In tomorrow’s New York Times, I’ve got a story about evolutionary biologists who make New York their Galapagos Islands. Working on this story was great fun–I traipsed around Manhattan parks and medians, checking out mice and ants and salamanders. I spoke to other researchers who study plants, fish, and bacteria in and around the city. All of them observe evolution unfolding in what might seem like a very unnatural place. But after four billion years, nothing can stop evolution. Not even New York.

The Times has posted some of Damon Winter’s wonderful photographs for the story along with some audio from some of the scientists I describe. You can also listen to the new podcast, which features the story too (link to come).

[ Photo: Creative Commons: NatalieTracy on Flickr ]

For several decades now, biologists have been puzzling over sex. In some ways, it seems like a huge waste of effort.

Sexual reproduction requires splitting a species into two sexes, only one of which will be able to produce offspring. There are some species of animals that do without males; the females simply trigger their eggs to develop into embryos without any need for sperm. All the offspring of an asexual animal can produce offspring of their own, instead of just half. So it would make sense that genes that gave rise to asexual reproduction would win out in the evolutionary race.

Clearly that hasn’t happened. The world is rife with sex. Animals do it. Plants do it. Even mushrooms do it. So evolutionary biologists have carried out a number of studies to get an answer to the question, “Why sex?”

In 2009, I wrote an essay for Science about this research. If I had been writing that essay today, I’d have focused some attention on an elegant experiment on the sex life of a humble worm. It gives a big boost to the long-floated idea that evolution favors sex because it lets hosts fight better against parasites.

Allow me to explain by self-plagiarizing:

In the 1970s, several researchers built mathematical models of how parasites influenced the evolution of their hosts and vice versa. Their research suggested that both partners go through cycles of boom and bust. Natural selection favors parasites that can infect the most common strain of host. But as they kill off those hosts, another host strain rises to dominate the population. Then a new parasite strain better adapted to the new host strain begins to thrive, leaving the old parasite strain in the dust.

This model of host-parasite coevolution came to be known as the Red Queen hypothesis, after the Red Queen in Lewis Carroll’s book Through the Looking Glass, who takes Alice on a run that never seems to go anywhere. “Now here, you see, it takes all the running you can do to keep in the same place,” the Red Queen explains.

The Red Queen conundrum, some researchers have argued, may give an evolutionary edge to sex. Asexual strains can never beat out sexual strains, because whenever they get too successful, parasites build up and devastate the strain. Sexual organisms, meanwhile, can avoid these dramatic booms and busts because they can shuffle their genes into new combinations that are harder for parasites to adapt to.

Red Queen models for sexual reproduction are very elegant and compelling. But testing them in nature is fiendishly hard, because biologists need asexual and sexual organisms that share the same environment and parasites.

Scientists have found some mixed populations in the wild where they’ve made some important discoveries. But it’s also possible to test the Red Queen in laboratories. It’s not easy, because scientists need to bring together a host that can reproduce sexually and asexually with a parasite, and then they both have to be able to evolve in response to each other. But that’s what a team of scientists at Indiana University managed to do recently.

As they describe in a paper published today in Science, they reared populations of a tiny worm called Caenorhabditis elegans. C. elegans are born either as males or hermaphrodites. A hermaphrodite worm can fertilize its eggs with its own sperm, or it can seek out a male. The worms typically don’t have a lot of sex, and the rate at which they do is partly programmed into their genes. The Indiana team of scientists were able to engineer the worms so that they could have no sex at all, or could only reproduce through sex.

For their parasite, they chose a species of soil bacteria called Serratia marcescens. Soil bacteria are the regular prey of C. elegans, but if they slurp up S. marcescens by accident, they get sick and can die in under 24 hours. Previous studies had shown that the worm can evolve stronger resistance to the germ, and the germ can evolve to be deadlier for the worm. So the Indiana researchers set about combining their evolution into one big experiment.

They mixed together worms and germs in several different arrangements and let them duke it out for 30 worm generations. In each trial, the worms were either sexual or asexual.  In some trials, the bacteria coexisted with the worms for the whole experiment, so that they could evolve along with the worms. In other trials, the worms were repeatedly presented with the same, fixed strain of S. marcescens. In other words, the bacteria could not evolve. And in control experiments, the worms enjoyed a Serratia-free life.

