Presidential Lecture Series | David W.C. MacMillan

Good evening, everyone. Good evening. Thank you for coming and welcome. And people ask, what is a university? We think that a university is a place for the curious and brilliant minds. And to maximize the vibrancy of intellectual life on our university campus, the Presidential Lecture Series plays a critical role. And this evening, I am excited and delighted to welcome a friend, a former colleague, and a scholar who has attained the pinnacle of excellence in scientific discovery, as well as in innovation and entrepreneurship to West Lafayette, Indiana. In particular, in 2000, he developed the iminium catalysis as the first organocatalytic activation mode that was designed rather than discovered. And he presented a general strategy for asymmetric organic synthesis. And in 2006, he also included radicals in this general strategy through the SOMO catalysis. In 2008, he further combined photorhodex catalysis with organocatalysis in an interwoven activation pathway for alkylation reaction. Please warmly welcome on stage the 2021 co-recipient of Nobel Prize in Chemistry, David McMillan. Hello. Thank you, Meng, for that very kind introduction. It's wonderful to come over here to Indiana, to Purdue today. I've had a fantastic day. Basically, when I contacted, or Meng contacted me to give a talk, he said, could you give a talk for 15 minutes, about 10 to 15 minutes, about kind of what you do. So I'm gonna lead off by giving a quick 10 to 15 minute overview of what we do. Now, this is not designed for chemists. If you're a chemist, this is gonna get really boring really, really quickly. This is really for, in general terms, for a general public to understand what we're doing. So, to get it started, I'll start off with, where am I from? This is a question everyone asks me as soon as I start talking. They kind of hear a weird accent, and immediately they say, where are you from? And so I always like to tell them, I am from Scotland. This is Scotland, and I always like to show this map. I apologize for those of you who know where Scotland is. This might be insulting to you. But it turns out, the vast majority of Americans have no idea where Scotland is, okay? So this is Scotland. It's right here, and there's a really easy way to remember where Scotland is. Scotland is always on top of England. Always, okay. Really easy, really, really easy, okay. All right, so this is where I'm from, the town of Glasgow, the city of Glasgow, just outside a small steelworking town. My father was a steelworker, my mom was a maid, and that's where I grew up. And I'll just show you this picture. This is, I always tell people we were working class. We were a very working class family, but I felt very wealthy because I had an amazing childhood growing up. It was very funny, typical Scottish traditional sense. Every day was all about joking, having fun, and making fun of each other. And this was an amazing group of people I grew up with. And you can tell this is the 1970s just by the wallpaper, basically. Some of the hairstyles as well. Okay, and this is where I grew up. This is a council house. A council house is a house, if you don't own your own house, you would rent a house from the local government. So we had to rent our home from the local government. Americans always ask me, why are you only showing half your house? And I would say that was the only part they gave us. So that's our house over there. And then I'll show you this picture, and you're probably wondering, why is he showing up to Purdue and showing baby pictures of himself? Well, I was born in 1968, and the reason why I'm showing these is after I won the Nobel Prize, the Nobel Foundation, they contacted me and said, can you send us photographs of you as a baby? And I said, why? Why would you want photographs of me as a baby? They said, well, we want to put it on our website. And I said, again, why? And they said, well, people like to see this stuff. So I was like, okay. So I looked to find photographs of me as a baby, and I couldn't find any. So I contacted my sister back in Scotland. She sent these to me, and I put them, I gave them to the Nobel people, and these are now all on the Nobel Prize website. Now, I think this is the greatest practical joke of all time because I'm pretty sure that's not me. I'm pretty sure that's my sister, actually, because she goes and checks that website every single day. Anyway, all right. So basically, 2021, October 6th, I woke up to the news that I had won the Nobel Prize in chemistry, and I was just gonna spend a bit, very quickly go over what it is that we actually do. The number one question I always get asked is what on earth does asymmetric organocatalysis mean? And I'm just gonna sort of quickly break down two parts of this. The first part is what is catalysis? What does that even mean? So catalysis is this amazing, amazing thing. So if you think about your surroundings right now, if you look around you, absolutely everything around you is made from a chemical reaction. This is a photograph of my office. Absolutely every material, every single piece of matter which is in my office was made by a chemical reaction. And here you can see this going through some of the chemical reactions that make the things in my office. Now, if I zoom in on one of these, this is my coffee cup, and this is the chemical reaction to make caffeine, which is obviously the key constituent of coffee. And chemical reactions typically require energy. They're typically not spontaneous. And that becomes really important because the way it would show this, so if I was teaching a class here at Purdue to undergraduates or even to high school students, the way we represent this is that there's what's called an energy diagram, the energy required for this chemical reaction to happen. Now, I don't want to get too technical, but if you think about it this way, imagine every night that you're going home, you have to basically walk over a pretty tall hill to get home every night. That would obviously require a good amount of energy. But imagine I could build a tunnel that goes through the middle of that hill. That would make it so much easier. It would require much, much less energy. And that's exactly what catalysis does. Catalysis makes existing chemical reactions easier, faster, but most importantly, allows previously impossible chemical reactions to happen that did not happen before, which is really important. Now, if you're wondering, does catalysis really impact our world? It does. And I can prove this in a couple of different ways, but quickly, this is the population of the Earth over the last 2,000 years. You can see it's roughly flat. It's roughly completely stable. Then at the beginning of the 20th century, there's an inflection point, and this rises all the way up to 8 billion people, where we are now. As it happens, you couldn't have 8 billion people on our planet without one catalytic reaction. This is this one shown here. Takes nitrogen and converts it over to ammonia. So why do we need this one catalytic reaction for 8 billion people to be on this planet It's really simple. We need it to grow food. We wouldn't have enough food to feed 8 billion people without this one catalytic reaction. My favorite small piece of trivia about all of this is if you think about your body right now, if you think about all the different atoms that are in your body and your protein and your organs and your tissue, and you think of all those nitrogen atoms which are in there, 50% of those actually come from a factory in Germany. If that doesn't freak you out, I don't know what will. All right. Okay, so other parts of this, 90% of industrial-scale chemical reactions use catalysis. 