The Daily - The Unlikely Pioneer Behind mRNA Vaccines

Episode Date: June 10, 2021

When she was at graduate school in the 1970s, Dr. Katalin Kariko learned about something that would become a career-defining obsession: mRNA.She believed in the potential of the molecule, but for decades ran up against institutional roadblocks. Then, the coronavirus hit and her obsession would help shield millions from a once-in-a-century pandemic. Today, a conversation with Dr. Kariko about her journey. Guest: Gina Kolata, a reporter covering science and medicine for The New York Times. Sign up here to get The Daily in your inbox each morning. And for an exclusive look at how the biggest stories on our show come together, subscribe to our newsletter. Background reading: Collaborating with devoted colleagues, Dr. Kariko laid the groundwork for the mRNA vaccines turning the tide of the pandemic.For more information on today’s episode, visit nytimes.com/thedaily. Transcripts of each episode will be made available by the next workday. 

From The New York Times, I'm Michael Barbaro. This is The Daily. Today. As vaccines against COVID-19 bring the worst of a pandemic to an end for millions of people, my colleague, Gina Collada, tells the improbable story of a scientist who played a crucial role in creating those vaccines and the decades of doubt, disinterest, and dismissal she had to overcome to do so. It's Thursday, June 10th. Gina, tell me about this scientist that you have been reporting on.

Well, you know, she is one of the rare people who not only had a really interesting, great idea, which sounded out of the realm of possibility, but never gave up. My name is Katalin Kariko. I am a biochemist. Her name is Katalin Kariko, but she goes by Katie. And once I started to talk to her, I wanted to hear more and more and more. So could you start by telling me where you grew up? I grew up in a small Hungarian town called Kisul Salas. There are 10,000 people lives there.

She grew up in a little town in Hungary, in communist Hungary. I grew up in a very simple household. We had an adobe house with a reed roof, and we didn't have running waters. We didn't have refrigerators or television, but I didn't know that we don't have this because none of our neighbors had one, so everybody was the same. Her father was a butcher, and her mother was a bookkeeper, but she was always interested in science. What made you think about science? You know, did you have a teacher? Was there anything in particular that made you think of science? When I was a child, my father was a butcher,

and I was always seeing how he cut up the pig, and I was watching. Meanwhile, my sister, older sister, run in the house and she didn't want to see any part of it. So, and of course, when I was a student, you know, I had a wonderful teachers and as a result of it, actually on eighth grade, I was the third in the country in biology. There was a petition. So I knew that I would be a biologist. And so Katie goes on to study biology in college. And then she goes to graduate school. And while she's in grad school, she learns about something that really grabs her attention.

A molecule that scientists had just recently discovered. That molecule was called messenger RNA. And the reason they called it the messenger was it was the messenger between the DNA in cells, which has all the instructions, like a blueprint, and the rest of the cell, which has to do something with that blueprint. So there's this little messenger that goes from the DNA and says, here are the instructions, and then it disappears. And what exactly was so interesting to her about this little messenger molecule? Well, the fact that this molecule told cells what to do made Katie think that mRNA, messenger RNA, held infinite potential. And so what fascinated her was that if she could get

her hands on the messenger, she could give the cells a new set of instructions to do what she wanted them to do. She could change the message. And, you know, I was like 21, two years old, and I said, oh my God, that's so great. And in her mind, if she could potentially change the message, what could happen? If you could change the message, you could tell a cell to make anything you wanted. Let's say you wanted a cell to make insulin for somebody with diabetes. You could give it a message saying, make insulin. And it would, briefly, not forever. But you will make some insulin. So if you could change the message, you would be in control of the cell in a way nobody had ever done before.

And how realistic is that line of thinking? Well, this is the late 1970s. And at the time, it was like a joke. In fact, while she was working on her PhD, she worked in a lab in Hungary trying to research mRNA. But the thing is, scientists didn't know how to make it. They didn't know how to make the actual message. When the first day I came to the lab, I learned, you know, different things about messenger RNA, but I couldn't make messenger RNA because there were no tools for that. And even if you could figure out a way to make it and get it into a cell, scientists didn't think you could survive long enough inside the cell to do anything. Nobel Prize winner who get for RNA acknowledges that he never thought that RNA would be ever a medicine.