As this graph to the left shows, the asexual worms that faced co-evolving germs were annihilated in just 20 generations. (“Obligate selfing” means no sex.) If the germs couldn’t evolve, however, the asexual worms did fine. The scientists also tested the bacteria for deadliness after the experiments were over. They found that the bacteria that were allowed to co-evolve with the asexual became much deadlier. The co-evolving sexual worms, on the other hand, suffered far lower mortality rates from their germs.

In another experiment, the scientists started out with ordinary worms, which only had sex about 20 percent of the time they reproduced. Again, they exposed the worms to unchanging bacteria, or co-evolving ones, or no bacteria at all. The graph to the right says it all. The worms not exposed to the bacteria went on having infrequent sex. The worms that could evolve but faced fixed bacteria had more sex for a while, but eventually crashed back down to their original levels. The coevolving worms, on the other hand, became mostly sexual.

In each of these results, the Red Queen has left her mark. Far from being a waste of time, sex may save organisms from a swift oblivion.

[Images: turtles via Creative Commons from man of mud/Flickr. C. elegans via Creative Commons licence from AJ Cann/Flickr.]

(Update: paper link fixed)

I just got back yesterday from the annual meeting of the Society for the Study of Evolution. It took place in a big hotel on the outskirts of Norman, Oklahoma, during a windy heat wave that felt like the Hair Dryer of the Gods. It had been a few years since I had last been to an SSE meeting, and I was struck by how genomic everything has gotten. No matter how obscure the species scientists are studying, they seem to have outrageous heaps of DNA sequence to analyze. A few years ago, they would have been content with a few scraps. Fortunately, SSE hasn’t turned its back on good old natural history. There were lots of fascinating discoveries on offer, about species that I had assumed had been studied to death. My favorite was a talk about the rough-skinned newt, the most ridiculously poisonous animal in America.

The scientific tale of the rough-skinned newt begins five decades ago, with a story about three dead hunters in Oregon. Reportedly, the bodies of the hunters were discovered around a camp fire. They showed no signs of injury, and nothing had been stolen. The only strange thing about the scene was the coffee pot. Curled up inside was a newt.

In the 1960s, a biologist named Butch Brodie got curious about the story. The newt in the coffee pot–known as the rough-skinned newt–has a dull brown back, but when it is disturbed, it bends its head backward like a contortionist to reveal an orange belly as bright as candy corn. Bright colors are common among poisonous animals. It’s a signal that says, in effect, “If you know what’s good for you, you’ll leave me alone.” Brodie wondered if the newts were toxic, too.

Toxic, it turns out, doesn’t do the newts justice. They are little death machines. The newts produce a chemical in their skin called tetrodotoxin, or TTX for short, that’s made by other poisonous animals like pufferfish. Locking onto sodium channels on the surface of neurons, TTX blocks signals in the nervous system, leading to a quick death. In fact, TTX is 10,000 times deadlier than cyanide. While we may never know for sure what killed those three Oregon hunters, we do know that a single rough-skinned newt could have easily produced enough TTX to kill them, and have plenty of poison left over to kill dozens more.

Now, if the whole idea of evolution makes you uneasy, you might react by saying, “That couldn’t possibly have evolved.” Experience has shown that this is not a wise thing to say. Brodie said something different: the most plausible explanation for a ridiculously poisonous animal is that it is locked in a coevolutionary arms race with a ridiculously well-defended predator. Another biologist mentioned to him that he’d seen garter snakes dining on rough-skinned newts, and so Brodie investigated. He discovered that garter snakes in rough-skinned newt territory have evolved peculiar shape to the receptors on their neurons that TTX would normally grab.

The coevolution of newts and snakes became a family business. Brodie’s son, Edmund, grew up catching newts, and today he’s a biologist at the University of Virginia. Father and son and colleagues have discovered that snakes have independently evolved the same mutations to their receptors in some populations, while evolving other mutations with the same effect in other populations. They’ve also found that both newts and snakes pay a cost for their weaponry. The newts put in a lot of energy into making TTX that could be directed to growing and making baby newts. The evolved receptors in garter snakes don’t just protect them from TTX; they also leave the snakes slower than vulnerable snakes. They’ve studied newts and snakes up and down the west coast of North America and found a huge range of TTX potency and resistance. That’s what you’d expect from a coevolutionary process in which local populations are adapting to each other in different environments, with different costs and benefits to escalating the fight.

