The principles of humane experimental technique: timeless insights and unheeded warnings

Summary In the Principles of Humane experimental technique , Russell and Burch said that “the central problem is that of determining what is and what is not humane, and how humanity can be promoted without prejudice to scientific and medical aims”. They then explained how the Three Rs can be used to diminish or remove direct inhumanity (“the infliction of distress as an unavoidable consequence of the procedure employed”) and contingent inhumanity (“the infliction of distress as an incidental and inadvertent by-product of the use of a procedure”). They concluded that “Replacement is always a satisfactory answer, but Reduction and Refinement should, whenever possible, be used in combination”. Many of the commonsense insights in the Principles are no less relevant today than they were in 1959. However, their warnings about the limited value of models and, in particular, the danger of succumbing to the high-fidelity fallacy (whereby it is assumed that the best models for humans are always placental mammals, because they are more like humans than other animals), appear to have largely gone unheeded. Of particular importance is their discussion on toxicity testing, which they saw as one use of laboratory animals “which is an urgent humanitarian problem, for it regularly involves considerable and sometimes acute distress”. How, then, can it be that mammalian models are still routinely used in attempts to detect chemical carcinogens and reproductive toxins, despite the fact that the relevance to humans of the data they provide has not been, and perhaps could never be, satisfactorily established? Nevertheless, there are signs that some significant changes in attitude are taking place, particularly in the USA, which could be more in line with the main thrust of The Principles, the belief that good science and human technique inextricably go hand-in-hand.