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Despite these constraints, Swaab and his colleagues were able to detect some intriguing patterns. They compared the brains of two dozen "ordinary" men and women. For the most part, the brains appeared to be the same until the researchers examined a section of the hypothalamus called the BSTc. Although no one knows for sure what this tiny patch of neurons does in humans, earlier studies have indicated that, in rats at least, it plays a key role in regulating male sexual behavior. Half the men in the control group were heterosexual and half were homosexual. Yet, regardless of their sexual orientation, they all had a BSTc that was 50% larger than that in the women.
When the researchers examined the BSTc of the transsexuals, they found a marked difference. The transsexuals' BSTc was more like the women's than the men's. In fact, the transsexuals' BSTc was, on average, slightly smaller than the women's. The researchers seemed to have found at least one biological motive for the transsexuals' desire to change sex, although it may not be the only one. Says Swaab: "Our results indicate that other structures in the brain could be involved."
How could the brain and the body become so mismatched? Several explanations are possible. One is rooted in the process by which embyros take on sex differences. All human embryos develop in the very earliest stages of gestation along more or less feminine lines. Those destined to become males differentiate from the master template after a complex series of hormonal secretions starts to masculinize the embryo. Miscues in this process could result in crossed signals in the portions of the brain that are responsible for gender identity. That would help explain why there are more male-to-female transsexuals than female-to-male.
Not everyone is convinced, however. All the transsexuals in the Dutch study took the feminizing hormone estrogen. The smaller BSTc may therefore have been the result rather than the cause of their quest to become women. Swaab concedes this possibility but notes that two women in the study's control group were postmenopausal and presumably no longer manufactured much estrogen. Their BSTc was still the same size as the younger women's, which may mean that estrogen has no effect on the structure's size.
There are simpler explanations--stress, for example. "Think about it," says Roger Gorski, a neurobiologist at UCLA who has studied rats' sexual behavior for 30 years. "These people undergo a lot of emotional trauma. To cut everything off to become a woman has got to be awfully stressful, and that has got to affect brain structures."
But for most transsexuals, there is no question that something deeper is going on. From the time she was a boy of six, Bea Jansen, 46, who lives outside Amsterdam, knew her body did not reflect her true gender. "I felt there was something that didn't fit," she says. "And that something was a penis." Jansen, who plans to donate her brain to Swaab's study when she dies, underwent a sex-change operation five years ago. She speaks for many transsexuals when she describes her transformation as a liberation: "I felt as if I could finally take off a mask that I had been wearing for a long time." With Jansen's help, scientists may someday understand how that mask got there in the first place.
--Reported by James Geary/Amsterdam and Alice Park/New York