It may seem as though we got the Pfizer and Moderna COVID vaccines incredibly quickly. But Hungarian biochemist Katalin Karikó had been trying to make mRNA vaccines work for 30 years while fighting scientific gatekeepers who thought her idea was absurd. Her grants were denied, her papers rejected, her speaking invitations withdrawn; eventually, the University of Pennsylvania demoted her. But she still refused to quit, and in 2005, she and collaborator Drew Weissman cracked the code. They figured out how mRNA could direct our own cells to manufacture medicines to order. Their breakthrough saved the world from the worst of the pandemic—and opened a new world of medicines and vaccines for a huge range of diseases.

Guests: Katalin Karikó, senior VP at BioNTech. Drew Weissman, Perelman School of Medicine, U Penn. Derek Rossi, co-founder of Moderna.

Episode transcript

Unsung Science Episode 2: 

How We Almost Blew the Vaccine

Hungarian biochemist Katalin Kariko spent 17 years working on a medical idea that was so far-fetched, the scientific community soundly denied her grant proposals.

KK: You know, I was demoted from my position.

DP: Why were you demoted?

KK: Oh, because I didn’t get funding!

And in the end, she did it: she and her collaborator invented the mRNA vaccine. Without her, there would be no COVID vaccines from Moderna or Pfizer.

I’m David Pogue, and this is Unsung Science

[BREAK]

Season 1, Episode 2: How We Almost Blew the Vaccine.

[music]

As I sit here recording this episode, the COVID pandemic isn’t what you’d call

over. But it’s definitely been beaten back. It’s nothing like the death-eater

Armageddon it would have been if we hadn’t had the vaccines.

And I’m not sure you realize how miraculous it is that we got a COVID vaccine so darned fast.

Scientists analyzed the coronavirus for the first time in January 2020—and the Pfizer and Moderna vaccines entered clinical testing in April! Three…months… later! And went into the arms of the first patients in December. 

It was by far the quickest vaccine ever developed. Modern vaccines usually take ten or fifteen years to create. 

And to make this story even more incredible: the Pfizer and Moderna vaccines are both mRNA vaccines, which I’ll define in a minute. No mRNA vaccine or drug had ever been approved before. 

And you know the two companies that developed those vaccines, Moderna and BionTech? Neither one had ever brought a product to market before. (You may know the BionTech one as the Pfizer vaccine, because Pfizer did the manufacturing and distribution.) 

And COVID was only the beginning. 

ROSSI: The vaccine industry is going to pretty much all move over to RNA vaccines, simply because they— they’re very effective. They can be made very, very quickly. And ultimately, I think the cost of goods will be much cheaper. 

It’s also being used —for, you know, oncology. So, cancer applications. I mean, I think the possibilities are limitless.

That’s Derrick Rossi, a former Harvard professor, a really good explainer, and the cofounder of Moderna. He’ll be back.

But to me, the juiciest part of this story of all is how we learned to create mRNA vaccines in the first place. It’s a story of two scientists’ relentless, almost irrational devotion to the concept, despite years of rejection, humiliation, and ridicule. This story’s redemption arc is so incredible, it almost sounds like cheesy fiction. 

But before I introduce you to our heroes, I want to introduce you to a little cellular biology. Don’t freak out—it’ll be fun! I’m going to explain mRNA in the form of a bedtime story. Tinkly music box, please?

[Cue the tinkly music-box music.]

Once upon a time, there was a sensational little restaurant. The recipes dreamed up by Deena, the master chef, were genius. Miso-glazed lobster tails with sesame bok choy! Scallop Sashimi with Meyer Lemon Confit! Apple galette with vanilla-raspberry drizzle! 

And she did it all in her head! She didn’t fiddle with ingredients—she didn’t even have ingredients to play with in her little office, locked away in the middle of the restaurant. She’d dream up the recipes, and then send them off to the kitchen, which Deena called the Site Operations Center, or Site Ops. They turned her recipe instructions into delicious dishes, to feed the waiting customers. 

