After millions of years of evolution, why do our bodies still seem so flawed? Why do we get disease at all? Why hasn’t natural selection prevented heart attacks, nearsightedness, and Alzheimer’s disease?
The common answer is that “natural selection isn’t powerful enough to get rid of disease.” This is usually the wrong idea.
Instead, it’s important to realize that the body is a bundle of careful compromises. The reason we have diseases today is that the very things that cause disease were helpful for us at one point, or are still helpful for us in certain situations. In this way, evolutionary medicine seeks to understand why we have disease.
Here are four principles of evolutionary medicine.
Adaptations that net promote reproductive success are selected for, even if they cause disease after the organism reproduces.
In other words, anything that kills or debilitates you after you already raise kids to independence is not strongly selected against. Further, genes that increase your lifetime reproduction will be selected for, even if they reduce your longevity or ‘happiness.’
In an extreme example, Huntington’s Disease is an intimidating disease—patients die between ages 40-60, and it’s autosomal dominant. But because it causes no apparent harm before age 40, all their kids are born, so the disease faces little selection pressure.
Genes that promote eating and fat storage may increase survival and thus reproductive fitness, even at the expense of later heart disease.
Traits that give an overall fitness advantage, despite increasing vulnerability to some disease, can still be selected for.
The modern environment is very different from the environment in which humans evolved over millions of years. Genes that were once helpful may cause disease today. Examples:
When thinking about human health, it’s tempting to wish we had near-superpowers, like immortality or the ability to regenerate lost limbs. However, the body is a careful set of compromises. The body needs to balance functions like reproduction, survival, recovery from damage, energy efficiency, growth, and susceptibility to disease.
Why don’t we regenerate limbs? This is a balance of utility vs. maintenance cost. Natural selection has apparently shown us that this type of repair capability is net negative.
For much of human history, losing a limb was likely fatal—a Stone Age man who lost an arm would bleed to death in minutes. If the chance of survival in such a case was low, then there was little point in having the machinery to regenerate limbs. If everyone who had limbs amputated died, then the gene to regenerate arms could not be selected for.
Furthermore, the maintenance costs include not just the energy expended in maintaining the machinery to regenerate limbs, but also an increased rate of cancer. It’s dangerous to let mature, specialized tissue have more than the minimum needed capacity to repair likely injuries.
Senescence has been stable over time. Over the past centuries, the average human lifespan has increased, but the maximum lifespan has not. Despite all our medical advances, humans cannot live past about 115 years.
Theoretically it would be a huge reproductive advantage to maintain health for more time - imagine humans who lived to be 300 and reproduced for 100 years. Why haven’t humans evolved to live longer?
Per evolutionary medicine principles, there must be a competitive equilibrium at play - living longer must confer some compensatory fitness disadvantage, and the inverse is true. The balance is between faster, more aggressive mating (which may necessarily cause decreased longevity) vs. longer lifespan (which may necessarily trade off with decreased fertility).
Animal experiments show that increasing lifespan causes lower and later reproduction. Somehow there is a tradeoff between longevity and vigor. For example, mice on caloric restriction extend their lifespans, but they don’t reproduce. They stay suspended in a pre-reproductive state waiting for adequate food supply.
In many animals, the male produces sperm and the female produces eggs. This contrasts with hermaphrodite animals, which can produce both sex cells within one organism.
The small size of sperm and large size of eggs make it easier to get sperm inside females, rather than the opposite. It would be much more difficult for a woman to transmit her egg into a male.
The size of the egg and sperm have huge consequences on the mating relationship between males and females:
Darwinian medicine can help us understand the diseases we face.
If something seems like a maladaptation of the body or an error in natural selection, we probably have missed something. Instead, Darwinian medicine asks questions such as:
Darwinian medicine can also help patients. If patients understood the evolutionary bases of their disease, they can have satisfying reasons for why the disease exists. This may prevent patients from feeling that disease is meaningless, and it may inspire hope that there are ways to circumvent the disease.
We are just at the beginning of understanding how the modern environment causes disease. Consider all the following aspects of modern life that would be utterly foreign to our Stone Age predecessors:
In the coming years, we may find a host of consequences resulting from today’s unnatural environment.
After millions of years of evolution, why do our bodies still seem so flawed? Why do we get disease at all? Why hasn’t natural selection prevented heart attacks, nearsightedness, and Alzheimer’s disease?
The common answer is that “natural selection isn’t powerful enough to get rid of disease.” This is usually the wrong idea.
Instead, it’s important to realize that the body is a bundle of careful compromises. The reason we have diseases today is that the very things that cause disease were helpful for us at one point, or are still helpful for us in certain situations. In this way, evolutionary medicine seeks to understand why we have disease.
In thinking about disease, it’s important to distinguish between proximate causes and evolutionary causes of disease.
In Darwinian medicine, evolutionary explanations of disease require explaining more than just the current function - they should explain aspects of the evolutionary adaptation that leads to the disease:
Evolutionary medicine is not just philosophizing. It’s also useful in predicting what to expect when treating disease. For example, infections usually cause low iron levels. The proximate viewpoint would suggest that giving iron as a treatment is an obvious choice. However, the evolutionary viewpoint would question, “is lower iron perhaps a defense against infection? Perhaps the body has adapted to lower iron during an infection, because it helps fight the infection? If this is true, wouldn’t giving iron actually worsen the infection?”
This still doesn’t completely answer the question. If natural selection is so powerful, then why do we still get disease? There are a range of causes:
We’ll dive into each of these causes and many more examples throughout this book.
A note on ethics: Darwinian medicine may sound a bit unsympathetic and even bordering on aspects of eugenics, with ideas that natural selection removes poorly adapted genes from the population. The authors of Why We Get Sick completely reject that medicine should assist in natural selection (i.e. “let the weak die”), or that any disease is good for pruning the genetically weak. Instead, this book’s approach is useful primarily to understand the origins of disease and to further the treatment of disease.
