While we may associate Messenger RNA (mRNA for short) with the COVID-19 pandemic vaccination programme, its study in fact began over 60 years ago.
Born in 1955 in rural Hungary, Katalin Karikó battled critics and scepticism for her research into mRNA for over 30 years before its role in the COVID-19 vaccination programme gained her recognition and, in 2023, a Nobel Prize in Physiology or Medicine.
In this interview, Karikó tells us about this journey and why she loves biochemistry, what it’s like to win a Nobel Prize, and how she would advise young scientists today.
Read Katalin’s book: Breaking Through: My Life in Science
Read more in Research Outreach
Image credit: Adobe Stock / OrionNimrod
Transcript:
Hello, I’m Todd. Welcome to Researchpod.
While the COVID-19 pandemic presented the world’s governments and health organisations with a vaccination challenge on a scale never experienced before, the study of Messenger RNA (mRNA for short) in fact began some 60 years ago. During this time, Katalin Karikó’s 40 years of research into mRNA proved essential in ensuring the production and distribution of affordable vaccines across the globe.
However, this was by no means an easy ride. Born in 1955 in rural Hungary, Katalin Karikó battled critics and scepticism for her research into mRNA for over 30 years before its role in the COVID-19 vaccination programme gained her recognition and, in 2023, a Nobel Prize in Physiology or Medicine.
After her move to the United States in 1985, Karikó was labelled by colleagues as ‘that crazy mRNA lady’, and her team head at Temple University even attempted to have Karikó deported to stop her taking a job at Johns Hopkins University. In this interview with our sister publication, Research Outreach, Karikó tells us why she loves biochemistry, what it’s like to win a Nobel Prize, and how she would advise young scientists today.
I grew up in a small town, so nobody was biochemist around me, but I was just like every kid, you know, wandering around in the nature and was interested to see things and understand. And I had great teachers. So eventually I was accepted at the university and the university, you know, how I end up biochemistry by chance, just that this was the only opening I could work there. is not that I have a visionary or special talent, super memory. No, none of these. Just I was curious and then I put my time in and every time, you know, whatever opportunity was given to me, then I tried to make the best out of it. That’s how it was, how I ended up biochemistry and all of this other mRNA research. I started to work with messenger RNA in 1989 when I started to work at University of Pennsylvania. And I was already working for almost 10 years when I met Drew Weissman at the Xerox machine. At that time, you know, we copied articles. If we wanted to read, we had to copy it. And that’s what we met and started to chat. And then he was interested to develop HIV vaccine, therapeutic or prophylactic. And I was telling him that I am working with mRNA and what I can do. And that’s how it started. So it is important for researchers or colleagues, you know, any organization to meet each other and talk to each other what they are doing. And he wanted to test whether messenger RNA would be good for vaccine. And that’s how it started. It was a great advantage. He used a very special cell type, human cell type, and we realized that when we delivered messenger RNA, that it responded with inflammation. And nobody understood what it was all about, why it is inflammatory. And we just were curious to understand. That’s how we discovered that we can make the RNA non-inflammatory. So everything was just a curiosity. We didn’t set up a goal that we will make a non-immunogenic mRNA. We didn’t even know that such exists, but that’s science all about. You never know what you are investigating something. You don’t know whether it is possible or not, but you believe in something and you keep trying and you fail a lot of times, but this is part of the work.
Is that the general attitude you take towards teaching, that open curiosity?
Yeah, I think that’s how it is important. let the child or the young one be curious and you have to have them to show them how to find answer for their questions and present them even more challenging things and then they can get engaged. And it is, I also find it very important to do with their own hands, to experiment. It can be a simple thing, just pick up a leaf from a tree and then just look against the sun and see things in it and understand.
That’s quite a philosophical way of engaging with the world around you. Is that also something that you’re interested in, the philosophical side to science?
Yes, it interests me that many things, why things are that way, as we can experience. I enjoy, so this is also why I emphasize every time, I enjoy the work and that’s important. If you enjoy your work, you will be good because you are doing even more work and then get more experience.
Would you be able to tell me a little bit about what it was like to win the Nobel Prize?