This story is so irresistible that I’ve written about it twice: first, ten years ago in Evolution: The Triumph of an Idea,, and then in updated form last year in The Tangled Bank. I figured that the Brodies et al had pretty much discovered all there was to know about these creatures. But in Oklahoma, I discovered that they had missed what is arguably the coolest part of the whole story.

Think about it: you’re a female newt, you’ve fended off attackers with a staggering amounts of poison in your skin, and now you want to pass on your genes to your descendants. You lay a heap of eggs in a pond, and what happens? A bunch of pond creatures come rushing in and have a feast of amphibian caviar.

What could you possibly do to ensure at least some of your offspring survived? Well, you have an awful lot of TTX in your system. You have enough of the stuff to give your eggs a parting gift to help them out there in the cruel, predator-infested world. Make your eggs poisonous.

That is exactly what female newts do. In fact, they load their eggs with TTX. To figure out if this poison provided a defense against predators, the Brodies and their students traveled to a group of ponds in central Oregon that are home to thousands of rough-skinned newts apiece. They collected dragonflies and other aquatic predators from the ponds and put them in buckets filled with newt eggs, along with muck from the pond bottoms. The scientists found that almost none of the predators would touch the newt eggs. Since these predators eat plenty of eggs of other species, this result shows that TTX does indeed help the newt eggs survive.

But there was one exception. Caddisfly larvae turned out to relish the newt eggs. In fact, the caddisflies actually grew bigger if they were supplied with newt eggs and pond muck than with pond muck alone. And yet the Brodies and their students estimate that there’s enough TTX in one newt egg to kill somewhere between 500 and 3700 caddisflies.

You know where this is going. At the evolution meeting, one of their students, Brian Gall, described feeding newt skin to caddisflies both from the central Oregon ponds and from ponds elsewhere without newts. The newt-free caddisflies would happily munch on newt skin from which all the TTX was removed. But if there was more than a trace TTX in the skin, they refused to eat. The caddisflies that fed on newt eggs, on the other hand, would eat the most toxic skin Gall could provide.

It appears that the caddisflies have evolved much like the garter snakes. In ponds where rough-skinned newts lived, the caddisflies have evolved defenses against TTX. In fact, Gall reported, the caddisflies appear to put the snakes to shame. Evolved snakes are 34 times more resistant to TTX than vulnerable ones. The caddisflies have increased their resistance 175 times.

It’s not clear whether the caddisflies and the newts are truly co-evolving, however. The Brodies will have to find out whether adding extra TTX to eggs increases their survival in the presence of caddisflies. Another intriguing possibility arises from their discovery that the caddisflies actually harbor some of the TTX they eat in their tissues for weeks after eating the eggs. Perhaps the caddisflies are stealing the poison to protect themselves, as happens in monarch butterflies eating toxic milkweed.

In other words, this wonderfully deadly story isn’t over yet.

[For more information, see this new paper in Can. J. Zool., and Understanding Evolution, an educational web site. Ed Brodie tells much of the story pre-caddisfly in a chapter of the new book, In The Light of Evolution (full disclosure: I wrote a chapter in it, too, which you can read as a pdf here)]

Image: California Herps

Brian Malow and I talked yesterday about some of my favorite things on the latest episode of Dr. Kiki’s Science Hour–including the evolution odometer. You can watch it on Youtube, or you can head over to Dr. Kiki’s Science Hour site to download the video or audio. (The Skype goes berserk briefly, but we get back on track.)

The Quarterly Review of Biology delivers a rave for The Tangled Bank: An Introduction to Evolution. Daniel McShea of Duke University writes:

This is the first textbook I have seen by a professional science writer. If this is a sort of experiment in textbook publishing, it is a spectacularly successful one…The result is an introduction to the field that is not only accurate and up to date, but—of course—well written. How important is the prose in a textbook? For students, lively versus leaden, or clear versus cryptic, can be the difference between understanding and not, between being turned on to a field and being turned off. For what it is worth, I solicited help for this review from a biologically inclined high school student, who read a few chapters and reported it to be both clear and engaging….In summary, this is an excellent textbook, one that ought to be—and will be, I predict—widely adopted.

