Discover, March 2012
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Eric Courchesne managed to find a positive thing about getting polio: It gave him a clear idea of what he would do when he grew up. Courchesne was stricken in 1953, when he was 4. The infection left his legs so wasted that he couldn’t stand or walk. “My mother had to carry me everywhere,” he says. His parents helped him learn how to move his toes again. They took him to a pool to learn to swim. When he was 6, they took him to a doctor who gave him metal braces, and then they helped him learn to hobble around on them. Doctors performed half a dozen surgeries on his legs, grafting muscles to give him more strength.

Courchesne was 11 when the braces finally came off, and his parents patiently helped him practice walking on his own. “Through their encouragement, I went on to have dreams beyond what you’d expect,” he says. He went to college at the University of California, Berkeley. One day he stopped to watch the gymnastics team practicing, and the coach asked him to try out. Before long Courchesne was on the team, where he won the western U.S. championship in still rings.

When Courchesne wasn’t competing at gymnastics, he was studying neuroscience. “I understood a neurological disorder firsthand, and I wanted to help other children,” he says. Fortunately, the polio outbreak that snared him in 1953 was the last major one in the United States; a vaccine largely eliminated the disease in this country. But in the mid-1980s, as a newly minted assistant professor of neuroscience at the University of California, San Diego, Courchesne encountered a 15-year-old with another kind of devastating neurological disorder: autism.

At the time, Courchesne was investigating how children’s brains respond to new pieces of information. “I encountered a clinical psychologist who studied children with autism,” he says. “She told me, ‘Autistic children aren’t interested in novelty. They’re interested in routine.’ ” Yet the young man Courchesne met showed more range. At first he responded to Courchesne’s questions only with short answers, “but when I talked with him further, I discovered he had a tremendous wealth of knowledge,” the neuroscientist recalls. “He had calendar memory. He just wasn’t interested in being sociable.”

Autism had cut the boy off from the social world, Courchesne realized. “I could see his loneliness, and I could see his parents’ heartache,” he says. He could also see that the boy’s parents refused to give up on him, in the same way his parents had refused. “As they say, that was it,” he says. He swung his entire career toward autism.

In the three decades since, autism has gone from obscurity to painful familiarity. The Centers for Disease Control and Prevention estimates that about 1 in 110 children in the United States are autistic. Yet the disorder remains enigmatic. “Every turn of my research has been about figuring out how this thing began,” Courchesne says. Gradually he built up a picture of the autistic brain from infancy to adulthood, zeroing in on a crucial distinction between those who have autism and those who don’t.

As they develop, autistic brains bloom with an overabundance of neurons, Courchesne finds. It might sound like bad news, implying that autism is rooted in such a fundamental change to the structure of the brain that there’s no hope of undoing it. But Courchesne says his findings could lead to key treatments in years to come.

Back when Courchesne began his work, the notion of a neuroscientist studying autism seemed a bit odd. Many researchers considered the disorder a psychological problem, perhaps the result of bad mothering. “It was a medieval way of thinking,” Courchesne says. As time went on, he became convinced that autism was not only a neurological disorder but more specifically a developmental disease that altered the structure of the nervous system as it matured.

Scientists had done a few anatomical studies on the autistic brain, but the results were ambiguous. Even normal brains can vary enormously in size and structure, so it was hard to see what, if anything, set autistic brains apart. To push past this confusion, Courchesne needed to look at a much larger sample of brains.

In 1988 he sought out parents of autistic children and got their permission to have the children lie in MRI scanners so he could take high-resolution anatomical pictures of their brains. Then he used computers to mark the boundaries of different brain regions and estimate their volume. The subjects spanned a wide range of ages, from adults down to toddlers as young as 2. Courchesne did not scan infants, but he went back through medical records to look at the circumference of the heads of his volunteers since birth.

Courchesne hoped to find something, anything, that set the autistic subjects apart. “We didn’t know what it might be or where it might be found,” he says. “We didn’t know if it would come on in the youngest stages or older. It was wide open.”

Gradually he saw a pattern. At birth, children with autism had normal-size brains. But by the time they were a year old, the brains of most autistic children had grown far beyond average. The average adult human brain weighs 1,375 grams, but Courchesne encountered one 3-year-old autistic boy whose brain weight was estimated at 1,876 grams.

The MRI scans further revealed that only certain parts of the brain became larger. The growth was striking in the prefrontal cortex, the region just behind the eyes that is responsible for language, decisions, and other sophisticated thinking. Courchesne also saw an increase in both the gray matter (consisting of dense clusters of neurons) and the white matter linking different regions of the brain. This explosive neural expansion continued in many autistic children until the age of 5, and then it stopped. Past that age, Courchesne found, the rate of brain growth slowed in autistic children, falling behind that of ordinary children. By the teen years, some brain regions actually started to shrink.

