Chemistry AND Reinventing Progress: Nobel Prize laureate Katalin Karikó on the mRNA covid vaccine

Professor Katalin Karikó’s research led to the creation of the messenger RNA Covid-19 vaccine, which has saved so many lives and helped curb the impact of the pandemic. She has quite literally changed the world! Ilham sits down with Professor Karikó to talk about her invaluable research; her passion for science; her upbringing in Hungary; women in science, technology, engineering and math (STEM) careers; her advice for young scientists, and much more

1:42 - Upbringing in Hungary
5:26 - Move to the United States
7:43 - Development of the Covid-19 vaccine
11:23 - mRNA technology as a potential solution for other diseases
13:49 - Receiving the covid-19 vaccine - the results of her work
15:19 - Story of resilience and determination amid challenges
21:15 - Adjusting to almost overnight fame
22:50 - Educating the public
24:06 - Championing women scientists
24:44 - Role models
28:28 - Advice to young scientists

Professor Katalin Karikó is an adjunct professor at the University of Pennsylvania, where she worked for 24 years before joining BioNTech SE in 2013 as a senior VP. She is also professor at University of Szeged, Hungary from where she received her PhD in biochemistry in 1982. For decades, her research has focused on RNA-mediated mechanisms with the ultimate goal of developing mRNA for protein therapy. She investigated RNA-mediated immune activation and together with Drew Weissman discovered that nucleoside modifications suppress the immunogenicity of RNA, which widened the therapeutic potentials of mRNA. Her patent, co-invented with Drew Weissman, was used to create the FDA-approved covid-19 mRNA vaccines by BioNTech/Pfizer and Moderna. 

Her groundbreaking contribution was to use chemistry to modify the mRNA so that it wouldn't be rejected by the immune system. In the future, her research could be applied to many other diseases such as cancer, influenza, malaria, tuberculosis, and so much more. 

Professor Karikó has won numerous awards for her incredible work, including the Solvay Prize. 

For additional details about the podcast, show notes, and access to resources mentioned during the show, please visit https://www.syensqo.com/en/podcast

Transcript

Chemistry AND Reinventing Progress with Professor Katalin Karikó

Ilham Kadri: Today, I'm thrilled to be speaking with professor Katalin Karikó, a dear friend and a brilliant scientist. Professor Karikó's research led to the creation of the messenger RNA Covid-19 vaccines, which has saved so many lives and helped curb the impacts of the pandemic. Her groundbreaking contribution was to use chemistry to modify the mRNA so that it wouldn't be rejected by the immune system. And she has quite literally changed the world. I had the great pleasure of meeting Kati when she was chosen as the winner of the Solvay Prize for her incredible achievement in the field of chemistry, and it was so well deserved. So thank you, thank you Kati so much for joining me today.

Katalin Karikó: Thank you Ilham for inviting me. It was such a wonderful celebration in March at Solvay, me and my daughter will remember  that forever.

Upbringing in Hungary

Ilham Kadri: And we will remember you forever. I'll tell you, our employees, our audience, our key stakeholders. So Kati, most people know about your scientific achievement now, but many people may not know your backstory and what led you on the path to your career. Can you tell us a bit about your upbringing in Hungary and what sparked your passion for science and chemistry?

Katalin Karikó: I grew up in a small town, 10,000 people lived there in Hungary. And it was a very simple household, my father was a butcher and my mother was a bookkeeper. 

Ilham Kadri: Yeah

Katalin Karikó: And also of course she was happy running the house, and I had an older sister. She's three years older than me. And she was very good in school, and so when I entered school, you know, everybody, the teachers expected that I will be a good student. Well, and our parents of course encouraged us to study well. And I don't remember, but I was told that when I was five years old, I watched my father opening a pig to, you know, because he was butcher and I want to see what is inside. My sister, who was, as I mentioned, was older, she ran away and she was not interested actually, eventually she ended up, becoming an economist, got a PhD in Economics, but that you know, she was not interested what is inside, but I don't remember it, but I was curious, and then the teachers were excellent in elementary school and high school. And so I just stayed curious and then wanted to learn more and successfully could enter to the university, which was a very big deal. It was very, very difficult to get to the University of Szeged. And I went there because there is a Biological Resource Center there, and when I was a student, I started to go there and I tried to do some kind of work. And first I ended up in the lipid lab, which for most of the people considered a very boring thing. But because at that time, I am talking about the seventies, mid-seventies, actually, genetics was the most important topic.

