Interview with the 2024 chemistry laureate David Baker, recorded on 6 December 2024 during Nobel Week in Stockholm, Sweden.

What influence did your parents have on you?

I grew up in a very very happy family. My parents were very interested in education. We talked about all kinds of things and it was really a very nice time. My parents are physicists. I felt from an early age, I wanted to do something different, so I wasn’t particularly interested in science as a child. Even when I went to the university, I was not planning to be a scientist and I didn’t start out studying science. I guess I would just like to encourage people not to plan too far ahead, and sometimes things take you where you don’t expect. 

How did you become interested in biology?

When I went to the university, I started off as a social studies major. I was interested in trying to understand why people did what they did and maybe how you could use that to make the world a better place. Then later on at college, I became very interested in philosophy, and then in my last year in college, I took a biology class that was really exciting, and that made me decide that I wanted to go to graduate school and see what doing research was like. I think I found in the social studies and the philosophy readings I was doing the questions were really interesting, but what really struck me about biology is the pace at which new advances were being made and the things I was learning about had been discovered only very recently. There was a real sense of forward progress, and I think that’s what really attracted me. 

Did you have a plan for your career?

I’ve never had a plan. As I told you, when I started college I never thought I would be a scientist. When I went to graduate school, I thought I would be working on something completely different. I did not start off planning to design proteins. I didn’t even know what that meant at the time I started graduate school. Even now, I mean, I have an idea, I think I have a plan for the next three months and maybe a little bit of an inkling beyond there, but I’m happiest when what I’m working on is something that I couldn’t have anticipated a few years earlier. Indeed that’s the case now. I had no anticipation of where we would be, that where we are today, say three years ago.

Why do you find proteins interesting to work with?

In nature, proteins solve pretty much all the problems that arose during evolution in marvellous ways. This is one of the things that fascinated me when I finally started, when I finally studied biology. Everything that was a challenge during evolution, there’s a protein that that kind of solves the problem. But now humans face a lot of problems that weren’t so relevant during evolution, like, we live longer, so we have new types of diseases. Understanding how proteins solve all the problems that were relevant during evolution makes one think that there very well could be new proteins that could exist that would solve these new problems. But there’d have to be a long period of evolutionary selection, which is very unpleasant and takes a long time, so if we could make new proteins, maybe we could solve those problems.

How important is it for scientists to address the world’s biggest challenges?

I think it’s one of the great things about doing science is that you can make new discoveries that can make the world a better place. I’m a believer that as we learn more things about the world and about ourselves, it will benefit all of humanity and some kinds of science can directly address some of the major challenges that we face today. 

How does it feel when your work has an impact?

It’s great to see some of the proteins that we’re making go out in the world. I would say though, at this point, what gives me even more gratification is seeing the people that I’ve trained go out in the world and do amazing things, really across many walks of life. I just had my hundred and first PhD student graduate just before I came here, and I’ve just worked with many, many absolutely wonderful people who are doing wonderful things now, and many of them have come to Stockholm this week, so it’s a really nice celebration of what everyone has done. 

Why is collaboration in science important?

I think collaboration in science is really important because … First of all, science is a human activity, and it’s best done closely working with other people. I think the more different perspectives that one gets on a problem, the better it can be. Also, there are many applications of scientific discoveries, and so the broader and the more diverse the group of people who are involved, the more new applications that come up. Then I think again, as far as the contribution that one can make as a scientist to the world, I think helping train and teach other scientists, younger scientists, is really important. Also collaboration is fun, it’s more fun to work with other people, and I really get a lot of pleasure out of it. Right now, my day, I pretty much never leave my group in Seattle, I’m there every day. Most people are half my age or younger, and they’re my colleagues, and I work with them every day, and it’s so much fun. I just enjoy it personally, I think it’s also great for the science. I really believe in an open atmosphere, open science, we have no secrets. There are people coming in from all over, coming in for a day or two, or coming in for six months or a year and then going out through the world. I think it makes it fun and it’s a great way of getting all the advances out to the world. 

How important is diversity and representation?

I think diversity and representation is important in research. I think it’s important for many reasons, for the science itself it’s important because people from different backgrounds and different kinds of people have very different perspectives. One sees this very clearly in the dynamics of a research group. The more diverse it is, the healthier it is, and the more vibrant it is. Also, in terms of being scientists have sort of a duty as being role models and helping be ambassadors of science to the outside world, the more diverse the group is, the better it can do that, the more people that can be connected with, so I think it’s really important for a lot of reasons. 

For you, what makes a good lab?

I think a good lab or a good research environment for doing science should be a place where people are really having fun, where they’re excited, where there’s a feeling that progress is being made, that there’s a feeling like this is the place where key problems that are facing humans are going to be solved. It should be an open environment so people can be coming and going, and there should be complete openness and sharing of the advances. There should also be a lot of free food, so we have different social events pretty much every day of the week, and there’s always a party to celebrate something or other. I believe that people do their best work and are at their most creative when they’re happy and when they’re working, really having fun working with their colleagues. My group is pretty big, there are a lot of people, but it oftentimes just feels like one big party.

