Dr. Melissa Ilardo on How Genes & Behavior Shape Us – Epigenetics, Evolution & Adaptation

This summary details an episode of the Huberman Lab Podcast, hosted by Dr. Andrew Huberman, featuring guest Dr. Melissa Ilardo, a Professor of Biomedical Informatics at the University of Utah. Dr. Ilardo is a world-renowned expert in human genetics and epigenetics, conducting pioneering studies on how behavior and environment can modify gene expression, even across generations.

The episode delves into the intricate relationship between our genes, our behaviors, and our environment. Key topics include the fundamental question of nature versus nurture, the mechanisms of epigenetics and how experiences like trauma or starvation can leave heritable marks on our DNA. The discussion explores fascinating aspects of human evolution, such as the origins of different eye colors and adaptations to extreme environments like high altitude. A significant portion is dedicated to Dr. Ilardo's research on unique human populations, including the Bajo sea nomads of Indonesia and the Henyo female divers of Korea, highlighting their extraordinary physiological adaptations for breath-hold diving. The conversation also touches upon mate selection influenced by immune system compatibility, the potential for rapid gene expression changes through specific behaviors like the mammalian dive reflex, and the ethical considerations surrounding emerging gene-editing technologies like CRISPR. This episode is highly relevant for anyone interested in understanding the dynamic interplay between genetics and behavior, human potential, and how our choices can influence our biology and that of future generations.

Key Insights

• Gene Expression is Malleable: According to Dr. Ilardo, while some traits are genetically determined, our understanding of epigenetics is revealing that gene expression can be significantly modified by behavior and environmental stimuli, sometimes rapidly and with effects that can even be passed down through generations. These epigenetic changes can be adaptive, like those potentially aiding survival during famine, but may become less beneficial in different contexts.
• Mate Selection and Immune Diversity: Humans, much like other mammals, exhibit a preference for mates with immune systems (specifically the Major Histocompatibility Complex) that are most different from their own. Dr. Ilardo explained that studies, including the "sweaty t-shirt" experiment, suggest this attraction is mediated by smell and likely serves to produce offspring with a broader range of immune defenses.
• The Mammalian Dive Reflex: Immersion of the face in cold water while holding one's breath triggers the mammalian dive reflex. This physiological response includes a slowing heart rate, peripheral vasoconstriction, and, crucially, the contraction of the spleen. Dr. Ilardo highlighted that spleen contraction can release a substantial (around 10%) boost of oxygenated red blood cells into circulation, enhancing oxygen availability to the brain and body during the breath-hold.
• Genetic Adaptations in Diving Populations: Dr. Ilardo's research on the Bajo sea nomads revealed they possess genetically larger spleens (about 50% larger on average) compared to neighboring non-diving farming populations, an adaptation likely crucial for their extreme breath-hold diving. This trait is linked to genetic variants affecting thyroid hormone pathways. Similarly, the Henyo female divers of Korea exhibit training-induced enhancements in their dive reflex (more significant heart rate slowing) and genetic adaptations that help manage blood pressure changes during dives, particularly important as they traditionally dived throughout pregnancy.
• Human Evolution is Ongoing and Complex: The podcast emphasizes that human evolution is not a completed process. It continues to be shaped by factors such as diet (e.g., lactase persistence, lipid metabolism in Inuit populations), environmental pressures (e.g., high-altitude adaptation in Tibetans, partly from Denisovan gene introgression), and mate selection. Interbreeding with archaic hominids like Neanderthals and Denisovans has also contributed to the modern human gene pool.
• Ethical Frontiers of Gene Editing: The development of gene-editing technologies like CRISPR presents profound ethical questions. While holding promise for preventing genetic diseases, concerns exist regarding off-target effects, the distinction between therapeutic correction and enhancement, accessibility, and who decides which traits are "defects" versus normal variation.
• Mindset Influences Physiology: The discussion touched upon research indicating that an individual's mindset or belief about their genetic predispositions can measurably impact their physiological responses and performance, independent of their actual genetic makeup. This underscores the complex interplay between psychology and biology.

Genetics, Epigenetics, and the Malleability of Our DNA

The episode began by tackling the age-old "nature versus nurture" debate. Dr. Ilardo stated that while some genetic traits are largely predetermined, scientific understanding, particularly in the field of epigenetics, is increasingly showing how much our gene expression can be modified by our environment and behaviors. Epigenetics refers to modifications to the genome, such as molecules attaching to DNA, that don't change the DNA sequence itself but alter how genes are expressed. These changes can occur within minutes or hours in response to stimuli.

Dr. Ilardo explained that some epigenetic changes can even be inherited across generations. She cited studies on refugee populations, where descendants show epigenetic marks related to trauma experienced by their ancestors, even if they did not experience the traumatic events themselves. Similarly, the Dutch Hunger Winter, a famine several hundred years ago, left epigenetic signatures in subsequent generations, possibly as an adaptive response to starvation. However, such inherited adaptations might not always be beneficial in modern environments with abundant food. The discussion highlighted that the adaptive or maladaptive nature of these inherited changes is still an area of active research. Beyond epigenetic modifications, actual changes in genes themselves (mutations or shifts in the frequency of existing variations) were traditionally thought to take thousands of years, but recent research suggests this timeline could be shorter, perhaps 1,000 to 2,000 years under strong selection pressure.