Natural selection is often thought of informally as “survival of the fittest,” but this is a confusing phrase. People often have the wrong idea of what “fitness” means. It doesn’t mean fitness in the everyday sense of good health and long life.
In Darwinian terms, a higher fitness means more reproduction and a greater number of viable offspring. If a gene leads to production of more viable offspring in future generations, that gene will be enriched in the population. Likewise, if a gene codes for characteristics that result in fewer viable offspring in future generations, that gene is gradually eliminated.
Taking the phrase “survival of the fittest” again, we now see that “survival” is important for natural selection only insofar as it increases reproduction. If a gene helps an individual survive longer, but at the expense of having fewer offspring, that gene will show up less often in the gene pool.
Genes that increase lifetime reproduction will be selected for, even if they reduce the individual’s longevity.
This is one reason that we haven’t evolved away common diseases—the genes that cause gout and dementia later in life may actually increase our reproductive fitness earlier in life.
A key takeaway: when we find something that seems like an error in natural selection, more likely we are missing some important function that compensates for the deficit.
There’s a parable of Henry Ford when he asked a car engineer, “Is there anything that never goes wrong with any of these cars?” The engineer responds, “Yes, the steering column never fails.” Ford responds, “Redesign it. If it never breaks, we must be spending too much on it.”
Likewise, the body has evolved to be a set of compromises. Some traits might increase vulnerability to some diseases, but still give an overall fitness advantage.
A gene’s contribution to fitness is not determined in isolation. It’s measured in a particular species in a particular environment. Change the environment, and the gene may no longer increase fitness.
For example, imagine a population of rabbits in the forest. Half of them have a gene that makes them more timid at venturing out in the open, which decreases their chance of being eaten by foxes. The other half doesn’t have this gene. The timid half spend more time hiding in their dens, and so they tend to be less well fed than the bolder half.
The environment changes, and a very harsh winter arrives. The timid half stay in their rabbits’ dens, and most of them starve to death. The bolder half venture out and get food; while the bold rabbits are more likely to be eaten by foxes, they also eat more in the winter, and so a greater fraction survives than the timid half. Over a series of harsh winters like this, the timid gene may be eliminated from the population.
Change the environment, and the gene may no longer increase fitness. As we’ll discuss later, this may be the case for a variety of genes that lead to disease in our abundant modern environment, like heart disease.
Natural selection operates by chance. Whether a population develops any particular trait depends on a string of random events:
This randomness has a number of implications:
A famous documentary about lemmings jumping off cliffs explained that when food becomes scarce, a fraction of lemming jump off the cliff to save enough food for others to survive. This was an example of the theory of “group selection”—some may sacrifice themselves for the sake of the species.
From a natural selection point of view, this is nonsense. Imagine that a gene codes for a lemming’s willingness to jump off a cliff to save the group. Some individual lemmings have a mutation that let them stay back and survive.
Over time, all the heroic, self-sacrificing lemmings die, and the selfish lemmings stay back and reproduced. The gene that promotes self-sacrifice is removed from the population.
The key point is that natural selection benefits genes, not groups. Natural selection acts on the level of the individual without a concern for the species. As Richard Dawkins noted in The Selfish Gene, the individual is merely a vessel created by genes for the replication of genes.
(So why did the lemmings jump off the cliff? It turns out it was staged—documentary producers used brooms to force the lemmings to jump into the water.)
From a natural selection point of view, we’re not completely devoid of reasons to help others to further our own genes. Your relatives share many of your genes. By helping your relatives, you increase their reproductive success, which in turn promotes the propagation of your genes.
The closer the relative is, the more apt you are to help them. Siblings share half of their genes with each other; cousins share one-eighth of their genes. From a genetic point of view, your sister’s survival and reproduction are half as important as yours, and your cousin’s are one-eighth as important.
Because of this, natural selection favors helping your relatives if the cost to you is less than the benefit to the relative, times the degree of relationship. A biologist said that he would not sacrifice his life for one brother, but he would for two, or eight cousins.
Good evolutionary hypotheses are testable and stand up to reason. Many speculations on traits and behavior don’t meet this criteria. Consider these superficially justifiable explanations that break down under scrutiny:
Proper evolutionary reasoning undertakes the “adaptationist program,” which is a method of investigation that essentially makes hypotheses testable.
If you understand the functional significance of some piece of human biology, you should be able to predict other unknown aspects, then investigate to confirm whether they are there or not.
For example, consider a species of bird who may lay between 3-5 eggs each mating season. One might naively think that the exact number happens merely by chance. Instead, consider that the individual bird lays a different number of eggs each season to maximize her individual reproductive success—the bird only lays as many eggs as she feels fit to provide for. This would predict that if you found birds who laid 3 eggs, then added an egg to those nests, the offspring would be more likely to die than those of birds who naturally lay 4 eggs.
As another example, consider the sex ratio in humans. One might reason that males and females are equally balanced is because the X and Y chromosomes are randomly chosen with equal probability. But this is a proximate explanation that doesn’t explain why this is important. The underlying evolutionary reason is that producing the gender that is scarce at any time has the reproductive advantage. Individuals that produce only male offspring will be selected against when females are scarce, and so the genes that predispose to male offspring are selected against. The same logic applies to genes that promote female offspring. Over time, these pressures balance out, so that individuals have genes that produce offspring at equal sex ratio.
The idea here is that a point of view based around natural selection can help make important medical discoveries. Darwinian medicine asks questions such as:
The war with bacterial and viral pathogens has gone on for millions of years and continues today. Our body has evolved defenses to combat infections, and in turn the pathogens evolve ways to overcome these defenses.
As previously described, the body is a collection of compromises. Maintaining the defenses at all times would be too costly—there’s no need to raise defenses when there are no pathogens around.
