In this bonus episode of C&EN’s Bonding Time, we hear from 2022 chemistry Nobel laureates Carolyn Bertozzi and K. Barry Sharpless, who shared the prize along with Morten Meldal for their work on click chemistry and bioorthogonal chemistry. After a November symposium honoring the US-based Nobel awardees at the Embassy of Sweden in Washington, DC, the two chemists discussed their long history of collaboration, how winning the 2022 Nobel Prize in Chemistry has changed their lives, and how they hope to use the spotlight to break down barriers within science.
To learn even more about this year’s Nobel-winning science, listen to our October bonus episode about the prize.
The following is a transcript of the episode. Interviews have been edited for length and clarity.
Gina Vitale: Are those antibody earrings?
Carolyn Bertozzi: They are, I was showing Barry my TNT ring, which I thought was apropos for the Nobel since he was an explosives chemist. And these are monoclonal antibody earrings. Nerd jewelry, today.
K. Barry Sharpless: Yeah, I know, that’s Richard Lerner style, right?
Carolyn Bertozzi: Yeah. [laughs]
Gina (voice over): It’s not every day you get to nerd out about nerdy jewelry with two of the most famous nerds in chemistry.
Kerri Jansen: The owner of the nerdy jewelry is Carolyn Bertozzi. And it was K. Barry Sharpless admiring her explosively cool ring. As you probably know, those two chemists won the 2022 Nobel Prize in Chemistry, along with Morten Meldal in Denmark.
Gina: So when we heard they’d both be in town for a symposium at the Embassy of Sweden, we made sure Stereo Chemistry was on the guest list. We actually got the very special chance to talk with Carolyn and Barry together, just days before they headed to Stockholm to be officially awarded their Nobel medals.
Kerri: And now, we are very excited to share that conversation with you as an extra special lightning round of C&EN’s Bonding Time. I’m your host, Kerri Jansen.
Gina: And I’m Gina Vitale.
Kerri: So Gina, let’s quickly give listeners some background. We know Carolyn Bertozzi, Barry Sharpless, and Morten Meldal won the chemistry Nobel. What did they win it for?
Gina: Right, so, the prize was for “contributions to click chemistry and bioorthogonal chemistry.” Barry and Morten independently discovered a reaction now called copper-catalyzed alkyne-azide cycloaddition, in which two chemical groups snap together and only react with each other. That kind of reaction is called click chemistry—a term coined by Barry’s wife, Jan. Carolyn figured out how to do a similar kind of reaction without copper, so that it could be done in living cells. That led to a whole new field called bioorthogonal chemistry. These reactions can be used to easily join almost any two molecules together while avoiding unwanted side products. That’s a pretty huge deal.
Kerri: And if you want to know more about Barry’s and Carolyn’s contributions to click chemistry and bioorthogonal chemistry, check out our bonus episode from October, co-hosted by Gina. We’ll link to it in the show notes.
Gina: Yeah, we briefly heard from Carolyn in that episode, but these two have a long history of collaboration, and we wanted to hear more of that story. Beyond their appreciation for nerdy jewelry, we also discussed how the Nobel Prize has changed their lives and how they hope to use the award’s spotlight.
Kerri: Coming up next, from the depths of the Swedish embassy . . . Carolyn Bertozzi and Barry Sharpless.
Gina (in interview): We wanted to take this unique opportunity to have you both together to kind of talk about both of your work and how it kind of interacts with each other. So the first thing we wanted to ask and I’ll start with Carolyn is, when you were coming up as a researcher, what did Barry’s work signify to you? You know, were you . . . What were you following? What are you aware of? You know, how did that inspire you?
Carolyn Bertozzi: Well, of course, Barry was a very famous chemist already back when I was in graduate school. So you know, the work that I followed from his lab, as a student, was his asymmetric catalysis work. And he came to Berkeley and gave several lectures that I heard one during graduate school, and then another one later, when I was a young junior professor. And in both of those lectures—this predated his click chemistry era. And I remember you gave a lecture at Berkeley, I must, it must have been like 1998, or something like that. And I was an assistant professor, and it was on the titanium catalyzed epoxidation and related chemistries. But you actually did a demonstration during your lecture, where you had a big Erlenmeyer flask and a stir plate. And at the beginning of the lecture, you showed, you mixed some things together and let it go during your lecture. And at the end of your lecture, you said, “Okay, everyone, see that? I just increased the chiral pool in the planet earth during this talk.” And that made such an impact on me.
