Organic synthesis has changed the world by empowering chemists to tailor complex molecules to specific purposes. To do so, chemists use an approach wherein a “lead” molecule is optimized for its function through iterative structural modifications. Despite the fact that this process philosophically involves changes that are imagined to the candidate in hand, syntheses of the imagined replacements require chemists to begin “from scratch”, discarding the existing lead compound. My laboratory aims to address the methodological gap responsible for this philosophical disconnect. Inspired in part by the ability for CRISPR to enable genetic editing, we are developing reactions which exert single-atom control over small molecules: targeted insertions, deletions, and replacements of carbon, nitrogen, and oxygen. Such precise manipulation promises to revolutionize the discovery of the next generation of world-changing molecules by streamlining molecular innovation.