Victor Ambros, Nobel Prize in Physiology or Medicine 2024: Official interview

Because if you fail only once every six months, you're not making much progress. But if you fail daily, let's say, you're learning daily. I think my childhood experiences were definitely influential in the sense that, as growing up on a farm in a large family, you had a lot of spare time. After we did our chores, we could go out and roam around. And our parents just let us go loose in the countryside and we learned to sort of investigate things out there and hunt down small animals and things like that. So it was a sense of freedom and exploration that I enjoyed right from the beginning. Also, on a farm, you have to help out with chores and harvest and so forth. And my dad, he was a very inventive man. And so I would work with him to repair machinery and things like that. And then he taught me how to build what I needed. He once helped me build a trap because I wanted a pet rabbit. And so I thought I would trap a wild rabbit. So I made drawings of the trap and we built it together. And finally, he told me that you didn't want to have a wild rabbit as a pet. And so we bought tame rabbits. But on a farm, you learn to be a do-it-yourselfer. And I learned that from my father. And I think that that helped me when I got into science because I learned that I could build something if I needed it. Well, the passion for science, for me, came pretty early. And it might have been books that I read. I know that I read books that were around about, my mom had some books about astronomy, for some reason she had in her library. And I got very excited about astronomy, especially because we lived out in the countryside and the sky was really dark at night and really beautiful. And so I was an amateur astronomer starting at about age 11. I think that was my touchstone, let's say, in my life, would be imagining myself an astronomer like these astronomers that I had read about in the books. And I wanted to be part of that tradition. Well, one hero was Clyde Tombaugh, who was a farm boy in the Midwest who was an amateur astronomer. And according to his biography, he was spotted by a professional astronomer to whom he had sent some drawings that he made. And that got him a position in an observatory and then in the Lowell Observatory in Arizona. And he eventually discovered Pluto. So this was, I think, a story, an arc of a story that I could envision, right? That if I could find myself in the right circumstances, I could be an astronomer like Clyde. So I was born in 1953. And so when the space race started between the Soviet Union and the United States in about 1960, 61, I was at a very impressionable age and also already interested in science. This was just very captivating, absolutely all-absorbing, captivating activity that was going on nationwide. And the launches were thrilling and frightening. And each launch was something that we anticipated and watched live. And we envisioned ourselves perhaps not as, at least I didn't envision myself as an astronaut because I was really averse to risk. But the engineers and the scientists who were backing up these programs were people that I admired. I remember being so amazed at the moon landing in 1969 because we knew that the technology they were using was all beyond state of the art for the time. And so I think we were inspired by the idea that you could do something that seemed impossible with resources, dedication, and putting enough people together to work on teams. And so that was, I would say, central. The space program was sort of central to my scientific upbringing. I love working with scientists. I just love the, I love being with people who are passionate about science in the natural world, who are thrilled by what we can learn about the world, what we can learn about things we can't see or we can never hope to see. Nobody's ever seen a microRNA. But we talk about it like we know all about it. It's because we and other people have done all these experiments where the structure of the way we design experiments and pose questions and then test them enables us to have a measure of certainty about things that we couldn't otherwise ever hope to see. And I love being around people who also are amazed by that. And so that has to be, I would say that if I were doing science alone, it wouldn't, it's almost like it would be a sad thing to do. And not only the collaboration, just being around scientists and sharing with them this passion that we have. And the folks who are doing science are always doing something really amazingly interesting. And so when you find out what interests another person, what they're passionate about, it's really thrilling, actually. Well, I like to say that I'm not a good case study. In other words, in terms of would I recommend that people do what I did, right? Because I find that my pathway in science has been a series of opportunities were presented to me, right? Where I was not really the agent that went and found those opportunities. So I feel really lucky. Now, what I mean is that I did go to a lab when I was an undergraduate and knock on the door and ask, could I work in your lab, please? But I didn't make rational choices about who I was going to work with or what I was going to do, right? So I guess my advice, one sort of component of advice to young people is maybe don't worry too much about whether you should be making long-range wise decisions about specific things, right? Specific things to study, specific people to work with. But really, definitely take advantage of every opportunity that presents itself to you. The other thing that's, I think, very, very important for young people to understand is that you're going to have doubts. You're going to have self-doubts. And all of us do. I mean, even at every stage of our career. So it might be helpful for young people to know that established scientists deal with self-doubt. And do I belong? Am I good enough to do this? Am I doing, is what I'm doing worthwhile? All these things. So as a young person, if you have doubts like that, don't think that, oh, there's a problem with