Nobel Prize Conversations

“When I was a young kid, my father would tell me, you can do anything you want when you go to work. The most important thing is to enjoy it. I found that”

How can we ensure that knowledge and science is spread globally? Medicine laureate Drew Weissman is an advocate for creating research centres around the world to give local researchers the means to have ownership and solve health issues by themselves. As Weissman puts it: ”A lot of people set up a clinic in a city somewhere, collect samples, take them home, and study them. To me, that compounds the problem, because it doesn’t teach people. It doesn’t make scientists better.”

Weissman also tells podcast host Adam Smith about how his interest in science was sparked and how he has maintained that curiosity for the rest of his life. 

This conversation was published on 13 June, 2024. Podcast host Smith is joined by Clare Brilliant.

Below you find a transcript of the podcast interview. The transcript was created using speech recognition software. While it has been reviewed by human transcribers, it may contain errors.

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Drew Weissman: You have to tolerate frustration to be able to work in a lab. But when you do make a finding, even if it’s a little finding, because of all of the frustration and all of the difficulty getting it, it makes it that much more important. It’s really, you know, kind of an inner joy. 

Adam Smith: It was a long series of those little findings, which Drew Weissman refers to, which led him and his colleague Katalin Karikó, to make the very substantial contribution they made to World Health by helping to develop the mRNA vaccines used during the Covid Pandemic. And it’s interesting to contrast the abundant positivism of Katalin Karikó. With that quiet optimism you hear in Drew Weissman’s voice, whether that optimism is derived from the experiences he went through as a child. I leave you to judge, it’s something we discuss in this conversation. But anyway, I hope you enjoy very much listening to Drew Weissman. 

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Clare Brilliant: This is Nobel Prize conversations. Our guest is Drew Weissman, who shared the 2023 Nobel Prize in physiology or medicine with Katalin Karikó. He was awarded the prize for discoveries concerning nucleoside based modifications that enable the development of effective mRNA vaccines against COVID-19. Your host is Adam Smith, Chief Scientific Officer at Nobel Prize Outreach. This podcast was produced in cooperation with Fundación Ramón Areces. Drew Weissman is the Roberts family professor in vaccine research at the University of Pennsylvania’s Perelman School of Medicine. He speaks to Adam about those aforementioned frustrations in the lab and other hiccups in life, how research is like raising a child and why he’s now involved in 250 different collaborations. But we kick off this conversation with a special introduction. 

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Smith: That is most definitely the most comfortable looking podcast recording setup I’ve ever seen. You sitting with your cat on your lap. Who are we in the presence of? 

Weissman: Yes. This is Zander. 

Smith: Zander looks particularly content and particularly beautiful. He’s a big fluffy guy. 

Weissman: Yes. When I’m home, he’s in my lap. 

Smith: Gosh, that’s lovely. Thank you very much indeed for taking the time to talk to me. I appreciate it very much. I also know that from what you said when you were awarded the Gerdner Award in 2022, you don’t much like attention. I guess these sort of things are not without their pain. 

Weissman: I’ve learned how to tolerate them. Nothing personal. 

Smith: How have you adapted? Because you have received many awards, you have very much been placed in the public spotlight. 

Weissman: Yes, even before the Nobel Prize, Katie and I were traveling around the world giving talks, getting awards. My life was incredibly busy. That started probably seven years ago, when people first got interested in RNA and RNA vaccines. The Nobel has certainly increased that. The number of requests I get for anything has quadrupled. But my life was busy before and it’s still busy after, and I’m afraid it’s always going to be busy. 

Smith: Do you have rules you live by that help you control everything? 

Weissman: The issue was last year, we were traveling so much. We were at our house maybe four days a month. That was too much. We were getting worn out. Now I limit it to one international trip and one national trip per month. We’re still away half the month, but we’re here half. 

Smith: It’s hard on your family. 

Weissman: Yes, my wife usually comes with me when it’s interesting. I was just in Houston, Austin and Durham. She didn’t come for those. When it’s Stockholm or Paris or Bangkok, she comes. 

Smith: What about just the interference in the daily routine? People like me taking an hour out of your day to talk to you. How do you control all that? 

