October 30, 2018

Inside Mizzou Podcast:
Nobel Prize, Ep. 7

When Dr. George P. Smith was announced as one of this year’s Nobel Prize in Chemistry winners, the Royal Swedish Academy confirmed what all of us at Mizzou have always known: Work that happens here changes the world.

Dr. Smith’s research has led to new treatments for arthritis, cancer, autoimmune disorders and more. Now, he joins a list of extraordinary scientists who, since 1895, have been honored for their breakthrough discoveries and innovative solutions to some of humanity’s biggest challenges.

Joining Chancellor Cartwright on this week’s Inside Mizzou special-edition, Nobel Prize podcast is Dr. George P. Smith. They discuss Dr. Smith’s journey as a scientist, a teacher and a Tiger.

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Moderator: [00:00:12] From the classroom to the cornfield, journalism to SEC athletics, the University of Missouri works 52 weeks a year, every year. This is Inside Mizzou — real stories, real discoveries and real impact of the Mizzou community.

Chancellor Cartwright: [00:00:31] In today’s episode, Dr. George P. Smith, MU Curator’s Professor of Biology and the 2018 recipient of the Nobel Prize for Chemistry, will be visiting with us today. Dr. Smith welcome.

Dr. George P. Smith: [00:00:45] Thank you.

Chancellor Cartwright: [00:00:46] So, can you — for the audience I think it’d be interesting for us to just talk about the work that you conducted for the Nobel Prize and sort of give an explanation to people so that they understand what phage display is and what it might be used for.

Dr. George P. Smith: [00:01:06] Oh, that’s a tough assignment. Do I have half an hour, and will this be on the test?

Chancellor Cartwright: [00:01:16] (Laughing) Within a few minutes.

Dr. George P. Smith: [00:01:17] Well, phage display — first, phages are bacterial viruses. They infect bacteria. The phage that I worked with infect E. coli bacteria. Not the harmful kind that, you know, can give you really serious disease, but completely harmless lab strains of E. coli, which can be grown very cheaply in vast numbers. So, they’re really easy biological entities to work with. So, phage display was a way of using these very easy-to-work-with viruses, using technology that has basically developed in the 1940s and 50s, to carry out a kind of test-tube evolution. And I’m not going to explain exactly why this is or how you use phage to make test-tube evolution, but the basic idea in test-tube evolution is that you have a big collection of entities. They’re like, say, living things in the biosphere. But these are much simpler than that. In the case of phage display, they’re pretty simple chemicals. But you have a huge variety of them, and phage display gives you a technology that allows you to select out of that huge array — maybe 10 billion or 100 billion structures or in some cases more — the very rare structures that have some activity that the experimenter is interested in. For example, it binds to a receptor involved in cancer. Something like that. So, it’s a way of getting around having to fish through 10 billion or 100 billion structures one at a time — an impossible task of course.

Chancellor Cartwright: [00:03:07] Right.

Dr. George P. Smith: [00:03:07] And instead select out of that mixture, physically separating the ones you want from the vast majority of the members of this biosphere of simple chemicals — throwing those away and capturing the remaining ones. And then because these structures are attached to phage particles, which replicate to huge volumes, being able to take one or two copies of a structure — something that’s way too few to analyze — and growing them up to trillions of copies that are very easy to analyze. In a nutshell, that’s what phage display is. So, it’s a kind of test-tube evolution because you have a biosphere of entities. They’re not animals or plants or something, they’re much simpler entities. And the experimenter imposes an artificial selection on them. Not natural selection, which is very complicated and depends on the environment in enormously complicated ways, but a much simpler, artificial kind of selection. So, that’s why we think of it — we often think of it as a kind of test-tube evolution.

Chancellor Cartwright: [00:04:28] Yeah, the whole concept of test-tube evolution is just incredible, and being able to demonstrate that is something that we’re certainly proud that you were at Mizzou and you were able to do it. And, you know, if you look at our faculty and the opportunities here — can you talk a little bit about what made Mizzou sort of a special place for you? How do you think this environment here contributed to you being able to do this?

