Reduction in Animal Use 35 Years after Russell & Burch's Principles of Humane Experimental Technique

Abstract

“Reduction” in animal use can be achieved by better experimental strategy and improved experimental design. In 1959, one strategy for discovering new drugs involved the random testing of thousands of chemicals in animal models of disease. This strategy was deplored by Russell & Burch in The Principles of Humane Experimental Technique (1959) as being inefficient and inhumane, and has now been almost completely superseded, following fundamental research resulting in an improved understanding of the mechanisms of drug action. Random screening is still done on a large scale, but by using in vitro methods. Good experimental design involves the control of variation. In 1959, it was not clear whether isogenic (inbred or F1 hybrid) strains of mice and rats were more uniform than outbred stocks and whether they should therefore be used preferentially in bioassays. It is now generally accepted that F1 hybrids and inbred strains tend to be more uniform, but, as precision also depends on sensitivity, which is unpredictable, there is no general rule for choosing the best strain for a bioassay. Choice should be based on pilot studies. However, the use of more-uniform, specific pathogen-free animals, which were only just becoming available in 1959, has certainly reduced the number of animals which are used. Other aspects of experimental design, such as the need to avoid bias, have a wide range of applicability; the importance of simplicity and the ability to calculate uncertainty are, apparently, not always appreciated by research scientists. The concept of “reduction” has been useful in focusing attention on the need for improved experimental design. In the long-run, animal welfare legislation and improved training for research scientists should lead to improvements, not only in the way in which animals are kept, but also in the way in which experiments are planned and analysed.