X-Message-Number: 13055
Date: Tue, 04 Jan 2000 16:04:20 -0500
From: Jan Coetzee <>
Subject: A Decade of Discovery Yields a Shock About the Brain

NY Times: A Decade of Discovery Yields a Shock About the Brain
Tuesday, January 04, 2000

      [By Sandra Blakeslee in today's paper.]

       As scientists look back at all the discoveries made in the
1990's,
the so-called Decade of the Brain, one finding stands out as the most
startling and, for many scientists, the most difficult to accept: people

are
not necessarily born with all the brain cells they will ever have.
      In fact, from birth through late adolescence, the brain appears to

add
billions of new cells, literally constructing its circuits out of
freshly
made neurons as children and teenagers interact with their environments.
In
adulthood, the process of adding new cells slows down but does not stop.

Mature circuits appear to be maintained by new cell growth well into old

age.
      Although the Congressionally mandated "Decade" produced many other

discoveries, from ways to obtain images of fleeting thoughts inside a
person's head to new drugs for a wide variety of mental disorders, the
finding that the brain develops and maintains itself by adding new cells
is
the most revolutionary.
      If these findings hold up to further scrutiny, the next decade of
brain research promises to generate a total revision of how scientists
think
human minds are organized and constructed.
      Findings have already shed new light on mechanisms of learning,
memory
and aging in normal brains and suggest daring new ways to treat strokes
and
other brain disorders. Moreover, they may provide solutions to some
abiding
mysteries -- including the way young children who have half their brains

surgically removed to treat severe epilepsy go on to develop normally,
as
if
they had whole brains in half the usual amount of space.
      Some researchers have begun isolating special cells that continue
to
divide and produce new brain tissue, with the hope of implanting such
cells
into areas of the brain that are damaged by disease or accidents.
      For decades, it was axiomatic that people were born with all the
brain
cells they would ever have. Unlike the bones, the skin, the blood
vessels
and other body parts, where cells divide throughout life to give rise to

new
cells, it was believed that the brain did not renew itself.
      Though the brain did add vast amounts of new connections early in
life
and could compensate somewhat for many injuries, it was thought that no
one
could be expected to grow more brain cells with age. Quite the opposite.

People were told that the only thing they could look forward to was
gradual
mental deterioration as cells died off and were never replenished.
      These ideas were so firmly established that many scientists have a

hard time believing the findings, reported in the last couple of years
by a
number of investigators, that the human brain makes new cells after
birth,
said Dr. Fred H. Gage, a neuroscientist at the Salk Institute in La
Jolla,
Calif. Even when they accept the idea that such cells may exist, they
argue
there is no proof that they do anything important, he said. And those
skeptical of the new developments, like Dr. Pasko Rakic, a
neuroscientist
at
Yale, say that if scientists expect others to change longstanding
thinking
about brain development, the standard of proof must be set very high.
      Dr. Per Andersen, a neurobiologist at the University of Oslo in
Norway, said neuroscientists had responded to several of the new
findings
with "resounding silence." This is probably not because of "active
neglect,"
he said, but "it takes some time to let unexpected results sink down in
the
mutual consciousness of neurobiologists." In short, the new findings are

simply too startling and revolutionary to digest all at once.
      Dr. Morten Raastad, also from Oslo, compared resistance to the
idea
of
brains' growing new cells to the way scientists once resisted the idea
of
plate tectonics and continental drift.
      The theory was first proposed in 1915, but it was not until
scientists
completed sea-floor magnetism studies in the 1960's that it was
accepted,
he
said.
      The traditional view of human brain development is based on
experiments done in the mid-1960's on macaque monkeys by Dr. Rakic.
      He said then that based on available techniques for detecting
dividing
cells in brain tissue there was no evidence that new cells were being
born
in the monkey brain.
      He and others inferred this must be true of all primates,
including
humans.
      According this theory, brains grow as new connecting fibers,
called
synapses and dendrites, proliferate around a fixed number of brain cells

after birth.
      Cells not connected into circuits through these growing fibers
would
die off.
      Thus brains develop by pruning and sculpturing, not by building
networks with billions of new cells, Dr. Rakic and others theorized.
      The fact that many people do not recover the ability to speak or
walk
after having strokes or other traumatic brain injury cemented the view
that
adult brains did not add new cells.
      If they did, people thought, recovery would be more common.
      The first crack in this belief occurred in 1965, when scientists
reported that new nerve cells were generated in a region of the adult
rat
brain called the hippocampus. This is where memories for places and
things
are first formed.
      A year later, they discovered that new cells were migrating to the

