“Nothing in biology makes sense except in the light of evolution.”

This statement was articulated by the renowned geneticist and evolutive biologist Theodosius Dobzhansky in a 1973 essay [1]. This document was specifically crafted to emphasize the importance of teaching evolution theory at school, in the context of the debate about creationism and evolution in the United States educational system. Earlier in the 1960s, Dobzhansky employed this quote to underscore the pivotal role that evolution plays in shaping all aspects of life, which cannot merely be reduced to a series of molecular interactions [2,3].

In Dobzhansky’s view, a comprehensive understanding of biology in its entirety is unattainable without the inclusion of evolution and its profound impact on living organisms. Indeed, evolution has molded every life form on Earth over countless millennia. The underlying principle is relatively straightforward: those organisms best suited to their environment have a greater likelihood of survival and passing on their genetic material to future generations. Consequently, beneficial mutations are favored by natural selection, while those offering no advantages tend to disappear. In essence, we are the result of millions of years of evolutionary processes, characterized by the rise and fall of numerous species. In other words: we are products of evolution.

This article aims to explore how evolution has not only influenced our physical structures but also our physiology and biology. While it won’t primarily focus on the process of human evolution, it will delve into the far-reaching implications that evolution has on human health and disease. Additionally, it will examine various human pathologies from the perspective of evolutionary medicine.

What is Evolutionary Medicine?

Evolutionary medicine is not an established field of study like biochemistry or epigenetics. Instead, it is a distinct approach to different aspects of medical science. This approach examines health and disease through the lens of evolution, aiming to provide insights into the mechanisms behind the development of illnesses. Through this perspective, we can also design more effective strategies for preventing and treating diseases. In essence, evolutionary medicine encompasses all aspects of medicine where evolutionary principles can offer valuable insights [4,5].

Let’s clarify this with a straightforward example — let’s consider astronauts.

The Astronaut’s Heart

Astronauts experience cardiac atrophy when they are exposed to microgravity conditions. The human cardiovascular system evolved on Earth's surface, where the heart pumps blood against gravity to supply the brain. To adapt to microgravity, the heart reduces its force during contraction, resulting in an 8-10% decrease in myocardial volume. Additionally, the distribution of bodily fluids shifts during spaceflight due to reduced gravity. For instance, leg volume is reduced while increased fluid volume in the head causes facial puffiness. To prevent these issues, astronauts engage in daily physical exercises, with personalized routines designed to maintain their health [6].

The effects of spaceflight and microgravity on the cardiovascular system serve as a clear and straightforward example of how the evolutionary medicine approach helps identify the causes of disease and establish effective preventive and therapeutic strategies. Before we delve into other examples, let’s briefly explore the history of evolutionary medicine.

The History of Evolutionary Medicine

The concept of evolutionary medicine is relatively recent. The works of Williams and Nesse during the 1990s are regarded as the inception of the field. They introduced the term “Darwinian medicine” to describe this emerging medical approach [7,8]. However, earlier studies in the realm of biological anthropology had already embraced the principles of evolutionary medicine. For instance, anthropologic research in the 1950s linked the high prevalence of back problems to “imperfections” in the evolution of bipedalism [9]. Others focused on the evolution of the lower jaw in the human lineage and its development in individuals to explain malocclusion problems [10]. Later in the 20th century, anthropologists emphasized the impact of modern lifestyle on our bodies, which evolved under vastly different conditions [11,12]. This discrepancy between modern living and our biological characteristics is a key factor in the development of various diseases and anomalies.

Now, let’s explore several examples where evolutionary medicine can shed light on the pathophysiology of different human diseases.

Combating Antibiotic Resistance: Phage Therapy

Antibiotic resistance poses an escalating threat to healthcare systems worldwide. Bacteria are evolving mechanisms to withstand antibiotics, making it challenging to find effective treatments for resistant strains. This escalation in drug resistance has elevated the mortality rates of once-treatable diseases [13]. The Centers for Disease Control and Prevention (CDC) reports an estimated 23,000 deaths annually in the United States due to resistant bacteria [14]. Antibiotic resistance is on track to become a substantial public health issue, prompting researchers to explore alternatives to antibiotics.

Bacteriophages, or phages, are viruses that infect bacteria. They were discovered about a century ago, and medical professionals initially studied their potential as therapeutic agents against bacterial infections before antibiotics became prevalent. Ironically, phage therapy now emerges as a possible alternative to antibiotics, the very molecules that led to a decline in phage research. Similar to the dynamics of predators and prey, phages and bacteria have co-evolved strategies to counter each other. For instance, bacteria evolved CRISPR as a defense mechanism against phages. Today, we can leverage this evolutionary relationship between bacteria and phages to develop therapies against antibiotic-resistant bacteria.

While promising results have been observed both in animal and human studies, additional clinical trials are necessary to gather substantial evidence regarding the practicality and safety of phage therapy. Several concerns need to be addressed in these clinical trials such as the body’s immune reaction to phages, the potential effect on beneficial microbiota, DNA transduction between bacteria, or possible harm to eukaryotic cells, among others [14].

Cancer Biology

Antibiotics marked a significant breakthrough in our battle against infections. However, other factors also played pivotal roles in reducing mortality from infectious diseases. Measures like vaccinations, access to clean water, sewerage systems, improved nutrition, and hygiene measures were just as crucial as antibiotics in lowering death rates from infections. As these measures took hold, the average human lifespan notably increased. However, as the population aged, age-related diseases such as dementia, cardiovascular issues, and cancer emerged as the primary causes of mortality [15]. It is possible that in the past, shorter lifespans may not have allowed natural selection to act on older individuals, revealing an “evolutionary oversight.”

