Álvaro Arana: «Science is teamwork: competitiveness is less fruitful than collaboration»

Collaboration and teamwork play a critical role in a scientific community that wants to be healthy and thriving, focused on generating and transferring knowledge that has an impact on our society. Sharing advances, sharing doubts that arise and keeping an open mind about colleagues are beneficial dynamics for research. And people like Álvaro Arana Díaz lead by example.

D. cum laude in Biology from the USC, postdoctoral researcher at Campus Terra and member of the ZebraBioRes research group, his way of working emphasizes the need to weave networks of scientific cooperation for the enrichment of research and the acceleration of discoveries. 

These values have accompanied Álvaro Arana in his research and professional career in recent years, with his sights set on a promising future that is already bearing fruit in the present.

His current research interests focus on topics that are important for society as a whole, such as the study of rare diseases through gene editing with CRISPR/Cas9 or the conservation of wild fish populations affected by the nervous necrosis virus. 

Today, we talked with him about this and other issues of great interest. Don't hesitate to spend a few minutes with him; it's well worth it.

-You became a doctor cum laude thanks to your doctoral thesis on the generation of a zebrafish model of CHARGE syndrome. What is the basis of animal modelling? What are the benefits of this practice at the scientific and social level?

-Animal modelling consists of using live, non-human animals to reproduce specific characteristics of specific human diseases to study and understand their causes and the alterations they produce in organisms to identify possible treatments. In this sense, it is prevalent to ask whether what happens in animals and humans is comparable, or why we study these diseases in animals and not in people or alternative methods.

To be a good animal model in research, it is crucial that the animal has biological similarities to humans and can reproduce at least part of the disease in question, that it is easy to handle in the laboratory, and that the results obtained are consistent and reproducible.

In our case, we work with zebrafish as an animal model for rare genetic diseases. Zebrafish have much more in common with humans than people are used to thinking. First of all, it is a vertebrate, like us, which means that many processes of vertebrate embryonic development are very similar, and the embryos share many homologous anatomical structures, organs and tissues. Many rare genetic diseases occur during embryonic development or in tissues and organs that form now, so vertebrates are an excellent model to reproduce them. Mutations in the DNA produce these genetic diseases, so the model animal we use must have that gene in which its alteration produces the disease in humans. Therefore, the zebrafish has a homology of 70% in the DNA, and about 85% of the genes that produce diseases in humans are present in the zebrafish. Thus, through gene editing techniques, zebrafish facilitate the creation of accurate models to study these human diseases.

There are about 7000 known rare diseases affecting 6-8% of the population. Although many rare diseases exist, they are so-called because few people suffer from them. This limited number of patients makes obtaining sufficient data in clinical trials difficult, so animal models allow working with a more significant number of individuals, thus providing more robust results. In addition, testing new therapies in animal models before clinical trials reduces the risks to patients and allows the efficacy and safety of treatments to be evaluated. Results in animal models, such as zebrafish, must be validated and transferred to other models before being applied in humans, ensuring that they are effective and safe.

Contrary to what many believe, it would be impossible today to altogether dispense with animal model studies in favour of computational studies. Computational approaches, helpful in simulating biological processes and predicting theoretical results, depend on the complexity and interaction of natural biological systems. Animal models are essential for providing detailed information and discovering new aspects that may go unnoticed in computational studies. They allow us to study the physiology, pathology and response to treatments in a whole organism, which is vital for validating and understanding computational results. Both approaches are complementary and necessary to ensure significant progress in biomedical research, with the ultimate goal of reducing and eliminating animal use.

-In the same field, you worked in the ZebraBioRes research group at USC. What is the main focus of the group? What role do these types of research groups play in the scientific landscape? 

-Our main focus is using zebrafish as a model to study human diseases, such as cancer, through xenotransplantation and genetic diseases through gene editing with CRISPR/Cas9. We also carry out toxicological studies of compounds used in the textile industry and screen new drugs.

Research groups such as ZebraBioRes are fundamental in scientific progress, especially in areas such as translational medicine and biotechnology. The use of animal models such as zebrafish allows us to study human diseases ethically and with more individuals than clinical trials, providing more robust data on the efficacy and safety of new treatments. In addition, in our research on aquatic species, we will also begin to use zebrafish to validate results from studies on viral resistance in sea bass and sea bream, thus improving the quality of life and sustainability of these vital species in our ecosystem.

ZebraBioRes is part of the ACUIGEN group, which specializes in technology transfer to companies and administrations related to aquaculture and the environment. ACUIGEN has the company GENEAQUA, a spin-off of the USC, which offers genetic services to aquaculture companies to improve production profitably and sustainably. ACUIGEN's lines of research include evolutionary genetics, cytogenetic and molecular genome analysis, the development of genomic tools, and the management and conservation of genetic resources.

-In previous interviews with other colleagues, the relevance of zebrafish as a model in research was explored because of its similarity to the human genome. Given that you enjoy a remarkable expertise in this topic, what other advantages does working with zebrafish bring? 

