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François Jacob died on 19 April in Paris at the age of 92. We have lost one of the great architects of modern biology, whose legacy touches all aspects of gene regulation from viruses and bacteria to humans, as well as in human diseases such as cancer. To an astonishing degree, his insights and elegant experiments established the framework for understanding the mechanisms that underpin gene control in every decision a cell makes on its journey through the cell division cycle, in embryogenesis, in tissue differentiation, and in the formation of a multicellular organism. He was not only a visionary scientist but also a humanist with extraordinary perception of the workings of the scientific mind and the literary ability to convey his insights with grace and compassion.