The meetings so far have gone very smoothly; the organizers have done a terrific job (despite us having to live out in the middle of nowhere), and there have been few glitches. What a great idea it was, too, to have a free happy hour from 5:30-7:30 every day after the last session, with all the drinks you can swallow and lots of people to talk to.
I want to report on one talk on evolutionary medicine. If you’ve followed this website, you’ll know that I was once down on the practical uses of evolution: I thought of the discipline more as a way to understand the world than to improve it. But I’ve changed my mind, largely at the instigation of Dave Hillis at the University of Texas at Austin, who has enlightened me about the real applications of evolution in medicine.
At the meeting yesterday there was an all-day symposium on “Darwinian medicine” (DM). This is the discipline that studies not only how the evolution of pathogens helps us understand disease (antibiotic resistance in bacteria is, of course, the classic example), but also how human evolution affects not only our susceptibility to disease, but explains some of our symptoms (fever, for example, may be an evolved adaptation to kill pathogens, and so you might want to hold off reducing mild fevers).
I didn’t go to all the talks, for there are many interesting talks to see on a given day, but I wanted to briefly summarize one talk on Darwinian medicine, by Randoph Nesse at the University of Michigan. Nesse, along with the late George Williams, has published extensively on Darwinian medicine and, in fact, is largely responsible for founding the discipline.
Nesse’s talk was called “What evolutionary biology and medicine offer to each other, and reflections on George Williams.” He began simply by recounting some statistics: how few evolutionary biologists there are on medical school faculty: almost none, but that’s not much of a surprise. More surprising is how little evolutionary biology actually gets into med-school curricula, despite its importance for medicine. Most schools teach things about antibiotic resistance, more or less because they have to, but other aspects of DM aren’t often taught in medical school: things like “adaptive” human symptoms of disease, or things that pathogens do to facilitate their own spread (the fact that malaria makes you prostrate, for instance, may actually be an adaptation of the malaria parasite to facilitate its spread; you’re more likely to be bitten by a mosquito, who transmits the parasite, if you’re laid out flat in bed).
Nesse gave six evolutionary reasons why humans are still susceptible to disease, despite the adaptive advantages of being resistant to disease:
1. Evolutionary constraints. We may be unable to evolve resistance to some diseases simply because to do so would entail a greater fitness cost than a fitness benefit, for there are constraints that prevent us from changing one thing without changing others, perhaps at a greater fitness cost. Although he didn’t give any disease examples, Nesse did use the example of the human eye, which is less than optimally designed because of its evolutionary origin as an everted part of the brain. (Light has to pass through blood vessels and nerves to get to the photosensitive cells, and this reverse-wiring gives us a blind spot that isn’t present in the camera eye of the octopus, which has an independent evolutionary origin). If a reader has an example of a constraint that keeps us from evolving resistance to a disease, let me know.
2. Mismatch between genes and environment. Many modern genetically-based diseases may reflect genes that were neutral or even adaptive in our ancestors, but maladaptive in a modern environment to which we haven’t yet adapted. Heart disease may result from genes that make us crave fats. Such genes may well have been adaptive in our ancestors but are now maladaptive in our fat-rich environment. Such diseases aren’t really purely “genetic diseases,” but reflect an interaction between genes and new environments.
Many “common” genes that cause disease, like those for hypertension or diabetes, may have been either neutral or adaptive in our ancestors, but are not so great to have in a modern environment. Do remember that we’ve only had about two thousand years of “modern” civilization in our 6 million years of living in small groups in Africa: modern life is thus about 0.03% of our total evolutionary history.
3. Coevolution with pathogen transmission. Pathogens have evolved in ways that make us susceptible to disease. Nesse used the example of malaria that I gave above, but this isn’t really coevolution: it’s simply an adaptation in the sporozoan parasite that facilitates its own transmission. In “coevolution,” two species each undergo evolutionary change in response to each other. I don’t really see any evolution in humans in response to malaria (except for the spread of the sickle-cell allele, which prevents malaria in heterozygotes, but that’s not what Nesse was talking about), so the point he was making here is unclear. If someone heard that talk and can explain why “coevolution” is something that explains our evolutionary susceptilibility to disease, please explain below.
