Laura Sánchez Piñon: «Genetic editing is the great advance in molecular biology, biotechnology and genetics»

Genetic editing, zebrafish, killifish, microplastics, the role of women in the world of research... A conversation with Laura Sánchez Piñon is very rewarding. Because of her extensive knowledge. Also because of her vocation to share it.

Professor of Genetics at the Terra Campus of the University of Santiago de Compostela, she was once the first woman in the university's Department of Genetics. In addition to her teaching work, she currently directs Zebrabiores, a line of research within the ACUIGEN group that has received important recognition for the quality and quantity of its research.
In this interview, we talk to Laura Sánchez Piñon about all this and much more. Read on and find out more...

-Your research career has covered everything from the ultrastructure of human chromosomes to fish genetics and the use of animal models in biomedicine. How has your experience within your fields of knowledge evolved since you started?

-The truth is that it's been many years. My scientific career, so to speak, began when I was finishing my degree in Biology in 1979. At that time, I was working in the Department of Genetics, and there I was researching population genetics with Drosophila melanogaster.

When I finished, I had the opportunity to get a place at what was then the University College of Lugo in 1981 to teach genetics and biology in the degrees of Biology and Chemistry. When I decided to do my doctoral thesis, I moved to the University Hospital of A Coruña (CHUAC) with the cytogenetics of human chromosomes. There, I worked a lot, for example, with electron microscopy techniques analyzing the ultrastructure of chromosomes and their variation in a Galician population. The thesis work was combined with teaching and this was very enriching.

During the preparation of my thesis, I spent two periods of time at Italian universities, in Rome and Cagliari. When I finished, thanks to one of the first grants awarded by the Xunta de Galicia for postdoctoral stays, I ended up at the University of Würzburg in Germany. There, I worked in the field of cytogenetics with new techniques, a field that would end up being central to my first stage of research activity.

On returning, I decided to study some species of fish, both from an evolutionary point of view and from the point of view of resource conservation, as was the case with trout, for example. In addition, Galicia was also very interested in supervising repopulation programs.

In line with this research, I obtained my first funding, which led to my first thesis. Later, I would focus on the field of aquaculture, which also led to the preparation and defense of multiple theses and finally to the creation of a strong research team with very fruitful activity.

All these fields in which I was immersed, as is logical, improved in terms of funding, technological equipment and infrastructure. It was not an easy time, and we did not have the means that we have now.

-You have worked in prestigious institutions such as the University of Würzburg and the Rosalind Franklin MRC in Cambridge. How have these experiences influenced your research approach?

-The stays I did during my thesis were very helpful. Before, having a bibliography was much more complicated than it is today. Without the possibilities of the Internet, you had to go to the journal libraries of the different universities, and there weren't always journals in the field that interested you.

For example, at the time, in the Department of Genetics at the University of Rome, as well as learning new techniques and discussing the results I was obtaining, having such a comprehensive library allowed me to have access to many publications that ultimately contributed to the discussion of my thesis.

On the other hand, when I was in Germany, at the University of Würzburg, after finishing my doctoral thesis, I gained another vision and another perspective. There, I was able to start a new line of research on my own, something I have to thank all the people around me for, such as the head of the department at that university, Professor Michael Smith. I remember that he was someone with whom you could engage in a very prolific conversation and discuss a wide variety of topics. He thought a lot about the future of the young people who came to his laboratory, and he was instrumental in starting a new line of research when I returned.

Later, as a senior researcher in my line of research, I went to Cambridge, to the Genome Campus, with a very prestigious scholarship from EMBO (European Molecular Biology Organization). At that time, the Genome Campus had three centers: the Rosalind Franklin, where I worked; the European Bioinformatics Center; and the Sanger Institute, where they were sequencing the human genome at that time and finally making our genome public. Historically, it was a spectacular period, and I was lucky enough to be able to experience it firsthand. There were incredibly interesting seminars every day, we had visits from Nobel Prize winners every other day...

During my stay, I also came up with some ideas to work on when I got back. Being there allowed me to think of new strategies and ways of tackling problems. I was also able to make many contacts and meet a lot of very diverse people. It was a very enriching experience, of course.

-You are currently working with zebrafish to study human diseases. Why is this the species of choice and where would you say the most substantial advances are to be found in the coming years?

-Zebrafish are what are considered model organisms, like mice or Caenorhabditis elegans. This species offers the possibility of working with it in the laboratory in a controlled way. In addition, its genetics are very well known; its genome has already been sequenced, and many laboratories work with it, which greatly facilitates research and collaboration.

What is true is that its introduction into laboratories was quite late if we compare it with other model organisms such as the mouse or the drosophila. I, for example, started to read about zebrafish, and it wasn't until 2012 that I decided to incorporate it into our laboratory. We began a very fruitful collaboration with the oncology department in Santiago to carry out cancer cell xenografts.

In relation to the latter, we started a line that is what is known as gene transplantation, which consists of introducing cancer cells into the fish embryo. As they are fluorescently labeled, we can follow them through the microscope and observe how they grow, metastasize, how they respond to chemotherapy... In short, we can see how they affect these cells and, consequently, test drugs. It is a very interesting line of research with a long way to go, and we are continuing to collaborate with many groups in Galicia, Spain and Europe.

Another of the most promising lines of research is the study of rare diseases. Zebrafish allow us to generate mutant lines for certain diseases or syndromes, such as Charge syndrome, making it possible to recapitulate the phenotype of patients with this disease very well. Several theses have been presented in this line of research, and the doctors are now in very prestigious research centers.

-Your research work also focuses on the evaluation of the toxicity of chemical substances and nanostructures. What impact can these studies have on the regulation of chemical compounds and public health?