35% of the world's global GDP is based upon catalysis. So it's clearly important, I'll let this slide play out, but this is just pointing out the fact that basically catalysis impacts our world from food to medicines to materials. So many different aspects of our life is simply based on catalysis. All right, so what does organo mean? So organo is really, if you go back to 1996, what were the branches of catalysis in 1996? There was two major branches. There was biocatalysis using the enzymes of life, things you'd find in humans and other animals, and also man-made catalysis, metal catalysis, using synthetic preparation, rational design to come up with ways of doing catalysis. So typical metal catalyst, it actually contains both a metal and organic components, at least the ones which were involved in this thing called asymmetric catalysis. Now, the really interesting thing about this, you can see you can obviously almost break this right down the middle, and the right-hand side is the metal component, and some cases, not all cases, but in some cases, metals can be expensive, toxic, difficult to work with. They're often not sustainable. I think we have 90 years of palladium left in the Earth's crust right now, and so that's a kind of scary thought. But the interesting part in all of this, the left-hand part is the organic part. Organic molecules, we're all organic, and typically, organic molecules are inexpensive, they're safe, they're sustainable. When you're finished with them, they go right back into the life cycle, so it's obviously completely renewable in interesting ways, and we became really interested in this idea, what if we only used the organic part as the catalyst? Okay, so this basically became known as organocatalysis, and basically, if you think about what would the advantages be of organocatalysis, this is what my first group became really interested in. This is 1998. We set up our lab at Berkeley, and I love this photograph because this is a very young group. It was a first-year assistant professor. This is 10 past 10 on a Friday night. We're in the lab working hard, trying to make a difference, and really didn't know what we were doing, but we were having a really fantastic time, but what we knew we wanted to work on was this idea of organocatalysis. The whole point of wanting to do organocatalysis, because these molecules are readily available from nature. They're not sensitive to air and water. You can be outside in their environment. They're inexpensive. You don't have to use special equipment like these large glove boxes to actually do this type of catalysis, and they're non-toxic, and they're completely recyclable, so on that basis, we became really interested in this idea. Could you actually develop a field of catalysis based on using these organic molecules? The only problem was, at the time, we had absolutely no idea how to do this. No idea. It was a grandiose idea, but we had no idea how to do it. If I fast-forward in the story about six months, though, we eventually came upon a catalyst that actually allowed us to do three chemical reactions, and then we generated a second-generation catalyst that literally allowed us to subsequently be able to do hundreds of different chemical reactions. Fortunately, other scientists came along, such as Jorgensen and Hayashi, who also added to these types of catalysts that were available, and then you start to move into the multiple hundreds of different chemical reactions that you can actually now do using this form of catalysis. Okay, so what are the applications? What are the real-world applications? And there's many different versions of this, and I'm only going to show you two, maybe, well, basically three. The first one is in the area of flavors and fragrances, or perfumes. And you might say, well, why would anyone care about perfumes? But if you think about fragrances and perfumes, they're used on an enormous quantity, an enormous volume, every day around the world. And one of these is Lily of the Valley, and along with Ferminique, which is a company in Switzerland, they were able to take a process that involved seven chemical steps and reduce it to just one chemical step. Now, to make this perfume in just one step, if you think about the energy savings, the cost savings, et cetera, that's very large. And now they also make all these rose perfumes in Northern India on hundreds of metric tons per day scale, really an enormous scale to do this. There's other applications, but probably the number one application has been in the area of medicine and being able to produce medicines on scale. I'll just show you one example. There's many of them. This is Tulsedupant. I think it's 3% of the world's population suffers from migraines every single day. And this, I like this example because it used this type of catalysis that we developed to allow them to be able to make this medicine on scale. I was actually at Merck about a month ago. They actually showed me a cancer treatment that they've developed that actually uses multiple organocatalysis steps to actually make that cancer treatment, which was obviously exciting to see. I'll show you one last application, then I'll stop talking, I promise. And that is about this thing called democratizing catalysis, which is something that I get very excited about. This is not something we ever set out to do, to be completely honest. But the point of this is this type of catalysis is extraordinarily affordable and an accessible field to the world. It's so cheap to do this type of catalysis that it's now performed daily, basically in every continent across the world, both for education, but also for research. My favorite aspect of this is people always ask me, what is the next big idea, the next big thing that's gonna come from organocatalysis? And I always say, I don't know, quite honestly. But the one thing I do know is it's not gonna be based on who has the most money or who has the most funding. It's gonna be based on who has the best idea. And I think that's something which is really, really cool. All right, I'll just finish off. What does the future hold