Russell and Burch's 3Rs then and now: the need for clarity in definition and purpose.

Russell and Burch's The Principles of Humane Experimental Technique was first published in 1959. A Special Edition containing the original text was reissued in 1992, after its ideas had gained widespread interest in the scientific community. In the Principles, Russell and Burch proposed a new applied science that would improve the treatment of laboratory animals while advancing the quality of science in studies that use animals. They introduced and defined the terms replacement, reduction, and refinement, which subsequently have become known as 'alternatives' or 'alternative methods' for minimizing the potential for animal pain and distress in biomedical research. Here we describe and explain the original definitions of the 3Rs in the Principles, examine how current definitions differ among themselves and from Russell and Burch's definitions, and suggest relevant considerations for evaluating all definitions of the 3Rs.