For animal research, the precautionary principle was written into public policy through the so-called three R’s of replacement, reduction, and refinement. These guidelines, as developed by Russell and Burch six decades ago, aimed to establish safeguards against the abuse of animals in the pursuit of science. While these safeguards, which started from the basic premise that science itself would benefit from a reduction of animal suffering, seem compelling at first, the three R’s have in practice generated a degree of confusion (...) while opening up loopholes that have enabled researchers to effectively dismiss some of the more inconvenient aspects of ethical concerns. Such problems have been discussed in detail by multiple authors. Here, we suggest a different approach by arguing that a clear parallel can be drawn between the shortcomings evident in the current three R’s model and the flawed practice of early modern judicial torture, in which a set of elaborate safeguards that were designed to prevent abuses served instead to create the same combination of confusion and easily exploited loopholes. In the case of judicial torture, attempts to refine the system from within produced limited results, and effective change only took place when individual legal systems succeeded in enforcing clear absolutes. We explore the implications of this for the regulation of animal research by pointing to the need for achievable absolutes, based on a clear, evidence-based, and publicly deliberated rationale, in order to facilitate and improve research ethics. (shrink)