To hand her recipes off to Site Ops, she relied on her trusty assistant Myrna as a messenger. Every day, in the sanctum of that inner office, Deena carefully recited her recipes. Myrna memorized every syllable—and then headed out to Site Ops, to relay the instructions to the chefs. They’d make the recipes, send them out to the patrons. And they lived happily ever after.

And…SCENE!

[Music concludes abruptly.]

Wasn’t that great? You just learned molecular biology!

Well, kinda. 

In this super-simplified analogy, the restaurant is a cell in your body. And obviously, your cells don’t make lobster flambée or whatever I said before. What they do make are proteins, these giant complex molecules that perform just about every important maintenance task in your body. Proteins fight disease, communicate between your organs, convert food to energy, clot your blood, and on and on. Derrick Rossi really admires proteins.

ROSSI: The real worker bees in the cell, do essentially all the cellular functions which give rise to life, are proteins. And people don’t know that. They think of proteins largely in the context of what they eat. You know, if they’re eating steak, they’re eating protein—or beans or something, if they happen to be vegetarian. 

But actually, proteins, there’s a large, very large diversity of them in our cells, upwards of 30,000. And they really are the worker bees. 

The master chef, Deena? That’s DNA, which really does live in an inner chamber of the cell known as the nucleus. The DNA keeps the recipes for all those proteins, and sends them to the outer area of cell, called the cytoplasm—Site Ops. (See what I did there? I’m a punning genius.) 

ROSSI: So DNA lives in the nucleus, which is a, you know, a very localized compartment of the cell. And proteins are made in a totally different part of the cell called the cytoplasm, and never the two shall meet. 

That’s why we need a messenger: Myrna, the messenger, and the star of our story. She carries the instructions from the nucleus, out to the ribosomes—the protein-making equipment—in the cytoplasm. 

And by the way, scientists don’t actually call her Myrna. They pronounce it mRNA, which stands for messenger RNA. 

You probably saw that one coming up Sixth Avenue.

ROSSI: If the if the recipe is contained in the DNA, which it is, you have to get the recipe to the kitchen. The mRNA is the thing that carries it to the kitchen and it goes into the protein production factory. 

I call it the trifecta of life: DNA gives rise to mRNA, gives rise to protein, gives life. 

DAVID I mean, in elementary school, we learn about DNA, but who’s ever heard of messenger RNA? 

ROSSI: It’s the— it’s the neglected middle child. And I’m happy to hear that  mRNA is finally getting its due. 

So here’s the question that had been dogging scientists for decades: What if we could write our own recipes for making proteins? Over 4 thousand diseases result from mutations in our DNA, including cancer. What if we could step into that process—DNA recipe, ribosome manufacturing—and influence it? Those recipes could teach our bodies to make proteins that cure old diseases, or fight new viruses.

That would be huge. Just for example, we know we’re going to get more viruses and more pandemics. I mean, they come along every couple of years, right? SARS. MERS. Zika. COVID. This could be amazing. 

Turns out, we have had some success modifying the DNA in patients’ cells.

ROSSI: DNA, of course, has been used. And if you’ve heard, you know, you’ve heard of gene therapy, different types of gene therapy, these are DNA based. 

But editing the first step in the process is not quick or easy or always even possible. Because as you know from our bedtime story, it’s a bunch of steps to go from the DNA to the kitchen.

We’ve also tried intercepting the third stage in the process, we’ve tried making the proteins in a vat, and just injecting them. And that sometimes works.

ROSSI: The first therapeutic proteins came —came into being in the 1980s. Genentech, a company in south San Francisco, led the way with insulin. And since that time, over 120 different FDA approved protein therapeutics have been approved, and are in use today. 

But injecting proteins directly isn’t optimal, either, because they can’t help you with diseases inside your cells. The injected proteins can only swim around in the gaps outside your cells, in what’s called the extracellular space.

ROSSI: But proteins are not very good at crossing over into the intracellular space. So pretty much all protein therapeutics are limited to deficiencies or diseases that are manifest and treatable in the extracellular space. 

