About one in 4,500 babies show ambiguous genitalia at birth, such as a clitoris that looks like a penis, or vice versa. For the Insights story, "Going Beyond X and Y," appearing in the June 2007 issue of Scientific American, Sally Lehrman talked with noted geneticist Eric Vilain of the University of California, Los Angeles, about the biology of sex determination, gender identity and the psychology and politics behind both. Here is an expanded interview.
When did you first discover your interest in intersex individuals and the biology of sex development?
I started in Paris as a medical student, and my first assignment was to a unit of pediatric endocrinology in a Paris hospital, and it was the center of reference for all of France for babies born with ambiguous genitals. And I was actually literally shocked by the way decisions were made on these patients. I felt it didn't rely on solid scientific evidence. I mean, I'm a scientist, I'm a big believer of you can't just do things without being supported by evidence. In this case it was more like people would say it was just common sense—if the clitoris sticks out this much, you have to fix it. Or if the penis is really too small, it has to be bigger. Otherwise what life is this child going to have? And you know, I was never convinced by common sense. I kept asking, "How do you know?" There was no good answer to that.
There were a lot of patients and it was always the same discussions. And it was mainly about clitoral reduction.
So there were sexual politics there, too?
Yes. I was reading at the time this book by Michel Foucault. He has book that's called Herculine Barbin. He basically tells the story of this girl who clearly has a large clitoris. She goes and gets sexually aroused as she sleeps in the bed of other girls, as it was normal for girls to do. She goes to this religious institution for girls until eventually someone finds out, and then it's a big scandal. She becomes a pariah, and she ends up committing suicide. I was reading that, I was pretty young, I was like 18.
Defining normality has always been an obsession of mine. How do you define what's abnormal versus normal? I guess it's the philosophical roots of the French educational system.
But why choose to study intersex questions for the rest of your career?
My scientific inclination was excited by this because not only was it understanding a rare condition that makes people different, all of these social aspects, but also it has scientific implications in the basic biology of developing male or female. Always in biology, you want to look at the exception to understand the general. So understanding intersex individuals makes us understand how typical males and typical females do develop.
So what has your research overall been able to say about sex development?
We've identified new molecular mechanisms of sex determination. In particular we've discovered genes, such as WNT4, that's female-specific and not present in males, and that's sort of shifted the paradigm of making a male as just activation of a bunch of male genes. In fact it's probably more complicated. What we've shown is that making a male, yes, is activating some male genes, but it's also inhibiting some antimale genes. It's a much more complex network, a delicate dance between pro-male and antimale molecules. And these antimale molecules may be pro-female, though that's harder to prove.
It sounds as if you are describing a shift from the prevailing view that female development is a default molecular pathway to active pro-male and antimale pathways. Are there also pro-female and antifemale pathways?
Modern sex determination started at the end of the 1940s—1947—when the French physiologist Alfred Jost said it's the testis that is determining sex. Having a testis determines maleness, not having a testis determines femaleness. The ovary is not sex-determining. It will not influence the development of the external genitalia. Now in 1959 when the karyotype of Klinefelter [a male who is XXY] and Turner [a female who has one X] syndromes was discovered, it became clear that in humans it was the presence or the absence of the Y chromosome that's sex determining. Because all Klinefelters that have a Y are male, whereas Turners, who have no Y, are females. So it's not a dosage or the number of X's, it's really the presence or absence of the Y.