I have to mention, Todd, that I have, for 40 years I worked, I never get any award, not even an accepted grant or some money, you know, for my research. I was very fine with that. I did not need any university authority to tap my shoulder that I am doing a good thing. I knew it. I don’t even explain to you when three, four years ago I get the first award. I mean, For days, I could not comprehend that, oh my God, I just went around in the house, you know, and saying that. And of course, people say, oh, every scientist dreaming about getting the Nobel Prize. I was never one of them. You never set up a goal to get the prize because this is other people’s decision. And my mantra and philosophy was that I always focus and put goals that I can do something about. It’s not other people’s decision. And of course, it is a greatest honour. And I am sure that some people were happier than me that I received the award. But for me, you know, those letters I received from people who were grateful, is more touching for me to know that I was part of the process that helped others and that feeling was so much more valuable for me.
Are there any downsides to scientific awards?
At the beginning, I was wondering what I should say when, you know, they had a microphone in front of me. And, you know, in 40 years in a laboratory, you don’t have to give interviews, especially if you are a scientists who is constantly demoted, nobody really from outside world. But I found that when a prize is given, it is a spotlight on the scientists and the science also, and it is important. And I tried to find, you know, what should I talk about? And one was realizing that the public understanding of what the scientist is doing is important, and we neglected that part. And so every time when I gave an interview together with reporters, together we need to educate the public. And I also thought that it is important for the upcoming generation to realize that science is an exciting thing. It is passion and it is solving problems, and my work shouldn’t portray that, you know, I am suffering or, you know, is something. I went to work the weekend because I wanted to be there, because I had some idea that I want to try out. And I had fun. You know, you could ask my husband, you know, whenever I went, he thought that I am having just fun there because I was happy. Even I did not get those funding and other things, but I keep trying and meanwhile I learn and that’s what’s important. You are learning and enjoying and try to find solution. And then, of course, many technical problem I had to solve in the bench. I was working at the bench when I was 58 years old, every experiment I did with my own hands. But I enjoyed that. I didn’t think that is a lower level of job if you are working at the bench. money ideas I get in my head. Oh, yeah, I can do this way or that way. So it is fun. That’s what finally, you know, I found that what I should say when I receive an award. And I always acknowledge all of the fellow scientists work because they single me out. But this research is a team sport. You need everybody’s contribution. Those who were not with us anymore because they died and but they did their research and published and we learn from that. and all of the colleagues working with company or an academic institution, they all contributed. And I just felt that I am happy that I’m one of that person. And I myself never crave recognition, that they would say my name somewhere. I was fine with it, that I was not known.
Like you said, science is like a long haul, isn’t it really? Like working on something 40 plus years, you’re not guaranteed to have solid results from that by the end of it. And I was just wondering over that 40 years, how has the field changed? Have you noticed things visually changing around you or in terms of theories?
When I started to work in 89, we were happy that, you know, we can generate, we could generate a messenger RNA. And when we put in cells that we could detect that messenger RNA translated to a protein. where are we now, you know, 30 years later, is more than 250 clinical trials are ongoing where messenger RNA is used, and many of them for different vaccinations for against viruses, bacteria, or parasites, and there are treatments or as a vaccine used for treating cancer patients. There are gene therapies ongoing, so you can see that money went in, of course, and the tension was on the mRNA. So the major advantage because making mRNAs very quickly can be done and very cheap. And so even if the final product is a protein, you know, screening and doing everything is on mRNA messenger RNA level is much faster and make it the product cheaper. But eventually, you know, if the mRNA is delivered to the body, the patient will generate the product, which has the biological activity, the drug, and that is much better and much cheaper. So that many of the drugs which is right now is unaffordable as a protein as we deliver messenger RNA level, it will be affordable for many, many people. So this is also important for me that it is not a million dollar therapy.
Is that something central to a lot of your research is actually being able to use it effectively rather than work on something that’s too expensive to actually use?
Yes, yes, of course, it is for me was important. Actually, we didn’t even want it to patent it because we said we want everybody to use it. But then they said that nobody will use it. Nobody will test because, you know, when they do the clinical trial and all of this investment, And then there is not a patent to protect that investment. If it turns out good or way, you know, then nobody will start. Then we have to file a patent. Because we are naive. All scientists want to create something that helps people. But we have to understand that All of these clinical trial authors need investment and those who are risking their money because many of these ideas and therapies not work out well and they lose the money. But you need the private money to develop different products.
Talking about investing in science, have you found it’s been difficult to deal with people that are sceptical of certain ideas throughout your career?
