The 3Rs principle of Replace, Reduce, and Refine has guided animal research welfare for over 60 years. Understanding what has been achieved and what remains shows the path to further reducing research animal welfare costs.
The 3Rs have achieved genuine welfare progress in research animal use over 60 years while navigating the genuine difficulty that many important biomedical questions still require animal models to answer responsibly. Replacement of animal tests with validated alternatives has eliminated animal use in vaccine potency testing, Draize eye tests, and some toxicology applications. Reduction through improved experimental design and sharing of animals reduces numbers used without reducing research quality. Refinement through improved anaesthesia, analgesia, housing, and humane endpoints reduces suffering per animal used. The development of organoids, microphysiological systems, and artificial intelligence models of biology opens new replacement possibilities that may transform research practice further in coming decades.