An evolutionary perspective for integrating mechanisms of acupuncture therapy.

This study applies an evolutionary medicine perspective to comprehend the therapeutic effects of acupuncture. It draws upon modern evolutionary theory to integrate the currently fragmented theories regarding the efficacy of acupuncture in alleviating pain and promoting healing. We explore the interaction between the nervous and immune systems in the context of survival and homeostasis, and elucidate both the local and systemic effects of acupuncture therapy on pain relief and tissue healing. The mechanisms involved are categorized into two main types: local effects, which include immune cell migration, local vasodilation, and the release of adenosine; and distal systemic effects, which involve the regulation of the descending pain control system and the autonomic nervous system, with a particular focus on the parasympathetic nervous system. In conclusion, this integrated perspective not only deepens our understanding of acupuncture within a scientific narrative but also underscores the need for further research to validate and expand our knowledge, thereby enhancing its scientific credibility and clinical applicability.

Egg donation and gestational surrogacy: Pregnancy is riskier with an unrelated embryo.

Modern medicine has revolutionized family planning. Remarkably, women1 can carry to term embryos with whom they share no genetic connection, a feat made possible through egg donation and/or gestational surrogacy. Our reproductive systems evolved to accommodate embryos that are 50% related to the carrier, not 0% related. Here, we apply evolutionary theory to explain how and why pregnancy is riskier with an unrelated embryo. When a woman gestates an unrelated embryo, she is significantly more likely to develop preeclampsia and other diseases above and beyond the known risks associated with advanced maternal age, IVF, multiple gestation, and subfertility. Such "allogeneic pregnancies" are riskier even in fertile, healthy, commercial surrogates and when the egg is donated by a young, healthy donor. We propose that unrelated embryos present a special immune challenge to the gestational carrier, because they have fewer matching genes to the maternal body-therefore exacerbating symptoms of evolutionary maternal-fetal conflict. Indeed, maternal risks seem lower when the embryo is more related to the carrier, e.g., if a sister donates the egg. Finally, we discuss microchimerism in egg donation pregnancies, whereby wholly foreign cells pass from mother to embryo and vice-versa. We conclude with several medical proposals. First, egg donors and surrogates should be informed of the increased health risks they would face. In considerations of risk, these young, fertile women should not be compared to older, infertile women undergoing IVF; the proper comparison group is other young, fertile women. Second, contrary to some medical advice, perhaps genetically-related egg donors and surrogates should be preferred, all else equal. An immunological matching scheme, like what is used for organ transplants, could improve surrogate pregnancy outcomes. Third, more research is needed on microchimerism, sperm exposure, and the long-term impacts of allogeneic pregnancies on maternal and child health.

Learning from disability studies to introduce the role of the individual to naturalistic accounts of disease.

Disability studies have been successfully focusing on individuals' lived experiences, the personalization of goals, and the constitution of the individual in defining disease and restructuring public understandings of disability. Although they had a strong influence in the policy making and medical modeling of disease, their framework has not been translated to traditional naturalistic accounts of disease. I will argue that, using new developments in evolutionary biology (Extended Evolutionary Synthesis [EES] about questions of proper function) and behavioral ecology (Niche conformance and construction about the questions of reference classes in biostatistics accounts), the main elements of the framework of disability studies can be used to represent life histories at the conceptual level of the two main "non-normative" accounts of disease. I chose these accounts since they are related to medicine in a more descriptive way. The success of the practical aspects of disability studies this way will be communicated without causing injustice to the individual since they will represent the individuality of the patient in two main naturalistic accounts of disease: the biostatistical account and the evolutionary functional account. Although most accounts criticizing the concept of disease as value-laden do not supply a positive element, disability studies can supply a good point for descriptive extension of the concept through inclusion of epistemic agency.

A burden shared: The evolutionary case for studying human deafness in Drosophila.