Over the past two decades, Courchesne has replicated these results in three additional sets of brain scans. And he has moved beyond MRI, working with tissue banks at institutions like the National Institutes of Health, which stores donated brains. Working with the brains of six normal children and seven autistic children ages 2 to 16, most of whom died of drowning, Courchesne has studied neurons under the microscope and even counted the number of neural cells in different tissue samples. Last November he reported the first results: On average, autistic brains had many more neurons in some regions than normal brains. In the prefrontal cortex, autistic children had 67 percent more neurons than average.

These results provide insight into the origin of autism. During the second trimester of pregnancy, the precursors to neurons in the brain divide furiously. Then they almost all stop, well before birth. When the brain gets bigger after delivery, all that is happening is that the individual neurons are growing and sprouting branches. The only time autistic children can get their extra neurons, in other words, is while they are in the womb. “We established a time zone,” Courchesne says.

That time zone rules out the old bad-mothering theory of autism, and also the notion that vaccines trigger autism in toddlers. Courchesne suspects that fetal brains become autistic due to a combination of genetic and environmental influences that strike during the second and possibly third trimesters, just as neurons are dividing. It may be no coincidence that many of the genes thought to increase the risk of autism are also involved in the division of cells. It’s possible that an environmental influence–perhaps a virus–can trigger these genes to produce too many neurons.

When autistic children are born, Courchesne’s research suggests, they have an abundance of neurons jammed into an average-size brain. Over the first few years, the neurons get bigger and sprout thousands of branches to join other neurons. The extra neurons in the autistic brain probably send out a vast number of extra connections to other neurons. This overwiring may interfere with normal development of language and social behavior in young children. It would also explain the excess brain size seen in the MRI scans.

For Courchesne, this provocative discovery is just the beginning. His initial results are based on only 13 brains, and he would like to look at more to see if the differences hold up. He also wants to figure out why the early overgrowth in autistic brains is followed by slowed or arrested growth. Perhaps the overgrowth triggers the brain to prune the extra connections, and the pruning becomes just as excessive as the initial burst.

It may take a long time to get those deep answers, but Courchesne’s findings could produce practical benefits much sooner. For one thing, they suggest that the earlier doctors can diagnose autism, the better. Using MRI scans along with blood and behavioral tests, “it might be possible to identify infants at risk at a much younger age, when circuits are just being established,” Courchesne says.

Once children are identified, they could be treated to help their brains develop properly. The treatment might take the form of behavioral therapy or pharmaceuticals that modulate the way the neurons grow. The most targeted drug interventions might not be available for a decade or more. That is quite a while to wait–but Courchesne knows not to give up hope.

Copyright 2012 Carl Zimmer

Smithsonian, March 2012
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On the front porch of an old Coast Guard station on Appledore Island, seven miles off the southern coast of Maine, Thomas Seeley and I sat next to 6,000 quietly buzzing bees. Seeley wore a giant pair of silver headphones over a beige baseball cap, a wild fringe of hair blowing out the back; next to him was a video camera mounted on a tripod. In his right hand, Seeley held a branch with a lapel microphone taped to the end. He was recording the honeybee swarm huddling inches away on a board nailed to the top of a post.

Seeley, a biologist from Cornell University, had cut a notch out of the center of the board and inserted a tiny screened box called a queen cage. It housed a single honeybee queen, along with a few attendants. Her royal scent acted like a magnet on the swarm.

If I had come across this swarm spread across my back door, I would have panicked. But here, sitting next to Seeley, I felt a strange calm. The insects thrummed with their own business. They flew past our faces. They got caught in our hair, pulled themselves free and kept flying. They didn’t even mind when Seeley gently swept away the top layer of bees to inspect the ones underneath. He softly recited a poem by William Butler Yeats:

I will arise and go now, and go to Innisfree, 

And a small cabin build there, of clay and wattles made:

Nine bean-rows will I have there, a hive for the honey-bee,

And live alone in the bee-loud glade.

A walkie-talkie on the porch rail chirped.

“Pink bee headed your way,” said Kirk Visscher, an entomologist at the University of California, Riverside. Seeley, his gaze fixed on the swarm, found the walkie-talkie with his left hand and brought it to his mouth.

“We wait with bated breath,” he said.

“Sorry?” Visscher said.

“Breath. Bated. Over.” Seeley set the walkie-talkie back on the rail without taking his eyes off the bees.

A few minutes later, a honeybee scout flew onto the porch and alighted on the swarm. She (all scouts are female) wore a pink dot on her back.
“Ah, here she is. Pink has landed,” Seeley said.