Meanwhile, my head was firmly baked in biology and trying to figure out how to do chemistry in biological systems. So, you know . . . And we had been doing azide chemistry around the Staudinger ligation, as we called it, and looking for alternatives where we could leverage the azide as a bioconjugation handle. And then we read Barry’s 2002 paper on copper catalyzed alkyne cycloadditions, which became one of the most important chemistries in all of chemical biology. But it wasn’t going to solve our problems for in vivo chemistry, but we certainly were an early adopter of the copper catalyzed click chemistry for chemistry outside of living systems, like everyone else in the chemical biology community.
K. Barry Sharpless: Yeah, well, I remember I don’t know what year it was, Carolyn. But you came to Scripps to give a talk. And we had time—probably a half hour, at most 40 minutes—but we ended up talking in my office for maybe 2 hours.
Carolyn Bertozzi: A long time.
K. Barry Sharpless: We just went missing.
Carolyn Bertozzi: We blew the schedule. Yeah.
K. Barry Sharpless: We went missing. And . . .
Carolyn Bertozzi: That was in 1990, about 2000, [audio starts to fade out] maybe something like that, around 2000, because we had just published on the Staudinger ligations.
Gina (voice over): As you can hear, Carolyn and Barry have a great rapport. They took a little detour down memory lane here to talk about more work they collaborated on, praise the research of German chemists, and remember a colleague who had passed. We took the chance after to ask how their storied collaboration might shift in light of the Nobel win.
Gina (in interview): So you guys have, obviously you’ve both been working together, it sounds like for a pretty long time. And I’m wondering, you know, you’re now part of a pretty exclusive club. Does your working relationship change now? Are you invited to more parties or, you know, do you get some more opportunities that you didn’t get before?
K. Barry Sharpless: I don’t bother her because she’s young. And she’s brilliant. And I don’t really . . . but if she has a question, or her students have a question . . .
I would say, everybody, you have to keep moving on. And for me, I just try another thing. I can’t do the same thing. As soon as I finish something, I have to leave it. And . . .
Carolyn Bertozzi: Well, first of all, Barry has already had a Nobel Prize for two decades.
Gina (in interview): I was going to say, you’ve been in the club for a while, but . . . right.
Carolyn Bertozzi: So he knows what life as a Nobel Laureate is all about. I’ve only been wearing that hat for a month.
K. Barry Sharpless: But we knew you were going to get one.
Carolyn Bertozzi: I couldn’t even tell you yet.
Gina: Yeah, sure.
Carolyn Bertozzi: But I, one thing I can say is that to the extent that having a Nobel Prize suddenly amplifies your voice, I guess? Maybe that’s one side effect?
K. Barry Sharpless: Yeah, Yeah. That’s right. People would not listen to me because I say things that are hard to understand or wander around. And then they started, my wife said, have you noticed in the last couple of people who are listening to you. You’re not saying anything wiser than you were before. But that’s the way nature is.
Carolyn Bertozzi: Right. Right. So to the extent that things that we’ve been saying all along suddenly have more gravity, that could be a really positive thing.
K. Barry Sharpless: That’s what leaders depend on, is that politicians and they have to convince us that something’s right, that we’re gonna be able to sleep and wake up tomorrow it’ll be here. I mean, like sitting around a campfire, I always think of leaders as the ones who can tell the stories that make people go to sleep and relax. And scientists, we don’t have that kind of, we’re looking for connections that we don’t quite know what, what they are. And if you’re really smart about science, you know that the things are subtle, often. And that’s the part that we can be wrong our whole life, but in a profitable way. Somebody else will find where we were wrong, but that’s okay. Because it works too. It has to fix the thing that it displaces, that’s all.
Kerri: Carolyn, is there anything in particular that you’re hoping to be able to draw some attention to now with this platform?
Gina: Great question.
Carolyn Bertozzi: Sure. You know, there is, of course, there are issues I’m very passionate about and some of them are scientific issues. And some of them are more, you know, having to do with the social science, you know, around chemistry, but I have a deep passion for glycoscience. And that’s an area of biology that’s kind of underrepresented, you know, compared to the importance that I think that these molecules have.