When the defenses do activate, they sometimes cause symptoms that appear to be the disease. In reality, the symptoms are the defense mechanisms at work. If this hypothesis is true, then treating these symptoms can counter-intuitively aggravate and lengthen the infection. Here are a few examples:
In all these defense mechanisms, treating the symptom for the sake of comfort might compromise recovery and worsen the illness.
But not all defenses are adaptive or essential, and sometimes there isn’t a need to suffer without reason. The authors aren’t suggesting never relieving these defenses, but rather to be mindful of when relief is and isn’t net positive.
Even when we’re not in an active infection, the body has a host of defenses that prevent disease. These include:
Less accessible body areas have less regenerative capability. Infections of the brain or heart are usually fatal, so maintaining regenerative capabilities in these areas would have little benefit. As a result, natural selection seems to have shown that defense mechanisms to protect the brain during the rare infection don’t outweigh the costs of maintaining this system.
Some defensive behaviors have dual purposes, benefiting both host and pathogen.
Sometimes, infectious disease really does cause damage to the host. Often this is done to procure more resources for the pathogen and support its spreading or reproduction. Beyond these purposes, damage to the host is often incidental and costly to both host and pathogen. It does no good for the tapeworm to cause its host to be malnourished; it does no good for hepatitis to destroy the liver completely and quickly kill the host. As we’ll discuss in the next chapter, any especially virulent strain that rapidly killed its host would have little chance to spread itself, and the mutations that caused its virulence would be selected against.
Just like animals, bacteria and viruses undergo natural selection to propagate their genes. The pathogens that can best overcome host defenses succeed in reproducing and spread their beneficial genes to the population.
Pathogens have evolved a variety of responses to host defense, including:
We’ve seen a variety of strategies for hosts and counterstrategies by pathogens. Some observations of infectious disease, like decreasing iron levels, benefit the host; others benefit the pathogen; some are merely incidental damage in the ongoing war.
Here is a classification of how infectious disease manifests, based on their function.
| Observation | Examples | Beneficiary |
| Hygienic measure by host | Killing mosquitoes, avoiding sick neighbors, grooming, removal of parasites | Host |
| Host defenses | Fever, iron withholding, sneezing, vomiting | Host |
| Repair of damage by host | Regeneration of tissues | Host |
| Compensation for damage by host | Chewing on the other side of the mouth to avoid tooth pain from infected tooth | Host |
| Damage to host tissues by pathogen | Tooth decay, hepatitis liver damage | Neither |
| Impairment of host by pathogen | Ineffective chewing, decreased detoxification of blood by infected hepatitis liver | Neither |
| Evasion of host defenses by pathogen | Molecular mimicry (MHC complex), change in antigens (trypanosome changes surface proteins) | Pathogen |
| Attack on host defenses by pathogen | Destruction of white blood cells; secretion of factors that inhibit inflammation | Pathogen |
| Uptake and use of nutrients by pathogen | Growth and proliferation of trypanosomes, viruses bind to cellular receptors and enter cells to hijack resources and replicate | Pathogen |
| Dispersal of pathogen | Transfer of malaria parasite to a new host by mosquito, sneezing | Pathogen |
| Manipulation of host by pathogen | Exaggerated sneezing, diarrhea, behavioral changes (rabies increases chance of bites) | Pathogen |
As discussed, hosts and pathogens adapt to each other in continuous cycles. One strategy is quickly defeated by a counterstrategy. This gives rise to the Red Queen Principle, named after the statement in Alice in Wonderland: “It takes all the running you can do, just to keep in the same place.”
Antibiotics were one of the great medical successes of the 20th century. However, due to widespread use, increasingly bacteria are evolving resistance to even our most powerful antibiotics. The multi-drug resistance strain of tuberculosis causes a 50% mortality rate.
Bacteria don’t become resistant to antibiotics through gradual tolerance. Instead, rare mutations occur that confer resistance. In an environment where an antibiotic is present, these resistant bacteria replicate more readily and take over the population.
Once bacteria evolve drug resistance, they can pass these genes to other bacteria through plasmids.
If the environment changes and the antibiotic is removed, the ancestral strain slowly replace the resistant strains. This suggests that maintaining the resistance causes a fitness disadvantage (once again, natural selection is a collection of compromises).
However, the disadvantage of the resistant mutation can itself be mutated away. Therefore, antibiotic resistance can persist in a population, even when no antibiotics are present for a long time.
Here’s an interesting thought—if parasites use host resources to survive and reproduce, why don’t they help the host thrive and get more resources? The longer the host lives, the more the parasite can reproduce, and the more they can spread offspring to new hosts. This would suggest that the natural evolutionary path of parasites is to gradually become more useful until it becomes indispensable to host survival.
The authors argue this thinking is flawed and ignores two critical points:
In contrast to the thinking above, infections are actually in a stable equilibrium right now. Both pathogens and hosts make tradeoffs between values like growth rates, reproduction, and defense.
A better model of virulence, or severity of disease, would include all the factors at play in the complex game of survival:
The balance between virulence and dispersal is especially important to the success of the pathogen. This leads to a few important ideas:
Importantly, changing the mechanism of dispersal and the ease of dispersal may change a pathogen’s virulence. The easier it becomes for the pathogen to spread to other hosts, the more the pathogen can afford to be virulent and damage the host. Here are a few examples:
Thus, epidemics may result when a novel environmental circumstance promotes virulence. For instance, the bubonic plague had festered in Asia for many years, but it only became an epidemic in Europe because of the environmental change. In Europe, the concentration of the population in cities with flea-infested rats gave the plague a novel way to disperse itself.
Sometimes even our efforts to improve the environment can counter-productively make pathogens more virulent. Polio exposure in early childhood has only mild effects, and until the early 20th century, it wasn’t much of a problem. Plenty of people got polio with mild effects. But in the early 20th century, sanitation limited polio infection until a later age, when it has much more severe effects.
