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Elizabeth Gould Photography by Reynard Li
Professor Elizabeth Gould has a picture of a marmoset on her computer screen. Marmosets are a new world monkey, and Gould has a large colony living just down the hall. Although her primate population is barely three years old, Gould is clearly smitten, showing off these photographs like a proud parent. Marmosets are the ideal experimental animal: a primate brain trapped inside the body of a rat. They recognize themselves in the mirror, form elaborate dominance hierarchies and raise their young cooperatively. If you can look past their rodent-like stature and punkish pompadour, marmosets can seem disconcertingly human.
In her laboratory at Princeton University’s Department of Psychology, Gould is determined to create a marmoset environment that takes full advantage of their innate intelligence. She doesn’t believe in metal cages. “We are housing our marmosets in large, enriched enclosures,” she says, “and with a variety of objects to support foraging. These are social animals, and it’s important to let them be social. Basically, we want to bring our experimental conditions closer to the wild.”
But Gould is not a primatologist. She doesn’t give her marmosets adorable names, or spend time cuddling with their young. In fact, these marmosets don’t even know she exists: Gould prefers to observe them remotely, on a little video screen. Staring at the televised frenzy of this little marmoset world, it is poignant to know how their lives will end. Their brains will be cut into thousands of transparent slices. Their dissected neurons will be stained neon green and the density of their dendritic connections will be quantified under a powerful microscope. They will live on as data.
The naturalistic habitat that Gould has created for these marmosets is essential to her studies, which involve understanding how the environment affects the brain. Eight years after Gould defied the entrenched dogma of her science and proved that the primate brain is always creating new neurons, she has gone on to demonstrate an even more startling fact: The structure of our brain, from the details of our dendrites to the density of our hippocampus, is incredibly influenced by our surroundings. Put a primate under stressful conditions, and its brain begins to starve. It stops creating new cells. The cells it already has retreat inwards. The mind is disfigured.
The social implications of this research are staggering. If boring environments, stressful noises, and the primate’s particular slot in the dominance hierarchy all shape the architecture of the brain—and Gould’s team has shown that they do—then the playing field isn’t level. Poverty and stress aren’t just an idea: they are an anatomy. Some brains never even have a chance.
Viewed through the magnified eyes of a confocal microscope, a newborn neuron looks fragile, almost lonely. Everything around it is connected to everything else, but the new cell is all alone, just a seed of soma and a thin stalk of axon desperately trying to plug itself into the network. If it doesn’t, it will die. Staring at this tenuous neuron, it is hard to believe that so much depends upon its presence.
Dr. Gould insists on being called Liz. She wears faded jeans to work and ties back her long dark hair in a loose braid. She smiles easily, and intersperses discussions of marmoset families with stories about her own children. Gould doesn’t talk about her research in listless sentences full of acronyms. Instead, she takes you through the experimental process, confessing all the difficulties and ambiguities along the way.
Gould’s casual air conceals a necessary tenaciousness: It is not easy to shift a paradigm. Four days after giving birth to her third child, Gould was back at work, lecturing to a room full of undergraduates. She has always worked long hours, and expects nothing less of her employees. (Saturdays in the Gould lab are indistinguishable from Mondays.) And even though her research has set off a frenzy of activity—neurogenesis is now one of the hottest topics in neuroscience—Gould has managed to remain at the cutting edge of the field she helped to
For such a high-profile scientist, Gould’s lab at Princeton is surprisingly small. Lavishly outfitted (she has her own $400,000 confocal microscope and large marmoset colony) the lab consists of just two post-docs and two grad students. They are a close knit group, and work on overlapping problems. “When I first began at Princeton,” Gould says, “I had tunnel vision. I was just so determined to answer my critics and prove that adult neurogenesis was real. But now I’m finally able to think about neurogenesis in a broader context. We are free to figure out what all these new cells actually do.”
To understand how neurogenesis—the process of creating new brain cells— works, Gould’s lab studies the effect of two separate variables: stress and enriched environments. Chronic stress, predictably enough, decreases neurogenesis. As Christian Mirescu, one of Gould’s post-docs, put it, “When a brain is worried, it’s just thinking about survival. It isn’t interested in investing in new cells for the future.”
On the other hand, enriched animal environments—enclosures that simulate the complexity of a natural habitat—lead to dramatic increases in both neurogenesis and the density of neuronal dendrites, the branches that connect one neuron to another. Complex surroundings create a complex brain.
Gould’s field is a new one. Only a decade ago, the idea that the primate brain is constantly creating new neurons, and that these new neurons are not only functional but responsive to changes in the environment, was unimaginable. Indeed, the fact that neurogenesis did not exist was one of modern neuroscience’s founding principles. This theory, first articulated by Santiago Ramón y Cajal at the start of the 20th century, held that brain cells—unlike every other cell in our body—don’t divide. They don’t die, and they are never reborn. We emerge from the womb with the only brain we will ever have.
The most convincing modern defender of this theory was Pasko Rakic, the chairman of Yale University’s neurobiology department and among the most respected neuroscientists of his generation. In the early 1980s, Rakic realized that neurogenesis had never been properly tested in primates. He set out to investigate. Rakic studied 12 rhesus monkeys, injecting them with radioactively-labeled thymidine which allowed him to trace the development of neurons in the brain. Rakic then killed the monkeys at various stages after the injection of the thymidine, and searched for any signs of new neurons. There were none.
“All neurons of the rhesus monkey brain are generated during pre-natal and early post-natal life,” Rakic wrote in his 1985 paper, “Limits of Neurogenesis in Primates.” “Not a single” new neuron “was observed in the brain of any adult animal.” While Rakic admitted that his proof was limited, he persuasively defended the dogma. He even went so far as to construct a plausible evolutionary theory as to why neurons can’t divide: Rakic imagined that at some point in our distant past, primates had traded the ability to give birth to new neurons for the ability to retain plasticity in our old neurons. According to Rakic, the “social and cognitive” behavior of primates required the absence of neurogenesis. His paper, with its thorough demonstration of what everyone already believed, seemed like the final word on the matter. No one bothered to verify his findings.
The genius of the scientific method, however, is that it accepts no permanent solution. Skepticism is its solvent, for every theory is imperfect. Scientific facts are meaningful precisely because they are ephemeral, because a new observation, a more honest observation, can always alter them. This is what happened to Rakic’s theory of the fixed brain. It was, to use Karl Popper’s verb, falsified.
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