for organocatalysis? Well, obviously, with this ever-increasing population of Earth, we have to keep thinking more and more responsibly about what types of catalysis we're gonna do. And in that context, organocatalysis, biocatalysis, photocatalysis, electrocatalysis, even metal catalysis, the metals that I told you sometimes can be problematic. Many of those metals, such as iron and other base metals, which are readily available, are gonna be part of the solution for sustainability as we move forward. Okay, with that, I will stop talking now. And I just want to thank you for your attention and listening to all this. Thanks a lot. Thank you. Well, please. Thanks, man. Wow, now here come the questions. Okay. And, you know, I've been studying chemistry a lot of the past few days. I'm sorry. And I got great teachers from our outstanding Department of Chemistry and the Davidson School of Chemical Engineering. But let me start with an easy question, easy for me to ask, that is, you grew up in Scotland. How's your charity foundation doing today with the Scottish school children? Yeah, so thanks for bringing that up. So what happened was when, after winning the Nobel Prize, I didn't realize this, but you win a reasonable amount of money. Good for you. Yeah, so what we decided to do, myself and my wife decided this quickly, we were gonna give it to charity. So we decided to set up a charitable foundation and it's for underprivileged kids to help underprivileged kids in Scotland predominantly to help them get to college or university and also to help them stay in college and university. So we started that a year ago. We gave our first grant this year and that was a wonderful, fantastic thing. We're really excited about it. The other part was my mom and dad have passed away, but we decided to name it after my mom and dad because they were so big into education as so many moms and dads. And so for us, it was great to do that. And so we just gave our first thing. So thanks for asking me about it. Well, fantastic. This is the first presidential lecture in 2023. Each one is gonna be populated with at least one embedded commercial about Purdue. So we'd love to see the scholarship recipients to apply to Purdue when they are for college or graduate school. I'll put that in the stipulation in the next grant we get. That's lovely. Thank you very much. Thank you, David. Well, so, you know, Nogishi at Purdue discovered how to use zinc compound to help palladium to make organic molecules. And he received the 2010 Nobel Prize. And he was a student with Brown at Purdue who was the first Purdue faculty to receive Nobel Prize in chemistry. So mentors matter. Can you share with us perhaps one of the favorite memories you had with your former advisors? Yeah, there's a lot of memories I don't want to share. This is being recorded, it will be on YouTube. Yeah, I learned some of my early management style which I've subsequently tried to forget. No, I was really, really fortunate to have two amazing advisors. When I first came over to Southern California to do my PhD, I'd never been in America. And I landed in Southern California and I had no idea where Southern California was which was kind of interesting. And I had this great, phenomenal advisor called Larry Overman. And what I learned from Larry was he was an absolutely brilliant chemist but he was an amazing human being. And it was this idea that every human being, every individual that he would interact with, he cared about the person more than he cared about necessarily getting the best out of that person for the program. He wanted the program to do well but he really cared about the people. So for me, that was the thing I probably learned most from Larry. Dave Evans who I worked for at Harvard was just, I mean, I've never, I watched this, I don't think I learned from it but he was a perfectionist at a level that was beyond a lunatic friend, right? And so whenever he would give presentations or talks, he would always have these amazing slides. And what he sort of taught me, I would say, is like every time you think it's good enough, it's not good enough. And I think it's that always, that idea that you can always push it further and push it further. Those are probably the two main things I learned from him. Well, David, what you said reminded me about my co-advisors, the late Tom Cover and Stephen Boyd, both at Stanford. And I remember both were perfectionists and Tom Cover would sit down with me to write a paper and spend three hours to draw and redraw one illustrative picture to demonstrate the concept. And then said, no, no, the annotation should be there. No, no, change it. No, no, change back. No, straight line, dotted line. And I was hungry. I was like, whatever line, it's the same thing. No, no, no, no, no, no. It actually generates different responses in the audience. So we have to be consistent, we have to be careful. Is it dotted line? Is it arrowed this way or that way? And Stephen Boyd, I remember, showed him a proof of a theorem. He said, the converse part is too complicated. I said, you haven't read it yet. This is too complicated, it's too long. I said, what does it matter if it's correct? Nope, you gotta make it simple. If it's not the simplest, then you haven't understood it. So I made it simpler. And then he looked at it, still too long. It's two paragraphs. I think this is a trivial result. So you should be able to prove in one. And then finally, I end up with one paragraph, two arguments. And they said, this is about right. But it doesn't make me look good anymore. This is like a trivial thing anybody could have proved, is that, well, then you probably have understood it. So now I forgot what the theorem was. But I cannot forget that Stephen Boyd and Tom Cover insisted on intellectual depth and simplicity as a beauty. Well, your students, your advisees, I heard some of them said, on the day of the Nobel Prize announcement, they got an email from you. They started by saying, despite recent events, we're still gonna have the group meeting today. So how was that day like? Yeah, that day was absolutely crazy. And this looks like a setup. But I was gonna, I actually brought this just in case you would ask these questions. So I have some slides, if you can. I'll show you real fast what it was. This might be the most frequently asked question for you in the past 15 months. Yeah, so I'll do this quickly. So hopefully this shows up. Does that show up? Yeah, so basically, how was that day like? So I promise I'll do this in five minutes. You are prepared. But I think it's a funny story, and I like telling it, as you can probably tell. But I woke, well, I didn't wake up. And I usually wake up early. And my wife, actually, who doesn't usually wake up early, was lying in bed, and she starts elbowing me. And she goes, you know, your phone is buzzing. It keeps buzzing. And it's five o'clock in the morning. And I was like, I don't