Animal models are essential to biological research: issues and perspectives

The use of animals for scientific purposes is both a longstanding practice in biological research and medicine, and a frequent matter of debate in our societies. The remarkable anatomical and physiological similarities between humans and animals, particularly mammals, have prompted researchers to investigate a large range of mechanisms and assess novel therapies in animal models before applying their discoveries to humans. However, not all results obtained on animals can be directly translated to humans, and this observation is emphasized by those who refute any value to animal research. At the same time, the place of the animals in our modern societies is often debated, particularly the right to use animals to benefit human purposes, with the possibility that animals are harmed. These two aspects are often mixed in confusing arguments, which does not help citizens and politicians to get a clear picture of the issues. This has been the case in particular during the evaluation of the European Citizen Initiative (ECI) ‘Stop Vivisection’ recently presented to the E uropean Commission [1]. Humans and other mammals are very complex organisms in which organs achieve distinct physiological functions in a highly integrated and regulated fashion. Relationships involve a complex network of hormones, circulating factors and cells and cross-talk between cells in all the compartments. Biologists interrogate organisms at multiple levels: molecules, cells, organs and physiological functions, in healthy or diseased conditions. All levels of investigations are required to get a full description and understanding of the mechanisms. The first two, and in some instances three, levels of organization can be studied using in vitro approaches (e.g., cell culture). These techniques have become very sophisticated to mimic the 3D and complex structures of tissues. They represent major scientific advances and they have replaced the use of animals. On the other hand, the exploration of physiological functions and systemic interactions between organs requires a whole organism. It is, for example, the case for most hormonal regulations, for the dissemination of microorganisms during infectious diseases or for the influence of the intestinal microorganisms on immune defense or on the development of brain functions. In these many cases, no in vitro model is currently available to fully recapitulate these interactions, and investigations on humans and animals are still necessary. Hypotheses and models can emerge from in vitro studies but they must be tested and validated in a whole organism, otherwise they remain speculative. Scientists are very far from being able to predict the functioning of a complex organism from the study of separate cells, tissues and organs. Therefore, despite arguments put forward by the promotors of the ECI, studies on animals cannot be fully replaced by in vitro methods, and it is still a long way before they can. Animal models have been used to address a variety of scientific questions, from basic science to the development and assessment of novel vaccines, or therapies. The use of animals is not only based on the vast commonalities in the biology of most mammals, Opinion