So: tackling disease by modifying the DNA isn’t easy, and tackling disease by injecting the proteins themselves is limited. But as Rossi points out—we’re forgetting about the intermediate step. Myrna.

ROSSI: So but what about that, you know, neglected middle sibling?

You know, like, what if we could hand new recipes to Myrna to deliver to the kitchen? What if you could inject modified mRNA? In other words, what if you could…shoot the messenger?

[Pun-reaction SFX] 

But seriously, folks. 

ROSSI: But mRNA, on the other hand—you could now have the ability to make intracellular protein therapeutics, which had never been doable before, not to mention extracellular as well. 

[Music]

Maybe you’ve heard of the spike proteins on the COVID virus—the tiny spikes that give the coronavirus its name. You know, cuz “Corona” means crown. The virus uses those spikes to inject itself into our cells.

Most vaccines work like this: You inject a weakened or dead version of the whole virus into the body. That teaches your cells to develop antibodies, which will attack the real thing if it ever comes along. 

But an mRNA vaccine wouldn’t require injecting the whole coronavirus. Our synthesized mRNA could trigger the manufacture only of COVID spike proteins. Your body would see the spike bits and go, “Ho-HO!, what are those? THOSE don’t belong in here!—I’d better manufacture antibodies.” Within hours, you’d start making antibodies that recognize the spike protein. Later, if you ever encountered the actual COVID virus, your cells would already know how to protect you!

Well, we’ve tried stuff like that. For decades. And we gave up. Until 2005, every modified-RNA experiment failed bigtime. Every time we tried to inject it, the body killed it on contact. Our cells didn’t appreciate that we were introducing a brilliant human-engineered invention intended to keep us healthy; it always saw the synthetic mRNA as some evil external virus, trying to sneak into our nuclei to reproduce. Here’s Derrick Rossi again:

ROSSI: It’s the story of when cells and viruses first met one another, really, which is, you know, hundreds of millions of years ago. And ever since that time, viruses have been trying to figure out ways of getting into cells to replicate, to, you know, complete their life cycle. And cells have been figuring out ways of detecting when viral DNA is injected, and combating that by various defense mechanisms. 

So it turns out that when you try to introduce RNA into a cell, you trip these very ancient antiviral pathways, which do a very good thing to the cell. They say, “bad news coming in, let’s shut down, let’s stop protein production. And if it looks really bad, if it really looks like an infection, let’s kill ourselves.” An altruistic suicide. 

Through many decades, people introducing mRNA into cells were very good at tripping these antiviral pathways, killing the cells in the dish. And basically, the field didn’t move forward because of that. 

DP: Is that the same immune response problem that Kariko and Weissman were worried about? 

ROSSI: It’s exactly that. It’s exactly that. And they’re the ones that solved it.

OK. You now know what modified messenger RNA is, and why we couldn’t use it to fight off viruses. After the break—you’ll meet the two people who thought they could crack the code—and the brutal years of rejection they faced for trying.

BREAK –

Before the break, I was explaining what modified mRNA is. But according to Derek Rossi, it’s also where the company name Moderna comes from.

ROSSI: Actually, I had originally some not so great ideas for the company. One of the first ideas that I had was Harbinger Therapeutics. So you know, the harbinger of of medieval times was that guy who would ride in on his horse to a town before an approaching army, and tell the town that, “hey, the army’s approaching. Here they come!”  So it was it was basically delivering a bad news, what you thought was a nice, happy town, life is all of a sudden about to be overturned by this approaching army. So that was the harbinger. So I thought that wasn’t a real great name for the company. 

So then just one day I was —it just struck me.

It was modified mRNA, which we shortened to mod RNA, and then was not hard for me to come up with Moderna from mod RNA. 

I was also explaining how a generation of scientists had given up on using synthetic mRNA to fight disease and viruses. Every time they injected the stuff, they got an immune response. Every time, our immune systems killed off the modified mRNA as though it were an invading enemy. Most researchers moved on to more promising areas of inquiry.

