How Should the 3 <i>R</i>’s Be Revised and Why?

The Principles of Humane Experimental Technique established what many know today as the "3 R's"-refinement, reduction, and replacement-when it was published in 1959. Since their formulation, these principles have guided decision-making for many about nonhuman animal subjects' uses in laboratory-based research. Discussion about how to amend or replace the 3 R's is ongoing, driven mainly by philosophical ethics approaches to nonhuman animal rights and by scientific advancement. This article explores merits and drawbacks of possible updates to and interpretations of the 3 R's.