The article by Nathan D. Wolfe, Claire Panosian Dunavan, and Jared Diamond explores the origins of major human infectious diseases, particularly those that emerged after the advent of agriculture. They identify five stages through which pathogens can evolve from animal-only infections to human-only infections, and propose an initiative to resolve disputed origins of major diseases. The authors highlight that many tropical diseases also originated in the Old World but for different reasons, often not from domestic animals. They emphasize the importance of understanding these origins for both practical and intellectual reasons, as infectious diseases have significantly influenced historical events and continue to pose significant health challenges. The article also discusses the need for a global early warning system to monitor pathogens infecting individuals exposed to wild animals, and suggests research priorities to address unresolved questions about disease evolution.The article by Nathan D. Wolfe, Claire Panosian Dunavan, and Jared Diamond explores the origins of major human infectious diseases, particularly those that emerged after the advent of agriculture. They identify five stages through which pathogens can evolve from animal-only infections to human-only infections, and propose an initiative to resolve disputed origins of major diseases. The authors highlight that many tropical diseases also originated in the Old World but for different reasons, often not from domestic animals. They emphasize the importance of understanding these origins for both practical and intellectual reasons, as infectious diseases have significantly influenced historical events and continue to pose significant health challenges. The article also discusses the need for a global early warning system to monitor pathogens infecting individuals exposed to wild animals, and suggests research priorities to address unresolved questions about disease evolution.