Stephen Stearns, teaching Yale's Evolution and Medicine course, takes up a practical question: can a treatment be designed so that pathogens cannot evolve resistance to it? Drawing on the framework of his textbook Evolutionary Medicine, Stearns walks through why single-drug therapies tend to fail over time as natural selection favors resistant mutants, and what strategies might close off those evolutionary escape routes. He discusses combination therapies that force a pathogen to acquire multiple mutations simultaneously, and the logic of targeting traits a pathogen cannot easily change without losing fitness. The lecture is short and focused, part of a longer sequence on pathogen evolution within the course, and assumes some prior grounding in evolutionary biology. It ends with the open problem still facing drug designers: attacking a moving evolutionary target without accelerating its escape.