Few questions in science are as fraught as those around gender. At worst, the politics deters researchers and funders, and leaves people needed to take part in studies feeling wary. As a result, most of the answers science has provided are on the less contentious basics: how girls are born girls, and boys are born boys. Why a person feels male when they are biologically female, or the other way around, for now remains uncertain.

“This is the key question at the moment,” says Qazi Rahman, a lead investigator into LGBT mental health at King’s College London. “We know much more about how nature shapes sexual orientation, and my view of the science is that nurture does very little, if any, shaping of sexual orientation. We know next to nothing about how people come to feel transgender.”

Embryos start to become male or female at about six to eight weeks. At that time, those with an active gene called SRY, most often found on the Y chromosome, starts to produce the male sex hormone, testosterone. Without the flood of the hormone, embryos remain female. With testosterone, masculinisation begins. It is the fork in the road that shapes a person’s anatomy and physiology, and potentially their behaviour.

By the time they reach puberty, 75% of children who have questioned their gender will identify with the one they were assigned in the womb. But for others, what gives rise to an unshakeable feeling of being assigned the wrong gender? Genes and the substances the foetus is exposed to in the womb probably play a part, but how large a part is unclear.

Brain scans of trans people suggest there are biological underpinnings, but even though research has been going on since the 1990s, the data is still sparse. Taken together, studies show the brains of trans people are not wholly male or female, but have regions and systems that are selectively masculinised or feminised. Whether these differences are short-lived or permanent, or change after treatment with hormones, for instance, all add to the pile of unanswered questions.

Transgender rights protesters in Cardiff last year. Photograph: Gareth Phillips for the Guardian

There is evidence that social conditioning may have some role to play in gender identity, too. When a person is born intersex and has treatment at an early stage to make them female, they tend to grow up feeling female, and vice versa. “A lot of conditioning might occur very early on, and it could be that it’s already started in late foetal life,” says Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute in London.

The delicate nature of sexual politics makes research difficult, but it is not the only hurdle scientists face. The proliferation of words used to describe gender identity adds a further complication: scientists need to know if such terms are stable psychological constructs, Rahman says. “That doesn’t mean they are not real or important to people, but researchers need to interrogate these constructs more thoroughly to see if they represent a real ground shift, and are connected in some real sense to non-heterosexual or transgender identities.”



The situation could yet become more complex. A person’s sexual identity can be thought of as a product of four related factors: their biological sex; their sexual orientation; the gender they feel; and the gender that dominates the way they behave. “There are going to be people on any part of any of those four different spectra,” says Lovell-Badge. “So it’s difficult to have terminology which is going to really fit with everyone.”



Rahman says the key lies in the crossover between physiological and psychological factors. “In some deeper sense, showing brain differences, or finding genetic differences, would not at all be surprising. The big question is how these biological influences shape the felt sense of gender identity,” he says.

“How do prenatal sex hormones shape the developing brain circuitry which controls your sense of gender identity? Where is that network? How does it work to make this happen and how does it map out over time, from early childhood to middle childhood through to adolescence and young adulthood? And how does that become different in some people to the sex they were assigned at birth?

“The answer is, we don’t know.”