(Shortform note: these ideas lead to more consequences of how our treatment of disease influences the evolution of pathogens:
Pain and fear are often considered negative conditions to be avoided. But both pain and fear serve vital functions in survival. Pain signals that tissue is damaged; fear signals that danger might be nearby, and so caution is warranted.
Both pain and fear are useful to avoid injury. Blocking either can worsen damage. People who lack the capacity to feel pain almost all die by age thirty; people born without fear tend to end up in the emergency room or the morgue.
Fear of some things is innate, since that mistake even once is very costly. A rabbit is born to be afraid of foxes, since slipping up once can cost a rabbit its life. But innate behavior is inflexible—it can’t mold to new situations that would merit more appropriate responses.
More flexibly, other fears can be learned so as to be situationally useful. A fawn might stare blankly at an approaching wolf until its mother flees. Then the fawn learns that wolves are probably bad and should be run away from, and the fawn passes this lesson to her children. These types of fears are not hardwired; they can be unlearned, and they can be extinguished when the cue is removed.
Humans have the benefit of reasoning and memory, so we can learn indirectly. We know that fire is dangerous and we install smoke alarms without personally knowing anyone who died in a fire.
Avoidance can be conditioned more easily to some cues than others.
Our modern environment has changed a lot in the past thousands of years, but we haven’t yet evolved visceral responses to new environmental dangers.
When repairing an injury, the body needs to make a series of balances:
As with infection, when we consider injury as a disease, we need to distinguish between impairment from injury from adaptive responses that heal injuries.
Some animals can regenerate whole body parts when lost, such as starfish regenerating arms and lizards regenerating tails. Wouldn’t it be useful for humans to be able to do so too?
As always, any trait requires balance. Here, the balance is between a) the benefits in improving the organism’s fitness, and b) the costs of maintenance. The genes to regenerate limbs will only be selected for if its benefits outweigh the costs.
In the case of regenerating limbs, the maintenance costs include not just the energy expended in maintaining the machinery to regenerate limbs, but also an increased rate of cancer. It’s dangerous to let mature, specialized tissue have more than the minimum needed capacity to repair likely injuries.
Natural selection has apparently shown us that this type of repair capability is net negative. For much of human history, losing a limb was likely fatal—a Stone Age man who lost an arm would bleed to death in minutes. If the chance of survival in such a case was low, then there was little point in having the machinery to regenerate limbs. If everyone who had limbs amputated died, then the gene to regenerate arms could not be selected for.
This is another example of how Darwinian medicine thinking helps us understand our biology on a deeper level. For any biological trait (or absence thereof), consider the pros and cons of having the trait, then reason about how that trait has been molded by natural selection.
Just like animals, plants undergo natural selection for reproductive fitness. In the wild, plants develop defenses from eating, like hard pods and toxins.
Plants have developed a wide range of toxins, including tannins (in wine), alkaloids, cyanide, glycosides (from foxgloves), diazepam (from potatoes), and solanidine (nightshades, potatoes). While the amounts of toxins in typical plants aren’t enough to damage humans, consider how much they might deter a hungry mouse weighing 1/3000th of a human’s weight.
If you’re ever foraging for plants in the forest, you obviously would like to know which plants are toxic and not. Darwinian thinking is helpful here: consider the natural competitive equilibrium that would result in the phenotype observed.
In Stone Age times, eating too much of one thing increased the risk of consuming an unhealthy amount of toxins. Eat a diet consisting entirely of wild potatoes, and you might actually be poisoned.
Therefore, we’ve evolved a preference for variety in food. We prefer to eat a buffet of options, rather than stick to a single diet daily. This is yet another example of how a trait was helpful in the Stone Age, but a bad adaptation for today’s food-plenty world.
Today’s environment likely exposes us to fewer toxins than ever in history. However, the body builds tolerance to toxins upon exposure. Therefore, today we might be the most susceptible to toxins, and the most incapable of handling large toxic insults, than ever before.
At the same time, the modern world has introduced a variety of new toxins to which we haven’t evolved an instinctual avoidance of. This includes heavy metals, antifreeze, cleaning products, and radioactivity.
Cooking neutralizes many toxins in wild food. This contributes to cooking cultural traditions that are passed down through generations.
People vary in susceptibility to pathogens depending on growth stage and gender.
Actively metabolizing tissues are more vulnerable to toxins than dormant ones; dividing cells are more vulnerable than quiescent ones; undifferentiated cells are more vulnerable than differentiated ones.
This might explain nausea in early pregnancy. In pregnancy, morning sickness peaks in first trimester, then subsides over time. Fetal vulnerability to toxins is also highest in the first trimester.
This thinking might also explain why children tend to hate bitter vegetables and prefer sweets. Toxins cause more damage in the young, developing bodies of children, and so we might have evolved to avoid toxins early in life. (Shortform note: Remember this when you next see children refuse to eat brussels sprouts!)
We now return to a question asked earlier in the summary: Why haven’t we evolved away genes that cause disease?
You now know a few reasons: the disease-causing gene may have benefits that are not as obvious. Also, the gene may have been beneficial during the Stone Age, but only cause disease in today’s environment (we’ll cover this explanation more later in the chapter).
Here are even more reasons that we haven’t evolved away genes that cause disease:
As we’ve learned, a major reason that disease-causing genes still exist is that they may have been beneficial during the Stone Age, but only cause disease in today’s environment.
Consider how vastly different the survival conditions of early humans were, compared to the modern age.
Humans (or our primate ancestors) lived this way for millions of years. Only in the past 20,000 years is agriculture believed to have been developed.
Therefore, it’s reasonable that ancestral genes promoted survival in the past, but have only recently become a liability in modern environments. Here’s a list of examples.
In a resource-scarce world, wanting more sugar, fat, protein, salt was a survival trait. Storing more weight in response to food was a survival trait in times of famine.