Last summer I wrote in the New York Times about a controversy over one of the most influential concepts in the recent history of evolutionary biology. Known as inclusive fitness, it basically says that helping relatives can be a good way to pass on your genes, because they’ve got your genes too.

In August, Nature published a lengthy paper by Martin Nowak, E.O. Wilson, and Corina E. Tarnita in which they argued that inclusive fitness was mathematically flawed and basically superfluous. I had no trouble finding other scientists who were ready to say all sorts of scathing things about Nowak et al. I’m no fan of ginning up fake debates, but when somebody says, “This paper, far from showing shortcomings in inclusive fitness theory, shows the shortcomings of the authors,” the story writes itself.

Seven months later, Nature has finally published some “Brief Communication Arising” letters from some of these critics. The first letter alone has 137 co-signers.

Their ranks include plenty of major players in the field of evolution (including John Alcock, Tim Clutton-Brock, Stephen Emlen, Paul Sherman, Mary-Jane West Eberhard, and Richard Wrangham). The tenor of the letters is more dignified than the comments I got for my story, but the message is unchanged:

We believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature.

The authors of the first letter argue that Nowak et al don’t get inclusive fitness. They claim it needs lots of stringent assumptions, when, in fact, it’s a general theory. They also challenge the idea that inclusive fitness doesn’t provide any more insights into biology. They offer a list of such insights, such as why animals cooperate with each other, why they can act spitefully, and why mothers produce different ratios of males and females. Inclusive fitness has proven particularly useful for addressing last question–what’s known as sex allocation. It explains how the ratio of males to females changes with the density of females, the mortality rate, and many other factors–and it does so for species as varied as mammals, birds, spiders, and plants.

Nowak et al respond to all the criticism and don’t budge in their own stand. They claim that their critics have misinterpreted their own argument. And they claim that sex allocation does not require inclusive fitness. Oddly, though, they never explain why it doesn’t, despite the thousands of papers that have been published on inclusive fitness and sex allocation. They don’t even cite a paper that explains why. They conclude by writing,

Inclusive fitness theory is neither useful nor necessary to explain the evolution of eusociality or other phenomena. It is time for the field of social evolution to move beyond the limitations of inclusive fitness theory.

[Image from Alex Wild]

Last week I wrote in the New York Times about a fascinating new paper in which scientists described a lamp shell embryo that is, in effect, a swimming eyeball. The paper itself, however, comes in two parts. Along with the part on the swimming eyeball, the scientists also described a later stage of the lamp shell embryo in which it developed simple eyes connected to neurons. It’s primitive version of our own eyes that reveals some interesting things about evolution–particularly about the different photoreceptors that evolved over half a billion years ago for sensing light. At the time, I was struck by the fact that this one paper had two newsworthy insights. So I was glad to see PZ Myer takes up the other half of the story in excellent detail over at Pharyngula. Check it out.

Tomorrow’s Science Times section of the New York Times has a special package of articles all about animals–the relationship between humans and the animals we raise, what makes us separate from animals, and so on. I took the opportunity to take a big step back and look at how animals came to be in the first place. The answer–or at least part of it–lies among some weird creatures, such as this tentacled creature that dwells inside snails. Check it out.

Here’s the video of the lecture I gave last week at Stony Brook University, which was the basis of my recent blog post. I’ve uploaded the slides as a pdf here. (You can read the slides online or download them by going to the File drop-down menu.) I’m not sure what the ideal combination of video and slides would be…if anyone has any suggestions, let me know.

[Update--the video url got switched around. This should work now...]

Nicholas Wade reports today in the New York Times on a tantalizing study that may offer some insight into the evolution of aging, the subject of my recent Darwin Day lecture. An extended family in Ecuador carries a mutation that seems to leave them completely free of cancer and diabetes. The mutation affects a growth hormone receptor on their cells, so that the cells produce low levels of a growth factor. As I mentioned in my lecture, scientists have studied animals with this same mutation, and they can live to amazingly old ages–the life span of C. elegans worms doubles, for example.