Pink was exploring the island in search of a place where the honeybees could build a new hive. In the spring, if a honeybee colony has grown large enough, swarms of thousands of bees with a new queen will split off to look for a new nest. It takes a swarm anywhere from a few hours to a few days to inspect its surroundings before it finally flies to its newly chosen home. When Pink had left Seeley’s swarm earlier in the morning, she was not yet pink. Then she flew to a rocky cove on the northeast side of the island, where she discovered a wooden box and went inside. Visscher was sitting in front of it under a beach umbrella, with a paintbrush hanging from his lips. When the bee emerged from the box, Visscher flicked his wrist and caught her in a net the size of a ping-pong paddle. He laid the net on his thigh and dabbed a dot of pink paint on her back. With another flick, he let her go.

Visscher is famous in honeybee circles for his technique. Seeley calls it alien abduction for bees.

As the day passed, more scouts returned to the porch. Some were marked with pink dots. Others were blue, painted by Thomas Schlegel of the University of Bristol at a second box nearby. Some of the returning scouts started to dance. They climbed up toward the top of the swarm and wheeled around, waggling their rears. The angle at which they waggled and the time they spent dancing told the fellow bees where to find the two boxes. Some of the scouts that witnessed the dance flew away to investigate for themselves.

Then a blue bee did something strange. It began to make a tiny beeping sound, over and over again, and started head-butting pink bees. Seeley had first heard such beeps in the summer of 2009. He didn’t know why it was happening, or which bee was beeping. “All I knew was that it existed,” he said. Seeley and his colleagues have since discovered that the beeps come from the head-butting scouts. Now Seeley moved his microphone in close to them, calling out each time the bee beeped. It sounded like a mantra: “Blue…blue…blue…blue…blue.”

When you consider a swarm one bee at a time this way, it starts to look like a heap of chaos. Each insect wanders around, using its tiny brain to perceive nothing more than its immediate surroundings. Yet, somehow, thousands of honeybees can pool their knowledge and make a collective decision about where they will make a new home, even if that home may be miles away.

The decision-making power of honeybees is a prime example of what scientists call swarm intelligence. Clouds of locusts, schools of fish, flocks of birds and colonies of termites display it as well. And in the field of swarm intelligence, Seeley is a towering figure. For 40 years he has come up with experiments that have allowed him to decipher the rules honeybees use for their collective decision-making. “No one has reached the level of experimentation and ingenuity of Tom Seeley,” says Edward O. Wilson of Harvard University.

Growing up in Ellis Hollow, in upstate New York, Seeley would bicycle around the farms near his house; one day he discovered a pair of white boxes. They each contained a hive. Seeley was seduced. He came back day after day to stare at the hives. He would look into the boxes and see bees coming in with loads of pollen on their legs. Other bees fanned their wings to keep the hives cool. Other bees acted as guards, pacing back and forth at the opening.

“If you lie in the grass in front of a hive, you see this immense traffic of bees zooming out of the hive and circling up and then shooting off in whatever direction they want to go,” said Seeley. “It’s like looking at a meteor shower.”

For his PhD at Harvard, Seeley took up a longstanding entomological question: How do honeybees choose their homes? He climbed into trees and poured cyanide into hives to kill the honeybees inside. He sawed down the trees and measured the cavities. Seeley found that bee hive hollows were very much alike. They were at least ten gallons in volume, sat at least 15 feet off the ground and had a narrow opening.

Seeley built 252 wooden boxes of different shapes and sizes and scattered them in forests and fields to test how particular bees were about these qualities. Swarms only moved into boxes that had the same features that Seeley had found in their tree cavities. “It’s really important to get them all right,” Seeley said.

The architectural tastes of honeybees are not mere whims. If honeybees live in an undersized cavity, they won’t be able to store enough honey to survive the winter. If the opening is too wide, the bees won’t be able to fight off invaders.

He took his research to Appledore Island because no native honeybees live here, and it has no big trees where the insects could make their homes. Seeley and his colleagues would bring their own honeybees and nest boxes. “This is our laboratory,” Seeley said. “This is where we gain control.”

In one experiment, Seeley set up five boxes of different sizes. Four of the boxes were mediocre, by honeybee standards, while one was a dream home. In 80 percent of the trials, the swarms chose the dream home.

Through years of study, Seeley and his colleagues have uncovered a few principles honeybees use to make these smart decisions. The first is enthusiasm. A scout coming back from an ideal cavity will dance with passion, making 200 circuits or more and waggling violently all the way. But if she inspects a mediocre cavity, she will dance fewer circuits.

Enthusiasm translates into attention. An enthusiastic scout will inspire more bees to go check out her site. And when the second-wave scouts return, they persuade more scouts to investigate the better site.

The second principle is flexibility. Once a scout finds a site, she travels back and forth from site to hive. Each time she returns, she dances to win over other scouts. But the number of dance repetitions declines, until she stops dancing altogether. Seeley and his colleagues found that honeybees that visit good sites keep dancing for more trips than honeybees from mediocre ones.