Hearing impairment is the most prevalent sensory disease in humans and can have dramatic effects on the development, and preservation, of our cognitive abilities and social interactions. Currently 20 % of the world's population suffer from a form of hearing impairment; this is predicted to rise to 25 % by 2050. Despite this staggering disease load, and the vast damage it inflicts on the social, medical and economic fabric of humankind, our ability to predict, or prevent, the loss of hearing is very poor indeed. We here make the case for a paradigm shift in our approach to studying deafness. By exploiting more forcefully the molecular-genetic conservation between human hearing and hearing in morphologically distinct models, such as the fruit fly Drosophila melanogaster, we believe, a deeper understanding of hearing and deafness can be achieved. An understanding that moves beyond the surface of the 'deafness genes' to probe the underlying bedrock of hearing, which is shared across taxa, and partly shared across modalities. When it comes to understanding the workings (and failings) of human sensory function, a simple fruit fly has a lot to offer and a fly eye might sometimes be a powerful model for a human ear. Particularly the use of fly avatars, in which specific molecular (genetic or proteomic) states of humans (e.g. specific patients) are experimentally reproduced, in order to study the corresponding molecular mechanisms (e.g. specific diseases) in a controlled yet naturalistic environment, is a tool that promises multiple unprecedented insights. The use of the fly - and fly avatars - would benefit humans and will help enhance the power of other scientific models, such as the mouse.

The Role of Selection and Migration in the Evolution of (Auto)Immunity Genes.

The genetic architecture of multiple sclerosis is complicated. Additionally, the disease incidence varies per population or per geographical region. A recent study gives convincing explanations about the north-south incidence gradient of multiple sclerosis in Europe, by analyzing ancient and modern human genomes. Interestingly, the evidence shows that multiple sclerosis associated immunogenetic variants underwent positive selection in Asian and European populations. Lifestyle and pathogen infections probably shaped the overall multiple sclerosis risk. These results complete the findings of previous studies that showed that a high percentage of the autoimmunity associated genetic variants are under selection pressure.

A seven-step guide to spatial, agent-based modelling of tumour evolution.

Spatial agent-based models are frequently used to investigate the evolution of solid tumours subject to localized cell-cell interactions and microenvironmental heterogeneity. As spatial genomic, transcriptomic and proteomic technologies gain traction, spatial computational models are predicted to become ever more necessary for making sense of complex clinical and experimental data sets, for predicting clinical outcomes, and for optimizing treatment strategies. Here we present a non-technical step by step guide to developing such a model from first principles. Stressing the importance of tailoring the model structure to that of the biological system, we describe methods of increasing complexity, from the basic Eden growth model up to off-lattice simulations with diffusible factors. We examine choices that unavoidably arise in model design, such as implementation, parameterization, visualization and reproducibility. Each topic is illustrated with examples drawn from recent research studies and state of the art modelling platforms. We emphasize the benefits of simpler models that aim to match the complexity of the phenomena of interest, rather than that of the entire biological system. Our guide is aimed at both aspiring modellers and other biologists and oncologists who wish to understand the assumptions and limitations of the models on which major cancer studies now so often depend.

Structurally divergent and recurrently mutated regions of primate genomes.

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Evolution of the human birth canal.

It seems puzzling why humans have evolved such a small and rigid birth canal that entails a relatively complex process of labor compared with the birth canal of our closest relatives, the great apes. This study reviewed insights into the evolution of the human birth canal from recent theoretical and empirical studies and discussed connections to obstetrics, gynecology, and orthopedics. Originating from the evolution of bipedality and the large human brain million years ago, the evolution of the human birth canal has been characterized by complex trade-off dynamics among multiple biological, environmental, and sociocultural factors. The long-held notion that a wider pelvis has not evolved because it would be disadvantageous for bipedal locomotion has not yet been empirically verified. However, recent clinical and biomechanical studies suggest that a larger birth canal would compromise pelvic floor stability and increase the risk of incontinence and pelvic organ prolapse. Several mammals have neonates that are equally large or even larger than human neonates compared to the size of the maternal birth canal. In these species, the pubic symphysis opens widely to allow successful delivery. Biomechanical and developmental constraints imposed by bipedality have hindered this evolutionary solution in humans and led to the comparatively rigid pelvic girdle in pregnant women. Mathematical models have shown why the evolutionary compromise to these antagonistic selective factors inevitably involves a certain rate of fetopelvic disproportion. In addition, these models predict that cesarean deliveries have disrupted the evolutionary equilibrium and led to new and ongoing evolutionary changes. Different forms of assisted birth have existed since the stone age and have become an integral part of human reproduction. Paradoxically, by buffering selection, they may also have hindered the evolution of a larger birth canal. Many of the biological, environmental, and sociocultural factors that have influenced the evolution of the human birth canal vary globally and are subject to ongoing transitions. These differences may have contributed to the global variation in the form of the birth canal and the difficulty of labor, and they likely continue to change human reproductive anatomy.

The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence.

