Professor Aaron Ciechanover, could you tell us how your passion for biochemistry began and if there was a particular moment—for example, when you received your first microscope—that inspired you to explore the world of science?
I've always been fascinated by nature and its most hidden mechanisms. Ever since I was a boy, I was intrigued by how living things worked "behind the scenes." At the time, biochemistry reigned supreme within biology: modern molecular biology, mouse genetics, or advanced tools like confocal or fluorescence microscopy didn't yet exist. For me, that first microscope represented a gateway to a new world. Biochemistry soon proved to be the perfect tool for unraveling the fundamental processes of life, including the ubiquitin system, which I would later help decipher. Over time, I realized that what fascinated me wasn't just observing, but understanding the profound rules that govern the cell.
What experiences or teachings most influenced your academic career, and how did you decide to focus your studies on cells and the processes that eliminate unnecessary proteins?
I'm a doctor by training, and from the very beginning, I sought tools that would allow me to understand the mechanisms underlying disease. Discovery always comes from a good combination of curiosity, method, and enlightened mentors. I chose as my supervisor Professor Avram Hershko, a doctor who had decided to dedicate himself to biochemical research and who, with extraordinary intuition, proposed studying protein destruction, a process that was then almost unknown. From him, I learned that great discoveries arise when we dare to explore the unexplained, when we accept the risk of scientific uncertainty. The topic of protein degradation immediately fascinated me because I sensed that, to truly understand life and its dysfunctions, it wasn't enough to study the construction of molecules: we also needed to understand how and why they are eliminated.
Could you explain, in simple terms, how you discovered the cellular system that eliminates unnecessary proteins and what were the most exciting moments of your research?
We used the reticulocyte as a model, an immature red blood cell that, during maturation, degrades almost all cellular machinery except those essential for transporting oxygen. We therefore knew it must possess an extremely efficient proteolytic system. By studying it, we identified an elegant and highly precise mechanism: ubiquitin, a small protein that acts as a "tag," marking proteins destined for destruction and allowing them to be recognized by the proteasome, the complex that degrades them. The most exciting moment was realizing that we were not simply describing an isolated biochemical phenomenon, but a universal system of cellular quality control, fundamental to vital processes such as cell division, stress response, and development.
What did receiving the Nobel Prize mean to you, both personally and professionally, and what did this prestigious recognition mean to your research team?
"The Nobel Prize was, above all, recognition of the work of a team that, for years, shared dedication, discipline, and creativity. Our discovery paved the way for understanding the underlying mechanisms of disease and the development of innovative therapeutic strategies, such as drugs against multiple myeloma, a cancer of the immune system. On a personal level, it was an immense honor, but also a responsibility: you become a listened to voice not only for what you have discovered, but for what you can still contribute to the scientific community and society."
How can the study of biochemistry and cellular processes concretely contribute to improving human health and preventing disease?
It's impossible to understand disease mechanisms or develop effective drugs without a thorough understanding of how healthy cells function. Biochemistry allows us to decipher the molecular abnormalities that cause disease and design targeted interventions. Today, many innovative therapies—from oncology to neurology—are based on the modulation of cellular processes that we have begun to understand thanks to research on the ubiquitin-proteasome system. Studying how cells maintain their internal balance is key to preventing and treating numerous degenerative conditions and tumors.
What advice would you give to young people or those interested in science and how do you see the role of biochemistry in improving the quality of daily life?
I would say to follow your instincts, cultivate what you feel naturally drawn to, but always choose a positive environment, with capable and generous mentors. Science is never a solitary journey: it's a community, a shared language, a collective commitment. Biochemistry will continue to have a huge impact on our daily lives, from nutrition to personalized medicine, from biotechnology to sustainability. Understanding the chemistry of life means understanding how to improve it.
Daron Acemoglu: Economic Inequality, Institutions, and Technology
