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This essay explores Sinclair Lewis's Arrowsmith (1925) through the medical-ethical and ecological contingencies of U.S. tropical medicine during the early twentieth century. With an eye kept on the novel's well-known "St. Hubert " chapters, the essay queries the dangerous compromises that even the most well-intentioned medical professionals have made and can make in the name of scientific progress. The novel, I argue, organizes around and yet moves beyond the traditional outbreak narrative to unravel the various political, economic, and cultural strands of U.S. imperial medicine. The novel's platform for applied sanitary science helps me revisit famed public health campaigns, particularly those from Cuba and Panama, and draw out new ways of understanding race and place in the context of global health intervention.