Dr Sharon Moalem on women having an extra X chromosome: “It’s like having two toolboxes. One toolbox may have a broken hammer, so you use the hammer from the second box." Credit:Getty Images

Men have more physical strength, but are women actually genetically hardwired to be tougher, thanks to their XX chromosomes? You bet, says a new theory … Not to mention those loafing Y genes preoccupied with sperm and ear hair.

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Normal text size Larger text size Very large text size Far from being the weaker sex, a new book, The Better Half, argues women live longer, have stronger immune systems, fewer developmental disabilities and higher cancer survival rates than men. Why? Its (male) author, Canadian physician and scientist Dr Sharon Moalem, says the extra X in every female cell, far from being redundant, is instrumental in ensuring that women have a distinct genetic advantage. As Moalem puts it, at every stage of life, “Genetic females triumph over males.” Evolution, it seems, has singled out one sex to be more resilient than the other. When did it first strike you that women are, as you put it, genetically superior to men? Ha! Well, I started my career working in Alzheimer’s disease, and always wondered why, at the far end of life, there are so few men. Eighty per cent of centenarians and 95 per cent of super-centenarians (110 or older) are women. Colleagues said, “Well, it’s behaviour. Men drink more alcohol, jump off more buildings, and die from violence and war.” And I thought, “Okay.” But years later, I was training in a neonatal intensive-care unit, and there again, boys had more infections, more assisted ventilation, and unfortunately more deaths. And people couldn’t tell me why. But it certainly wasn’t behavioural. That sparked a 10-year journey to answer a fundamental question: why do women have a survival advantage, at every data point in life, over men? And so I’m proposing a new biological law. In a species, the sex that gets the same two sex chromosomes has an immense advantage. Why? Humans have 23 chromosome pairs. One of those pairs consists of our two sex chromosomes. Females have two X chromosomes (XX), males have one X, one Y (XY). The X chromosome has about 1000 genes; the Y has maybe 70. The X is one of the biggest chromosomes; the Y is very short and stubby. The X contains extremely significant genes: genes that make and maintain the brain, and control immune function. Most Y genes are involved with making sperm, and ear hair! The X is just a very unique, important chromosome. But men do have an X.


But only one. All my cells are using an identical X – the one I got from my mother. So if that X has any problems – genetic mutations, spelling mistakes in the genetic code – tough luck for me. But a woman has two Xs: one from her mother, one from her father. So if one X has a problem, the healthy X can compensate. Take Hunter syndrome, for example. That’s a disease where a faulty X chromosome can’t produce a necessary enzyme. So if a male has Hunter syndrome, his body must use his one faulty X in every cell. But a female can utilise her alternative, healthy X cells to produce enough enzymes to support her faulty X sister cells. And so although they’re the carriers, women are almost never affected by Hunter syndrome. Their XX protects them. And there’s another advantage. Because the healthy X cells keep the faulty X cells alive, they’re still available to the body. It’s like having two toolboxes. One toolbox may have a broken hammer, so you use the hammer from the second box. But the broken-hammer box might also have a really awesome screwdriver. So by keeping both toolboxes alive – this metaphor is breaking down! – you can still use that screwdriver for another problem down the track. How does a woman end up with two toolboxes? Well, right at the start of female development, at the multicellular stage, it seems there’s a random turning-off of one X in each cell. That creates two populations of cells, each one using an alternate X. And then when, say, the baby’s heart is being built, if her father’s X can build a better heart, his X cells will outperform her mother’s, and she’ll end up with 80 per cent of her heart cells using her father’s X, and only 20 per cent using her mother’s. Whereas in her skin, it might be reversed. It’s like you’re building a house, and for every room, there are two blueprints you can build by, and the foreman decides which is better. And every organ and every system in a female body has that massive advantage over mine. That’s why boys around the world consistently outnumber girls in congenital malformations: problems in the way things are built. From relatively benign things like tongue-tie, to much more severe things like club foot, webbed toes and organ malformations.


So, what happens to the X not chosen in each female cell? It gets turned off in that cell. But the really big surprise is that almost a quarter of its information is still turned on! There’s a group of genes called EXITS – Escape from X-Inactivation Tumour Suppressor Genes – on the turned-off X that are actually working. That’s extra genetic horsepower in every cell that women have and men don’t. And that’s probably an important piece of the puzzle as to why men have a 20 per cent higher risk of cancer, and a 40 per cent greater chance of dying from cancer than women. "Testosterone makes men them stronger; but testosterone also suppresses the immune system, whereas oestrogen usually enhances it. So men fight better, but die of infections more easily!" Credit:Getty Images But there are conditions which affect more women than men. Autoimmune disease, for instance. Absolutely! And the one big push-back I’ve had from doctors is: “But when it comes to auto-immunity, all we see is women!” But in fact, autoimmunity is the expected outcome. Say you’re an immune cell using your father’s X, and you meet a kidney cell using your mother’s X. If I’m the immune cell, I interrogate you: “Hmmm, you don’t look exactly like me. I’m a little bit concerned about you …I’m not going to kill you right now, but I’m keeping my eye on you.” But if the body’s fighting an infection, I may well just kill you as a potential invader. And that’s how you get autoimmune disease: the body turning on itself. Something like lupus, which attacks the kidneys, is about nine to one, women to men. Women significantly outnumber men in virtually every autoimmune disease. And yet you also say that women’s immune systems are often better than men’s.


Loading Right! A perfect example may be COVID-19. Of course we can’t be sure yet, but according to the World Health Organisation [WHO], early figures show that more men than women are dying of corona. And if we look at another corona-virus, MERS – Middle Eastern Respiratory Syndrome – it certainly kills more men. Now if you ask the WHO why that is, I’m not kidding, they still say it’s because men don’t wash their hands, and smoke more. But what we’re seeing is that tobacco consumption doesn’t actually correlate to COVID-19 deaths. I think the real reason is that all male immune cells are identical, whereas females have a choice of two. Maybe the immune cells using your mother’s X are better at fighting corona than the ones using your father’s X. And so over time, they will divide more swiftly and dominate your body’s response to that infection. It seems odd that the Y chromosome is so … useless! Evolutionarily speaking, why isn’t it better? Well, the ultimate point of all this is that the sex with the same sex chromosomes has a significant survival advantage. Now, from an evolutionary perspective, which sex needs to survive? I would say it’s the sex that does the most care-giving of young. So, in mammals, the female provides the milk; she must survive; she gets the two XXs. But in birds, the male bird often does a lot of the calorie provision for young; and so you find male birds get the equivalent of the double X. So it’s not a sexist argument: it’s an evolutionary adaptation to best ensure the survival of the species. Loading Given all this evidence of women’s superior function and survival, why do you think men have dominated human societies for so long?


When I say females are the stronger sex, the genetically superior sex, people say, “But hang on, males have more physical strength by every measure.” That’s true, but it doesn’t help them in the game of survival. It’s testosterone making them stronger; but testosterone also suppresses the immune system, whereas oestrogen usually enhances it. So men fight better, but die of infections more easily! But the better fighter gets to organise society. Yes, but only until machines come along that replace physical strength. Then it’s the people controlling the machines who have the power. Historically, men. Yes. But not necessarily. And that’s the root of the seismic cultural shifts we’re seeing in societies all over the world right now. It seems a slow shift! True, but you’ve got time. You’ll be a super-centenarian, and I’ll be waving to you as you go past!

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