Therapeutics as the Next Frontier in the Evolution of Darwinian Medicine

Evolutionary medicine (also referred to as Darwinian medicine) is the application of evolutionary theory to the understanding of human ailments.1 2 3 It explores evolutionary mechanisms of disease, offering a complementary framework to the proximate mechanistic explanations that prevail in medicine today. In this paper, we consider the application of evolutionary theory to the treatment of ailments.

A major contribution of evolutionary medicine is the framing of human diseases as maladaptations of our prehistoric factory settings. Our physiologic processes were shaped during prehistoric evolution to meet the needs of the era, but those same processes may behave maladaptively in the modern environment and produce disease. We take that notion one step further and propose an overarching therapeutic paradigm for human ailments based on evolutionary theory—the induction of adaptations in the body as a way to treat disease. It is the idea of creating somatic traits in the body that evolution might otherwise need to create over many generations through the sheer force of variation and natural selection. In the same way, that evolution has endowed us with traits that shield against biotic and abiotic stress to maintain homeostasis, we propose treating patients by endowing the body with buffers against ailments.

Most modern therapies provide relief in the short run, but chronic use can worsen the underlying condition, as the body remodels in the presence of the therapy and decompensates further. Caffeine stimulates acutely, but continued use leads to lowered baseline alertness. Virtually all drugs exhibit this phenomenon, known as tachyphylaxis, to varying degrees. Modern medicine effectively provides the body with an adaptation, which ultimately de-adapts the body and creates dependence on further therapy. We suggest that providing therapy to induce an adaptation may represent an alternative model for
relieving ailments.4

In this model, hypertension would be treated by offering patients drugs that elevate rather than lower blood pressure. This is effectively how exercise works. During exercise, we raise our blood pressure and heart rate, such that in the long run our baseline blood pressure and heart rate go down. An appropriate autonomic stimulus, whether physical activity or sympathomimetic drug, would induce vagal strengthening—thereby leveraging preexisting capacities within the body instead of overriding or replacing them.

These types of solutions would reverse the current trend of greater dependence on medicine, which is expensive, inelegant, and ultimately, ineffective. Induced adaptations may offer far superior therapies at a fraction of the cost, exactly the kind of outlier solution needed in this time of crisis in the healthcare system.

In some ways, the idea is hardly new. Vaccination induces a somatic adaptation. Priming the immune response prepares the body for potential future exposure to a dangerous pathogen. Vaccination is arguably one of the greatest inventions in medical history in terms of its efficacy and impact.

While vaccination provides the most sweeping example of induction of adaptation, a number of recent examples suggest the idea can be more broadly applied. Asthma is a pulmonary condition where the insufficient sympathetic response in the smooth muscles of the respiratory tract predisposes to spasm and closure of the airways. For a century, symptomatic relief of asthma has featured the use of sympathomimetic drugs. However, chronic use of beta-agonists induces down-regulation of beta receptors and furthers autonomic dysfunction. On the other hand, Richard Bond has shown that administration of beta-blockers may be a way to treat asthma by inducing an appropriate adaptation.5

Similarly, administration of the antigen in small doses has been shown to induce adaptation to cope with both environmental allergies and food allergies.6 Positive pressure ventilation for respiratory dysfunction can produce not only diaphragmatic weakening but also a host of other physiologic dysfunctions.7 On the other hand, diaphragmatic pacing promotes negative pressure ventilation and strengthening of the diaphragm, which becomes an adaptation for the patient. Exercise, which has been associated with amelioration of many chronic diseases, is a natural example of adaptation induction.

The progression of life is defined by the accumulation of buffers (traits) against stresses over evolutionary epochs. As advances in technology enable them to live to unprecedented ages, modern humans are now facing many unprecedented stresses, both externally from the environment and internally from within their own bodies. Evolution has not kept pace with these changes; in many ways, diseases can be viewed as maladaptations awaiting the forces of evolution to eventually endow adaptations over the generations. We believe that human innovation can harness the knowledge of evolution theory and accelerate the induction of adaptations within generations rather than across them.

In the final analysis, adaptation is the end, and evolution has been nothing more than the means to that end. Over the very long haul, if humans learn to create adaptations to maintain homeostasis, human evolution itself could be at risk of extinction.


1 Williams GC, Nesse RM. Why we get sick: the new science of Darwinian medicine. New York: Vintage Books. 1996.

2 Weiner H. Notes on an evolutionary medicine. Psychosom Med 1998;60(4):510–20.

3 Williams GC, Nesse RM. The dawn of Darwinian medicine. Q Rev Biol 1991;66(1):1–22.

4 Yun AJ, Lee PY, Bazar KA.  Paradoxical strategy for treating chronic diseases where the therapeutic effect is derived from compensatory response rather than drug effect. Med Hypotheses 2005;64(5):1050–9.

5 Hanania NA, Dickey BF, Bond RA. Clinical Implications of the Intrinsic
Efficacy of Beta-Adrenoceptor Drugs in Asthma: Full, Partial and Inverse Agonism. 
Curr Opin Pulm Med. 2010;16(1):1–5.

6 Burks AW, Laubach S, Jones SM.  J Allergy Clin Immunol. Oral tolerance, food allergy, and immunotherapy: implications for future treatment. 2008 Jun;121(6):1344-50.

7 Yun AJ, Lee PY, Doux JD. Negative pressure ventilation via diaphragmatic pacing:
a potential gateway for treating systemic dysfunctions.
Expert Review of Medical Devices May 2007;4(3):315–9.

Originally published in The Journal of the Palo Alto Institute on February 2012.