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Why We Get Sick by Randolph Nesse and George Williams.
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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.

1) Natural selection selects for reproductive fitness.

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.

2) Behaviors that seem entirely harmful may have unobvious benefits that improve fitness.

Traits that give an overall fitness advantage, despite increasing vulnerability to some disease, can still be selected for.

  • Physical pain is useful—it signals indicating injury, causes you to withdraw from the injuring agent, and stores painful memories to avoid the behavior that caused the injury.
  • Morning sickness in pregnancy makes the mother avoid risky foods that might contain toxins.This protects the early fetus from toxins when it is most vulnerable. Then, when the fetus has grown and is less susceptible to toxins, morning sickness subsides.
  • Sickle cell allele protects against malaria.

3) Adaptations that might have been helpful in the Stone Age are maladaptive in the modern environment.

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:

  • Genes that make you engorge on foods helped humans survive famine periods. But in today’s food-abundant world, this leads to nutritional excess and obesity.
  • Energy conservation and laziness helped us avoid wasteful activity, but today they get us to sit for most of the day.
  • Alcohol addiction was not really a problem until distillation made high-concentration alcohol, and mass markets made alcohol readily available. The trait for alcoholism may have beneficial effects, such as the persistence to seek rewards despite obstacles.
  • Nearsightedness—even though 20% of humans are near-sighted, this might not have been a problem in the Stone Age. It only appeared when humans started doing close reading.
  • Sadness has the function of stopping you from wasting energy on unlikely goals. For instance, during the Stone Age, you might have received feedback that you’re no good at hunting. This would make you sad and reconsider whether you might do better as a gatherer.
    • 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...

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Why We Get Sick Summary Why We Get Sick Guide 1: Why Haven’t We Evolved Disease Away?

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.

  • Proximate questions ask “what caused the disease? How did the disease start and progress?” For heart attacks, the proximate cause is atherosclerosis, and its associated causes like high blood pressure and cholesterol.
  • Evolutionary questions ask, “why hasn’t natural selection eliminated the genes that lead to heart disease? Why hasn’t it eliminated our craving for fatty foods and for...

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Why We Get Sick Summary Why We Get Sick Guide 2: How Natural Selection Works

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...

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Why We Get Sick Summary Why We Get Sick Guide 3: Infectious Disease

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:

  • Fever increases effectiveness of the immune system. While it might superficially seem like the pathogen is causing the fever directly as a result of its havoc, in actuality the fever is our defense against infection.

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Why We Get Sick Summary Why We Get Sick Guide 4: A Never-Ending Arms Race

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.”

  • The arms race can escalate to the point where the host organism expends so much on defense that it’s hard put to meet other basic needs, but the cost of losing the arms race is so great that it must continue defenses.
  • Bacteria and viruses have the edge in numbers. Bacteria can have 300 generations in a week (each time generating novel mutations that may help it infect), and viruses may have even more. Furthermore, they have vast numbers, with trillions in count for one human host. Humans therefore have a huge handicap in natural selection, and instead must compensate with adaptable mechanisms, like an antibody production system that can generate millions of unique antibodies.

Case Study: Bacterial Resistance to Antibiotics

Antibiotics were one of the great medical successes of the 20th century. However, due to widespread use, increasingly bacteria are evolving...

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Why We Get Sick Summary Why We Get Sick Guide 5: Injury and Fear

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.

How Do We Learn Fear?

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...

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Why We Get Sick Summary Why We Get Sick Guide 6: Toxins

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), [restricted term] (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.

Using Darwinian Thinking to Forage

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.

  • Plants that are readily accessible, with little seeming defense around them (such as tubers, mushrooms, and leaves) must have selected other defense mechanisms, like potent toxins. In contrast, those that have clear defenses (like hard shells around nuts, or thorns on berry bushes) are less likely to be toxic.
  • Plants create fruits for animals to eat and disperse the seeds...