Weissman: The first thing I always schedule are my lab people and lab work. Then any opening is available for non-lab stuff. 

Smith: You obviously are very happy in the lab. I suppose you’re very fortunate to have found something that absolutely drives you endlessly. 

Weissman: No, and it’s been 40 years. When I was a young kid, my father would tell me, you can do anything you want when you go to work. The most important thing is to enjoy it. I found that. 

Smith: Did you know from a young age that science was your thing and that you wanted to be a scientist or did it take time? 

Weissman: No, I think I knew from a very young age and my parents knew that they would tell stories that in our house, the doorknobs, the toaster, any appliance never worked because I was constantly taking things apart to see how they worked. I was curious and investigative from a young age. 

Smith: How nice to have parents who didn’t mind that you did that. 

Weissman: Mostly. 

Smith: In the old days, young scientists used to fiddle around with things like chemistry sets and make explosives or build crystal sets? I don’t know what people do as the equivalent now, but what did you do apart from take things apart? 

Weissman: No, I had the same thing. I had the sixth grade chemistry sets and physics sets and all of those sort of things. When I got a little older, I got into electronics, and I would put together electronic devices on circuit boards with soldering and make speakers and radios and that sort of thing. 

Smith: Were there any hiccups on the route or did science just go smoothly for you? 

Weissman: There were hiccups to life. When I was five, I developed type 1 diabetes that severely changed and constrained my life. I had to learn how to deal with that and how to take care of myself and regulate insulin and eating and what was limited and what I could do. 

Smith: That’s a terrific blow for your parents at five. I suppose at five one just takes things like that in one stride, because you don’t think about anything too much then. 

Weissman: Yes, at five. When you hit 12, then you start to think about it. 

Smith: How did it constrain life apart from eating? 

Weissman: Back then there wasn’t a good way to control blood sugars. What the doctors would tell my parents is ”he’ll be lucky if he makes 40”. They kept that from me until I was an adult. But, back then diabetics didn’t live full lives. I had to watch what I eat. I couldn’t go out to friends to a pizza place or a hamburger shop and pig out with everybody else. I couldn’t get sundaes for dessert. I had to control my diet, control my eating. 

Smith: Did it figure into your thinking about what sort of science you wanted to go into, the fact that you had this genetic disease? 

Weissman: When I was in college, I spent a summer at the Jocelyn Diabetes Foundation, which is the main hospital in Massachusetts for child diabetics. I did basic science research there. I didn’t choose to research diabetes. I chose immunology instead probably for a variety of reasons. But I certainly spent time researching diabetes. 

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Weissman: When I was in high school, my father is an engineer and he was laid off from work and couldn’t find another job. It was back in the 70s where engineers were laid off when they hit 40 and nobody would hire them. He ended up starting his own business and I ended up being his only worker. In addition to going to high school, I used to spend afternoons and weekends working in his company making mirrors. 

Smith: That work ethic that you developed then, obviously it stood you in good stead later, did you resent it at the time or was it just part of life and you wanted to help? 

Weissman: No, not at all. I wanted to help. I wanted to be part of my father’s company. 

Smith: It’s also, I suppose, a rare privilege to get to work so closely with your father as a teenager. Some teenagers and fathers drift apart. It sounds like you would very much together. 

Weissman: We had always worked together. When I was younger, we would build furniture together, fix the house together. For a lot of engineering and construction things, we spent a lot of time together. 

Smith: I think of this because there’s this lovely video circulating of you telling your parents that you’d been awarded the Nobel Prize just after the announcement, which is an unusual thing to have out there and to share. Talk about that moment for a second as an aside. 

Weissman: There’s one part that was left out that I’ll fill you in on, but we got the call at four in the morning and my older daughter had just returned from a honeymoon in Sri Lanka. She had gotten married in August and she had flown back to DC around 1am that night. At 6 a.m. I called her and said, I won. She hopped on a train and came up to Philadelphia. I suspect because she didn’t trust that we could handle it without her. After she got here, it was probably around nine and I thought it was a good time to call my parents. I didn’t realise that the cameraman was filming this. I thought it was just a personal moment and I called them. When I spoke to them I said, ‘Mom and Dad, Rachel’s here, we have something to tell you.’ My mother screams out, ‘Rachel’s pregnant?’ Which we quickly doused and then they cut that part out of the video. 

