Brain May Grow New Cells Daily

        By NICHOLAS WADE

               In a new challenge to the
               longstanding belief that adults never
        generate new brain cells, biologists at
        Princeton University have found that
        thousands of freshly born neurons arrive
        each day in the cerebral cortex, the outer
        rind of the brain where higher intellectual
        functions and personality are centered.

        Though based on research in monkeys, the
        finding is likely to prove true of people,
        too.

        If so, several experts said, it may overturn
        ideas about how the human brain works
        and open new possibilities for treating
        degenerative brain diseases.

        If the new brain cells,
        or neurons, are
        involved in memory
        and learning --
        perhaps with each
        day's batch of new
        cells recording that
        day's experiences --
        scientists will have to
        make major revisions
        in the longtime view
        that the adult brain's
        neurons are static in
        number and that
        memory is stored
        only in the way they
        interconnect.

        In addition, if the
        brain's cells are in
        constant turnover, as
        the new finding
        suggests, physicians
        may discover ways to
        use the brain's
        natural regeneration
        system for replacing
        cells that are lost in
        diseases of aging.

        The discovery, by Elizabeth Gould and
        Charles G. Gross, is reported in Friday's
        issue of the journal Science.

        The belief that the adult brain does not
        make new cells rested on careful,
        well-known studies by Pasko Rakic of Yale
        University, who looked for the formation of
        new neurons in the monkey brain and
        found none.

        But the Princeton work is likely to be
        convincing, because it builds on previous
        reports of brain cell turnover, notably by
        Fernando Nottebohm of Rockefeller
        University, who showed that canaries grow
        new neurons to learn new songs, and
        recent studies showing that new cells are
        formed in the hippocampus, a brain region
        where initial memories of faces and places
        are formed.

        "The scientific community can easily
        believe something it is 50 percent ready to
        absorb, but not something that comes out
        of left field," said Eric R. Kandel, a leading
        neuroscientist at Columbia University. "But
        here, we are prepared for it."

        Kandel compared the likely change in view
        to the paradigm shifts described by the
        historian of science Thomas Kuhn as
        occurring when one major scientific theory
        is replaced by another.

        Although the new study was done in
        macaque monkeys and has yet to be
        confirmed in humans, as fellow primates
        monkeys are usually quite predictive of
        what occurs in people.

        Gould, who has studied new cell formation
        in the hippocampus, and Gross, an expert
        on the cerebral cortex, injected macaques
        with a chemical that is incorporated in the
        new DNA formed when a cell divides.

        They found that a stream of new neurons
        were generated in the monkeys' brains in a
        zone just above the brain's fluid-filled
        central chambers. This zone was recently
        identified by other scientists as the home
        of the brain's stem cells, the source cells
        from which an organ is replenished.

        The new neurons migrated toward the
        cortex, matured and sent out axons to
        make connections with other brain cells,
        the Princeton biologists found.

        The researchers looked for new neurons in
        four areas of the cortex, and found them in
        three areas where memories are known to
        be stored: the frontal cortex, used for
        decision-making, and two areas on the side
        of the brain used for visual recognition.

        No new neurons were detected in the
        fourth area, the striate cortex, a region at
        the back of the head that simply processes
        visual information from the eyes and
        passes it on to other parts of the cortex.

        Whatever the new cells are doing in the
        cortex, they affect regions of the brain that
        are central to human thought and identity.
        The Princeton work, said Ronald D. G.
        McKay, an expert on brain stem cells at
        the National Institutes of Health, "places
        new neurons in the region of the brain
        involved in the highest level of
        personality: it's the frontal cortex that is
        important in determining who you are in a
        very human way."

        Gould said it was possible that the new
        neurons arriving in the cortex would be
        particularly sensitive to recording
        information for a certain period while they
        matured.

        "They would become integrated in the
        circuitry and represent the information
        being learned at that particular time," she
        said, after which they would not record
        anything more.

        In other words, the conveyor belt of new
        neurons might record successive days'
        experiences almost like a moving tape.

        "We know the characteristic of memory is
        that events are tagged with times," Gross
        said. "We have no idea how that is done.
        But since we have now shown there are
        new cells added every day, which cover a
        spectrum of ages, these cells could possibly
        provide the substrate for the temporal
        dimension of memory."

        Kandel, of Columbia University, said the
        idea was perfectly possible, given how little
        was now known about the brain's system
        for ultimate long-term memory storage.

        "How do you distinguish the memory of 20
        years ago from the memory of 30 years
        ago? You would have to mark the birthday
        of the cell in some way," Kandel said,
        suggesting that the train of new neurons
        offered a plausible mechanism whereby the
        brain might somehow do this.

        The notion that new memories are stored
        in a train of new nerve cells was advocated
        in the 1960's by Joseph Altman, then of
        the Massachusetts Institute of Technology.
        But his proposal was not widely accepted.
        And when Rakic, an authority on neuron
        formation in the embryonic monkey brain,
        reported in 1985 that no new neurons
        were formed in the adult monkey's brain,
        this became the accepted view.

        Even when Gould and others showed
        recently that new cells were formed in the
        hippocampus, Rakic argued that this was a
        primitive area of the brain -- even reptiles
        have a hippocampus -- and that brain
        organs acquired more recently in
        evolution, like the primates' cerebral
        cortex, would not be expected to behave
        the same way.

        Gould said it was this argument that had
        made her determined to look for new cells
        being formed in the cerebral cortex,
        despite the expense of doing work on
        monkeys and the risk in "redoing an
        experiment that a very well respected
        person," Rakic, had already performed.

        Rakic's office said he was traveling
        yesterday and unavailable for comment.

        If indeed the brain is constantly renewing
        the cells in its cortex, hippocampus and
        maybe other areas, the prospects for
        learning how to repair the aged or
        damaged brain begin to look much more
        hopeful.

        "Degenerative diseases of the brain are
        really defined by loss of nerve cells,"
        Kandel said. Though diseases like
        Parkinson's affect specific areas of the
        brain, it might become possible to channel
        young new neurons into the areas of
        disease. "This is pie in the sky," he said,
        "but at least there is now the possibility of
        thinking about it."

        William T. Greenough, a neuroscientist at
        the University of Illinois, said the Princeton
        work created a "whole new ball game" for
        addressing brain diseases, by harnessing
        the brain's own restorative potential.

        The Princeton biologists plan to follow up
        their discovery by blocking the formation
        of new neurons in monkeys' brains and
        seeing what happens. If the new neurons
        are essential for memory and learning,
        then serious deficits should appear in the
        monkeys' performance.

        The researchers as yet have no idea
        whether the loss of brain cells and the
        generation of new ones are separate
        events or part of the same cycle.

        "Our discovery," Gross said, "suggests
        more questions than answers."