How has schizophrenia, a condition that significantly reduces an individual's evolutionary fitness, remained common across generations and cultures? Numerous theories about the evolution of schizophrenia have been proposed, most of which are not consistent with modern epidemiological and genetic evidence. Here, we briefly review this evidence and explore the cliff edge model of schizophrenia. It suggests that schizophrenia is the extreme manifestation of a polygenic trait or a combination of traits that, within a normal range of variation, confer cognitive, linguistic, and/or social advantages. Only beyond a certain threshold, these traits precipitate the onset of schizophrenia and reduce fitness. We provide the first mathematical model of this qualitative concept and show that it requires only very weak positive selection of the underlying trait(s) to explain today's schizophrenia prevalence. This prediction, along with expectations about the effect size of schizophrenia risk alleles, are surprisingly well matched by empirical evidence. The cliff edge model predicts a dynamic change of selection of risk alleles, which explains the contradictory findings of evolutionary genetic studies.

Evolutionary medicine approaches to chronic disease: The case of irritable bowel syndrome.

Irritable bowel syndrome (IBS), a gastrointestinal disease, is a global phenomenon correlated with industrialization. We propose that an evolutionary medicine approach is useful to understand this disease from an ultimate perspective and conducted a scoping literature review to synthesize the IBS literature within this framework. Our review suggests five potential evolutionary hypotheses for the cause of IBS, including (a) a dietary mismatch accompanying a nutritional transition, (b) an early hygienic life environment leading to the immune system and microbiotic changes, (c) an outcome of decreased physical activity, (d) a response to changes in environmental light-dark cycles, and (e) an artifact of an evolved fight or flight response. We find key limitations in the available data needed to understand early life, nutritional, and socioeconomic experiences that would allow us to understand evolutionarily relevant risk factors and identify a need for further empirical research to distinguish potential causes and test evolutionary hypotheses.

Integrating microbiome science and evolutionary medicine into animal health and conservation.

Microbiome science has provided groundbreaking insights into human and animal health. Similarly, evolutionary medicine - the incorporation of eco-evolutionary concepts into primarily human medical theory and practice - is increasingly recognised for its novel perspectives on modern diseases. Studies of host-microbe relationships have been expanded beyond humans to include a wide range of animal taxa, adding new facets to our understanding of animal ecology, evolution, behaviour, and health. In this review, we propose that a broader application of evolutionary medicine, combined with microbiome science, can provide valuable and innovative perspectives on animal care and conservation. First, we draw on classic ecological principles, such as alternative stable states, to propose an eco-evolutionary framework for understanding variation in animal microbiomes and their role in animal health and wellbeing. With a focus on mammalian gut microbiomes, we apply this framework to populations of animals under human care, with particular relevance to the many animal species that suffer diseases linked to gut microbial dysfunction (e.g. gut distress and infection, autoimmune disorders, obesity). We discuss diet and microbial landscapes (i.e. the microbes in the animal's external environment), as two factors that are (i) proposed to represent evolutionary mismatches for captive animals, (ii) linked to gut microbiome structure and function, and (iii) potentially best understood from an evolutionary medicine perspective. Keeping within our evolutionary framework, we highlight the potential benefits - and pitfalls - of modern microbial therapies, such as pre- and probiotics, faecal microbiota transplants, and microbial rewilding. We discuss the limited, yet growing, empirical evidence for the use of microbial therapies to modulate animal gut microbiomes beneficially. Interspersed throughout, we propose 12 actionable steps, grounded in evolutionary medicine, that can be applied to practical animal care and management. We encourage that these actionable steps be paired with integration of eco-evolutionary perspectives into our definitions of appropriate animal care standards. The evolutionary perspectives proposed herein may be best appreciated when applied to the broad diversity of species under human care, rather than when solely focused on humans. We urge animal care professionals, veterinarians, nutritionists, scientists, and others to collaborate on these efforts, allowing for simultaneous care of animal patients and the generation of valuable empirical data.

Human behaviors driving disease emergence.

Interactions between humans, animals, and the environment facilitate zoonotic spillover-the transmission of pathogens from animals to humans. Narratives that cast modern humans as exogenous and disruptive forces that encroach upon "natural" disease systems limit our understanding of human drivers of disease. This review leverages theory from evolutionary anthropology that situates humans as functional components of disease ecologies, to argue that human adaptive strategies to resource acquisition shape predictable patterns of high-risk human-animal interactions, (2) humans construct ecological processes that facilitate spillover, and (3) contemporary patterns of epidemiological risk are emergent properties of interactions between human foraging ecology and niche construction. In turn, disease ecology serves as an important vehicle to link what some cast as opposing bodies of theory in human ecology. Disease control measures should consider human drivers of disease as rational, adaptive, and dynamic and capitalize on our capacity to influence ecological processes to mitigate risk.

