Wednesday, November 25, 2015

The impossible machine

The immune system is an impossible, incomprehensible, machine. It is not even a ’system’ — evolution is not so modular. We name it as a thing so we can model it, but it is not made by a mind. It is made by evolution, so it is bizarre and emergent. Like a machine that pumps water and makes potato chips on the downstroke.

The thing we name, which is in truth not a bounded thing, allows us to exist, briefly, in a seething sea of self-organizing energy. Presumably its antecedents emerged with the bounded sack of water we call a cell. It has grown in complexity since then, a complexity that often resembles the nervous system. It is, after all, a processing machine. Brains must tell lies from truth, the immune system must distinguish friend from enemy from frenemy. It must often attack the non-self, except when the non-self is a fetus. It should not attack the parts of the self, except when those parts are broken or rogue. It ages as the body ages, but even as it grows frail the body grows more rogue.

Sometimes the non-self is a frenemy, at least for the moment. We are walking biomes, ecosystems in motion. Billions of microbes live within us, often helpful, sometimes the enemy of our enemy. Except when they turn on us. The immune system must manage this, even as the enemies and frenemies adopt the face of the self.

We created the idea of the immune system, and we created the idea of diseases of the immune system — though the boundary between disease and individual variation is not sharp. Some immune systems are poor at stopping some enemies — we usually die then. At other times the immune system confuses self and non-self, and it turns on the organism. We call this an auto-immune disease.

We can do very little about auto-immune diseases. System Lupus Erythematosis is a classic of this genre, our treatment has changed very little in thirty years. We have some newer treatments for diseases like rheumatoid and psoriatic arthritis, but our treatments don’t correct the error of the immune system, they merely induce selective immune dysfunction to slow the progress of disease. We know so little. We aren’t even quite sure that there isn’t some bizarre infection lurking in the tissues of affected people; maybe sometimes the immune system has the right idea but the wrong execution.

Auto-immune diseases are common. We used to think osteoarthritis was a disease of aging tissues, of wear and tear. Now we think this name we made contains multitudes, some related to aging, others to an attack of self on self (“erosive inflammatory OA”). We have no truly effective treatments for these conditions. We don’t even know if sleep and exercise are a good idea — what strengthens healing also strengthens the enemy within. The war on joints and tendons wears on the body, inducing metabolic syndromes and accelerating aging.

If we could reverse auto-immunity, if we could re-induce tolerance, we might be able to manage organ transplants and even stop the enemy within. Inducing tolerance is now an active research area — at least in rats. We have a very long way to go. I hope the next 30 years improves on the last 30, but we have had many false starts.

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