Science and Innovation

Interview by Joan Burdeus for Barcelona Science and Universities and Núvol.

Nuria Montserrat Pulido (Barcelona, 1978) is one of the most renowned scientists in our country, the person of reference in regenerative medicine. A bioengineer specialising in pluripotent stem cells and the generation of complex multicellular systems to understand the development of diseases in humans, Montserrat will talk to us about a type of mini-organ known as organoids. In 2013, Science magazine recognised her work with kidney organoids as one of the ten scientific discoveries of the year. In the field of teaching, Montserrat is ICREA research professor and head of the “Pluripotency for organ regeneration” research group at the Institute for Bioengineering of Catalonia (IBEC), and in the field of dissemination, she stands out for having curated the first two editions of the City and Science Biennial. We talked about regenerating kidneys, the ethical dilemmas of a researcher and certain prejudices surrounding a career in research.

What is the latest thing that has been discovered through your work?

Right now, one of our goals is to bring organoids into the context of transplantation and to use them as cell therapy to regenerate organs. And we are very excited about this. It’s a project that we haven’t published yet, and I want to be very careful about what I say. But it is one of the great dreams of regenerative medicine: to generate functional structures at a real level, starting from scratch. We have been working for a long time to learn how to transform virgin cells into cells that can look like kidney cells. We have used pig kidneys into which we have infused intact organoids as a form of therapy while the organ is still alive. This project is very exciting because the size and morphology of a pig kidney is very similar to that of a human kidney, which brings us into a very close context to the patient and the clinic.

How do organoids regenerate an organ?

It has never yet been done in humans. There have been studies with intestinal organoids for cases such as Crohn’s disease. Organoids are micro-organs generated from pluripotent cells. What we see when we put these organoids in vivo, in their environment, inside a living organ, is that they interact very well. The organoid cells engraft with the tissue of the organ we are studying and allow us to restore the damage. With these pig models we are studying safety issues, because in order to reach a human patient it is necessary to go through several stages. Other projects that we have, consist of using these micro-organs to study diseases in humans that cannot be studied in any other way, either because the tissues are difficult to access or because the disease is rare. For example: with organoid technology, we can make micro-brains to study mutations associated with certain diseases.

This is the realm of research, but your work has already achieved very important practical applications.

We worked with COVID-19 as the world’s first research group, along with two other large groups. And the organoids revealed to us how viruses infect human cells, something that in 2020 was impossible to find out any other way. We were also able to use them to test the efficacy of drugs. And one of the drugs tested with our work quickly jumped to patients with COVID-19. Thanks to the organoids, we knew very quickly that the infection was not just in the lung, but could become multi-organ.

A few years ago there was a lot of cultural, religious or ethical resistance to stem cell research.

I have never had the feeling that anything we do is ethically wrong. Every project we submit has to go through different levels of review by committees of all kinds, ethics being one of them. The most important question we should always ask ourselves is what is the purpose of the experiment, and if it cannot be done in any other way. If the questions we are asking can be answered in other ways, there is no need to work with these cells. Here in Spain, we are a pioneering country in the world in the study of this type of cell. I have been able to work with jurists, bioethicists and philosophers, and it is wonderful: the debate is there and should be there. I also think it is important that society questions us and that we can explain what we do to society. We must constantly ask ourselves whether what we do makes sense in order to avoid falling into dead ends.

What is the controversy right now?

A few years ago there were issues around embryonic stem cells, but I didn’t even live through it because I was finishing my pre-doctoral studies and now all this is totally behind me. Lately, there has been a lot of controversy about generating chimeras, which are cultures that mix human and non-human cells. Imagine you want to implant certain organoids into a pig embryo because you want to study how it develops. This raises questions about whether this experiment is the right one to get the information we are looking for and, if we get it, what it would bring to humanity. I have participated in many forums and debates explaining what a chimera is, why we have given it that name, and what questions it can help us solve.

Within the animal kingdom, are humans a species that does not regenerate very well?

Not very well at all: the kidney is very weak when it comes to regeneration. On the other hand, evolutionarily inferior organisms, which have been on Earth longer than us, have a much greater capacity for regeneration. A lot has been learned from the frog, from the chicken… we continue learning from animal models. We have seen that there are genes in zebrafish that help regenerate the kidney, and we have them dormant, so we are investigating ways to try to wake them up. A lot of research is being done on this and there is a lot of room to run. Thanks to advances in bioinformatics we can read the genome of spices and now all this is growing exponentially.

Why is the kidney so important?

Because the kidney is affected by many primary pathologies, and because it is one of the two organs most affected by particularly prevalent pathologies: obesity and diabetes have a major impact on the kidney, as does the heart. A very high percentage of people with type 2 diabetes end up with kidney problems. The European population tends to become increasingly obese and diabetic, and the kidney will become more and more important.

What do you think of all the hopes that have been pinned on epigenetics lately and all the literary boom it has generated?

I try not to talk about things I am not an expert in. I do believe that we have very powerful researchers, such as Manel Esteller, who have seen how epigenetic changes are directly involved in certain diseases, such as cancer. But it is very difficult to prove the causal relationship. And this is where we see that people accept certain dogmas with much less scientific evidence. For a long time, until it could be shown that tobacco caused death, they wouldn’t let it be put on packets. What we see in epigenetics is that they have to prove their conclusions even more than other fields of study. I think epigenetics explains everything, but I say that as a person who works with epigenetics for validation, without being an epigeneticist myself.

Do you remember the origins of your scientific vocation?

I have a very boring story [laughs]. I’ve wanted to be a biologist since I was four years old. I suppose it comes from certain inputs at home: I had a microscope that didn’t work at all and a very dynamic mother who answered everything I asked her. I didn’t have to go far to look for referents or have epiphanies: my mother didn’t finish secondary school, and she is my absolute referent. Through research, I have realised that research is something that is done very much in a team, and I love getting to know the world and other people. Everyone makes their own personal journey, and it is very difficult to give general advice in this vocation. Surely, the formula that worked for me to become a scientist will not be useful for someone else. I do think it is important to give people time to reflect on what they want. Here in Catalonia we are extremely lucky: there are mechanisms for you to become a scientist, you find environments like IBEC, which takes gender issues and professional growth very much into account. I have been very privileged, and I have experienced a great systemic transformation: life science careers have a high percentage of women at the beginning, and as the years go by, the numbers are reversed. Institutions must make policies that help to achieve parity. I think we have very good policies here, and what we have to do is to get into the habit of being vigilant and insistent. And, having said all this, we must be very careful and vigilant so that there is excellence regardless of gender.

Finally, are there any prejudices about a career in research that you would like to dispel? And what advice would you give to a young woman who wants to go into science?

That it is not all a thorny path. A career in research also brings many satisfactions. It can be long, and sometimes it can be hard, because you stabilise yourself professionally and conceptually at an age when there are many other changes in your life. But it is a path you do not take alone. It should be explained more that science is fascinating and stimulating because it is done in a team. It can be very hard, but there are many people who help you get back on your feet.