know what's going on. So she jumps out of bed, picks up my phone, and looks at it, and then, because it's making noise, moves it from my bedside table to the window ledge to get it away for the noise. And she says, by the way, it looks like someone from Sweden is trying to reach you. And it looks like Ben List, who is the other co-recipient, is trying to reach you. And I'm like, what is going on? So I thought, so I jump out of bed. I pick up my phone. And this is literally the text that came. And I don't know if you can see this, but this says, Dr. MacNillan, please call me Goran Hansson, Royal Swedish Academy of Sciences. And I immediately look at this and went, Dr. MacNillan? Who's Dr. MacNillan? Like, this is obviously fake, all right? So. There's a lot of these kind of phone calls these days. Yeah. And so then I get this message from Ben List that says, wake up, smiley face. And so I was like, I know what's going on. Because I've had a lot of mischievous students over the years. And I'm like, this is a completely brilliant, this is them trying to do a prank. This is clearly a prank. So I get off, I actually talk to Ben. Ben has been told, you can't tell him he's won the Nobel Prize. They have to tell me. So, but you can infer it. So he's on, and he's saying all these things to me about, you know, Dave, this is happening. And I'm like, what's happening? And so on and so forth. I wouldn't read this all to you, but basically I explained to him that I think this is a prank by text. He says, I'll tell you, it's a pretty good prank. I know the voice of the people, Dave, this is happening. And I literally said, I bet you $1,000 it's a prank. And then he said. I'm glad you got some money from the guys. And then he said, well, call me if they reach you. I look forward to receiving the $1,000, which was really nice of him. And he says, dinner together, which is very generous. And I said, no, going back to sleep, cheers. And I went back to sleep. My wife would say, I went back to sleep for 30 minutes. And then I got up about 30 minutes later, went downstairs, I was like, okay, I want to see who won the Nobel Prize. So I went downstairs to the kitchen counter, opened up my laptop, went to the New York Times. And in the New York Times, on the website, this is what I saw. And so I was looking at this and I was like, well, that kind of looks like Ben List. I'm like, who the hell is that? And so people always ask me, what did it feel like that moment you realized you won the Nobel Prize? And I always say, I was kind of elated, but I was also somewhat offended. So that was how it started. It doesn't capture your facial expression very well. Well, that's very interesting. I'm so glad that text works these days. But when I was undergrad, freshman year, I took quantum mechanics from Professor Laughlin, and he ended up winning Nobel Prize. You know what he did? He came back next day, actually that morning, he said, well, the good news is that I got a Nobel Prize in physics. The better news is that since I don't really care about giving you a final exam at this point, everybody gets an A. The easiest A ever in quantum mechanics. So to date, I still don't understand quantum mechanics. Well, now, you made at least two major discoveries. One is in 2000, this cookbook going from sort of happens by nature into a systematic way to synthesize organocatalytic activation modes. And then in 2008, you published a paper that combined photorhodics with organocatalysis. So the photochemistry is not only good for displays, but also good for carbon-carbon bond formation. In either of the two cases, is there a particular aha moment, or a moment to say, ah, that was all wrong, time to pivot? For the organocatalysis there was, it was basically, as I gave in that short summary, we knew we wanted to do this thing called organocatalysis, and we had no idea how to do it. And, you know, you kept sort of thinking of things and thinking of things that wasn't very good. And then one of my students, a first-year student, asked me the mechanism of a really simple reaction. And I went to the board in the lab, and I started drawing it up. And as I was drawing it up, I literally had that sort of quintessential eureka moment and said, wow, this should be able to work for organocatalysis. And we literally tried it that afternoon, and it worked that afternoon. And so it's funny, because you sit with all these other Nobel Prize winners and they talk about how they worked on this for 15 years to get this breakthrough. And I was like, yeah, we did it that afternoon. And you were a first-year assistant professor. First-year assistant professor, and it actually worked. Four radars was slightly different. We got it working pretty quickly, but it wasn't obvious to, I think, everyone, probably including ourselves, that it could go in all these different directions. But after about, working on it for about 18 months, we were working on about two or three different things, and I suddenly realized, I felt I realized that we had to really just focus on that particular idea. And then I would say it's about another two and a half years before the world really caught on, or it took off. And so it became really very large now, but it took probably four years to get to that point. Well, were you listening to some music while you were getting that aha moment? No. Did you just finish exercising? I'm just trying to get a clue as to how to get aha moments. I think everyone has aha moments. I think what it was for me, and I tell my group this all the time, is that it was, we knew we wanted to do the systematic organocatalysis. We just didn't know how to do it. So we were, it's the old fortune favors the prepared mind idea. Like, you know what you want to do, but you just don't know how to do it. So whenever someone asked me this completely trivial question, it was at that moment you went, wait a minute, this should be able to be working over here. And I think if we hadn't been thinking about this idea, we would have never, I'd have never made that connection. So I always keep telling people who are leaving my group, think about the big problems that you want to solve, even if you have absolutely no ideas about how you solve them. Because then you're prepared, you're in that mindset. Yeah, you know, I've many dreams during which I thought I discovered how to solve the balance sheet financial situation of a particular college. And then I woke up, it dissipated. I could not recreate that process. People say that if you listen to classical music, it helps. So I've been listening to Brahms every other night, and then always just fell asleep right away. So it doesn't work for everyone, but I guess you're right that, you know, luck favors those prepared. You've been thinking about it before that afternoon. Well, you picked a sort of unpopular topic in the 1990s, because I guess since 1971, organocatalysis at least by nature has been