This decaying dance allows a swarm to avoid getting stuck in a bad decision. Even when a mediocre site has attracted a lot of scouts, a single scout returning from a better one can cause the hive to change its collective mind.

“It’s beautiful when you see how well it works,” Seeley said. “Things don’t bog down when individuals get too stubborn. In fact, they’re all pretty modest. They say, ‘Well, I found something, and I think it’s interesting. I don’t know if it’s the best, but I’ll report what I found and let the best site win.’”

During the time I visited Seeley, he was in the midst of discovering a new principle. Scouts, he found, purposefully ram one another head-on while deciding on a new nest location. They head-butt scouts coming from other locations–pink scouts bumping into blue scouts and vice versa–causing the rammed bee to stop dancing. As more scouts dance for a popular site, they also, by head-butting, drive down the number of dancers for other sites.

And once the scouts reach a quorum of 15 bees all dancing for the same location, they start to head-butt one another, silencing their own side so that the swarm can prepare to fly.

One of the things Seeley has been thinking about during his vigils with his swarms is how much they’re like our own minds. “I think of a swarm as an exposed brain that hangs quietly from a tree branch,” Seeley said.

A swarm and a brain both make decisions. Our brains have to make quick judgments about a flood of neural signals from our eyes, for example, figuring out what we’re seeing and deciding how to respond.

Both swarms and brains make their decisions democratically. Despite her royal title, a honeybee queen does not make decisions for the hive. The hive makes decisions for her. In our brain, no single neuron takes in all the information from our senses and makes a decision. Millions make a collective choice.

“Bees are to hives as neurons are to brains,” says Jeffrey Schall, a neuroscientist at Vanderbilt University. Neurons use some of the same tricks honeybees use to come to decisions. A single visual neuron is like a single scout. It reports about a tiny patch of what we see, just as a scout dances for a single site. Different neurons may give us conflicting ideas about what we’re actually seeing, but we have to quickly choose between the alternatives. That red blob seen from the corner of your eye may be a stop sign, or it may be a car barreling down the street.

To make the right choice, our neurons hold a competition, and different coalitions recruit more neurons to their interpretation of reality, much as scouts recruit more bees.

Our brains need a way to avoid stalemates. Like the decaying dances of honeybees, a coalition starts to get weaker if it doesn’t get a continual supply of signals from the eyes. As a result, it doesn’t get locked early into the wrong choice. Just as honeybees use a quorum, our brain waits until one coalition hits a threshold and then makes a decision.

Seeley thinks that this convergence between bees and brains can teach people a lot about how to make decisions in groups. “Living in groups, there’s a wisdom to finding a way for members to make better decisions collectively than as individuals,” he said.

Recently Seeley was talking at the Naval War College. He explained the radical differences in how swarms and captain-dominated ships make decisions. “They realize that information is very distributed across the ship,” Seeley said. “Does it make sense to have power so concentrated? Sometimes you need a fast decision, but there’s a trade-off between fast versus accurate.”

In his experience, Seeley says, New England town hall meetings are the closest human grouping to honeybee swarms. “There are some differences, but there are also some fundamental similarities,” he said. Like scouts, individual citizens are allowed to share different ideas with the entire meeting. Other citizens can judge for themselves the merit of their ideas, and they can speak up themselves. “When it’s working properly, good ideas rise up and bad ones sink down,” says Seeley.

Groups work well, he argues, if the power of leaders is minimized. A group of people can propose many different ideas–the more the better, in fact. But those ideas will only lead to a good decision if listeners take the time to judge their merits for themselves, just as scouts go to check out potential homes for themselves.

Groups also do well if they’re flexible, ensuring that good ideas don’t lose out simply because they come late in the discussion. And rather than try to debate an issue until everyone in a group agrees, Seeley advises using a honeybee-style quorum. Otherwise the debate will drag on.

One of the strengths of honeybees is that they share the same goal: finding a new home. People who come together in a democracy, however, may have competing interests. Seeley advises that people should be made to feel that they are part of the decision-making group, so that their debates don’t become about destroying the enemy, but about finding a solution for everyone. “That sense of belonging can be nurtured,” Seeley said. The more we fashion our democracies after honeybees, Seeley argues, the better off we’ll be.

The New York Times, February 21, 2012
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Fruit flies may seem as if they lead an uneventful life. They look for old fruit to lay their eggs. The maggots then hatch and graze on the yeast and bacteria that make the fruit rot.

In reality, however, these flies have to do battle with horrifying enemies. Tiny wasps seek out the maggots and lay eggs inside them. The wasps develop inside the still living flies, feeding on their tissues. When the wasps reach adult size, they crawl out of the dying bodies of their hosts.

The flies are not helpless victims, however. In the journal Current Biology, Todd Schlenke, an Emory University biologist, and his colleagues report a remarkable defense the insects use: To kill their parasites, the flies get drunk.

