Irene Miguel Aliaga, geneticist: "That there are differences between the sexes does not mean that one is better and the other is worse"

Just over a decade ago, an almost fantastical creature was introduced to the world:

an animal that was a rooster on his left half and a hen on his right half.

The scientists who investigated him, from the University of Edinburgh, baptized him

because he was Samantha and Samuel at the same time.

Geneticist Irene Miguel Aliaga, born in Barcelona 49 years ago, usually shows a photograph of this gallinaceous chimera in her talks.

showed that cells, at least bird cells, had an intrinsic sexual identity.

A cell is male or female.

Miguel Aliaga's groundbreaking research has revealed unknown differences between the sexes, with implications for diet, fertility and susceptibility to cancer.

The geneticist, from Imperial College London, has shed light on these enigmatic mechanisms with bold experiments on flies, especially the intestines, where she claims that there is "a second brain", different between males and females.

Miguel Aliaga's results are so powerful that, on July 15, she and fellow geneticist Carola García de Vinuesa will become the first Spanish scientists to join the Royal Society of the United Kingdom, an exclusive club founded in 1660 to which geniuses such as Isaac Newton, Charles Darwin, Albert Einstein and Rita Levi-Montalcini belonged.

'Sam', an animal that was a rooster on his left half and a hen on his right half. University of Edinburgh

Ask.

What does that animal that is half rooster and half chicken tell us?

Response.

Those experiments were quite revealing.

When we think of differences between the sexes, we always think of the ovaries and the testicles: I have estrogen, you have testosterone and that is why we are different.

What those experiments showed is that the size of the male half was totally different from that of the female half.

If everything depended on hormones, which are floating around everywhere, why would one part be smaller than the other?

Those experiments showed that there are more factors in sex than just hormones.

This is what we are investigating: the sex of the organs, the sex of the cells.

There is an intrinsic component of sexual identity in cells.

Q.

In any biology book, the only organs that appear differentiated by sex are the penis and testicles in males and the vulva and ovaries in females, but you show that all the organs are different by sex.

A.

Yes, we work with the intestine, but it is also seen in the pancreas, the liver… There are a lot of sexual differences and they can also change during adult life.

The plasticity of adult organs is not well researched.

Q.

In your talks, you often show the image of a python eating a crocodile, an exaggerated case that illustrates the ability of the organs to change shape and volume.

A.

It is an extreme case of the extent to which adult organs can change.

You are born with a gut and you think, "This is my gut for life."

But what the python illustrates is that the intestine can grow a lot and then shrink in adult life.

And you think, "Well, this is a python thing that just ate a huge crocodile."

But, in reality, this happens in all the animals that we are investigating.

Initially, we saw it in flies, but mice's guts also grow a lot during pregnancy and lactation.

And now we're starting to scan humans and it seems to happen too.

The organs change inside us, they grow and shrink, and that matters.

The organs change inside us, they grow and shrink, and that matters

Q.

Can you give an example?

A.

In flies and mice, the length of the intestine grows up to 20%.

And the ability to reproduce goes down if you interfere with that process and don't let the mother's intestine grow during pregnancy and lactation, or, in the case of flies, when they're laying eggs.

It is important that the intestine grows so that these species can reproduce.

In humans we're looking at it now and it seems to grow a bit during pregnancy and lactation as well.

We don't know yet if it's important.

Q.

You regret the confusion between sex and gender.

What is one and what is the other?

A.

Sex is a biological variable: you can be male, female or intersex.

Gender is a social construct: as a society we assign values ​​of men, women... Now there are several categories, because being a social construct it is not a fixed thing.

I am a woman and a female, but sex and gender do not always coincide.

Potentially, both biological factors and this social construct can have an impact on physiology and pathophysiology: if you develop a certain cancer, for example.

The social construct can be associated with a gender tending to eat more of a certain diet, and that can influence the cancer that you end up developing.

Q.

Sex differences in the human brain are also being investigated.

R.

Yes, it is a complicated issue.

If I catch a fly or a mouse, there is no gender, there is only sex.

Many people have a hard time seeing the difference between sex and gender, including many scientists.

In my flies or my mice, gender doesn't matter.

I can say that there is always a difference between the male fly and the female fly.

And that difference is of sex, clearly.

In humans there are many differences between males and females, between men and women, but it is more difficult to find out if they are due to sex (biological) or gender (social) differences.

Therein lies the complication, but people are quite dogmatic.

Normally, you have people who believe everything is sex and people who believe everything is gender.

And the reality is that it is difficult to separate them.

Many people have a hard time seeing the difference between sex and gender, even many scientists

Q.

Where are you located?

R.

What I can say is that, in any animal that I have looked at, there are differences due to sex.

In any.

So, I can't believe that in humans there are no sex differences.

In any tissue, in any organ that I have looked at, there are obvious sex differences.

Sometimes these differences are seen as an attack on equality, but the fact that there are differences does not mean that one sex is better and the other is worse.

Q.

