All known forms of life rely on DNA as the carrier of genetic information and on proteins as the primary functional agents. The present-day molecular systems that implement DNA replication and protein synthesis are highly-evolved, and it’s reasoned that life began by leveraging much simpler systems. In the late 1960s scientists began to hypothesize that a molecule that could serve both as a carrier of information and as a catalyst that facilitates replication was critical to the emergence of life. That molecule was -and is- thought to be a version of RNA called a polymerase ribozyme, and the aforementioned hypothesis has come to be known as the RNA World Hypothesis. This polymerase ribozyme would possess the unique ability to copy RNA sequences, including its own, and thereby sustain a self-replicating, evolving system. While biology has revealed naturally occurring ribozymes (RNA molecules with the enzyme-like ability to catalyze chemical reactions), none are known to possess the ability to replicate RNA. Funds from this grant support work by Gerald Joyce, President and CEO of the Salk Institute for Biological Studies, to use directed evolution -a method that mimics natural selection- to develop a ribozyme that catalyzes its own replication and undergoes Darwinian evolution.  Directed evolution is a laboratory technique that uses cycles of mutation, selection, and amplification to evolve molecules with targeted functions. Joyce and his research team have made impressive strides using directed evolution to incrementally enhance the catalytic ability, speed, accuracy, and generality of polymerase ribozymes. Their current ribozymes can synthesize ancestral (smaller) versions of themselves and drive exponential amplification (increase the number of selected molecules), but they are not yet capable of full self-replication. A crucial requirement for evolution is, of course, the ability to accurately propagate genetically encoded information across generations. If the replication process introduces too many errors, information important to the successful propagation of an organism is lost. Joyce seeks to increase the fidelity of polymerase ribozymes to facilitate the faithful replication of longer and more information-rich RNA sequences; ultimately achieving the synthesis of an entire polymerase ribozyme itself. If successful, the  project will realize an artificial lifeform that serves as a platform for studying emergent complexity, adaptive evolution under environmental pressure, and the origins of more sophisticated genetic and metabolic networks from simpler molecular systems.