It was almost 10 o’clock in the evening, when Katalin Kariko and her husband grabbed a taxi from the Novartis Campus back to the hotel in the city of Basel. A long day had ended, which was overflowing with lively discussions with diplomats, scientists, managers, and students and an hours-long lecture in front of a packed audience in the 600-seater auditorium of the Gehry Building where Kariko talked about her career as a researcher.

It was an exceptional story Kariko had to tell, both for its major setbacks and huge successes, which culminated in being awarded the Nobel Prize in medicine in 2023 for her research in mRNA technology, which had led to the development of novel vaccines that helped free the world from the grip of the pandemic. But more than the rollercoaster of her professional trajectory, what stood out was her humility and refreshing directness, which was nourished by her unrelenting fascination for the work at the bench.

The public listened in awe. The guests – young and old – were not just following the words of one of the most important scientists of the modern era, whose discoveries helped save millions of lives and are set to pave the way for novel treatments that could help change medical practice in cancer and cardiovascular diseases, among many other disorders. The guests, many of whom waited in a long line for a short chat and an obligatory selfie after the lecture, knew instinctively that Kariko held some crucial insights for a long and happy career as her story held the secret of turning hardship into gratitude.

Humility and hard work

When I was able to meet Katalin Kariko on that Friday afternoon in the summer of 2024 for a podcast interview, I was surprised to meet a woman in her late sixties who despite her global fame had preserved her childlike wonder of the world. When she talked about science and the many unanswered questions in her field, her eyes seemed to glow, and her voice rose to an almost singing pitch as if she was grasping for air in anticipation of what she might still discover.

It all started in an unassuming village in rural Hungary, where she was born in 1955. Together with her sister, she would roam the flat plains around her hometown, enthralled by the beauty of nature. Planting a seed and watching it grow was pure magic to her. Her father, a butcher, often retold the story from her childhood about how she would try to figure out why the animal he had just slaughtered would not move anymore. She would stand there transfixed, thinking about life and death, fully immersed in the experience.

These early days would prove formative. In school, she excelled in mathematics, physics, and biology, even winning a major national prize that motivated her to go to university and pursue a career in science. But already during these early academic days, she encountered her first major obstacle and would soon need to learn how to overcome it.

One of her teachers proved obstructive. Although Kaliko had good grades, the teacher threatened to block her path to university, insinuating that he had good contacts with the administration. After all, this was communist Hungary, where careers were made and unmade through cronyism. But Kariko did not give in. She had already acquainted herself with such emotionally demanding situations through her study of the work of Hans Selye, a famous Hungarian intellectual who was the first to write academically about stress – a term which previously was only used in physics. As part of her school curriculum, she had written a letter to Selye and, to her surprise, received an answer – an experience that would inspire her to work closely with students throughout her career.

“Thanks to Hans Selye, who coined the word ‘stress,’ I learned how to manage difficult situations,” she said. “Later, I learned that those were the ideas of the stoics; that you should focus only on things that you can influence, that you should not spend any energy on things you can’t control.” Thus, she was able to cope with the threatening teacher. “The challenge forced me to excel; I had to be the best. Over time, I realized that his resistance made me stronger and more resilient, teaching me to focus solely on what I could control – my own effort and excellence.”

The importance of self-confidence

This mental quality would help her during her career as she seemed to face more obstacles than many of her colleagues. In Hungary, soon after the fall of communism, the lab where she had started to work on RNA technology closed and she was forced to leave the country and search for a job in the United States. There, she had little luck during her academic career. A colleague threatened to have her kicked out of the United States. At the University of Pennsylvania, where she had worked for more than 20 years, she was fired unceremoniously. These experiences made her stronger, she says, and may have helped her stay single-minded in her pursuit of perfecting RNA technology.

When I asked Kariko how she was able to stomach such blows, she was clear about the importance of self-confidence: “It’s crucial for everyone to believe in themselves. Imagine growing up in a humble home on a dirt road, scarcely seeing a car pass by, and then years later, finding yourself at an Ivy League school. Despite my modest beginnings and not having perfect English, I challenged myself to think beyond what others could.”