Dr. Schlenke discovered this tactic while studying the common fruit fly species Drosophila melanogaster. As they eat yeast, they also eat the alcohol that the yeast produce while breaking down sugar. Their fermentation can leave a rotting banana with an alcohol concentration higher than that of a bottle of beer.

This boozy environment can be toxic to animals. The only reason Drosophila melanogaster thrives on rotting fruit is that it has evolved special enzymes that quickly detoxify alcohol.

Dr. Schlenke was well aware that many insects gain defenses from their food. Monarch butterflies, for example, are protected from birds by the toxic compounds they get from the milkweed plants they eat. To see how alcohol influences the enemies of the flies, Dr. Schlenke unleashed a parasitic wasp, Leptopilina heterotoma.

Dr. Schlenke allowed the wasps to attack two kinds of fly larvae: one kind reared on alcohol-free food, and another that ate food spiked with 6 percent alcohol. In the presence of alcohol, the wasps laid 60 percent fewer eggs, possibly because of the fumes wafting from the food. “Presumably the wasps felt really ill,” Dr. Schlenke said.

It turned out that alcohol was even worse for their eggs. Wasps growing in flies that ate alcohol-free food always grew normally. But inside boozing flies, 65 percent of the wasps died.

Dr. Schlenke discovered they suffered a hideous death: Each wasp’s internal organs had shot out of its anus. “All their guts are outside the wasps,” he said. “I don’t know how to explain that.”

This deadly effect occurred only if the flies consumed alcohol after the wasps laid eggs in them. Taking in alcohol beforehand, by contrast, had little effect. This discovery led Dr. Schlenke to wonder if the flies might seek out alcohol to kill the wasps, using it like a medical drug. “I wondered if they were smart enough to know that,” he said.

To find out, he and his colleagues filled petri dishes with alcohol-rich food on one side and alcohol-free food on the other. They then placed flies that did not have wasps inside them on the alcohol-free side. A day later, they found that 30 percent of the flies had crawled over to the side with alcohol. When they repeated the experiment with wasp-infested flies, 80 percent of the flies headed for the spirits. “There’s a big difference there,” Dr. Schlenke said.

Likewise, when the flies started out on the alcohol side of the dish, 40 percent of the healthy flies crawled to the other side after 24 hours. Many infected larvae started moving to the other side as well, but then returned to the alcohol. Dr. Schlenke speculates that they were exploring for even higher alcohol concentrations that would be even more toxic to their parasites.

“They know the wasps are infecting them, and they seek out the alcohol,” Dr. Schlenke said. “The flies self-medicate by getting schnockered.”

Some wasps appear to have evolved ways around this tipsy defense. Dr. Schlenke repeated these experiments on another species, L. boulardi, which unlike the other wasp can lay its eggs only in D. melanogaster. Dr. Schlenke found that the specialist wasp L. boulardi suffered far less when its host consumed alcohol. Only 10 percent of its larvae died, compared with 65 percent for L. heterotoma. Dr. Schlenke suspects that its specialization allowed L. boulardi to overcome the alcohol. “The wasps are tracking their hosts over evolutionary time,” he said.

“This article is exciting in several ways,” said Michael Singer, a biologist at Wesleyan University who was not involved in the study. Over the years, scientists have gathered a few examples of animals medicating themselves. Chimpanzees eat plants with antiparasitic compounds when they get intestinal worms, for example. Dr. Singer and his colleagues have shown that woolly bear caterpillars go out of their way to feed on toxic plant leaves when parasitic flies lay eggs in them. But Dr. Schlenke’s research is the first to show that an animal uses alcohol as medicine.

Alcohol is common in nature, and Dr. Schlenke speculates that other species may seek it out to self-medicate. When it comes to humans, however, Dr. Schlenke has no idea whether a bout of heavy drinking has any effect on a parasite.

“As far as I can tell, no one’s ever tested whether we humans can make life hard for our bloodborne pathogens by getting our blood alcohol levels up,” he said.

Copyright 2012 The New York Times Company. Reprinted with permission.

Discover, January 2012
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There was no way the blind mice could see, yet somehow, they could. The year was 1923, and a Harvard grad student named Clyde Keeler had set out to compare eyes from different animals, starting with mice that he bred in his dorm room. Keeler cut open one mouse’s eye and put it under a microscope. Immediately he realized something was wrong. Missing from the eye was the layer of rods and cones, the photoreceptors that catch light. Turning back to his colony, Keeler realized that half of his animals were blind. Somehow a mutation had arisen, wiping out their rods and cones.

The mutation had blinded those mice with surgical precision, yet for reasons lost to history, Keeler got the strange idea to shine a light in their eyes anyway. Based on everything that scientists knew about mammalian eyes, nothing should have happened. After all, the mice had no way to capture light and relay it to the retinal ganglion cells, the neurons that normally pass visual signals on to the brain. And yet something did happen: The mouse pupils shrank.

