Applying evolutionary principles to understand disease vulnerabilities and develop innovative healthcare solutions
Imagine visiting a region where the drinking water contains arsenic levels 20 to 100 times above safety standards. For most people, this would cause severe health problems—inorganic arsenic is associated with cancers, skin lesions, heart disease, and diabetes. Yet for thousands of years, the Indigenous peoples of the Bolivian highlands have not only survived but thrived in these conditions. The secret lies not in advanced technology, but in their evolutionary adaptations—specifically, genetic variants around the AS3MT gene that allow them to efficiently metabolize this notoriously toxic substance 9 .
Indigenous populations in the Bolivian highlands have evolved genetic adaptations to metabolize arsenic efficiently, demonstrating how evolutionary processes can shape disease resistance.
This remarkable example represents just one glimpse into a revolutionary new field called evolutionary biomedicine, which applies principles of evolution and ecology to understand, prevent, and treat human diseases. For decades, medicine has largely viewed the body as a machine to be fixed, focusing on proximate causes of disease—how a virus invades cells or how a cancer tumor grows. While this approach has yielded tremendous advances, it has largely ignored the ultimate question: Why has evolution left our bodies vulnerable to these diseases in the first place? 3
Evolutionary biomedicine addresses this fundamental gap, providing an integrative framework that links otherwise disparate bits of medical knowledge. It replaces the prevalent view of bodies as machines with a biological view of bodies as products of evolutionary processes 3 . This perspective is sparking transformational innovations across biomedical research, clinical care, and public health—from new strategies against antibiotic resistance to novel cancer therapies that work with, rather than against, evolutionary principles 4 .
Evolutionary biomedicine (sometimes called Darwinian medicine) applies insights from ecology and evolution to inform, direct, and ultimately improve biomedical research and public health. The field was pioneered in the early 1990s but is now experiencing rapid growth thanks to advances in genetics, genomics, and a growing recognition of its potential to address some of medicine's most persistent challenges 4 .
The core insight of evolutionary biomedicine is that vulnerability to disease is often the product of evolutionary processes. As noted by Williams and Nesse in their seminal work, understanding these evolutionary origins provides a crucial framework for medicine that has been largely missing from traditional medical education and research 4 .
Modern pathologies result from mismatches between ancestral and modern environments.
Evolution makes compromises rather than creating perfect designs.
Explains energy allocation between growth, reproduction, and maintenance.
Rapid evolution of pathogens and cancer cells challenges treatments.
Many modern pathologies result from mismatches between the environments in which we evolved and our modern environments. Our bodies were shaped by thousands of generations of hunter-gatherer life, yet we now live in dramatically different conditions. This explains the rise of diseases like obesity, type 2 diabetes, and cardiovascular disease—our ancient metabolisms struggle to cope with modern diets and sedentary lifestyles 4 .
Evolution doesn't produce perfect designs—it works with what's available, making compromises along the way. Our bodies represent a series of trade-offs. For instance, the same strong inflammatory response that helps fight infection can contribute to autoimmune diseases and age-related disorders when persistently activated 3 .
This explains how organisms allocate energy between growth, reproduction, and maintenance. Variations in these investment patterns help explain patterns of disease burden, particularly in reproductive health and aging. The weakening of selection with age explains why we're vulnerable to diseases like cancer and Alzheimer's in later life 3 4 .
The ability of pathogens and cancer cells to rapidly evolve represents one of medicine's greatest challenges. Antibiotic resistance and chemotherapy resistance are essentially evolutionary processes—organisms adapting to survive our treatments 4 .
One of the most compelling demonstrations of evolutionary biomedicine in action comes from a landmark experiment that tracked the evolution of cancer cells in laboratory conditions. Researchers at the Trinity College Dublin conducted a revolutionary study using TP53-deficient human gastric organoids to observe how normal cells transform into malignant ones over time .
