In the early 1980s, Rakic realized that the idea that neurons never divide had never been properly tested in primates. The dogma was entirely theoretical. Rakic set out to investigate. He studied twelve rhesus monkeys, injecting them with radioactive 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 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 influential paper “Limits of Neurogenesis in Primates,” which he published in 1985. While Rakic admitted that his proof wasn’t perfect, he persuasively defended the dogma. He even went so far as to construct a plausible evolutionary theory as to why neurons couldn’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 modify the connections between 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. His experiments were never independently verified.
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.
In 1989, Elizabeth Gould, a young postdoc working in the lab of Bruce McEwen at Rockefeller University, in New York City, was investigating the effect of stress hormones on rat brains. Chronic stress is devastating to neurons, and Gould’s research focused on the death of cells in the hippocampus. But while Gould was documenting the brain’s degeneration, she happened upon something completely miraculous: the brain also healed itself.
Confused by this anomaly, Gould went to the library. She assumed she was making some simple experimental mistake, because neurons don’t divide. Everybody knew that. But then, looking through a dusty twenty-seven-year-old science journal, Gould found a tantalizing clue. Beginning in 1962, a researcher at MIT, Joseph Altman, published several papers claiming that adult rats, cats, and guinea pigs all formed new neurons. Although Altman used the same technique that Rakic later used in monkey brains — the injection of radioactive thymidine — his results were ridiculed, and then ignored.
As a result, the brand-new field of neurogenesis vanished before it began. It would take another decade before Michael Kaplan, at the University of New Mexico, would use an electron microscope to image neurons giving birth to new neurons. Kaplan discovered these fresh cells everywhere in the mammalian brain, including the cortex. Yet even with this visual evidence, science remained stubbornly devoted to its doctrine. After enduring years of scorn and skepticism, Kaplan, like Altman before him, abandoned the field of neurogenesis.
Reading Altman’s and Kaplan’s papers, Gould realized that her mistake wasn’t a mistake: it was an ignored fact. The anomaly had been suppressed. But the final piece of the puzzle came when Gould discovered the work of Fernando Nottebohm, who was, coincidentally, also at Rockefeller. Nottebohm, in a series of remarkably beautiful studies on bird brains, showed that neurogenesis was required for bird song. To sing their complex melodies, male birds needed new brain cells. In fact, up to 1 percent of the neurons in the bird’s song center were made fresh every day. “At the time, this was a radical idea,” Nottebohm says. “The brain was thought to be a very fixed organ. Once development was over, scientists assumed that the mind was cast in a crystalline structure. That was it; you were done.”
Nottebohm disproved this dogma by studying birds in their actual habitat. If he had kept his birds in metal cages, depriving them of their natural social context, he would never have observed the abundance of new cells that he did. The birds would have been too stressed to sing, and fewer new neurons would have been created. As Nottebohm has said, “Take nature away and all your insight is in a biological vacuum.” It was only because he looked at birds outside of the laboratory’s vacuum that he was able to show that neurogenesis, at least in finches and canaries, had a real evolutionary purpose.
Despite the elegance of Nottebohm’s data, his science was marginalized. Bird brains were seen as irrelevant to the mammalian brain. Avian neurogenesis was explained away as an exotic adaptation, a reflection of the fact that flight required a light cerebrum. In his Structure of Scientific Revolutions, the philosopher of science Thomas Kuhn wrote about how science tends to exclude its contradictions: “Until the scientist has learned to see nature in a different way, the new fact is not quite a scientific fact at all.” Evidence of neurogenesis was systematically excluded from the world of “normal science.”
But Gould, motivated by the strangeness of her own experimental observations, connected the dots. She realized that Altman, Kaplan, and Nottebohm all had strong evidence for mammalian neurogenesis. Faced with this mass of ignored data, Gould abandoned her earlier project and began investigating the birth of neurons.
She spent the next eight years quantifying endless numbers of radioactive rat brains. But the tedious manual labor paid off. Gould’s data shifted the paradigm. More than thirty years had passed since Altman first glimpsed new neurons, but neurogenesis had finally become a scientific fact.
After her frustrating postdoc, during which time her science was continually attacked, Gould was offered a job at Princeton. The very next year, in a series of landmark papers, she began documenting neurogenesis in primates, in direct contradiction of Rakic’s data. She demonstrated that marmosets and macaques created new neurons throughout life. The brain, far from being fixed, is actually in a constant state of cellular upheaval. By 1998, even Rakic admitted that neurogenesis was real, and he reported seeing new neurons in rhesus monkeys.* The textbooks were rewritten: the brain is constantly giving birth to itself.
Gould has gone on to show that the amount of neurogenesis is itself modulated by the environment, and not just by our genes. High levels of stress can decrease the number of new cells; so can being low in a dominance hierarchy (the primate equivalent of being low class). In fact, monkey mothers who live in stressful conditions give birth to babies with drastically reduced neurogenesis, even if those babies never experienced stress themselves. But there is hope: the scars of stress can be healed. When primates were transferred to enriched enclosures — complete with branches, hidden food, and a rotation of toys — their adult brains began to recover rapidly. In less than four weeks, their deprived cells underwent radical renovations and formed a wealth of new connections. Their rates of neurogenesis returned to normal levels. What does this data mean? The mind is never beyond redemption, for no environment can extinguish neurogenesis. As long as we are alive, important parts of the brain are dividing. The brain is not marble, it is clay, and our clay never hardens.
Neuroscience is just beginning to explore the profound ramifications of this discovery. The hippocampus, the part of the brain that modulates learning and memory, is continually supplied with new neurons, which help us to learn and remember new ideas and behaviors. Other scientists have discovered that antidepressants work by stimulating neurogenesis (at least in rodents), implying that depression is ultimately caused by a decrease in the amount of new neurons, and not by a lack of serotonin. A new class of antidepressants is being developed that targets the neurogenesis pathway. For some reason, newborn brain cells make us happy.
And while freedom remains an abstract idea, neurogenesis is cellular evidence that we evolved to never stop evolving. Eliot was right: to be alive is to be ceaselessly beginning. As she wrote in Middlemarch, the “mind [is] as active as phosphorus.” Since we each start every day with a slightly new brain, neurogenesis ensures that we are never done with our changes. In the constant turmoil of our cells — in the irrepressible plasticity of our brains — we find our freedom.
The Literary Genome
Even as neuroscience began to reveal the brain’s surprisingly supple structure, other scientists