studied, but by the 1990s, most people were focusing on metal catalysis. So as a first year faculty member, how did you pick up the courage to study an unpopular topic? Oh, I don't know if there was courage involved. I would say that it was more, I think scientists quite often by nature were contrarians. Like we kind of like to just do things which are different. I think we're all slightly rebellious. We're like rebels without a clue, basically. And so it's this question, what are the things that you, so I personally love doing research, which kind of slightly goes against the grain just a little bit, just to, just for fun, just to see where it takes you. I think a lot of other people do as well. So when everyone else was doing sort of metals, I think I became really interested in why are we using metals? Who ordained that we have to use metal? Metals are fantastic, but it's this kind of question of why are we doing what we're doing? And is there any other alternatives out there that could be interesting? And that's what kind of gets you off on these directions. And at some point you start to realize, wow, there could be huge advantages by doing all these other things. And you've just got to sort of break out some of the current ways that we do things. Yep, one of the most prominent beauties of academia is that professors do not have to listen to a particular authority. Certainly not to the president of the university. Now, these chiral molecules, they have the same chemical structures, but you cannot superimpose one onto its mirror image. So speaking of symmetry breaking, I've heard of two philosophical views on this. One says that, well, symmetry is an artifact of how human beings get to understand and describe nature. It's really an artifact of our language to describe and think about science. And therefore, symmetry breaking is just an artifact of that. Nothing is broken. It's just the way we describe it, we have to resort to that. The other view is that there is, indeed, a conflict at some point, and nature picked one hand versus the other, and then self-amplification makes symmetry breaking useful for things to happen. What's your reading on this mystery? All right, so I feel like you, absolutely, I'm really being honest here, we did not set this up ahead of time, so. Yeah, yeah, this one absolutely is not a typical question. But I think this is a kind of really interesting point. For those of you who are not chemists, I find this personally completely fascinating. And so the whole point here is that, so if you think about this, this symmetry breaking, what does that mean? It sounds very sophisticated and complicated. It's really simple. It's like if you look at your hands right now, and you ask yourself, are they identical? And they kind of look like they're identical, right? They sort of look like they are. But we know they're not. They're actually mirror images which are not superimposable on each other. And what does that mean? But if I took my glove from my left hand, and I tried to put that on my right hand, it wouldn't work. It doesn't recognize it, right? So we know they're different. Why is that important? Organic molecules, actually lots of molecules, have that property. And you might say, okay, okay, why is that interesting to have this property that they're mirror images, but they're not superimposable? Well, if I go into a lab, and I try to tell them apart in a lab, it costs an incredible amount of time. You have to use really expensive equipment just to tell these two molecules apart. Really, really difficult. However, if I was to take my daughter, when she was just three years old, and a much nicer person, when she was three years old, and you would literally give her these two molecules, she could tell them apart instantly simply by smelling them. So why is that? Why is it in a lab? It's almost impossible, but yet for a three-year-old, it's instantaneous. Well, this is the crazy part. The crazy part is human beings are made up predominantly of one mirror, or animals in general, were made up of one mirror image, but not the other one. And nobody knows really why. So that's fascinating, if you think about it. All our bodies are made up of one mirror image. People sort of talk about this. Maybe there's some other world somewhere else. It's the opposite mirror image of our world. We'd look identical, we'd be identical, but we couldn't eat the same food. We wouldn't be able to digest it. We wouldn't be able to eat the same things. So it's a really, so the big implication there is that when you make drugs, you have to make drugs which are one mirror image, and not the other mirror image, because the other mirror image could be dangerous. It could have side effects. It could be toxic. And that's why it's so important that you make the right mirror image of a given drug. So this whole business about how do you sort of view it, at least physically, it's so difficult to tell these molecules apart, but it's still unbelievably important that we understand them. Otherwise, it has these really important implications for biology. Absolutely. Well, I venture to guess that in the other parallel universe where the conflict picked the other hand, Neil Armstrong is still a bottle maker. Well, you showed some lab equipments. Those can be expensive. Now, I know that you work extensively with companies such as Merck and Pfizer, as a lot of your fundamental breakthroughs have a lot of implications to pharmaceutical industry. So what do you think is the university research unique value add when we have very well-funded industry research labs? It's a great question. So industry by its nature is extraordinarily applied, and that's their job. Their job is to go and do things which will have societal impact. The hardest part for them, however, is if they don't have the fundamentals to do societal impact research, they're gonna be stuck. They're gonna be stuck doing exactly the same thing. You talk about H.C. Brown, you talk about Nogishi, both won Nobel Prizes from department here at Purdue. They invented new fundamental chemical reactions that changed the way that people made medicines. And without those chemical reactions, it would have taken so much longer and so much more time to have gotten to those really important medicines. So what we bring in a university setting is our curiosity or drive, our interest in doing things differently, but also inventing these fundamental new chemical reactions or processes or ideas or innovations that industry will subsequently be able to employ as they go off and do extraordinarily, specifically applying types of research. But they wouldn't be able to do that without what the university does. So that's why it's critical that we maintain resourcing and funding for great departments such as the one here at Purdue. Thank you, David. Well, in terms of working with industry, I know that you've also been a co-founder of several