There was, however, one scientist who had not given up—and would not give up.

KK: So, you know, I am a daughter of a butcher. And when I decided I would be a scientist, I was in high school in a small city. I had no idea. I have never seen a scientist. I just figured out that I would be a scientist, and I would go to work. 

Katalin Kariko grew up in Communist Hungary, in a home without TV, refrigerator, or running water. She became fascinated by mRNA in grad school—but when her lab ran out of funding in 1985, she decided to come to the States with her husband and 2-year-old daughter. They sold their car for 1300 bucks, and she stuffed the cash into her daughter’s teddy bear, because Hungarian law limited how much money you could take out of the country.

Their daughter, the one with the teddy bear? Grew up to be Susan Francia, who’s won two Olympic gold medals on the U.S. women’s rowing team. That’s a harbinger of the kind of family we’re dealing with here.

Anyway, back to her mom. Katie Kariko, as her colleagues call her, was more or less obsessed with figuring out how to master modified mRNA.

KK: For 10 years at University Pennsylvania, from ‘89, I started that there to 1998 maybe, that I was trying to use mRNA for therapeutic purposes. 

And for ten years, the scientific community thought she was nuts. 

DP: Can you tell us how much success you had with—with grant proposals during the 90s? 

KK: Yeah, I did not get money. They always ask me that—you know, who is my supervisor? The woman, an accent, probably she wouldn’t come up with ideas like that. 

A woman with an accent—whatever the reason, nobody believed in her idea, and nobody would fund her research. She wrote proposal after proposal. In one of the talks she gives these days, she’s got a slide that consists of nothing but the rejection letters. Sooo many stories of slammed doors.

KK: It was 1993. We went to Princeton and we presented. So they could have been invested.  They promised the 70,000. That would be the best 70,000 dollar. But they never gave me the money, and…they never even return my phone call, not even today. I don’t name them, because they are still around.

Well, you know what they say about academia: Publish or perish. If you don’t bring in the grant money, you get demoted. And sure enough—

KK: You know, I was demoted from my position. 

DP: Why were you demoted?

KK: Oh, because I didn’t get funding! 

Penn took her off the professor track, because she wasn’t landing the grants—but once she wasn’t on faculty, a vicious cycle began. 

KK: And then later, I didn’t get funding, because they question that I am not faculty. 

DP: Today, how do you think about the people who turned you down or demoted you? Did they have good reasons? 

KK: They said that many things I didn’t do well, I could not articulate well enough, you now, the ideas, because I couldn’t attract the money. I acknowledge maybe I was not doing well, because they couldn’t see it, I couldn’t explain well.  

Drew: Most of them basically said, “yeah, we’ve heard of this before. RNA’s too difficult to work with, we’re not interested.”

That voice belongs to Dr. Drew Weissman. She met him at a Penn photocopier one day in 1998.

Weissman is a physician and an immunologist who had come from the National Institutes of Health, where he worked on an HIV vaccine with another immunologist whose name you might know—Anthony Fauci. 

Weissman told Kariko that he’d been looking into using genetic material to make vaccines, and she told him that she’d learned how to modify mRNA. He invited her to join his lab.

Which brings us back to that infuriating inflammation problem, the problem that made the rest of the science world consider the whole field a dead end:

Drew: Inflammation occurs whenever the body doesn’t like something. It can be a virus, a bacteria, it can be hitting yourself on the head with— with a brick… there’s lots of different types of inflammation. And it’s the body’s response. And that includes high fever, low blood pressure, feeling lousy, a variety of things. 

David: So that kind of response would not be ideal in medicine, you’re giving somebody no, 

Drew: You don’t want to make people sick with your medicine. 

Or your mice. Whenever Kariko and Weissman injected modified mRNA into lab mice, they’d lose their appetite, or their fur. They couldn’t get around the immune-response problem—or the no-support problem.

David: Is it normal for researchers to stick at it like that for so long when you were getting so many naysayers? 