Smith: What a moment for Rachel to have all that on film as well. 

Weissman: Yes, she was happy to cut that part out. 

Smith: One has to ask, do you think your mother was more pleased with the real news than she would have been with the news she assumed was going to be the reason for the call? 

Weissman: That I’m not sure, I suspect so. There’s an old story that they tell. When I was probably around five years old, they did a trip of Europe that included Stockholm, and their tour guide took them into the Nobel Hall. I assume as a joke, but my father turned to the guide and said, reserve these two seats. 

Smith: Prescience or what? I am fascinated by the pleasure that the lab gives you, because obviously to sustain you for 40 years, and for it’s still to be, as I gather it is, just as fulfilling as ever, it’s a magical thing. Can you describe the pleasure of being in the lab and finding things out? 

Weissman: Yes, so in general, people don’t understand what lab work is. It, of course, varies by your age and experience. In general, I characterise it as four steps back, one step forward. It isn’t a place where if you seek pleasure, you go. You have to tolerate frustration to be able to work in a lab. When you do make a finding, even if it’s a little finding, because of all of the frustration and all of the difficulty getting it, it makes it that much more important. At least for me, it wasn’t one big finding. It was 25 years of finding after finding, some very small, some moderately big. It was a continuous development. The vaccine, the RNA just didn’t pop off the page one day. It was years and years of work and continued development and optimisation. To see something come along, to see something develop. It’s kind of like a child growing up. It’s 21 years of taking care of something with lots of frustration and potentially setbacks to then see them go off to college or get married or do whatever. It’s really kind of an inner joy. 

Smith: The idea of RNA as a therapeutic had been explored and basically abandoned by companies because of the problems they encountered, just didn’t produce the protein levels they wanted to see etc. I can see the attraction of trying to tackle the problem, but it must require a special sort of confidence to think that you can solve a problem that is so big. 

Weissman: I don’t think I ever looked at it that way. I think I looked at it that much of science, much of life fails the first few times. I’m sure Henry Ford didn’t drive away in the first car he made and Orville and Wilbur crashed a few times before their plane ever flew. It’s an incremental thing. I think what was important is that both Katie and I saw the potential that RNA had. That if we could solve these problems, it would be useful for hundreds or thousands of different treatments. It’s not so much confidence, but it’s seeing the potential. and the importance of it, that kept me going. I joke to my friends and family, if RNA vaccines didn’t work, I would have been some lonely researcher at Penn investigating something for his entire life that had papers and grants, but that’s it. 

Smith: Would you have been happy? 

Weissman: I would have been happy because I was doing research. I was investigating. I was learning. I was creating knowledge for other people to learn. 

Smith: I suppose that is the key right there. Not to say you’re not happier that it does work and that it has an applied benefit, but you have to be content with the search and the finding. 

Weissman: Yes. 

Smith: Talking of that, in 2005, you and Katie published the paper that basically said it was possible to use RNA as a therapeutic, and then not much happened immediately. 

Weissman: Yes, Katie won’t let me forget that night. It was the evening before the journal was to be published and I said to her, tomorrow our phones are going to ring off the hook. We both went home. We waited years before the phone ever run. It didn’t ring much until, so Derrick Rossi called in 2008 to tell us about his findings. Then Moderna called us in 2010 wanting to start a company based on our technology. 

Smith: Then you’ve got to go forward another, what, seven years or so until vaccine trials started with mRNA vaccines, yeah. It says a lot about how long it takes ideas to be received and to filter through and start having application. What do you think all of this has taught us about the way that science needs to be funded and treated? 

Weissman: Yes, so I’ve been contacted a lot by people in general, but by funders who ask the question, how do we prevent what happened to you and Katie from happening again? My response is usually, you can’t. You don’t know when you start something whether it’s going to turn into a vaccine for 2 billion people or just another experiment that gets you nowhere. There are thousands and thousands of people, all of whom think they’ve got groundbreaking experiments, ideas, and there isn’t enough money to fund them all. I have no idea how you find that one or two that has potential to be great. I don’t think it’s possible. 

