Evolutionary Medicine: Expanding the Insights from Animal Models

An evolutionary perspective is increasingly being embraced in medicine and is now considered essential for a comprehensive understanding of disease. This perspective has important potential applications in both basic biomedical research and drug development as much of what is known about human disease mechanisms has been learned from the study of animal models. However, since animal models have been developed almost solely based on their similarities to human clinical and tissue pathology, the evolutionary influences determining animal disease phenotypes and why and how they are different from the human have rarely been considered. Because of this focus on similarities, animal models have not been utilized to their full potential. This has contributed to a serious ‘prediction problem,’ which is the failure of animal studies to suitably predict human responses. Another important factor in the prediction problem is that the current disease definitions do not reflect the genetic/molecular complexity underlying disease phenotypes. Diseases have predominantly been classified and studied based upon observable findings including: clinical signs and symptoms, pathology, and response to treatment. Currently advances in technology are allowing genotypic and bioinformatic information to also be incorporated into disease definitions. While this shifting paradigm is leading to a more evolution‐based approach to medicine that will ultimately enhance our understanding of what constitutes ‘health’ and ‘disease’, it is also having a major impact on how animal models are developed and studied. For example, several (in mice often numerous), genetic/molecular changes have been found to produce the same clinical signs and tissue pathology in animals and humans. An important implication of this is that many animal models are more uniform in mechanism than the human diseases they are modeling, and treatments effective in animal models should ideally be tested in the subset of human patients affected through the same genetic/molecular disease mechanisms, not all those with the disease phenotype. Thus, some treatments developed using animal models that fail in the human general disease population and are abandoned may not necessarily be ineffective, while others that are ineffective in the animal models might have efficacy in humans. Evolutionary medicine provides the perspective needed to fully develop the potential and improve the predictive value of animal models. In particular the development of a cross‐species, evolution‐based understanding of disease would improve diagnoses and identify novel therapeutic and preventive interventions for both human and veterinary medicine.