave of the pandemic was successful in reducing the number of fatalities from influenza.
The second section of this paper is a study on the translational control mechanisms of influenza virus infected cells. Specifically through microarray and Taqman validation studies I compared the gene expression of the type I interferon response pathway between a low pathogenic human influenza virus (A/Texas/36/91 [H1N1]) and the low pathogenic human influenza virus with the NS1 protein from the 1918 influenza virus. These studies found that the greatest differences in these proteins occur early (2 and 6 hours post-infection), and although no dominant pattern was seen in overall gene expression, genes related to inflammation, immune response, and stress did show different patterns of expression for the two NS1 species. In addition, I also conduction translational control experiments with the cellular protein P58IPK, which is known to aid in viral mRNA translation of influenza infected cells. My objective was to indentify additional protein-protein interactions independent of eIF2-α phosphorylation. Using transient-transfection techniques to over express P58IPK in mammalian cells, we confirmed that proteins involved with protein synthesis and RNA post-transcriptional modifications are overly expressed in the presence of over expressed P58IPK.