Lost Women of Science Conversations: Breaking Through
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This episode is brought to you by Progressive Insurance. You chose to hit play on this podcast today. Smart choice. Make another smart choice with AutoQuote Explorer to compare rates from multiple car insurance companies all at once. Try it at Progressive.com. Progressive Casualty Insurance Company and affiliates. Not available in all states or situations. Prices vary based on how you buy. I invite you now to step forward to receive the Nobel Prize from the hands of His Majesty the King.

And first to receive the Medicine Prize is Katalin Karikó, born in Hungary, affiliated to the Sjöged University in Hungary and the University of Pennsylvania in the United States. Welcome to the latest episode in our series Lost Women of Science Conversations, where we talk to authors and artists who have discovered and celebrated female scientists in books, poetry, film, theatre and the visual arts.

My name is Deborah Unger and I'm a senior managing producer at Lost Women of Science. Today we're going to do something a bit different. In all our conversations so far, we've talked about people in the past, forgotten female scientists from the 19th and 20th centuries who are no longer with us. Our subject today is very much with us. That clip at the beginning is from the Nobel Prize ceremony in 2023.

But Dr. Catalin Carico was essentially forgotten for almost her entire career. That is, until she shared the Nobel Prize with her colleague, Dr. Drew Weissman. Now everyone knows her as the COVID vaccine lady, even if they don't quite recall her name. Her science made the production of a COVID vaccine possible in record time. And it was because she had spent her whole life working on something that nobody thought was worthwhile.

She writes about that in her memoir, Breaking Through: My Life in Science. It's a story that resonates so strongly with Lost Women of Science that our co-founder and co-host today, Katie Hafner, who's right here with me. Hello, Katie. Hello, Deborah. Sat down with Kathleen recently to have a conversation about her book.

So, Katie, let me just ask you, how did you feel talking to a lost woman who actually isn't really all that lost today? It was so wonderful to talk to a scientist who actually isn't lost. And it was inspiring to meet Kate. That's what she said I could call her. And I'd read her book. I thought it was exceptional.

It was exceptional for its rigorous science, but also it was exceptional because of how she went about doing that science. Throughout her career, she faced indifference, skepticism, and sometimes just outright dismissal of her work for years and years and years. So she was ignored, she was belittled, she was demoted. And then as if that wasn't bad enough, she was even threatened with deportation back to Hungary.

But she never gave up on her belief in the potential of something called messenger RNA.

So before we hear from Kate herself or go more deeply into the science that made the COVID vaccine possible, can you fill us in a bit about where she comes from? How did her life in science actually start? So Dr. Katalin Karikó is a Hungarian-American biochemist, and she was born in 1955 in what was then communist Hungary. She was the daughter of a bookkeeper and a butcher. The next year was the year of the Hungarian uprising, 1956.

and her father got caught up in activities that the Soviets deemed anti-communist, and he lost his job. He'd had his own business as a butcher, and then he was forced to become a day laborer. The family was poor, but it wasn't until later that Kate realized how poor they were.

She writes beautifully about her early years. And here she is describing the village. We didn't have even at the beginning television. I was first 10 years, I didn't see television. But I didn't know because my neighbors, nobody had refrigerator, nobody had running water. So, you know, that's how we live. We were very happy there. She went to a good primary school and she was always curious.

She tells a story that her parents told her about watching her father work and how she explored around her village. My parents told me that I watched my father opening the pig. I wanted to see something, what is inside. My mom and my older sister, they didn't want to see any part of it, but I was want to see what is inside. You know, I could climb the tree so quickly and I checked out the nest, whether the

eggs are there, whether the little birds are out and everything was, you know, just my curiosity. So it makes sense that she described it as a very happy time. Oh yeah, but she also talks about the difficult moments too.

And one thing about this book, Deborah, and Kate in general, is that she's not a whiner. The book is filled with life lessons that she learned from adversity. So here she is describing her experience at school and university. In elementary school, I remember that some of my classmates could remember what the teacher said exactly, and I had no special memory.

