While chemical theory cannot yet support an engineering vision that allows molecules, DNA sequences, and proteins to be interchangeable parts in artificial constructs without “tinkering”, progress can be made in synthetic biology by pursuing challenges at the limits of existing theory. These force scientists across uncharted terrain where they must address unscripted problems where, if theory is inadequate, failure results. Thus, synthesis drives discovery and paradigm change in ways that analysis cannot. Further, if failures are analyzed, new theories emerge. Here, we illustrate this by synthesizing an artificial genetic system capable of Darwinian evolution, an ability theorized to be universal to life.The full text of this article is available in PDF format.