startup companies focusing on screening to identify drug-like molecules. So what do you see as the linkage between scientific discovery and entrepreneurship and a new enterprise creation? That's a great question as well. So one of the parts which is probably also true is sometimes you can invent the best, what you think is the best new chemical reaction or the best new technology. And sometimes the rest of the world doesn't see it that way. There's no God-given right that someone has to adopt your ideas and jump on them and industrialize them immediately. And many times that doesn't happen. And that's because you can see the value of it, but you're having a hard time convincing other people of the value of it. And so that's where there's this connection that goes on. And I think this has happened in the last 50, 60 years, started, but it's really now becoming more and more employed is this idea that academics have to sometimes go out and do these startup companies and sort of demonstrate the applied component of it. And it's really important that they do this because you don't want necessarily PhD students or undergraduate students doing this heavily applied research. But at the same time, if you can't get another company to take interest in them doing it, you have to bridge that gap. And that's where the sort of entrepreneurial component of this I think really kicks in. What's really fantastic about the United States is United States mechanism, the culture, the community really allows you to do that and provides resources to do that. And long may it continue because without those startup companies, some of those bigger companies would never end up pushing those things forward. And this goes for medicines, but it also goes for materials. It goes for so many different things that's in society that we care about came from tiny startup companies that academics had to launch to get the appropriate attention. Well, David, when we were working together at Princeton Entrepreneurship Council about eight, nine years ago now, you were also serving as the department chair of the chemistry department. So how did you find the time and the balance between chairing the chemistry department and your own research? I feel like I should be asking you this question. You do more work than anyone I know. For me- That's not true. That's very true. I think for me, being a chemistry department, it's one of those things people talk about being a chemistry, or being any chair has been really hard work. I was talking to the chemistry department chair here, and we were having this great conversation about how we actually love doing it, because it was actually fun. And people tell you it should not be fun, but it actually ended up being a huge amount of fun because you get to be involved with helping people, but you also get to be involved with growing something, building something. And if you really enjoy what you're doing, then building it and seeing it prosper is one of the best things. It's like building your own research group, watching your department grow, watching your company grow, watching anything build and grow is almost addictive on some level to see that growth in the whole thing. So for me, I thoroughly enjoyed it. It didn't feel like you were really having to work at it. It was just one of those things that was really enjoyable to be doing. But you work more than anyone I know. So, I mean, you're so good at this. Well, look, David, the president's job is the easiest. Department chair, on the other hand, each position is very difficult, and they got a lot more work. I just go watch a game, and usually Purdue wins anyway. So, and I host parties, and somebody else is doing the work. So for me, actually, I even have time these days on Saturday evenings to do a bit of research myself. That's been proven to be very healthy to my mind. So department chairs, on the other hand, they really bear the burden. Well, we've got some questions from students, and actually more than 60 questions. We could only have the time to accommodate a handful of those. I think they have lined up here in the front row. Yes, please. Hello, my name is Wyatt Kenyon. I'm a sophomore in chemistry, and our first question is from a first-year PhD student in chemical engineering. Do you face any resistance from the chemistry or catalyst community in the early days of your discovery when organic catalyst was not as well-established as a field? If you did, how did you stay motivated to further develop the field? Yeah, that's a great question. At the very earliest stages, yeah, there would be people who would make fun of it, and you kind of get used to it. There's lots of, in all walks of life, no matter chemistry or whatever you do, there's professional jealousies and annoyances, and nobody really likes, when you're doing something and someone does something new, it's really easy to sort of make fun of it and laugh about it, and there was lots and lots of that that came along. I think for me, it was never really, I never took it that personally. I always realized it was just, change is a weird thing. Nobody loves change, because when things are over here, nobody necessarily wants to have to reconfigure everything to go over there, and so I never took it personally, and I think it was one of those things where you just believe in something. When you believe in something and you think, this has to be, this is a natural level of usefulness that people are going to find their way to, that just helps you just keep moving forward, because you just literally believe in it. None of that criticism really registers along the way, so I think it's one of those things, I think we all do this, right? When we face criticism, I think deep down inside, when we know what we're doing is right, that just helps you propel yourself forward. I think that's just a human nature thing. Next question, please. Hello, my name is Tristan West. I'm also a sophomore chemistry student. The next question is from Eduardo A., a visiting chemical engineering student. Considering the advantages and possibilities of using asymmetric organocatalysts, how do you think this approach can deliver more effective, accessible drugs with non-reduced side effects? Yeah, so the honest answer there is, side effects are, that comes with the drug, right? So making better drugs leads to a lot less side effects. It's not necessarily related to how you make the molecule, but it is related to how you discover the molecule. So I would say that what we've done, has been with organocatalysis and with photoradarcs, is allowing these people called medicinal chemists. These are the people who go into your lab and work on making, or trying to discover new medicines every day. One of the things that people don't realize, everyone thinks that MDs and doctors invent medicines. They don't. They're very good at understanding people's problems and giving them medicines. But the