Comment in 2024

Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation. Despite their broad acceptance, interpretations of the 3Rs vary substantially, shaping statutory frameworks at various levels, with both technical and practical impacts.

Mice with a natural microbiome are a promising research model for basic and applied science because of their closer resemblance to the human superorganism compared to mice born and raised under stringent hygiene conditions. Consequently, biomedical therapies developed and tested in “Wildling mice” hold great potential for successful translation into clinical applications. Over the past four years, scientists, veterinarians and institutional officials at Charité – Universitätsmedizin Berlin, supported by the University Hospital Erlangen, have designed a facility for Wildling mice and developed a conceptual framework for safe and ethical preclinical research involving mice with a natural microbiome.

In the rapidly evolving field of biomedical research, the role of animal models has long been a topic of scientific and ethical debate. However, despite advancements in alternative modeling approaches, animal models remain an essential component of scientific discovery and medical advancement.

In biomedical research, particularly for rare diseases (RDs), there is a critical need for model organisms to unravel the mechanistic basis of diseases, perform biomarker studies and develop potential therapeutic interventions. Within Solve-RD, an EU-funded research project with the aim of solving large numbers of previously unsolved RDs, the European Rare Disease Models & Mechanisms Network (RDMM-Europe) has been established.

A strategic and statistically based experimental design is a key component of Reduction, and the backbone of reproducible research. Design basics consist of formal structuring of input variables and clearly defined experimental units. Formal designs can evaluate two or more input factors simultaneously, identify and prioritise the most important inputs, and identify interactions where most discovery occurs.

The 3R principles provide an ethical framework for animal research throughout the world. However, despite the increasing awareness of these principles, there is still a lot of room for improving their implementation, especially when it comes to reduction. By combining Bayesian statistics with a shift in experimental design, here we present an entirely new idea to reduce animal numbers within experiments.