4. Tradeoffs. Bilirubin is one product of the metabolic breakdown of hemoglobin. It’s a very toxic compound, and if you have too much of it you get jaundice (it’s responsible for not only the yellow color of jaundice, but also of urine and the yellowish tint around bruises). About 5% of the population has elevated bilirubin, which causes Gilbert’s syndrome, which in some people has mild deleterious effects but is often asymptomatic. Why do we get this disease? Because bilirubin, though toxic, is also beneficial in some ways: it acts as a potent antioxidant and thus can prevent the damaging effects of too much oxygen on cells, which can include heart disease.
As Nesse pointed out, people with Gilbert’s syndrome have a significantly reduced incidence of coronary artery disease because of the elevated bilirubin. His point was that although bilirubin is a toxic compound that can cause mild (or asymptomatic) disease in a substantial number of people, that disease is a byproduct of a greater good—a tradeoff between producing a toxic compound and the net beneficial effects that that compound has on the body.
5. Reproduction trumps health. The currency of natural selection is not longevity or bodily well-being, but reproduction. Nesse argued that, for example, men get sick and die more often than women simply because there’s a tradeoff between their evolved tendency to compete with other men for women, thereby spreading their genes, and the fact that this competition wears men out physiologically, making them die earlier. He cited one surprising statistic: for every 100 Oklahoma women who die at age 20, there are 300 men who die at that same age. And we all know that the tour buses of old folks you see in your city are largely women, for many of the men who would be their contemporaries died long ago.
6. Some “disease” symptom and defenses against mortality are useful, even if costly. Pain, fever, and vomiting may be signs of sickness, but can be useful in preventing or mitigating illness. Pain, of course, is a way of alerting you that something is wrong: people without the ability to feel pain often suffer infected wounds and other injuries, simply because they don’t get the signal that there’s something wrong. (I think this is why sufferers of leprosy—now called Hansen’s disease—often lose noses, ears, and fingers.) Vomiting helps us purge our bodies of toxic substances.
Similarly, many of our anxieties may also reflect adaptation. As Nesse pointed out, if our ancestors got anxious and ran away from a noise that could be a leopard, maybe 99 times out of 100 it would be nothing, and that energy and anxiety would be wasted, but it’s that one time in 100 when it’s really a leopard that the anxiety and flight reaction really pay off. It will often be useful to be fearful and anxious even without much cause, if those reactions can save your life on the rare occasion when something really is around to harm you.
It was interesting to contemplate these issues, which of course are only one part of DM, for they concern only susceptibility to disease in humans, not other aspects of human disease or evolution in the pathogens themselves.
I have only one small quibble about Nesse’s talk. He gave one example of what he considered an untenable “just-so story” about human disease: the speculation that juvenile (type I) diabetes was an adaptation for the ice ages 10,000-20,000 years ago. Those individuals with high levels of blood glucose, so the story goes, were better able to avoid freezing to death, and so the genes producing higher glucose, i.e., those that now give us juvenile diabetes, were adaptive in our recent evolutionary past.
This does seem to be a bit of a just-so story, and Nesse is right to be wary of it. For one thing, juvenile diabetes has severe side effects that can kill you when you’re young, before you can reproduce. The curious thing is, though, that Nesse included clinical depression on his list of one of the “diseases” that probably were adaptive in our ancestors. Yet the evidence that depression is adaptive is even less convincing than for type I diabetes (see my posts about this here, here, and here).
While I now think that Darwinian medicine is a useful and intriguing discipline, its practitioners must be careful not to fall into the same trap that’s snared many evolutionary psychologists: uncritical and untestable storytelling. So far, many advocates of DM, including Nesse, seem to be largely avoiding that trap.