Katalin Karikó

Katalin Karikó remembers her first vaccination campaign quite clearly.  “Students from the veterinary school came into our yard, and my sister and I handed over our chickens to them, one by one.” And science lessons were all around her in her childhood in the Hungarian countryside – birds nesting, hatching, and migrating, soap-making, tackling potato pests, and learning about wildflowers and how they grow.

But it was in elementary school that she first had a formal introduction to science. “I joined a chemistry club. We constructed elements from playdough and then formed them into molecules using toothpicks.”  And the biology teacher encouraged their interest in the natural world by taking the class out for walks to observe such things as the mechanism that allows waterlilies to float.

You might think such a precocious interest in chemistry and biology led naturally to early excellence in the subjects, but that was not the case, she says. “I compensated with effort for what I lacked in natural ability. I worked and studied, and I got better. By third grade I was earning straight 5s.” By eighth grade she was the best biology student in the town, then in the county, and then third in the whole country. After finishing high school, she started to study biology at the University of Szeged, where she is now a professor.

She performed her PhD and post doc studies at the Biological Research Centre of the Hungarian Academy of Sciences, also in Szeged, before leaving for a post doc position at Temple University, Philadelphia, USA, and the University of Health Science, Bethesda. In 1989 she was appointed Research Assistant Professor at the University of Pennsylvania, where she remained until 2013. After that she became vice president and later senior vice president at BioNTech, Mainz, Germany. Since 2021, in addition to her professorship at Szeged, she remained an Adjunct Professor at the University of Pennsylvania.

Her interest in the possibility of using RNA for medical purposes started at the Biological Research Centre, where she was researching interferon. “It was at a time when the molecular mechanism of interferons and their antiviral activity was just beginning to be understood. We were making so-called 2-5A RNA molecules in lab and testing out their antiviral effects.” Experiments were going well when the funding was pulled, and she had to make the difficult decision to emigrate to the US. A letter to Dr Robert Suhadolnik, a nucleoside analogue expert at Temple University, led to a job offer. “I thought I’d work there for a year, learn, and then return to Hungary.”

But things didn’t turn out that way. A complicated parting of the ways with Suhadolnik led to a position at Bethesda and then to work with Elliot Barnathan, a cardiologist at the University of Pennsylvania. “Elliot was working on plasminogen activators, molecules that help to dissolve blood clots and their use in minimising the chances of clots forming in the blood vessels. He was planning to do this using DNA, but I suggested mRNA instead. Even though I hadn’t synthesised it yet, the science of mRNA was advancing fast.”

A series of setbacks and breakthroughs followed over the next few years. “The setbacks were on full display, though the breakthroughs were hardly mentioned at the time. But at the end we had succeeded in using mRNA to make a specific protein within cells.”

And then, at Penn, she met Drew Weissman, who shares the Nobel with her. “He was an immunologist without RNA experience, and I was an RNA scientist who didn’t know much about immunology. And we needed to find a way by which mRNA could evade detection by the immune system. Finally, after I’d been working on RNA for thirty years, we did it. We could make mRNA in the lab, deliver it into immune cells without causing inflammation.”

The paper on this ground-breaking discovery was submitted to Nature, but rejected within 24 hours as merely an ‘incremental contribution.’ Submitted to Immunity, it was accepted but didn’t create waves, not even ripples. This discovery was met with silence. It took a pandemic for it to receive the acclamation it deserved.

The Covid-19-causing SARS-CoV-2 virus was first sequenced in January 2020, and the first vaccines became publicly available less than a year later. Not only did the mRNA vaccines limit mortality and morbidity to an impressive extent, but the vaccines have opened the way to many other applications of the technology – not just vaccines but many other therapies for acquired and genetic diseases. She will be telling the conference about the decades of scientific achievements that preceded this;  from the discovery of mRNA in 1961, then the generation of mRNA in a test tube in 1984 and finally evaluating it in animals as a vaccine against infectious diseases and cancer. “A great extent of progress toward a viable treatment was made during those years. We warded off the immune response and demonstrated that mRNA formulated with lipid nanoparticles could be a potent vaccine. These discoveries eventually led to the development of the mRNA vaccine that has now helped to fight the global pandemic and opened the door for developing breakthrough therapeutics for incurable diseases and unmet medical needs.”

The lesson from all of this, says Katalin Karikó, is don’t ever give up. “Trust what’s inside you. Nurture what you find there, especially when no-one else does. And be prepared to go out and explain your research, particularly if the science is difficult to understand and risks being misrepresented. If people are to benefit from life-saving medical advances, it is our duty to close the gap between what they know and what they need to know.”