Xenovation: Innovation from the Outside In


The immune system defends hosts against internal and external biologic threats. It also records an antigenic map of the environment such that it can appropriately respond to stimuli as benign or threatening.

A lesser-known function of the immune system may be to sample the microbiome for potentially beneficial traits it can add to the host inventory. Rather than executing wholesale destruction of pathogens, the host can benefit by domesticating invading organisms or parts thereof. The function can be summed in the word “xenovation”, innovation achieved through the selection and integration of foreign traits. Implications for biologic evolution, meme evolution, and computing evolution are discussed.


Components of pathogens can be processed and rendered benign or useful through various mechanisms. A historical example of this phenomenon is the domestication of one prokaryote (or at least its energetic machinery) by another to form a eukaryote. A current example is the processing of pathogen antigens for surface redisplay to other players in the immune system. The ability to protect against reinfection is a trait acquired via the pathogen. It is intuitively appealing to speculate that the immune system is in a perpetual state of exploration for innovative traits through domestication.

The exact mechanisms by which immune cells domesticate microbial traits remain to be elucidated. How sequences associated with those traits might end up in the germline also remains to be investigated.
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Food Allergy, Asthma, Anaphylaxis, and Autonomic Dysfunction

Written with Charles Cho

Food allergies are a rapidly growing medical and public health problem. Recent studies estimate an incidence of 5% in children younger than 5 years old and 4% in adults. In severe cases, subjects can experience anaphylaxis and even death if exposed to a food to which they are sensitive. There is no known cure. Rather, doctors recommend that the sufferer avoid exposure to the allergen. The mechanism of disease is thought to be immunologic.

A number of drugs can be used during an acute food allergy attack, but only one — intramuscular injection of epinephrine — immediately resolves all of the symptoms associated with the episode. Tellingly, epinephrine is a neurotransmitter/hormone of the autonomic nervous system (ANS) that augments sympathetic function. Emerging data in the literature supports a neuro-immune connection, particularly in light of how the ANS innervates and regulates lymphoid tissues and other constituents of the immune system. It is possible that food allergy syndrome (and perhaps all cases of anaphylaxis) may require both an allergic sensitivity and an underlying inability to generate an adequate sympathetic response (or an underlying parasympathetic/ vagal dominance).1
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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.
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Darwin in Medical School

Some scientists call for a bigger dose of evolution in doctors’ educations


Joon Yun, MD, began considering how evolution applies to human health a decade ago when his first heart disease patients died. These cases disturbed Yun, then a Stanford radiology resident. But they also intrigued him.

Having studied evolutionary biology in college, Yun tried fitting these medical failures into that framework.

His mind wandered to the early days of humans when heart disease was a rare trigger of death. In the prehistoric era, a more likely cause of death would have been an attack by a predator. The human body’s response to trauma handles this type of assault by immediately springing to action: The blood forms clots and the blood vessels tighten, together with slowing blood loss, and inflammation kicks in to combat infection. The genes governing these responses to trauma presumably were favored during evolution and have become the “factory setting” in modern humans.
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