So just as Katie got kind of possessed by this idea of using messenger RNA, her lab ran out of money. And this was my dream place, this research center. And then I was so happy in Hungary and we lost financial support and I lost my job. And this was my... He looked around and there really was nothing for her in Hungary. So she made this very difficult, momentous decision that she had to leave the country if she was going to pursue her idea and stay as a scientist.

I felt that it is so, so important. I always felt whatever I was doing, it is so important. And, you know, people's life will depend on that I have to do it. And she went to the United States to become a scientist there. Her husband and her two-year-old daughter were going to come with her. And of course, I was shocked when I was just thinking about that. Oh, my God, you know, I have to buy food for dollars and I will be in America. And we didn't have credit cards. We didn't have telephone, iPhone. There is no, you know, we are in 1985. At that time in Hungary, there's only so much money you could take out of the country. So if they wanted to get to the United States and have any money at all, they had to smuggle it.

So we sold the car and we get 900 pounds for it. And I put into my daughter's little teddy bear and we gave it to her and kept our eyes on her and the bear. And anyway, so we arrived there lucky to Philadelphia. And the next day I went to work. They land in the United States and she ends up in Philadelphia at a low level postdoctoral position. I started my salary was 17,000 that, yeah, we didn't starve. We had food. And not long after that, she got a low-level job at the University of Pennsylvania. There, she wanted to pursue her idea of messenger RNA. And how does that go? Well, remember back in Hungary, she couldn't even make messenger RNA.

But by this point, the science had advanced enough that she and other scientists could, in fact, make mRNA. And so Katie's idea was, let's make the mRNA, put it into a cell, and see if we can instruct the cell to make something it never would have made before. So Katie and the senior scientists had experiments set up. And if they worked, they would know because they had a machine called a gamma counter that would detect whether the protein that they wanted the cells to make was there. So they were standing in this little tiny room hovering over this machine. We were standing there in front of the gamma counter that we tried to see what was the result. Is it functional?

And the data started pouring out. Oh my God, yes, it was functional. They did it. And we were like elated there. They had made a cell produce something it would never have made normally. Hmm. When you learned this about the mRNA, did you celebrate? What did you do?

Did you just say, oh, wow, it worked? Or did you say, oh, let's break open the champagne? I have to tell you that I have never kept a champagne bottle in my refrigerator. I know scientists who did. I did not. And what does this breakthrough mean to her? What is now going to be possible that perhaps wasn't before?

It tells her that her dream, that she could have a cell produce anything she wanted, a drug, anything, was now within reach. Oh my God, I felt immediately that it's very important. I felt like I can do anything.

It will be good for somebody, something. We'll be right back. So Gina, after Dr. O'Carco has this initial victory, what happens next? She suffered a series of major setbacks, kind of almost reminiscent of what happened in Hungary. So right after this breakthrough, where she suddenly saw that things could work, the man that she was working with left Penn. And now she had no permanent position. She had to find another lab that would take her in.

Then she found another lab, starts working with someone there who was very enthusiastic about her work. He left. Now here she is. She knew that it would be incredibly important to get a grant, to get some money to do the research. And she tried. And she wrote grant proposals. some money to do the research. And she tried. I mean, she wrote grant proposals. I remember the whole New Year's Eve I spent because the deadline was January 6th. And even my sister was visiting me and I told her that I'm sorry, I need that money. And I learned that

seven applications arrived and six slots were there. And it was mine was the one. Right, of course. Oh, my gosh. In one case, they were going to award grants to six applicants. Seven people sent in applications. One was not funded. And that one that was not funded was hers. So I tried to reach out

also other people on campus. She tried repeatedly to find people who would fund her and work with her. I met people like I went to a lecture and somebody sit next to me and we agreed that okay we will talk and then we follow up and then learning that I'm not funded scientist and then later call me back that, you know, some other things come up and they cancel the meeting. But all too often when they found out her low level position, the fact that she had no grants and that she had no publications, they walked away. Yeah. So that was the kind of hurtful little bit.

But I tried to shake off all of these things because not to let to get define me. So I said, OK. And for most people, you think you say, OK, I get the message. I don't have a permanent position. I'm not getting any grants. Can't publish any papers. I have nowhere to go. I'm not getting any grants. Can't publish any papers. I have nowhere to go. I'm going to leave science.

