EDITORIAL RESEARCH Evolutionary medicine In recognition that evolutionary theory is critical for understanding modern human health, eLife is publishing a special issue on evolutionary medicine to showcase recent research in this growing and increasingly interdisciplinary field. GEORGE H PERRY ur individual and collective health is One area of particularly active research is O shaped and affected by many factors. studying how various pathogens and parasites These factors include our environ- evolve within and among human hosts, between ment, our inherited and somatic genetic var- human and non-human hosts and/or vectors, iants, our variable exposure to pathogens, our and in response to drug treatments. Work on diets and lifestyles, our social systems, and our the evolution of bacterial pathogen resistance to cultural innovations. antibiotics (Bakkeren et al., 2020), virus resis- None of these factors are static, and they all tance to antivirals (Irwin et al., 2016), fungal interact with each other. Human genetic adapta- resistance to antifungals (Robbins et al., 2017), tions to our past environments, disease burdens, and parasite resistance to other antimicrobials and cultural practices can affect disease risks (e.g., Haldar et al., 2018) is understandably today, especially if any of the underlying envi- prominent. Yet the evolutionary forces of muta- ronmental, disease, or cultural factors have tion, genetic drift and gene flow (including that changed in the interim. Meanwhile, human mediated by human host, animal host, and pathogens and parasites continually adapt to insect vectors movement and behavior), and the our biology and to cultural innovations, including interplay between these forces and human advances in medicine, the development of new immunity, are also critical components of human drugs, and infrastructure improvements (such infectious disease dynamics. water-treatment plants or the availability of mos- Basic and applied questions in this area of quito nets). The progression of cancer within an evolutionary medicine research include: How individual is also often viewed as an evolutionary does resistance develop and spread? How process (Merlo et al., 2006). repeatable is it (Igler et al., 2021)? What cul- Growing numbers of scientists are applying tural factors – beyond the drug treatment itself – evolutionary theory to study these interactions play major roles in this process? How does resis- across different timescales and their impacts on tance evolve in multiple drug treatment scenar- modern human health, including with predictions ios (McLeod and Gandon, 2021), and what are of how our health might be affected by these the interaction effects with co-occurring patho- processes in the future and how we can take gens? What are the best practices for treating informed action. This field of study is known as Copyright Perry. This article is patients, given this knowledge (Morley et al., distributed under the terms of the evolutionary medicine (Stearns and Medzhitov, 2020)? What features of newly designed drugs Creative Commons Attribution 2015). To help set the stage for a special issue License, which permits unrestricted are optimal in the face of these evolutionary pro- of eLife on evolutionary medicine, I will highlight use and redistribution provided that cesses? How do other evolutionary forces acting a subset of concepts and research approaches in the original author and source are on our pathogens impact human health, credited. this field. Perry. eLife 2021;10:e69398. DOI: https://doi.org/10.7554/eLife.69398 1 of 4 Editorial Research Evolutionary medicine separately and in combination with resistance When a genetic signature of positive selec- evolution (D’Aeth, 2021; Huddleston et al., tion for an allele (or set of alleles) associated 2020)? with an increased risk of a disease is identified Taking a longer-term view, many people (see, for example, Clemente et al., 2014 and today live in environments that are markedly dif- Richard et al., 2020), scientists can assess ferent from those of their ancestors. This may whether evolutionary mismatch, pleiotropic reflect histories of migration or forced transport, trade-off, or both are involved. By then consider- climate change, and/or cultural change (such as ing the shifting environmental context shifts from hunting and gathering to subsistence (Byars et al., 2017; Zhang and Gems, 2021) or agriculture, and to industrialization). Evolution- the molecular mechanisms and epidemiology of ary ‘mismatch’ is the phenomenon whereby linked diseases, our knowledge of disease biol- genetic variants that were adaptive in the past ogy, potential treatment pathways, and interven- are now associated with an increased risk of dis- tion approaches can grow in compounded