Ilham Kadri: Hmm 

Katalin Karikó: It’s kind of a boring thing, but this is where it happened that we formulated and put plasma, DNA, lipid wrapping and delivered to the cells. And it was in the end of the 70s and it was voila, we delivered this molecule inside the cell, and then the cell expressed the endocytic protein. And it was for me was very important. Because I keep thinking about this first experiment and that's why I suggest for students that doesn't matter what you do, you know? You just have to make your hands wet, try something. And of course, how I started to work in 1978 with RNA, it was just by chance, the head of the RNA team walked in one day to the lipid team. And then my supervisor at the lipid team said that Kati wants to make a PhD. And then the next time I already went to the RNA team. So everything was by chance. I did not come up with the idea to work with RNA but of course, when I started to work there, I found it very exciting and interesting molecules. And so I liked to work with RNA. Those were, we made chemically enzymatically, short RNA.

Move to the United States

Ilham Kadri: And it's amazing, Kati, you talk about curiosity, right? And the importance of being curious, which is important for scientists, for our researchers in the industry these days, but also for leadership. And I remember you told me when we met a few months ago, that experiments do not fail only our expectations fail, which since then I've been stealing it from you, which was so inspiring. And one thing that really struck me. And you are in Hungary today, right? That's what you told me, right? Visiting your sister. I remember when you were speaking about you leaving Hungary to go to the US and that back then, you could only take a hundred dollars out of the country or euros. I don't know what it was at that time, so you had to get creative. Can you tell us more about that?

Katalin Karikó: Yes, so in 1985, you know, when you get a job offer from a Western country, only your family member were allowed $50 to take. So my daughter who was two and a half years old, and my husband could take $50 / $50 dollars you know, from the bank. But me, you know, getting the job offer. They said, you know, I have to get money from whoever offered. Of course, why the American University would pay me in advance. Of course this wouldn't happen. And so we sold our Russian made car and then we had a student from Arab countries at the medical school, and then they had currency that I could exchange. And finally, I think it was 800 pounds, which I could manage to convert, and we had to hide it because it was illegal. And finally, we, I opened up, my daughter had a teddy bear get from my mother. I opened up the back and then I put the money, wrapped it up and we were watching my daughter and, you know, with the Teddy bear and actually, so she was, she was the smuggler because, you know, nobody found nobody was looking for, know, that extra currency.

Development of the Covid-19 vaccine 

Ilham Kadri: I’m curious. Do you have still the teddy bear somewhere? Do you have it? Yeah, okay. So. I would love to see the teddy bear. Now, let's talk about your scientific breakthrough, actually the messenger RNA technology, and what is interesting, is sometimes timing can be everything, right, Kati? And imagine we are in January 2020, right? We all lived this right painfully in our ways from China to Europe to the US. And it just happened to be the case that you were already working on I think a flu vaccine, if I remember, well, and then the coronavirus hits and everything came together quickly. How come a vaccine can be developed in nine months, Kati, where, you know, people were telling us you need years. So can you tell us more about that?

Katalin Karikó: Of course. So the development of messenger RNA for therapeutic application, for vaccine application, it was decades, several decades, and the scientist painstakingly learned more and more and improved the RNA quality in a way that more protein could be produced from the RNA. We learned how to clean it, how to make it pure. We also learned what kind of material we can wrap it up so it can deliver easily. Because this RNA had to be protected when it is injected into the body. So that was also a lot of development there. If we don't have this technology, you know, we had it 20 years, but we wouldn't have, then everybody would wait to start to make a vaccine to receive a package from Wuhan, which would contain some kind of viral material. We didn't need that because we just needed the information. So when information became public in 2020, January 12, everybody could read it and they could proceed without getting material in their hands because everybody could order or you know, synthesize the genes and started with their procedure, which was you know, their favorite one, whether they made protein, whether they made DNA or RNA based vaccines or incorporated some kind of viruses, so different kind of viral vaccine technology existed at that point. And everybody could proceed because they already had the information and that was sufficient. 

Ilham Kadri: Mm-hmm

Katalin Karikó: We already learned from each other, we've learned how to work together. And by the end of 2019, we were ready to proceed to the human trial with you know, the influenza against the influenza. But of course the technology is so simple and so straightforward, you just have to change the template from which you copy the RNA. So that changing the template was efficient to switch from influenza to the new pandemic candidate, this coronavirus. And so this timing was perfect and if it would would happen earlier, of course we would have much more difficulties, but by 2020, you know, we could act all of the animal experiments were done already with the vaccine, the formulation was identical, which was, you know, the composition of the nucleic acid was identical from the four basic nucleotide. Everything was identical, which we already tested out for influenza in animals, even in monkeys. So it was very safe. 

mRNA technology as a potential solution for other diseases

Ilham Kadri: So, yeah, so it's amazing, you know, you were working and you have the framework and as soon as probably you had the sequencing, right of this coronavirus, you could just mimic and bring it to the influenza framework. But then this mRNA technology kit can be applied to many other diseases. Can we dream about curing cancer, malaria, tuberculosis, right? What is the next big thing for mRNA?

