Science and Innovation

Interview by Virginia Sarabia for Barcelona Science and Universities and Núvol.

The origin of life is in the oocytes, the immature cells that will later develop into eggs. Poor oocyte quality causes most female fertility problems. However, despite the falling birth rate in the West, there has been little investment in oocyte research, unlike in areas such as male reproduction or erectile dysfunction. This is changing and Elvan Böke (Turkey, 1986), group leader at the Centre for Genomic Regulation, has recently received several large grants to fund her projects. Böke stresses the importance of “leaving a better world for the next generation”.

What got you interested in science as a child and made you decide you wanted to be a scientist? I read something about Spider-Man…

Yeah, totally: Spider-Man and the Ninja Turtles. I still joke with my friends because I had two favourite cartoons, and they’re both genetically modified organisms. I think I probably liked those things and got interested in them, in genetics as a concept. And then Dolly the sheep was cloned when I was 12 or 13, and it was on the news everywhere. So from very early on I said I wanted to be a geneticist, and that never changed. But my parents were really discouraging. They were like, “What are you going to be, a geneticist?”. There was no supportive environment, it was all like, “Are you crazy? Do you know what you’re going to do if you’re a geneticist?”.

But they also work in science.

My mother is a physicist and my father is an engineer, it’s true, but… I’m a geneticist. My mother was a physicist and wanted to practice, but then I was born. And she told me something like: “this is Turkey in the eighties.” It was difficult to have a career as a physicist and a family, so she decided to become a physics teacher. So basically, my parents were a teacher and an engineer. When I talked to them, they told me: “be a pharmacist, be a doctor.” Their favourite job was as a pharmacist [laughs]. But [with genetics] they said, “no, this is crazy.” They tried to discourage me until the last minute.

You were a Postdoctoral Fellow at Harvard’s Department of Systems Biology. What did you study there?

There I studied cytoplasmic organisation in oocytes, the cells that end up becoming eggs, and the structure called the Balbiani body. It’s a very enigmatic organelle. It has a lot of mitochondria and nobody knows exactly what it does, and it’s present only in dormant oocytes. I found that in all oocytes this structure was bound to a physiological amyloid protein. And that was important, because amyloids were associated with neurodegenerative diseases, such as Alzheimer’s or ALS. But this was a physiological amyloid, which means it wasn’t associated with the disease, it was just a normal part of cell function. It was like building this structure and, when the oocytes are activated to grow, the structure dissolves.

What prompted you to change direction in your career to choose oocytes?

When I was studying this structure called the Balbiani body, I realised how little we know about oocytes. The Balbiani body contains a lot of mitochondria, as I said, and I realised that very little was known about oocyte mitochondria. I was very surprised that there was so little knowledge and that motivated me to start working on it because, well, I’m a woman [laughs]. So little is known about most of the human female reproduction that we can’t solve the problems, because we don’t know how.

Why is there no research on oocytes, given that they are the beginning of life?

There are a couple of reasons. The biological reason is that they are difficult to study, because they don’t divide, so you have to get the oocytes from animals or from human donations. And it is difficult to have samples. The second reason is historical sexism. When I proposed to my professor at Harvard that I wanted to study reproduction in its entirety, he told me that there is so little funding for that I should choose something else. But in Europe and the United States, demographics are changing. Governments are now worried that the population decline will be too great. For example, Spain’s population has been declining for some time. It was increasing because of immigration, but there is a gap in the birth rate versus the death rate. And the government encourages immigration so that there is a younger workforce. But today, in some countries, birth rates are so low that even current levels of immigration are not enough to fill the gaps in the system. The answer to your question is that, historically, nobody cared about this. They just said: “women, you’d better have children in your twenties and if you can’t, you’re bad”. But today this has become a social problem and the age of the mother at first birth is steadily increasing in developing countries. So now everybody is interested in understanding it. Now there is funding. But this is very, very recent.

Your group showed that oocytes can remain in a dormant mode, that is, on ‘standby’ for decades without signs of ageing. How is this possible?

We believe there are several mechanisms, and we have recently published on one of them. There are many factors that lead to the accumulation of damage, and we showed last year that one of these factors is suppressed in oocytes. So, for example, mitochondria generate energy and are also an inherent part of the conversion of building blocks to each other in the cell. And we show that, as in normal oocytes, the mitochondrion doesn’t have one of the main damage-generating machineries. Basically, if you don’t generate growth, if you don’t generate one of the most damaging molecules in the cell, of course there will be less damage. But I don’t think there is a single mechanism that does this. I think there are more things that keep the oocytes dormant and as free from damage as possible.