Mate Selection, Immune Diversity, and Human Evolution

The conversation explored intriguing aspects of human genetics and evolution, starting with common examples like eye color. Dr. Ilardo shared a fascinating fact: all blue-eyed individuals descend from a single common ancestor who first exhibited this mutation. Green eyes, on the other hand, are considered rarer and may have arisen from multiple genetic origins. While largely fixed, eye color can subtly change with UV exposure over a lifetime.

A key theme was how genetic diversity influences mate selection. Dr. Huberman raised the concept of "hybrid vigor," where offspring from genetically diverse parents may be more robust. Dr. Ilardo confirmed that in both mice and humans, there's an unconscious drive to select mates with different immune system genetics, specifically variations in the Major Histocompatibility Complex (MHC). A famous study involved participants smelling sweaty t-shirts of the opposite sex; individuals were more attracted to the scent of those whose MHC profiles were most different from their own. This suggests that smell acts as a primal cue for selecting partners who can contribute to offspring with a more diverse and resilient immune system.

The discussion also touched upon ongoing human evolution. Dr. Ilardo emphasized that as long as factors affect our ability to reproduce, evolution continues. Globalization, leading to individuals from diverse genetic backgrounds having children, is creating novel genetic combinations, potentially fostering new forms of resilience or, conversely, new disease susceptibilities. An example of rapid adaptation from introduced genetic material is the Tibetan high-altitude adaptation, which is believed to involve a gene acquired through interbreeding between early humans and Denisovans, an archaic hominid group. This highlights that Homo sapiens were capable of reproducing with other hominid species like Neanderthals and Denisovans, and these intermingling events contributed advantageous genes to the human population. Dr. Ilardo also clarified the concept of "survival of the fittest," noting it's more accurately "survival of the best fit" – evolution favors traits that best match the current environment, not necessarily an abstract notion of superior fitness.

The Mammalian Dive Reflex and the Bajo Sea Nomads

Dr. Ilardo detailed her research on the Bajo people of Indonesia, a group of "sea nomads" renowned for their extraordinary breath-hold diving abilities. They traditionally live on houseboats, and their lives revolve around the sea, with some children learning to swim before they walk. Divers among the Bajo can reportedly hold their breath for remarkable durations (anecdotal claims up to 13 minutes) and dive to significant depths (over 100 feet to collect black coral) while actively hunting. This extreme lifestyle creates strong selective pressure: those less adapted are less likely to survive and reproduce.

The physiological basis for such abilities is partly the mammalian dive reflex, an innate response present in all mammals. Dr. Ilardo explained that when the face is submerged in cold water and breath is held, several things happen: heart rate slows, blood vessels in the extremities constrict (shunting oxygenated blood to vital organs like the brain), and the spleen contracts. The spleen acts as a reservoir for oxygen-rich red blood cells. Its contraction can provide about a 10% boost in circulating oxygenated red blood cells, effectively acting as a "biological scuba tank." This reflex is triggered by stimulating the vagal nerve in the face.

Dr. Ilardo's research found that the Bajo have significantly larger spleens—about 50% larger on average—than neighboring farming populations who do not dive. Importantly, this enlarged spleen size was observed in both diving and non-diving Bajo individuals, suggesting a genetic basis rather than a training-induced adaptation. Further genetic analysis identified a variant in a gene called PDE10A, which is associated with higher than average (though not clinically hyperthyroid) thyroid hormone levels. This genetic variant correlates with larger spleens and increased red blood cell counts, not just in the Bajo but also observed in European populations carrying the same variant. Animal model studies in mice replicated these findings, showing that the mouse equivalent of this genetic variation led to larger spleens and higher red blood cell counts, independent of erythropoietin (EPO) levels, the hormone typically associated with red blood cell production. This suggests a novel pathway for increasing oxygen-carrying capacity.

The Henyo: Female Divers, Cold Adaptation, and Cardiovascular Health

The podcast also explored Dr. Ilardo's work with the Henyo, a community of female divers on Jeju Island, Korea. These women, with an average age of around 70, have a tradition of diving for seafood (like sea urchin, abalone, and octopus) that spans thousands of years. They dive in extremely cold waters and, historically, did so with minimal thermal protection (cotton swimsuits until the 1980s). A remarkable aspect of their culture is that they traditionally continued to dive throughout pregnancy, sometimes up to the day of birth.

Dr. Ilardo's team identified two types of adaptations in the Henyo. First, a training-induced adaptation: Henyo divers exhibit a more pronounced slowing of their heart rate during dives compared to non-divers. In one instance, a diver's heart rate dropped by over 40 beats per minute in less than 15 seconds. This enhanced bradycardia is a learned physiological response from a lifetime of diving.