We do have natural limits to overeating in a single meal, stopping us from overburdening our GI systems. But we don’t have built-in limits to long-term overeating. This is why people can carry a body weight far beyond what is normal.
We’re not even prepared for today’s selection of food. As hunter-gatherers in the Stone Age, we adapted to pick the sweetest fruit. But what happens if you surround yourself with cheesecake and candy bars? Modern food triggers supernormal stimuli that excite your senses far beyond natural foods.
Our genes also work against us during weight loss. Because we evolved to survive famine, when our bodies detect a deficit in calories, they cut our metabolism to conserve calories. This makes further weight loss difficult.
Finally, today’s diet may cause diseases that never appeared in the past. In the prehistoric past, dental cavities were never a problem, as evidenced in skeletal remains. It’s only today’s sugar-rich diets that cause them.
Ironically, our resource-rich environment may promote dietary inadequacies.
When agriculture was developed, humans often developed vitamin C deficiency, due to less foraging of vitamin-rich foods like berries, and more eating of wheat and corn.
Today, artificial sweeteners trigger the body’s expectations for actual ingestion of sugar. Humans never lived in a time when artificial, non-digestible sweeteners existed. The body reduces glycolysis and blood sugar in response to sweeteners; iff no real sugar is absorbed, the body may go into hypoglycemia (low blood sugar) and thus crave more food.
In human history, it was adaptive to conserve energy by being lazy whenever possible.
Clearly in today’s sedentary environment we move far less than hunter-gatherers.
25% of the human population is myopic, or near-sighted. A simple line of thinking would ask, “How could this portion of people possibly have survived in ancestral times?”
Instead, consider that myopia might be a modern artifact of how we use our eyes—namely, that we do much more close reading than Stone Age people did.
What’s the mechanism behind myopia? During development, the eye grows in response to visual blurriness fed to the brain. (If only one part of the visual field is blurry, only that part of eye grows, leading to astigmatism). This system is usually remarkably accurate—the margin of error for focusing the lens on the retina is 1% the length of the eyeball.
For 25% of people, something about reading or other close work causes the eye to keep growing inappropriately, leading to myopia. This could be the blurred edges of letters, or a focus on a close book with blurred surroundings.
If today’s near-sighted people had been born in a hunter-gatherer society, where no reading was done, they likely wouldn’t have vision problems.
Alcoholism is only a modern problem with the widespread availability of alcohol and distillation into high-proof spirits. In the historical past, alcoholism wasn’t as much a problem with low-alcohol content drinks like fermented fruit, or when homes had to prepare their own alcohol.
Likewise, addiction to drugs arose when opium was processed into the more addictive heroin, and coca into cocaine. Substance abuse seems to be largely a consequence of today’s environment.
Why might genes predisposing to alcoholism have been helpful in older times? These genes may have increased the ability to pursue rewards despite difficulties, or psychological reinforcement in response to certain rewards. These are hallmarks of alcoholic behavior, and would have been useful in many situations.
Humans adapted their skin color for the areas they developed in. In northern areas with low sunlight, humans developed light skin to absorb and avoid vitamin D deficiency. In equatorial areas with plenty of sunlight, humans developed dark skin to limit UV radiation.
Now that different colored humans live all around the globe, the skin can now cause disadvantages in different climates. Light-skinned people in sunny areas get skin cancer. Dark-skinned people in low-sunlight areas get insufficient vitamin D.
A common line of inquiry is to ask whether disease is caused by genetics or the environment. In some cases, it’s clearly one or the other.
But in the cases above, it’s the wrong perspective. Both the gene and the environment are insufficient by themselves, but interact together to produce the disease.
In fact, discovering that a disease has a genetic cause may actually be a blessing, if a specific feature of the environment is causing the disease.
We are just at the beginning of understanding how the modern environment causes disease. Consider all the following aspects of modern life that would be utterly foreign to our Stone Age predecessors:
In the coming years, we may find a host of consequences resulting from today’s unnatural environment.
What people call aging is biologically termed senescence, the bodily deterioration accompanying age. Human organ systems tend to wear out at the same rate, on average. Maintenance and repair systems lose their efficacy, and old people become progressively more vulnerable to diseases and injuries.
Senescence has been stable over time. Over the past centuries, the average human lifespan has increased, but the maximum lifespan has not. Despite all our medical advances, humans cannot live past about 115 years.
Theoretically it would be a huge reproductive advantage to maintain health for more time - imagine humans who lived to be 300 and reproduced for 100 years. Why haven’t humans evolved to live longer?
Early theories suggested senescence was necessary to make room for the young. But as we’ve learned with lemmings in Chapter 2, natural selection doesn’t occur on the group level. It’s also prone to exploitation by individuals who don’t follow the same strategy—the gene that caused individuals to reproduce rapidly and live longer would overtake the population.
Later theories, in line with our other explanations of why genes persist, suggest that genes that promoted early survival and reproduction would be selected for, even if they cause disease later in life. In a Stone Age world where most people die for reasons other than old age, there wouldn’t be adverse selection against senescence.
Again, per evolutionary medicine principles, there must be a competitive equilibrium at play - living longer must confer some compensatory fitness disadvantage, and the inverse is true. The balance is between faster, more aggressive mating (which may necessarily cause decreased longevity) vs. longer lifespan (which may necessarily trade off with decreased fertility).
Here are examples of genes that confer advantages early in life but cause later disease:
Here’s more suggestive evidence that lifespan and fertility trade off with each other:
(Shortform note: Modern culture is selecting for a later age of reproduction in women, pushing many to have babies in their 30’s when they might have had them in their teenage years centuries ago. This might select for women who are able to reproduce later and unintentionally select for decreased senescence.)
