The future of evolutionary medicine: sparking innovation in biomedicine and public health.

Evolutionary medicine - i.e. the application of insights from evolution and ecology to biomedicine - has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health. Fundamentally, a systematic mapping across the full diversity of life is required to identify animal model systems for disease vulnerability, resistance, and counter-resistance that could lead to novel clinical treatments. Evolutionary dynamics should guide novel therapeutic approaches that target the development of treatment resistance in cancers (e.g., via adaptive or extinction therapy) and antimicrobial resistance (e.g., via innovations in chemistry, antimicrobial usage, and phage therapy). With respect to public health, the insight that many modern human pathologies (e.g., obesity) result from mismatches between the ecologies in which we evolved and our modern environments has important implications for disease prevention. Life-history evolution can also shed important light on patterns of disease burden, for example in reproductive health. Experience during the COVID-19 (SARS-CoV-2) pandemic has underlined the critical role of evolutionary dynamics (e.g., with respect to virulence and transmissibility) in predicting and managing this and future pandemics, and in using evolutionary principles to understand and address aspects of human behavior that impede biomedical innovation and public health (e.g., unhealthy behaviors and vaccine hesitancy). In conclusion, greater interdisciplinary collaboration is vital to systematically leverage the insight-generating power of evolutionary medicine to better understand, prevent, and treat existing and emerging threats to human, animal, and planetary health.

Cataracts Across the Tree of Life: A Roadmap for Prevention and Biomedical Innovation.

PURPOSE: Spontaneous cataracts have been identified in the lenses of animals across a phylogenetically wide range of species. This can be a source of insights and innovation for human health professionals, but many persons may lack awareness of it. By providing a phylogenetic survey and analysis of species with cataract vulnerability, this paper demonstrates how a broad comparative perspective can provide critical information about environmental hazards to human visual health and can spark potential innovations in the prevention and treatment of cataracts in humans. DESIGN: Perspectives. METHODS: Review and synthesis of selected literature with interpretation and perspective. RESULTS: We found 273 recorded cases of spontaneously occurring cataracts in 113 species of birds, 83 species of mammals, 30 species of actinopterygii fish, 10 species of amphibians, 6 species of reptiles, and 1 species of cephalopod. CONCLUSION: A phylogenetically wide range of species, including many living in and around human environments, are vulnerable to cataracts. These animals may serve as sentinels for human visual health. Variation in cataract vulnerability across species may also facilitate the identification of resistance-conferring physiologies, leading to accelerated innovation in the prevention and treatment of cataracts in humans.

Glaucoma through Animal's Eyes: Insights from the Evolution of Intraocular Pressure in Mammals and Birds.

Glaucoma, an eye disorder caused by elevated intraocular pressure (IOP), is the leading cause of irreversible blindness in humans. Understanding how IOP levels have evolved across animal species could shed light on the nature of human vulnerability to glaucoma. Here, we studied the evolution of IOP in mammals and birds and explored its life history correlates. We conducted a systematic review, to create a dataset of species-specific IOP levels and reconstructed the ancestral states of IOP using three models of evolution (Brownian, Early burst, and Ornstein-Uhlenbeck (OU)) to understand the evolution of glaucoma. Furthermore, we tested the association between life history traits (e.g., body mass, blood pressure, diet, longevity, and habitat) and IOP using phylogenetic generalized least squares (PGLS). IOP in mammals and birds evolved under the OU model, suggesting stabilizing selection toward an optimal value. Larger mammals had higher IOPs and aquatic birds had higher IOPs; no other measured life history traits, the type of tonometer used, or whether the animal was sedated when measuring IOP explained the significant variation in IOP in this dataset. Elevated IOP, which could result from physiological and anatomical processes, evolved multiple times in mammals and birds. However, we do not understand how species with high IOP avoid glaucoma. While we found very few associations between life history traits and IOP, we suggest that more detailed studies may help identify mechanisms by which IOP is decoupled from glaucoma. Importantly, species with higher IOPs (cetaceans, pinnipeds, and rhinoceros) could be good model systems for studying glaucoma-resistant adaptations.

Female Health Across the Tree of Life: Insights at the Intersection of Women's Health, One Health and Planetary Health.

Across the tree of life, female animals share biological characteristics that place them at risk for similar diseases and disorders. Greater awareness of these shared vulnerabilities can accelerate insight and innovation in women's health. We present a broadly comparative approach to female health that can inform issues ranging from mammary, ovarian, and endometrial cancer to preeclampsia, osteoporosis, and infertility. Our focus on female health highlights the interdependence of human, animal, and environmental health. As the boundaries between human and animal environments become blurred, female animals across species are exposed to increasingly similar environmental hazards. As such, the health of female animals has unprecedented relevance to the field of woman's health. Expanding surveillance of animal populations beyond zoonoses to include noncommunicable diseases can strengthen women's health prevention efforts as environmental factors are increasingly implicated in human mortality. The physiology of nonhuman females can also spark innovation in women's health. There is growing interest in those species of which the females appear to have a level of resistance to pathologies that claim millions of human lives every year. These physiologic adaptations highlight the importance of biodiversity to human health. Insights at the intersection of women's health and planetary health can be a rich source of innovations benefitting the health of all animals across the tree of life.

Stress, Subordination, and Anomalies of Feeding Across the Tree of Life: Implications for Interpreting Human Eating Disorders.

Eating behaviors of animals living in naturalistic environments offer unique insights into several dysregulated eating patterns observed in humans. Social subordination is a known precipitant of hyperphagia and hypophagia in human beings, and examples of similar responses have been identified in a phylogenetically widespread range of vertebral species. This points to potentially conserved, patterned responses to animals navigating lives within social hierarchies. Self-imposed food restriction in subordinate fish and hyperphagic responses in socially subordinated bird and primate individuals may represent evolved adaptations to the stress of social subordination. As such, hyperphagic and hypophagic responses to social subordination in these species may model the natural history, neurobiology, and behavioral ecology of human dieting and bingeing more accurately than some current animal models. Phylogenetically widespread similarities in eating patterns under the stress of social subordination point to potentially shared biological benefits of these behaviors across species and the role of evolutionary trade-offs, adaptations, and other processes in shaping them. The application of a broadly comparative lens to disordered eating behaviors in other species exposes important similarities and differences between neurophysiology of eating across species. In doing so, it highlights the value of phylogenetic analyses and macroevolution as tools for identifying novel, naturally occurring models for understanding disordered human eating. Moreover, this approach introduces the intriguing possibility that human cultural influences on disordered eating may have far more ancient origins than previously considered.

Biomimetics - Nature's roadmap to insights and solutions for burden of lifestyle diseases.

There are over 8 million species in this world that live in widely varying environments, from hot thermal fissures to cold arctic settings. These species have evolved over millions of years and vary markedly in how they have adapted to their environments. In the last decades, studies of how species have succeeded in surviving in different environments and with different resources have been recognized to provide not only insights into disease but also novel means for developing treatments. Here, we provide an overview of two related and overlapping approaches (biomimetics and zoobiquity), which are turning to the natural world for insights to better understand, treat and prevent human 'burden of lifestyle' pathologies from heart disease and cancer to degeneration and premature ageing. We suggest that expanding biomedical investigation beyond its decades old conventional practices to new approaches based on a broad awareness of the diversity of animal life and comparative physiology can accelerate innovations in health care under the motto 'Nature knows best'.