Katalin Karikó: You might be aware that many of the vaccines are you know, in advanced stage actually Moderna already has a phase three trial, the CRV and RSV virus already injected subject at phase three trial, and they also have, you know, HIV and of course biotech also the influenza, and others in human trial. So in human trial and we also can see some is advancing towards human trial, like herpes simplex II for example and not just viruses, but also for parasites like malaria, you mentioned.  A couple of years ago, we have seen already data animal studies data. The difficulties, of course there is that you know, the microbes has much more genome and you have to identify what you had to fight. What the RNA should code to have very effective vaccines. And this is you know, is ongoing and also for tuberculosis, which is a intracellular bacteria and identifying what are the critical elements that we should code by the mRNA to get a very effective vaccine. So these are ongoing, but you could see that some vaccines, we already have tried to replace it with cheaper vaccine because the RNA is cheap and so it is much of the equalizer, many drug, which was unaffordable for people with the mRNA based materials, not just for vaccine, but for passive immunization or therapeutic protein. Those are very expensive. But if you deliver the messenger mRNA for the protein, it will be affordable for everybody.

Receiving the covid-19 vaccine - the results of her work 

Ilham Kadri: Yeah. So maybe before we switch gears to your journey, right? And some of the attributes I'm keen to share with our audience, those attributes, you know, I talked about curiosity, risk taking there are more in the journeys of Kati. What was it like the day you received a vaccine that was the result of your research, Kati? 

Katalin Karikó: It was special. I thought about that. I am, you know, I know so much about what is inside that wire because you know, we worked very hard, optimizing different elements of the RNA and the cap structure and other things. And of course, it was just so unbelievable that it happened. We worked on something and here I am, and I am benefiting by protecting myself. And those people who were around, healthcare workers waiting for another room for the vaccine and they're cheering us and clapping and being so happy, you know, they could finally breathe and go home, you know, with knowing that they are not infecting their families or something is because they are the real heroes, you know? We all know because they went day after day for a whole year and they treated their patients and risking their lives.

Story of resilience and determination amid challenges

Ilham Kadri: Yeah absolutely, Kati. And it's good to pause and applaud, recognize our invisible heroes. You're right. But yes, I think there is another attribute, which is humility from your end. We all cheer you by the way. And coming back to your story, I mean it's an incredible, you know, story of resilience and determination you faced throughout the journey, many challenges right in your career. But I know you persevered and went on to make one of the most important scientific discoveries that has and will continue to have such profound impact on us, on healthcare. Can you tell us a bit of the setbacks and explain to our listeners what was like, and how did you stay resilient and never give up?

Katalin Karikó: Yes, actually the Sunday Le Monde has inside article about, you know, I wouldn't be here if - and I followed - if I wouldn't be terminated in my position several times. So with that, what I want to say that is never the decision what other may you know, that you have to leave your position, but what you will do. So the power is in your hands and instead of you know, complaining and saying that why I am terminated because probably I can look around and find other people who might, you know, produce less, and so I suggest everybody do not spend any time, you know, agonizing, licking their wound, that why they are terminated. They have to focus all that energy on what's next and what to do now. And be full of optimism that they are able to do that. And so I was terminated in my position in Hungary and I never wanted to leave and go to the United States. I was, you know, it was a sleepless night when I realized that I cannot stay in Europe, where I applied for three positions and everybody wanted me to bring them stipend or some kind of scholarship with me and come to the lab. And I had to go to so far away that I never wanted to go there. So sometimes, you know, you're in a position and then you just have to do it. And then also, even in the United States, I lost my position and simply just, I was kicked out. I really, Ilham, I said loudly that I am in the United States of America. Where else if not here, I can do what I wanted to do, you know? And then I just encourage myself that doesn't matter, you know, that I am not faculty anymore. And again you know, when finally I was ready to leave the university, we had the patent and we established with my colleague and company, we had our patent, but finally the university decided not to give it to us. So again you know, that was more painful. And again, when I was 58 years old and finally, you know, shown the door that you know, I was not successfully getting money, grant money. Again I understand because there in the United States, if you don't have money, you don't have space. I don't have any grudge against any of these colleagues. You know, they were in a position and then they followed the rules. So again, you know, I wouldn't go, but again, at 58 I was told that, you know, it's time to go. And then I decided to go to BioNTech again at a conference that other people wouldn't go, wouldn't even know about it because they didn't have a website. They just have the faith that okay. I go there and start, and we all work together and it was a very wonderful time.