I had to study. And when I went to the university, others already could speak English. You know, I couldn't. Others already had chemistry class. They knew how to use the pipettes and durets and other equipments. And I have never seen in my life. And then I always had to kind of catch up.

extra classes I had to take to be at the same level. And, you know, I just enjoyed and doing. And finally, you know, I did more and more and studied more. And then I enjoyed studying. And you know how it's often one great teacher early in your life who could make a huge difference?

Oh, yes. I remember mine, Sister Mary Ann, my English literature teacher in high school. Oh, gosh, she was something. That's funny, Sister Mary Ann. Yeah, I had one in high school who, Mr. Langeza, I remember I liked him a lot. Anyway, Kate, she had a high school teacher and his name was Mr. Tote.

Mr. Toth actually lived across the street where my father grew up, and then he knew my father. So he was sometimes visited our home, and my father respected very much. And he was talking about, you know, that I have a talent to be

a scientist. I was like 15 years old and he said, "You could be a scientist." You could be a scientist. Yes, Kate believed she could too. She started competing in local chemistry and biology competitions and winning them.

So this, the winning of these things, allowed her to travel to a national biology competition in Budapest, and there she won third place. But just as her father had run afoul of the authorities, it looked like the same thing would happen to Kate. Oh, dear. Like father, like daughter. Mm-hmm. She tells a story about her Russian language teacher, Mr. Bitman.

I love this sense of irony she has because that was obviously not his real name, Mr. Bitter. But anyway, he felt that Kate had disrespected and disobeyed him. Her high school class was enlisted to pick corn outside of her town one day, and groups of students were given rows to complete, and because her family had cornfields, she was used to the work, and she had reached her quota before the end of the day and before all the other students.

So while she was sitting there relaxing and taking in the sun, having completed her job, Mr. Bitter came along and told her to keep going.

But she said she'd done all the work she needed to do, so she pushed back. And because of this, she wrote in her book and told me he threatened her and tried to block her from getting into university. He gave me some notification about that I am against the community and whatnot. And then eventually when I get my last exam at the high school,

After I get straight A, I was a valedictorian, he came to me and he said that he knows somebody at the university and make sure that I will be not accepted. When he said that, I was just shocked. But in retrospect, that's why I say always thanks to all of those people who try to make my life difficult. Because if he says, "I know somebody and I will arrange that you will be accepted

Maybe I will spend less time at the book during the summer, you know, now that he said that he will try to prevent me, I realized I have to be the best. And so I have to know everything. That's a terrible story. I know, right? Kind of encapsulating all that is bad about petty tyrants. But there she is again, making the best out of a situation and working even harder.

What happened next? Well, Mr. Bitter failed in his mission and Kate got into university anyway. And in the book she writes, and I'm quoting here, "I learned something important from him. Not everyone is rooting for me. Not everyone wants good things for me. Not everyone wants my contributions. Some people may even choose to hate me."

That sounds a little bit like foreshadowing. Indeed. In any case, in 1973, she starts at the University of Szeged, and this is where her fascination with messenger RNA begins. And this is where we need to pause to explain what messenger RNA actually is. Okay, I'll try to summarize passages from the book because when Kate got going talking about it, I could not keep up. So deep breath.

Essentially, messenger RNA is a messenger molecule that transports genetic information or instructions from DNA to the ribosome, which is a structure found in all cells. The messenger RNA instructions get translated to form a protein.

DNA is the blueprint of what everything in the world becomes. It stays inside the nucleus of a cell. So in order for things to happen, the DNA has to send instructions outside the nucleus. And the molecule that does this is called messenger RNA, or mRNA for short.

And the important part of the process is that the mRNA delivers its message to the ribosome where proteins are constructed. This could ultimately be used to derail a virus's ability to use the cell to replicate itself. Kate writes in her book that in the five years she was doing her undergraduate degree, genetic sciences were advancing really quickly. And what scientists knew about mRNA was developing and changing.