Drew: I wouldn’t let any of my people work that long on something. The reason that I didn’t give up, and Katie didn’t give up, is that we saw the potential from— from the very beginning, we knew that there was enormous potential for RNA as a therapeutic. And it was more a matter of just figuring out how to make it work. 

David: And there weren’t family or colleagues saying, “dude, what are you doing? It’s a dead end now!”

Drew: No, I would get that all the time. I would go to meetings, and I would talk with other leaders in science and even Tony at some points. 

That would be Tony Fauci.

Drew: (continued) And he would listen to the data and say, “yeah, that’s really interesting, but what are you going to do with it?” And I basically knew I was being blown off. And I went back to work and kept working at it. 

David: So here’s my favorite part. How did you discover the way around this immune response? 

Drew: Yes, that was years and years of work. 

Now, I’ll let Weissman explain the solution, but first I kind of need to set this up. 

It turns out that your cells often dress up the proteins they make with little chemical attachments, little molecular modifications, that make them work better, last a little longer, or whatever. They’re like aftermarket mods. You’ve got the same car, but now it has a nicer stereo. You can think of them as decorations, or embellishments, or, as Derrick Rossi calls them,

ROSSI: —Dongles, if you will. You know, phosphorylation here, ubiquitination there, glycosolation here, it gets sort of decorated with all of these sort of modifications that are required for it to function properly in its day-to-day business as a worker bee. 

You know what else sometimes comes decked out with modifications? RNA molecules. And some types of RNAs have more of these extra aftermarket modifications than others, including RNAs from different animal or bacterial or plant cells.

OK, so getting back to the Kariko and Weissman experiment that changed medicine forever:

WEISSMAN: And the key experiment, we took a bunch of different kinds of RNAs. So RNA from bacteria, from mammals. There’s ribosomal RNA, transfer RNA, nuclear RNA, messenger RNA, mitochondrial RNA. We took all of those, and we tested them for inflammation. And they were all different! 

Some RNA types triggered the body to attack—and others didn’t. What was it about the winning types that let them slip by?

And the answer? The ones that didn’t produce inflammation—were the ones with a lot of mods!

Drew: And what we noted is that RNAs that had a lot of modification/ didn’t have any inflammation, and RNA that had none was highly inflammatory. 

To test that theory, they whipped up a batch of synthetic RNA that had a mod of its own—they added one molecule, called pseudo-uridine—and bingo. No more inflammation. Kati Kariko was ecstatic that there was no more immunogenic response, meaning that the immune system stayed quiet.

KK: I was so happy, not just because now that we could make a messenger RNA, which is not immunogenic, but what was important, / 10 times more protein was produced. I mean, you couldn’t even dream that— that finally is not immunogenic and so much more protein is made from it, you know, compared to the conventional RNA we made before. 

They had done it. After ten years on her own, and then seven years working with Weissman, Kariko had broken through the barricade. They had figured out how to introduce modified mRNA into human cells—that could trigger the production of any proteins they wanted. They’d figured out how to send Myrna into the kitchens of your cells, carrying recipes that never came from the master chef. They’re recipes we gave her to carry.

Kariko and Weissman published their results in 2005, in the journal Immunology—and then waited for the scientific world to lose its mind. 

DP: So in 2005, you published this paper. Did it set the scientific world on fire?

KK: No. Drew Weissman said, “oh they will, they will notice”— but nobody! nobody, nobody said anything. Nobody invited us, nobody cared!

They started a company; nobody would invest. They tried to get grants; they got one. 

But at least two people cared a lot about the breakthrough. One of them was Ugur Sahin (OOgoor ZAHin), cofounder of the German drug company BionTech, which would go on to develop the Biontech/Pfizer COVID vaccine. He hired Kariko in 2013; she works at Biontech to this day. 

The other person who read that 2005 paper was Derrick Rossi.

ROSSI: When we read the paper, we thought, well, let’s try this. And lo and behold, now, when we introduced mRNA into cells, we could get it to express whatever protein we wished. And the cells were as, you know, happy as pigs in mud. They were not dying. So this was— this was the key. And it was at that point that I founded Moderna —co-founded Moderna to— to bring this technology to development for mRNA medicines. 