Could this be applied in the future to something else, for example, other cells?

Absolutely, because after our paper was published, they discovered that some cancer cells might have the same thing. Of course, more people are going to start looking at their own cell types, and the cancer group has already found that some cancer cells do this to reduce damage. This is because cancer cells also want to divide and stay there as long as possible.

Could their research help prevent amyloid plaques?

The Balbiani body I mentioned earlier is a physiological amyloid formation. A small part of my lab is working on how to dismantle the Balbiani body, that is, how to dismantle this amyloid structure. The idea is that, if we can dismantle physiological amyloids, maybe we can emulate some aspects of the dismantling of pathological amyloids. We will see. There is always hope.

Let’s go back to infertility. Infertility rates are much higher in women than in men, and we don’t know why.

Yes, exactly. It’s much easier to study men, because if you want to get a sperm sample, you know, you ask a man, and then you have a lot. And if you want to study oocytes, there are very few. So it’s a longer process. Male fertility has been studied a lot more, has had a lot more research funding in the past.

And also, research into erectile dysfunction receives more funding than research into female reproduction…

It’s historical. Fifty years ago, we lived in societies that were unquestionably male-dominated. So, if you have a board of men funding projects, of course they’re going to be more interested in their own problems than in some hypothetical female problem they’ve heard about. It’s very human nature. I think that’s one of the reasons why representation is important, for example, in the decision-making units of boards. Maybe sometimes a group of men is not going to be aware of a problem and a woman is going to point it out. One of the most striking examples is endometriosis. About 10% of women, or a very significant portion, have it. And yet it takes forever to diagnose it. How is it possible that there is this disease that affects a large part of society, and we still do not have a good diagnosis for it? It’s because only women were suffering and nobody really highlighted that it was a major problem.

You have been in Spain for about seven years. If you could, what would you change about working conditions or access to positions for researchers in Spain, especially for young people?

I would start doing things as if we had a better chance of doing them in the long term. This is not about Spain: it is about science funding at European level and science policies at European level. I think more posts and more long-term possibilities would improve things. A project is going to last three, four years, and all you want to do is invest all your energy in it and keep it going. Ten years are fine. What else would you change…? I would say I’m very happy here. Establishing collaborators has been really… well, nothing is easy, but I imagine it would be more difficult in other countries. Because Spain is very nice and Barcelona is very nice. There is an atmosphere of collaboration, you approach people, they are open. They don’t say: “I’m too busy, I can’t do it”. They really want to help, and that’s something I really appreciate. They really want to do a greater good.

But yes, what I would ask for is for people to be able to have long-term positions. And more funding, of course. I have been very lucky to get international grants. But Spanish funding… If you want to study something that requires a lot of use of animals or human donors, it costs a lot, because it costs a lot to keep animals. So any time you want to embark on a big project, it’s expensive. If you have international funding, like me, it is possible. But if I only had Spanish funding, it would have been difficult. And I am happy with the Spanish funding. But in comparison with Germany, Austria, the United States… National funding in those countries is superior.

In your experience, are there enough women mentors in science?

In my personal experience, yes, because often the reproductive biologists, many of them, are women. Surprise! So in my particular field it’s not difficult to find female mentors. But if you look in other fields, of course not. If you look at previous generations, women are very rare. But among junior group leaders, I see a good gender balance.

How does the fact that there are few female mentors and few female scientists influence these women scientists?

As I said before, issues of representation matter, sometimes for practical reasons. It’s not just a numbers game. It’s very important to have sympathetic and empathetic people at the top, but representation is important. Look: there is a drug that was given to pregnant women to prevent morning sickness [in the early 1960s: this was thalidomide]. It was approved in Europe, and it caused a lot of birth defects there. But in the United States, on the pharmaceutical committee that met to approve this drug, and apparently it was almost certain to be approved, there was only one woman. And this woman said: “pregnancy can have complications, I want to see evidence before approving it, I can’t rely on what the pharmaceutical company tells us”. So she blocked the approval of this drug in the US for a while. And during this time, birth defects in Europe became evident, so the drug never made it to the US. All this because she said, “I can’t just approve this”. So sometimes presence and just basic knowledge does matter, because this woman said, “I know about pregnancy” and did not approve the drug. She probably prevented thousands of birth defects. [She’s referring to Dr Frances Oldham Kelsey, who was awarded for this].

