Biologists long thought they understood how genetic mutations cause disease. But recent work has revealed an important twist in the tale and uncovered surprising—even counterintuitive—ways that alterations in DNA can make people sick. The classic view assumed that what are termed “silent” mutations were inconsequential to health, because such changes in DNA would not alter the composition of the proteins encoded by genes. Proteins function in virtually every process carried out by cells, from catalyzing biochemical reactions to recognizing foreign invaders. Hence, the thinking went, if a protein’s makeup ends up being correct, any small glitches in the process leading to its construction could not do a body harm.