The story with the Ecuadorians is not cut and dried, however. While they may be blissfully free from cancer and diabetes, they don’t live to be 160 years old. They die at a normal age of other causes. What’s more, as I mentioned in my lecture, the Methuselah worms trade long life for reproductive success–a prediction that comes out of evolutionary theory. There’s one obvious trade-off that the Ecuadorian family experiences: they have a severe form of dwarfism. On the other hand, their mutation does not cause any obvious reduction in reproductive success. (This picture is of a man from the family with his children.)

Since the subject of trade-offs didn’t come up in the paper itself, I contacted Valter Longo, one of the co-authors, to find out more. Here’s his reply:

They seem to be generally normal. However, it would be very surprising if they did not have at least some reduced reproductive capability. In fact, we are studying the equivalent GHR deficient mice, and it is very difficult for them to reproduce when they have 2 copies of the mutation. Naturally, this would not be an issue if the GHR signaling deficiency was obtained with a drug that blocks the receptor, since a person could get off the drug temporarily to reproduce and then get back on it. Nonetheless, the Laron in Ecuador, can reproduce and some of them have large families. In all cases, as far as I know, they married someone without the syndrome.

So this study is probably not going to produce a quick-fix panacea, but it certainly is a fascinating natural experiment.

Over the weekend, Charles Darwin turned 202. I celebrated in Stony Brook on Long Island–which just so happens to be a very appropriate place to mark the event. Stony Brook University was the intellectual home of one of Darwin’s most important followers, the scientist George Williams. Williams may not be a household name, but for evolutionary biologists he looms large. Some fifty years ago, he framed some of the most important questions they are still seeking to answer today.

I was invited to Stony Brook University to give a Darwin Day lecture, and since Williams died last September at 84, I decided to make it a kind of scientific eulogy for him. It was an honor to have the chance to do so, but there was also a bittersweet irony to the experience. For the last few years of his life, Williams suffered from dementia (which may have been Alzheimer’s disease or Lewy body dementia, according his wife, Doris). The fact that millions of older people get dementia was exactly the sort of phenomenon that fascinated Williams throughout his career. Why, he wondered, do we get sick, and why do our sicknesses take their particular forms? Part of the answer, he realized, lies in our evolutionary past. Even as natural selection fine-tuned our ancestors for millions of years, it left us burdened with a susceptibility to many diseases. Evolution may be able to give rise to eyes, brains, and wings. But it’s not in the business of making us healthy.

At the end of The Origin of Species, Darwin made it clear that he did not see his theory of evolution as the last word on the subject. Instead, he saw it opening up a wide door, through which future generations of biologists could pass.”We can dimly foresee that there will be a considerable revolution in natural history,” he wrote. That revolution would extend to developmental biology, to paleontology, even to psychology. “Light will be thrown on the origin of man and his history,” he added.

But there’s one field that Darwin didn’t mention: medicine.

I am puzzled about why he left it out. Perhaps Darwin didn’t consider medicine as much of a science. His own experience with Victorian doctors certainly couldn’t have left him with a good impression. Darwin suffered from many ills during his life, which are summed up nicely on their very own Wikipedia page:

“For over forty years Darwin suffered intermittently from various combinations of symptoms such as malaise, vertigo, dizziness, muscle spasms and tremors, vomiting, cramps and colics, bloating and nocturnal intestinal gas, headaches, alterations of vision, severe tiredness, nervous exhaustion, dyspnea, skin problems such as blisters all over the scalp and eczema, crying, anxiety, sensation of impending death and loss of consciousness, fainting, tachycardia, insomnia, tinnitus, and depression.”

Darwin’s doctors had lots of theories for why he suffered all these symptoms. (They still sustain a cottage industry of speculations today, from Oedipal complexes to assassin bugs.) They prescribed him a long train of cures, including bismuth, laudanum, water therapies, and electric belts. They sometimes gave Darwin brief respites of relief, but he always relapsed sooner or later into suffering.

