Startling evidence that the human brain can grow new nerves began with unlikely studies of birdsong
By Edwin Kiester, Jr., and William Kiester Smithsonian magazine, June 2002
The barn where he works is in the horse country of Millbrook, New York, but it echoes with trills, tweets and obbligatos—the raucous music of more than a thousand caged canaries and finches. "Hear that one singing his heart out?" Fernando Nottebohm asks. "He has more than a dozen songs. He’s telling the males, 'This is my territory.' He’s telling the females, 'Hey, look at me.'"
Deconstructing birdsong may seem an unlikely way to shake up biology. But Nottebohm’s research has shattered the belief that a brain gets its quota of nerve cells shortly after birth and stands by helplessly as one by one they die—a "fact" drummed into every schoolkid’s skull. On the contrary, the often-rumpled Argentina-born biologist demonstrated two decades ago that the brain of a male songbird grows fresh nerve cells in the fall to replace those that die off in summer.
The findings were shocking, and scientists voiced skepticism that the adult human brain had the same knack for regeneration. "Read my lips: no new neurons," quipped Pasko Rakic, a Yale University neuroscientist doubtful that a person, like a bird, could grow new neurons just to learn a song.
Yet, inspired by Nottebohm’s work, researchers went on to find that other adult animals—including human beings—are indeed capable of producing new brain cells. And in February, scientists reported for the first time that brand-new nerves in adult mouse brains appeared to conduct impulses—a finding that addressed lingering concerns that newly formed adult neurons might not function. Though such evidence is preliminary, scientists believe that this growing body of research will yield insights into how people learn and remember. Also, studying neurogenesis, or nerve growth, may lead them to better understand, and perhaps treat, devastating diseases such as Parkinson’s and Alzheimer’s, caused by wasted nerves in the brain.
Few would have predicted that canary courtship would lead to such a breakthrough. Nottebohm’s bird studies "opened our eyes that the adult brain does change and develops new cells throughout life," says neurobiologist Fred Gage of the Salk Institute in La Jolla, California, whose lab recently found evidence of nerve cell regrowth in the human brain.
Nottebohm’s research has achieved renown in biology and beyond. A scientist who advances an unconventional view and is later vindicated makes for compelling drama, presenting a hero who appeals to the rebel in us and a cautionary lesson to stay open-minded. Yet Nottebohm prefers being a revolutionary to a statesman. "Once I was in the 5 or 10 percent of scientists who believed in neurogenesis," he says. "Now 95 percent accept that position. I rather liked it better being in the minority."
He has been a bird lover since his boyhood, in Buenos Aires. "Listening to birds was sort of my hobby," he says. "Other boys had cars, I had birds. I liked to try to identify them by their songs." He obtained a doctorate at the University of California at Berkeley—yes, studying birds—before moving to Rockefeller University.
A key moment came in 1981 when he showed that the volume of the part of a male canary’s brain that controls song-making changes seasonally. It peaks in the spring, when the need to mate demands the most of a suitor’s musical ability, and shrinks in the summer. It then starts expanding again in the fall—a time to learn and rehearse new tunes. Those fluctuations, Nottebohm and his coworkers later showed, reflected the death and also birth of thousands of neurons. "Astonishing," Gage and a colleague recently wrote.
Over the years, numerous labs have presented evidence that adult neurogenesis occurs in a range of animals, including the rat, the tree shrew and a type of monkey, the marmoset. Meanwhile, scientists gained clues about the source of the new neurons. Working with birds, a young colleague of Nottebohm’s, Arturo Alvarez-Buylla, traced the new nerves to particular stem cells in the lining of the ventricles, which are fluid-filled cavities in the brain. Stem cells (so much in the news) exist throughout the body. They’re undefined cells that can develop a specialized function, turning into, say, a liver or blood cell. The discovery that neurons can arise from stem cells in the brain fires hopes of a potentially limitless material for repairing damaged brain tissue. But researchers caution that, for now, it’s mere speculation that stem cells capable of becoming neurons can be used this way.
In 1998, researchers reported that neuronal growth also occurs in the adult human brain. The studies made use of brain tissue from people who died of cancer. The patients had been treated in Sweden and injected with a chemical called BrdU. Because BrdU is incorporated into the DNA of dividing cells, the chemical could serve as a marker for any new nerve cells in the brain. In the study, Swedish researchers shipped the brain samples to Gage in La Jolla. He and his coworkers found BrdU in the hippocampus, part of the brain that lays down memories, suggesting that new neurons had developed and perhaps played a role in storing information.
Nearly all evidence of adult neurogenesis in mammals is limited to the hippocampus, and no one is sure what those new neurons do, if anything. Until scientists establish that new, functioning nerves also appear in the cerebral cortex, where higher thoughts are processed, Rakic and others remain skeptical that adult neurogenesis makes much difference to actual brain function. "We start life with a lot of uneducated neurons, but at some point they all become college graduates," he says. "With neurogenesis in the cerebral cortex, you would have neurons that never went to elementary school. New cells would erode all your memories. You would give up all you have labored to acquire."
Elizabeth Gould, a Princeton University neurobiologist who found neurogenesis in the marmoset and other adult primates, argues that the new nerve cells must be useful. "I can’t believe that nature would go to all the trouble of creating thousands of new cells a day to no purpose," she says. "The body is not profligate with its resources."
Nottebohm says the aging brain probably has to develop nerve cells to learn new things. "The brain runs out of memory space," he says. "Everyone past 50 knows that. If we remembered everything, we’d be in overload."
With the same zeal he showed when he first confounded the received wisdom, Nottebohm began new work with blackcapped chickadees in the mid-1990s. One of the American bird species to weather the northern winter, chickadees subsist in that season on seeds and other foods they’ve hidden in trees. Nottebohm found that come autumn, the birds grow new cells in a brain center dealing with spatial memory, the capacity to navigate and find things. The added brainpower helps the chickadees pinpoint their hidden troves months later, Nottebohm says.
Such insight wins admiration. "Fernando has always been ahead of everybody," says Gould. "So far ahead that people for a long time were not able to accept his findings as interesting or important. Now they’re coming around."
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