The authors believe that extending maximum lifespan is a fool’s errand because there are too many biological forces working against this goal. But delaying senescence and maintaining ability up until maximum lifespan may be more tractable.
In humans, males live an average of seven years less than females. The authors argue this is because males must compete for female mates, and much of male physiology is devoted to this competition. Less concern is paid to preservation of the body. If an unusually fit male can mate with many women and have a lot of offspring, while mediocre males mate with no women and have no offspring, it makes sense to devote resources to this competition.
Menopause is somewhat of a mystery. Why should women stop reproducing at any age?
This might be explained by a mother needing to split finite resources over children. Having too many children might decrease the fitness of the mother’s children. Menopause is a natural safety switch to conserve resources for her limited number of offspring.
(Shortform note: Why don’t males undergo something like menopause? They stay capable of reproduction will into old age. As we’ll discuss in Chapter 13, because for most of history men could not prove that a child was theirs, they tend to participate less in childcare. Their strategy, then, is to mate as frequently and over as long a period of time as possible. Any male that that ceased reproduction early would be at a large reproductive fitness disadvantage.)
Some genes may do the opposite of the above, conferring advantages throughout adult life at some cost to reproductive fitness.
For example, gout is caused by urate, an antioxidant that scavenges radical oxygen species. It’s possible that people who suffer from gout may show decreased senescence.
Evolution makes incremental changes on what came before. It does not totally scrap a current design and start from scratch. This can lead to some historical artifacts that cause problems today, and that we might redesign should we have the choice.
For example, in all vertebrates, the esophagus (leading to the stomach) and the trachea (leading to the lungs) have the same input (the mouth). This can lead to choking. This arrangement came from an early wormlike ancestor that used the same tube for both respiration and digestion. All vertebrates descended from this ancestor and inherited this design.
In contrast, insects and mollusks have complete separation of the breathing and eating structures. They evolved on a different lineage and aren’t beholden to this evolutionary artifact.
Here are more examples of evolutionary legacies:
(Shortform note: The ideas in Chapter 10 were integrated into previous chapters, so our summary is skipping to Chapter 11.)
Allergies show such a strong reaction, are so inconvenient, and form a system of such complexity that, per evolutionary medicine principles, it seems unlikely they have no useful function to compensate, else they’d have been selected out.
Briefly, how do allergies work? They are the consequence of a series of steps upon exposure to a foreign substance:
IgE makes up just 1/100000 of the total antibody in blood, but it produces an outsized response. In an allergy, 10% of IgE may be specific to the antigen, such as pollen;.
The function of allergy is unclear, though there are a few leading hypotheses:
Why are allergies becoming more common over the past century? There are a few suggestive reasons:
Cancer arises when normal mechanisms for cell growth go awry.
The human body has 10 trillion cells, many of them replenishing themselves. With each division of a cell, mutations in genes are introduced. Given all this activity, it’s really a wonder that we’re typically protected against cancers for decades at all.
Cells have a number of mechanisms to prevent cancers:
The relationship between cancer and host operates in some ways like that between virus and host. Cancer can be considered a parasite that appropriates resources for its own gain at the expense of the host. But there’s one big difference between virus and cancer—the cancer is noncommunicable and thus dies with the host.
Why have cancer rates increased over the past centuries?
There is one clear linkage between the modern environment and cancer in women: more menstrual cycles means more cancer in female organs (breast, ovaries, and uterus).
Compared to modern women, Stone Age women experienced fewer menstrual cycles for a few reasons:
Today’s environment promotes an early menarche and late menopause. Furthermore, women have fewer children, and they breastfeed less. All of this cause modern women to have 2-3x the number of menstrual cycles of Stone Age women.
The underlying mechanism could be that the hormonal responses promoting reproduction cause increased vulnerability to some cancer.
Optimistically, this also provides an angle of attack for finding a way to simulate Stone Age menstruation patterns to reduce cancer risk. For example, blocking menstruation through long-term hormonal birth control might decrease the rate of cancer.
There are perhaps few mysteries as intriguing and perplexing as the courtship between females and males. Darwinian thinking has explanations for this too.
Some animals reproduce asexually, with mothers essentially giving birth to a clone of itself. Why do mammals and humans go through all the trouble of sexual reproduction?
The classical explanation is that sexual reproduction promotes genetic diversity, through the combination of genetic material from the mother and father. Having more genetic diversity avoids over-optimization to one genome, and it promotes survival in changing environments.
In comparison, a woman who could bud off offspring without sex may have a short-term advantage in producing offspring, but the entire enetically identical clan may be wiped out in one calamity. If ten thousand clones of one woman are all especially vulnerable to influenza, they may all die in one epidemic, whereas a genetically diverse population would only lose a fraction of its members.
Different animals have different reproductive strategies. They vary in these factors:
For example, a female salmon releases hundreds of eggs into the water, and a male fertilizes the eggs. The fish then hatch from eggs with no parent supervision and forge onward into life. This is obviously very different from how humans reproduce.
In many animals, the male produces sperm and the female produces eggs. This contrasts with hermaphrodite animals, which can produce both sex cells within one organism.
The small size of sperm and large size of eggs make it easier to get sperm inside females, rather than the opposite. It would be much more difficult for a woman to transmit her egg into a male.
Human sperm are much smaller than eggs, which contain most of the resources for the developing embryo. This size disparity arose through natural selection. Consider a situation where eggs and sperm started out being the same size. The sperm that carries fewer nutrients travels faster and wins the race to the egg. To compensate for the lower-nutrient sperm, the eggs that contain more nutrients end up producing more viable offspring. Both these forces continue, with the sperm getting smaller and the egg getting larger, until we arrive at today’s equilibrium.
The size of the egg and sperm have huge consequences on the mating relationship between males and females:
Suddenly, human courtship rituals might make more sense! But there’s more—how the child is taken care of also influences mating behavior.