Second, they found a genetic adaptation likely driven by the practice of diving during pregnancy. Pregnant women who experience sleep apnea (which involves breath-holding and can lead to hypoxia) are at higher risk for hypertensive disorders like preeclampsia. Dr. Ilardo posited that diving, a form of voluntary apnea, could similarly increase this risk. The Henyo divers were found to have a higher frequency of a genetic variant that leads to a lowering of their diastolic blood pressure specifically while diving. This adaptation is thought to be protective against developing high blood pressure complications during pregnancy due to their diving activities. The fact that this adaptation acts on pregnant women makes it a potent target for natural selection, as it can affect the survival of two generations simultaneously.

Culturally, Dr. Ilardo noted that while the Henyo may have faced some marginalization in the past (due to sun-darkened skin or hearing damage leading to loud voices), they are now highly revered, with their tradition recognized as a UNESCO Intangible Cultural Heritage.

Super-Performance, Mindset, and Genetic Determinism

The discussion broadened to consider other examples of exceptional human performance and the interplay of genetics and training. The Mokin children of Thailand, another sea nomad group, were found to have better underwater visual acuity than European children, an ability that European children could also develop with training. Dr. Ilardo cautioned against dismissing a potential genetic predisposition simply because a trait is trainable. The genetic component might provide an initial advantage or a greater capacity for improvement with training.

Exceptional endurance runners, like Eliud Kipchoge, often hail from specific regions (e.g., Ethiopia), suggesting potential genetic contributions related to biomechanics (like bone length proportions) or physiological adaptations to high altitude. However, disentangling genetic factors from environmental influences and rigorous training is complex.

Cognitive abilities were also considered. Dr. Ilardo mentioned observations like the higher incidence of autism spectrum traits among family members of individuals in STEM fields, suggesting that traits like hyper-focus, common in some individuals on the spectrum, could be advantageous in such careers. However, quantifying complex traits like creativity or mathematical ability for genetic studies (like Genome-Wide Association Studies or GWAS) is challenging due to significant environmental and developmental influences.

A crucial point raised was the impact of mindset. Dr. Ilardo referenced a study where participants were told (falsely, in some cases) whether they had genes predisposing them to improve with exercise. Those told they had favorable genes showed greater physiological improvements, irrespective of their actual genetic makeup. This highlights the powerful effect of belief and expectation on biological outcomes and serves as a warning against oversimplified genetic determinism, where genes are seen as rigidly dictating one's potential.

The Ethics of Gene Editing and the Future of Human Genetics

The conversation concluded with a look at the ethical implications of advancing genetic technologies, particularly CRISPR gene editing. The case of He Jiankui in China, who announced he had created gene-edited babies, sparked international outcry and a call for a pause on such research. Dr. Ilardo noted that current CRISPR technology still has limitations, such as "off-target effects" where unintended parts of the genome are altered. As the technology becomes more precise, the ethical dilemmas will intensify.

A core ethical challenge is distinguishing between using gene editing for therapeutic "correction" of diseases (like Huntington's or BRCA mutations) versus "enhancement" of desired traits. Defining what constitutes a "defect" versus normal human variation is subjective and culturally influenced. Furthermore, questions of accessibility and equity arise, as these technologies are initially likely to be expensive, potentially creating a divide between those who can afford genetic modification and those who cannot. While technologies like whole genome sequencing have become much cheaper over time, the implications of embryo selection based on deep genetic sequencing (already offered by some companies for IVF) raise concerns about how much information parents want or should have, and the potential for societal pressure towards certain genetic profiles.

Finally, Dr. Ilardo addressed the concept of "admixture" (the mixing of different ancestral populations) and its complexities in genetic studies. When asked if humans, with all their genetic variation, could be considered more than one species, she affirmed that despite significant diversity (sometimes stemming from single base-pair changes), Homo sapiens are indeed one species, capable of interbreeding and sharing a common, albeit diverse, gene pool.

Conclusion

Dr. Melissa Ilardo’s discussion on the Huberman Lab Podcast paints a dynamic picture of human genetics, where our DNA is not a fixed blueprint but a responsive system constantly interacting with our behaviors and environment. The core message is that while genes lay a foundation, our choices, experiences, and even the experiences of our ancestors can shape how those genes are expressed, influencing everything from our physical capabilities to our health and perhaps even our mate preferences. The study of unique populations like the Bajo and Henyo offers profound insights into human adaptability and the power of natural selection, revealing remarkable physiological feats and the genetic underpinnings that make them possible.

The significance of these topics for listeners lies in understanding the agency we may have in influencing our own biology through behavior, the deep evolutionary roots of some of our unconscious drives, and the complex ethical considerations we face as a society with the advent of powerful gene-editing technologies. Dr. Ilardo’s work encourages a nuanced perspective, moving beyond simple nature vs. nurture dichotomies to appreciate the rich, ongoing interplay between our genetic inheritance and the lives we lead.