Carolyn Bertozzi: And, and so so you know, maybe there’s a brighter spotlight I can cast on glycoscience as a really important area for biomedicine. But then at the same time, as you might have gleaned from my, my little monologue up there, it’s very important to me that I contribute to diversification of the science workforce. I think it’s really important for humanity, because science can do so much good in the world. But if people don’t participate, who come from different places, different backgrounds, different mindsets, then we run the risk of developing science to benefit only a small fraction of society rather than all of humanity, which is what I believe we should be doing. So maybe I can get more people to kind of get on board that train, you know, now that I have a Nobel Prize backing me up.
Gina: Now, Barry, you mentioned you, you’ve gotten this a couple of times. And I’m wondering, did you ever, you know, after you first received the prize in 2001, did it ever cross your mind, you know, maybe I’ll be back here again, receiving yet another?
K. Barry Sharpless: No, not really. I just kept doing things. I just changed. And then by accident, we just tripped over the copper reaction, which the copper reaction is really unique and Meldal tripped over it at the same time, the Dane. And, yeah, those things. But the things that are sort of anticipatable, they’re normal science, and science that isn’t good is when somebody just says they’re going to measure x to z, and nothing is going to distract them, they’re going to get that data there for life and God and country. But, you know, it’s not really where . . . Often you don’t get what you find, you don’t set out to get what you find. If you do. It’s not. My wife’s a writer. She said, discovery, I’m sorry, this discovery is a surprise. I mean, a surprise has to be a surprise, right? I mean, because don’t you think, wow, what’s something funny? That’s what I remember saying a couple of times. I said, “Well, that’s very funny.” That’s something funny there. And that’s the way discovery happens.
Carolyn Bertozzi: So the disruptive discoveries are by definition, surprising, shocking, unexpected. Unbelievable at first, you know, that’s really common, I think.
K. Barry Sharpless: Yeah, somebody who wants to control everything will be unlikely to make it, because they’re going to want to just, maybe if they’re smart, they’ll see it, but they’ll just look over it because it didn’t fit what they expected. I think that’s human nature to look over. Otherwise, we’d be distracted to the point where we’d be eaten by the saber-toothed tiger, right?
Gina: Sure, sure.
Carolyn Bertozzi: I think something that concerns both of us is that the scientific funding structures and the reward systems . . .
K. Barry Sharpless: Oh, yeah.
Carolyn Bertozzi: . . . need to be set up to incentivize people to do risky things, to pursue unexpected surprises, and that’s not always the case. Right?
K. Barry Sharpless: No, no.
Carolyn Bertozzi: So now we run the risk of having the money focused on the least risky science, right. And that’s, that’s not what you want for discovery and creativity. So I think that’s another, that’s another sentiment that . . .
K. Barry Sharpless: I thought they ought to take some really good people who have ideas and proven ideas several times, and let them read the proposals of the younger people who are starting out and give some of the best ones that you think are the best, say, 5 years to show what they can do without asking them so many questions. They have so many reports. Well, you’re good at that. But I don’t, that kills me. I couldn’t write. I hated to write the reports. The grant, I couldn’t, I had to go down to the lab and do it. So almost everything I did, I’ve tested already. And I said I was going to do it. And so that’s the way it was with me. I couldn’t possibly get an empire together because I couldn’t plan anything. But you know, it’s the person’s at the end of the day what they produce in their in their lifetime and you don’t have to it’s not integrated. Exactly. You don’t expect the person to just keep going up. You know, it’s just like I can do something great and then go down and do something great. That’s a person that needs to be doing that and inspiring other people. And if they don’t have the money, they can’t make an effect in this world, right?
Gina (voice over): We weren’t given very much time with the Nobel winners in the embassy, but we did make sure to squeeze in the one question that’s on everyone’s mind.
Gina: They’re starting to play us off over there, but just super quickly, I just want to throw in—Carolyn, when should we expect your second prize?
Carolyn Bertozzi: [laughs] I don’t even know what to say. I’m still in shock from the first one.
Gina: We’ll give it another month and then ask you again.
Kerri (voice over): This episode was written by Gina Vitale with audio editing by Mark Feuer DiTusa. Stereo Chemistry’s executive producer is me, Kerri Jansen. Full credits for this episode are in the show notes. Many thanks to the Embassy of Sweden for arranging this interview.
Stereo Chemistry is the official podcast of Chemical & Engineering News. C&EN is an independent news outlet published by the American Chemical Society.
Gina: Thanks for listening.