Evolution and medicine began creeping towards each other after Darwin’s death in 1882. It gradually became clear, for example, that infectious diseases were caused by rapidly-evolving viruses and other pathogens. But even if we could eradicate every last infectious microbe on Earth, we would still get sick, thanks to inherent weaknesses of our constitution. We would keep getting heart attacks. We would keep getting cancer. These diseases were more mysterious from an evolutionary perspective. In the late 1950s, George Williams came up with one of the most important concepts for explaining them.

At the time Williams would have seemed like the last person to forge such a bond. Williams was not a doctor. He was not a cell biologist. He was, rather, a newly-minted Ph.D. who had written his dissertation on the ecology of blennies, a kind of fish.

For Williams, blennies were just one small part of the diversity produced through evolution. And he wanted to find rules that could explain all of that diversity. He spent much of his time lost in these reflections. “George was gentle, quiet, and intensely thoughtful,” wrote James Bull, Eric Charnov, and Teresa Carlson wrote in the January 2011 issue of American Naturalist.

It was not uncommon to sit down with him and toss out an initial idea for discussion. Then, when his ensuing silence grew uncomfortably long, one would toss out another idea, ultimately another, and then another. When he finally spoke, it became clear that he was still thinking deeply about the first or second idea.

In the late 1950s, while he was a post-doctoral researcher at the University of Chicago, Williams was thinking a lot about natural selection. He saw some serious flaws in how leading scientists were thinking about it.

Many scientists believed, for example, that natural selection often produced adaptations that benefited entire groups.Why did animals get old and die, for example? Why didn’t animals just keep humming along until they were killed by a predator or a pathogen? Death had to be good for something, and one popular idea was that death benefited entire groups of animals. By dying, older individuals stepped out of the way for younger ones.

One day, Williams heard this idea for the umpteenth time,during a lecture by a renowned ecologist named A.E. Emerson. “My reaction was that if Emerson’s presentation was acceptable biology, I would prefer another calling,” he later wrote.

Williams believed that scientists like Emerson were making an error of reasoning. They were seeing natural selection at work in cases where it was both unnecessary and impossible. For a thought example, Williams liked to contemplate a fox paying a visit to a chicken coop on a snowy day. After the fox kills a hen, it trots back along the same path it took to the coop, simply because that’s easier than trotting through undisturbed snow. The next day the fox heads down the same path again for another meal. As it travels back and forth, it establishes a nicely cleared trail.

Now, does that mean that its legs are for clearing snow? Did natural selection drive the evolution of fox legs because a certain shape made them good snow plows? Of course not. They are for walking, not for snow clearing. The snow clearing is just a side effect.

Behaviors that seem to be adaptations for groups could also be side effects of natural selection acting on individuals, Williams argued. If you look at a school of fish escaping a predator, for example, it seems like it is behaving like a single body, all working as a unit. But Williams maintained that the behavior of a school could just be the result of individual fish trying to get deep into a group of fish because they’ve be less likely to be eaten.

Selection for group adaptations wasn’t just logically unnecessary in a lot of cases. It was also less likely to occur than selection on individuals. Imagine herds of wildebeest scattered across the savanna. In order for beneficial death to evolve, aging herds would have to do better than ones that didn’t. It would take a long time for winners to emerge in this process. Meanwhile, natural selection would be acting on individuals at a much faster rate in the opposite direction.

Imagine that some of the wildebeest in a herd have genes that program them to live for, say, 20 years. And others live for 25 years. Both kinds of wildebeest do what wildebeest do: eat, mate, stampede, and have calves. The 25-year wildebeest has an extra five years’ worth of calves. So in the next generation, there will be more calves with genes for living longer. Over successive generations, the wildebeest herd will live longer and longer (all other things being equal). A shorter lifespan might indeed make a herd more successful, but natural selection can’t reach such a happy solution, Williams decided.

So how did death evolve? “Walking home from the lecture with my wife, Doris,” Williams wrote later, “I regaled her with my unhappiness about the lecture and proposed the obvious idea that selection among individuals in any population would be biased in favor of the young, as long as the likelihood of living to age X was greater than to age X+1.”

Here’s what Williams meant: Imagine a fish–we’ll call it the Williams eel–that never ages. But despite its eternal youth, it is at a constant risk of getting killed by predators. In a population of Williams eels, the percentage of surviving eels will decline with age, simply because sooner or later a lot of eels get killed. When the eels reproduce, therefore, most of the parents will be young. As a result, mutations will have different effects if they strike at different times in a fish’s life.

