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In the mid-19th century, the German hygienist Max von Pettenkofer viewed cholera as resulting from the interaction between a postulated cholera germ and the characteristics of soils. In order to cause cholera, the cholera germ had to become a cholera miasma, but this transformation required prolonged contact of the germ with dry and porous soils when groundwater levels were low. This hypothetical germ-environment interaction explained more observations than did contagion alone. Despite its attraction, von Pettenkofer's postulate also implied that cholera-patient quarantine or water filtration was useless to prevent and/or control cholera epidemics. The disastrous consequences of the lack of water filtration during the massive outbreak of cholera in the German town of Hamburg in 1892 tarnished von Pettenkofer's reputation and marked thereafter the course of his life. von Pettenkofer's complex mode of thinking sank into oblivion even though, in hindsight, germ-environment interactions are more appropriate than is bacteriology alone for explaining the occurrence of cholera epidemics in populations. Revisiting the fate of von Pettenkofer's theory with modern lenses can benefit today's quest for deciphering the causes of complex associations.

Epidemiologic Interactions, Complexity, and the Lonesome Death of Max von Pettenkofer