To place us in time, mRNA was discovered in 1961, so a good decade before she was at university. But it wouldn't be until 1984 that it was synthesized in a tube. And why is that important? Well, it's important because if you can make a messenger in a lab that tells cells what to do and you can be specific about what message it sends, then you have a way to influence what goes on inside the body.

Kate began to understand how that could be important in fighting diseases when she was working with lipids or fats in Hungary. So here's how she put it. It's a little complicated, but for her it was a real kind of aha moment. This is a process, you know, it is not like one day you just go to the lab and realize, oh, messenger RNA is important.

As another graduate, I started to work in the lipid team. Okay, just a little bit more biology instruction here. Lipids are a class of biomolecules that are insoluble in water.

Lipids are used as building blocks for the formation of cellular membranes, and they play a really important role as signaling molecules. So they're key to research in a variety of areas, including diseases and in agriculture and the food industry. Liposomes are artificial membranes that act as messengers, and they're used in the research for vaccines. Eventually, one team needed the lipids and then we delivered DNA.

And we made liposomes. And then because we have to have through the nucleic acid, through the membrane. And I was undergraduate. I didn't know. I don't, I'm not a visionary. You said, okay, I will do RNA. And then how I started my PhD studies with RNA. Okay.

And then I synthesized RNA and then we tried to use it for antiviral as a short RNA to inhibit viruses. And then I had to set up antiviral screening laboratories, you know, all of these things from scratch. So Kate was still in Hungary, now working at the Biological Research Center in Szeged, pursuing this new antiviral compound. And she writes in her book that it was her dream job.

But as all scientists know, science can be slow and tedious, and her team was not making the progress that the funders had hoped for. So the funding for her position was pulled. So it's 1984, and at this point, Kate and her husband, Bella, were new parents to a daughter named Susan.

And around that time, her father died unexpectedly. So it was a really, really difficult time for her. And she found herself thinking, "Why me?" But then she stopped herself. She remembered a book that her high school teacher, Mr. Tote, had introduced her to, and the book was called "The Stress of Life."

by Hans Schelye, and it had a huge impact on her. It still does to this day, and she brings it up in her book a lot as a guide for when she was dealing with difficult situations. She remembers in particular this one line: "Do not blame. Focus on what you can control. Transform bad stress into good stress." Good stress.

That almost sounds like an oxymoron, don't you think? Yes. But I think I understand what she's getting at, the kind of stress that helps you rise to an occasion or jump higher or run faster. Yeah, that's what I glean from it too. I mean, I'd have to read the book, which actually now I really want to. But what she learned from that was that what she needed was to find a new place to work. I was very happy in Hungary. I had my daughter, I had my little family, and then

And then I tried to find job first in Hungary, didn't even respond in my letters. Then I tried in Europe, closer to home. Everybody responded there from London, from Madrid and Montpellier. They were the one that using this short RNA for antiviral compounds. So they were similar things. They did what I was doing in Hungary, but they want me to bring the money with me. So I

I had to realize that I have to maybe go to the United States. And then I applied for a couple of place, everybody responded and the quickest was in Temple University. In a couple of months, they say that I can start. So in 1985, really quickly, Kate moved her family all the way to Philadelphia to work as a postdoc in a lab in the biochemistry department at Temple University under a boss who was doing similar work to what Kate

Kate had been doing before in Hungary, looking into this short RNA molecule that held promise as an antiviral.

So at first, Kate writes that her new boss was charismatic and helpful and picked her up from the airport and was a great host. But soon she learned that this same guy had an explosive temper. He would yell, he would slam doors, and he would berate students. And she found herself wondering, is this how things are done in America? I think most of the people, they are not black and white or bad or, you know, they are bad.

can be nice and sometimes is not. He liked me and I work very hard and that's what he wanted me to work in his lab forever. But when it looked like that might not happen, his dark side surfaced. But when I mentioned that I get the job offer from Johns Hopkins, then he got very angry.

I spent there already three years and we had many good publications in Lancet and biochemistry, good papers. In one issue of biochemistry we had three papers. But he wanted this to continue. And, you know, he threatened because he thought that I would be afraid if he said that, you know, he would deport me and I would rush back. But he didn't know me that you can reach the opposite.