-In addition to its genetic similarity to humans, the zebrafish offers several practical advantages. It has a short life cycle and a high fecundity rate, allowing studies of multiple generations in a short period. Its embryos are transparent, facilitating real-time observation of development. The small size of both the embryo and the adult allows for many individuals in a smaller space than other species. In addition, their rearing and maintenance are relatively inexpensive compared to other animal models, allowing large-scale studies to be carried out at a lower cost.

We are currently introducing the killifish into our research. This small fish species is known for its short life expectancy of 3-6 months and accelerated ageing. This addition will allow us to expand our ability to study age-related diseases and explore potential therapies in a rapidly ageing biological system, complementing our work with zebrafish.
 

-You also do research with other fish species. One of your current projects involves sea bass and sea bream. What makes fish as an animal such a widely used research model or such a valuable object of study? 

-In this case, sea bass and sea bream are not a model, they are the object of study. In this research we are trying to discover the implication of a specific gene in the resistance of certain individuals to the nervous necrosis virus. This virus causes a lot of mortality in wild populations of sea bass and sea bream, which has a significant impact on the fishing industry. The identification of this gene could allow the development of strategies for the selection of resistant individuals, thus contributing to the conservation of populations and the sustainability of the fishing industry.

-Part of your work is related to identifying candidate genes which are potentially linked to different diseases. Once the results are found, how is the process of knowledge transferred to the world of human medicine? 

-Part of our work, carried out by Diego Robledo's group in Edinburgh, involves the identification of candidate genes that are potentially related to resistance to specific viruses in fish species used in aquaculture. This process involves first identifying genes that may play a critical role in virus resistance, using advanced sequencing techniques and bioinformatics analysis. Once identified, we proceed to study these genes in cellular models to better understand how they interact with the virus and what is the mechanism that confers resistance. These types of studies are crucial for aquaculture, but they cannot be directly transferred to the world of human medicine, since they are focused on specific fish diseases.

On the other hand, in human genetic disease studies, we work with genes that are already known to cause disease in humans. We use zebrafish as a model to perform gene editing and study the effects of mutations in these genes. This process begins by establishing a model of the zebrafish carrying the gene mutation in question, so that it reproduces the human disease as closely as possible. We then study the altered biological processes that produce the disease, searching for treatments that can mitigate the previously observed symptoms.

Effective treatments are tested in the zebrafish model to assess their efficacy and safety before being transferred to human clinical trials. This process ensures that treatments have a sound scientific basis before being tested in humans, which reduces risks and maximizes the chances of success in clinical trials.

-Throughout your training period, you made several stays outside Galicia. One of them took place at the i3S institute in Porto, where you focused on techniques such as in situ hybridization or immunohistochemistry. What is the importance of establishing collaboration channels between international scientific institutions? 

-International collaboration is fundamental for the advancement of science. It allows the exchange of ideas, techniques and resources, enriching research and accelerating discoveries. Stays in prestigious research centres, such as i3S, offer the opportunity to learn new techniques and methodologies that can be applied and adapted to one's projects. In addition, these collaborations foster the formation of research networks that can result in multidisciplinary and innovative projects.

In addition, something that is not naïve, this type of interaction allows us to get to know new cultures and to be enriched by local history and architecture. It is a unique opportunity to broaden your horizons, learn new languages and establish personal and professional relationships that can last a lifetime. These personal experiences are as valuable as academic ones, as they contribute to forming a global and multicultural perspective that is essential in today's interconnected world. Meeting new people and being part of international collaborative networks opens doors to future opportunities and strengthens the global scientific community.

These stays allow you to be aware of whether other groups are working on the same thing as you, to know how they are doing it and to avoid competing for the same results. Competition is less fruitful than collaboration. Working collaboratively rather than in competition fosters a more productive and positive environment where resources and knowledge are shared to achieve common goals. This cooperative philosophy enriches science and accelerates progress, benefiting the entire scientific community and, ultimately, society as a whole.

-Genetic manipulation and mutation of animal species holds great promise for the treatment of inherited diseases. What advice would you give to young people who want to go into this scientific field? 

-My recommendation for young people is to follow their curiosity and passion for science. It is essential to acquire a solid foundation in biology, genetics and laboratory techniques. Seek opportunities to participate in research projects from the early stages of their training and spend time in different laboratories to gain a broad perspective.

In addition, this is a fast-moving field, so it is crucial to keep up to date with scientific advances, attend conferences to report your progress, listen to the progress of others and resolve your doubts with the experts. Be bold, ask questions, and learn from the most experienced. Science is a team effort, and as I already mentioned, collaboration is much more fruitful than competitiveness. Keeping an open mind, being persistent, and being willing to work hard are essential ingredients for a successful career in genetic manipulation and inherited disease research.

It is also important to remember that, in science, it can sometimes be frustrating when you don't get the results you expect or when experiments don't go as they should for a variety of reasons. However, it is essential not to give up at these times. Every challenge and mishap is part of the learning process and helps us grow as scientists. Perseverance, asking your peers and keeping your motivation high are essential qualities that will help you overcome those difficult moments and move forward.