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In the nineteenth century, maritime quarantine officials often paid more attention to ships’ cargo than they did to the health of passengers or crew members. Based on a close reading of the everyday practice of quarantine at Philadelphia’s Lazaretto (1801–1895), this article suggests that the historical significance of quarantine has been distorted by its association with the etiological debate over contagion and with xenophobic responses to immigration. In fact, the practice of quarantine rested neither on contagionist medical doctrine nor on nativism. Rather, it was based on the danger of infection, an elusive but fundamental concept in nineteenth-century public health. The concern about cargo rather than people—and the logic of infection it reflects—bespeak a widely shared set of perceptions of illness and public health in the first three-quarters of the nineteenth century that is not captured by discussions of contagion or of anti-immigrant bias.