Dr. George P. Smith: [00:05:03] Well, there’s a lot of academic freedom at Mizzou. I think that I had a tremendous amount of freedom to pursue the lines of research, the ideas that were really interesting to me. I was hired as an immunologist, and when I decided very shortly after — a couple of years after that — I was not any longer going to focus on immunology but work in an entirely different field of research, that was something that I could do. And there are places where it would be hard to do that. There were fewer pressures on me here than I think many academic scientists feel and certainly way less than industry scientists feel. So, that kind of academic freedom and the commitment to inquiry I think was really vital for someone like me. I think I’ve flourished especially in an atmosphere that I experience at Missouri.

Chancellor Cartwright: [00:06:16] So, you know, with anybody who’s conducting research at an academic institution like Mizzou, a lot of the work that you do is working with students — graduate students, undergraduate students, teaching. Can you talk a little bit about the impact that students have had on the work that you’ve conducted?

Dr. George P. Smith: [00:06:41] Maybe I should talk more about the impact that students have had on ambition.

Chancellor Carwright: [00:06:47] Yeah.

Dr. George P. Smith: [00:06:47] Because I’ve had an ambition to be an effective teacher, to try to have students value the things that they learn in class for their own sake and also to make clear that the privilege of studying — of learning science and so on — comes with an obligation to use it for good. I mean, I think that there’s a moral dimension to all education. And my closest colleague in the biology department, Miriam Golomb, is kind of a role model for me in that regard. I mean, she has extraordinarily committed to teaching and is indefatigable. I absolutely cannot match her in that respect, and she’s still teaching well after retirement. She’s still teaching here. That’s maybe a higher ambition than actually like doing research. But it goes with research because I think people who are doing research have a — it keeps challenging them. And that’s kind of important in the classroom. I think if you go into the classroom and think you have got everything down pat, then that’s a problem. A classroom teacher should not be a fount of knowledge but be a facilitator and also learn from his or her students as well.

Chancellor Cartwright: [00:08:36] Yeah. You know, I really resonate with that, and I agree that that is one of the things that research allows us to do. It’s humbling at times, and it certainly makes you want to continue to work harder and harder to be successful. If you were to look over your career — it’s easy for us to look at the Nobel Prize and say how successful you were — but have you had any failures?

Dr. George P. Smith: [00:09:08] Oh, my gosh.

Everyone: [00:09:09] (Laughing)

Dr. George P. Smith: [00:09:12] So, I think I should say that when my colleague, my postdoc, Jamie Scott, and I got the first results that really showed that phage display worked, it was extraordinarily exciting. We were looking at what’s now really old-fashioned technology for DNA sequencing on a huge piece of X-ray film with little dark bands on it. We were reading that, and we got the results from an experiment. And, oh man, they just stood out. And we knew it was a success, and we knew it was pretty important, too. I mean, it was pretty clear in the context at the time that this was going to be important. But really my ambition was very soon turned to using this technology to try to develop new approaches to vaccines for really hard diseases, and malaria was specifically on my radar at the time. You know, a devastating disease that has huge economic impact. It doesn’t kill nearly as many people as it did before, but it still has an impact. Well, I wasn’t very successful at that. In fact, many beautifully written National Institutes of Health (NIH) proposals were not funded. There was a lot of lack of success. But I would say that I’m a very optimistic person. This did not devastate me. I knew that, you know, lots of stuff you do in science doesn’t work.

Chancellor Cartwright: [00:10:59] Yeah.

Dr. George P. Smith: [00:11:00] I would say that that’s maybe my worst lack of success, and that came towards the end of my career. But I don’t think I was devastated by that at all. I mean, I think I remained a very contented faculty member.

Chancellor Cartwright: [00:11:17] Yeah, the only reason I ask is because I think it’s important for people to know, you know, that as part of science and moving science forward, there are failures along the way. And those are important because they teach us things that we can then use subsequently to even improve on what we’re doing. And I think, you know, in your work — can you speak a little bit about how what you did, how it may have been the impact that others may have had on that work? How do you look at the entire scientific community, and how do we work together to actually forward science collectively?

