Three Stages of Health Encounters Over 8000 Human Generations and How They Inform Future Public Health (2024)

The remarkable prolongation of human life expectancy is a testimony to advances in standards of living, public health, and modern medicine. Previous analyses by Omran1 and others2 described distinct eras of transition from pestilence and famine, to receding pandemics, to the rise of degenerative and man-made disease. However, since 1990, the life expectancy of White Americans without a high school diploma declined by approximately four years, and US age-adjusted death rates rose slightly in 2015.3 In my opinion, this striking change can be best explained by three overlapping stages of public health and medical encounters (Table 1) rather than by distinct eras.

PALEOLITHIC STAGE ENCOUNTERS

The first encounters began about 8000 generations ago in the Paleolithic era when approximately 75% of deaths were caused by infection, including diarrheal diseases that resulted in dehydration and starvation. Life expectancy was approximately 33 years of age. To perpetuate our species, the genes of our ancestors mutated over time, with beneficial mutations accumulating to protect them against the hazards they faced. They craved food, especially the tastes of sugar and protein, and gorged when it was available. They benefitted from their “thrifty genotype”—genes that individually helped them store a little more fat, and that collectively explains why at least 25% and perhaps as much as 80% of modern obesity and type 2 diabetes is heritable. They loved the taste of salt, which combined with thirst and our renin-angiotensin-aldosterone axis helped avoid dehydration during water shortages, diarrheal illnesses, and exercise. Because almost 15% of Paleolithic humans died violently, they learned how to be fearful and submissive to minimize confrontation when neither fight nor flight was possible. To avoid severe bleeding, whether from trauma or childbirth (which probably killed approximately one mother in 100), their genes evolved toward efficient clotting rather than avoiding later-in-life thrombotic diseases.

INDUSTRIAL STAGE ENCOUNTERS

The second stage of encounters began approximately 150 years ago when the Industrial Revolution brought rising standards of living that mitigated many of these challenges. However, it also ushered in a litany of man-made consequences. For example, eight million annual worldwide deaths are probably attributable to air, water, and industrial pollution.4 Altogether, man-made hazards, including tobacco smoking, drug and alcohol abuse, and road injuries, represent about one third of current global mortality. Nevertheless, a variety of public health advances contributed to the doubling of life expectancy between 1850 and the mid-20th century.5

LEISURE STAGE ENCOUNTERS AND GENETIC MISMATCH

Since the onset of the era of leisure in the late 20th century, life expectancy further increased and now exceeds 80 years in many countries. Medical advances, such as vaccinations, antimicrobial agents, antihypertensive agents, and the treatment of heart disease, are estimated to account for 85% to 90% of this most recent increase in US life expectancy.6 However, all three stages of encounters remain relevant in some parts of the world. For example, second encounter pollution and other man-made hazards are major causes of death worldwide, and the developing world faces an emerging epidemic of third-encounter obesity and diabetes.

Our modern lifestyle of longevity, material abundance, and leisure developed over about six generations, which is far too short a time for our genes to adjust.7 This mismatch between our genes and our modern environment helps explain why approximately 38% of Americans are now obese, 12% to 14% have diabetes, one third have hypertension, and 25% die from thrombotic heart disease and stroke. Anxiety and depression, linked to our ancestors’ tendencies toward fear and submissiveness, are the 9th and 11th leading causes of disability-adjusted life-years lost in the United States, and suicide now kills far more Americans than murder and war combined. Other leading modern causes of death and disability, such as cancer, neurodegenerative diseases, and musculoskeletal maladies, may not be as specifically related to modern gene–environment mismatches but rather represent previously indifferent genes that had not been widely exposed to the consequences of aging in prior generations with shorter life expectancies.

POTENTIAL FUTURE STRATEGIES

In light of past public health and medical successes and failures, what are the best strategies for the future? Options include changing behavior (e.g., diet, exercise, reduced salt intake), legislation and regulation (e.g., emissions standards, clean energy), and advancing medical science.

BEHAVIOR, LEGISLATION, AND REGULATION

I contend that reliance on personal behavior change, although laudatory and worthwhile, is unlikely to solve leading modern causes of morbidity and mortality, as evidenced by the increasing global epidemics of obesity and physical inactivity. Part of the problem is how our genes drive behaviors. For example, weight loss stimulates appetite and decreases metabolic rate, which is a wonderful adaptation to avoid starving to death in the Paleolithic era, but is also a major limitation for modern dieters.

Regulation and legislation were critical for industrial era pollution, and more targeted interventions (e.g., banning smoking in public places, increasing tobacco taxes, and seatbelt laws) have addressed specific health issues. Recently, legislation has also addressed some third-encounter problems. For example, the United States banned most trans fats; changes in the food supply in England and Finland lowered salt consumption by approximately 25%, with corresponding reductions in blood pressure, stroke, and coronary heart disease; and a Mexican excise tax on sugar-sweetened beverages reduced consumption. However, regulation and legislation seem unlikely to be the dominant solution for third-encounter health challenges.

BLUNTING OVERPROTECTIVE GENES

If neither behavior changes nor regulation or legislation are likely to be sufficient for addressing the leisure era mismatch between our genes and our lifestyle, a promising approach is to blunt or block overprotective genes that we no longer need. We already use antihypertensive medications to block the overprotective renin-angiotensin-aldosterone system in hypertension and use statins to block the overproduction of low-density lipoprotein (LDL) cholesterol. However, we now know of multiple other targets, such as the PCSK9 gene, in which a hom*ozygous mutation can reduce LDL cholesterol levels to 14 milligrams per deciliter without any obvious adverse effects. Food and Drug Administration–approved antibodies against this gene’s protein product can lower LDL cholesterol levels by approximately 60%. In individuals with a hom*ozygous deletion that inactivates ANGPTL4 E40K, lipid levels are reduced by approximately 40% and coronary disease by 90%; an experimental medication is in development. These targets are “proof of principle” that third-encounter health issues may be more amenable to blocking genes we no longer need than to the potential benefits of voluntary behavior change or legislation.

No one doubts that vaccines, originally the simple cowpox vaccine, but now increasingly sophisticated vaccines (e.g., against polio and hepatitis B) have had enormous impact on public health. Behavior change and regulation certainly helped slow the AIDS epidemic, but antiretroviral medications, undreamed of barely 30 years ago, have made the largest impact. Ivermectin, not behavior change, is the key approach to onchocerciasis (river blindness). Hypertension might be prevented if salt intake were decreased and physical activity increased to Paleolithic levels, but no one suggests that behavior change is as effective as antihypertensive medications or that behavior change should replace medications for addressing the current global epidemic of hypertension. Even the solutions to obesity, smoking, alcohol, and the opioid epidemic ultimately may follow a similar sequence as we face the realistic limitations of behavior change, legislation, and regulation.

PUBLIC HEALTH MEETS MODERN MEDICINE

Public health should always use current best strategies, but it also should consistently develop and evaluate new strategies for specific challenges. Behavior change, as well as legislation and regulation should be used whenever helpful. However, they should not be considered intrinsically more virtuous than the incorporation of modern scientific advances, which have made the largest contribution to prolonging US life expectancy since the onset of the leisure era and, in my opinion, also have the largest potential benefit for improving future US health and life expectancy.

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