Smith: Gosh, that is the absolutely essential question though, isn’t it? Can you not say anything about the type of problem, the type of person that you should back, should have trust in? 

Weissman: No, because the way NIH works for grants is they fund things that the answer is already in. You put in your preliminary results the answers to everything you propose to do. They’re actually funding future experiments. The other thing that determines funding is how established and successful you are. Getting NIH to stop doing that would certainly be a step in the right direction. But I don’t think it would solve the problem. After I published my Nature paper showing the modified RNA LNP vaccine worked in macaques and worked fantastically in both species, I submitted three NIH grants to do to make three different vaccines, three different pathogens. None of the three were even read by the study sections. They all came back and said, RNA will never work. You’re wasting your time. Forget it. Even after Nature papers were out showing that it works and companies had been starting trials, the reviewers were still dismissive and uninterested.  

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Brilliant: Adam, why was there initially so little interest in using mRNA as a therapeutic? What made it so tricky? 

Smith: Because there had been a lot of interest, but what people found was that if you made RNA outside the body and put it into the body, it evoked an immune response and people couldn’t find a way around that. It looked like you just couldn’t use it. It’s obviously very desirable to put RNA into a part of the body and have the body make the protein you want it to make. There was another problem, which is that you have to deliver it to the right target. It wasn’t so easy to package RNA in a way that would get it to the right place. But those two things, especially the immune response just put everybody off and they decided this wasn’t gonna work. 

Brilliant: How did Weissman not get put off and help to overcome these problems? 

Smith: He and Karikó had managed to find a way to circumvent the problem. They identified the problem, which is that in the body, mRNAs are modified in a way that makes them acceptable. So when Weissman and Karikó realised that they needed to make these modifications that would con the body into thinking that this was its own product, then they circumvented the problem and that was what they revealed in their big paper. 

Brilliant: This sounds like a really big deal. Why then wasn’t that very quickly picked up by others? 

Smith: I think that’s so interesting because you know, there’s a sort of feeling that, okay, problem solved, everybody should jump on it. But of course there’s a sort of received wisdom in the field after so many attempts at not making things work. People basically understand that it doesn’t work and then to change people’s mind and to make them see that this has been got around takes time and that happens again and again in science that uh, you know, some groundbreaking paper comes along. But it takes time for the field to, I suppose, notice it, believe it reproduce it all important. So although the person who solved the problem must expect immediate response, hooray, I suppose it’s not so surprising that people take a little time to come around to it. 

Brilliant: What do you think it was about Karikó and Weissman that sort of made them keep on going together in partnership with their work? 

Smith: That’s the extraordinary thing, that they didn’t seem to be put off. Um, they seemed to have a fundamental belief that they could get this solved. And I suppose it was that they brought two very different perspectives to the problem. Karikó believed fundamentally that RNA therapeutics could work and she was being, if you like, blocked by the immune system. Weissman was an expert on the immune system and that combination of skills and I suppose deep understanding of their respective fields was just an ideal combination. But they’re obviously both pretty dogged personalities who having got their hands on something just don’t want to drop the bone <laugh> <laugh>. And uh, it’s lucky for them both that they found each other, 

Brilliant: They found each other over a photocopier. Is that right? 

Smith: That’s how the story goes. It’s the joy of having shared lab equipment. If you had your own photocopier, you just wouldn’t meet anybody. But because they had to share the photocopier, they found each other waiting for one to finish. They started talking and those talks seemed to be very productive. Many institutions purposefully build their environment so that people are forced to share equipment and therefore they’re forced to meet each other. A famous case is the laboratory of Molecular biology in Cambridge which has always been so productive. There they have centralised lab facilities in each floor and it’s very purposefully designed to get people to intermingle in the middle of the floor. 

Brilliant: There’s sort of informal encounters that can then lead to interesting conversations and potentially good discoveries. 

Smith: Yes. As long as you are not so cross about not being able to get your hands on the equipment when you need it, keep just not in the mood to talk to anybody. 

