Daniel MacArthur is intrigued by the prospect that hidden in the human population are people who lack certain genes yet remain healthy. Finding such natural human "knockouts" and looking for differences between their physiology and that of people with the intact gene may be the only way to fully understand the function of many of our genes, he and others contend. It could also have biomedical payoffs. To get started, MacArthur and others want to comb through many thousands of people's genomes for missing genes to seed what MacArthur calls the Human Knockout Project. But identifying dispensable genes is only the start of the challenge.