Many of the major human infectious diseases, including some now confined to humans and absent from animals, are 'new' ones that arose only after the origins of agriculture. Where did they come from? Why are they overwhelmingly of Old World origins? Here we show that answers to these questions are different for tropical and temperate diseases; for instance, in the relative importance of domestic animals and wild primates as sources. We identify five intermediate stages through which a pathogen exclusively infecting animals may become transformed into a pathogen exclusively infecting humans. We propose an initiative to resolve disputed origins of major diseases, and a global early warning system to monitor pathogens infecting individuals exposed to wild animals.

1. Department of Epidemiology, School of Public Health, University of California, Los Angeles 90095-1772, USA
2. Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles 90095-1688, USA
3. Departments of Geography and of Environmental Health Sciences, University of California, Los Angeles 90095-1524, USA

Correspondence to: Nathan D. Wolfe¹Jared Diamond³ Correspondence should be addressed to N.W. (Email: nwolfe@ucla.edu) or J.D. (Email: jdiamond@geog.ucla.edu).

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