The Likeness

Around 1901 Paul Ehrlich gave the body's refusal to attack itself a name with real dread in it: horror autotoxicus, the horror of self-poisoning. He meant something close to a law. An immune system that turned on its own tissue would be a catastrophe so complete that nature must have forbidden it — must have built in some deep regulatory revulsion that kept the body's weapons from ever pointing inward. And you can feel why he believed it: the whole apparatus is a standing army with the power to dissolve cells and rupture membranes, quartered inside the very body it is meant to defend, and a version that could not tell the body from the enemy would kill its owner in days. Ehrlich was not being foolish. He was reasoning from the size of the danger to the strength of the safeguard, which is usually sound.

He was also, in the particular way that careful people are wrong, wrong. The safeguard is real — the immune system does hold its fire against the self, reliably, for most people for a whole life — but it is not a law. It is a defended border, and a border can be crossed. It took most of fifty years to say so out loud, in part because Ehrlich's phrase had hardened from an observation into a doctrine, and a good doctrine is very hard to see past. When Noel Rose found, in the mid-1950s, that a rabbit injected with its own thyroid protein would raise antibodies against its own thyroid, his senior colleague Ernst Witebsky — who held to Ehrlich's doctrine — made him repeat it, and repeat it, before he would credit a result that by everything they had been taught could not be real. The body does attack itself. It happens under a name — autoimmune disease — and one of the ways it happens is stranger than a simple failure of the guard. Sometimes the guard is not fooled by the enemy. It is fooled by how much the enemy looks like home.

The immune system is, at bottom, the one organ of the body whose entire function is a distinction: self from not-self, mine from foreign. It learns, early and continuously, the molecular signatures of you — and then it is licensed to destroy more or less anything that does not match. This is a magnificent solution and it has a flaw sitting inside its own definition. It cannot check identity directly; it can only check resemblance. It does not know what is you. It knows what looks like you. And a thing that looks enough like you passes — which means the whole scheme has a hole in it shaped exactly like a good copy.

Pathogens found the hole — anything a defense measures can eventually be forged. A bacterium whose coat resembles the host's own molecules is harder to raise an alarm against, and evolution has dressed a great many microbes in something like the body's own clothes; the resemblance is straightforward camouflage. But the resemblance does not stop being true once the alarm goes off. And this is the turn the disease is built on: when the immune system finally does see the invader and mounts its response, the antibodies and cells it raises are shaped to that molecular face — the face the pathogen borrowed from you. They go out looking for the invader, and they also, helplessly, recognize the original. The disguise and the self-injury are not two things. They are one resemblance, read from opposite ends.

The clearest and cruelest example was, for centuries, just called rheumatic fever, and generations of doctors watched it without knowing the shape of it. A child gets a strep throat — an ordinary one, the streptococcus gone from the throat in a week or two. And then, two or three weeks later, after the infection is over, the damage begins: the joints, the skin, sometimes the movements of the body going strange and involuntary, and worst, quietly, the heart. The particular villainy is in the coat of the streptococcus. Its M protein is built as a long coiled rope of a molecule, and the human body builds some of its own proteins to that same coiled pattern — the cardiac myosin deep in the muscle of the heart, and the structural proteins laid through the heart's valves. The antibodies raised against the strep coat cannot help but fit these too. The myosin they cross-react with is sealed away inside the muscle cells, out of their reach; but the valve is not, and there they settle — on its lining and the coiled proteins of its surface — calling in cells that were only ever meant for the invader, and over the following weeks they inflame and thicken and scar the delicate mitral valve until it no longer closes cleanly. The strep is long gone. The child is not sick with infection anymore. The child is sick with the precise shape of the immune system's memory of it — a memory that, it turns out, was also a memory of the child's own heart.

That such a thing was really the mechanism, and not just a suggestive story, was proven most cleanly somewhere else, in the nerves. There is a common gut bacterium, Campylobacter jejuni, an ordinary cause of food poisoning, whose sugar coat happens to mimic the gangliosides studded across the surface of our peripheral nerves. In a small number of people, weeks after the diarrhea has passed, the antibodies against that bacterial coat turn on the nerves those sugars resembled, and the person is suddenly, ascendingly paralyzed — Guillain-Barré syndrome, weakness climbing from the feet. What makes it the cleanest proof is that the loop was closed backward: the immunologist Nobuhiro Yuki took the bacterial coat, injected it into rabbits, and watched the rabbits make antibodies against their own nerve gangliosides and go weak in the limbs. The disease was reconstructed from the disguise alone. Give the body a good enough copy of its own nerves, and it will build the weapon that reads both.

So there is no horror autotoxicus, no revulsion built in to keep the body from turning on itself — only a discriminator that can know the self by its likeness and by nothing else, and a likeness is a thing the world can copy. The immune system does not fail here by breaking. It fails by working.