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

Manipulating the exposome to enable better ageing

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic approach that will provide insight into how evolution through natural selection in other species has solved many age related human health issues. In particular, we will emphasise the need to reconnect a more mechanistic approach to medical science with a broader natural sciences approach, using biomimetics to mitigate the global burden of age related ill health. In particular, we will discuss how such an approach indicates leverage of the activities of the Nrf 2 gene to enhance health span via reintroduction of the classical 'Food as Medicine' concept, including modulation of the microbiome and the creation of more salutogenic and biophilic environments. Additionally, we will discuss how this approach integrates with novel and developing senotherapies

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)-a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF

A Blueprint to Evaluate One Health

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the “Network for Evaluation of One Health,” an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy

Incorporating one health into medical education

One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers

A Physician’s View of One Health: Challenges and Opportunities

One Health is one of the most important movements and emerging concepts in health today. The convergence of the fields of human and animal medicine has the potential to generate novel scientific hypotheses, create effective new therapies and potentially transform how physicians, veterinarians and their patients understand health and disease. Despite this potential, One Health has not yet gained significant awareness or traction in human medical communities. From its inception, One Health, sometimes also called One Medicine, has been piloted primarily by leaders from the world of veterinary medicine. Although the specific term was coined perhaps 10 years ago, comparative medicine has been quietly evident on university campuses with veterinary and medical schools for decades longer. Although a few physicians have played major leadership roles in One Health, in the United States, despite over ten years of the movement’s robust growth, many have still not heard of it. Furthermore, physicians with some awareness of One Health often believe it to be primarily and exclusively about zoonotic infections and global health. The much broader scope and potential of One Health as also including comparative physiology and medicine is not being communicated effectively. Consequently, the human medical community remains largely disengaged. This is problematic because without significant engagement from physicians, nurses and other human health care professionals, the potential of One Health cannot be realized. To advance One Health it is imperative that we first understand the roots of under-engagement of the human medical community. This, in turn, can guide the development of novel and engaging opportunities for physician which demonstrate the power relevance of One Health’s comparative, collaborative and cooperative approach.[...

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

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

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