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Q&A with 2021 Nobel Laureate, chemistry professor David MacMillan

<h5>Professor of Chemistry and 2021 Nobel Prize Laureate David MacMillan.</h5>
<h6>Sameer A. Khan / Office of Communications&nbsp;</h6>
Professor of Chemistry and 2021 Nobel Prize Laureate David MacMillan.
Sameer A. Khan / Office of Communications 

In 2021, Princeton University had a record-high number of University-affiliated Nobel Prize winners, claiming five of the year’s 13 laureates. Princeton professor David MacMillan shared the Chemistry prize with Benjamin List of the Max Planck Institute for Coal Research in Mülheim an der Ruhr, Germany, “for the development of asymmetric organocatalysis.”

MacMillan sat for an interview with The Daily Princetonian to discuss his upbringing, research, and Princeton influence. The following transcript has been edited for clarity and concision.

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The Daily Princetonian: Would you please walk me through how you found out that you were awarded the Nobel Prize? What was your immediate reaction?

David MacMillan: So basically, I was laying in bed and my phone started buzzing. My wife got annoyed because it woke her up. So she got up and moved my phone away from our bed. [My phone] kept buzzing and buzzing. So I groggily went over and picked it up and looked at it. And there was a message from someone from the Swedish Academy, and it spelled my name wrong. And it said, please call us back. Then there was another one from the other winner Ben List that said, “Dave, wake up, and please call me.” So I called Ben and said, “What’s going on?” He said, “Oh, we just won the Nobel Prize!” And I was like, no, that’s not true. I’ve always had a big group, and they've always been pretty mischievous and up to no good. So I was pretty convinced that they were sort of pulling a fast one because we have people who are back in Switzerland and Sweden. So they would absolutely be up to the idea of calling me up at that time in the morning to try and sort of prank me. 

So I basically told Ben that I didn’t think this was happening. And I said, I’m going back to sleep. But my phone kept buzzing and buzzing. And so I was trying to figure out what was going on. So I went downstairs to our kitchen counter to a laptop and opened up the laptop to see who’d won the chemistry Nobel Prize. I went to the New York Times front page, and there was my picture with Ben List. It was probably, and still is, one of the most surreal moments of my entire life. I mean, it was just the bizarrest, bizarrest feeling. 

So then I went back upstairs and told my wife, and she didn’t believe me at first. But eventually she got up, and it was pretty fun. We woke up my 16-year-old daughter, which is not easy at six o’clock in the morning, and managed to get her to come downstairs. Then we all did a little dance in the kitchen together. It was pretty funny.

DP: You grew up in Scotland and later moved to the U.S. for your graduate studies. What was your upbringing like and what role do you think that upbringing has played in shaping who you are as a scientist today?

DM: I mean, Scotland is an amazing place. We were very working class, but I grew up in this culture where it’s all about enjoying yourself and having fun and teasing each other.

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Also, as a country, [Scotland] has a fantastic education system for being a working class place. So I got an amazingly good education, but also grew up learning how to be reasonably fast on my feet, telling jokes and other kinds of things. Both of those things were instrumental in enabling me to become, I think, a pretty good scientist, because in sciences, as you know, you have to be able to convey information, and be able to take the audience along with you when you’re trying to get through sometimes some pretty complicated systems or complicated ideas. I certainly learned how to do that in Scotland based upon my education and based upon the culture there. That was absolutely foundational to who I became as a scientist.

DP: What sparked your interest in chemistry in the first place?

DM: No one I knew had gone to university except for my brother, which was a kind of shock to everyone. People tried to convince him not to go but he went. Then when he got a job, he actually made more money than my dad who was a steel worker. So as soon as he started making more money, my family said, alright, you have to go to university. But he went to university to do physics … so I went to do physics. I would go in there, and it was a really cold freezing lecture theater, and when it rained, the rain would actually come through the roof and leak. However, in chemistry, which was an hour later, it was really nice and warm. It was this really nice lecture theater, so it was much more comfortable. 

At that stage, I started to think, you know, this chemistry thing is actually pretty good. Probably when I was a sophomore, I started doing organic chemistry, and organic chemistry was just fantastic. I mean, that was the first time in my life that I was like, yeah, this is really cool, I really kind of get this, It makes an awful lot of sense to me. So that’s why I basically ended up doing organic chemistry.

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DP: You were awarded the Nobel Prize for your work on the development of asymmetric organocatalysis. Would you please explain this for an audience that may not be necessarily familiar with the bits and pieces of chemistry?