Imagine there’s a beneficial mutation that makes a fish more resistant to diseases. If it makes fish resistant only in their old age, it won’t spread much, because so few old fishes will be around to pass it on to their offspring. It will spread much faster if it boosts the health of young fish, because they make up most of the parents. More fish will have it in the next generation.

The flip side is true for harmful mutations. If a mutation causes a devastating disorder when the Williams eels are still young, it will be very likely to wipe out a lot of their potential offspring. But if mutations only make eels sick when they’re older, they will have very little effect because most of the eels will already be dead anyway. In such a population, natural selection can act strongly on genes for survival and reproduction in youth. Mutations that cause harm in old age can pile up over the course of many generations.

Williams also observed that one mutation can have more than one effect on an organism. So imagine that a single mutation is beneficial in youth and harmful in old age. If the benefit is big enough, a mutation will spread through a population despite the harm it causes. Aging, according to Williams’s theory, was the price of youth.

Williams presented this explanation for aging (known as antagonistic pleiotropy) in papers and his influential 1966 book Adaptation and Natural Selection. It was an enticing idea, but was it true? The answer is, in a number of cases, yes.

One of the most striking examples from nature came to light in the 1990s. At the time, Steven Austad, then at Harvard, was studying the ecology of opossums. He would put bands on female opossums and then trap them every few months to count the babies in their pouches. He was amazed at how fast the animals would fall apart as they got older. In just a few months, a healthy opossum might develop cataracts, arthritis, and a host of other ailments.

Austad realized that opossums were part of a natural experiment in aging. Several thousand years ago, a population of opossums in Georgia were stranded by rising sea levels on what is now Sapelo Island. They had the good fortune to end up on an island with no predators. As a result, the percentage of older opossums still alive was higher. Williams had predicted that in such a case, natural selection would lead to slower aging. That’s because mutations that caused harm in old age would be more likely to interfere with reproductive success.

Austad compared the opossum of Sapelo to a population living on the mainland in which 80 percent of the animals get killed by predators. He discovered that the island opossum live 20 percent longer than their mainland cousins. They also enjoy better health for a longer time. Their tendons, for example, remain springier far later in life than the tendons of mainland opossum.

Some studies have failed to find evidence for antagonistic pleiotropy; it’s possible that the actual tradeoffs faced by natural selection are more complex than the ones Williams laid out. Nevertheless, evolutionary biologists still praise Williams for giving them a new way of thinking about health.

George Williams would go on to do pioneering work on a lot of other fundamental questions. Why do most animals have sex? Why are some species altruistic? He used the same elegant approach he had developed in Adaptation and Natural Selection, focusing on individuals and their genes, rather than the good of the species.

But Williams also wanted to expand the sphere of evolutionary biology. He believed that medicine, if done right, would be a kind of applied evolutionary biology. Doctors were trying to foster the health of their patients, but the biology they were contending with was the product of evolution. As he wrote in his book Why We Get Sick (co-authored by Randolph Nesse), an understanding of the ways evolution has shaped human biology would help doctors do a better job.

Antagonistic pleiotropy is particularly useful for medical researchers. We inherited our genes from a common ancestor with opossum and other mammals, and natural selection continued to negotiate a trade-offs between youth and old age in our primate forebears. Accidents, murders, and diseases all struck down our ancestors, leaving fewer older people to reproduce. Just as with opossum or chimpanzees, selection is biased towards youth in our species. George Williams was convinced that antagonistic pleiotropy had a lot to say about why we age. During his fifties, he chronicled his own decline at a track in Stony Brook, where he would time himself running a mile. With clinical detachment, he graphed his steady slowing.

Medical researchers have been tracking human aging at a molecular level, and they’re finding signs of antagonistic pleiotropy as well. The rate of most cancers is low in the young, for example, and rises steeply in old age. Yet pre-cancerous cells develop in our bodies every day, as dividing cells accidentally mutate in dangerous ways. If this was the whole story, cancer might well be far more common in young people. Low rates of cancer in the young are thanks to many lines of defense. One of the most important of these is made up of “gatekeeper” proteins that can response to DNA damage and abnormal growth. They can neutralize potentially dangerous cells by forcing them to commit suicide or by permanently pushing them into an enfeebled “senescent” state, where they can grow slowly at best.