people who invent medicines are actually called medicinal chemists. It's actually chemists who invent medicines. And these are actually the largest number of practicing chemists who all do different things on a daily basis. There's hundreds of thousands of these people out there inventing or discovering new drugs. However, the faster they can get to those drugs, the faster they can get to society. And to do that, you're constantly needing new chemical reactions that allow them to get there faster. And the faster they get there, the faster they can get rid of the ones with the bad side effects and get to the really, really good ones. So it's really the medicinal chemists who are the real experts at doing this. What we do is provide some new tools for them to actually do that. Well, I have to also put in a second commercial for Purdue. We've got also an outstanding College of Pharmacy. And we have some outstanding interdisciplinary research centers that cuts across multiple colleges, exactly along the lines that you just described. That's cool. Well, we have two more students here, please. My name is Ola Adegbongwe. And the next set of questions are from undergraduates majoring in chemistry. This one is from Mackenzie, a chemistry senior. And she says, you've been described as rebellious in articles describing your achievements. How do you think acting outside of the norm and thinking differently than others in your field influenced your work in discovery of your new catalyst? Okay, so all right, so this is a set up. Okay, I didn't, all right. Let me show you one thing, because this is fun for me, and I feel like I always have to do this wherever I go. But I am slightly rebellious, and I think it's good to be slightly rebellious, within reason, as long as you're respectful. So basically, I think I showed you before, I discovered these catalysts. And then when I went to give my Nobel lecture, which is gonna go out to millions of people, and I knew I had to put this lecture together. And when I was doing it, I thought, how do I put something just kind of fun in the middle of this? And so I pointed out, to change this catalyst is a bit like doing precise molecular engineering. And I said, these were the two fantastic graduate students who developed precision molecular engineering, looking for a beautiful outcome. And I said, how do you explain that to people who are not chemists? And so I said, well, if you think about it in terms of really famous athletes, and this is an incredibly famous athlete who's Swedish, called Zlatan Ibrahimovic. And I then went on to say, he's an amazing athlete who does precise things with beautiful outcomes. And this was the goal. This was a goal he scored, it was an unbelievable goal, right, an unbelievable goal. Now, at the time, a lot of people gave me a really hard time about this, when I showed this in the Nobel lecture, because I said, oh, you know, I just realized. Purdue University is also beautiful. I'm talking to myself. We're gonna wait for the beautiful and accurate. Did I lose the athletic feat? Well, never, all right. Here we go. All right, so I'll show you, this is the goal he scored. All right, and hopefully you can see this. That's an unbelievable goal, right? Right, so okay, now I understand why people were like, what is he talking, all right. So, but I got a lot of hard time about this, because people said, you know, I showed this. They said, the only reason you showed this is because the goal was scored against England. So that's, and I said, that's really unfair, but let's watch the goal again. Okay, so, but the point being is that I thought this was kind of funny, right, to do this. But the Times of London, who are the biggest newspaper in Britain, the most substantial newspaper, ran a whole article about it the next day, about Scottish chemists making fun of the English football team. And you know, I thought winning the Nobel Prize was great, but this was like, chef's kiss and the whole thing. And so, the one thing I'll say is like, a little bit of rebellion is kind of good, right? It's okay, as long as you're being reasonably respectful, I think it's good to be a little bit rebellious, because you know, you're trying to get a little bit more out of it, and try to do something a little bit different, and I think that's good. Well, to some of the American audiences, they may have to be explained what this, what is this sport? Why is this called football? Well, you know, that's an interesting news article. They picked up on that, not organochemistry. They did not pick up on, well, it was really funny, and I'll do this really quickly, I apologize for, you know, I'm not trying to just do an infomercial here, but they actually showed this, right? This was the, I'll bring it, I'll just, might as well show it now. So, this is, that's the times of when, so, and I thought this was really, really funny. So, the very best part is, I don't know if you can see this, it says, a Scottish professor mocked the England football team, while accepting his Nobel Prize for chemistry, by revealing a spectacular goal against them, helped inspire his scientific return. That's amazing, that's like the best thing in the world. So, it's not Brahms, it's actually watching football. Yeah, yeah. Or soccer. The other best part about this was, so, when I went to Sweden, they actually had me meet, this is the coach of the Swedish football team, and that was amazing, my whole family got to meet, and so Zlatan Ibrahimovic, who's this football guy, he actually, his very last ever uniform he wore, he gave it to me, and he signed it, which was spectacular, and then I went too far, and I said to him, I wish I'd put a goal in by Messi, but anyway. So, but that was fantastic. Well, from organic catalysis to soccer. Well, we have one more student question here, please. Hello, my name's Lauren Kale, I'm a sophomore studying chemistry and materials engineering. Our next question is from Elizabeth, who is a sophomore chemistry major, and she asks, how many failures led to the creation of your organic catalyst, and how did you persevere? Yeah, that's a great question. So, obviously, as I mentioned, we literally ran it that afternoon, so I can't say there was a great deal of failure to get the initial proof of concept. There was a lot of failure along the way in making it general, and I would say the other world that we've been involved with, photoradarcs, there was a huge, huge, huge number of failures along the way, and that's kind of part of being a scientist, and it's interesting, that is the number one question that people will ask you as you go around the world, how do you deal with failure? And you realize the reason why is because you usually talk to scientists, or people who are learning science, and they realize that there's a ton and ton of failure that's happening around them, especially for graduate students. That's what you deal with, you're