The skulls of humans are relatively larger compared to primate relatives and ancestors. The size of the human skull allows for a larger, more intelligent brain. However, how large the fetus’s skull can be is limited by the size of the female birth canal. Human children are therefore born with under-developed brains, and they require a long period of care to become self-sufficient and for their skulls to continue growing outside of the mother. Contrast this to other animals like baby deer, who are much more self-sufficient when born.
This long period of childcare requires the participation of both males and females, which has engendered the following mating-related behaviors:
From a biological point of view, males and females want different things in relationships.
Males want women who are:
Females want men who are:
Over time, the selection pressure may cause species to develop traits that are not all that practically useful. Male peacocks have large plumes of feathers that serve no purpose other than reproduction, and may actually hamper their survival among predators.
Some female primates change color when they’re ovulating, signaling that it’s mating season.
In contrast, female humans conceal when they’re ovulating—there’s no external difference between ovulating women and non-ovulating women. This has a number of benefits:
Both women and men are concerned about the loyalty of their mates. Women want men to provide for their family, and men want women to be faithful so they don’t bear the children of other men.
People in relationships might therefore want to test their relationships for loyalty. They can provoke their partner with arguments or instigate jealousy, and see if the partner sticks around and stays committed.
(Shortform note: If true, then this suggests that relationships where the parties are unsure of each other’s capacity for commitment tend to be more volatile, with more arguments.)
The father can’t guarantee the child is his, while the mother can. Therefore, the man is fearful of being cuckolded and raising a child that is not his.
In response, the father shows jealousy and a threat of anger. This is a response that discourages other mates from intruding, and dissuades the mother from straying.
Sexual jealousy is so strong that it’s been institutionalized in many cultures. In China, women’s feet were bound as children to limit their mobility and independence. It was tradition to demonstrate virginity on wedding night by observing blood on the marital sheets. The authors say that for much of history, in nearly all societies, men created social institutions to control female sexuality.
(Shortform note: This might also point to why there’s a modern double standard of sexual activity. Females who are promiscuous are chastised by males (since they fear cuckolding), and by women (for possibly drawing away men). In contrast, men are admired for their sexual conquests, because it makes them more appealing as possible mates.)
According to evolutionary medicine, pregnancy is a conflict between mother and fetus. The fetus carries only half the mother’s genes, so their interests are not perfectly aligned. The fetus will manipulate the mother to provide more nutrition, and the mother will resist this.
Here are two examples of how the mother and fetus combat for control of resources:
Both these examples incur risks to the mother, and possible death of the fetus, but on average the fetus wins. Therefore the fetus can be seen as playing the odds for its own benefit.
Women giving birth are more successful when a supportive woman is around—they show a lower rate of C-section by 66% and lower use of forceps by 82%. This may be because human babies are born in an odd position, facing backward, and if the mother were to finish labor by pulling on the child, she might injure it. A supportive woman would have been able to help reduce the risk dramatically, and so women may have evolved a preference for another woman during labor.
During birth, pressure on the vaginal walls causes oxytocin to be secreted. Oxytocin makes the mother bond to her child. C-sections don’t have this signal and oxytocin secretion. In sheep, birth by C-section usually causes the mother to reject the baby as her own offspring.
Babies naturally cry to get attention, and this sound is naturally aversive to parents so they try to make it stop.
Crying could increase fitness by promoting bonding with the mother through contact. It also encourages feeding and lactation, which prevents competing pregnancies from taking resources from the baby.
Babies who cry more for no apparent reason are often diagnosed with colic, but colicky babies don’t cry more frequently or at special times, just for longer. The authors hypothesize that this may result from modern habits of infrequent feedings and less contact. Some native tribes carry their babies around constantly and feed multiple times per hour, compared to once every few hours in typical Western societies.
As babies grow, they may manipulate the mother to pay it more attention. Spitting up milk prompts the mother to produce more milk. Also, infants may regress, or act younger and more helpless than it really is. Both these behaviors attempt to convince the mother to pay the baby more attention and limit future pregnancies.
Sudden Infant Death Syndrome causes more deaths in babies than any other cause except for accidents.
SIDS may be caused by the immaturity of the infant’s nervous system. As we’ve discussed, human babies are born with immature brains because the mother’s birth canal restricts how large the fetus’s skull can get.
SIDS may be higher in modern days because babies and mothers sleep apart. In the past, sleeping together led to coordination of sleep cycles and intermittent arousals that might sustain babies who are vulnerable to SIDS.
The field of psychiatry has tried to codify mental illness through clear-cut symptoms, rather than as gradations of emotions that are influenced by psychology and life experiences. Patients also understand their mental illness as imbalances in brain chemicals; they might be offended if the psychiatrist insisted that their illness were just a maladaptive psychological process.
The authors argue that ignoring the underlying function of emotions is like ignoring physiology in medicine.
As an analogy to today’s approach to psychiatry, imagine if we investigated “cough disorder,” creating objective criteria for diagnosis and subtyping (like coughing more than twice per hour). We then discover a cough center in the brain and muse about what dysfunctions lead to coughing, then investigate genetic causes for people prone to coughing.
This is clearly silly, but only because we know cough is a defense. We know not to look for causes of cough in the nerves and muscles, but rather upstream in the stimulus that provokes a cough (like the common cold).
Emotions are no different. They provide a valuable function to us in everyday life. Understanding this normal function should give us insight into when emotions go wrong.
As with everything else discussed in Darwinian medicine, our emotions are adaptations shaped by natural selection and have powerful uses.
Emotions adjust multiple aspects of our body to respond effectively in a situation—they change our cognition, physiology, subjective experience, and behavior.
Unpleasant emotions like fear and anxiety protect us from bad situations. Positive emotions like optimism and joy help us seek opportunity and seek more of what is good for us.
When we feel an emotion, we may not be conscious of its cause, but the cause likely does exist.