There's got to be something else I can do. But not Katie. Uncertainty is a double-edged sword because it is, you know, makes you maybe nervous or in the edge if you are that type of person, or maybe encouraging you, you know, because if somebody would have a permanent position, wouldn't be pushed that hard. True, it's a motivator. You have to keep going. That's true. Wow. She was not going to let setback after setback after setback drive her out of science. So when does the tide start to turn for her? Actually, it was a weird coincidence.

You know, it was in 1998. Now I was almost 10 years, I was doing this messenger RNA, making better and better. She happened to be standing at a Xerox machine and somebody else came by. I have to tell you, from 2002, I never used anything, copy, paper, nothing. Everything is digital. But luckily, it was 98 and I was still Xeroxing and I went there and Drew Weissman was there. I didn't know who he is. His name was Andrew Weissman, Drew. And she and Drew struck up a conversation.

Mm-hmm. Drew Weissman, Drew. And she and Drew struck up a conversation. And then I just introduced myself, who I am, and I work here, and I work with RNA. And Drew said that he came using DNA to try to make vaccine. And because I was always offering other scientists also during the years, I always kind of the pusher for the RNA. So I offered him also that, yeah, I can make an RNA for you. And so he said, okay, okay. She can do it? That's interesting.

He didn't say, do you have a grant or anything? No, no. Actually, Drew is, you know, open, very open-minded. And so Dr. Weissman invited her to join his lab. And the two of them started working side by side, even though he had the grant, he had the prestige, he had the lab, and they worked side by side to try to make mRNA do what they wanted it to do inside of a living animal. No longer just in a petri dish. That's right. Now they wanted to get it into an animal and have that animal make the protein that they told it to make. So a real-world experiment of this theory that she has now been nurturing for years.

That's correct, yes. And so how does that go? Well, it didn't start out too well. In fact, it started out pretty badly. They had their mRNA. They injected it into mice mice and the mice got really sick. They lose their appetite. Their fur looks bad. They look just so horrible. So the first thing she did was to ask a question. Why are these mice getting sick? After all, every cell in my

body, every cell in everybody's body, every cell in the mouse's body is making mRNA all the time. And we aren't getting sick. And so what was her solution to this problem? She and Drew Weissman discovered, after another few experiments, that all they had to do was slightly modify the messenger RNA in a way that it's normally modified in our own bodies. They had to add one molecule. It's actually called pseudouridine to the mRNA. And then they inject the mice with this modified messenger and they wait with bated breath.

Are the mice going to get sick? Are they going to make the protein? It was like a, that's a dream come true. It is like just this amazement that, wow. The mice made the protein. And then actually I had to repeat the experiment because I couldn't believe that could it be that I made some mix up, but I did repeat it

and I found that, okay, it is just more protein is made. And we were very excited, of course, you know, we look at the data and wow, you know. It was an incredible moment. was an incredible moment. It was culmination of everything she had worked for, for all those years, starting in Hungary, when no one even knew how to make messenger RNA. All those years when people said, this is crazy, this molecule doesn't last, it's not useful for anything. All of a sudden she realized, yes, we can inject an animal or a person with this. We can ask their body to make whatever protein we want it to make. With this really significant breakthrough in hand that validates everything she's been saying and trying to prove for years, does she finally start to get the recognition and the funding and the status that she has been hoping for and no doubt deserves?

Not really. I wrote a grant, yes, and that was the first and last and only grant I got. She and Drew really struggled to get grants. They tried to publish a paper on this really important discovery, and most journalists just turned it down. They even started a company. But nobody wanted to invest in their company. They still were. They made this great discovery, and it's like the world shrugged. Why do you think that would be? I think people didn't get it.

I think they didn't. And I'm not sure they understood what was the significance. Nobody really cared about messenger RNA, even though she showed it would work. So they're back where they started from again. She was kind of nowhere. But then, finally, something happened that changed her life, stopped all this constant scrambling and struggling. It was 2013, July. And I gave a lecture and Uwur Zahin, I met there. She met somebody who founded a small company called BioNTech. And he was interested also that modified RNA will be used at the company.

