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This course will use our current experience with the COVID-19 pandemic as a lens to study the processes by which infectious diseases emerge. Because of recent developments in the "historicist sciences" (bioarchaeology and palaeogenetics), it is possible to piece together the origin stories of some of the world's most impactful diseases. How does a "microbe's-eye view" of disease emergence change our understanding of past (and present) pandemics? Is it possible that understanding emergence might help us better understand why certain diseases have continued to proliferate, refusing to yield to modern interventions?We will focus on several major diseases transmitted between the Old and New Worlds before and after 1500. At issue is not simply the original spillover event (the transfer of a pathogen from one host species to humans), but the question of how these diseases exploit human connectivity to proliferate. These early globalizing stories will be compared with the story of SARS-CoV-2 as its own "origin story" continues to unfold. Given current critiques of the failures of "global health," what do these origin stories have to tell us about how diseases become "endemic"? Is humankind both the cause of its major diseases, but also doomed to endure them in perpetuity?