Evolutionary medicine principles can generate hypotheses to explain why we:

1) have body parts that are vulnerable to disease

2) suffer infectious diseases

3) are susceptible to diseases of aging (and more!)

Evo Med hypotheses fall broadly into two main categories: Phylogeny and Function

I. Phylogeny  (history)

How does evolutionary history explain a trait? For instance, “accidents of history” explain why we have a hole in our retina and why the spermatic cord punches an unnecessary hole in the abdomen, predisposing males to hernias.

1) Constraints include inverted arrangement of photoreceptor cells and ganglion cells whose axons carry the neural signals to the brain. Constraints can be thought of as by accidents of history. Early vertebrates likely featured eyes with this inverted arrangement of photoreceptors and transmitting neurons.  Octopus and squid have the opposite pattern. (clinical example: inverted photoreceptors may contribute to the likelihood of retinal detachments)

2) Non adaptive historical effects, such as population bottlenecks and the founder effect, can explain many genetic diseases. (example: Tay Sachs disease is common in Ashkenazi Jews, likely because of a founder effect)

Natural selection may or may not be involved in the preservation of alleles that make patients sick. Here is one example:

Human genetic variation. Because of a variant allele (CYP2D6) that causes hypermetabolism of codeine to morphine, some children are at increased risk of respiratory complications and even death when prescribed codeine. In one example, a child died because of codeine after a routine tonsillectomy. Understanding how evolution maintains genetic variation, leading to the persistence of sometimes harmful alleles, is critical when reaching for the prescription pad for an opiate prescription. (Bottom line: no codeine for kids!)

II. Function (adaptation resulting from natural selection)

What function or adaptation might be associated with a disease? (This function might not be obvious and might not be adaptive from the perspective of the patient!)

Many features of pathogens are functional and adaptive (from the perspective of the microbe – increasing their fitness) while at the same time causing human illness (decreasing human fitness).

Here is an example:

Antibiotic resistance evolution.  We know that an unnecessary prescription of antibiotics is likely to promote the evolution of resistant and virulent microbes in the gut. Resistance evolution in microbes that have colonized our bodies can later cause a life threatening and difficult to treat infection. Similarly, a broad spectrum antibiotic can wipe out beneficial gut microbes that have evolved with us, thus setting the stage for superinfection with the often lethal Clostridium difficile infection. Each time I consider an antibiotic prescription, I have to weigh the potential infection-fighting benefit (non-existent for a viral infection) versus the likelihood of destroying helpful microbes and selecting for resistant microbes. The same considerations help guide my decisions about dosing and duration of therapy. See Andrew Read’s article on a counterintuitive approach for antibiotic prescribing,  supported by theoretical evolutionary modeling and empiric evidence. Read and colleagues suggest a benefit in avoiding resistance when physicians prescribe the minimum dose and minimum duration of treatment. A final consideration about antibiotics for pediatric patients is the chance of increasing asthma and allergy risk. Antibiotic exposure is linked to auto-immune disease and atopy in kids. This link may occur because antibiotics wipe out commensal gut microbes that have a beneficial effect on immune regulation. On the other hand, the only intervention in early sepsis that has strong evidence to support it is the swift initiation of broad-spectrum antibiotics.

Selection is powerful, but has limits in maintaining function, especially with advancing age. Moreover, tradeoffs involving selection are ubiquitous in biology, and can help explain the evolution of aging:

As an example, I am more likely to admit a 70 year old with chest pain than a 20 year old. Understanding age-related risk of death and age-related complications of procedures can be best understood as an outcome of evolution of life history traits. We have discussed antagonistic pleiotropy and declining power of selection in previous posts. Read more about those concepts here.

Evolved conditional strategies. It is well appreciated in ecology and evolutionary biology that traits can be expressed conditionally. Selection has shaped many traits to give the organism the ability to respond differently to different environments. This variation in phenotype is termed norms of reaction, and it reflects an adaptive strategy to cope with external threats to survival.  Because trauma and infection represent commonly encountered threats with a high risk of death, it makes sense that the humans, and other species, would evolve strategies to cope with them. Thus, we would expect to see reaction norms in many of our patients suffering from infection and trauma. This perspective can be useful in understanding why a great many once-standard critical illness treatments have been overturned in recent years: tight glucose control, anti-inflammatory treatments, goal directed treatment of central venous pressure, etc. If some variation in those parameters evolved as a conditional strategy, it would make sense that our efforts to thwart them would fail.

Sometimes traits that tended to increase fitness in the past fail spectacularly in a new environment. This mismatch between old and new environments might be involved in the epidemic of drug abuse:

Drugs that hijack evolved reward pathways. Some days it can seem like half the patients (or more) in the emergency department are there because of complications from alcohol or narcotic abuse. We physicians are not responsible for the ongoing tragedy of widespread alcohol abuse. But we certainly have something to do with epidemic narcotic abuse and dependency. Evolution has shaped human neurobiology and behavior in ways that reward fitness-enhancing behaviors. The dopamine reward system is central in reinforcing motivation for behaviors that historically increased survival and reproduction; behaviors that induce dopamine reward circuitry include success in competition, eating nutrient-dense foods, and sex. These days, the evolved connection between evolutionary fitness and brain reward is often short-circuited by drugs, such as dilaudid, oxycodone, and hydrocodone. Even when medically indicated, many prescribed opiates are diverted for black market sale and recreational use, which too often leads to dependency, addiction, maladaptive behaviors, and overdose deaths. Just like antibiotic prescribing leads to microbial resistance evolution, opiate prescribing leads to misuse and harm, because of an evolved neurobiological vulnerability. This is what makes the problem of opiate abuse such a hard nut to crack. My guess is that any good solution to the problem of narcotic abuse will also rely on evolutionary principles too.