I gotta tell you three things that really struck me about both Kariko and Weissman. First, of course, their sheer refusal to give up. For YEARS.

David: Is there something in your character and Katie’s character that made you guys so dogged to keep to keep working at it? 

Drew: I think that’s our personalities. We’re both pain in the butts. We we don’t give up. We —when we’ve got an idea that we think is good, we keep going after it. 

Their employer, Penn, owned their patents, and then soon sold them to an obscure chemical company in Wisconsin for $300,00.  Of course that was the best deal that little company ever made. It’s already made hundreds of millions of dollars off that deal, by licensing Kariko and Weissmann’s technology to Moderna and Biotech. Nice going there, Penn lawyers

So the second thing that surprises me is that they seem to hold no grudges. They’ve stood by and watched their invention make millions of dollars for other people.

David: Did you want to protect the technologies, so that you would be the beneficiary instead of other people? 

Drew: Well, we tried. We just couldn’t do it. We —we tried to license the technology from Penn, but we couldn’t come to an agreement with Penn. And so we had to give up. 

David: Wow. That would make me sort of bitter. Is there any bitterness on your end? 

Drew: You know, I’m sure we have —we’re unhappy about some things that have happened. We’re scientists. To us, solving the problem, developing the new findings, new technology, new treatments —to us that’s —what’s important. Grievances, who cares? 

KARIKO: I have to tell you, when I was hired at Penn in ‘89, my salary was $40,000 a year. And 20 years, so 2010, it went up to all the way to 60,000. 

My husband once told me that probably in the McDonald’s, I would get a better hourly pay. But it is —you know, I enjoyed what I was doing. 

Listen, if —I am 66 old. My family, my husband, we never have a new car. We always had the car which was coming in the trailer and he fixed it up. Probably I’d never buy a new car, because we’re so used to it not to have a new one! Probably I would freak out in the, you know, parking lot that somebody would scratch it! 

Of course, she said that before she and Dr. Weissman won 3 million dollars from

the Breakthrough Foundation, which was created by Sergey Brin, Mark

Zuckerberg, and other billionaires, to award important achievements in science.

She told the Philadelphia Inquirer that she plans to pour it back into her research,

and to support science education for financially strapped students. No mention of

a new car.

And the third thing: They both insist that the glory means nothing to them, either. These days, Kariko and Weissman are invited everywhere. Institutions celebrate and honor them, and the media harasses them. 

Drew: I mean, my family keeps pushing me to enjoy the —the spotlight. And anybody that knows me, the two things I don’t like are attention and talking. So to me, this has put me into uncomfortable situations where I’m doing things I don’t like and taking me away from the science. 

David: Does that include interviews?

Drew: Unfortunately, yeah.

KK: Listen, I do it for me. For me, it was important that I knew that what I am doing is good, reproducible and would be helpful. 

Even the knowledge that I know that I contributed to something is —is sufficient. For me, I didn’t need it that people will know that. No, it is not important. I know that, and that’s it. 

And many times I just thinking about, you know, that a hundred years from now, nobody will know that we existed. So what is this fighting for? 

DP: A lot of people think that there’s a Nobel Prize in your future. 

KARIKO: I’m not interested in money or prize and anything. [00:34:00] I was just recently asked, can —can I explain that how to be successful? I don’t know. I don’t know.

Some measure how many times you fail, then you still have enthusiasm, and keep your enthusiasm, and you just keep going. That’s maybe success. Other people, maybe money is the success. I don’t know how you measure it, but being happy is important. Happy, enjoying the work you are doing. 

DP: How about this for success? How about laying the scientific groundwork that saves millions of lives? 

KK: Yeah. And —and more people get vaccinated and they feel safe, you know, to go out, or meeting their relatives and, yes, I am very happy. 

By the way, Kariko, Weissman, and Rossi all stressed to me that every breakthrough stands on the work done by previous scientists.