olfactory bulb, where smells are decoded.
      These researchers identified a zone within two hollow cavities of
the
rat brain, called ventricles, where new cells are born and then migrate
to
the brain's interior.
      The zone contains so-called stem cells that give rise to many
other
cell types, including neurons and glial cells that nourish neurons.
      The new cells seen in the rat brains appear at a higher rate after

challenges like intense training, injury or an infection, Dr. Raastad
said.
Within a few years, researchers found the cells in adult mice, guinea
pigs,
rabbits and monkeys. In the mid-1980's, other researchers found
irrefutable
evidence that new cells were born in the brains of adult canaries
learning
new songs and chickadees that were remembering where they had stashed
their
winter seeds. But researchers still did not believe that new cells were
created in human brains, Dr. Raastad said.
      In 1997, Dr. Elizabeth Gould, an assistant professor of
neuroscience
at Princeton and colleagues showed that neurogenesis, or the birth of
new
cells, occurred in the hippocampuses of tree shrews and marmoset
monkeys.
But Dr. Rakic and others said this was not possible in humans.
      In 1998, Dr. Gage demonstrated that the number of brain cells in
the
hippocampuses of mice raised in stimulating environments increased by 15

percent -- and that the cells were born in the ventricle zone.
      "This made us go look for the same in humans," Dr. Gage said.
Swedish
colleagues were using a special substance that integrates into the DNA
of
dividing cells to track tumor cells in cancer patients, he said.
      Last year, this substance was found in the hippocampuses of five
cancer patients whose brains were dissected immediately after they died.

      This was a "thrilling" discovery, Dr. Gage said. It means that the

human brain makes new cells in an area already known to be involved in
short-term memory.
      Some sort of neurogenesis may be widespread in the brain and
spinal
cord for maintenance, he said. Like skin, the brain may be repairing
itself
all the time. But like a big gash to the skin, a large brain injury like
a
stroke can overwhelm the repair system.
      As for the rest of the brain, including the cortex, where complex
functions like language and long-term memories reside, Dr. Gould
injected
the same dye used in the human experiments into macaque monkey brains.
By
tracing the chemical, she found that neurons had been born in the
ventricles
and had migrated into the higher cortex, where they made new axons.
      They appeared to connect up to local circuitry and perhaps extend
into
wider circuits, she said, adding that the same might be true for human
brains.
      But the most surprising finding about new cell growth in the human

brain has been virtually ignored by most neuroscientists.
      This part of the story began more than two decades ago when a
young
doctor in training, , William Rodman Shankle, salvaged a stack of
cardboard
boxes containing the largest database ever collected on the developing
human
cerebral cortex.
      The data had been collected from 1939 to 1967 by Dr. Jesse L.
Conel
of
Boston Children's Hospital, who examined the brains of infants and
children
up to age 6 who had died from accidents or diseases not affecting brain
cells. Before his death, he made more than four million measurements,
including the width, thickness and packing density of brain cells at
birth
and at 1, 3, 6, 15, 24, 48 and 72 months of age.
      Dr. Conel published eight volumes of research. Several boxes of
his
raw data were about to be thrown out -- tissue samples and slides
already
having been discarded -- when Dr. Shankle, now a neurologist at the
University of California at Irvine, noticed them stacked in a hallway at

Boston University and rescued them.
      Dr. Conel did not have computer tools to measure exact numbers of
cells, Dr. Shankle said, but he did describe, at each age and within 35
brain areas, the appearance of vertical columns of neurons.
      It is now known that higher brain functions stem from arrays of
these
columns.
      Dr. Shankle and his colleagues re-examined Dr. Conel's data using
modern mathematical and computer techniques to allow for cell shrinkage
and
to distinguish neurons from other kinds of brain cells.
      They found an astonishingly dynamic pattern in all 35 areas.
      In each square millimeter of tissue, Dr. Shankle said, the number
of
neurons rises by a third from birth to 3 months as new cells are added.
      Then the number plummets back to birth level between 3 and 15
months.
      After this point, the number increases rapidly, doubling by the
age
of
6 years. It probably continues increasing, although at a slower rate, up
to
age 18 or 21, Dr. Shankle said.
      The brain enlarges by making new columns, not by making existing
ones
larger, Dr. Shankle said.
      "I suspect that a single set of rules constructs all brains," he
said.
"Children progress through the same stage of development at same rates
independent of their culture."
[continued at
http://www.nytimes.com/library/national/science/010400sci-brain-development

html ]

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