Brilliant: In this case it clearly worked for Karikó and Weissman. 

Smith: It did indeed. Actually it’s very interesting to listen to Drew Weissman talk about what made them such a good team.. 

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Weissman: The central thing was we cared about the science. We cared about investigating, learning, trying to find people to work with as collaborators, there’s a lot of things that are important. Certainly, personalities matter. But with Katie and I, the central thing was that we both were interested in the research. We didn’t let hiccups or bad data stop us. Instead of giving up, we said, well, let’s figure out why we got results we didn’t expect. We both had that same approach. I think that’s why we worked together so well. 

Smith: It’s very interesting that a question shared can be even better, because often I suppose when you get a good question there might be a tendency to keep it to yourself and to try and crack this nut on your own.  

Weissman: Yes, but I think what was important with Katie and I was also our previous training. It was completely different. Katie was a molecular biologist who worked on RNA. I was an immunologist who had never worked with RNA or made RNA before. Putting those two knowledge sets together is what solved the problem. 

Smith: Yes, it’s recognising where the partnership can be very fruitful. Let me ask you about what it’s like to be, they call you the father of the mRNA vaccine. I guess it’s a title you don’t much care for given what we’ve talked about so far. What’s it like to have contact with all these people who either do or do not love the vaccine and who I know write to you? 

Weissman: Yes, so most of my calls, Zooms, whatever, that aren’t lab-related or aren’t outside people-related involve people wanting to collaborate. I almost never say no to a collaboration. I at least listen to what people are proposing. I don’t always say yes. If it’s something we’ve been working on for years already, or it’s something that didn’t work or won’t work, then I don’t. But many of them, we end up collaborating. We end up helping. My lab works with about 250 labs right now on a variety of projects. 

Smith: That’s a bewildering number of collaborations. 

Weissman: We want to make this work and we want to help the world understand. The other side, the people who send me death threats and those sort of things, those are annoying. The problem is they’re not only directed at me, they’re directed at my lab, they’re directed at my family. That’s when I get very upset when people threaten lab members and threaten my family. 

Smith: You have been very engaged though in this question of vaccine hesitancy and how to change people’s mindset. What has that engagement so far taught you? 

Weissman: We’ve put together a new institute at Penn that will address hesitancy and misinformation. The main goal is to figure out the messages for each group of people that will help them be convinced to take the vaccine. There’s many parts of hesitancy that others are addressing. We’re looking at the message. How do you convince people? What I’ve learned so far is that there are some people, no matter what we do or say, we’re never going to convince them to take the vaccine. We give up on those people. It’s a waste of time trying to convince them. There’s a lot of people who surround them, who interact with them, who aren’t sure, who haven’t made up their minds yet. They’ve got this very vocal minority who’s telling them vaccines give you cancer, vaccines make you magnetic, Bill Gates puts chips in them, all of these crazy things. Those are the groups that we’re working with to give them the message of what vaccines actually are, how they’ll help them. We work with a Philadelphia pediatric surgeon named Ala Stanford. When the pandemic hit and vaccines first were released, she’s African American. She went back to where she grew up and talked to the people and asked them why they weren’t getting the vaccines. Her assumption was that they would say, we don’t trust the government, they experimented on us. We don’t want them putting their new drugs in us. But that’s not what they said. What they said is, I can’t take a day off from work to drive into the city to get the shot over and over. On her own, she stopped being a surgeon. She set up a clinic in a local church, got vaccine, and started vaccinating people on weekends, on evenings. She vaccinated hundreds of thousands of people who otherwise wouldn’t have received a vaccine. She found the message that worked for this group of people. We know it’s possible. Now we have to address other groups of people who don’t want the vaccine. We’ve got a big group of experts at Penn and elsewhere who are working on this. 

Smith: That is so fascinating and it is so much about understanding people and meeting people on their own terms, if you like. There is a sort of, not just with vaccine hesitancy, but with all sorts of ongoing problems, the challenges to democracy that are so much a feature of conversations this year in particular. There is a sort of feeling that people just ought to understand and be able to react in the way that you think is the right way. Often it’s that people seem not to be hearing, not to be able to hear what’s being said because nobody’s actually talking to them. 