He understood her vision. He understood what she wanted to do. And he offered me a job right there on that day. And then I said, OK. Now she had stability. And not too long after that, Pfizer and BioNTech partnered. The idea was to make an mRNA vaccine. partnered. The idea was to make an mRNA vaccine. We signed in 2018 to collaboration to develop mRNA-based influenza vaccine. So she was working on this flu vaccine for a couple of years and then COVID hit. So how did you first hear about the coronavirus and what were your thoughts when you first heard this? so far away, China. But luckily, the visionary CEO of our company, he realized that there will be a problem. And so he very early on decided that we have to do something. BioNTech realized they were in a unique position. And that was because they already knew from

working on the flu vaccine how to make an mRNA vaccine. That's what they've been working on. The messenger RNA program for vaccine, but against the influenza, was already well advanced. All of the studies went on and it was like ready for human trial. All of the studies went on and it was like ready for human trial. And so it was like everything had conspired. Everything had come together at this one moment. So when this unique pandemic hit, all of a sudden they were set to go. And so instead of the influenza specific sequence had to be, you know, removed and then put back the corona-specific.

So that was... So it's immediately clear to Dr. Carrico and to those around her that this concept that she has been pursuing for all this time, it might do the work of instructing the body to fight the coronavirus. Absolutely, yes. Katie knew all of a sudden, and so did her close colleague Drew, by the way. They knew all of a sudden that they had it. A normal vaccine would take forever, but this odd thing that they'd worked on that nobody had cared about for so many years, all of a sudden could save the world. And what exactly was their theory for how they would use messenger RNA to fight the coronavirus?

All they had to do is they had to know what protein does the virus absolutely need to infect a cell? The spike. The spike protein, right. It's like a hypodermic needle. The virus uses the spike protein to inject itself into cells. If you can block the spike protein, the virus can't get in. So the idea that they had is that they would put instructions to make a spike into an mRNA vaccine. Give people this mRNA vaccine, which is basically just giving them the mRNA, and get that mRNA into cells.

The cells would briefly make the spike protein. When the immune system sees the spike, it makes antibodies to it. Then if a virus ever gets in to your body, the antibodies will block the spike so the virus cannot get into cells. Got it. All that being said, was there a moment of hesitation for Dr. Carrico where she wondered, you know, I know on paper this is all supposed to work. I've seen it done in a petri dish. I've seen it done in mice. But will this actually work in a vaccine against a new emerging virus? You know, it's really interesting because she had complete confidence. She said the science was good. And then the results from the large studies of the vaccine in human volunteers came in in November.

Actually, Ugo called me up, my CEO, on November 8th, it was a Sunday, and he told me that, you know, the result of the phase three shows that it is effective. And asked me that, is there anybody in that room? And I said, you know, my husband is here. And I didn't know whether I can tell him or not. And finally, I told him it worked. She turned to her husband and said, oh, it worked. I knew it would. And then I decided that, you know, eat that goobers, which is a chocolate covered peanut, which is my favorite.

You know, this movie theater box. And I usually, you know, I don't eat the whole, you know, all of them, which is in one box. But then I told my husband, today I will eat the whole. And so this eventually becomes what we refer to as the Pfizer-BioNTech vaccine, the vaccine that so many of us, myself included, have received. Yes, absolutely. It was based on the mRNA technology, and without it, it couldn't have existed. And at the same time, another company, Moderna,

also made an mRNA vaccine. The two vaccines are extremely similar, and they are amazingly effective. I remember in the beginning when they said, if we could have a vaccine that was like 60% effective, boy, that would be amazing. And all of a sudden, here's a vaccine that's more than 90% effective. This is like success beyond people's wildest hopes. How quickly does Dr. Cargo get to take this vaccine that she herself has played such

a pivotal role in developing. The first people to get it were medical research workers and medical personnel like doctors and nurses. That was in December. And both she and her colleague, Drew Weissman, actually got vaccinated with the Pfizer-BioNTech vaccine back at the University of Pennsylvania, the place she'd spent so many years trying and trying to advance her research. And how did you feel getting a vaccine that your own research helped make possible? Yes, we were sitting there for a while, setting up, so I had enough time to reflect back all

