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1 April 2020updated 27 Jul 2021 11:34am

The female of the species is more healthy than the male

Physician Sharon Moalem on the role our sex chromosomes play in immunity and genetic advantage.

By Emily Bootle

When Sharon Moalem has a doctor’s appointment, he often finds the room is set up for a cervical smear test, and is forced to tell the same story all over again: he is a cisgender man but his parents always wanted a girl, so they called him Sharon.

Moalem’s experiences may have lent him a certain intuitive understanding of the nuances of sex and gender. In his new book, The Better Half: On the Genetic Superiority of Women, he provides evidence that people with two XX chromosomes have an inherent survival advantage over people with an X and a Y.

Born in Canada in 1977, Moalem began his career in Alzheimer’s research. He found it difficult to find healthy older men for his studies. His colleagues told him this was because of behavioural factors: men drink and smoke more; they are more likely to die young by suicide. During his medical training he was taught that women were the more fragile sex, and that over the course of his career he should expect to see more women. 

But when he and his wife had a serious car accident in 2016, she recovered quicker than he did, despite having worse injuries – prompting Moalem to write The Better Half.

Certain biological assumptions have perpetuated the idea of female weakness in medicine. “It wasn’t a patriarchal conspiracy,” Moalem told me when we met in London. “Medicine was developed using males because they were thought to be more disposable. You wouldn’t hurt the reproductive organs – sperm regenerates – so you could risk giving them a drug.”

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By this logic, drugs are tested more on men for fear women cannot cope. The Better Half argues that genetic females are better at fighting viruses and surviving epidemics and famines, however. One of 23 pairs of chromosomes – which comprise the genetic code contained in every human cell – determines the sex of an embryo: XY makes a male and XX a female. Since the Y chromosome can only be created by the father, it follows that a male’s X is always from the mother. This means that in a chromosomal male, all the cells are identical: the Y is always the father’s and the X is the mother’s.

When there are two X chromosomes, however, things become more complex. The X chromosome is large, containing around 1,000 genes; an embryo with two of these cannot survive with so much genetic information – so one is “switched off” during foetal development. “So the dogma has been that a woman is like a man: she only has the use of one X,” Moalem explained. 

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In fact, the X that is supposedly “silenced” retains 25 per cent of its genes: “Every one of your cells has more genetic horsepower. What makes the X chromosome unique is that it maintains the brain and the immune system.” The Y chromosome carries only 70 genes, the majority of which are for sperm production. So in every cell, a chromosomal female has around 250 more “active genes” than a male.

One way this genetic difference manifests is colour-blindness. If one X chromosome has mutated to limit colour vision, someone with XY has no other gene to fall back on. This explains why 5-10 per cent of European males are colour-blind next to 0.1 per cent of females.

Moalem takes this theory a step further: “With colour vision, almost the same percentage of male defect is female superiority.” Research shows about 12 per cent of chromosomal females have tetrochromatic vision: they can see 100 times as many colours as someone with normal colour vision (though they might not realise it). 

The advantage of a second X also applies to cancer, trauma injury and autism. That chromosomal females have another X means that each cell in the body can use the chromosome with the better gene for any given ailment. Generally, 50 per cent of the female cell population is dominated by the mother’s X. But if the body is damaged, it automatically replicates the genetically advantageous 
cells for repair.

The mixed population of cells can also have a negative impact: autoimmune diseases are more common in women. This is partly because the immune system is more “trigger-happy”, as Moalem put it. “If I’m the coronavirus, I may put a protein on my surface that signals, ‘let me in, don’t attack me’. Female immune cells are more demanding of further information,” he explained. Women, therefore, may be better protected against these kinds of viruses. At the same time, the mixed population of cells means sometimes the immune cells recognise normal cells as foreign, causing the body to attack itself. 

These chromosomal differences could have knock-on effects for drug testing, such as the one Moalem is developing for cancer: an “immune checkpoint inhibitor”, which would work differently in chromosonal females due to their increased autoimmunity. There are also sociological implications: many people do not recognise the existence of a female prostate and women are misdiagnosed with stress incontinence because physicians deny the reality of female ejaculation. 

Recognising the complexity of two XX chromosomes could help increase understanding of women’s pain, including conditions such as vulvodynia and endometriosis. And it is crucial to recognise the difference between chromosomal sex, biological sex and gender: “We don’t change our sex chromosomes, we choose our gender,” Moalem said. “To understand a patient, I need to know everything about them.”

This article appears in the 24 Mar 2021 issue of the New Statesman, Spring special 2021