Appendix appendix

Carl Zimmer (The Loom) is back from appendicitis, and has a Times article on ... appendicitis!

When I got back home, I began doing some research and found that each year, more than 250,000 Americans had appendectomies. The more I thought about that figure, the more absurd it seemed. Why should an organ fail in so many healthy people? What makes it more puzzling is that no one ever needs an appendix transplant. Appendix-free, I can expect a normal life.

It's an oldie, but a goodie, in evolutionary terms. Zimmer interviews Rebecca Fisher (Midwestern University) about her research on appendices in primates (apes have them, some monkeys do, others don't):

Still, I wondered how such a dangerous and disposable organ could survive over evolutionary time. "We consider it maladaptive because we want to live to a very old age," Dr. Fisher said. "But from a strictly Darwinian view, it might not be."

Fisher describes a stabilizing selection hypothesis: the appendix kills some people, but it saves others because of a role in immune defense. This would especially be powerful if the defensive role was greater in childhood (and thereby highly effective in getting people to survive to reproduce) and the killer role greater in elderly people.

Zimmer's Loom post also describes a hypothesis by Nesse and Williams, who proposed that smaller appendices might be even more prone to infection, thus leading to an evolutionary blind alley --- they can't get smaller, because smaller is worse.

Either of these could be true. Or there are other explanations. Indeed, one reason the appendix is such a difficult problem is that there are so many unknowns.

For example, 250,000 appendectomies a year sounds severe --- it's around 1 in 1000 people. This means that your odds of going 60 adult years without an appendectomy would be around 94 percent. Lifetimes in the past were shorter, but if the incidence was the same per year, then the odds of a Pleistocene human going 30 adult years without needing an appendectomy would be a bit greater than 97 percent. All added up, that would seem to amount to pretty strong selection.

Moreover, epidemiological data show that appendicitis is most frequent among people nearing or at childrearing age. The highest incidence overall is in women ages 35 to 44, with all people ages 10 to 19 also having a high risk. So it's not just a disease of the old and infirm. If it had a similar incidence in other groups and in the past, it would have been a strong target of selection.

But that's a problem: we just don't know what its incidence may have been in the past. One recent study found that children with appendectomies had consumed significantly less dietary fiber; that would imply that today's diets have increased appendicitis.

And we don't know another key fact necessary to infer selection: how many of those people with appendectomies would have died without them? Of course, surgeons want you to think the number is close to 100 percent. I know that I sure wouldn't risk a perforation: the surgery is relatively easy, routine, and very low-risk compared to the high risk of peritoneal infection.

However, the fact remains that a substantial proportion of people with inflamed appendices will not have the burst. And a substantial proportion of burst appendices will not kill. We don't know what proportion that might be. And so, we can't say how much selection there may have been on the appendix.

And adding insult to surgery, around 5 percent of appendectomies are entirely negative.

Does it matter? Isn't any selection enough to take the appendix away, given enough time? That depends.

In particular, it depends what other structural effects may be caused by the genetic pathways that make the appendix. For a genetic change to result in no appendix, it must alter the regulation of developmental genes in the lower intestine. These genes probably don't only influence the appendix, but also other structures, a relation called "pleiotropy". Fixing one thing can break something else.

Another barrier to selection is genetic drift. If selection was small enough -- say less than one in a thousand over a lifetime, then it may have been very weak relative to genetic drift in the ancient human population.

Still, if I were taking odds, I would bet on Fisher's adaptive explanation. The conservation of an appendix in apes, along with its fairly distinctive form, argue that it it probably has a function that in the old days we couldn't have done easily without. It probably isn't just hanging around as a hanger-on.

References:

Fisher RE. 2000. The primate appendix: a reassessment. Anat Rec 261:228-236. PubMed