Let’s cover a range of conditions considered mental illness, question the function of the root emotion, and consider why mental illness might be so common today.
Anxiety causes the fight or flight physiological response that is useful in aiding an escape from danger—a rapid heartbeat, faster breathing, sweating, and an increase in blood glucose.
Anxiety is triggered in the face of danger or an emergency. Justifiable modern day triggers include hearing a gunshot or having a paper due.
But the anxiety-provoking system may be overly sensitive, just like a smoke alarm. A false positive (being anxious when you don’t need to be) isn’t very costly, but a false negative (not being anxious when you should be) can be fatal. As a Stone Age person, imagine you hear a stick break in the forest. It’s better to be overly cautious and assume it’s a tiger, than to have too little anxiety and assume nothing is wrong.
If anxiety is protective, why not be anxious at all times? The stress from anxiety uses extra calories, makes us unable to perform many everyday activities, and damages tissues. Like driving a car to its absolute limit, anxiety is a costly defense mechanism that pushes the body past its normal operating limits, and it should be released only in the case of emergency.
There might be a whole class of people who feel too little anxiety, but these aren’t classified as a mental disorder. People who feel too little anxiety may be impulsive and end up fired from their jobs or in emergency rooms.
Sadness often stems from a personal loss that can harm reproductive fitness. This includes losing resources (like a job), losing a mate, losing reputation, and losing friends.
The evolutionary function of sadness is to stop current losses and prevent future ones. Specifically, sadness has a few functions:
Interestingly, some depressions go away after a person gives up a long-sought goal and turns her energies in another direction.
Depression has other functions in signaling social standing:
Researchers studied a primate group and removed the alpha male. They then randomly chose another male and gave him antidepressants. That male reliably becomes the new alpha male.
Serotonin may therefore function in mediating hierarchies within a social group.
Compared to prehistoric environments, our modern environment may increase the risk of depression by disrupting our place in society.
Mass communications make all of humankind one competitive group.
In the Stone Age, we happily compared ourselves within a tribe of 100. Within this small group of people, you were likely good at something and valued for what you did. This made your life feel purposeful.
Now, with the advent of mass media, we compare ourselves to the best of 7 billion other people. You find it harder to be particularly good at anything. Compared to sports stars, beautiful models, and dashing entrepreneurs, you may feel average in nearly all respects, and you see your family and friends as similarly inadequate. (Shortform note: Because of social media, you might also believe your life is less fulfilling and exciting than those of your friends.)
We have a primal need for a secure place in a supportive group. In the past, this was served by a close-knit clan of dozens of people.
Today, people often live in competitive communities with no blood relatives nearby. Extended families have disintegrated. Many of us have a hard time finding someone who loves us for who we are, not what we can do for them.
Other institutions have substituted for the supportive group, such as religion, social groups, and psychotherapy.
Monkeys raised in isolation with no bonding to mothers never recover behaviorally—they don’t get along, have trouble mating, and treat their own offspring poorly.
Those growing up with absent or indifferent mothers may have trouble trusting people, feel prone to rejection, and are eager to please to protect themselves from abandonment. This might manifest in clinging and withdrawal behaviors.
A lack of genetic relation between parent and child strongly increases the risk that the parent will abuse the child fatally.
Sadly, this has precedent in evolution. The adaptive strategy for males who take over a group is to kill unrelated children. This prompts the mothers to mate with the new alpha male and concentrates resources on his children.
This pressure is so strong that in mice, just the smell of a strange male can induce miscarriage. The function of this might be to avoid bringing to term a baby that will likely be killed anyway.
Non-fatal child abuse may be an extension of this natural drive.
Unlike sadness and anxiety, the authors believe that schizophrenia—with its paranoia, bizarre beliefs, and hearing voices that don’t exist—is not normal functioning.
Yet with a high prevalence of 1%, schizophrenia is common enough that it should confer an advantage. Perhaps it increases creativity or sharpens intuition about others’ thoughts?
Relatives of schizophrenics who don’t have full schizophrenia themselves seem highly accomplished.
Is sleep shaped by natural selection? It seems so because it’s so widespread among animals. Universally sleep deprivation causes poor performance.
How did sleep arise?
Dreaming may function to purge unnecessary memories. Deprivation of dreaming sleep in cats shortens lives and disrupts their behavior.
Note that during dreaming, we have strong visual sensations and perform actions, but we perceive little sound, smell, or touch. This may be evolutionarily defensive—while sleeping, we need sound, smell, and touch to detect danger. But during sleep, our closed eyes block sight and we can’t move because our brains paralyze our muscles, so there’s little risk of using these capabilities during dreaming.
To be clear, the authors understand that many mental disorder cases are pathological and should be treated to reduce suffering.
But we should take a broader view of mental disorders. They can result from a variety of influences, including genes, early life events, drugs, relationships, life situations, and more.
We should be wary of how we think about negative emotions. What will happen when we try to neutralize all negative emotions and thus avoid their protective functions?
Furthermore, are there disorders resulting from too little emotion? Should we treat people with limited fear, anxiety, and sadness?
The human body has been shaped over millions of years as a well-functioning bundle of compromises. What looks like mistakes in evolution more likely continue to exist for these reasons:
The authors wish to broaden discussions of disease to include these questions:
The authors call for more funding of research for evolutionary medicine.
There have been barriers to adopting evolutionary medicine in practice, including:
But evolutionary medicine may help patients come to terms with their disease. It may make them easier to address.
If patients understood the evolutionary bases of their disease, they can have satisfying reasons for why the disease exists. This may prevent patients from feeling that disease is meaningless, and it may inspire hope that there are ways to circumvent the disease.
Reflect on what you've learned about the evolutionary causes of disease.
What were your most surprising takeaways from what you learned in this book?
How has your view of disease changed based on the ideas in this book?
What's an apparent defect of human health that might actually have a good evolutionary reason for existing?