Female genetic superiority: when it comes to survival, two X chromosomes beat an X and a Y

Men, on average, tend to be the stronger sex, when it comes to lifting and carrying, thanks to their bigger muscles. But according to physician and geneticist Dr. Sharon Moalem when it comes to health and long term survival, women are the stronger sex. 

Men are more vulnerable to diseases like COVID-19, which seems to be killing more men than women. And this isn't just a COVID thing. Women are also better at surviving cancer. They're less likely to suffer from developmental disabilities. And they live longer. 

It all comes down to the chromosomes. Most women have two robust, redundant X chromosomes. Most men have a single X and a relatively genetically impoverished Y chromosome.  And this makes a world of difference. 

Dr. Sharon Moalem said this female biological advantage really crystallized for him a few years ago in a very personal and painful way.  It's one of the stories he tells in his new book, The Better Half: An Argument For The Genetic Superiority of Women.

Dr. Moalem joined Quirks & Quarks host Bob McDonald to talk about his new book.

This interview has been edited and condensed.

Tell me about that moment a few years ago when you realized why females seemed to have the biological upper hand.

I was spending one of these quiet lovely afternoons with my better half. We were  traveling on a pretty empty street and out of the blue someone ran a red light and hit us broadside. Our car flipped, we rolled twice, it was a pretty horrific accident, we were really lucky to be alive. 

I started to think how lucky she is and how grateful I was that she has the use of two X sex chromosomes, while I only have the use of one. That's because females having that extra X gives them a survival advantage throughout the entire life course. 

Women are actually a mosaic. They're made up of two populations of cells everywhere you look in their body. And each population of cells is using one X over the other predominantly and cooperating and then sharing that genetic knowledge between them.

And so for example for my wife, while her skin was healing, if one X had genes that were much better for her skin to heal in a much more rapid way,  that population of cells would take over and give her the ability to heal much faster than I would.

And if, say, the other population of cells in her immune system that are using the X from her mother as opposed to her father are much better at fighting infections that would also explain why my wife did so much better when it came to overcoming the infections that we both had while overcoming that horrific car accident.

Just to make it clear here is some basic biology. Women inherit an X chromosome from each parent so they have XX and men get an X from their mother and a Y from their father. So they are XY. 

Correct. Females really are just endowed with a backup. And so this helps explain the reason that females' cells are constantly cooperating everywhere in the body, sharing this genetic knowledge. They have  two populations of cells using two different Xs. This is the origin of the survival advantage that I'm arguing that allows females to overcome every biological challenge throughout the course of their lives compared to men.

How does this play out in Covid 19 mortality rates between the sexes?

When we look at the gene which COVID-19 uses, it has a spike protein which is like a key that unlocks an ACE2 protein that's sitting on the cell surface, and that's the way the virus gets in. 

And so that ACE2 lock that protects us from COVID, males only have one, because it's on the X chromosome.  So if COVID-19 has the perfect key, it will unlock all male cells.

Females have two ACE2 genes because it's coded on the X chromosome, so 50% of their cells will have one version of the lock, and 50% will be using another. So again this makes it much more difficult for this virus to have that perfect key to unlock all female cells equally.

Does this female genetic superiority come with a downside?

It does. When you look at conditions when the body decides to attack itself, women are over-represented. The cost is because to survive you really need a robust and aggressive immune system to help you overcome any type of infectious process. So at times in women that aggressive immune system is turned on itself.

How crucial is it for women's health as scientists really tease apart these differences between the sexes?

Well I go into great detail in the book about this because I made exactly the same naive mistake as many of my colleagues because I was taught and under the assumption that  men and women are more similar that they are different.  

And if you want to see how this works in the clinic, your listeners should ask their physician the next time they receive a prescription, 'Does this drug work differently in men and women and is the amount that you're prescribing for me  be tailored by sex?'

Most physicians cannot answer that question because we don't have that knowledge when the drugs were approved. 

The one example that I give in the book that's pretty striking is the sleep aid Ambien. When the drug was approved they actually tested in men and women and the dose agreed upon was ten milligrams. Many women taking that amount were waking up the next day still groggy still feeling the effects of the medication.

Enough physicians got reports from patients and they reported this to the FDA that the FDA went back and reviewed and said we're actually overdosing women. Women actually break down this drug a little bit slower. They're much more sensitive to it. And so the dose now has been changed to five milligrams. 

Again the more we understand that the basic biology between the sexes is different, this shouldn't actually be surprising. 

Do you have any concerns that this idea of women being superior in this way could be used to justify more bias in medical research on the grounds that men need more help?

If we think about the example of melanoma, the most deadly type of skin cancer, most people are not aware that men, especially young men, are at twice the risk of dying of melanoma skin cancer than women. 

So for many years the explanation fell back on behaviour. We said well you know men aren't good at putting on sunscreen, they're not good at adhering to staying out of the sun, and they're not good at going to their doctor to get their skin examined.

Yes behaviour does play a role in health outcomes but even when we control for all those things and you still see a striking biological difference between the sexes. 

So beginning to look at these differences and studying both men and women separately we will end up with knowledge that I believe will help us to be able to help both sexes more effectively.