The Three Rs (animals)

The Three Rs (3Rs) in relation to science are guiding principles for more ethical use of animals in testing. They were first described by W. M. S. Russell and R. L. Burch in 1959.^[1] The 3Rs are:

1. Replacement: preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aims.
2. Reduction: use of methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
3. Refinement: use of methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals used.

The 3Rs have a broader scope than simply encouraging alternatives to animal testing, but aim to improve animal welfare and scientific quality where the use of animals cannot be avoided. In many countries, these 3Rs are now explicit in legislation governing animal use.

History

In 1954, the Universities Federation for Animal Welfare (UFAW) decided to sponsor systematic research on the progress of humane techniques in the laboratory. In October of that year, William Russell, described as a brilliant young zoologist who happened to be also a psychologist and a classical scholar, and Rex Burch, a microbiologist, were appointed to inaugurate a systematic study of laboratory techniques in their ethical aspects. In 1956, they prepared a general report to the Federation's committees, and this report formed the nucleus of the book which was completed at the beginning of 1958. Over much of the period they worked with a special Consultative Committee, chaired by Professor P.B. Medawar.

As a contribution to the centenary of The Origin of Species, the quotations at the head of each chapter are all from the works of Charles Darwin.

Scope and development

A common misconception of the 3Rs is that they refer only to replacement,^[2] however, their scope is much broader.

Replacement: In the original book, the 3Rs were restricted, arbitrarily, to vertebrates. Russell and Burch discussed the possibility of suffering with reference to sentience. They used the term "replacement technique" for any scientific method using non-sentient material to replace methods which use conscious living vertebrates. This non-sentient material included higher plants, microorganisms, and the more degenerate metazoan endoparasites which, they argued, had nervous and sensory systems that were almost atrophied. They acknowledged that the arbitrary exclusion of invertebrates meant that in several contexts, these species could be considered as possible replacements for vertebrate subjects; they termed this "comparative substitution". Russell and Burch also considered levels of replacement. In "relative replacement", animals are still required, though during an experiment they are exposed, probably or certainly, to no distress at all. In "absolute replacement", animals are not required at all at any stage.

Replacement strategies include-

1. Tissue culture
2. Perfused organs
3. Tissue slices
4. Cellular fractions
5. Subcellular fractions

More recent interpretations of the replacement principle suggest the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aims, i.e. invertebrates are not considered suitable replacements for vertebrates. However, others such as the National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) advocate the use of some invertebrates in replacement studies. ^[3]

Reduction: Russell and Burch suggested a reduction in the number of animals used could be achieved in several ways. One general way in which great reduction may occur is by the right choice of strategies in the planning and performance of whole lines of research. A second method is by controlling variation amongst the animals used in studies, and a third method is careful design and analysis of studies. With the advent, development and availability of computers since the original 3Rs, large data-sets can be used in statistical analysis, perhaps most notably meta-analysis, thereby reducing the numbers of animals used. In some cases, by using previously published studies, the use of animals can be totally avoided. Modern imaging techniques also allow reductions in the numbers of animals used.

Refinement: Russell and Burch wrote "Suppose, for a particular purpose, we cannot use replacing techniques. Suppose it is agreed that we shall be using every device of theory and practice to reduce to a minimum the number of animals we have to employ. It is at this point that refinement starts, and its object is simply to reduce to an absolute minimum the amount of distress imposed on those animals that are still used." Amongst areas of experiments that can be refined are the procedure to be used, the appropriateness of the species (its suitability for the procedure and its responses to a laboratory environment in general). Other refinements include-^[4]

1. Non-invasive techniques
2. Appropriate anaesthetic and analgesic regimes for pain relief
3. Training animals to voluntarily co-operate with procedures (e.g. blood sampling) so that they have greater control over the procedure and are less stressed
4. Accommodation and environmental enrichment which meets the animals' physical and behavioural needs (e.g. providing opportunities for nesting for rodents)

The definition of refinement has evolved since Russell and Burch's. A newer definition is now commonly accepted, any approach which avoids or minimises the actual or potential pain, distress and other adverse effects experienced at any time during the life of the animals involved, and which enhances their wellbeing.^[5] Refinement encompasses not only the direct harms associated with animal use, but the indirect, or contingent harms associated with breeding, transportation, housing and husbandry.

Organisations

The Home Office (UK) led the Inter-Departmental Group on Reduction, Refinement and Replacement, which aims to improve the application of the 3Rs and promote research into alternatives, reducing the need for toxicity testing through better sharing of data, and encouraging the validation and acceptance of alternatives. The Data Sharing Group drafted the Inter-Departmental Data Sharing Condordat published in August 2000 and was re-formed in June 2002 to consider the scope for the greater application of the 3Rs. Arising from the Government response to the report of the House of Lords Select Committee on animals in scientific procedures, the Group was asked to explore the scope for a UK centre for research into the 3Rs. The Group reported to Ministers that there was support for a body which would act as a means to better publicise and co-ordinate what is already done by way of research into the 3Rs. In May 2004, the NC3Rs was announced in the UK to act as a focal point for research into the 3Rs.^[6] Although the principles of the 3Rs were implicit in UK law under the Animals (Scientific Procedures) Act (1986), the Directive governing animal use within the European Union ^[7] makes the principles explicit and researchers must demonstrate the use of replacement, reduction and refinement techniques in research involving animals.

See also

Bateson's cube

References