“You have to be a champion of failure”

21.06.2024Paul Karrer Medal

Last week, Katalin Karikó visited the University of Zurich to accept the Paul Karrer Medal. The Hungarian-born biochemist has faced numerous setbacks in her groundbreaking mRNA research before winning the Nobel Prize in 2023. She told us how she always found the strength to carry on and what advice she gives to young scientists.

Carole Scheidegger

Kategorien

• Mathematics and Natural Sciences
• Awards

Roland Sigel, Dean of the Faculty of Science, and Katalin Karikó.

I tell students what I had learned over the years: the most important thing is that they should enjoy what they are doing.

Do you have any advice for female scientists in particular?

Well, I would rather address the government: they should help female scientists by providing affordable, high-quality childcare, which I had in Hungary. A female scientist shouldn't have to decide between a career and having a family. They can have both. And they should find a partner who supports them and understands that they too have a dream.

You seem to be very resilient when things get tough.

I wouldn't be sitting here if I hadn't learned in high school how to handle stress. I read the book The Stress of Life by Hans Selye. I later realized that it is similar to the stoic philosophy: you have to focus on what you can change. Whatever it is, if your paper or your grant gets rejected, you should always ask: "What can I do?", not what other people can do.

You went into mRNA research very early on. What inspired you originally to get into this field?

I must admit that I am not a visionary. I can get focused and persevere, that's what I can do. After graduating from university, I wanted to work in a laboratory. I loved plants and genetics, but the only open position was in a lab that worked on lipids, which is like grease. Boring. But then scientists came to the team who wanted some phospholipid mixture to make liposome. So, I started to work with them and we delivered DNA using liposome to the cell. And then, one day, the head of the RNA team walked in, he said he had an opening and that I could do my PhD there. I said okay and that's how I ended up in this field. That's why I suggest to students also: whatever is given, take it, dig in, dig deep, and learn.

In 1985, you left Hungary and went to the United States.

My position in Szeged was terminated. I first wanted to work somewhere in Europe, but because we were behind the Iron Curtain, I couldn't apply for grants in Europe. So, I had to go to the US.

There, you continued your research on mRNA. Did you anticipate the role that mRNA could play in vaccines, and if so, from when on?

I was interested in developing mRNA for therapeutic reasons and wasn't focusing on vaccines. In the 1990s, treating HIV was a big topic.

How did you get into vaccine research?

At the University of Pennsylvania, I met Drew Weissman at the copier. We were in different departments and different buildings: I was in neurosurgery, he is an immunologist. We combined our expertise in different fields and worked on mRNA vaccines. Initially, the inflammatory nature of mRNA hampered its medical use. Replacing one of the building blocks of mRNA, uridine, with pseudouridine made the mRNA non-immunogenic, more stable and highly translatable. These discoveries eventually led to the development of the COVID-19 mRNA vaccine.

You worked closely with Drew Weissman, with whom you were awarded the Noble prize. What does it take for a scientific collaboration to be successful?

We educated and respected each other. You have to be willing to listen to each other. I learned all about immunology from Drew. About the dendritic cells for example, which had only just been discovered. And he learned about RNA from me.

It is best not to dwell on decisions other people take. Normally I just look ahead and put all my energy in what I can do next.

You had to cope with the fact that you were demoted from your position at Pennsylvania University. How did you find the energy to continue your work?

Again: it is best not to dwell on decisions other people take. I was 58 years old at the time and after I lost my position, I got offered two jobs: one at Moderna, the other at Biontech. So, I started at Biontech, I had to move to Germany. It wasn't easy at first, but normally I just look ahead and put all my energy in what I can do next.

mRNA has become known by people outside of the scientific community.

Yes, and I think that it is very important that we communicate science and the scientific process to the public. We have to acknowledge what we know, but also what we don't know. Thus, people can come to the understanding of how the process works, and trust it. But there is misinformation circulating about mRNA vaccines. In Hungary, there is even a small political party that says that I am a mass murderer because of the vaccinations. The coronavirus is actually an RNA virus, I think that is also important to know. For the vaccination, we're just using a little piece. So it won't infect you, but this little piece will help to properly educate your immune system. And, of course, every medicine has side effects, they may be positive or negative. It is always about measuring out what the benefit of not getting the disease itself is in comparison to what side effect you might have.

What other applications for mRNA technology are there?

At present, more than 250 human clinical trials are ongoing. Most are focusing on vaccinations for viruses where there is no vaccination so far, like HIV, the Epstein-Barr virus, or quickly emerging diseases like monkeypox. Moderna announced a short while ago that they developed a vaccination for RSV, which is now FDA approved. There are other trials going on for diseases for which we already have vaccines. But mRNA vaccines will be much cheaper, and thus more affordable and accessible for people.

But there are also non-viral diseases like Nipah, which is a big problem in Asia. mRNA can also be used for bacterial diseases, like Lyme disease, which is caused by borrelia bacteria. Also, a malaria vaccine has already reached the human trial stage. Other applications are in cancer treatment: individualized cancer vaccines for the patient after removing the tumor. This is researched for pancreatic cancer and melanoma, for example.

What are you working on now?

I am a consultant for Biotech, where I resigned from my position in 2022. And I work at the University of Szeged and help their students with different RNA projects. I try to help people by advising, or I try to make connections for people who are working on something but don't receive an answer from people in a higher position.

How has your life changed after receiving the Nobel Prize?

Even prior to that, my life was quite hectic from 2021 onwards. In February 2021, I received the first prize. At first, I didn't even know what to say. As a scientist, you are mostly in a quiet place. After winning the first awards, it was a process, I had to come up with a message to the public. You know, I had never dreamed about receiving any kind of award. I knew that my research was good, even without awards, and that one day somebody would take on and there would be a disease which can be treated because of it. As a scientist, you imagine something nobody tried before, otherwise you wouldn't be a scientist, and you just imagine things that maybe are doable, and keep trying. And when it fails, you have already come up with many, many other solutions. But as a scientist, there is always a lot of failure, and you have to be a champion of failure.

Carole Scheidegger, Editor UZH News

Paul Karrer Lecture and Medal

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