Time to move beyond the 3R principles

This recently published study says the time has now come to prioritise the Replacement of animals used for scientific purposes, over refinement and reduction strategies. The 21st Century has already seen the development of a wide range of non-animal methods incorporating complex cell cultures, organs-on-a-chip and computer modelling. These methods are more relevant to human biology and are already enabling the replacement of animals as the default option in life science, particularly in the areas of toxicology and regulatory testing, but also in biomedical research.



This year marks the 60th anniversary of the Three Rs, aimed at promoting the ‘Replacement’ of animal use in science, the ‘Reduction’ of the number of animals used per experiment, and the ‘Refinement’ of experimental procedures to minimise suffering and improve welfare. These principles were first described in 1959 by the UK scientists Russell and Burch and have contributed considerably ever since to progressing humane research methods and excellence in science. Not surprisingly, sixty years after Russell and Burch proposed the 3Rs, the landscape of animal experimentation and alternatives-related technology has changed. Despite successes in developing non-animal methods, especially for toxicological testing, the scale of animal use in Great Britain – home of UFAW, Russell and Burch, and the 3Rs – has more than tripled (Home Office, 2018). What must the 3Rs community change to become more effective?


The authors propose to focus on a new set of 3Rs as a strategic priorities for the current era:

  1. replacement over refinement and reduction
  2. biomedical research over safety testing
  3. relevance to humans rather than to non-human animals.


In addition, the authors recognize that advancing human-relevant, animal-free approaches in biomedical research should be a multi-faceted effort involving, inter alia, funding targeted at laboratory research, graduate and post-doctoral research fellowships, and alternatives prizes. However, a key step in transforming the current animal use paradigm is increasing the awareness of currently available animal-free methods. Without knowledge of these methods, scientists

cannot adopt them, funding agencies cannot create programs to fund them, ethical review committees cannot ask why they are not employed in a given protocol, and so forth. Consequently, knowledge-sharing through education and training plays a central role in achieving the move away from animal experiments and towards human-biology based research methodologies.


This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Humane Experimental Technique. Their 3Rs framework has helped to inspire humane and scientific progress in experimental technique. However, it is time to update its strategic application. The 21st century has already seen the development of promising, high-tech non-animal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as the default option in biomedical experimentation. How fast this transition will take place will depend on the pace at which these new models are optimized to reflect the biology of humans, rather than that of non-human animals. While the new methods are likely to reshape all areas in which animals are currently used in science, we particularly encourage their application in biomedical research, which accounts for the bulk of animals used. We call for the pursuit of a three-prong strategy that focuses on (1) advancing non-animal methods as replacements of animal experiments, (2) applying them to biomedical research, and (3) improving their relevance to human biology. As academics and scientists, we feel that educational efforts targeted at young scientists in training will be an effective and sustainable way to advance this vision. Our strategy may not promise an imminent end to the use of animals in science, but it will bring us closer to an era in which the 3Rs are increasingly perceived as a solution to a receding problem. Russell and Burch themselves surely would have welcomed these positive changes.

Source: Herrmann K, Pistollato F, Stephens ML. Beyond the 3Rs: Expanding the use of human-relevant replacement methods in biomedical research. ALTEX. 2019;36(3):343-352. 10.14573/altex.1907031