#BIOSPAIN2023Interview | "Exploring space with robots and humans opens new frontiers and allows access to unknown terrain"

Since the dawn of humanity, without being aware of it, we have been accompanied by biotechnology. It was an invisible ally that we didn't begin to comprehend until 70 years ago, thanks to the research conducted by James Watson, Francis Crick, and Rosalind Franklin, who revealed the double-helix structure of DNA to the world. At that moment, the foundations of biotechnology were laid, and it emerged as a source of answers and solutions to numerous challenges.

Over these seven decades, biotechnology has transformed the world and established itself as a guarantor of health, social and economic well-being, and the preservation of the planet. The disruptive innovation capability of biotechnology knows no bounds, and one of its upcoming goals is space.

The extreme conditions in space allow for the study of processes that could lead to the creation of new materials with mechanical or chemical properties never before seen, new discoveries about seed germination processes that could yield improved food, or an expansion of existing knowledge about organisms. Paradoxically, the study of biology in extreme conditions can reveal vital new data about life on Earth.

Biotechnology is taking its first steps on a promising path, not without challenges and unknowns, in which knowledge is the fundamental basis for understanding the profound implications even the smallest discovery can have. This is why BIOSPAIN, an internationally recognized event in the biotechnology sector, will feature the participation of Sara García Alonso, a molecular biologist selected in 2022 as a member of the Astronaut Reserve of the European Space Agency (ESA).

With a degree in Biotechnology and a Ph.D. in Molecular Cancer Biology and Translational Research, she has been working as an advanced biomedical scientist at the Spanish National Cancer Research Center (CNIO) since 2019, leading a project on experimental oncology and drug discovery.

AseBio: Curiosity and the quest for answers that allow us to understand and improve our world are the foundations upon which scientific and technological development rests. What were the reasons that led you to dedicate your life to biotechnology?

Sara García Alonso. What attracted me to biotechnology was the array of opportunities and possibilities it offered; applications that may not have even been imagined yet. I've been drawn to STEM professions since I was a child; I've always believed they serve to improve society and the world around us. Additionally, Biology was one of my favorite subjects in high school.

For all these reasons, when I discovered the field of Biotechnology, I felt it was perfect for me, as it involved using Biology to enhance our environment, with applications in various sectors, from agriculture to biomedicine. I began my laboratory training in my early university years (in 2008), and I haven't stopped researching since then. Furthermore, it was in Biotechnology where I met great professionals who inspired me back then and continue to do so today.

AseBio: You lead a project on experimental oncology and drug discovery at CNIO. What does that project entail?

Sara García Alonso. Dr. Barbacid's group, to which I belong, has been studying signaling pathways involved in different cancers driven by mutations in the KRAS oncogene for years, such as lung adenocarcinoma and pancreatic ductal adenocarcinoma. In genetically modified mouse models that mimic these human pathologies, they found that the genetic elimination of the RAF1 protein caused the disappearance of lung tumors. To translate these findings into a clinical scenario, it's necessary to develop drugs capable of eliminating the RAF1 protein from cells. That's our goal. Last year, we managed to isolate, purify, and solve the atomic structure of this molecular target. This achievement has provided us with the necessary tools to find a drug that can be applied to lung cancer patients.

AseBio: What role does biotechnology play in the discovery of new drugs?

Sara García Alonso. Biotechnology plays a crucial role in both drug discovery and the development of new medical therapies. To focus on the stages of the drug development process that my research group is currently working on:

• After identifying RAF1 as a therapeutic target, we have used cryo-electron microscopy techniques, combined with computational analysis and artificial intelligence, to find regions of the protein with suitable physicochemical properties to potentially host a drug.
• Biotechnology is also used in the design and development of new pharmacological compounds, ranging from small molecule engineering to biomolecule-based therapies and gene therapy.
• After in silico (computer-based) identification of a battery of candidate compounds, we use biotechnology to conduct high-throughput screening assays and validate the effectiveness of these compounds. These techniques allow us to quickly identify which substances have the potential to become effective drugs.
• Once the most promising molecules are selected, biotechnology comes into play again for the optimization and production of candidate drugs.
• Before being tested in patients, these molecules must undergo rigorous preclinical trials. Biotechnology is also employed to design and conduct such studies, which focus on evaluating the safety and efficacy of new drugs.