That's a horrible way to treat anyone. Yes, but even facing the threat of deportation, Kate never felt sorry for herself. After the break, we'll hear how Kate manages.

Marguerite Hilferding basically created the field of psychoanalysis that Freud and Jung credited in their papers, yet no one's heard of her. Dr. Charlotte Friend discovered the Friend's leukemia virus, proving that viruses could be the cause of some types of cancers. Yvette Cauchois discovered the element astatine and should have won the Nobel Prize for that.

Is there a lost woman of science you think we should know about? You can tell us at our website, lostwomenofscience.org, and click on Contact, where you'll find our tip line. That's lostwomenofscience.org, because it takes a village to tell the stories of forgotten women in science. So before the break, we heard about Kate's situation with a boss who threatened to have her deported for leaving his lab.

In our interview, I asked Kate what she learned from that experience. You say in the book that you learned a really important lesson, which is that it was really about him and not about you, that your work and the science that you were doing was for him. Yes, yes.

And looking back, I also concluded that what I suggest to everybody, when you are terminated, you don't start to agonize on why you died.

and feel sorry for yourself. Immediately focus on what next, what I will do next. And here that was. I had no recommendation letter. Kate's boss was successful at getting her offer withdrawn from Johns Hopkins, but she had a plan. She decided to write to people who didn't like her boss and they would understand her predicament. And the plan worked? Yes and no. She got a job, but

That complicated her life. The job was in Bethesda, Maryland, and her family was in Philadelphia. So for a year, she commuted back and forth until she finally got back to Philly in 1989. And in her book, Kate pauses here, and she mentions that we've reached the part of her story that journalists have characterized as a series of unfortunate events. I'd say there have already been a series of unfortunate events.

Well, we would need a much longer podcast to get into every single incremental twist and turn that happened during Kate's time at the University of Pennsylvania, which is where she ended up. So let's summarize. In her book, she writes, "My time at Penn would span decades. These decades split into three distinct episodes involving two different departments and three very different physician partners.

My three pen episodes, for all their differences, followed a similar pattern: a series of setbacks punctuated by moments of extraordinary breakthrough. The breakthroughs, for the most part, remained almost entirely invisible. The setbacks, though, were on full display. Oh, I'm guessing, Katie, that this is the time when she experienced some of those things that you listed in the intro: being ignored, belittled, demoted,

Etc., etc. Correct. She applied for grant after grant, and she never received funding, which in academia is crucial because it's the way academics pay themselves and prove that they should actually be there. So this was a challenge for Kate, who told me she liked writing grants despite never getting any.

In the book and in our interview, she attributes a lot of this lack of interest and skepticism to the fact that mRNA is really difficult to work with. They said that I hate to work with RNA. When I run it, everything is a smear, is always degraded. I said, because your laboratory is contaminated. Your apparatus is contaminated.

But the people did not. They thought that, no, no, no, it's just the RNA is such. Penn tells her in no uncertain terms, you need to get funding or you are out. And well, she basically takes a demotion to continue her work on mRNA. That is how devoted she was to this.

She just continued to believe in its potential. And this is what she told me. So the messenger RNA is not something that the scientists created. They discovered and it is present in our cells. And that's the information for making the protein. And it seemed that if we could deliver this information to a cell, the cell will do that

protein, which we want to investigate. And it seemed like so logical. It will be good for something. And of course it was good for something, but it would still be years before Kate understood exactly what. A lot changed when she met Dr. Drew Weissman, the man she would later go on to share a Nobel Prize with.

Oh, Katie, I think I've heard this story before. It involves a photocopier, doesn't it? Yes, yes, correct. Their first meeting was a chance encounter at a copy machine at Penn in 1997. So Kate did a lot of photocopying. She liked to make copies of interesting articles from journals like Nature and Science. And there was one photocopier in particular that she sort of considered hers. And then one day...

