George Whitesides (PhD '64), Chemist and NMR Spectroscopist
As one of the world's most prolific and wide-ranging chemists, there is almost no research area that George Whitesides has not delved into. When pressed to identify topics he hasn't touched, Whitesides notes total synthesis and modern chemical biology, simply because his students have not expressed interest therein. To consider the remainder - from NMR spectroscopy, pioneering efforts in microfluidics, and nanotechnology, among many others - is to appreciate the simple and effective approach that encapsulates the breadth and depth of Whitesides's career. As he reflects in the discussion below, Whitesides maintains a sharp awareness of what others are doing, and he focuses his efforts elsewhere.
In well over a thousand peer reviewed papers garnering hundreds of thousands of citations, Whitesides has always seen basic and translational sides as component parts of a scientific approach that is both curiosity-driven and motivated by social impact. He has been a consumer and pioneer of technological advances to unravel the mysteries of polymers and to advance human health, and he has been a leading voice in national policy initiatives on scientific competitiveness.
Born and raised in Kentucky, Whitesides cultivated his scientific interests at Phillips Andover and as an undergraduate at Harvard. At Caltech, he completed his PhD thesis on Grignard reagents under the direction of John Roberts, and the wide range of application in NMR spectroscopy remained a mainstay of his research as he built up his laboratory at MIT. Seeking a change of scenery and in appreciation of the value of broader humanities offerings, in 1982 Whitesides returned to Harvard, where he attained the rare honor of becoming a University Professor in 2004. In recent years, Whitesides has become interested in robotics and research into the origins of life, and at 83 years old, he maintains a five year plan to wrap up his lab and to graduate his remaining students.
Whitesides is the recipient of numerous scientific awards and recognitions, including the National Medal of Science, the Kyoto Prize, the Linus Pauling Award, the Priestley Medal, and the Kavli Prize. In reflecting on all the ways he has been honored, Whitesides ends the discussion with an important, and probably overlooked point: success in academic science goes beyond hard work and even brilliance in the lab. To make progress, scientists must operate within an administrative system, and that means there is wisdom and perspective to be gleaned from secretaries, from technicians, and from the general public. Science is a communal exercise, and Whitesides's humble and plain spoken demeanor is quite obviously a foundation point of his achievements.
DAVID ZIERLER: This is David Zierler, Director of the Caltech Heritage Project. It is Friday, February 24th, 2023. It is my great pleasure to be here with Professor George M. Whitesides. George, it is great to be with you. Thank you so much for joining me today.
GEORGE WHITESIDES: My pleasure.
ZIERLER: To start, would you please tell me your current title and institutional affiliation?
WHITESIDES: I am a Professor of Chemistry at Harvard University. Strictly speaking, I was until recently a University Professor, but I gave back the University Professorship.
ZIERLER: Is it the Department of Chemistry and Chemical Biology, or that's a previous appointment?
WHITESIDES: It's Chemistry and Chemical Biology. That's correct.
ZIERLER: When did those departments merge, or when was the creation of that as a single department? How did that happen?
WHITESIDES: I don't know how it happened. It was the addition of the name of Chemical Biology to the Chemistry Department, and I think it occurred simply because biology has become an important part of chemistry. When exactly it occurred, I don't know, but it was sometimes after I joined Harvard, which meant in 1984.
ZIERLER: When you were University Professor, the named chair was Woodford L. and Ann A. Flowers University Research Professor?
WHITESIDES: That sounds roughly right. Woodford L. and Ann A. Flowers, yes.
ZIERLER: Do you know who they are or were? Did you have a chance to interact with them?
WHITESIDES: Not with them, but with their son.
ZIERLER: What does it mean to be a University Professor at Harvard? I know it's a very rare honor. Is it simply an honorific, or are there specific responsibilities or roles that go along with that?
WHITESIDES: It seems to me that nothing changes, so I would say it is primarily an honorific title. What the then-dean told me was that you could teach a course on anything you want, whether you knew anything about it or not. I have plenty to do with my life, so making up new courses with no background is not a thing that I do in my spare time.
ZIERLER: You gave up the University Professor honorific, but you're not emeritus? You're still active?