AseBio: In 2022, you were selected as a member of the ESA Astronaut Reserve. What led you to take this step?

Sara García Alonso. The role of an astronaut is something extraordinary (in the most literal sense of the word) and inherently captivating, but I had never considered it as a future option, in part due to the slim chances of achieving it no matter how much you desire it. Since I was a child, what I sought was to advance knowledge and contribute to society through research in oncology. I considered applying for an astronaut position when the European Space Agency (ESA) announced a call for applications, 13 years after the previous astronaut selection.

Motivated by curiosity, I began to explore exactly what the job entailed and what operations were carried out during missions. Surprisingly, I found many analogies with what I was looking for in the "ideal job" and what I believed I had found in research: advancing inspiring scientific projects, promoting technological development, and collaborating in multidisciplinary and multicultural environments. What this other job offered me in addition was the opportunity to do all of that from space, with the adventure and fascination that it awakens.

AseBio: How did this process unfold?

Sara García Alonso. The entire process took around 18 months, from when the call for applications closed (in June 2021) with a total of 6 phases, in different European cities. Nearly 23,000 valid applications were submitted for the call, which underwent an initial screening to evaluate resumes, motivation letters, and responses to a questionnaire posted on the ESA job portal. 1,400 candidates were invited to Hamburg, Germany, for a full day of mathematics, physics, English, and numerous cognitive tests. The 400 who passed the tests were summoned to the EAC (European Astronaut Centre) in Cologne, Germany, for a full day of team dynamics, additional psychometric tests, and psychological evaluations.

100 aspirants advanced to the next phase and were called to Toulouse, France, or Cologne for medical examinations, during which around 30 different tests were conducted over about 5 days. The penultimate phase, with 50 candidates, involved a panel interview at the EAC, and the final phase, with only 25 finalists, consisted of an interview with the Director General at the ESA headquarters in Paris, France.

AseBio: Biotechnology continues to offer answers and solutions through disruptive innovations. Outer space emerges as its next target. Where do we stand in this regard?

Sara García Alonso. Exploring space with robots and humans opens new frontiers and allows access to unknown terrain. It benefits society at large, addresses fundamental questions, fosters international partnerships, creates jobs, and promotes business growth. The knowledge and know-how required to carry out space missions translate into applications and benefits that help make life on Earth more productive, clean, and sustainable. This has been the case since the beginning of space missions, and the applications are observed today in various sectors.

As the decades pass, technological development grows, as do the achievable milestones. Biotechnology has been part of this process from the start and plays an increasingly significant role.

AseBio: What kind of biotechnological studies are being conducted with a focus on space?

Sara García Alonso. Research in microgravity, such as that conducted on the International Space Station, opens up a world of possibilities for generating knowledge and new applications that cannot be replicated on Earth. There are multiple examples of applications and research, including:

• Related to oncological research: protein crystallization, new formulations of cancer drugs, tumor monitoring systems, or tumor models like organoids.
• Related to Biology: experiments to understand how microgravity and space radiation affect living organisms, such as bacteria, cells, plants, and animals.
• Related to human health: biotechnological solutions to mitigate the negative effects of microgravity on health, such as muscle loss (applicable in rehabilitation protocols after muscle damage) and bone demineralization (applicable in people with osteoporosis). Real-time medical diagnosis and biomarker detection systems have also been developed.
• Related to agriculture: food production in space, developing plant and microorganism cultivation systems.
• Related to recycling and sustainability: biotechnological technologies for water purification and the conversion of organic waste into useful resources.

AseBio: What opportunities does this new research avenue present?

Sara García Alonso. Research in microgravity, conducted under conditions that are nearly impossible to reproduce on Earth, opens up countless possibilities, and as with biotechnology, in my opinion, the limit is human imagination. It's a unique environment for conducting physics studies and developing new materials; it can reveal vulnerabilities in cellular or animal models that provide new perspectives on how to treat diseases or diagnose them differently; it can generate more sustainable cultivation systems; and perhaps most importantly, it drives innovation and the development of technologies that can have applications both in space and on Earth.