In the highly acclaimed 1991 play Angels in America, which explores AIDS in the United States in the 1980s, one of the characters muses about the nature of knowledge and novelty: "Imagination can't create anything new, can it? It only recycles bits and pieces from the world and reassembles them into visions." Although the scene's intent is to ponder the limits of human experience and how the constraints of day-to-day reality are inescapable, the description of imagination aptly describes the creative shuffling that can lead to breakthroughs, like the ones recognized by Science at this time every year. In naming the drug lenacapavir as the 2024 Breakthrough of the Year, Science acknowledges the next, but by no means final, step in the drive to fight HIV/AIDS, where the rigors of the laboratory and the needs of humanity are inseparable.