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there had to be a genetic link, researchers hunted for more than a
decade before they found the gene responsible.
The big break came in 1998, when University of Oxford geneti-
cists led by Anthony Monaco and Simon Fisher identified a distinct
chunk of chromosome 7 linked to the speech and language prob-
lems found in the KE family. Yet the region held dozens of genes,
and they couldn't pinpoint the one bad actor. Enter Jane Hurst, a
clinical geneticist who worked at a hospital on Oxford's grounds and,
coincidentally, had coauthored the first report on the KE family.
The chromosome 7 paper led Hurst to reëxamine the results of
an amniocentesis, for a pregnant woman unrelated to the KE fam-
ily, that she had reviewed four years earlier. Hurst had found that
the fetus had a chromosomal hiccup called a translocation, and she
later learned that the child developed speech and language prob-
lems strikingly similar to those seen in the KE family. Looking at the
results again, she saw that the translocation had occurred in the very
same region of chromosome 7 that Fisher had identified. "I phoned
up Simon and said, 'I found you the patient who's going to get you
the gene,' " recalls Hurst, adding that she wasn't serious. But that's
precisely what happened: the translocation in the boy disrupted a
gene called FOXP2, which it turned out had been mutated in the 15
members of the KE family who exhibited severe problems.
When Monaco, Fisher, Hurst, and coworkers reported the con-
vergent FOXP2 findings in the October 4, 2001, issue of Nature, it
made international headlines---and, more important, announced
the start of a new era in speech and language research.
Even then, the scientists knew that FOXP2 does not single-
handedly wire the brain for language. In the grand theater of the
genome, it is cast as a transcription factor, turning other genes on or
o by telling them whether to transcribe their DNA into messenger
RNA, which leads to the production of proteins. And FOXP2 has a
broad repertoire in embryonic development, playing critical roles
in the formation of the lungs, heart, and intestines.
Yet FOXP2 is clearly involved, too, in the molecular pathways
behind speech and language. Clinicians in several countries have
now reported patients with aberrant FOXP2 genes and KE-like
speech and language problems. Geschwind has taken some of
the first steps in uncovering the connection between FOXP2 and
language. He and Fisher recently studied human fetal brains and
neural-cell cultures to identify which genes the FOXP2 protein
turns on or o in the brain. They connected FOXP2 to more than
200 genes that control the development of neurons, the release of
neurotransmitters that send messages between nerves, and the
changes in synapses that underlie learning and memory. Some of
these genes will very likely turn out to be involved in speech and lan-
guage. To sift this genetic river for the gems, Geschwind is zooming
in on about 15 genes that also have ties to schizophrenia, as well as
34 genes to which FOXP2 binds in two areas of the brain that other
studies have shown are involved with language and speech.
To date, the discovery of FOXP2's link to speech and language has
yielded more questions than answers. But it has kicked open a door
that neuroscientists had been knocking on for over a century.
THE KNOTTY MIND
In 1861, Pierre Paul Broca came to a meeting of the Anthropologi-
cal Society of Paris with another man's brain. Broca, a surgeon
and neurologist who was the society's founder, had retrieved the
brain from an unusual patient who had been hospitalized for 30
years. The patient was known as Tan because he would answer
"Tan, tan" to any question put to him. He eventually lost the ability
to speak altogether, although he understood almost everything he
heard. Broca first met Tan only five days before his death, when
he arrived in the surgery unit because of a massive, gangrenous
infection. On autopsy, Broca found that Tan's brain contained a
number of lesions, the most extensive and oldest of which was in
the middle of the left frontal lobe. Broca asserted that this damage
caused Tan's loss of speech.
Thirteen years later, the German physician Carl Wernicke
described the brain of a stroke patient who could speak but had
immense di culty understanding what was said to him. Again,
a lesion in the left hemisphere stood out, although it was farther
back, near the intersection of the temporal and parietal lobes.
As Geschwind explains the importance of what are now known
as Broca's and Wernicke's areas, he points out the cerebral real
estate they occupy on the plastic brain he has finally assembled.
Subsequent research has shown that both areas do play critical
roles in speech and language. Though damage to either does not
always cause problems, the neural circuitry for speech typically
runs along the left Sylvian fissure---a sort of neural Grand Canyon
that stretches from Broca's area to Wernicke's.
Geschwind has been captivated by this asymmetry, and by its
relationship to handedness. Roughly 90 percent of us are right-
handed, and nearly all righties depend on that left "perisylvian"
region for speech and language. (About 40 percent of lefties instead
rely on the right perisylvian region or use both hemispheres.)
"There's some kind of benefit to the kind of processing that's going
on in language---which is extremely rapid processing---to keep
everything in one circuit in one hemisphere," he concludes.
The process that creates asymmetry often goes amiss in people
with dyslexia, schizophrenia, or autism---all disorders with links
to language problems. So Geschwind and others have set about
hunting for genetic aberrations implicated in language disorders
and for genes linked to di erences in brain asymmetry, such as
those related to handedness.
While the discovery of the mutation in FOXP2 required great
e ort (and a dollop of luck), all told it involved analyzing the DNA
of no more than 50 people. In contrast, no simple mutation of a
single gene is likely to disrupt brain asymmetry or cause dyslexia,
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