me, right? That's just human nature. And encourage yourself and also seek people who can encourage you. I mean, one of the most important things, I think, is don't give up because you think that maybe you're not suited for this or you're not good enough. If you're feeling a passion for it, that's, I mean, passion for science is essential, right? And it's most of what you need, right? Because that's going to drive you to learn as much as you need to learn about something and to really take advantage of the opportunities that are presented to you. Right, so science involves investigation, right? And it involves investigation of phenomenon that we don't understand. We do the best we can to imagine what sorts of investigation we need to apply, what kinds of questions are the important ones to ask. Well, we draw up hypotheses that we can test with experiments. And we do the best we can. But often, the hypothesis is wrong. And you find it's not true. And you've been able to disprove it. So now you rethink everything, right? Science involves a lot of learning new skills, new methods, things that are new to you, new bodies of knowledge that you didn't know about before. So you're always being sort of tested in new contexts. And I think it's important to learn to welcome that, but also expect that there's going to be pitfalls in that. You know, you're going to find out, I often find out that there was a whole area of that knowledge that I had missed. And had I known that, I wouldn't have wasted my time on that particular experiment or something like that. And sometimes, yeah, experiments don't work. Machines break and so forth. Sometimes, this can be very frustrating. It can sometimes take a long time to, let's say, until you feel you're back on track. But that's a natural part of the process. I think everybody who does science will report the same things, that there's lots of failures. And of course, you learn from them. And those are the best kind of failures. And so I think one of my co-laureates, John Jumper, said something the other day that was interesting is you try to adopt a strategy of some sort where you are paraphrasing, where you fail often, right? Because if you fail only once every six months or every year, you're not making much progress. But if you fail daily, let's say, you're learning daily, right? So I think that's what he meant. Yeah, like anecdotes, I can say, I mean, the anecdotes that I can offer that are, I think, hopefully really revealing is I have colleagues whom I really admire a lot, right? And these are colleagues who I feel have it all together. I say, whoa, wouldn't it be awesome to be her? I mean, what a publication record. What an amazing series of discoveries she's made, right? And then there'll be an instance of some kind where we're being frank with each other about something. And this person reveals that she's been fighting imposter syndrome her whole life. And I'm thinking, I don't understand this. I feel like, you of all people, you've got it all together, right? And then another colleague, a man, will intimate the same thing to me after we've gotten to know each other for 25 years. And so you realize that even all these people that I feel I know are incredibly talented and are incredibly successful feel the same thing, right? So then we've come to understand this as a natural part of human nature. It's just something that happens to everybody, right? And sometimes you have to live with it daily. You go to work and you wonder if you belong, but you do the best you can. And you kind of, as you get older, you just learn to smile at yourself about it and just say, well, there you go, that's it. You think you're an imposter, but what can you do about it? You just gotta keep working, doing the best you can and pretending that you've got it all together. I've heard that we witness ourselves day-to-day, minute-to-minute, because here we are in our own head, right? And we're very concerned about what other people think about us, right? And we interact with people in a way that involves trying to kind of project a certain self. And you're hoping that's your best self, but you know it's not your best self, because my self is in here and I know it. You know what I mean? So you're working always with this dichotomy between what you think people think of you and what you sort of know you are, you know? And it's a wonderful, it's just a wonderful, crazy part of being human. But until you understand it as normal, it can be debilitating, you know? And I think, especially for people who already feel out of place, people who's, let's say, you know, you're a minority, a woman, you know, people who already feel they look different from everybody around them, you know? And I'm lucky I'm a white guy, and so the world just sort of opens up like this for the white guys, frankly. But so I can't complain about suffering imposter syndrome, because the circumstances for my career have been extraordinarily sort of straightforward for me, almost welcoming for me, you know, in a way that nobody deserves. I don't know, I first met Gary Rufkin in Bob Horvitz's lab where we were both postdoctoral fellows. I was Bob Horvitz's first postdoctoral fellow and Gary was Bob's second postdoctoral fellow. So we were, came together to the lab and were both inspired by Bob to study the same sort of set of genes that Bob had identified as having very interesting impact on development in the nematode, Caenorhabditis elegans. So there we were in this worm lab with Bob as our supervisor, and Gary came from his PhD studies where he did a lot of genetics and molecular biology. So he taught me and other members of the lab fundamentals of molecular biology as it pertained to, you know, recombinant DNA and DNA sequencing and sort of, you know, that kind of technology. So we had a good time taking molecular biology lessons from Gary, who's very expansive and funny to listen to. Gary is, Rufkin is a very creative person, very creative thinker and a free thinker, I would say. He has lots and lots of ideas and notions and he'll make associations and connections between and amongst phenomena