Scientific American Mind-June/July 2007

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Head Lines The Genetic Roots of Autism Many studies have traced the history of families with more than one autistic member, but few scientists have attempted to crack the code of sporadic autism—which arises unexpectedly in a formerly unaffected lineage and is more common than inherited autism. Now a group at Cold Spring Harbor Laboratory believes it has found a distinct mechanism by which autism can strike sporadically. Led by Jonathan Sebat and Michael Wigler, the team examined the entire genomes of more than 150 families with at least one autistic member. They scanned for new genetic mutations, comparing any fi ndings with parental DNA to assure the variation was not inherited and therefore truly sporadic. They found that sporadic autism sufferers had a higher incidence of copy number deletions—regions where segments of DNA had been spontaneously deleted—than healthy subjects or people who inherited autism. The researchers estimate that these random DNA deletions, ranging from one to 69 genes in size, most likely contribute to mental illness in at least 15 percent of all autism patients. That proportion could rise as developing technology allows the group to fi nd previously undetectable genetic alterations. Now that these large-scale mutations have been identifi ed, the Cold Spring Harbor group and other researchers can begin investigating individual genes within the target region. Having already used this method to pinpoint cancer genes, the team is currently turning its eye to schizophrenia. Ultimately, the fi ndings may elucidate how these affl ictions arise and provide early detection tools so that treatment can begin sooner and be more effective. —Nikhil Swaminathan 8 June/July 2007 COPYRIGHT 2007 SCIENTIFIC AMERICAN, INC. VICTOR DE SCHWANBERG Photo Researchers, Inc.
GETTY IMAGES (top); ALFRED PASIEKA Photo Researchers, Inc. (bottom) Emotional Morality Would you take one human life to save many? The obvious answer might seem to be “yes”—but what if your choice also meant you would be sacrifi cing your own child? Such dilemmas suggest that moral decision making has an emotional component, and now scientists have found the brain region responsible for generating these feelings. Researchers studied patients with damage to their ventromedial prefrontal cortex, an area in the forebrain where social emotions such as compassion, guilt and shame arise. They asked the patients to respond to a variety of hypothetical moral dilemmas evoking emotional reactions of different strengths, then compared their responses with those of people whose forebrains were intact. The subjects with damage showed a utilitarian approach in their answers, favoring the greater good regardless of the means required to achieve such ends. For example, many of them said they would smother their own baby to save a group of other people, whereas those with intact forebrains more of- Mind Map For years, the human brain has been compared to a computer—but it is a computer without a wiring diagram. Researchers simply do not know how the billions of neurons in the brain are connected to one another, and without this information they cannot fully understand how the brain’s structure gives rise to perception and behavior. Now, for the fi rst time, scientists have found a way to track the connections between a single neuron and other cells—a discovery that could eventually lead to a 3-D map of the brain’s wiring. A team led by Edward M. Callaway of the Salk Institute for Biological Studies in San Diego illuminated neuronal links by modifying the rabies virus. The investigators remove the gene for a protein that allows the virus to move between cells and let the crippled virus infect each nerve cell they want to study. Then, by inserting the viral gene into these neurons, they cause each brain cell to manufacture the missing protein, thereby restoring the virus’s ability to move into directly connected cells. From there, the virus cannot spread any farther because its new neuronal hosts do not make the vital protein. Within a few days, the fl uorescent-dyed virus creates a glowing map of a single neuron’s every connection. ten said they would not do so. In less emotionally fraught scenarios, all the study participants responded similarly. For instance, nearly everyone would choose to redirect deadly fumes from a room with three strangers to a room with one. The fi ndings show that our natural aversion to harming others emerges from two previously documented systems in the brain—one emotional and one rational. The emotional system pinpointed in this study triggers a fast, refl exive response; it provides a shortcut to what is right in situations requiring immediate action. The rational side aids us when deliberation and calculation are advantageous. Scientists do not yet understand how the two systems interact or how one supersedes the other when they dictate contradictory courses of action. Moreover, people with damaged forebrains can still rely on their rational side to respond to moral dilemmas. “This study doesn’t mean that people who lack social emotions are dangerous,” says neuroscientist Michael Koenigs, then at the University of Iowa, a member of the research team. “They tend to show little empathy and guilt, but they are not killers.” —Graciela Flores “Circuitry is the basis for all complex neural function,” Callaway says. “Without knowing the circuit, there is no way to know how the brain works.” Although every brain has different synaptic connections resulting from individual experiences, the researchers believe they will be able to identify common circuits and eventually fi gure out the function of specifi c neuronal pathways. The team hopes to work with live animals within months and to begin to construct “a precise wiring diagram of the mouse brain.” —Jonathan Beard www.sciammind.com SCIENTIFIC AMERICAN MIND 9 COPYRIGHT 2007 SCIENTIFIC AMERICAN, INC.
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