Long-term evolution of antibiotic tolerance in Pseudomonas aeruginosa lung infections.

Pathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as tolerance. While a variety of resistance mechanisms and underlying genetics are well characterized in vitro and in vivo, an understanding of the evolution of tolerance, and how it interacts with resistance in situ is lacking. We assayed for tolerance and resistance in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to 40 years of evolution, with 3 clinically relevant antibiotics: meropenem, ciprofloxacin, and tobramycin. We present evidence that tolerance is under positive selection in the lung and that it can act as an evolutionary stepping stone to resistance. However, by examining evolutionary patterns across multiple patients in different clone types, a key result is that the potential for an association between the evolution of resistance and tolerance is not inevitable, and difficult to predict.

Spatial simulation of autologous cell defection for cancer treatment.

Cancer cells are highly cooperative in a nepotistic way and evolutionarily dynamic. Present cancer treatments often overlook these aspects, inducing the selection of resistant cancer cells and the corresponding relapse. As an alternative method of cancer elimination, autologous cell defection (ACD) was suggested by which modified cancer cells parasitically reliant on other cancer cells are implemented to the cancer cluster. Specifically, modified cancer cells should not produce costly growth factors that promote the growth of other cancer cells while receiving the benefit of exposure to such growth factors. Analytical models and rudimentary experiments up to date provide the medical feasibility of this method. In this study, I built comprehensive spatial simulation models by embracing the effects of the multiple growth factors, the Warburg effect, mutations and immunity. The simulation results based on planar spatial structures indicate that implementation of the defective modified tumours may replace the existing cancer cluster and defective cells would later collapse by themselves. Furthermore, I built a mathematical model that compares the fitness of the cells adjacent to the hypertumour-cancer interface. I also calculated whether anticancer drugs that reduce the effects of the growth factors promote or demote the utility of ACD under diverse fitness functions. The computational examination implies that anticancer drugs may impede the therapeutic effect of ACD when there is a strong concavity in the fitness function. The analysis results could work as a general guidance for effective ACD that may expand the paradigm of cancer treatment.

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.

Using evolutionary principles to make clinical decisions: a case series of urinary tract infections.

The principles of evolutionary medicine have significant potential to be useful in a wide variety of clinical situations. Despite this, few demonstrations of clinical applications exist. To address this paucity, a case series applying evolutionary medicine principles to urinary tract infections, a common medical condition is presented. This series demonstrates how applying evolutionary medicine principles can be used to augment clinical decision-making.

Evolution and disease.

This essay questions evolutionary or Darwinian medicine for its uncritical adherence to evolutionary theory to explain diseases, which leaves aside the very vital process that transformed an "inert planet" into a "living one" where the nascent biological order subordinated the physicochemical one to prevail. The biological order is comparable to an "infinitely diverse harmonic concert", which has created and recreated, for eons, the environments conducive to its own permanence and evolution. The arrival of homo sapiens meant the cultural order emergence, which progressively supplanted, in its effects, the biological order by causing drastic and vertiginous changes in the planetary ecosystem that silenced the evolutionary process "without time to manifest". Adaptation as an ability to overcome adverse situations is a non-sense in the "harmonic concert"; instead, it is characteristic of the cultural order that imposes inhospitable and stressful environments on humans as inescapable adaptive demands. The vital quality of the biological order is the sequential anticipation of situations of interaction with significant objects in the environment, which enables the consummation of basic vital activities, emblematic of the state of maturity of living beings. To think that evolution explains chronic diseases is not only illusory but counterproductive because it covers up the root of our problems: a humanity in constant disharmony between bellicose ethnocentrisms, perpetrator of planetary devastation, whose supreme value is profit without limits.

