Practical lessons of the 3Rs: Learning from the past and looking toward the future

Replacement, reduction, and refinement, known as the 3Rs, is a well-known and broadly applied concept in biomedical science. Since its formal introduction in 1959, application of the 3Rs have refined approaches to reduce or eliminate distress, reduced overall use through repeated measures approaches and use of appropriate numbers of animals, or have replaced animals altogether. However, adoption of the 3Rs is not always easy, due in part to initial lack of awareness of the importance of animal well-being to the outcome of scientific investigation, a lack of understanding of use of results from in vivo model verses in vitro models, lack of effective communication about model benefits, or other technical issues with the development or use of an assay. In understanding the history of the 3Rs, we can learn from or avoid previous challenges as we look to the future of the application of the 3Rs. For instance, there is little doubt that awareness and use of the 3Rs influenced the concept of new approach methods (NAMs), a term describing assays that include traditional in vitro cultures, microphysiological systems, and in silico approaches, and is certainly part of the 3Rs future and the ultimate replacement of an animal-based assay.