2012 : WHAT IS YOUR FAVORITE DEEP, ELEGANT, OR BEAUTIFUL EXPLANATION?

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Psychologist, Autism Research Centre, Cambridge University; Author, The Science of Evil

Sex At Your Fingertips

We all know males and females are different below the neck. There is growing evidence that there are differences above the neck too. Looking into the mind reveals that on average females develop empathy faster and that on average males develop stronger interests in systems, or how things work. These are not necessarily differences in ability, but more differences in cognitive style and patterns of interest. These differences shouldn't stand in the way of achieving equal opportunities in society, or equal representation in all disciplines and fields, but such political aspirations are a separate issue to the scientific observation of cognitive differences.

Looking into the brain also reveals differences: for example, whilst on average males have larger brain volume even correcting for height and weight, on average females reach their peak volume of grey and white matter at least a year earlier than males. There's also a difference in the number of neurons in the neocortex: on average, males have 23 million and females have 19 million, a 16% difference. Looking at regions within the brain also shows sex differences: for example, males on average have a larger amygdala (an emotion area) and females on average have a larger planum temporale (a language area). But all this talk about sex differences. Ultimately what we want to know is what gives rise to these differences, and here is where I at least enjoy some deep, elegant, and beautiful explanations.

My favourite is foetal testosterone, since a few more drops of this special molecule seems to have 'masculinizing' effects on the development of the brain and the mind. The credit for this simple idea must go to Charles Phoenix and colleagues in 1959 (University of Kansas), an idea picked up again by Norman Geschwind in 1985 (Harvard). This is not the only masculinizing mechanism (another is the X chromosome) but it is one that has been elegantly dissected.

How scientists get to see the causal properties of foetal testosterone can however be through unethical animal experiments. Take for example a part of the amygdala called the medial posterodorsal (MePD) nucleus that is larger in male rats than in females. If you castrate the poor male rat (thereby depriving him of the main source of his testosterone) the MePD shrinks to the female volume in just 4 weeks. Or you can do the reverse experiment, giving extra testosterone to a female rat, which makes her MePD grow to the same size as a typical male rat, again in just 4 weeks.

In humans we look for more ethical ways of studying how foetal testosterone does its work! You can measure this special hormone in the amniotic fluid that bathes the foetus in the womb. It gets into the amniotic fluid by being excreted by the foetus, and so is thought to reflect the levels of this hormone in the baby's body and brain. We measured the baby's testosterone in this way and then simply waited for the baby to be born, and then invited them into an MRI brain scanner 10 years later. This allows a test of how individual differences in testosterone levels before birth shape the development of the human brain. In a new paper in the Journal of Neuroscience our group shows for example how the more testosterone there is in the amniotic fluid, the less grey matter in the planum temporale (that language area of the brain).

This fits with a finding we published some 10 years ago: that the more testosterone in the amniotic fluid, the smaller the child's vocabulary size, at the age of 2 years old. This helps make sense of a longstanding puzzle about why girls talk earlier than boys, and why boys are disproportionately represented in clinics for language delays and disorders, since boys in the womb produce at least twice as much testosterone as girls.

It also helps make sense of the puzzle of individual differences in rate of language development in typical children irrespective of their sex: why at 2 years old some children have huge vocabularies (600 words) and other children haven't even started talking. Foetal testosterone is not the only factor involved in language development (so are social influences, since first born children develop language faster than later born children) but it seems to be a key part of the explanation. And foetal testosterone has been shown to be associated with a host of other sex-linked features, from eye contact to empathy, and from detailed attention to autistic traits.

Foetal testosterone is tricky to get your hands on, since the last thing a scientist wants to do is interfere with the delicate homeostasis of the uterine environment. In recent years a proxy for foetal testosterone has been proposed: the ratio between the second and fourth finger digit lengths (or 2D:4D ratio). Males have a lower ratio than females in the population, and this is held to be set during foetal life and remains stable throughout one's life. So scientists no longer have to think of imaginative ways to measure the testosterone levels directly in the womb. They can simply take a xerox of someone's hand, palm down, at any time in their life, to measure a proxy for levels of testosterone in the womb.

[Image credit: Linda Wooldridge and Mathew Clement, in "Resolving the role of prenatal sex steroids in the development of digit ratio", by John T. Manning, PNAS.]

I was skeptical of the 2D:4D measure for a long time, simply because it made little sense that how long your 2nd and 4th fingers were should have anything to do with your hormones prenatally. But just last year, in Proceedings of the National Academy of Sciences, Zheng and Cohn showed how even in mice paws, the density of receptors for testosterone and oestrogen varies in the 2nd and 4th digits, making another beautiful explanation for why your finger ratio length is directly affected by these hormones. That same hormone that masculinizes your brain is at work at your fingertips.