Este ensayo cuestiona a la medicina evolutiva o darwiniana por su adhesión acrítica a la teoría evolucionista para explicar las enfermedades, que deja de lado el propio proceso vital que transformó un planeta "inerte" en uno "viviente", donde el orden biológico naciente subordinó al fisicoquímico imperante para prevalecer. El orden biológico es equiparable a un "concierto armónico infinitamente diverso", que ha creado y recreado, por eones, los ambientes propicios para su propia permanencia y evolución. El arribo del homo sapiens significó el surgimiento del orden cultural que suplantó progresivamente en sus efectos, al orden biológico, al provocar cambios drásticos y vertiginosos en el ecosistema planetario que silenciaron el proceso evolutivo "sin tiempo para manifestarse". La adaptación como aptitud para sobreponerse a situaciones adversas, es un contrasentido en el "concierto armónico"; en cambio, es característica del orden cultural que impone a los humanos ambientes inhóspitos y estresantes como exigencias adaptativas ineludibles. La cualidad vital propia del orden biológico es la anticipación secuencial de las situaciones de interacción con los objetos significativos del ambiente, que posibilita la consumación de las actividades vitales básicas, emblema del estado de madurez de los seres vivos. Pensar que la evolución explica las enfermedades crónicas no solo es ilusorio, sino contraproducente, porque encubre la raíz de nuestros problemas: una humanidad en constante disarmonía entre etnocentrismos belicosos, perpetradora de la devastación planetaria, cuyo valor supremo es el lucro sin límites.

Hunter-gatherer diets and activity as a model for health promotion: Challenges, responses, and confirmations.

Beginning in 1985, we and others presented estimates of hunter-gatherer (and ultimately ancestral) diet and physical activity, hoping to provide a model for health promotion. The Hunter-Gatherer Model was designed to offset the apparent mismatch between our genes and the current Western-type lifestyle, a mismatch that arguably affects prevalence of many chronic degenerative diseases. The effort has always been controversial and subject to both scientific and popular critiques. The present article (1) addresses eight such challenges, presenting for each how the model has been modified in response, or how the criticism can be rebutted; (2) reviews new epidemiological and experimental evidence (including especially randomized controlled clinical trials); and (3) shows how official recommendations put forth by governments and health authorities have converged toward the model. Such convergence suggests that evolutionary anthropology can make significant contributions to human health.

Evolución y enfermedad / Evolution and disease

Resumen Este ensayo cuestiona a la medicina evolutiva o darwiniana por su adhesión acrítica a la teoría evolucionista para explicar las enfermedades, que deja de lado el propio proceso vital que transformó un planeta "inerte" en uno "viviente", donde el orden biológico naciente subordinó al fisicoquímico imperante para prevalecer. El orden biológico es equiparable a un "concierto armónico infinitamente diverso", que ha creado y recreado, por eones, los ambientes propicios para su propia permanencia y evolución. El arribo del homo sapiens significó el surgimiento del orden cultural que suplantó progresivamente en sus efectos, al orden biológico, al provocar cambios drásticos y vertiginosos en el ecosistema planetario que silenciaron el proceso evolutivo "sin tiempo para manifestarse". La adaptación como aptitud para sobreponerse a situaciones adversas, es un contrasentido en el "concierto armónico"; en cambio, es característica del orden cultural que impone a los humanos ambientes inhóspitos y estresantes como exigencias adaptativas ineludibles. La cualidad vital propia del orden biológico es la anticipación secuencial de las situaciones de interacción con los objetos significativos del ambiente, que posibilita la consumación de las actividades vitales básicas, emblema del estado de madurez de los seres vivos. Pensar que la evolución explica las enfermedades crónicas no solo es ilusorio, sino contraproducente, porque encubre la raíz de nuestros problemas: una humanidad en constante disarmonía entre etnocentrismos belicosos, perpetradora de la devastación planetaria, cuyo valor supremo es el lucro sin límites.

Abstract This essay questions evolutionary or Darwinian medicine for its uncritical adherence to evolutionary theory to explain diseases, which leaves aside the very vital process that transformed an "inert planet" into a "living one" where the nascent biological order subordinated the physicochemical one to prevail. The biological order is comparable to an "infinitely diverse harmonic concert", which has created and recreated, for eons, the environments conducive to its own permanence and evolution. The arrival of homo sapiens meant the cultural order emergence, which progressively supplanted, in its effects, the biological order by causing drastic and vertiginous changes in the planetary ecosystem that silenced the evolutionary process "without time to manifest". Adaptation as an ability to overcome adverse situations is a non-sense in the "harmonic concert"; instead, it is characteristic of the cultural order that imposes inhospitable and stressful environments on humans as inescapable adaptive demands. The vital quality of the biological order is the sequential anticipation of situations of interaction with significant objects in the environment, which enables the consummation of basic vital activities, emblematic of the state of maturity of living beings. To think that evolution explains chronic diseases is not only illusory but counterproductive because it covers up the root of our problems: a humanity in constant disharmony between bellicose ethnocentrisms, perpetrator of planetary devastation, whose supreme value is profit without limits.