Why is it important for science to be open access?

I think as scientists, part of the world is putting resources into you to do things, and I think you have a responsibility to make what you do available. The more openly you share things the more impact you have, and the more able you are to change the world. I’ve seen that very clearly over my career, that if you don’t share things, then they kind of shrivel up and die, but if you share things, they grow and expand. For example, in Stockholm this week there are a hundred people coming from the Rosetta commons community, which is an organisation we started when people were leaving my group, we wanted to keep working together, and it’s grown and grown to have many, many hundred, I think probably close to a thousand members now. It’s just been a great thing, and having many of those people here is just a real celebration of how wonderful it’s been. We couldn’t have this kind of worldwide community if we weren’t sharing everything openly, because if each group just kept everything to themselves, then it would be all very siloed. 

How important is building a community among colleagues?

I think building community and social interactions are super important for science. Science also is hard. I’m only interested in working on problems which are not solved, and that’s what scientists should really focus on, problems which are hard. Usually when you work on problems, it’s inevitable that when you work on trying to solve problems that are really hard, you’re going to fail most of the time. Failing on your own can be kind of depressing, but if you’re doing it with other people and you’re working together and you’re still not cracking the problem, it’s like you have this feeling of the teamwork and you can solve the problem together. Then when you solve it, which will almost always happen, then you can celebrate with all your colleagues who worked so hard with you in solving it. 

Do you enjoy mentoring?

Yes, I love mentoring. It is fun having, I didn’t realise I was up to 101 PhD students. It’s funny, just last year, 22 new PhD students joined my group, so the number will be continuing to go up. I think it’s fun. Like I said, it’s not just me doing the mentoring. In my research group, there’s a really strong emphasis on mentoring. Everyone who comes in is assigned several mentors, and that changes over time. When I meet with them, I meet with them and their mentors, and then after a year, you become a mentor yourself. I think it’s just a good thing to learn, and I really like love working with other people and everyone coming in. It’s really exciting, I get all these super smart, enthusiastic people from all over the world, from all different kinds of backgrounds. I don’t travel now because – this is my big exception of the year this week – but I don’t have to because people come from all over the world, so it’s like I’m traveling around the world but never leaving my lab. 

How do you maintain your work-life balance?

I think a work-life balance is very important. I love my job, it’s very intense. I go into work and I might meet with 10, 15 students over the half-hour intervals throughout the day. It’s pretty much all I do is meet with people in my group. So, on the weekends, I’m up in the mountains, I ski or hike or climb, I have to get away. It’s funny, sometimes I go away for a little bit longer and I’ll go do a bunch, go climb some mountains or go hike somewhere or go skiing. Sometimes afterwards – I’ve done this a few times – where I explain the importance of being a good mentor as being part of science, and then I say as part of being a mentor. In my role, it’s also important to be a role model. I think it’s a role model, it’s important to show how being a scientist can really be a lot of fun, so more people would like to become professors. Sometimes I get discouraged because a lot of my students don’t want to become professors. In the interest of being a good role model, I’ve made a great sacrifice, torn myself away from doing the research I love and gone for a week to do all these wonderful, beautiful things just to be a good mentor. And then I show them pictures. 

How do you keep going when nobody believes in your ideas?

I think it is important when you’re a scientist or doing almost anything, that you should always be out there, because you only live once. Just doing things which are kind of boring and safe is not so exciting. I have been out on the lunatic fringe for much of my career, and I think you convince people or people are attracted to work with you because they appreciate how crazy what you’re saying is, but they also can see that if you could actually do what you say you’re trying to do, that it could be really, really impactful. It’s like maybe “high risk, high reward” would be sort of a cliche way to say it. Then again, if you have a community of people working together then it is like you’re not out there on a cliff by yourself. Even right now, even with things like the Nobel Prize, the things I’m really excited about are kind of the crazy new ideas. Just as I was leaving yesterday or the day before a new person had joined the group, a new postdoc had come in and a super talented undergraduate and I said to them “Well, tell them about the cool new project.” He said: “Well, David has this crazy idea.” I think that’s one of the fun things about doing science. That’s just kind of the way I like to live.

What message do you have to others that think outside the box?

My message to people would be really follow your dreams. Don’t worry about exactly what’s going to happen in your future, just do what you’re most excited about at any point, generally things will work out. But don’t be afraid to try to solve really hard problems because that’s really what is important for scientists. 

How do you deal with failure?

I said, we’ve always worked on hard problems, so there’s generally been a lot of failure. It’s even now when we start working on a new problem, we almost always fail for a long time. But I’ve seen enough, I know that’s just natural and that a period of failure means that you’re working on a problem, which is really important, so that when you start making progress and solve it, it will be all the more exciting and impactful. In fact, I see the most danger on working on problems that are too easy because everything takes work. If it’s something which is too straightforward, then it won’t really move the needle, there are probably lots and lots of other people doing it, so you don’t really have to do that, you could do something else.