I could see this guy who I had never seen before, and he was copying also. And so I, you know, tried to brag about a little bit that, you know, I am doing, I am here, I'm doing RNA. So she meets Drew, an immunologist who had just started his own lab at Penn. He was looking into new vaccines for infectious diseases like HIV.

Kate writes that in those days, she was a bit of a street vendor for mRNA, selling it to anyone who might want it, and Drew was a buyer. Here's how she described it in her book.

Drew and I were very different, but each of us had exactly the knowledge and skills that the other needed. I was an RNA scientist who didn't know much about immunology, and he was an immunologist without RNA experience. So let's fast forward here to Kate's next aha moment. She ends up working with Drew, and they make a pivotal discovery. Their experiments showed that mRNA was actually causing inflammation, which was bad.

It meant that it would not be able to deliver a useful message, a useful vaccine. It was inflammatory. I mean, I was shocked that I was already at that point, I was working like 10 years developing messenger RNA for therapy. So they needed to figure out why the mRNA was causing inflammation. And that took time. As a scientist, you always have something that nobody did that

And somehow you think that, oh, maybe we can do it and try this and try that and try many, many different things. And maybe something will work. But you just so believe, you know, you just...

somebody would say, "Oh, cannot be done. Even you feel stronger that you will do it." And so that's eventually how we could make messenger RNA, which was modified and was not immunogenic. And we were so elated. So in this case, they found that modified mRNA was not immunogenic, meaning it didn't work against the virus?

Correct. Unmodified mRNA created an inflammatory response, but when they modified mRNA, there was no inflammation. Kate says that this breakthrough in 2005 was the one they'd been waiting for. It was amazing news, and it meant that the world could begin developing safe mRNA therapies.

So did the world take notice this time? Did Penn finally recognize Kate and Drew for their work? Well, no. The crazy thing is that Kate and Drew's big discovery didn't get much attention at all at the time.

Okay, now fast forward eight years to 2013. She's still a researcher. It's basically a dead end. And so she finally decides to leave Penn and academia behind for the private sector. One day, she's told about a company called BioNTech. The founder, Uga Zayin, tells her about all the work they've been doing with RNA. I wanted a company who can make clinical grade.

For cancer, they injected the RNA in a patient already. They had a small clinical trial ongoing in 2013. And then when I went there and I talked to Ugur, I want to say that I would just stay if I work on nucleoside modified RNA. That's what I believed that it will be the solution. And he said, okay.

That's how I was hired. This was your moment. Your moment. Yeah, that's amazing. I mean, you must have thought, "Okay, finally, finally, finally." Yeah. I have to say that in age of 58, the old lady get two job offers, one from BioNTech and other is Moderna. Both of them is vice president, but now that looking back, old lady, still wanted.

That's how I felt. Oh, that's almost heartbreaking. Old lady still wanted. And she's worked so hard all her life because she's believed that her insight into mRNA would be useful. I know, kind of heartbreaking, but inspiring. Kate didn't see it as heartbreaking and the rest, I guess, is history. So it's early 2020.

The CEO and the founder of BioNTech was reading in January about in China this mysterious disease occurred and he realized that some people get infected and not having symptoms, he was worried that it will be spread.

And it will be all over because, you know, if there is an infectious disease and, you know, you drop dead, you are not traveling. But, you know, if you have no symptoms, you spread. And then he decided that we have to do something. That's how it happened.

So they'd been working on mRNA for vaccines for years, for flu, and then they realized it could be used for COVID. Right. You'll remember that the COVID vaccines were called the fastest vaccines ever developed. Well, that's in many ways thanks to Kate and Drew and their work on mRNA in all those years preceding.

Kate didn't develop the COVID vaccine itself, but her discoveries made its development possible. It must have been remarkable to finally get some recognition after all those years of skepticism and dismissal. You know, Kate is extremely humble, and she's careful not to take any credit for the actual making of the COVID-19 vaccine.

But when I interviewed her, she did describe the deeply emotional moment of her and Drew going to Penn to get their vaccines alongside the frontline health care workers. I arrived there and the hallway already in the other room line of people every six feet apart getting the vaccine.

