Get out the spittoon. Men produce twice as much saliva as women. Women, for their part, learn to speak earlier, know more words, recall them better, pause less and glide through tongue twisters.

Put aside Simone de Beauvoir's famous dictum, "One is not born a woman but rather becomes one." Science suggests otherwise, and it's driving a whole new view of who and what we are. Males and females, it turns out, are different from the moment of conception, and the difference shows itself in every system of body and brain.

It's safe to talk about sex differences again. Of course, it's the oldest story in the world. And the newest. But for a while it was also the most treacherous. Now it may be the most urgent. The next stage of progress against disorders as disabling as depression and heart disease rests on cracking the binary code of biology. Most common conditions are marked by pronounced gender differences in incidence or appearance.

Although sex differences in brain and body take their inspiration from the central agenda of reproduction, they don't end there. "We've practiced medicine as though only a woman's breasts, uterus and ovaries made her unique -- and as though her heart, brain and every other part of her body were identical to those of a man," says Marianne J. Legato, M.D., a cardiologist at Columbia University who spearheads the new push on gender differences. Legato notes that women live longer but break down more.

Do we need to explain that difference doesn't imply superiority or inferiority? Although sex differences may provide ammunition for David Letterman or the Simpsons, they unfold in the most private recesses of our lives, surreptitiously molding our responses to everything from stress to space to speech. Yet there are some ways the sexes are becoming more alike -- they are now both engaging in the same kind of infidelity, one that is equally threatening to their marriages.

Everyone gains from the new imperative to explore sex differences. When we know why depression favors women two to one, or why the symptoms of heart disease literally hit women in the gut, it will change our understanding of how our bodies and our minds work.

The Gene Scene

Whatever sets men and women apart, it all starts with a single chromosome: the male-making Y, a puny thread bearing a paltry 25 genes, compared with the lavish female X, studded with 1,000 to 1,500 genes. But the Y guy trumps. He has a gene dubbed Sry, which, if all goes well, instigates an Olympic relay of development. It commands primitive fetal tissue to become testes, and they then spread word of masculinity out to the provinces via their chief product, testosterone. The circulating hormone not only masculinizes the body but affects the developing brain, influencing the size of specific structures and the wiring of nerve cells.

But sex genes themselves don't cede everything to hormones. Over the past few years, scientists have come to believe that they too play ongoing roles in gender-flavoring the brain and behavior.

Females, it turns out, appear to have backup genes that protect their brains from big trouble. To level the genetic playing field between men and women, nature normally shuts off one of the two X chromosomes in every cell in females. But about 19 percent of genes escape inactivation; cells get a double dose of some X genes. Having fall-back genes may explain why females are far less subject than males to mental disorders from autism to schizophrenia.

What's more, which X gene of a pair is inactivated makes a difference in the way female and male brains respond to things, says neurophysiologist Arthur P. Arnold, Ph.D., of the University of California at Los Angeles. In some cases, the X gene donated by Dad is nullified; in other cases it's the X from Mom. The parent from whom a woman gets her working genes determines how robust her genes are. Paternal genes ramp up the genetic volume, maternal genes tune it down. This is known as genomic imprinting of the chromosome.

For many functions, it doesn't matter which sex genes you have or from whom you get them. But the Y chromosome itself spurs the brain to grow extra dopamine neurons, Arnold says. These nerve cells are involved in reward and motivation, and dopamine release underlies the pleasure of addiction and novelty seeking. Dopamine neurons also affect motor skills and go awry in Parkinson's disease, a disorder that afflicts twice as many males as females.

XY makeup also boosts the density of vasopressin fibers in the brain. Vasopressin is a hormone that both abets and minimizes sex differences; in some circuits it fosters parental behavior in males; in others it may spur aggression.

Sex on the Brain

Ruben Gur, Ph.D., always wanted to do the kind of psychological research that when he found something new, no one could say his grandmother already knew it. Well, "My grandmother couldn't tell you that women have a higher percentage of gray matter in their brains," he says. Nor could she explain how that discovery resolves a long-standing puzzle.

Gur's discovery that females have about 15 to 20 percent more gray matter than males suddenly made sense of another major sex difference: Men, overall, have larger brains than women (their heads and bodies are larger), but the sexes score equally well on tests of intelligence.

Gray matter, made up of the bodies of nerve cells and their connecting dendrites, is where the brain's heavy lifting is done. The female brain is more densely packed with neurons and dendrites, providing concentrated processing power -- and more thought-linking capability.

The larger male cranium is filled with more white matter and cerebrospinal fluid. "That fluid is probably helpful," says Gur, director of the Brain Behavior Laboratory at the University of Pennsylvania. "It cushions the brain, and men are more likely to get their heads banged about."

White matter, made of the long arms of neurons encased in a protective film of fat, helps distribute processing throughout the brain. It gives males superiority at spatial reasoning. White matter also carries fibers that inhibit "information spread" in the cortex. That allows a single-mindedness that spatial problems require, especially difficult ones. The harder a spatial task, Gur finds, the more circumscribed the right-sided brain activation in males, but not in females. The white matter advantage of males, he believes, suppresses activation of areas that could interfere with work.

The white matter in women's brains is concentrated in the corpus callosum, which links the brain's hemispheres, and enables the right side of the brain to pitch in on language tasks. The more difficult the verbal task, the more global the neural participation required -- a response that's stronger in females.


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