Ilham Kadri: Yeah, an amazing story. A few months ago, Kati, I had Nobel prize winners, Stephen Chu and Ben Feringa, you met at Solvay, our founder's home, right in Brussels, who were on the jury by the way to choose you as the winner of the Solvay prize. And we had such fascinating discussion about failure in scientific research. And am I saying our modern word failure is a bad word while in science and with my background as well. I mean, it's something you are not ashamed about, right? And I remember Steven Chiu mentioning that in scientific research, you had to go from failure to failure to failure with continued enthusiasm, which I thought was a great way of putting it. So yeah, I think failure in science and what it leads, but also in your journey as a professional, as you said, right? But it looks like you didn't get frustrated and you were just focusing on your journey, right? And you know, just pursue your dreams, right, Kati?

Katalin Karikó: You have to see the progress. And that was important. I could see the protein translation getting better, the RNA is more effective and. I could see it. Of course, you couldn't see that I am advancing because many time I said, you know, my career was like this Hungarian Czárdás, you know, there is not forward that it is always left and right, and left and right. Nothing forward, but things happening. So that's what I'm saying. Also for these young ones, they don't try to, you know, please somebody, the supervisor, and don't feel that you work for the company or the university. Now you have to focus on that. You try to understand part of nature and this would be your primary goal, not your advancement in career. Then you wouldn't be disappointed if you could see somebody's publishing what you are working on, because you say, okay, they have me in to understand better. 

Adjusting to almost overnight fame

Ilham Kadri: Yeah, what's another lesson it's about inside out, right? And how to make, you know your journey. So I mean, your life has completely changed Kati, right? I mean, you've gotten more awards than we can probably count by now, including I'm proud to say the Solvay prize, right? But what has it been like adjusting to this almost overnight fame? Are you enjoying it? Do you miss the lab? Do you miss, you know, the bench? Where are you?

Katalin Karikó: Yes. I, most of the thing I miss is that when I can see a paper and I can see the title and I can skip a little bit to the abstract and I have the feeling that I just do not have time to read, and I think that is something important. So I decided that next year, 2023, I go back to science. I have to do this because there are so many things we need to solve. And then I accumulated so much knowledge that I can have in, and listen, Ilham, I never dream about that my name will be put forward. I never wanted the personal recognition. Many times I thought that oh, hundred years from now, nobody will remember who we are. It's not important, you know? Focusing on something, some project, which really makes difference in somebody's life, treat some disease. That's what we have to focus on. And then now that I became known and in the spotlight, I tried to find some voice, what should I do? 

Educating the public 

Katalin Karikó: And the one thing I tried to, you know, help with the many reporters to educate. And now today with you to educate the public, because I realized that some resistance against the vaccines is coming, that we were not doing good job to educate the public. And we learned that they can learn, they can talk about mRNA, they talk about PCR, and other things. They have some idea about. And we should rely on that. They should know more and understand. Because if they feel only the unknown and if they would understand better, then they would you know, embrace it and they would understand, and champion the scientists. I really was shocked when I asked people, you know, to name scientists and they name people who are not with us anymore. And they cannot name a contemporary person who is a scientist. They are taking medicine which is saving their lives. And then they don't know, they know the football player, the actress' name, but who is the person who just discovered and came up with this checkpoint inhibitor? James Allison, and then saved my life. And then I don't even know their name. So that's, who's responsible for it?

Championing women scientists 

Katalin Karikó: So I try to champion the science and champion the women. So I also try to have, you know, more attention will be on women than their importance because you know, we are differently thinking and we are multitasking, and we are just as valuable for science, and there are so many things which, you know, people are asking me, you know, how I could work and be a parent and raising a child and science. And you never ask this in a fellow male scientist. 