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Why We Get Sick Summary Why We Get Sick Guide 7: Genes and Disease

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:

  • Natural selection may not be able to completely eliminate disease genes due to insufficient adverse selection.
    • A harmful recessive gene that confers no disadvantage for heterozygotes has a low rate of adverse selection, even if the unfortunate homozygous recessive die without reproducing.
    • The math shows that if a lethal recessive gene that is created in one out of a million pregnancies will stabilize in frequency at one out of a thousand individuals. In other words, mutation can create the defective gene as fast as natural selection eliminates it.
  • Genes that cause serious diseases may have some less obvious benefits that allow persistence.
    • Consider a gene that is lethal if homozygous....

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Why We Get Sick Summary Why We Get Sick Guide 8: Why We Still Age

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...

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Why We Get Sick Summary Why We Get Sick Guide 9: Legacies of Evolutionary History

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:

  • In our eyes, the retina is inside-out—it’s covered by a layer of blood vessels and nerves. Light entering the eye has to pass through this layer before hitting the layer of rods and cones. This is an artifact of how blood vessels...

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Why We Get Sick Summary Why We Get Sick Guide 11: Allergy

(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:

  • The substance is consumed by macrophages.
  • Macrophages present the foreign proteins to helper T cells, which in turn present them to B cells.
  • B cells secrete IgE antibodies, which bind to basophils or mast cells.
  • Mast cells release chemicals that cause the symptoms of allergic reactions—histamine, defensive enzymes, platelet activators, amd smooth muscle stimulators.

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:

  • **Defense against internal parasites and...

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Why We Get Sick Summary Why We Get Sick Guide 12: Cancer

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:

  • They repair DNA mutations.
  • Tumor suppressor genes inhibit cell growth when they detect problems with the cell.
  • For cell replication to proceed, multiple checkpoints need to be active. If any one is defective, perhaps because of mutation, replication stops.
  • Mechanisms internal to the cell detect a cancerous state and induce apoptosis, or cell death. (The p53 pathway is an example.)
  • Immune cells recognize the target cell is cancerous from the outside, and they trigger apoptosis or inhibit growth in the cancerous cell.

The relationship between...

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Why We Get Sick Summary Why We Get Sick Guide 13: Sex and Reproduction

There are perhaps few mysteries as intriguing and perplexing as the courtship between females and males. Darwinian thinking has explanations for this too.

Sex and Mating

Why Sexually Reproduce?

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 Reproductive Strategies

Different animals have different reproductive strategies. They vary in these factors:

  • The number of...

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Why We Get Sick Summary Why We Get Sick Guide 14: Mental Disorders

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...

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Why We Get Sick Summary Why We Get Sick Guide 15: The Evolution of Medicine

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:

  • Behavior that seems harmful likely have unappreciated benefits that outweigh costs.
  • Natural selection doesn’t punish genes that cause damage late enough in life.
  • Novel environments make some evolved genes maladaptive today.
  • Some attributes are purely historical legacies.

The authors wish to broaden discussions of disease to include these questions:

  • Which aspects of the syndrome are direct manifestations of disease, and which are defenses?
  • If the disease has a genetic component, why does it persist? What possible benefits might it confer?
  • Is the disease partly caused by novel environmental factors that didn’t use to exist?
  • If the...

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Shortform Exercise: Reflect on Darwinian Medicine

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?

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Table of Contents

  • 1-Page Summary
  • 1: Why Haven’t We Evolved Disease Away?
  • 2: How Natural Selection Works
  • 3: Infectious Disease
  • 4: A Never-Ending Arms Race
  • 5: Injury and Fear
  • 6: Toxins
  • 7: Genes and Disease
  • 8: Why We Still Age
  • 9: Legacies of Evolutionary History
  • 11: Allergy
  • 12: Cancer
  • 13: Sex and Reproduction
  • 14: Mental Disorders
  • 15: The Evolution of Medicine
  • Exercise: Reflect on Darwinian Medicine