dealing with failure all the time. And sometimes you don't realize it, because when we go out and give talks, it makes it look like everything works. It looks like everything's fantastic, everything's wonderful, look, you can't fail. And it's exactly wrong. And I think the baseball analogy is the best one. I think if you're an ERA of 0.4 or so, you'd be the world's richest baseball player. And so I think it's basically the same thing. In science, you're gonna fail a lot more than you're ever gonna succeed, but you have to know that that's part of the process, and get comfortable with it. But I think you also have to explain that, and I think we do a bad job of explaining that to especially incoming graduate students and undergraduates, that that's part of it, and it's fine. It's okay, it's good to fail. And failure, this is a cliche, but it's my cliche that I love, is failure is, another word for failure is experience. And when you learn from failure, the failure tells you something. It's not just negative, you learn something every single time. And if you utilize that well going forward, it's another brick in that wall that you're building, or ladder you're building, to get up to that success that you're looking for. I think failure is as important as success. I really, really do believe that. But I do think we don't do a great job talking about what failure means. Well, David, you just gave us an idea. Maybe Purdue should start a open access journal asking Nobel laureates to write an article about something that didn't work. The entire journal, issue after issue, is all about things that didn't work. I'd have a lot more papers than I have right now. Would be also equally highly cited. I heard it's 44,000. If you start writing about things that didn't work, the citation number will go even higher. Well, you mentioned the word beauty. I'm gonna take that as a segue coming back to my second to last question. Do you think that chemistry is beautiful? Yes, that's an easy, easy, easy question to answer. I think all science is beautiful. I think all engineering is beautiful. I think there is something inherently just gorgeous in this idea that you can think of things and write them down on paper and then walk into a lab and see that in the real physical world, those things actually can go from a thought process to a reality, to the outside world, to a medicine, to a material, you name it. That is an inherently beautiful thing to see that we can influence our outside world and hopefully make our world better. But also in chemistry, the one thing I love about chemistry specifically, to give a plug for chemistry, the chemistry world we live in is very, very three-dimensional. It's all about shapes and the way things look and how they interact with each other. And I think there's just this unbelievably inherent beauty in how molecules basically interact with each other. The satisfaction you might get when you put the last jigsaw piece into the last part in a puzzle and finish it, and it just fits beautifully, and it just feels like, wow, that's great. And that's the way that chemistry works with the world. It all interacts with this beautiful interaction, which is very aesthetically pleasing. It's also very three-dimensional, and it really has this quality of beauty that I think is almost magical. Well, this conversation reminds me that the chemistry folks really got the visualization done best. They got a table, and then they got equations with all the pathways and all the pictures, and then they got the colored different molecules in a three-dimensional chart. And these days, you can wear a goggle and enter it with AR, VR, like Minecraft style, right? With, you know, how do I steal an electron here? You know, how do I break a carbon bond over there? You know, it's just chemists really got this right from the get-go. So, well, my last question related to that table. I'm sure, David, you like the entire periodic table, but what is your favorite element? Oh, boy. Favorite element. I'll try and answer this slowly. So someone actually came once. I was a professor at Caltech at one point, and someone once gave a talk. It was an organic chemist, and he said, I bet you, everyone, organic chemists, your favorite molecules are always circular or in a cycle, or not acyclic. And I said, no, no, my favorite molecule is not that. And he said, well, what is it? I said, my favorite molecule is ethanol. You know, being Scottish, that's a very common answer. So I don't know. My favorite answer. A little more about element. Element. I think with elements, I would probably see there's some really interesting elements which are out there. I would say the ones I find really, really interesting is probably, there's two. Can I say two? Is that OK? Well, since this is the first Presidential Lecture of the year, you get two, yes. Two. So I love this molecule called tin. Tin. So tin is really interesting, because it's got this two-faceted component to it. One is, when tin is what's called tin four, it means it can have four bonds. It's very, very reactive. It does all these incredibly reactive things, but it's also really, really toxic, which is obviously a problem. And then there's tin two, which has this big, what's called a lone pair on it, and it distorts all the things associated with it. But when it's tin two, it's completely benign. It doesn't do anything to you. And it has all this other really interesting reactivity. So I always love that, because it's this atom that can sort of just jump back and forward between these two completely different states. And it's unbelievably interesting. The other one, obviously, and this is boring, is carbon. I mean, carbon is just an amazing atom. If you think about the world, what we're doing, everything around us, the fact that we've been working, humans have been working with carbon since Adam was a boy, right? And so basically, we're still learning completely new things about carbon every single day. That, to me, is unbelievably fascinating. So clearly carbon, but also tin. Oh, well, I sort of guessed carbon, because I can sense a bit of a bias towards organic chemistry here. Well, but tin, that's very interesting. Huh, are there other elements like that? Oh, yeah, I mean, the periodic table is just full of these crazy elements that do all these, based upon just whether you take an electron in or out of them, their properties completely change. You know, it's a bit like a human. You know, you give it two glasses of whiskey, and they completely change, right? It's completely like atoms. You give it an electron, it completely changes. Well, I just would like to remind those in the audience, I'm watching the recording here, that you have to be of legal age in order to try that experiment. Well, David, you make me want to learn chemistry again. Well, give it up to David McMillan. Thank you so much. Thank you, thank you so much. Thank you so much.