Abstract In recent years, the established paradigm of the three Rs of animal researchrefinement, replacement, and reductionhas come under scrutiny. A crucial weakness in use of the three Rs is uncertainty about how they should be prioritized. Events like pandemics have the power to alter the research landscape, fasttracking innovation and setting new precedents. Existential threats can raise perceptions of social benefit and can lower animalwelfare thresholds. The rush to develop new research models may also undermine progress in reducing or replacing animal models. By circumventing the barrier posed by animal models that are poorly matched to human conditions, new technologies like CRISPR can enhance the refinement component while undermining reduction and replacement. This pandemic has exposed the need for an urgent review of the efficacy of the three Rs, with the potential to establish a new set of protocols for animal research, both inside and beyond the context of an emergency .
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