Keeler struggled to find an explanation. “We may suppose that a rodless mouse will not see in the ordinary sense,” he wrote in one journal article. But for pupils to shrink, such mice had to have some kind of cell besides rods and cones–one that scientists knew nothing about–that could also capture light and send a signal to the brain.

Most vision experts scoffed at the notion that the eyes contained hidden sensory cells and ignored Keeler’s findings. It took nearly eight decades for scientists to investigate his claim and prove him right: The eye really does contain a third type of photoreceptor cells that sense light intensity without detecting images.
These sightless cells seem to perform a variety of important functions. They set our body clock and regulate our sleep. They may explain why bright light can trigger migraines. They may even reveal why depression is so commonly associated with winter’s darker days.

Some of the first validation of Keeler’s research came in the 1990s from University of Oxford neuroscientist Russell Foster, who studied the daily cycle of our bodies–the so-called circadian rhythms that define the pattern of vital signs in a 24-hour day. We become sleepy and then alert; our body temperature cools and then warms; hormones are released, then subside. The changing level of light each day keeps these rhythms synchronized with Earth’s rotation. If people live in windowless rooms for days on end, experiments have shown, their circadian rhythms gradually drift out of sync, so that they might end up sleeping in the daytime and staying awake all night.

Yet no one knew exactly how light acts as a reset button. To search for a mechanism, Foster ran a new experiment. He essentially re-created Keeler’s blind mice by shutting down genes essential for the development of rods and cones while still exposing his subjects to cycles of light and dark. Foster also set up the same experiment using mice with normal eyes. If the rods and cones acted as the reset button, then the circadian rhythms of the sighted mice should hold to the classic pattern while circadian rhythms of the blind mice drift away. But that’s not what
happened. In 1999 Foster reported that the blind mice behaved the same as regular mice. Only when Foster surgically removed their entire eyes did the blind mice drift out of sync. Keeler’s sightless cells must have been at work.

Studies like Foster’s prompted a number of researchers to look for those missing cells. The first clue came in 2000, when neuroscientist Ignacio Provencio, now at the University of Virginia, found a light-capturing pigment called melanopsin in the ganglion layer of the retina. It was a bizarre discovery, since the ganglion layer was thought only to relay electric signals from the rods and cones, not catch its own light. But in 2002, Samer Hattar of Johns Hopkins University and David Berson of Brown University identified individual retinal ganglion cells containing melanopsin. They further demonstrated that the cells–called intrinsically photosensitive retinal ganglion cells, or ipRGCs–could detect light.

Like the rods and cones, ipRGCs are most sensitive to a particular color: blue, in this case. And like other retinal ganglion cells in the eye, the ipRGCs grow long fibers that snake out to join the optic nerve. When the optic nerve reaches the brain, individual fibers split away to make contact with different regions. Hattar and Berson inserted genes for glowing proteins that would activate only in melanopsin-producing cells. In this way they were able to show that rods and cones make most of their connections in the image-producing regions of the brain. But ipRGCs largely stop short of those regions, ending up elsewhere, including the suprachiasmatic nucleus, a patch of neurons in the brain’s midline. When scientists surgically remove these regions, test animals lose their circadian rhythms.

Hattar and other scientists then set out to determine exactly what ipRGCs do by creating mirror images of Keeler’s blind rodents. These engineered mice see as well as their normal counterparts but they lack ipRGCs. Subsequent experiments have confirmed what previous generations suspected: Even under normal light, mice without these cells drift out of sync with day and night. But the ipRGC-free mice
exhibit a number of other changes, too. Unlike intact mice (whose circadian rhythms align to keep them up at night and asleep during the day), they are immune to the sleep-inducing powers of light. Shine a light on them, and they stay awake. This discovery suggests a new connection between the eye and the brain. It appears that some ipRGCs are not just linked to the body’s clock centers, but also plugged directly into the brain’s sleep circuitry.

Another surprise: Not all ipRGCs are the same. After photographing these cells under microscopes and mapping their connections, Hattar has identified five different types of ipRGCs. In one recent experiment, he found a distinctive mouse version that makes a protein called Brn3b. If mice lacked this type of ipRGC, the only change Hattar could find was that the animals could no longer constrict their pupils. Their circadian rhythm still responded to the reset button of light.
In short, rather than being a one-size-fits-all light sensor, ipRGCs may be a sophisticated guild of specialist cells, each channeling light to different parts of the brain to do different things–all of which happens outside our visual awareness.

