The three Rs of animal research: replacement, refinement, reduction

Following on from last week’s blog discussing animal research, this week’s blog discusses the work of the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs). But before discussing how NC3Rs are reducing the numbers of animals in research, how many animals are currently used in research?

The Home Office statistics for 2011 show that, in the UK,  just over 3.7 million animals were used in research, 93% of which were mice, rats or fish. While this sounds a lot, to put this number into perspective, this means that for each member of the 63 million strong UK population, 0.06 of an animal was used in research in 2011. Furthermore, this means that, assuming an average life expectancy of 80 years, for each person in the UK, 4.7 animals will be used in research in their lifetime, 3.4 of which will be mice, and 1 of which will be a rat or a fish.

NC3Rs was set up in 2004 by the UK government to investigate the role of animals in research, and to provide a scientific lead in discussions surrounding this issue. Their mission is to use the principles of replacement, refinement and reduction to support scientific discovery, and address societal concerns about animal research. In 2013, NC3Rs awarded over £8.2 million to 3Rs projects investigating ways to reduce the numbers of animals used in research, or to improve the welfare of those currently used.

Replacement describes the use of an alternative method that avoids the use of protected animals. Exciting technological advancements in this area have yielded a number of alternatives to using animals in research: a lung-on-a-chip to replicate pulmonary oedema (Huh et al., 2012); growing mouse mini-livers from stem cells to use for drug screens (Huch et al., 2013); and the use of amoeba to determine the biological mechanism behind seizures and to screen for better epilepsy drugs (Chang et al., 2014). Together, these advances are estimated to avoid the use of tens of thousands of mice.

Refinement refers to improving scientific procedures in order to improve the welfare of the animals used in the experiment. For example, it takes less than 40 minutes to train a macaque to voluntarily give blood without being restrained. Not only is the procedure less stressful for the animal, but the experiment is not confounded by increased levels of stress hormones in the animal’s blood, thus simultaneously improving the animal’s wellbeing, and the accuracy of the experiment.

Reduction refers to the use of methods that allow researchers to collect a similar quantity and quality of data using fewer animals. This can be achieved by improved experimental designs and statistical analysis, or more sophisticated analysis techniques. For example, improved non-invasive scanning techniques mean a single animal can be analysed multiple times. However, using too few animals to obtain a conclusive result is as wasteful and unethical as using too many animals. Therefore experiments must be designed carefully beforehand to ensure that they do not need to be repeated.

By engaging with the public about animal research, NC3Rs, Understanding Animal Research and researchers hope to communicate the messages that animal research is necessary for medical progress, it is highly regulated, it is being constantly monitored to identify where improvements can be made, and that animal use will inevitably decrease as technology improves. This will hopefully increase public support for the use of animals in research where there is no viable alternative.

Animal research is, quite rightly, a complex and emotive issue. However, it is worth bearing the following in mind: as described above, fewer than 5 animals, most of which will be mice, rats or fish, are used in research during the lifetime of each person in the UK. While not everyone will get seriously ill, more than 1 in 3 people in the UK get cancer and will need treatment, most people will have surgery in their lifetime, and nearly all will take paracetamol for a headache. None of these interventions would be possible, or as effective, without the use of animals in research.


Useful resources:

Understanding Animal Research Website

Government guidance on research and testing using animals

The National Centre for the Replacement, Refinement and Reduction of Animals in Research


  • Chang P, Walker MC, & Williams RS (2014). Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid. Neurobiology of disease, 62, 296-306 PMID: 24148856
  • Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries RG, Grompe M, & Clevers H (2013). In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature, 494 (7436), 247-50 PMID: 23354049
  • Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, Thorneloe KS, McAlexander MA, & Ingber DE (2012). A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Science translational medicine, 4 (159) PMID: 23136042 – the primary online resource for anyone interested in BHD Syndrome.

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