Hard work, she said, is essential. And one should also care less about promotions or awards. “Aiming for a Nobel Prize isn’t practical because it depends on decisions beyond your control. Instead, my focus was always on understanding science, an endless puzzle that is always there to be solved. This mindset helps avoid disappointment because you’re not dependent on external validation but are driven by curiosity and the quest to solve problems.”

A researcher’s mind should focus on science only, she said. “In my experience, the true joy of science comes from the direct process of experimentation and problem-solving,” Kariko said. “I’ve spent countless hours at the bench, tackling technical challenges and reveling in the thrill of understanding something new for the first time. While some of my colleagues were promoted for their administrative capabilities or their ability to secure grants, I focused on the science itself… This is what drives my philosophy: stay engaged with the core of scientific work. The satisfaction of making a personal discovery, of understanding a complex concept, and contributing new knowledge to the world – that’s the essence of a fulfilling scientific career.”

RNA research

Kariko’s involvement in RNA research started early. Already in 1978 at the age of 23, Kariko was charged by her Ph.D. supervisor to set up a screening lab. “ ‘We have to make something useful,’ he told me and said: ‘Katia, you have to set up a viral screening lab.’ ” She agreed, and so the journey began.

In the 1980s, RNA technology was in vogue, with experiments focusing on the realm of vaccines for infectious diseases and cancer. However, despite these promising developments, many researchers who initially worked on mRNA vaccines struggled to secure funding by the 1990s, when the scientific community started to focus on gene technology. Kariko, meanwhile, kept focusing on her field. “I argued that mRNA could be crucial for short-term protein synthesis to alleviate symptoms, but this idea received little attention initially. Nonetheless, I continued research, which led to innovations in mRNA modification and purification, enhancing its stability and efficacy in protein production without triggering immune reactions.”

Her collaboration with immunologist Drew Weissman, who received the Nobel Prize together with Kariko, changed the outlook for the technology, however. They made a groundbreaking discovery that revolutionized the use of mRNA in medicine by addressing its inherent inflammatory responses. Kariko and Weissman found that modifying nucleosides, the building blocks of RNA that include a sugar and a base, within the mRNA structure could significantly reduce its immunogenicity, preventing it from triggering harmful inflammatory reactions when introduced into the body. Their collaborative research focused on isolating and modifying the mRNA to mimic the natural behavior of cellular RNA, which does not cause inflammation. This key insight enabled the safe and effective use of mRNA technology in vaccine development, including for COVID-19. The rest is history…

The alchemy of gratitude

Kariko seems sometimes oblivious to the accolades she has received. But while she is proud of the academic recognition, which she keeps in several specially designed cabinets at home, she is adamant that young and aspiring scientists should not focus on promotions but on the science itself. She also recommends that people should always have a plan and keep themselves busy, like her 99-year-old former schoolteacher. “Yeah, Kati, I still have to live. I have this task … I have to rearrange all the photo albums,” she told her recently.

This is how Kariko also overcame one of the darkest moments in her career, by asking what’s next. “I recall the day I left the University of Pennsylvania after 24 years of service,” Kariko said. “There was no farewell party, no goodbyes; just a solitary walk to my car in the parking lot, pondering what might come next. Such endings had become a recurring theme in my career. From being sacked in Hungary and forced into retirement later on, each exit marked a significant turning point. Yet, it was crucial not to dwell on the why or the injustice of it all – such thoughts only poison the mind.”

Instead, she focused on the future. After leaving Penn, she went to BioNTech, a company that back then did not even have a website. She learned about it through another colleague who had also faced professional setbacks. This new beginning was an opportunity to redirect her energy and continue contributing to science, affirming Hans Selye’s advice against seeking revenge. “He taught me that the best way to alleviate anger was through gratitude, even towards those who had wronged us,” she said.

This philosophy proved effective even when she encountered the professor who had once threatened her with expatriation from the United States. “At a lecture, I thanked him for his impact on my career, highlighting the positive without dwelling on past grievances. He didn’t remember the negatives, and many people don’t. Holding onto resentment serves no purpose; letting go and focusing on gratitude not only frees you but leads to a far happier life.

This simple truth has been a guiding principle in my approach to personal and professional challenges.” This stoic insight seems more powerful than the Nobel Prize itself.