Mice and humans are so closely related that it seemed likely we have the same basic collection of ipRGCs in our eyes, carrying out the same tasks. In 2007 sleep researcher Steven Lockley of Harvard Medical School started gathering the proof after he met a human version of Keeler’s mice–a blind 87-year-old woman who had lost all her rods and cones decades before but whose ipRGCs were still intact.
Lockley performed a battery of tests to look for things the ipRGCs might be doing. In one trial, he switched a light on and off while asking the woman to report its state. The woman was baffled. Why would he want her, blind for years, to tell him about a light that she could not see? Nevertheless, she gamely guessed. If the light was blue, she got the answer right most of the time. For any other color, her guesses were little better than random. Lockley and his colleagues concluded that her brain was using the light caught by ipRGCs to make sense of the outside world, even if her conscious mind wasn’t in on the secret.

Studies on migraine headaches, which are often exacerbated by bright lights, are revealing another role of ipRGCs in the human brain. Harvard headache researcher Rodrigo Noseda had observed that light could trigger migraines even in blind people; he therefore theorized that the headaches might be triggered by ipRGCs. To explore the idea, he dissected the brains of rats, staining both ipRGCs and pain-signaling neurons to trace their paths.The ipRGCs connect to pain neurons in the thalamus, he found, suggesting that exposure to light could disturb pain-signaling neurons as well. Light sensitivity can be devastating for some migraine sufferers. They can’t drive, write, or even read. Once researchers understand the pathway well enough to manipulate it pharmacologically, such patients might find relief.

Unfortunately, switching off the ipRGCs entirely is not a viable option. These
neurons are now known to extend into the thalamus, a region of the brain known for promoting awareness. Presumably they deliver some kind of essential information there. When neuroscientists find out what kind of message it is, they will make real progress–perhaps toward fighting pain, and definitely toward getting a better look at our secret selves.

Copyright 2012 Carl Zimmer

National Geographic, February 2011
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Selected for The Best American Science and Nature Writing 2012

Most of us will never get to see nature’s greatest marvels in person. We won’t get a glimpse of a colossal squid’s eye, as big as a basketball. The closest we’ll get to a narwhal’s unicornlike tusk is a photograph. But there is one natural wonder that just about all of us can see, simply by stepping outside: dinosaurs using their feathers to fly.

Birds are so common, even in the most paved-over places on Earth, that it’s easy to take for granted both their dinosaur heritage and the ingenious plumage that keeps them aloft. To withstand the force of the oncoming air, a flight feather is shaped asymmetrically, the leading edge thin and stiff, the trailing edge long and flexible. To generate lift, a bird has merely to tilt its wings, adjusting the flow of air below and above them.

Airplane wings exploit some of the same aerodynamic tricks. But a bird wing is vastly more sophisticated than anything composed of sheet metal and rivets. From a central feather shaft extends a series of slender barbs, each sprouting smaller barbules, like branches from a bough, lined with tiny hooks. When these grasp on to the hooklets of neighboring barbules, they create a structural network that’s featherlight but remarkably strong. When a bird preens its feathers to clean them, the barbs effortlessly separate, then slip back into place.

The origin of this wonderful mechanism is one of evolution’s most durable mysteries. In 1861, just two years after Darwin published Origin of Species, quarry workers in Germany unearthed spectacular fossils of a crow-size bird, dubbed Archaeopteryx, that lived about 150 million years ago. It had feathers and other traits of living birds but also vestiges of a reptilian past, such as teeth in its mouth, claws on its wings, and a long, bony tail. Like fossils of whales with legs, Archaeopteryx seemed to capture a moment in a critical evolutionary metamorphosis. “It is a grand case for me,” Darwin confided to a friend.

The case would have been even grander if paleontologists could have found a more ancient creature endowed with more primitive feathers–something they searched for in vain for most of the next century and a half. In the meantime, other scientists sought to illuminate the origin of feathers by examining the scales of modern reptiles, the closest living relatives of birds. Both scales and feathers are flat. So perhaps the scales of the birds’ ancestors had stretched out, generation after generation. Later their edges could have frayed and split, turning them into the first true feathers.

It made sense too that this change occurred as an adaptation for flight. Imagine the ancestors of birds as small, scaly, four-legged reptiles living in forest canopies, leaping from tree to tree. If their scales had grown longer, they would have provided more and more lift, which would have allowed the protobirds to glide a little farther, then a little farther still. Only later might their arms have evolved into wings they could push up and down, transforming them from gliders to true powered fliers. In short, the evolution of feathers would have happened along with the evolution of flight.

This feathers-led-to-flight notion began to unravel in the 1970s, when Yale University paleontologist John Ostrom noted striking similarities between the skeletons of birds and terrestrial dinosaurs called theropods, a group that includes marquee monsters like Tyrannosaurus rex and Velociraptor. Clearly, Ostrom argued, birds were the living descendants of theropods. Still, many known theropods had big legs, short arms, and stout, long tails–hardly the anatomy one would expect on a creature leaping from trees. Other paleontologists argued that birds did not evolve from dinosaurs–rather, their similarities derived from a shared common ancestor deeper in the past.