I have to say that scientists are also always sceptical. They don’t believe and they don’t want to prove it, and that’s why they do the next experiment and the next experiment. And the advancement also in science is had by sceptic scientists who point out shortages, and then the other scientists try to prove this way or that way. So this is how it progressed, the science. And of course, there are people that who has venture capitalists can invest, and they do understand. that is risking money, and then it is no guarantee, because if it would be so sure, then, you know, already would have been done. So I think it’s natural that they act and do things. But here, you know, in the United States, it’s more likely that people are giving money in Europe. And, you know, it’s a little bit different. Coming to the United States, I was surprised that people are giving out, you know, just even as charity, the alma mater, their schools. Even those people had children. At that point, you know, in Hungary, when we left 1985, if somebody had money, they always give only to their children, not to the community.
Was it quite a shock when you moved to the US? Did it take a while to adjust?
Yes, of course. You can imagine there were no credit or no telephone, nothing, you know. And we didn’t know anybody in this country. Other people had, you know, their teachers, their classmates, their parents, relatives, and we had nobody. And the system, coming from a communist Hungary, and I remember on the first day when I went to work, they said that you have to select a bank. I said, why do I need a bank? I never had a bank. And they said, yeah, but how did you get your salary? I said, oh, it was in an envelope, all of coins, everything was there. Everything was different. Today, it is not as much difference between, let’s say somebody’s coming from Hungary, but in 1985, coming here, you know, everything was a shock for us, culturally, and of course, because that we were just not knowing anybody, and then we just have to do to survive.
Going back to a sort of scepticism, I was just wondering what it was like to communicate particularly ideas around COVID, for example. I was just wondering if you had to adapt your strategies.
Yes, of course, because realising that for a product which is FDA approved is not meaning that it is accepted by the public. You know, we need the public understanding and then acceptance by the public that the drug was developed. And somebody had to explain, you know, that messenger RNA, which is in this vaccine, is not something that we discovered, nature discovered. Actually, I had to explain that the virus itself has mRNA, messenger RNA, but it has many, many other genes which can make you sick. And we just selected one little piece of it, which can help to educate your immune system to recognize when you get infected. But, you know, the complexity, all of this biology, of how vaccine works. For example, the immune system is changing so much. Even if what I learned at the university, how our immune system recognized, let’s say, a virus, it changed. You know, I learned from Drude how today we understand this. We had to find words somehow to explain to the public all of these things and use simple words. But listen, During the COVID, we learned, people learn messenger RNA. They were, oh, did you get PCR test? You know, they can learn. They can get some ideas what it is. And so we have to have them. That’s what I realized, that we have not done enough and there is a job for us to educate the public and better understanding. You know, they feared because many people did not understand that what it is, what is happening. And, you know, scary things were surfaced on the social media that it will change your genome and two years from now everybody drops dead and you never have children and so on. And I don’t know why people are doing this, but according to the US, it was most of these were people who were selling something, another product. and they wanted the public to buy that thing from them. That’s what I learned. Making profit, you know, on people who had limited understanding was even 100 years ago, actually, in England, when it turned out that, oh, x-ray is going through the clothes. That’s what they take part of the truth. They didn’t say that, oh, the flesh also, and there will be bone. No, they just said it through clothes. And then in England, they start to protest against that. that x-rays should not be put in the binoculars at the theatres because people will see through your clothes and they see you’re naked. And then some companies started to sell x-ray resistant underwear. People are making money on people. And you can read the story about x-ray in the Nobel Prize site that this is what happened. You know, people are making money on these things and made people fearful. And then they would buy those things, you know.
I was just wondering whether there’s any advice you might give to any up-and-coming scientists as sort of a general piece of guiding advice to get into biochemistry or original research?