of these years that we worked on it. This needle goes in her arm, and she thinks back on all those years, all those struggles, all those rejections, all the disbelief. And yes, I became a little emotional. Usually I'm not emotional. I'm usually a very cheery person, but sometimes I get emotional, especially when I have seen people line up,

the health care workers, the physicians were lining up there. On the next room, they got their injection. And when we entered to the hallway, the chairman at neurosurgery said that, you know, that here are coming the inventors of this vaccine. And then some people started to clap. And that made me like emotional and cried a little bit, even now I am saying to you. You know, Gina, I'm struck in hearing you and Dr. Kariko tell the story behind this vaccine by all the moments where things went wrong and this almost didn't happen.

In fact, it seems from the history of this that it's kind of a shock that it ended up working out. It is kind of incredible that it all came together and worked. And it made me think about all the other Katie's out there who have really good ideas and get thwarted so many times. And here's Katie. It was not just her persistence. Things happened to work out. She happened to find somebody who believed in her again and again.

And it could have gone the other way. It could have been that nobody would take her on. And I know that there are a lot of people who are in positions like she was in. They're enthusiastic. They're hard workers. They never get a foot in the door. And that's really a tragedy of science and also some of the other fields, too. You hate to think of the people who could have made a huge difference who were shut out too early on. I have to wonder what role gender

played in this because it occurred to me as you spoke with her that at almost every key juncture, a male scientist or academic or executive either walks away or walks into the picture? Well, I asked her this question, the question you just asked me. She said that she didn't see it that way. I personally, I didn't feel that the male colleagues were treating me differently. So I have... Katie says she really didn't think it was a gender thing. She thought it was just an academia thing, the way the world works. The way if you have an idea, but you don't have a grant,

you don't have a publication, you don't have a position that's at all permanent, you're kind of rejected by the world unless you happen to find mentors and she happened to find men. So she rejects the idea there's any sort of gender issue going on here. And it's hard to know unless you're in her shoes. this vaccine has been so widely used over so many months and been put into the arms of millions of people around the world and has protected so many of them from this virus. I wonder how she thinks about her place in this pandemic. My impression of Katie is that she is not somebody who is grandiose, but she knows how important the work was. She knows that her persistence paid off in the end. She knows that she's written into the history books forever.

But when I asked her about her fame, she said that was not the kind of fame she wanted. The worst pandemic in over a hundred years, millions of people affected. I mean, it's kind of incredible to play a role, seems to me. It's kind of... I mean, I gave the lecture in Hungarian Academy on Monday, and I mentioned that I am here because the pandemic made me famous, but I wish not to be there. Then I wouldn't be famous and then I wouldn't, we wouldn't have any pandemic. So that if I have a choice, I would select that. Well, I hope you have some goobers today. I have some more here.

Thanks again, Katie. Yeah, thank you. Thank you, Gina. Gina, thank you very much. We appreciate it. Thank you, Michael. It was really a pleasure talking to you. On Wednesday afternoon, the Times reported that the Biden administration had reached an agreement with Pfizer and BioNTech

to provide 500 million doses of their mRNA vaccine to about 100 countries over the next year. The agreement is designed to make the vaccine far more accessible to the world's poorest countries and to their citizens. We'll be right back. Thank you. said, was to reassure allies that the hostility of the Trump era is over, to coordinate policies on global warming, China, and the pandemic, and to confront Russia. During his trip, Biden will hold an in-person meeting with Russia's President Vladimir Putin, who U.S. intelligence agencies have concluded repeatedly sought ways to undermine Biden and help try to

re-elect his rival, Donald Trump. We do not regard a meeting with the Russian president as a reward. We regard it as a vital part of defending America's interests and America's values. During a news conference, Biden's national Security Advisor, Jake Sullivan, defended the meeting with Putin. Joe Biden is not meeting with Vladimir Putin despite our country's differences. He's meeting with him because of our country's differences. Today's episode was produced by Rachel Quester, Jessica Chung, and Rob Zipko. It was edited by Anita Badajoe and Paige Cowett, engineered by Chris Wood, and contains original music from Dan Powell,

Brad Fisher, and Marian Lozano. That's it for The Daily. I'm Michael Barbaro. See you tomorrow.