Dr. George P. Smith: [00:12:01] I think that’s really important. In fact, it touches on your previous question about failure.

Chancellor Cartwright: [00:12:07] Yeah.

Dr. George P. Smith: [00:12:08] So, let’s say, you know, there are many really smart scientists who go through their whole career. They do research. You know, publishable research. Perfectly good, absolutely not going to get the Nobel Prize, and there’s no way to predict, you know, “Oh, this person is going to get the Nobel Prize. This person isn’t.” The scientific enterprise — and I absolutely know this very personally in my own case — the scientific enterprise depends on a whole big community of people that are considering ideas, throwing out ideas, talking with each other. You could sort of think of it as an evolution of ideas. You know, like a sort of family tree of ideas. But it’s an extraordinarily complicated family tree with branches going every which way. Each node is not a clean individual with a few descendants. There are hundreds of descendants and hundreds of parents, intellectually. And I really know this in my case because I know very well the influences that I experienced in the milieu of the scientific community that I was a member of. This would be classical molecular biology, cell biology and immunology. Those were kind of the main, big influences in my life. Maybe I would add mathematics to that as well. But the ideas that were very current at the time I could bring together because I was in a position to do so. I was in a position to bring them together to what ended up being phage display. But I can’t imagine that that would have occurred to me if I didn’t have all those influences.

Chancellor Cartwright: [00:14:04] Yeah.

Dr. George P. Smith: [00:14:06] And then that in turn influenced a bunch of other people in ways I absolutely couldn’t have anticipated.

Chancellor Cartwright: [00:14:12] Yeah, that’s great. So, if we, you know, go to more current times and the last few days or week since you’ve been announced — what was it like the moment you received the phone call telling you that you had won a Nobel Prize?

Dr. George P. Smith: [00:14:32] Well, the call came through from Stockholm at 4:30 a.m. on our landline. And our landline is now really devoted to robocalls, you know.

Everyone: [00:14:49] (Laughing)

Dr. George P. Smith: [00:14:49] So, I thought it was a little odd that something would come through at that time. 4:30 a.m. — I had already gotten up about 4:10 a.m. I had gone downstairs to prepare to make coffee, and Margie, my wife, — that woke her up, and she answered the phone. She said, “I think you better get this call.” So, I got the call, and I’ve told this. This is another wheeze that I’ve told several times that, you know, it’s kind of an old joke in science that one of your friends puts on a fake Swedish accent and calls you at 4:30 a.m. and says that you won. But actually we knew that this wasn’t the case because the connection was so bad. But anyway, I knew when it was Stockholm that that’s what it was. And, like no false modesty here, I knew that I was on the radar because I’d been invited to the ceremony in 2001, to a conference just before, and everyone at that conference had been invited to the ceremony. So, I knew I was on the radar. But it was a huge surprise to me because that was 2001. I thought that time had long since passed. It was a big surprise.

Chancellor Cartwright: [00:16:16] Well, that’s great. And how has it been? You know, what’s your favorite part since then? Connecting with other people? What’s the best conversations you’ve had since then?

Dr. George P. Smith: [00:16:31] Ok. I think I would say it happened to me just before I came here. I connected with Meg Mathias, who was my senior advisor at Haverford College in my last year. And we talked for half an hour. It took me a long time to get her because she’s retired. She’s 83. She’s five years older than me. She’d retired in 2002, but obviously in great physical shape and everything. And we had this terrific conversation about our common connection. So, her Ph.D. advisor, Abe Stavitsky, was a really prominent immunologist at, well it was called Western Reserve Medical School, now Case Western Reserve Medical School. And Abe Stavitsky was a great friend of my father — Margie’s father and mother: Hank Sable and Florence Sable. And I talked with him maybe a couple of years ago — with Abe Stavitsky. So, when Meg and I were talking about this, it turned out that she had had Hank Sable, my father-in-law, in a biochemistry class when she was there, and she talked at great length about that. She was ambitious to be a college teacher at a small liberal arts college, and that was her career. She was 37 years at Claremont McKenna College and totally active, intellectually. She remembered so much about, you know, like the intellectual climate at college at that time. It was a very exciting time for biologists because this was the time when the genetic code was being worked out. But when I went to college, we didn’t know it. In fact, it wasn’t really clear that there was what we would understand as genetic code. When I graduated in 1963 — I went in 1959 — when we graduated in 63, the whole code was pretty much worked out.

