Advancing the 3Rs: innovation, implementation, ethics and society

Abstract

The 3Rs principle of replacing, reducing and refining the use of animals in science has been gaining widespread support in the international research community and appears in transnational legislation such as the European Directive 2010/63/EU, a number of national legislative frameworks like in Switzerland and the UK, and other rules and guidance in place in countries around the world. At the same time, progress in technical and biomedical research, along with the changing status of animals in many societies, challenges the view of the 3Rs principle as a sufficient and effective approach to the moral challenges set by animal use in research. Given this growing awareness of our moral responsibilities to animals, the aim of this paper is to address the question: Can the 3Rs, as a policy instrument for science and research, still guide the morally acceptable use of animals for scientific purposes, and if so, how? The fact that the increased availability of alternatives to animal models has not correlated inversely with a decrease in the number of animals used in research has led to public and political calls for more radical action. However, a focus on the simple measure of total animal numbers distracts from the need for a more nuanced understanding of how the 3Rs principle can have a genuine influence as a guiding instrument in research and testing. Hence, we focus on three core dimensions of the 3Rs in contemporary research: (1) What scientific innovations are needed to advance the goals of the 3Rs? (2) What can be done to facilitate the implementation of existing and new 3R methods? (3) Do the 3Rs still offer an adequate ethical framework given the increasing social awareness of animal needs and human moral responsibilities? By answering these questions, we will identify core perspectives in the debate over the advancement of the 3Rs.

Keywords: 3Rs; animal research; ethics; implementation; innovation.

Figure 1

The complexities of advancing 3Rs: Innovation, implementation and societal issues as interrelated core dimension. Advancing 3Rs. This schematic illustrates the intersection of innovation (blue), implementation (grey) and ethics & society (orange), all directed toward advancing 3Rs. Concerning innovation, the recent development of non-aversive methods for manipulating rodents such as tunnel handling have provided major improvements in the refinement of animal welfare, whereas and in vivo bioluminescence imaging has enabled the long-term non-invasive monitoring of animals leading to a reduction of their use for research purposes. As innovation is directly causal to implementation, the development of skin cell cultures for the replacement of in vivo testing, has led to validated and approved toxicity assays, followed by the ban of cosmetic testing on animals. Likewise, imaging techniques such as MRI have been adapted to small animals and helped assessing organ function in living animals. Lying at the conference of ethics and implementation are the ARRIVE guidelines that have been developed to improve research reporting and quality and minimize the waste of animals used in research. Within ethics and society, since the publication of Russell and Burch in 1959 on the 3Rs principle, its incorporation within the legislation has contributed to the development of the harm and benefit analysis (HBA) in ethical committees that legislate the use of animals in experimentation. From innovation toward ethics & society, as the science goes public, there is an increased involvement of the society in the ethical debate and political decisions regarding the use of animals in research. In the periphery are shown all the domains where challenges are found as for instance in innovation (e.g., 3D co-culture or organs-on-a-chip), implementation (e.g., use of pain killers in surgical practice or enrichment for improved animal welfare), and in ethics & society (e.g., harmonized EU legislation and the contribution of the public opinion), all of which should be addressed for generating a responsible scientific knowledge.