In the previous chapters I discussed the limits of reductionism and illustrated the limits of genetic reductionism. In this chapter, I present a novel argument for why organisms are irreducible. To present this argument, I begin by addressing a fundamental question: Why are there sign-mediated interactions in biology? According to Polanyi, biological hierarchies are constituted through boundary conditions. I argue that signs, or more accurately the processes of signification, function as these boundary conditions. Moreover, based on general insights from the physics of computation, I argue that the organism cannot be computed directly from DNA without the loss of critical information. In this context, signs as boundary conditions mediate biological construction in a way that prevents the loss of information and the destabilization of DNA.