Chancellor Cartwright: [00:18:44] That’s amazing.

Dr. George P. Smith: [00:18:44] There were a few bells and whistles that were remained to be done. And that was very influential, and we were very naive when we look back on a project that I did with her. That was probably the most exciting thing that I did. Maybe to others it wouldn’t seem that exciting, but to me it was exciting to relive the ferment, the scientific-intellectual ferment of that era.

Chancellor Cartwright: [00:19:16] That’s great to hear that. Can you talk a little bit about what’s next? You know, when do you go and actually receive the medal?

Dr. George P. Smith: [00:19:31] I think it will be the 7th of December, and there’s a whole bunch of things culminating in the actual — there’s a lecture, the Nobel lecture, that would be on the 8th. You know, I can’t remember if I go on the 7th. Some time before that. But the Nobel lecture is on the 8th. You know, I’m used to extemporaneous talks. It’s got to be 25 minutes, so that’s pretty hard for a professor, but I hope I’ll master that art. When I went to the ceremony in 2001, there were some laureates who didn’t master that challenge. So, that will be a challenge. Then there will be the ceremony where you get the medal from the king: His Majesty the King of Sweden. Very stylized, very formal. I asked the people there if I could wear Mizzou colors rather than — I graduated from, my Ph.D. is from Harvard University. I think I was there for five years, and I’ve been here for 40 years. Now 43 years. And so, maybe I’ll wear Mizzou colors when I get it. And then afterwards it’s this huge extraordinary banquet. It’s just unbelievable. And this is the moment of truth because the winners come down this ornate staircase. They stop in the middle. Then they give a two-minute address. So, when you’re asking a professor to talk for two minutes, that is a real challenge.

Everyone: [00:21:21] (Laughing)

Dr. George P. Smith: [00:21:21] That’s the thing that’s most daunting. And, you know, my contact in Stockholm warned me — and I knew very well this was the case — that that was going to be the most daunting thing that I would face when I was there. So, then there’s, you know, like receptions and things like that.

Chancellor Cartwright: [00:21:42] That’s great. Dr. Smith, it really is a pleasure to have you here today. We want to let you know how proud we are at Mizzou to have someone like you among our faculty. I believe you know that this shows the type of talent and type of people that we have at this great institution. And I’m so proud to be part of it and, you know, to work with the faculty, the students, the staff that we have at this institution that enable great research like the research that you’ve done. So, thank you so much for sharing you time.

Dr. George P. Smith: [00:22:16] Well, you’re very welcome, and I’m always glad to welcome young, new people to the campus.

Everyone: [00:22:21] (Laughing)

Chancellor Cartwright: [00:22:21] Well, thank you. Before I go, we have this tradition on the show where we actually tell a joke, and we’re supposed to figure out what it is.

Dr. George P. Smith: [00:22:30] (Laughing) Oh no. Do I have to stay?

Chancellor Cartwright: [00:22:30] (Laughing) You have to stay for it. And I’ll ask you, and then we’ll see if you can come up with what might be a potential answer. So, it is: Why did the scarecrow win the Nobel Prize?

Dr. George P. Smith: [00:22:45] Why did the scarecrow? Let’s see, strong in the field? Uh, I don’t know, the master of, something about the field. I don’t know.

Chancellor Cartwright: [00:22:56] Very close! Because he was out standing in the field!

Moderator: [00:23:09] Our audio engineer is Aaron Hay. Our featured music is “Forest Park Rhapsody,” composed by MU undergraduate and music composition major Ben Colagiovanni. You can find more information about Ben and his piece on the Inside Mizzou webpage. Make sure to join us next time, and keep an eye out for the Chancellor’s newsletter to stay on top of what’s happening at Mizzou. Thanks for joining us on this episode of Inside Mizzou. See you around the columns!