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Russell and Burch introduced the principles of replacement, reduction, and refinement of animal experimentation in 1959 in their groundbreaking book, The Principles of Humane Experimental Technique, to eradicate inhumanity to­ wards non-human animals (hereinafter referred to as animals). They utilized the term inhumanity to indicate negative mental states experienced by animals used in research and the procedures that cause such mental states. Their goal was to avoid the use of animals wherever possible and to improve significantly the treatment of the animals still deemed indispensable, while improving the quality of scientific and medical research and testing (Russell and Burch, 1959 ). Since the 1990s, the 3Rs have slowly gained more acceptance within the animal research community. They have been recognized by organizations such as the Council of Europe (1986) and the World Organisation for Animal Health (2018), and they have been implemented in law in several countries, for example in Germany and in the UK (Herrmann, Kopemik and Biedermann, 2009; Zurlo, Rudacille and Goldberg, 1996). Today, the principles are not only embedded in legislation in the European Union (Eu) but around the world (Bayne et al., 2015). In the EU, Directive 2010/63/EU on the protection of animals used for scientific purposes came into effect in 2013, thereby requiring all EU Member States to implement the

Refinement on the Way Towards Replacement: Are We Doing What We Can?