ROSSI: To get anything done in science is a large, generally speaking, a large community of people building off the work of others, and building on the shoulders of others, to move things forward. / Science—Science has to work this way, and it worked this way very well this time. 

By 2019, Kariko had been at Biontech for six years, working on an mRNA vaccine for the flu. The company was already talking to Pfizer about manufacturing and distributing what would have become the world’s first mRNA vaccine. That flu vaccine was just about to begin human trials—when COVID hit. 

That’s one of the reasons we got the COVID vaccine so fast—because both Biontech and Moderna already had other mRNA vaccines working. Once they had sequenced the coronavirus, they were able to repurpose those vaccines and get them to trials fast.

Maybe it’s just a coping mechanism. But Katalin Kariko, who spend her entire career working on RNA, who was rejected from grants, demoted at her job, and had her name taken off of papers, sees all of it as part of the journey. Just bumps on the road that led her to the mRNA breakthrough that’s helping to end the pandemic. Because it led her, eventually, to BioNTech.

KK: I truly feel that, you know, if with my colleague, I’m not going over there in Biontech and we work—I don’t think that that would be BionTech Pfizer vaccine. So we have to thank those people who showed me the door, kicked me around!

Drew Weissman is still at Penn, working on an even more impressive vaccine.

Drew: Well, so we’re thinking ahead. There have been three coronavirus epidemics in the past 20 years. There’s going to be more. I mean, it would be foolish to think we’re not going to have more. 

So we started last spring working on a pan-coronavirus vaccine. So the next time there’s, you know, a new pneumonia somewhere in the world that turns out to be a coronavirus, we’ll have the vaccine made./ to stop the next pandemic. 

Derek Rossi left Moderna in 2014; today, he has two new drug-development startups, one working on cancer drugs, and the other on a multiple sclerosis therapy. 

ROSSI: What’s cool is that the success of these RNA vaccines has led to new mRNA companies sprouting up like mushrooms in Boston, Cambridge and around the planet. An industry has been born, that’s for sure. And I think that’s great because it just means more money and more resource and more brainpower, more people working on cool ways to, you know, affect our health when we’re unhealthy. 

Moderna itself is plowing full-steam ahead into more mRNA-based treatments. It’s in human trials for vaccines against HIV, Zika, Chikungunya, RSV and CMV, a few kinds of cancer, and, of course, that flu vaccine.

We make flu vaccines as we have since the 1930s, in a hilariously old-fashioned process that entails injecting the virus into, I kid you not, chicken eggs. 

Unfortunately, there are many different variants of the flu. So every year, researchers have to guess which flu strains will be common in the U.S.—a year from now. If they’re lucky, the flu vaccine’s effectiveness might be as high as 60%, as it was in 2010. If not, it can be only 10% effective, as it was in 2004.

But if we had mRNA flu vaccines, like the ones Moderna and Pfizer-Biontech are developing, we could have the vaccine only weeks after we know about the virus. We wouldn’t have to guess which flu strains would be here—we’d know! We could make the vaccine based on the kind of flu that’s already here.

Oh—and no chicken eggs would be involved. 

Moderna plans to combine its new mRNA flu vaccine with the COVID booster shots, so every year a single shot would protect you against both.

And it all started with Katalin Kariko and her unshakable belief that mRNA could be used to fight and prevent disease. So I’ll give her last word. I asked her if she had any advice for younger scientists. She mentioned hard work, and being a good networker with your colleagues. And…

KK: And it is also important to select a good partner. And my husband is very supportive. So he was not complaining that I am not cooking, you know, things. And I’m coming home, you know, Saturday and carrying, you know, the little machine. And I asked him to fix it because I need the next day. (laugh) And he was doing that, and he was always said, “OK, just go.” So —so he was very supportive. 

DP: You got lucky there. What a guy. 

KK: And I have to tell you, by the way, that when I met him, he was 17 years old. And when we married, my mom didn’t even give us a one year. And we were just celebrating 40 years together!

DP: Oh, my gosh!

KK: I always was, like, knowing what I am doing.