Role models 

Ilham Kadri: Absolutely, and it's so true. And I bet you will be remembered in a hundred years, you know? I think you are becoming, I know you didn't want it and you don't wake up every morning thinking you are a role model, but you are an incredible role model for so many girls and women in science, technology engineering, and math. And this is so important considering we desperately need more women to take this path. When I was a young girl, my role model was Marie Curie. I wanted to be Marie Curie, another one, inventing things. I didn't know how to do it because just loved STEM. And she was the only woman I knew of. So tell me, I'm curious, did you have role models, who were your role models? Who inspired you and what are your thoughts? I think you start talking about diversity, equality and inclusion in STEM careers? 

Katalin Karikó: I mean, when I was in school, I remember that my high school Biology teacher, whenever we talked, he already knew so much about it and I wanted to be like him to know everything about everything. And you know, of course my parents who work very hard, you know, and then also that I learned from them so that, um, working hard is part of our life. And then, you know, learning constantly, that when I went to the university, others could speak English, you know, at 18, I couldn't say you can hear the heavy accent. I couldn't speak anything. And then others already had chemistry. And then what meant that I could see the enormous progress I have to catch up. Meanwhile, others maybe laid back and you know, more complacency was there because they already so much advanced. And by the time they woke up, they realized maybe this, I already took the English exam. I took, you know, I advanced and I couldn't not ever lay back and think because the more I learned, the more I realized that I have knowledge so little, I have to learn that, and that, many times I was just shaken that, Oh my God, you know, I took 10 years doing something. And I didn't know that, didn't know that. And then spent whole weekend just studying, studying, and it was fun. That's what I have to emphasize for the little girls also, because people said, oh, you struggle, come on. I was so happy in the lab. I was in the chair, running the sample, figuring all things, and it was fun, it was, you know, yes, you know, demotion and send me away. Yeah it was, but always came up with a solution what to do next and get back to where I am full control, and it is fun to like solving problems. And even you ask the questions, you try to find the answer, you do an experiment and more, more techniques, you learn the more knowledge, you have, you know, that's just a delight to work and we get paid for it. So it is, I want see that part, you know, not from what right now can be seen outside that somebody's working day and night. And I went there because I wanted more as to be, not that I will be promoted. I went there because I came a new idea what to do, and that's why I went the weekends. Nobody forced me. nobody. If I don't go, that's fine. You know, I wouldn't get kicked out from there. It is just, I want it, because that's where I have fun and enjoyed. And I have a wonderful husband who did not complain about it and who fixed up the equipment and so on. So this is a fun thing to do, and you spent all your life working. So why not to spend it with something that you are enjoying?

Advice to young scientists 

Ilham Kadri: I mean, I know that lots of young scientists will tune to this podcast to listen to you. So is there any other advices, would you give to this scientist, right, who are starting out?

Katalin Karikó: Many young scientists get disappointed because they are comparing themselves with others and they can see and conclude that, oh, they are better and these others are, you know, maybe getting more advancement and promotion and more money and whatnot. And they get disappointed and they just leave because I'm telling, you know, do not pay attention on those things you cannot change and you cannot change that. Some people advancing and they are already doctorate or whatnot, you know, and I can figure I am 40 years old. I am just demoted. Doesn't matter. You are getting better and better, better if you keep learning, understanding, doing more experiments. And of course you have to enjoy it. If you do not enjoy the laboratory work and thinking about reading about science, then you have to go to another profession. And if you like to be in the spotlight, you have to be an actor, actress, or some other performing art or you know, to do something. When you have criticism, you have to listen, do not take it personal. Somebody already spent time to tell certain things to you. Listen, think about what you should do. I, I grant when I was rejected, you know, my grant. Not saying that, oh, those people are stupid. Do not understand, even if I would say that. Okay. They didn't didn't understand because I did not write well or something. So focus on that. Okay. How can I make it better? Actually I just got an honorary doctorate. And when I thanked all of the people who have on my journey, I also said I have all of those people who try to make my life more difficult without that I wouldn't be here. They make me, you know, more resilient. So you will learn from everything. If somebody treats you badly, you learn from it that you won't do this to another person, you learn always whether good thing or bad, but learning is part of it. That's what I can tell the young ones.

Ilham Kadri: And I always say feedback is a gift. So take it as a gift, right? And you know, it's so profound and resonates with, with me and with us. Well, thank you so much for joining me, Kati. Not only you are brilliant scientists, but frankly, and more importantly, you are a beautiful soul and, and I got to see you even, even in private setting and such an incredible inspiration for many young woman and not as young woman like me, by the way. So I have Marie Curie and Katalin Karikó by now as a role model. So this was a fascinating conversation and I can't wait to see what's next for you, Kati. Thank you.

Katalin Karikó: Oh, thank you very much.