A little over a decade ago, a fantastic creature was introduced to the world: Sam, an animal that was a rooster on their left half and a hen on their right half. The researchers who examined them, from the University of Edinburgh, named the animal Sam for both Samantha and Samuel. Geneticist Irene Miguel Aliaga usually shows a photograph of the chimera in her lectures. Sam showed that cells, at least bird cells, had an inherent sexual identity: a cell is male or female.
Miguel Aliaga’s groundbreaking research has revealed previously unknown differences between the sexes, with implications for diet, fertility and susceptibility to cancer. The geneticist at Imperial College London has elucidated these enigmatic mechanisms with bold experiments on flies. Her research on intestines led her to note that the intestines house “a second brain”, which differs between men and women. As a result of her research. on July 15, Miguel Aliaga and co-geneticist Carola García de Vinuesa will be the first Spanish researchers to join the Royal Society of the United Kingdom, an exclusive society founded in 1660 whose members have included Isaac Newton, Charles Darwin, Albert Einstein and Rita Levi – Montalcini.
Question. What does that half rooster, half the chicken, tell us?
Response. These experiments were quite revealing. When we think about differences between the sexes, we always think of the ovaries and testicles: I have estrogen, you have testosterone, and that’s why we are different. What these experiments showed is that the size of the male half was completely different from the size of the female half. If it was all due to hormones 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 examine: the sex of the organs, the sex of the cells. There is an inherent component of sexual identity in cells.
F. In all biology books, the only organs distinguished by sex are the penis and testicles of men and vulva and ovaries in womenbut you show that all organs differ by sex.
A. Yes. We work with the intestines, but it is also seen in the pancreas and liver. There are many sexual differences, and they can also change during adulthood. The plasticity of adult organs is not well studied.
F. In your lectures, you usually show the image of a python eating a crocodile, an exaggerated case that illustrates the organs’ ability to change shape and volume.
A. It is an extreme case of how much adult organs can change. You are born with a gut feeling and you think, “This is my gut feeling for life.” But what the python illustrates is that the gut can grow a lot and then shrink in adulthood. And you think, “Well, this is a python that just ate a huge crocodile.” But in reality, this happens to all the animals we research. We saw it at first on flies, but mice’s intestines also grow a lot during pregnancy and breastfeeding. Now we’re starting to investigate people, and that seems to be happening to us as well. The organs change within us. They grow and shrink, and that matters.
F. Can you give an example?
A. In flies and mice, the length of the intestine grows up to 20%. The ability to reproduce goes down if you disrupt that process and do not allow the mother’s gut to grow during pregnancy and breastfeeding, or, in the case of flies, when they lay eggs. It is important that the gut grows so that these species can multiply. In humans, we look at it now, and it seems to grow a bit during pregnancy and breastfeeding as well. We do not yet know if that is important.
F. You regret the confusion between the sexes and the sexes. What is one and what is the other?
A. Gender is a biological variable: you can be male, female or intersex. Gender is a social construction: as a society, we assign values to men and women. Now there are several categories, to be a social construction it is not a fixed thing. I am a woman and a woman, but gender and gender do not always match. Potentially, both biological factors and this social construct may have an impact on physiology and pathophysiology, for example if one develops a particular cancer. The social construct can be associated with a gender tending to eat a certain diet, and it can affect the cancer that you eventually develop.
F. You are also researching gender differences in the human brain.
A. Yes, it’s a complicated subject. With a fly or a mouse, there is no gender. There are only six. Many people have a hard time seeing the difference between the sexes, including many researchers. In my flies or in my mice, sex does not matter. I can say that there is always a difference between the male fly and the female fly. And that difference is by gender, of course. In humans, there are many differences between men and women, between men and women, but it is more difficult to find out whether they are due to gender (biological) or gender (social) differences. Therein lies the complication, but people are quite dogmatic. Normally you have people who think everything is sex and people who think everything is sex. And the reality is that it is difficult to separate them.
F. Where do you stand?
A. What I can say is that there are differences due to the sex of all the animals I have looked at. In them all. So I can not believe that people do not have any gender differences. In any tissue, in all the organs I have looked at, there are obvious gender differences. Sometimes these differences are seen as an attack on gender equality, but the fact that there are differences does not mean that one gender is better and the other worse.
F. If I showed you a woman’s brain and a man’s brain, would you know which one is which?
A. If you look at the genes that are activated, wherever you look, you will see differences between the sexes. Where do these differences come from and what do they mean? I do not know. The brain is obviously the most controversial case.
F. Whether it’s a brain or a liver, you take any cell and you know if it’s a man or a woman.
A. Obviously, yes.
F. It’s not controversial.
A. No, it is not possible to question. It is fact. If I look at which genes are turned on or I look at the chromosomes, I can see if the cell is male or female.
F. How is the biological sex of a human cell recorded, apart from 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 where the cell is located: hormones, nutrients …
F. And a male or female cell is neither better nor worse.
A. Exactly. In a lecture, I showed that the female fly’s intestinal stem cells multiply more, and I explained that this is important for the mother fly when it reproduces, because it needs the intestine to grow. As the gut grows, it helps fertility, fly fertility. And a boy in the audience got angry and said to me, “But how can you say that the gut of the females is better?” And I replied, “No, I’m not saying what’s better, I’m just saying that their stem cells multiply more.” The fly is a good example of how something can be good in one context, but bad in another. For example, intestinal stem cells that multiply more in the female fly are a good thing during reproduction, but if you genetically develop tumors, the female fly develops larger tumors, because those cells multiply much more. There is never better and worse. It’s always a yin and yang thing, in a way.
F. Your intestinal research has shown that the organs of men and women are more different than we thought.
A. Yes, we did not expect to find so many differences. We see that they are very different and that how they communicate with other bodies is also very different. For example, the communication between the gut and the brain can be quite different between men and women. That’s a great thing.
F. What are the consequences of these differences?
R. They have made us aware that we must take sex into account in all research. 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. It depends on a combination of many factors: diet, environment, genetic variants. But our research says that one must also take into account the cells’ inherent gender. It was commonly assumed that gender differences in cancer were due to male or female hormones. We have seen that there is also an inherent component in the cell, of the sex of the cell, at least in the fly.
F. Your research with fruit flies has won six Nobel Prizes.
A. Yes, flies are very powerful when it comes to discovering new processes, as they allow you to experiment without necessarily having an a priori hypothesis. If you want to see which genes control a process, you can delete different genes in different flies. To see differences between the sexes, you can take stem cells from the intestines of an adult female fly and turn them into males. And you can do it very quickly. On the go, all of these tests can be done in a couple of months, while in mice it takes a year or two.
F. 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 can sense nutrients and influence physiology and behavior, at least in model organisms like the mouse. We also see that even the non-neuronal digestive cells in the gut can detect nutrients such as zinc. So the “gut feelings” are justified.
F. How should society understand these differences between the sexes?
A. In ecology, the diversity of an ecosystem is important for it to survive all external challenges. I see society in the same way. The diverse society – at the level of gender, gender, ethnicity or whatever – is the one that can best survive challenges. We are stronger that way. I can not see gender and gender differences, or different needs, as a problem. I always see it as a good thing. There is nothing wrong with acknowledging these differences.
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