Watson and Crick’s discovery of the structure of DNA led to developments that transformed many biological sciences. But what were the relevant developments and how did they transform biology? Much of the philosophical discussion concerning this question can be organized around two opposing views: theoretical reductionism and layer-cake antireductionism. Theoretical reductionist and their anti-reductionist foes hold two assumptions in common. First, both hold that biological knowledge is structured like a layer cake, with some biological sciences, such as molecular biology cast at lower levels of organization, and others, such as classical genetics, cast at higher levels. Second, both assume that scientific knowledge is structured by theory and that the productivity of scientific research depends on whether the underlying theory identifies the fundamentals upon which the phenomena to be explained and investigated depend. In the first part of this paper, I challenge these assumptions. In the second part, I show how recasting the basic theory of classical genetics made it possible to retool the methodologies of genetics. It was the investigative power of these retooled methodologies, and not the explanatory power of a gene-based theory, that transformed biology.