60 Years of the Three Rs and Their Impact on Animal Welfare

Dear Colleagues,

Laboratory animals have been used for a wide range of purposes for many years, including understanding basic physiology in health and disease, pharmaceutical research and development, safety assessment, and applied veterinary research. Animal experiments in the fields of biology, animal welfare, veterinary science, and agricultural science are usually designed to translate directly to the studied species. The vast majority of animals, however, are used for medical research and safety testing. Here, animals are almost exclusively used as substitutes or “models” for humans.

Although the ethical and animal welfare concerns associated with animal use are widely recognized, and investment into humane alternatives is increasing, full replacement is currently not possible and over 100 million animals per year are used worldwide in research and testing. Mice and rats are currently the most frequently used animal species, but the use of zebrafish is continuing to rise rapidly.

The field of laboratory animal science, a multidisciplinary branch of science that contributes to the quality of animal experiments and to the welfare of laboratory animals, was established in the 1950s. The growing understanding that animals are not simply “research tools”, and that better welfare leads to better science, led directly to the concept of the Three R’s—replacement, reduction, and refinement—launched by Russell and Burch in 1959 in their book “The Principles of Humane Experimental Technique” (developed while the authors held scholarships from the Universities Federation for Animal Welfare). This year we will celebrate the 60th anniversary of the Three Rs!

Replacement means the substitution of living animals using in vitro techniques (e.g., established cell lines that do not use animal sera, or human tissues), the use of lower organisms (e.g., yeasts), human volunteers, computerized models, genomics, proteomics, or organ-on-a-chip techniques. Partial replacement means the use of invertebrates that are not believed to suffer (e.g., nematode worms), out-of-scope developmental stages, and cell lines using animal sera. Replacement can also include avoiding animal use, for example, by systematic reviews or meta-analyses of previously published data, or taking a different approach to resolving a human health problem.

Reduction means taking every measure to decrease the number of animals used to the minimum amount necessary in order to answer the scientific question, for example, by employing optimal biostatistical methods, standardizing animals in terms of genotype and microbiological quality, or standardizing (and accurately reporting) the experimental procedures and animals’ environment. Imaging methods, using historic controls, and tissue sharing can also be used to reduce animal numbers.

Refinement means decreasing discomfort and promoting wellbeing throughout every animal’s lifetime. There are many ways to achieve this, including providing adequate anesthesia, analgesia, and care; guaranteeing the skills of the researchers and animal technologists through education and training; and improving the experimental procedures and determining a humane endpoint, where the animal can be humanely killed so as to prevent avoidable suffering. Concerning housing conditions, refinement can be achieved by translating the behavioral and physiological needs of the animal into adequate housing and husbandry.

For this Special Issue, we invite submissions on any aspect of the Three Rs, related to any research field or species. These may include papers describing current good-practice and/or evaluation studies, as well as commentaries and opinion pieces that review what the Three Rs have achieved in specific areas, or taking a forward look. Submissions relating to the ethical implications of the Three Rs, as well as concepts such as the culture of care, are also welcome.

Prof. Vera Baumans
Dr. Penny Hawkins
Dr. Paulin Jirkof
Guest Editors

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• three Rs
• animal welfare
• replacement
• reduction
• refinement
• systematic reviews
• culture of care, reproducibility
• planning animal experiments
• organ-on-a-chip