The use of animals in physiological science: the past, the presence, and the future.

Physiology is a scientific discipline of how people's and animals' bodies function that requires traditionally suitable experimental models that often rely on animals. However, at the end of the 50th of the last century, researchers themselves addressed concerns about the use of animals for biomedical science and physiology in particular. At that time, the so-called 3R strategy was implicated where the three "R" stand for replacement, reduction, and refinement. When addressing these concerns, researchers nevertheless realized that a critical dispute about experimental models in the light of the 3R initiative may require further attention to other points such as robustness, registration, reporting, reproducibility, and rigor of the work. The question that has to be addressed now is first whether the use of animals in physiology changed in the post-3R period, whether it led to a replacement, reduction, or refinement of animal handling, and most importantly, how this affected the scientific progress in (patho)physiology. In order to address open questions concerning the relationship between the use of animals and physiological research, complete volumes of the Pflügers Archiv - European Journal of Physiology were analyzed every 10 years starting in 1950 and ending in 2020 and compared to volumes of the Journal of Physiology. It analyzed how scientists organize their projects published in the journal and what kind of models they used. The results show that physiological science has dramatically changed in the last 70 years. Replacement, reduction, and refinement were achieved to a certain level. However, during the last years, no further achievement could be seen. It seems that a certain level of animal testing is required for biomedical science and physiology in particular. Physiological studies in the present time are dominated by investigation of the physiological function of small rodents mainly mice and rats with only a few exceptions. The analysis also shows that in the future, researchers must have a critical look at further requirements of their research such as data robustness, improvement of reproducibility of data, and generation of rigor data as a prerequisite to improve our physiological view on life.