For the next generation, I could tell them that the most important thing, they have to enjoy what they are doing. So maybe science and research is not for them. Maybe, you know, if they like to follow instruction, they might be in the military or somewhere else, or if they want to make money, The money doesn’t really make you happy. This fulfilment feeling that you did something, even you won’t be able to see the outcome, you have to think about what one day somebody will have. So that’s what science is, and to be scientist is exciting. So my daughter was, you know, the rower, rowing going backwards, and I used to tell her that it is like science, you know, we don’t see the finish line and we don’t even know that we are going to the right direction, but, you know, we are pulling like they are doing. The young one, I also would say that what I found important is the physical and mental health. They won’t be able to proceed unless they physically and mentally healthy. So, you know, I was always exercising. I just told you this morning I swam two kilometres. Other times, you know, I run six kilometres. And even I run the marathon just to test out myself, whether I can last for 42 kilometres. And I made it four hours, 30 minutes, so anybody can beat my time. And I was like 45 years old. you don’t have to run that much. Because again, this running is something like, you know, you don’t happen that you get up in the morning, oh, today I run a marathon. No, you know, the marathon was in November, and in March, I already started to increase my distance and so on. So you have to prepare just like science. Preparation is important to reach your goal. So physically, if you don’t like to run, then you do something else, but you have to take care of your body. And the mental health, I mean, I wrote a book where I mentioned many things that how I was helped by understanding how to handle stress. Because at age 16, I read the book from János Seye, who was a Hungarian who immigrated to Canada, and he coined the word stress. And then he described that the stress can kill somebody, but not the stress itself, but how the person perceives. He also mentioned that you need stress, positive one, expectation, excitement. All of this is also stress, but it is positive, and you have to learn the negative stress to convert to positive one, and then you have to practice this. This is important mantra, but also it was already Marcus Aurelius also described that you have to focus on what you can change, what you can have an effect. And that’s what he was saying also. So not to compare yourself to others, because you always conclude that the others are not doing as hard work like you are doing, but they are advancing and they are the favourite of PI and so on, and then they get more salary and what not. But in that point, already you have to recognize you already took away your attention, what you can change. And if you focus on what you can change, then you can have fun. So many things you can do and learn. The stress, what Shaya described, is coming from that you always wanted somebody else to do something. Critics of your paper, or those people deciding for Grant, or your children, your wife, your spouse, your neighbour should be quiet. You want everybody else to do something and they are not doing. And that’s what the frustration is coming. And what he said that you have to always think, what I should do so those things would happen. So they would accept my grant or my paper and other. I have to do more work. Because if you just blame others, you cannot do anything about. You just, it is their fault. And he’s saying that you have to improve yourself. work harder and so on. So that’s what it is important. You have to find a happy life and enjoy what you are doing and do not worry about. If I would worry about all of these people who are promoted around me and get more salary and I was there all weekends and because I was focusing on my work and, you know, I was demoted and so on. And so if I would pay attention that, oh, what I am doing is not worthy, then I would change, but I could see the progress. And that’s what I also suggest to those who are doing research. And so if you don’t see the progress and you are repeating, repeating, then you should stop and change. But I could see myself the progress and I enjoy because it was a success there at the bench. Other people couldn’t see it and they talk behind me and I didn’t care. And that’s also very important. So sometimes, you know, some person’s superiority who I respected, said bad thing about me in case, and then I think about, you know, whether this is any good advice in it. And when it was not just a mean comment, then I put down the person from the pedestal. So I did not respect it anymore, because it could destroy you. So don’t let this happen. And the other thing, what I would tell the young ones, they have to believe themselves and believe that with hard work, they can achieve their goals. That’s what’s important, because you can lose your sight and you could still feel that, you know, you are not good enough or something. Can you imagine I am coming from a small town, lived with a whole family in one room and no running water, nothing, and then coming to an Ivy League school here, you know, everybody’s perfect English. I started to learn English when I was 18, so I have accent and my English is not correct many times. If I wouldn’t believe in myself that, oh, maybe I can think about something that all of these smart people here won’t think, I would just would lower the bar and would think about that, okay, maybe I can assist them or help them, but I cannot get on their level or something. So that’s what I would say to the young one. Just have fun, enjoy life, be healthy and handle the stress and don’t take seriously all of this stupid thing around you or people are talking about. One important thing was also what I learned from Cheyenne is that never carry grudge against anybody because it will poison you and the other person won’t even remember. So forget it. and move on. And if something bothers you or something you shouldn’t, you know, in the past, you shouldn’t close it down and move on. You have to think of what you have, what you can work and what you can do. Because if you think always about what you don’t have and you don’t have any effect on it, you will be so bitter. So that’s my long, long, long advice.
Yeah. Like you said, if you just highlight all the things that aren’t happening, rather than the things that actually are happening around you, then it’s quite a negative way of viewing the world. Have you found with students, the technology and social media is sort of a classic example of having to compare yourself to other people. Have you found that that’s been a big influence in some of the people that you teach?
Yeah, you know, I have to say also it is very difficult to compete with the media because some award ceremony was there, you know, for a whole week and we had to present to scientists as well as high school students. And you know that when 300 students with their telephone are in the audience, you know, you have to say something that they will not look at and sending another message to somebody sitting next to them and try to compete with that. And you know that all of this presentation there, everybody’s so wonderful, beautiful. I presented in my book also as I am. I am not a super talent. I am just the person that who is working and putting time in and get fun and enjoying and no glamour there. Although I made the glamour magazine cover, my daughter insisted that mom, you have to take that.
You are a glamour woman and you have to show that you don’t need big nails and makeup and something that you can be glamorous and you have to take that job.
Leave a Reply