and observations that are sometimes astonishing, you know. We'll joke with him that he's often wrong, but, you know, if you really, if you're creative and you invent a lot of ideas and some of them are right, you know, you end up with a lot of really good ideas, you know, and so that's what Gary is like. He also inspires somehow his trainees to be incredibly successful. So I admire him a lot because folks in his lab, many, many people in his lab have set up their own labs and done really, really well. So I think part of that is the sort of the open, kind of intellectually openness that Gary brings to the, you know, the community that he's in, yeah. Collaboration is absolutely vital in science. It's rare, very, very rare that any scientist does anything alone, especially these days. Now, there's two, well, probably many reasons for that, but amongst the reasons for why collaboration is so vital is that we, when we think together and we have conversations amongst two or more people about something that those people are really passionate about and really interested in and really curious about, there's, you know, marvelous synthesis when you have, I mean, you know, two people talking about something that they're really interested in is more than just twice one person, right? Because the exchange of ideas can be catalytic. You can see it happening and experience it happening that neither one of us would have thought of that, right? Ever, let's say, and you realize now that's happened, right? And so having experienced that over and over, then you know that that collaboration is absolutely vital for this thing to work at all. Now, the other part of that is that nowadays, the investigations that we conduct are very interdisciplinary. They can involve somebody who's, let's say, a human geneticist, somebody who's a structural biologist, somebody else who's a molecular biologist, you know, people who are computational biologists. You could even have an artificial intelligence expert on your team for that component, some sort of component of the investigation. And so there, the synthesis is more than just the minds getting together and sort of, you know, creating new perspectives and new ideas and things like that, but we also literally are bringing a parallel and complementary expertise into play so that the experimentation is, you know, has multiple dimensions. And so, and that now can be done quickly. You could imagine that you could say, all right, I'm gonna do this project, and in my lab, I'm gonna now hire a data analyst, and I'm gonna get a, you know, artificial intelligence expert, and I'm gonna get, you know, I'm gonna somehow bring in a clinical geneticist into my lab, right, and build this team. Great, of course, that would take a decade to build the team, you know, and so the collaboration is so exciting because it allows us to do things, you know, that we never would have imagined doing just by walking down the hall or writing an email or two, you know? You know, as somebody who, let's say, grew up in science during the 1970s and 1980s and 1990s, and then have the privilege of still being doing science today, I've seen, I think, major cultural changes in science. For one thing, I've been in environments where the idea was science is done by elite intellects. It's very special people, and if you want to belong to our institution, you know, show me that you're amongst the elite, you know? Right? So there was a kind of, the opposite of welcoming is kind of like an extreme meritocracy, but where, you know, it left young people feeling like, all the time, do I measure up? And I probably won't, you know, that kind of thing, right? And gradually, things have changed a lot, right? We've come to understand, you know, institutions have worked on trying to diversify their workforce, and that includes, you know, people working in science. But what we've, you know, as a working scientist, we've come to sort of organically experience how the diversification of the research team that I'm associated with has evolved over the years as the culture has changed. You see that the way we work becomes so much more, I don't know, just sort of much more alive, because folks, you hope, are willing to offer what they think, what their perspective is on a problem you're working on, right? And the folks come from, there was a time when my lab had people from eight different countries in the same lab. I mean, there was only a dozen of us in the lab, but, you know, and so sometimes we just, I just sit back and think, like, what's going on here? You know, these people came from everywhere. They have so many different backgrounds, right? And the way this conversation is going has to be because of the fact that they have so many different backgrounds, you know? Can you imagine I had a whole, if it was a whole room full of meat, you know, the white guy from the farm in Vermont, you know, how many perspectives would we bring to the table? You know, it just, if you do the experiment in your mind, you realize that, and you know, from direct experience, I feel that this has happened. It's making, you know, us better at science, and it's gonna only get better as we grow in this area. One of the things I learned from my dad was woodworking. My dad was, he was a farmer, and then after that, he was a cabinet maker, and he had a business in town making furniture, and he was a very gifted cabinet maker. And so me and my brothers learned from him how to do woodworking, and I also love guitars. And so, you know, about maybe 10 years ago or so, I started building guitars as a hobby, and I find it really fascinating because it's an amazing instrument. Involves a lot of engineering compromises as you're trying to build it, and it involves wood, and wood and the sort of the nuances and the sonic qualities of wood and so forth. And it has a certain serendipity to it. You build a guitar and you don't really know what it's gonna sound like until you string it up and try it. So it's really dramatic, you know, kind of an event when you finally try it out. So it's a combination of, you know, woodworking and music.