What Does Not Kill

Hormesis: The Stimulus at the Boundary

When I tell a patient undergoing chemotherapy, “Please exercise,” many are astonished. “I am already this exhausted, and you want me to tax my body further?” It is a fair reaction. And yet the research of the past twenty years points consistently in one direction. Appropriate exercise reduces the side effects of cancer treatment and lowers the risk of recurrence and death in a range of cancers. In 2019 the American College of Sports Medicine convened its experts and issued the formal statement that exercise is safe for cancer patients and should be recommended. How does exercise, which puts the body under stress, keep the body alive? That secret is the key to today’s story.

Exercise physiology has a concept called hormesis: the principle that a small dose of stress in fact makes an organism stronger. The word shares a root with “toxin,” and it holds the paradox that a little poison wakes immunity and triggers adaptation. Exercise is exactly this. Exercise tears muscle finely, burdens the heart, exposes cells to oxidative stress. And in response to that small damage the body recovers stronger than before. A stimulus just short of killing is what brings us to life.

“What does not kill me makes me stronger.” Nietzsche’s sentence is, in fact, also a sentence of cell biology. But there is one condition. It must be just short of killing. Too great, and it is not training but destruction; too little, and it is not safety but decline.

A boundary hardens by being struck. An untested boundary is no boundary at all.

I too play often at that just-short-of-killing edge. On a day climbing a mountain in Banff, Canada, I left the cable car aside and walked six kilometers of trail to the top.

Two-thirds of the way, perhaps? My heart rate is 165. Given my age, that is close to maximum. … I am dizzy. … When I reached the summit, the view opening before me was rapturous.— 2023, Facebook

I drove my heart to the point of dizziness, but it was just short of killing, and so I came down stronger. Imagine a body raised in a sterile room. An immune system that has never met a single germ is not strong but weak. Having never met an enemy, it collapses before a real one. This is one reason allergy and autoimmune disease are increasing today. We grow up in a world too clean, our boundaries never tested. It is the same logic as raising a child only in a greenhouse: not stronger but weaker. The Age of Coddling described in Chapter One is precisely this sterile room, this greenhouse. Gentleness that has erased the wound keeps us from growing.

I learned this principle — that difficulty just short of killing makes us grow — from the body. But someone saw the same thing in civilizations: the historian Arnold Toynbee. He held that civilizations too grow by “challenge and response.” Civilization does not arise in comfortable places; it arises where difficulty is met and answered. Moreover, he said, a challenge has a fitting size. Too small and it is no stimulus at all; too great and it does not stimulate but crushes. The principle of hormesis I saw in the cell, he confirmed again in civilizations.

In truth, the fitting size is what I have spent my life measuring. Deciding how much exercise, at what intensity, how often to prescribe for a patient is exactly that work, and we call the relationship dose-response. Too little has no effect, too much does harm, and somewhere between lies the band that changes the body. The curve Toynbee drew for civilizations and the curve we draw in exercise prescription have the same shape. He merely saw it in the rise and fall of civilizations, and I see it on a patient’s blood panel.

A single fish shows this fitting size. The koi carp, it is often said, stops growing at about twenty centimeters when raised in a small tank, and grows up to a meter when released into a large river. People like to use this story to say: leave the tank, go out to the river. But I think that conclusion is only half right. The river gives growth, and it gives danger with it. There are rapids and there are predators. The tank is stifling but safe.

So the question is not tank or river but timing. A small fish belongs in a tank; a grown fish belongs in a river. Knowing when to stay and when to leave — that is maturity. And a human being has one thing a fish does not. A fish cannot change the size of the river, but a person can build the strength to bear it. What makes the river bearable is not the size of the fish but the fact that it is not alone in that water. What separates a challenge that drives one to death from a challenge that leads to growth is not the size of the challenge but who is beside you.