DM: I’ll break that down into two quick parts. The first part is asymmetric and what that means is to make one molecule, but you make one mirror image of that molecule and not the other mirror image. Why that’s important is because there are so many molecules that the structure of them can look like they’re identical to each other. But they can exist as mirror images of each other. You may think, well, why is that important? Why would we care about this? But it turns out that our body and life is made up of one mirror image of molecules combined, and not the other mirror image, which is a sort of interesting question in and of itself, why is life based on one of these mirror images. But the reason why that’s important is, for example, drugs of one mirror image will interact with you in a positive way. Sometimes the other mirror image can actually interact with you in a negative way, or not do anything, which is also dangerous to put molecules in your body that are not doing anything, and there’s many, many cases of this. So to be able to determine among two molecules which one is which mirror image can take you hundreds of thousands of dollars worth of instruments to figure out which one is which. So sometimes I did this with the undergraduates that I’ve taught in the past. I would give these molecules to them, and say smell one or smell the other — and just by smelling them, they could tell the difference. So your nose can tell the difference, whereas all these instruments can’t. That’s because your body can recognize one of these mirror images. That’s the asymmetric part. 

So being able to make drugs or molecules, where you’re making one of those mirror images and not the other is really really important, but then the second thing is what can a catalyst use? Before we came along, the central way that you would do catalysis was to use metals. Metals in many cases are fine, but in many other cases are problematic, because they can be toxic, they can be non recyclable, and [they] can be very, very difficult to work with and very precious in ways where they’re very reactive and so it’s difficult to actually use them. What we came up with was this idea of why don’t we come up with catalysts that are based upon organic molecules instead of metals? Because as you and I know, we are just combinations of organic molecules. Human beings, animals are just organic molecules and we exist out in the environment just fine in the presence of air, no problem. Also we’re biodegradable, which is a weird concept. But as such if you can come up with catalysts that are just organic, they should be usable in the environment and completely recyclable as part of their life cycle. So that was the idea. We actually combined those two ideas. We had the asymmetric part, but we also came up with the organo part, which is using organic molecules to be catalysts instead of using metals. 

DP: Have you had any challenges throughout your research career? If so, how did you overcome those challenges?

DM: Oh, boy, I think in almost all research, you have more challenges than you ever have successes. But the challenges are fine, right? There’s two different types of challenges you can face as an academic. The first one is the project itself. You know, can you make this thing work? And one of the biggest issues I would say is that not everyone knows what the big questions are, and I would argue that most people don’t even know or haven’t thought about what are the best questions to be going after. So the number one challenge is coming up with a question of, “would it be possible to do this?”

The second challenge is once you’ve done something that you think is important or interesting, how do you convince the community that that’s true. Sometimes it can take you a year, two years, or even five years to get people to realize, you know, “holy moly, that's really important.” So that’s all about how to sort of communicate the work such that people really begin to understand what’s been accomplished. This whole idea of taking the audience with you is really really important.

DP: What’s the environment of your lab like and how do you make sure you have an innovative and creative environment?

DM: People think that creativity is an innate skill set, and I don’t agree with that. I think creativity is something that you can train someone to have. It is just how do you sort of put them in a position where you say, okay, go solve this problem, and you have, I don’t know, three, four days to think about it. And if someone has only got four days to think about it, they suddenly become really creative and they start to come up with really good ideas. Human beings are just really good at it. So I think for us, it’s really this idea of pushing ourselves to do things which, at least on paper at the beginning, look effectively impossible. And that’s how you keep that innovation really really high.

DP: Do you have any advice for Princeton students who are specifically interested in science on how to be more innovative and how to succeed in the field?

DM: The only things I would say are the things I would have said beforehand. Number one, you’ve got to have fun. If you don’t have fun doing something, just don’t do it. When you find that fun component to the research or the career direction you’re taking, it’s no longer a job. It’s a full time hobby that you just love to do. You jump out of your bed in the morning and go do this thing because it’s so cool to go do it. In my lab, we have a great time. We socialize, we go out, we have fun, we do lots of things together. And we make sure we’re enjoying ourselves. Number two is being able to be satisfied at the end of the day with what you're doing. If you’re doing something, and even if you’re having fun, but you think this is not really meaningful and you don’t think it is really having an impact, then don’t do it. Go find something that has impact. And I would say just keep following your compass toward where you believe that you’re going to have an impact, and you go to bed at night really satisfied. You’re thinking yeah, I did that today. So I think those are the two bits of advice I’d probably give.

DP: I think it’s been about three months since you won the Nobel Prize. How does this Nobel life feel like?

DM: Oh, it’s completely exhausting. It’s bizarre. It’s strange. It’s fantastic. It’s exhilarating. I think the part which I find slightly strange is people always say to you, are you going to become a different person? And you suddenly realize you’re not really going to become a different person. But you do start to notice that people treat you differently. That’s the really strange thing. And sometimes that’s fun, you know. But when your friends who have known your whole life treat you differently, you have to tell them, hey, cut it out. I think one of the main things is just being sort of grounded through the whole thing. But it is a wild ride. And it has definitely been an adventure, and I’m certainly enjoying it.

Mahya Fazel-Zarandi is a staff writer for the ‘Prince.’ She can be reached by email at mahyaf@princeton.edu or on Twitter @MahyaFazel.

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