But there are many, many examples of failure. For example, when I first started at my independent career at the University of Washington, the problem that we worked on, that I thought we were going to try to solve, I realised that the problem wasn’t properly posed. I thought we were going to discover something, and I realised after a couple years that it wasn’t going to be possible. That happens quite frequently, so I think one thing you have to be able to do is recognise that you’re wrong and switch course. You should try for hard things, but you also have to keep paying attention to what’s coming in and what you’re learning. Sometimes you have to be able to flip things around. That’s what happened at the beginning. We had certain approach to try solve a problem, and it just wasn’t working. Then I realised, well, we can turn, make the fact it wasn’t working into a virtue. I think overcoming challenges is just an important part of doing science. Both challenges, both scientific challenges and personal challenges – everything’s hard. 

What advice do you have for young scientists?

My advice for a young scientist starting out would be to really follow your passions. What are you really excited about? What is it that you really want to work on? and do that. And again, not worry too much about what the future will bring, because if you work on something you’re really excited about, you’ll make progress and that will open new doors for you. Sometimes people say, “Well, I want to do this to learn a new technique or a new approach.” I think it’s more about what problems are you excited about solving? I would say also that it’s very important to be in a research environment where you can learn. So, a collaborative research environment, go to a place, decide what you want to do, and then try to go to a place where there’s a vibrant research community working on that. Because you’ll learn more and it will be more fun and you’ll get further. 

How has AI transformed your research field?

AI has really transformed our research. This is again an example of the unexpected and not planning too far ahead. So, for many years we were developing a computer program collectively with this huge group internationally called Rosetta. That was based on a physical model where we had all the atoms present. It was about five years ago that we started experimenting with using deep learning approaches to apply them to protein design. Really inspired by, in part, John and Demi’s work with alpha fold for protein structure prediction. We figured if deep learning was so powerful for protein structure prediction, which they had shown, it should be powerful for protein design too. We really went into that full steam ahead.

I didn’t know much about it, and people in my group didn’t know much about it, but again, collectively, we were able to learn quickly. Then the methods that we’ve developed, the deep learning methods, turn out to be much more powerful than the Rosetta method we had before. They’re actually easier to use, so we’ve made these methods freely available, and scientists all around the world are using them to design proteins. In fact, it’s now happened I think three times that we’ve been designing proteins to solve a particular problem. We’ve made some progress and we’ve written to the world expert on that problem and saying, “Hey, we’d like to collaborate with you because we’ve made these really cool proteins that we think could help solve the problem”, and they said, “That’s great. We’d love to collaborate with you, but we’ve used your methods to make proteins too,” so it’s been it’s been really fun.

AI is, as a technique, it’s very powerful. It’s very powerful when there’s a lot of data, and in the case of proteins hundreds of thousands of scientists worked over 50 or 60 years and spent tens of billions of dollars to solve the structures of hundreds of thousands of proteins. That’s a huge data set, and that’s why AI has been so powerful for structure prediction, and now for protein design. In terms of what it will do in the future, there are other data sets which are very big, like all the text on the internet or all the text in all the books and all the images. Of course things like ChatGPT and Dolly or language models and image generation models are powerful, so that’s exciting. I think where AI stops being as powerful is when there aren’t those kind of large data sets, but overall, I guess I’m an optimist, I think that that the AI is helping with a lot of things. There certainly are issues like employment, as AI might replace certain types of jobs, but I have no doubt that new types of jobs will open up. People ask me sometimes about whether I’m worried that the AI methods we’re developing for designing proteins could be used to do bad things. I think that’s certainly possible in principle, and it’s something that our community is taking seriously, but on the whole, Nature’s already come up with lots and lots of bad things like the 1918 flu and Ebola virus and stuff. I think there’s much more potential for AI-based protein design to do good things than to do bad things. 

How did you celebrate receiving the Nobel Prize?

Let’s see. I got the call about 1.30 in the morning and it was very exciting. There were press conferences and there were a lot of things. We had a big party in the lab, and by that evening I said, “Okay, I’m just going to keep on doing everything I normally do.” So the next day I had my 12 meetings with students, did all the work, did all the stuff I normally did, and meanwhile the number of emails I was getting, I was already getting a ton, it kept growing and growing and growing. I was trying to do absolutely everything, so I even very proudly sent an email to my lab saying, “Okay, I missed a few meetings with some of you on Wednesday,” – that was when the prize was announced – “but don’t worry, I’m going to be just as present”. Indeed that happened, but after about two weeks … The thing is I’d already been at 110% of what was possible before I got that phone call, so I thought, well, okay, I need a break. I took five days off, I went I went backpacking in the canyons in Utah, which is beautiful, it’s very otherworldly, and I realised I had to make some changes. I came back so now everything’s great. This is my first trip since getting the phone call, it is probably going to be one. This may be my only trip of the year, I may do one other. I’m really excited about the science but I have had to make some adjustments. 

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