It’s a pretty good strategy, as demonstrated by what happens when scientists shut down gatekeeper genes in mice: they get cancer a lot sooner than they would otherwise. But it’s only a stop-gap measure. Senescent and suicidal cells damage the surrounding tissue and make it harder for the body’s stem cells to regenerate new tissue. In other words, they cause our bodies to age. This aging can even lead to new cancer later in life. Gatekeepers show all the signs of antagonistic pleiotropy: they keep us healthy during our childbearing years, but we pay the cost later in life.

Not that long ago, a lot fewer people had to pay those costs, because so many people died young. Over the past 400 years, the life expectancy in Europe has more than doubled. As we live longer, we have to cope with more evolutionary side-effects. Williams himself appears to have suffered from one of the dreaded of these: the decline of the brain.

Alzheimer’s disease is associated with tangled clumps of protein in the brain called plaques. These plaques don’t pop up at random in the brain. They tend for form in a network of regions that plays a special function in our inner life. Known as the default network, it’s actually active when we’re not thinking about anything in particular. Neuroscientists suspect that the default network is vital for our very human sense of self, which we can project into the past and into the future. It’s a vital part of what it means to be human, but it is, in effect, always on. These hard-working neurons may make more proteins, and be at greater risk of making defective ones.

To understand how Alzheimer’s disease works, researchers have been investigating genes involved in it. One of these genes, called ApoE, comes in several different forms, and the form called ApoE4 appears to make people more prone to Alzheimer’s. In the latest issue of Functional Ecology, Lynn Martin of USF Health Byrd Alzheimer’s Institute, University of South Florida, and her colleagues step back to look at ApoE4′s full impact on people who carry it. It turns out to have several different effects. Early in life, it actually brings some benefits, including resistance to various infections, better memory recall, and enhanced learning. In old age, it makes people more prone to Alzheimer’s disease as well as heart disease. It is, in other words, just the sort of gene George Williams had in mind fifty years ago.

It would be a mistake to claim that evolutionary medicine can produce instant cures as soon as doctors open up The Origin of Species. The germ theory of disease did not lead immediately to antibiotics, either. But it certainly helped in the long run, by showing doctors what their proper target should be. Evolution provides doctors with new possibilities as well as unexpected warnings. A lot of research has gone into the possibility of reversing aging by manipulating our biochemistry. One of the most exciting results from this line of research has been the discovery that shutting down certain genes can make animals live longer. The worm C. elegans can live twice as long, for example, if scientists switch off a gene called daf-2.

Sounds great, right? Let’s start taking pills that shut down these genes getting in the way of eternity! Williams would have warned us to not leap so fast. Daf-2 might well shorten our lifespan when it’s working normally. But that might be because it has been shaped by antagonistic pleiotropy. Such a gene may harm us in old age, but it may also have benefits in our youth.

Studies on C. elegans have shown that this is, in fact, the case. Worms that can’t use daf-2 produce fewer offspring than ones that can. Austad has recently surveyed the medical literature and found a dozen genes in worms, flies, and mice with a similar double-edged effect: shutting them down lengthens life but also causes harm in youth. The side-effects range from sterility to delayed maturation to cognitive impairment.

These results don’t mean that the search for anti-aging medicine is a lost cause. Williams may not have escaped antagonistic pleiotropy, but perhaps his descendants will someday. But for that to happen, we will have to bear in mind Williams’s advice and get to know what we’re up against: namely, hundreds of millions of years of history.

Images:
Young Darwin, George Williams, Old Darwin, The William Eel, skull, fox, wildebeest herd, Austad and possum courtesy of Austad, running graph, cancer cells, nematode

Hurrah! Choice, the leading magazine for academic book reviews, has named The Tangled Bank: An Introduction to Evolution one of the outstanding academic titles of 2010. Here’s a line from the announcement: “These outstanding works have been selected for their excellence in scholarship and presentation, the significance of their contribution to the field, and their value as important–often the first–treatment of their subject.”