No more excuses about dead brain cells allowed. The dogma that people are born with all the neurons they will ever possess is utterly turned on its head.

Even the fellow who is widely cited as tamping that dogma into place 15 years ago with a study on the limits in primates of making new brain cells says now that he was misunderstood.

"I was misquoted as saying, 'Read my lips: No new neurons,' " said Pasko Rakic, a developmental biologist at Yale University in New Haven, Conn. "I didn't say no, I said limits."

Having fun with the turn of history, the professor of neuroscience told an audience of fellow scientists this weekend that he's been accused by his 80-year-old aunt Maria of being a pessimist. "Pasko," she asked, "why are you staying in my way to get new neurons?"

Aunt Maria would have liked hearing the session on adult neurogenesis -- the making of new brain cells -- at the annual meeting of the American Association for the Advancement of Science, which continues this week. She would have heard not only about recent evidence that some brain cells are refreshed even in elderly people but also newer research that suggests scientists can manipulate immature cells to repair parts of the brain that wouldn't naturally be renewed.

She also would have heard details of a study that laboratory mice that run regularly sprout more new neurons and retain those neurons longer than sedentary mice.

And she would have seen new life given to old work by Fernando Nottebohm, a neuroscientist and bird-watcher who, during the same period that Rakic looked fruitlessly for brain-cell growth in monkeys, found that parts of the canary brain are reborn seasonally, enabling the birds to learn new songs each year.

Nottebohm, a researcher at Rockefeller University in New York City, remembers giving a talk to scientists in 1985 about new hope for neurology. People didn't listen as respectfully in those days. "I was in the minority then," he said. "Now I'm part of a very (large) club."

The "club" draws more significance today from Nottebohm's discovery that cells in parts of the male canary brain die off in spring as breeding season begins and are replenished in fall, helping the birds learn a fresh musical repertoire for courtship the next year. Nottebohm believes the old cells must die to make room physically for the new ones.

He also found that the birds that exercised their new brain cells by singing retained those cells longer. Birds whose songs were interrupted -- by a researcher waving his hands -- produced less of a particular chemical that advances cell growth and survival. "The more you use a circuit, the more you promote cell survival," Nottebohm said.

Conceptually, that finding jibes with recent research by Fred Gage at the Salk Institute in La Jolla that mice that run grew more brain cells and retained them longer. Gage also has found that brain cells survived better in mice given an "enriched" environment consisting of more cage space, a running wheel and a tunnel like those given to pet hamsters.

It was Gage and collaborators who made the revolutionary announcement in the fall of 1998 that even adult humans grow new brain cells. This they discovered by studying the brains of five Swedish cancer patients ages 55 to 75. Three weeks to two years before their deaths, the patients were injected with chemicals that mark dividing cells. Later, the
researchers found the markers that indicated that immature brain cells were proliferating and producing new neurons.

Gage said Saturday that scientists know of only two sites in the brain that produce new cells. One is in the dentate gyrus, a portion of the hippocampus, which controls learning and short-term memory. The other, deep inside the brain, is called the sub-
ventricular zone.

But it's possible that the source of a new cell does not determine its fate in the brain as much as its environment. Gage said his lab has found that immature cells from the spinal cord grafted to the hippocampus can give rise to new neuronal cells. Even more fantastically, spinal stem cells imported to an adult optic nerve took on the characteristics of optic nerve cells.

Rakic, though now an avowed believer in neurogenesis, said there may be good reason that humans evolved to be born with most of the 100 billion neurons they will ever have. "In evolution, we traded the ability to regenerate neurons for the ability to retain them," he said. "Unlike birds, we don't need to learn a new song every year. ... For (long-term) memory, it would be a disadvantage. These cells didn't go to college. We could maybe work on another approach -- how to preserve (existing) cells."

Then he offered his version of President John F. Kennedy's famous saying: "Ask not what new neurons can do for you. Ask what you can do for your old neurons."

On Sunday, Paula Tallal described research about just that -- helping existing neurons to function better. Co-director of the Center for Molecular and Behavioral Neuroscience at Rutgers University in New Jersey, Tallal has helped develop a computer program that helps children overcome language disabilities. Essentially, the children's brains are slow to hear subtle differences between sounds -- the difference between ball and doll, for instance.

The software slows the sound so that the child can hear the difference, then slowly speeds up the enunciation as the child catches on. As with muscles trained to lift weights, the brain can be trained to overcome weaknesses.

Tallal acknowledged that the concept behind this is not new, although the exercise is. "We've always known that practice makes perfect," she said. Now scientists are beginning to understand why.