Self & Other
2. The First Responders
In the summer of 1882, a Russian zoologist named Élie Metchnikoff was on vacation in Messina, on the eastern coast of Sicily. His family had gone to a circus. He had stayed home, not because he was bored of circuses but because he had recently become obsessed with starfish — specifically, the transparent larvae of starfish, which you can see straight through, the way you can see through a piece of frosted glass — and he wanted to keep an eye on the ones in his microscope.
Watching the larvae move under the lens, Metchnikoff had a thought. He went out to the garden, snapped a thorn off a tangerine tree, and used it to jab one of the larvae. Then he sat down to watch what happened.
What happened, over the next several hours, was this. Certain cells inside the larva — cells that normally drifted around, doing whatever it is cells do in starfish larvae — began to move toward the thorn. Not randomly. Deliberately. They surrounded it. They piled onto it. Some of them seemed, under the microscope, to be trying to eat it.
Metchnikoff watched this for a long time, and then, by his own account, he went a little crazy. He paced around his apartment. He could not sit still. He understood, in a way that almost no one else in 1882 understood, that he was looking at something enormous: he was looking at a body defending itself. Not with magic. Not with vapors or humors or any of the other ideas medicine had been carrying around for two thousand years. With cells. Specific cells, with specific jobs, doing specific work.
He named them phagocytes — Greek for “eating cells” — and he spent the next thirty years arguing with most of European medicine about whether they were important. (They are. He won the Nobel Prize in 1908.)
The cells Metchnikoff saw that afternoon are still in your body, right now, doing the same thing they did in his starfish. We have better names for them now and we know more about what they do. But the basic idea — that your body is full of cells whose entire job is to crawl around looking for trouble and eat it — has not changed in a hundred and forty years.
These are the first responders. This is the chapter where we meet them.
The Big Eaters
Macrophage means, literally, “big eater.” It is one of the few biology words that does exactly what it says.
A macrophage is a large, lumpy, slightly amoeba-shaped cell that lives in your tissues — in your liver, your lungs, your skin, your gut, the lining of your bones, basically everywhere. There are different specialty macrophages in different tissues; the ones in your liver have a different name (Kupffer cells), the ones in your bones another (osteoclasts), the ones in your brain a third (microglia). For most of this book we’ll just call them macrophages, but it’s worth knowing they’re a family, not a single thing.
What macrophages do is patrol. They roam through their tissue at a slow, steady pace, sampling whatever they bump into. If they bump into a piece of you, they leave it alone. If they bump into something that is not you — a bacterium, a fragment of a dead cell, a piece of dust that you breathed in — they wrap themselves around it, swallow it whole, and digest it inside themselves with chemicals so harsh that nothing organic survives.
That’s the main job. But macrophages do something else, too, which turns out to be even more important: they talk.
After a macrophage eats something it considers dangerous, it sends out chemical signals. We call these signals cytokines. They are tiny proteins that float through the local tissue and the bloodstream like flares, and they say, in chemical language, things like: trouble here. More help needed. Whatever you’re doing, drop it and come this way. It’s a virus. It’s a bacterium. I think I’ve got it but stay alert.
The cytokine system is, more or less, the city’s communication network. We’ll come back to it many times. For now, just hold onto this: the macrophage isn’t only eating things. It’s the first one to sound the alarm.
The Kamikazes
If a macrophage is a steady, watchful firefighter, a neutrophil is the firefighter who is currently sprinting toward the burning building screaming.
Neutrophils are the most abundant white blood cells in your body. Right now, you have somewhere between two billion and ten billion of them in circulation, and your bone marrow is making about a hundred billion more every day. They live for about a day and then they die, are flushed out, and replaced. Their entire existence is a brief, intense, slightly alarming sprint toward whatever the macrophages are yelling about.
When the cytokine signals reach the bloodstream, neutrophils respond by sticking to the walls of the nearest blood vessel, squeezing through the gaps between vessel cells, and crawling — through tissue, against gravity, around obstacles — toward the source of the signal. They arrive in waves, and they fight dirty. They release enzymes that dissolve bacterial walls. They produce bursts of bleach, more or less literally — chlorine-based chemistry, the same family of chemicals you’d use to clean a bathroom. They sometimes sacrifice themselves entirely, exploding outward in a kind of suicide attack and trapping nearby bacteria in nets made of their own DNA. (This is a real thing. It’s called a NET — a neutrophil extracellular trap — and it was only discovered in 2004. There is still a lot we don’t understand about how it’s regulated.)