Nor is the size of the stimulus the only thing that matters. What we call it changes the body too. In one experiment, the psychologist Alia Crum taught people that stress is something that helps them meet a challenge. The group taught this way showed increased positive affect and cognitive flexibility, and even increased secretion of a hormone known to benefit immunity and the musculoskeletal system. No such change appeared in the group taught that stress is simply bad and to be avoided. The same stimulus — only the name was different. This story returns in Chapter Nine, in a scene where one person gives two names to the same forty years.

An earlier experiment by the same researcher is more startling still. Workers who cleaned hotel rooms were simply told that the work they did all day was itself exercise. Not one thing in their routine changed. Yet weeks later their weight and blood pressure had dropped meaningfully. The same labor — but when the name changed, the body responded differently.

The way we measure how far a body can go follows this principle as well. Maximal oxygen uptake is measured just before a person collapses. At the very moment one says “I can do no more” and steps down, the body is using the most oxygen. The maximum is always just before failure. I have been rejected on grant applications more than a hundred times, and one paper was turned down twenty times and published eleven years later. I do not write those numbers out of pride. Had I not gone as far as that place, I would never have known where my limit lay.

This phrase — I came to know because I went through it — has a name twenty-five hundred years old. The Greeks called it pathei mathos: through suffering, learning. It appears in Aeschylus’s tragedy Agamemnon, written in 458 BCE, where the chorus calls upon Zeus and sings that he has laid it down as a law for mortals that we learn by suffering. Pathos is what is undergone and mathos is what is learned, so the two words resemble each other not only in sense but in sound.

What held me longest was the name of that learning. What the original text points to as coming to the one who has suffered is not strength. It is discernment — coming to one’s senses; in Korean, closer to cheol i deunda, growing up in judgment. Nietzsche said what does not kill me makes me stronger, but the Greeks saw what comes to the sufferer not as power but as a sense of the good. It is the very sense this book has been describing all along. One who has been through it does not become mightier; he comes to know how far his own place extends.

Only, once you know where Aeschylus sang this song, it becomes hard to use the phrase carelessly. The song was not sung in a place of comfort. It was sung over the scene of a father sacrificing his daughter. And when the chorus reaches the moment of the girl’s death, it falls silent, saying it neither saw what came next nor will speak of it. The line about learning through suffering comes immediately after that silence. Which means it was not a phrase brought out contentedly where things could be explained, but one barely brought out where explanation was impossible. So this saying may be spoken belatedly about a suffering one has already passed through, but it must never be said to someone who is inside it now. The moment we tell a person passing through what cannot be borne that this will make them grow, it ceases to be comfort and becomes a verdict.

Colder still is what follows. Immediately after the chorus sings that we learn by suffering, Agamemnon kills his daughter. He has learned nothing. This placement cannot be accidental. Aeschylus proclaims the principle and, in the same breath, shows that it almost always fails for the very one who suffers. So when we read this passage to mean that hardship makes me grow, we are standing precisely in Agamemnon’s place. Then to whom does that learning go? I will take up that question again in Chapter Twelve.

Here the story of Chapter One returns. The person who only swells avoids real stimulus. He refuses the small poison called failure. And so he never grows strong. A muscle that has only swelled without stimulus is not muscle but edema. It looks large and has no strength. So refusing the wound is not safety. It is the refusal of growth. Living things are wounded a little at the boundary, and through those wounds they grow. This truth will visit us again later under the name of the wounded healer. For now let us remember only this. A fitting poison is a medicine. And a wound is proof that the boundary is alive.

Notes for this chapter

Friedrich Nietzsche, Twilight of the Idols · Aeschylus, Agamemnon, lines 176–183 (pathei mathos) and 248–250 — the argument of the trilogy as a whole is taken up in Chapter Twelve · Arnold Toynbee, A Study of History (challenge and response) · Campbell et al. (2019), Medicine & Science in Sports & Exercise 51(11):2375–2390 — ACSM Exercise-Oncology Roundtable · Crum & Langer (2007), Psychological Science 18(2):165–171 — hotel room attendants · Crum, Salovey & Achor (2013), JPSP 104(4):716–733 — stress mindset · The koi example is a widely circulated story