Until recently it was thought that feathers first appeared in an early member of the lineage of theropods that leads to birds. In 2009, however, Chinese scientists announced the discovery of a bristly-backed creature, Tianyulong, on the ornithischian branch of the dinosaur family tree–about as distant a relative of theropods as a dinosaur can be. This raised the astonishing possibility that the ancestor of all dinosaurs had hairlike feathers and that some species lost them later in evolution. The origin of feathers could be pushed back further still if the “fuzz” found on some pterosaurs is confirmed to be feathers, since these flying reptiles share an even older ancestor with dinosaurs.

There’s an even more astonishing possibility. The closest living relatives of birds, dinosaurs, and pterosaurs are crocodilians. Although these scaly beasts obviously do not have feathers today, the discovery of the same gene in alligators that is involved in building feathers in birds suggests that perhaps their ancestors did, 250 million years ago, before the lineages diverged. So perhaps the question to ask, say some scientists, is not how birds got their feathers, but how alligators lost theirs.

If feathers did not evolve first for flight, what other advantage could they have provided the creatures that had them? Some paleontologists have argued that feathers could have started out as insulation. Theropods have been found with their forelimbs spread over nests, and they may have been using feathers to shelter their young.

Another hypothesis has gained strength in recent years: that feathers first evolved to be seen. Feathers on birds today come in a huge range of colors and patterns, with iridescent sheens and brilliant streaks and splashes. In some cases their beauty serves to attract the opposite sex. A peacock unfolds his iridescent train, for instance, to attract a peahen. 
The possibility that theropods evolved feathers for some kind of display got a big boost in 2009, when scientists began to take a closer look at their structure. They discovered microscopic sacs inside the feathers, called melanosomes, that correspond precisely in shape to structures associated with specific colors in the feathers of living birds. The melanosomes are so well preserved that scientists can actually reconstruct the color of dinosaur feathers. Sinosauropteryx’s tail, for example, appears to have had reddish and white stripes. Perhaps the males of the species flashed their handsome tails when courting females. Or perhaps both sexes used their stripes the way zebras use theirs–to recognize their own kind or confuse predators.

Whatever the original purpose of feathers, they were probably around for millions of years before a single lineage of dinosaurs began to use them for flight. Paleontologists are now carefully studying the closest theropod relatives of birds for clues to how this transition occurred. One of the most revealing is a recently discovered wonder called Anchiornis, more than 150 million years old. The size of a chicken, it had arm feathers with black-and-white portions, creating the spangled pattern you might see on a prize rooster at a county fair. On its head it wore a gaudy rufous crown. In structure, Anchiornis’s plumes were nearly identical to flight feathers, except that they were symmetrical rather than asymmetrical. Without a thin, stiff leading edge, they may have been too weak for flight.

What the plumes lacked in strength, however, they made up for in number. Anchiornis had an embarrassment of feathers. They sprouted from its arms, legs, and even its toes. It’s possible that sexual selection drove the evolution of this extravagant plumage, much as it drives the evolution of peacock trains today. And just as their long, heavy trains pose a burden to peacocks, the extravagant feathers of Anchiornis may have been a bit of a drag, literally.

Corwin Sullivan and his colleagues at the Institute of Vertebrate Paleontology and Paleoanthropology in Beijing have found a way that Anchiornis could have overcome this problem. In the theropods that were closely related to living birds, a particular wristbone was wedge-shaped, allowing them to bend their hands. Anchiornis’s wrist bone was so wedge-shaped that it could fold its arms to its sides, keeping its arm feathers off the ground as it walked. Modern birds use a similar bone in flight, drawing their wings toward their bodies during an upstroke. If Sullivan and his colleagues are right, this crucial flight feature evolved long before birds took wing. It’s an example of what evolutionary biologists call exaptation: borrowing an old body part for a new job. It now looks like bird flight was made possible by a whole string of such exaptations stretching across millions of years, long before flight itself arose.

The way in which that final transition occurred continues to inspire lively debate. Some scientists argue that feathered dinosaurs evolved flight from the ground up, flapping their feathered arms as they ran. Others challenge this notion, pointing out that the “leg wings” on Anchiornis and other close relatives of birds would have made for very clumsy running. These researchers are reviving the old idea that protobirds used feathers to help them leap from trees, glide, and finally fly.

Ground up, trees down–why not both? Flight did not evolve in a two-dimensional world, argues Ken Dial, a flight researcher at the University of Montana-Missoula. Dial has shown that in many species a chick flaps its rudimentary wings to gain traction as it runs from predators up steep inclines, like tree trunks and cliffs. But flapping also helps steady the chick’s inevitable return to lower terrain. As the young bird matures, such controlled descent gradually gives way to powered flight. Perhaps, says Dial, the path the chick takes in development retraces the one its lineage followed in evolution–winging it, so to speak, until it finally took wing.