And then the new chairman of neurosurgery just said that, you know, these are the people who created this vaccine. And everybody started to clapping there, you know. And then I was like, you know, that was the effect I got. Oh, my God. You know, these people, how happy that they have.

this vaccine because they go home to their family and they didn't know that how they could might infect. And those are the real heroes in my eyes, all of the healthcare workers, you know, taking care of the patient and risking their own lives. I never risk my life, you know, I just have fun in the lab. But those people were the one that are the real heroes. Well, I might beg to differ here. I really do think she is a hero.

Oh yeah, and if you think that's humility at work, when I asked her about the Nobel Prize, she said she didn't really put a whole lot of value on awards like that, but just knowing that she had helped people, real people, now that made her happy. I have to say that getting a letter from Meadowbrook Elderly Home where they described that they received a vaccine and one week later,

people started to get positive and nobody died. And then they celebrated and how happy they were. And they sent me pictures that now that the children can visit their elderly parents in that home. For me, that was more important

It more influenced me than getting any kind of prize. I have to say honestly that. People would say, "Yeah, because you get it." No, even before it, at 40 years, I didn't get anything, not even a grant. And I still could go with all of the enthusiasm, feeling that, okay, what I'm doing is important and that's what you have to. And it is fulfilling to know that, okay, I was part of it helping others. Helping others.

And after such a long and difficult journey. Katie, what's your sense of why she wrote the book? Well, for starters, to tell the story, of course, but also to let the story, I mean, this is what I think, serve as a lesson about resilience. You know, when I am invited to different places and then there is an option to talk to students, I will talk to the students.

They need some guidance. If my book helped scientists to get somebody like me,

just through the book, be a cheerleader for them. You know, come on, you can do it. They feel that they work for it and then they will be very proud and you need that. You know, we all need cheerleaders like Kate. Yeah, I mean, you can say that again. And you know, at the very beginning of our conversation, I asked her about a particular thing she wrote in the book about being a scientist.

One thing that you start out with is that you write, to understand my story, you must understand that what may look like stillness is sometimes the complete opposite. What did you mean by that?

You know, I have to mention that writing this book was never in my mind. And when I was writing, I thought that everything is so boring for an outsider. Scientists, what they are doing is just nothing. They just sit there, you know, maybe something they are doing with their hands. And, you know, there is no drama to show them the excitement, the process of discovery. You know, it is very difficult. How can I explain that?

An outsider can see me as unsuccessful for years, but I myself, I felt that I am very successful. Every day I solved technical problems there and many questions were there and I could answer some. And then, of course, I get more questions with the experiments. And it was full of excitement. How many times I told myself, oh, I wish I would be a weak person.

So by that time I would know the outcome or a month older, you know, I always ask to be older. It is so many excitement there, but it is difficult to present it. And that's what I thought that somehow I have to explain it. And the book does exactly that. And thank you, Katie, for sharing your conversation with Kate with us. My pleasure.

This has been Lost Women of Science Conversations. Dr. Katalin Kariko's book, Breaking Through My Life in Science, is now out in paperback.

This episode was hosted by me, Deborah Unger. And me, Katie Hafner. Gabriela Saldivia was our producer and our sound engineer for this episode. Thanks to my co-executive producer, Amy Scharf, and program manager, Eowyn Bertner. Lexi Attia was our fact checker, Lizzy Yunin composes all our music, and Lily Weir designed our art.

We had help with the science from Dr. Ellen Lyon. Thanks also to Jeff DelVisio at our publishing partner, Scientific American. Lost Women of Science is funded in part by the Alfred P. Sloan Foundation and the Ann Wojcicki Foundation. We're distributed by PRX.

If you've enjoyed this conversation, please go to our website, lostwomenofscience.org, and subscribe so you never miss an episode. That's lostwomenofscience.org. Oh, and don't forget to click on that donate button. And wherever you listen to your podcasts, please share it and give us a rating. See you next time.

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