The concept of the 3Rs remains more prevalent than ever in global discussions related to humane animal use in aspects of research, teaching and testing. The 3Rs serve as a touchstone, in terms of refinement, reduction, and replacement, for veterinary staff, ethical review committees and scientists. Russell and Burch established these words as part of a new applied science in 1959, aiming to improve animal welfare with the 3Rs as a launchpad for future development of scientific methods and medical discovery. In all aspects of animal use, the anticipated benefits of scientific inquiry are to be weighed against the potential detriments borne by the animals themselves; this ethical balance is referred to as the ‘harm-benefit’ analysis. Over time, aspects of the use of the 3Rs in study design (refinement), statistical analysis (reduction), and selection of alternatives to live animals (replacement), have strayed into the potential for abuse by groups that seek to constrain the spirit of their interpretation. For example, with the generation and availability of novel techniques (e.g., CRISPR) and development of human disease (e.g., COVID-19) in animal models, any rigid 3Rs interpretation of ‘reduction’ to minimal numbers until we achieve ‘replacement’ of all animals is incompatible with the necessity to support science and production of reliable and reproducible results. The 3Rs have remained ubiquitous in large part because of their benefit to animals, although importantly they are also of benefit to those stakeholders invested in the animal research enterprise. The exquisiteness of the 3Rs is that, much like a classical piece of art, they are inherently subject to broad interpretation across the contemporary biomedical community. Reconsidering the foundational 3Rs with progressive interpretations, in combination with other ethical tools of analysis and validity assessments, will be essential in the ongoing intricate considerations of appropriate and future animal use.
1. Review the foundational 3Rs for animal use and welfare and discuss limitations of rigid interpretation of the terminology
2. Provide expanded definitions of the 3Rs that better address the complexity of appropriate animal use and welfare in contemporary society