Is it easy to reconcile work and family for scientists who are also mothers in Spain? It is sometimes said that we are not a country that makes it easy to reconcile work and family life.

It depends. It is much better than in the United States. I am Turkish, I was educated in the UK and the US and my husband is American. And most of my best friends are German and Italian. So I know a lot of places. And one thing I always notice here is that people are very critical of what they have without really appreciating what they have. For example, in the US there is no maternity leave, so you have to take unpaid leave. And if you’re in a ‘sophisticated’ company, you may have paid leave in your contract, but that’s not always the case. For example, in Boston the average cost of childcare is $2,000 a month, and some are more expensive. In the UK, the figures are a bit better, but very similar. They have maternity leave, but childcare costs are much higher than in Spain. Spain is not Scandinavia, but it is much better than many other countries. Going back to your question, it is better than the US and the UK. And I really liked the equalisation of paternity and maternity leave. I took four months and so did my husband. It was a very good thing for our family.

Two of my post-docs are women, and they gave birth a year after me. So we went from a lab of zero babies to one of three. And I saw that their partners were also grateful to have equal leave. In some Scandinavian countries, you can transfer time [in Sweden, parents have 480 days leave to be split between them]. The father can say: “I’m not going to take a year, I’m going to take three months, and I’m going to transfer nine months to my wife”. And that doesn’t help equality, because women stay at home longer, losing more career opportunities. But if you say you have equal time, use it or lose it, but you can’t transfer it. Why not stay at home and spend time with the family? I don’t know the rest of Spain, but in Barcelona there is a system of schools from zero to two years, where you can take your children. Those schools are really good. So, in general, I found it much better than what I was used to. Again, I’m not comparing Spain with Denmark, but compared to the United States or the United Kingdom, I think Spain is much better.

What are your female references in science now or in the past?

When I was doing my PhD in the UK there was a professor, who is now in the US, called Julie Cooper. I really liked her because she was very scientific. I always liked very colourful things [shows her colourful skirt], and I was in the UK and nobody around me was really into colour. But every time I listened to Julie Cooper’s talks, she had a super colourful slide background. And she was dressed in a very colourful way, very fashionable. And that impressed me. I was like, ‘OK, so I can have a personal touch and be successful’. I always say her name because I think some people you meet in formative times, or in more vulnerable times, really affect how you think about things.

You also have to bear in mind that in science there is this stereotype of the ‘nerd’. I mean, you have to be very dedicated, but it seems like you also have to be a nerd to be successful. And I never was. I was and am dedicated, but I never became a nerd in my PhD. I would go out, and my supervisor would always talk about work at dinner; she was very nice and very motivated. She didn’t have a family at the time, she just talked about science. And I always thought, ‘is this really for me, I can’t find the motivation after a long day at work to talk about work at dinner’.

But I met a couple of key people at that time who had lives, who had hobbies. They made me think that I could be a scientist. And then, in my current field, there is another scientist who does good studies on women’s reproduction. She has four children! These are the great students, someone who can deal with four children and still be very successful. Furthermore, she is a charming person. That’s possible. How you do it is, of course, a different story.

What advice would you give to a young person who wants to go into scientific research?

That’s a difficult question. The classic answer is: you have to find something you are passionate about. Because science is hard, things don’t work 90% of the time and, for example, when I was doing my PhD there were times when I questioned why I was doing it because I wasn’t so passionate about some aspects of cell division. Then your experiments don’t work, you come to work, and you think: “I don’t care about this”. And that’s very bad. And I forced myself to go on, because I just thought: “this is what I’m going to do, this is my PhD”. And I found something that I was passionate about later on, at the end of my PhD. I find female reproduction and everything to do with it fascinating. Every morning I get out of bed with the idea that I’m going to go to work, and it’s going to be beautiful and interesting.

Science is fascinating. It has its challenges, but at the end of the day, I’m 37 years old, and sometimes this question comes up: ‘If you made a billion dollars, would you change jobs?’ I’m the only person who says no among all my friends. I answer that I would donate half the money to my lab. That’s the thing about being a scientist. I think, if you persevere and if things work out, you have a beautiful job that you enjoy doing.