Basic research is a long-term investment essential for continually discovering innovative and effective solutions, as Dr Silvia Monticelli, Researcher and Director of the Molecular Immunology Laboratory at the Institute for Research in Biomedicine (IRB) , explained in an article written in collaboration with laRegione.
Scientific research known as "basic" research focuses on understanding the fundamental principles of nature. It is driven by curiosity about why phenomena occur, without necessarily aiming for immediate biomedical applications. Although this research may initially seem unrelated to practical objectives, the continuous pursuit of understanding mechanisms serves as the real driving force behind revolutionary biomedical innovations. Numerous historical and recent examples demonstrate how studying organisms and systems far removed from humans has led to discoveries of great importance, such as CRISPR-Cas9 technology, which is now the foundation for new gene therapies, and the applications of RNA in medicine.
Basic research as the foundation for innovation
The inestimable value of "the search for why" lies in its ability to create new avenues for knowledge. Without this inquiry, applied research-focused on developing practical solutions to specific problems-would be more restricted in its innovative potential and rely on weaker foundations.
Many important discoveries have emerged from research that is not directly related to medicine. This exploratory approach helps accumulate knowledge that can be applied in often unexpected ways. One notable example is the discovery of DNA’s structure in 1953 by James Watson and Francis Crick. Their achievement was made possible by images produced by Rosalind Franklin through X-ray crystallography. This breakthrough was the culmination of decades of fundamental research in molecular biology and chemistry, which began with Friedrich Miescher’s identification of DNA in cells at the end of the 19th century. Although it was difficult to foresee the practical implications of this discovery, it laid the foundation for future innovations, including molecular diagnostics, recombinant therapy molecules like insulin, and gene therapies. The possibility of sequencing and mapping the human genome to understand the genetic basis of many diseases was unthinkable fifty years ago. Today, researchers equipped with artificial intelligence will see technological progress accelerate even further.
Discoveries born from microbiology
A classic example of the significance of studying organisms that are very different from humans is the discovery of penicillin, which revolutionised medicine in the 20th century. In 1928, Alexander Fleming accidentally noticed that a fungus from the genus Penicillium produced a substance that could inhibit the growth of bacteria. This observation, resulting from basic research in microbiology, led to the development of the first natural antibiotic that could be widely used to treat various bacterial infections. This groundbreaking discovery paved the way for the creation of many other antibiotics, which have saved millions of lives. Recent discoveries highlight the remarkable impact that fundamental research can have on medicine, particularly with the emergence of CRISPR-Cas9 technology. This is one of the most powerful and versatile genome editing techniques developed to date. Just like humans, bacteria need to defend themselves against infections from viruses known as bacteriophages. The understanding of CRISPR sequences arose from studies focused on bacteria and their defence mechanisms against these viruses. Initially, this research stemmed from a curiosity about bacterial immunity and had no immediate practical applications. However, the groundbreaking work of Emmanuelle Charpentier and Jennifer Doudna, who won the Nobel Prize in 2020, has transformed this natural defence system into a precise DNA-cutting tool. Today, CRISPR-Cas9 is being tested to correct mutations responsible for genetic diseases such as Duchenne muscular dystrophy. In 2023, the first therapy based on this technology was approved to correct genetic defects underlying sickle cell anaemia and beta thalassaemia in patients, marking a historic milestone for precision medicine. None of this would have been possible without the curiosity of researchers who, decades earlier, were investigating how bacteria defend themselves against infections.
Messenger RNA and CAR-T cells: two new frontiers in therapy
Another recent example of the potential of basic research is the development of messenger RNA-based vaccines. During the COVID-19 pandemic, this molecule gained significant attention. However, this technology has actually been studied for several years, particularly in the area of cancer immunotherapy.
What is it exactly? Let us think of our genome as a cookbook containing all the "recipes" needed, i.e. all the instructions necessary to produce the proteins and various components of our body. While having this cookbook is essential, it is not enough on its own. Our cellular "chefs," known as ribosomes, cannot read the entire book directly but can only read one individual recipe at a time. These individual recipes are messenger RNAs. Research on these molecules, carried out over several decades without a specific biomedical application in mind, has provided insights into how RNA can be utilised to deliver a synthetic message into human cells. This process has the potential to enable the production of proteins necessary for therapeutic purposes. Researchers such as Katalin Karikó and Drew Weissman (Nobel Prize winners in 2023) have worked for years on chemical modifications of RNA, an essential advance for its subsequent therapeutic or prophylactic use, as in the case of COVID-19. Today, in addition to vaccines against viruses, messenger RNA is being studied experimentally to stimulate the immune system of patients against certain types of cancer, such as melanoma. This and other extraordinary new technologies that have only been available to us for a few years are leading us towards a real possibility of developing targeted personalised medicine therapies. Another modern example of the impact of basic research on medicine is CAR-T cells. This technology involves the genetic modification of immune cells known as T lymphocytes. The patient’s immune cells are altered so that they can recognise specific tumour targets. Once these modified cells are reinfused into the patient, they function like a customised army, specifically targeting and attacking the tumour.
The origins of CAR-T cells lie in decades of basic research in immunology and molecular biology. In particular, understanding the mechanisms that regulate T cell activation and function has been crucial to the development of this therapy. In this sense, pioneering studies such as those by Swiss immunologist Rolf Zinkernagel (Nobel Prize winner in 1996 together with Peter Doherty) laid the foundations for many of the therapies that were subsequently developed. Currently, CAR-T cells are primarily used to treat refractory leukaemia and lymphoma, providing hope for patients with tumours that are resistant to more conventional treatments. Recent research is also exploring the use of CAR-T cells for certain autoimmune diseases, aiming to eliminate abnormal lymphocytes that attack healthy tissue. This is a promising area of study, but it remains entirely experimental at this stage. At the IRB, there are also several laboratories studying T lymphocytes and other immune system cells in the context of autoimmunity and cancer. In our Molecular Immunology laboratory, we are investigating how specific genetic variations found naturally in the population can affect T lymphocyte behaviour. By examining the mechanisms that regulate the inflammatory response, we aim to understand why certain genetic factors may increase the risk of developing particular autoimmune diseases.
A path that is not always easy
Basic research is a crucial part of biomedicine, as it generates knowledge that can lead to groundbreaking applications. However, this type of research comes with its own challenges, including numerous unknowns and often lengthy timeframes. In the laboratory, researchers develop hypotheses based on the data available to them at the moment. It is common for them to be unable to predict exactly where a project will lead or how long it will take to see results. The journey for each researcher is long and complicated, with no shortcuts available. This uncertainty can be frustrating at times, requiring patience and resilience, but it is also what makes the work so fascinating. Without uncertainty, nothing new can be discovered! Scientists engaged in fundamental research are driven by a deep curiosity and the awareness that the "search for why" is the fertile ground from which many small and large innovations can spring. Investing in basic research means having confidence in knowledge and its ability to improve the world we live in.
produced by the Institute for Research in Biomedicine (IRB) in Bellinzona, affiliated with USI, on its 25th anniversary, in collaboration with laRegione .
