A, T, G, C: the alphabet code for the nucleotides that are the building blocks of life. Minor, but consequential, changes in this DNA coding can change gene function. Researchers have long sought better ways to edit the genetic code in cultured cells and laboratory organisms to silence, activate, or change targeted genes to gain a better understanding of their roles. This, in turn, could open the door to beneficial applications, from ecological to agricultural to biomedical. Over the years, several editing methods have been developed, but they have suffered from a lack of specificity, difficulty in assembling the molecular constituents, or concerns about off-target effects. Recently, accomplishments in genome editing across biological disciplines have been so remarkable that the method known as clustered regularly interspaced short palindromic repeats—or CRISPR—is Science 's 2015 Breakthrough of the Year (see p. 1456).