HIV evolves inside the body

This post is also taken from the excellent Evolutionary Dynamics course taught by Martin Nowak at Harvard.

The progression of HIV in the human body was a mystery for a long time. It sits in your body for years, not doing much, then suddenly it takes over your immune system and BAM!---you have AIDS. (The actual sound it makes when it reaches this point is unclear.) Pictorially, the process looks like this:



The red line represents the amount of disease in your body. When HIV is first contracted, the amount of virus shoots up dramatically, but then decreases sharply as the immune system responds. The virus load then stays at a small level, increasing only gradually, until the mysterious trigger happens and it shoots up again, this time impervious to immune responses. The upper blue line represents the amount of CD4 cells in your body, which are the immune cells that HIV attacks. (The slide is stolen from Martin's lecture.)

The question, then, is what is HIV doing in the long "asymptomatic" phase, and how does whatever it's doing enable it to suddenly explode after such a long time?

Nowak gave a surprising answer in a 1999 paper: it is evolving.

The idea is that when a person is first infected, they have only one strain of the disease in them (i.e. whatever strain they got from whoever transmitted it to them.) The immune system can handle this: it makes an antibody designed to attack that strain, at beats it back down to a miniscule level. It can't kill it completely though, because HIV can hide in healthy immune cells.

Now, while HIV is hiding in plain sight, it's also reproducing and mutating at a very high rate. Once it's mutated enough, the antibodies can't recognize it, so different antibodies must be produced to contain it. This processes continues and the disease becomes more and more diverse within you.

But there's a limit on the number of different campaigns your immune system can wage at once. Nowak found a mathematical diversity threshold--i.e. a critical number of strains of the virus, beyond which the immune system can't deal with all of them at once (though any one of them at a time would be fine.) And then, BAM!

I found this fascinating because, while we all know the power of evolution to produce remarkable organisms, we don't usually think of this process happening within our own bodies. Also, this hints at the difficulty of finding a cure for HIV, since it is specifically designed to mutate its way out of trouble.

Evolution of Irregular Verbs

I'm currently taking an amazing class offered by the Program for Evolutionary Dynamics (PED) at Harvard. The goal of the course (and the research program) is to study evolution---of animals, diseases, languages, and other entities---with full mathematical rigor. Today's class included a presentation by one of the PED researchers on the evolution of irregular verbs, based on an article that appeared in Nature in 2007.

Anyone who has ever studied a foreign language will remember with a sense of frustration that all the screwy irregular verbs were precisely the verbs like "to be" or "to go" that get used more often than any others. Obscure, rarely used verbs tend to conjugate in regular patterns.

These researchers found that early on in the English language, many verbs that are now regular, such as "help" or "walk", were once irregular ("I halp my friend study for his quiz yesterday.") As time went on, these verbs regularized (their conjugations evolved to the regular form) one by one, except for those very common verbs like "to be" and "to go" that remain highly irregular (how do you get "went" from "go"?)

Moreover, the speed at which these verbs regularized is directly related to the frequency of their usage. This relationship can be expressed in a remarkably simple mathematical law: the speed at which a verb regularizes is inversely proportional to the square root of its frequency. In other words, if verb A is used 100 times as much as verb B, verb B will regularize 10 times as fast.

The simplicity of this law suggests that there must be some kind of fundamental explanation---a simple model of language use that predicts this law mathematically. No such explanation has been found to date, but you can bet I'll be looking for one!