If I put a woman's brain and a man's brain in it, would you know which is which?

R.

If you look at the genes that are activated, wherever you look, you will see differences between the sexes.

Where do those differences come from and what do they mean?

I do not know.

The brain is the most controversial case, obviously.

Q.

Whether it's a brain or a liver, you take any cell and you know if it's male or female.

R.

Obviously, yes.

Q.

That cannot be controversial.

R.

No, that cannot be questioned.

It is a fact.

If I look at which genes are turned on or I look at the chromosomes I can tell if the cell is male or female.

Q.

In what is the biological sex of a human cell noted, besides the XX or XY sex chromosomes?

A.

The sex chromosomes, for example, will dictate the type of genes that are turned on in the cell.

And the activation of genes will also depend on the environment in which the cell is found: hormones, nutrients...

Q.

And a male or female cell is neither better nor worse.

A.

Exactly.

In a talk I was showing that female fly gut stem cells proliferate more, and I explained that this is important for the mother fly when it reproduces, because it needs the gut to grow.

When the intestine grows, that helps fertility, the fecundity of the fly.

And a boy in the audience got angry and said to me: “But how can you say that the intestine of the females is better?”.

And I replied: "No, I'm not telling you which is better, I'm just telling you that their stem cells proliferate more."

The fly is a good example that a thing can be

in one context, but

in another context.

For example, gut stem cells that proliferate more in the female fly is a good thing during reproduction, but if you genetically induce tumors, the female fly develops larger tumors, because those cells proliferate much more.

There is never a better and a worse.

It's always a yin and yang thing, in a way.

Gut-brain communication can be quite different between males and females

Q.

Your investigations with intestines have revealed that the organs of males and females are more different than we thought.

A.

Yes, we did not expect to find so many differences.

We are seeing that they are very different and that how they communicate with other organs is also very different.

For example, communication between the gut and the brain can be quite different between males and females.

It is an amazing thing.

Q.

What are the implications of these differences?

R.

They have made us aware that we have to consider sex in all investigations.

We should not assume that the physiology and pathophysiology of animals, or of humans, will be the same.

For example, in humans, susceptibility to cancer is different in men and women.

Surely it is due to a combination of many factors: diet, environment, genetic variants.

But our research is saying that you also have to consider the intrinsic sex of the cells.

It used to be assumed that sex differences in cancer were due to male or female hormones.

We have seen that there is also an intrinsic component of the cell, of the sex of the cell, at least in the fly.

Q.

Research with fruit flies has won six Nobel Prizes.

A.

Yes, flies are very powerful in discovering new processes, because they allow you to carry out experiments without necessarily having an

If you want to see which genes control a process, you can remove different genes in different flies.

To see differences between the sexes, you can take stem cells from the intestine of an adult female fly and make them male.

And you can do it very quickly.

In the fly all these tests can be done in a couple of months, while in mice it takes a year or two.

Q.

What happens when stem cells from the intestine of a female are masculinized?

A.

Stem cells are what make the intestine grow normally and regenerate itself.

When we masculinize them into a female fly, we see that the mother fly's gut doesn't grow as large as it should.

With other experiments we have revealed that there is a link between the intestine and reproduction.

It was not known that the sex of the gut controls a fly's ability to reproduce.

We have seen it in females and we have also seen that the intestine has to be male in males for them to have male fertility.

In cancer susceptibility you have to consider the intrinsic sex of the cells

Q.

What do you think would happen if you masculinize a woman's intestine?

A.

I have no idea.

In humans we are beginning to investigate whether during pregnancy and lactation the intestine grows.

And it seems so.

P.

And in mice?

R.

In mice we are beginning to see that it does matter.

We haven't sexed the gut yet, but we do know that if we don't let the gut grow during pregnancy and lactation, there seems to be a tiny effect on a female's ability to have babies.

It's interesting, because women and female mice have an organ created specifically for reproduction: the placenta.

Our question was whether the intestine is so important in flies because they do not have a placenta and the intestine assumes its functions during reproduction.

Perhaps if we looked at mice or humans, the intestine would not grow or it would not matter, because they already have the placenta, which is what gives all the nutrients to the baby.

It seems that is not the case.

In mice, the intestine grows the same or almost more than in flies.

And it seems that it does matter.

Q.

Do we have a second brain in the gut?

A.

Yes, we have many neurons in the gut, and the gut is connected to the brain by neurons that appear to be able to sense nutrients and affect physiology and behavior, at least in model organisms like the mouse.

In addition, we are seeing that even the non-neuronal digestive cells of the intestine can detect nutrients, for example, zinc.

So the

thing is justified.

Q.

What does society have to do with these differences between the sexes?

A.

In ecology, the diversity of an ecosystem is important for it to survive any external challenge.

I see society the same way.

The diverse society —at the level of sex, gender, ethnicity or whatever— is the one that can best survive challenges.

We are stronger that way.

I don't see sex and gender differences, or different needs, as a problem.

I always see it as a good thing.

There is nothing wrong with admitting these differences.

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