-This line of research, in particular, arose as a result of contacts with companies, especially in the textile sector, that are interested in what is known as a compound replacement, with the aim of replacing a highly toxic substance with another with less impact.

What we do is study basic toxicity using a methodology that is approved by the OECD and applying embryo toxicity tests. It is, so to speak, a line of service: we work on a contractual basis with companies in the sector.

At the same time, we also have other lines of work that revolve around microplastics, in which we study their ecotoxicity. How can we know what microplastics do in organisms? We can observe it in fish, seeing in which parts they accumulate more and thus obtaining information that we then try to transfer to humans.

Similarly, we also work with nanostructures, a very broad field in which we offer our services to carry out tests and delivery tests, for example.

-You have recently incorporated killifish as a model for studying aging. What makes this species so interesting for researching senescence, and what progress have you made so far in this field?

-The killifish is a species that has only recently been incorporated into laboratories. It is not yet a model organism in the strict sense of the word because it has not yet achieved all the conditions necessary to be one. In addition, both its handling and feeding are quite complicated. That is why very few laboratories work with this fish: in fact, we are the second laboratory in Spain to work with this species, together with the laboratory of the Andalusian Center for Developmental Biology.

The real interest of this species lies in its life cycle, which is very short. It is the shortest-lived vertebrate known, living between four and seven months. That is why it is extremely useful for studies of aging, allowing the testing of drugs against this phenomenon or for the treatment of neurological diseases closely related to aging, such as Alzheimer's or Parkinson's.

Another factor to bear in mind is that it is a species that develops very few cancers, basically because it does not have time to develop them.

-From your perspective as a geneticist, how do you think genomics can influence the development of personalized treatments for human diseases?

-We are seeing more and more that genomics studies undoubtedly help to create personalized treatments in such important fields as cancer. In genomics, in the discovery of new markers, in order to be able to classify better, for example, the type of tumor a patient has and to be able to provide them with the best possible treatment.

On the other hand, a very interesting technique is also being widely used, which is that of liquid biopsy. Through a blood sample from the patient, we can discover if there are cancer cells, and thanks to genomics and new markers, specific cancers can be defined that are detected through this technique.

Genomics, in turn, contributes to a better classification of rare diseases, expanding the identification of more genes that can mutate and influence the disease itself. In the same way, it also allows us to decipher 'junk DNA', which is repeated DNA whose specific function is unknown and which, thanks to its sequencing, can be related to the development of certain diseases.

Therefore, advances in genomics, thanks in part to the enormous reduction in the cost of processes and techniques, allow us to generate, for example, an exome (the expressed part of the genome) of a human being in a matter of hours and at a low cost, which makes it possible to obtain genetic information from a large number of patients in a short period and in a simple way.

-Ethical debates arise in the study of animal models and gene editing. How do you balance the need to advance science with ethical responsibility in your research?

-It is an issue, especially with editing, that is currently being tried to be legislated in Europe, the United States and China, but there is no uniform legislation. In fact, it is more flexible in the United States and China.

The ethical debate is very important. For now it is not considered to be the same as the debate on transgenics, which is good because it really is very different. But undoubtedly, the capabilities of genetic editing are impressive, and we have to think about how far we can go in the case of humans.

It is true that when we talk about using it to, for example, correct a disease, we have no objection to it. In fact, a treatment for sickle cell anemia has already been approved, and others are on the way for eye diseases.

However, when we talk about things that are beyond the capabilities of genetic knowledge, such as improving the human species in the field of intelligence, it isn't easy to know how to act. There are other things, such as disease resistance, where it may be possible to act, but the line in these cases can be very fine.

The debate is going to be a long one, but it has to be had. Suppose we look back, for example, at in vitro fertilization, which is completely different but was also very controversial. Now, we have millions of people who came into the world through this system; sometimes, they have a hard time fitting in when they are not well understood.

Genetic editing is a great advance in molecular biology, biotechnology and genetics. And it is going to continue growing. The technology is getting better and better, it has more control over off-target effects, therefore, it is something we are going to have to live with.

We must learn, understand and explain the advantages and disadvantages to the public that is not trained in the subject. For many treatments, we assume the disadvantages.

-Finally, as a professor and leader in your field, what was your experience as a woman in the field of science, and what advice would you give to young female researchers who want to pursue a career in genetics and biomedicine?

-My experience in this field was always positive. At the beginning of my career, I did feel a certain loneliness because I was the first woman in the Department of Genetics at USC. This can have advantages or disadvantages, but I have to say that I always had fantastic colleagues; I worked in a very positive environment, and in the development of my career, I did not suffer any discomfort due to the fact of being a woman.

In the case of children, the person you have at your side is very important. I have three daughters, and my husband is a scientist, and that is the most important part.

In relation to advice, I think the most important thing is to lead by example and to be passionate about science. This is a way of life, in many cases, much more than a job. Sometimes, it almost becomes a hobby.

Being in contact with young researchers is very important. It gives you a different and enriching perspective. And on this point, I have to say that I don't see differences between being a man and a woman; what I do see are differences between people who are more enthusiastic about this type of work.

It's true that in the field of women, there is a lot of talk about motherhood, but I believe that being away from the laboratory for a few months does not imply any deficit in a career that is very long, especially if you are part of a good team. This is my opinion.

Here in our laboratory, we have several examples of mothers who were first students, then assistants and tenured professors, and now they are going to be full professors. Obviously, there are all kinds of cases, but I don't like to generalize on this issue.

What I do think is important is the fact that there are more and more women, especially in positions of relevance in leadership. This part is definite, that we see women leading groups, directing projects... Perhaps this is going slower than we expected.