The chromosome 7 paper led Hurst to reëxamine the results of an amniocentesis, for a pregnant woman unrelated to the KE family, 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 problems 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 convergent 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 off 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 off 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 language. 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 Anthropological 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 difficulty 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.