WHITESIDES: I'm still active, yes. I still have a research group. I still do research.
ZIERLER: As a snapshot in time, what are some of the things you're currently working on?
WHITESIDES: Origin of life. Self-assembled monolayers. We do a fair amount of work on magnetism in various forms, magnetic levitation, and origins, and finding new ways of using it. Some work in chemical biology, finding things out about how to inhibit virology and related subjects. What I tell the group is if somebody else is doing it, we don't do it. What we try to do is to do things that are different than what most chemists do. Some work stemming from this approach includes the nature of quantum tunneling through organic monolayers (SAMs), for development of soft robotics (fabrication and motions of robotics fabricated from soft elastomers, organic polymers, and uses of soft actuators (actuators) activated pneumatically or by weak electromagnetic forces).
ZIERLER: Some overall questions about the research that you have conducted in your career. In reviewing your publication list, it is difficult to see what areas of chemistry you haven't taken on. Are there any that jump out in your memory that you simply haven't been involved in?
WHITESIDES: We haven't done much total synthesis, which is what chemistry has been deeply involved in for a while. We haven't been involved in conventional chemical biology, finding out enzymatic mechanisms and things of that sort. We probably could do that if we wanted to, but it just isn't something that the students have wanted to do.
ZIERLER: What explains that? What are some of the trends that guide student interest?
WHITESIDES: That's a really good question. One thing is where they think they can find a job, a fairly sensible approach. Another thing is what's new. New can be new because it's new, or new can be new because it's fashionable and it has come to people's attention. One of the things I have learned over the course of running a research group for years is that the group runs best if it is for the benefit of the students rather than for the benefit of me. From that point of view, I would say it depends on the student and what the student wants to do and my cleverness, my ability, to figure out what those things are.
Melding Translational and Basic Science
ZIERLER: What aspects of your research have been purely fundamental, basic science research, and where have you been motivated by applications for societal benefit?
WHITESIDES: We do both, and we try to meld them, so that the general structure of a good research project is one that starts from curiosity and then builds a science base, and based on that science, we find applications, and based on the applications, we go on in some way to try to commercialize what is going on. My view is that if my neighbors pay for my research, they do so on the general grounds that, (A), they don't know what's going on, but (B), they hope that it leads to a better world. So, I should do something to show that what we're doing actually benefits them or their children in some way. That's the underlying circular theme of this.
ZIERLER: What have been some of the happiest surprises, where you took on a research project simply out of curiosity and you realized that this was something that really could be translated into things that help people?
WHITESIDES: A recent example is soft robotics, where we were interested in the modes of action and the mechanisms of movement of things that are alive but are not us. How do those things work, and can you replicate them? Because there must be a reason why snakes do what snakes do and insects do what insects do. That has turned out to be actually a very productive area. There are a lot of people working in soft robotics now. Part of the applications in a practical sense for what you do is in food handling. Now, we don't handle food—that's not our business—but there's a company, and the company handles food, and everybody is really happy with it, and it does something that can't be done with conventional robotics.
ZIERLER: What have been some of the technological advances for which nanotechnology became an area of interest for you?
WHITESIDES: Nanotechnology was a very important area which existed long before we had anything to do with it. As somebody who is familiar with Caltech's background, you know the importance of nanoelectronics. That's really the core of the subject as far as nano goes. How do you make things smaller, make them work, and do so in such a way that the pieces don't interfere with one another? Also, the programs that you see now coming out of Washington is an appreciation of how important it is in both civilian and military life.
ZIERLER: In thinking about application, translating the research, when have you been inspired to create a company yourself, not to just share this idea with others?
WHITESIDES: I think the fair answer to that is that it's very difficult to create a company yourself in a university environment. My rule of thumb is it takes about 10 to 15 years and about $100 million to create a real company from nothing. We don't have that kind of resource basis, so we have to work with others. Another thing that I've learned over the course of time is that good, experienced engineers can do things we can't do. The job of a company is to hire good, experienced engineers, and our job is to do things that make the science base for something interesting. An experienced CEO's way of doing that is to start from curiosity, and I'm a great believer in curiosity as a motivating force in science, engineering, and also business.