The researchers designed their experiment to mirror the evolutionary processes that occur in human cancers:
The experiment provided remarkable insights into the evolutionary journey from healthy tissue to cancer:
| Type of Genomic Change | Frequency in TP53-Deficient | Frequency in Controls | Biological Consequences |
|---|---|---|---|
| Aneuploidy (abnormal chromosome numbers) | Present in all populations | Rare | Increased genomic instability |
| Copy number alterations | Multiple events per population | Minimal | Gene dosage effects |
| Complex structural variations | Recurrent | Absent | Chromosome rearrangements |
| Specific pathway alterations (NF-κβ, etc.) | Common across populations | Absent | Malignant transformation |
The single-cell RNA sequencing data revealed that cells evolved toward malignant transcriptional states through a predictable sequence:
| Time Point | Key Genomic Events | Cellular Phenotypes | Clinical Correlation |
|---|---|---|---|
| Initial TP53 loss | Minimal changes | Slight increase in division rate | Pre-cancerous state |
| 6-12 months | Aneuploidy emerges | Increased proliferation | Early neoplasia |
| 12-18 months | Copy number alterations | Heterogeneous marker expression | Advanced precursor |
| 18-24 months | Complex rearrangements | Invasion capability | Frank malignancy |
Perhaps most importantly, the researchers observed that multiple independent cell populations followed similar evolutionary trajectories, suggesting that cancer development follows certain predictable patterns despite its random elements. This parallel evolution provides hope that we might eventually predict cancer progression before it becomes irreversible .
From a cell biological perspective, the experiment allowed researchers to compile a detailed overview of the transition to malignancy. The TP53-deficient cultures showed increasingly heterogeneous marker expression profiles compared to stable wild-type organoids. Multiple pathways commonly implicated in malignancy (such as NF-κβ) were altered across multiple evolved samples, providing new insights into the essential changes required for cancer development .
Evolutionary biomedicine relies on a diverse set of research tools that allow scientists to observe and manipulate evolutionary processes in controlled settings.
| Tool/Method | Primary Function | Research Applications |
|---|---|---|
| Experimental Evolution | Studies evolutionary processes in real time | Tracking adaptation in microbes, cancer cells, or model organisms under defined conditions |
| CRISPR-Cas9 Gene Editing | Creates precise genetic perturbations | Introducing specific mutations (e.g., TP53 deletion) to initiate evolutionary experiments |
| Organoid Cultures | Provides realistic 3D tissue models | Studying tissue evolution in environments that mimic human organs |
| Single-Cell RNA Sequencing | Measures gene expression in individual cells | Tracking heterogeneity and evolutionary trajectories within populations |
| Phylogenetic Analysis | Reconstructs evolutionary relationships | Identifying disease resistance mechanisms across species 4 |
| Long-term Evolution Experiments (LTEE) | Observes evolution over thousands of generations | Understanding general principles of evolutionary dynamics 7 |
These tools have enabled researchers to move beyond observational studies to actively test evolutionary hypotheses about disease origins and progression. For example, the evolutionary repair experiment—where researchers introduce a genetic defect and then observe how organisms evolve to compensate—has revealed how cellular networks can be rewired through evolution .
This revolutionary gene-editing technology allows scientists to create specific genetic changes in model organisms and cell cultures, enabling them to study how these changes influence evolutionary trajectories and disease development in controlled experimental settings .
The growing field of evolutionary biomedicine represents a fundamental shift in how we understand health and disease. By asking not just "how" diseases occur but "why" our bodies are vulnerable to them in the first place, this perspective offers powerful new approaches to some of medicine's most challenging problems.
Evolutionary principles are already guiding innovative cancer therapies that intentionally manage tumor evolution rather than simply trying to eliminate all cancer cells. They're informing new approaches to antibiotic resistance that account for bacterial evolution. They're helping us understand why chronic diseases like diabetes and autoimmune disorders have become so prevalent in modern environments 4 .
Perhaps most excitingly, evolutionary biomedicine offers a systematic approach to learning from nature's solutions. By studying the diverse adaptations across the animal kingdom—from the naked mole-rat's resistance to cancer to the remarkable abilities of other species to tolerate toxins, infections, and other disease triggers—we can identify new strategies for preventing and treating human diseases 2 4 .
As the research continues to advance, the integration of evolutionary thinking into medical education and clinical practice promises to transform our approach to health. As one researcher noted, "Evolutionary biology is not just another topic vying for inclusion in the curriculum; it is an essential foundation for a biological understanding of health and disease" 3 . The future of medicine won't just fight disease—it will understand disease's ancient origins and evolutionary logic, creating smarter, more effective approaches to healing.