Weissman: Yes, but the problem is the leaders of these groups are close-minded. If you look at their motivation, it’s not always pure. RFK Jr., who’s a politician who is anti-vax, he works for a law firm who handles vaccine injury cases. All of his screaming and yelling about how vaccines aren’t safe are how he makes his money. They did a study and they identified 13 physicians in the United States who were responsible for 70 percent of the misinformation on social media. When they investigated them, many of them were selling made-up homeopathic treatments. What they were saying was, don’t take the vaccine, it’ll kill you, take my medicine. You can buy it on my website. I don’t know if they were anti-vaccine, but they were pro-capitalist, and their way of selling their drug was to say the vaccines were bad, take theirs. 

Smith: Yes, it’s really a meeting of two different cultures, isn’t it? It’s the reasonable arguments of scientists and policymakers against the often very unreasonable behavior of others. This idea that lies spread whatever it is five or six times faster than truth and all the rest of it. Perhaps to combat this you need to play by different rules. 

Weissman: Yes, and we have to figure out the rules that will work. 

Smith: You also get emails from just individuals, don’t you, who are just immensely grateful to you and Katie and the entire establishment for producing the vaccines. 

Weissman: Quite a few. Those emails I respond to. I don’t respond to the hate mail. But often it ranges from people asking for a picture or an autograph to just thanking me saying, I was able to see my grandmother, or grandmother says, I was able to see my grandkids again. Thank you. 

Smith: Alongside the idea of combating vaccine hesitancy, there’s also of course the question of distribution of vaccine and the whole idea of equity in access to health resources. You’re active there as well. 

Weissman: Yes, that’s something that I actually started working on when I first started in science. When I was at the NIH during my fellowship, I set up a lab in Chiang Mai, Thailand to study HIV transmission. The way the lab was set up is that it was run by Thai scientists. who did the research, did the work, did the analyses. Nothing was sent back to the United States. Everything was done there. A lot of people set up a clinic in a city somewhere, collect samples, take them home, and study them. To me, that compounds the problem, because it doesn’t teach people. It doesn’t make scientists better. It doesn’t give people ownership of the data and the ideas that come out of it. We’ve built or we’re building 15 GMP centers, mostly in South America, sub-Saharan Africa, Southeast Asia, and Eastern Europe. We’re also setting up research consortia in all of those places. My ultimate hope is that the researchers who are investigating local diseases of the local population will come up with new vaccines and new therapeutics to treat what’s in their area. Pharmaceutical companies have little interest in treating malaria or dengue or things that they don’t make their money back on. Local regions do because they’re serious diseases for them. Now the local researchers will make the vaccines, make the therapeutics. They’ll have the GMP production site so they can do the clinical trials and then distribute the drug. I started this with Bangkok, Thailand, 10 years ago. They’ve got one drug finishing phase three trials, another one in phase two, and another one entering phase one, which are all things that were developed in Thailand for Thai diseases. 

Smith: That’s fantastic. Thank you very much. I’m delighted to see that Xander stayed with this, fell asleep, but… 

Weissman: He’ll sleep all day if I let him. 

Smith: I doubt he often gets the chance. I can’t imagine that you spend days sitting on the sofa, not doing anything. 

Weissman: No, rarely. 

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Brilliant: You just heard Nobel Prize Conversations. If you’d like to learn more about Drew Weissman, you can go to nobelprize.org where you’ll find a wealth of information about the prizes and the people behind the discoveries.

Nobel Prize Conversations is a podcast series with Adam Smith, a co-production of Filt and Nobel Prize Outreach. The producer for this episode was Karin Svensson. The editorial team also includes Andrew Hart, Olivia Lundqvist, and me, Claire Brilliant. Music by Epidemic sound. If you would like to explore the journey of another laureate whose work has significant implications for medicine listen to our earlier episode with chemistry laureate Emmanuelle Charpentier. You can find previous seasons and conversations on Acast or wherever you listen to podcasts. Thanks for listening. 

Nobel Prize Conversations is produced in cooperation with Fundación Ramón Areces.

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