In the advanced stages of cancer, metastasis to distant organs is frequently observed. Despite treatment, certain cancers can progress to advanced stages, ultimately leading to the patient’s death. Chemotherapy, one of the primary cancer treatments, can inadvertently trigger a natural selection progress, driving clonal evolution among cancer cells. Tumors are highly heterogeneous tissues, comprising a range of cells with different genetic alterations. Chemotherapy targets and eliminates cells (or clones) sensitive to the treatment, but those that are resistant (often relying on alternative pathways) survive. Over time, the majority of cancer cells become resistant, rendering chemotherapy ineffective for that specific patient. To address this challenge, adaptive therapy is designed to manage cancer growth by adjusting chemotherapy doses to allow some sensitive cells to survive. The underlying idea is that by promoting the survival of sensitive cells, resistant cells face heightened competition [16,17].

Understanding the principles of evolution and its mechanisms equips us with the knowledge needed to comprehend how cancer forms and progresses, as well as how tumors develop resistance to specific treatments. In this context, evolutionary medicine offers invaluable insights to aid researchers and physicians in developing new drugs and alternative therapeutic approaches.

Helminths: Too much hygiene?

We have previously discussed how advancements in hygiene, including clean water supplies and sewerage systems, have extended our lifespans. In 1989, David Strachan introduced the hygiene hypothesis, proposing that early childhood infections transmitted between siblings are linked to reduced allergy risks later in life [18]. Over the past 30 years, this hypothesis has evolved, incorporating evolutionary, microbiological, and immunological elements to become a more comprehensive concept [19]. Enhanced hygienic conditions have reduced our exposure to bacteria, viruses, fungi, and parasites over our lifetimes. Consequently, our microbiota, and also helminths, have been inadvertently altered. This has resulted in a mismatch between our immune system, which evolved in constant interaction with parasites, and the modern, cleaner environment, potentially leading to autoimmune diseases [20].

Helminths, or parasitic worms, are macroscopic parasites that typically infect the gastrointestinal tract and exert an immunomodulatory effect on the gut immune system. They directly interact with the host’s immune system by producing proteins, glycans, and miRNA-containing exosomes. Additionally, they stimulate the growth of bacteria that produce short-chain fatty acids, which are metabolized by immune cells like Treg [21]. Some of these molecules can interact with interleukins and cytokines, which are essential for modulating the host’s immune response. Notably, helminthic infections have been associated with a lower prevalence of autoimmune diseases such as inflammatory bowel disease (IBD), type I diabetes, and multiple sclerosis. Current research focuses on developing drugs mimicking the immunomodulatory effects of helminths [20,22]. This underscores the significance of helminths and microbiota in maintaining a balanced immune system.

Reproductive Health

Evolution revolves around the concept of reproductive success: when an organism is better adapted to its environment, its chances of reproduction and transmitting genetic information to its offspring increase. Consequently, it is not surprising that one of the primary focuses of evolutionary medicine is reproductive health.

The reproductive patterns of humans have undergone significant changes, from early hunter-gatherer cultures to modern societies. In Paleolithic cultures, women had a significantly higher number of children than is typical in contemporary Western societies. This shift has resulted in shorter pregnancy and breastfeeding periods for modern women, along with a higher number of ovulations throughout their lives. Additionally, the increase in lifespan has given rise to menopause, a phenomenon unique to humans. These alterations have led to changes in modern women’s hormone levels, potentially contributing to reproductive health issues such as infertility [23,24].

Evolutionary Medicine and Health Optimization Medicine and Practice (HOMe/HOPe)

The HOMe/HOPe Essential Certification includes a deep dive into Evolutionary Medicine. Written by Dr. Ted Achacoso, the founder of HOMe/HOPe, the module describes the evolutionarily conserved Cell Danger Response and why this is so important across the spectrum of health and disease.

The module also goes deep into Dr. Ted’s 3-3-7-3 framework that he developed to teach a comprehensive way to use Evolutionary Medicine as the foundation for all the modules in the HOMe/HOPe Essential Course.

Although Metabolomics is the foundational module, the Evolutionary Medicine module is the true tour de force that underpins all of the modules of the HOMe/HOPe Essential Course.

Check out the Evolutionary Medicine module in the HOMe/HOPe Essential Course here.

Conclusion

When we ponder evolution, our minds often depict epic images of nature’s spectacle: predators adapting for faster hunting, plants evolving captivating flowers to attract pollinizers, or animals developing camouflaging skills to elude predators. Yet, there are other, perhaps subtler, adaptations to the environment that can have significant, albeit less noticeable, effects on our health. Whether it is the absence of gravity, interactions with helminths, or the use of antibiotics, these seemingly minor alterations can leave enduring imprints on our well-being.

This article has offered a cursory exploration of some human pathologies viewed through an evolutionary lens. Evolutionary medicine might initially appear blurry and scattered, as it is not a properly defined field of study or discipline. Nonetheless, recognizing the profound importance of considering the influence of evolutionary processes on our health renders evolutionary medicine an invaluable approach. It equips us with the knowledge and tools needed to improve and develop preventive and therapeutic health strategies.

Written by Ferran Riaño-Canalias, PhD

References

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