Moving beyond the Three Rs in Biomedical Research

A new study co-authored by the JRC prioritises human relevant methods and the replacement of animal models in biomedical research.

This year marks the 60th anniversary of the Three Rs, aimed at promoting the 'Replacement' of animal use in science, the 'Reduction' of the number of animals used per experiment, and the 'Refinement' of experimental procedures to minimise suffering and improve welfare. These principles were first described in 1959 by the UK scientists Russell and Burch and have contributed considerably ever since to progressing humane research methods and excellence in science.

However, the 21st Century has already seen the development of a wide range of non-animal methods incorporating complex cell cultures, organs-on-a-chip and computer modelling. These methods are more relevant to human biology and are already enabling the replacement of animals as the default option in life science, particularly in the areas of toxicology and regulatory testing, but also in biomedical research.

This recently published study says the time has now come to prioritise the Replacement of animals used for scientific purposes, over refinement and reduction strategies.

The emerging paradigm in research likely foreshadows an era in which the Three Rs are increasingly perceived as a solution to a receding problem.

Replacing animal experimentation in biomedical research

In the European Union, basic and applied research accounts for about two-thirds of the animals used in science. To date however, replacement of animal methods with human-based models has been mainly discussed in the context of regulatory toxicology and chemical safety. This can be linked to several factors including the relatively limited number of standard studies performed and significant public concern over this use of animals.

Moreover, biomedical research is traditionally more diverse and decentralised compared to toxicity testing, encouraging originality and combinations of both animal and non-animal approaches, despite the limited capacity of current preclinical animal models to accurately predict the safety and efficacy of new drugs.

Promoting Human Relevance in Biomedical Research

Prioritizing animal-free methods of high human relevance is a sensible way to avoid the limited translational value of animal models of human biology.

Non-animal approaches and technologies, such as patient-derived cells and biological samples, large clinical data repositories, computational and imaging tools, machine learning and micro-dosing approaches, are already enabling scientists to incorporate human relevance as a primary design criterion of biomedical research models and approaches.

Such a human-oriented perspective is particularly relevant to the study of chronic, degenerative, non-communicable diseases, which are characterized by complex interactions between environmental and genetic factors.

It is important to prioritize human relevant methods and the replacement of animal models in biomedical research in order to deepen our understanding of human pathologies and increase the likelihood of success in the development of drugs that are truly effective in humans.

Increasing Awareness, Dissemination and Education on Non-animal Approaches

Knowledge sharing through education and training is pivotal to increase the awareness of currently available animal-free methods.

The JRC's EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) has recently coordinated a study to review available education and training resources that support the 3Rs approach.

EURL ECVAM is also collaborating with Directorate General for Environment (DG ENV) in an initiative aimed at engaging experts to design and produce eLearning modules to provide interactive instruction to students and professionals involved in lab animal use.

To reach early career scientists, the JRC organised Summer Schools on non-animal approaches in science in 2017 and 2019. Similar activities and initiatives are ongoing in the USA and in Canada.

Read more in:

Herrmann K, Pistollato F, Stephens ML. Beyond the 3Rs: Expanding the use of human-relevant replacement methods in biomedical research. ALTEX. 2019;36(3):343-352.

DOI: 10.14573/altex.1907031

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Beyond the 3Rs: Expanding the use of human-relevant replacement methods in biomedical research