ease in the context of one’s current environment fashion. (Manus, 2018). Evolutionary mismatch as an Evolutionary medicine research with diverse appropriately cautious concept has validity and human groups can be broadly informative as this idea has motivated promising gene by envi- each local population has its own eco-evolution- ronment interaction research (Benton et al., ary history and potentially distinct biological 2021). adaptations. For example, an allele that was However, it is important to keep in mind that likely driven by positive selection to relatively evolutionary processes are continuous. That is, high frequencies in Polynesians – but is rare or our individual genomes reflect complex histories absent in other populations – is associated with of past adaptation and genetic drift across many a substantially increased risk of obesity but a time periods. This means that connections decreased risk of type II diabetes, which is in between past evolutionary ecology, subsequent contrast to what we would expect based on typi- environmental change, and modern health are cal risk factor relationships (Krishnan et al., not always straightforward. Take the example of 2018; Minster et al., 2016). A more complete diet: some argue that for optimal health modern understanding of the underlying biological path- humans should follow a ‘paleo diet’ (which is way in this case could lead to new strategies for focused on consuming meat, fish, fruit and vege- treating type II diabetes. tables, and on avoiding grains, dairy products In principle, worldwide participation in scien- and processed foods). However, there is exten- tific research and expansive sharing in its bene- sive scientific evidence of ongoing human bio- fits can improve equity. However, researchers logical adaptations in response to post-‘paleo’ must pay attention to important ethical consid- diet-related cultural changes (Chang and Now- erations, especially when partnering with Indige- ell, 2016; Zuk, 2013), contradicting the absolut- nous populations (Hernandez and Perry, 2021). ism of the paleo diet industry. In particular, efforts should be made to ensure Meanwhile, genetic variants that may have that communities are fairly compensated and been subjected to positive selection in the past receive other longer-term benefits related to the because they reduced the risk or severity of one knowledge and any new treatments that are disease may simultaneously confer increased risk developed on the basis of their participation for other diseases (Williams, 1957; Byars et al., (Fox, 2020). 2017). As an example of such a ’pleiotropic Another strand of research within evolution- trade-off’, variants in a human gene called ary medicine is the use of comparative phyloge- APOL1 confer resistance to infection by Trypa- nomic and experimental approaches to uncover nosoma brucei parasites that cause African the mechanisms responsible for naturally occur- sleeping sickness. These APOL1 variants are ring variation among diverse animal taxa to help associated with strong signatures of past posi- advance our understanding of human health. For tive selection in some African populations. How- example, we might expect cancer risk to be pos- ever, the same alleles are also associated with itively correlated with body size and lifespan: an increased risk for kidney disease in African this is true within species, but not between spe- Americans (Cooper et al., 2017; cies. One article in the special issue examines Genovese et al., 2010). the duplication of tumor suppressor genes in Perry. eLife 2021;10:e69398. DOI: https://doi.org/10.7554/eLife.69398 2 of 4 Editorial Research Evolutionary medicine elephants (which have relatively low cancer risk) [email protected] and related, smaller-bodied mammals https://orcid.org/0000-0003-4527-3806 (Vazquez and Lynch, 2021). Other researchers Competing interests: The author declares that no have explored the molecular underpinnings of competing interests exist. unexpected (relative to body size) longevity in Published 22 July 2021 bats (Seim et al., 2013), and oxidative stress resistance and longevity in naked mole rats References (Fang et al., 2014; Kim et al., 2011; Bakkeren E, Diard M, Hardt W-D. 2020. Evolutionary Takasugi et al., 2020). causes and consequences of bacterial antibiotic persistence. Nature Reviews Microbiology 18:479–490. Given that research in evolutionary medicine DOI: https://doi.org/10.1038/s41579-020-0378-z can involve the intersection of human health, cul- Benton ML, Abraham A, LaBella AL, Abbot P, Rokas tural diversity, bioethics, broad organismal biol- A, Capra JA. 2021. The influence of evolutionary ogy, pharmacokinetics, environmental science, history on human health and disease. Nature Reviews short-to-long