ZIERLER: On that basis, I wonder if you can reflect on the idea that you have used chemistry as a springboard to focus on questions that are of relevance to all of science, not simply chemistry.
WHITESIDES: Well, matter is matter, and matter is made of atoms, and the job of chemistry, a job of chemistry, is to manipulate atoms into new forms of matter, for new purposes. That ranges all the way from antivirals to new rubbers to—take your choice. But every field needs new ideas, and every once in a while one hopes, if you have new ideas, that one of them catches hold and becomes something interesting and important.
ZIERLER: You have a career span that goes back to before computation was terribly important in the field, and today it's central. What has that meant for you in your research, the rise of computational power?
WHITESIDES: The rise of computational power means that we can now use canned programs to calculate magnetic fields and electric fields and whatever we want to. It's very good for that kind of thing—heat capacities, magnetic field strengths, all the properties of materials science—because we're as much materials scientists as we are chemists. But over and above that, I would say that it causes one to think about what you know and what you don't know in interesting and unusual ways. We have finally in the last couple of years started programs that have the characteristics that they are applications of chemistry to materials science, to information technology. An example of this is using molecules to store information. Not DNA—because a number of people are working on DNA as a method of storing information—but I think that storing in simple molecules is a much more promising way to go. But we'll see, in the course of 20 years, whether that works out or not. It takes a while.
ZIERLER: A question in historical perspective. By the time you got involved in NMR spectroscopy, did it already seem to be a mature field, or do you feel like you were really part of the beginning of using this technology?
WHITESIDES: It was a mature field, but still had many new careers to attract and fields to explore. It was a field which everyone accepted was a vital part of chemistry. That was proton NMR spectroscopy, and carbon was reasonably well accepted. But then all these other things—the applications in biology, and time-dependent methods, and MRI scanning, and things of that sort—they were all either research or advanced forms of physics and quite new, and very unusual in their possibilities for chemistry or medicine or whatever.
ZIERLER: What have been some of your most significant areas of research within the field of polymers?
WHITESIDES: Probably the most important stuff has been polymer surface chemistry. We've done a lot of work on surface chemistry over some years. In thinking about polymers at the very beginning, we wanted something that we could do that other people were not working on, or not working on in very productive ways, and so we chose surface chemistry. From that came the work—we did a chunk of work on polyethylene surface chemistry, which came—when you take a piece of polyethylene film and use conventional chemistry to oxidize the surface, and then you take the surface groups that you introduce by oxidation and do chemistry with them. That seems like a very simple idea, and it is, but it actually led to a lot of information about surfaces.
Chemistry and National Policy
ZIERLER: Tell me about some of your motivations to become involved in public policy issues in Washington D.C.
WHITESIDES: One of the things which I've done from the beginning is to try to provide a scientific point of view to things that people are interested in who are not scientists, and public policy is certainly one of them. It's public health. It's biowarfare. It's a bunch of other things that one wants to do (or wants other not to do). You find that of the people who go to Washington, some of the people are breathtakingly smart, and some are not. Many of the people who go to Washington, just because they're donating time and expertise and knowledge and skill, are just extremely competent, extremely bright people. I would have gone cheerfully, just to talk to those people. They were of course very interested in having me around, similarly, because I was a bright youngster, and they could do something with some of what they had learned. So, I just learned a staggering amount from being involved in things that go on in committees in Washington, how to run committees, the subject matter of the committees, how the people thought about things, all the usual things that a young person learns from those who are older and more experienced.
ZIERLER: Your interest in climate science and energy efficiency, how far back does that go? Does that go back to even the 1980s when scientists started to ring the alarm bell about climate change?
WHITESIDES: We don't do very much with climate change, but the basic notion is that whatever solution there is going to be to any problem has to be economically sensible. We can't say it's a terrible thing to do, and all one has to do is to put up a vast collection of diamonds around the Earth at 50,000 feet and have them reflect light. How do you do whatever you're going to do, economically? Actually this touches on a sensitive question. I'm trying to think now of sensible ways of teaching graduate students how to do economics in a way that is effective but doesn't take a staggering amount of time and doesn't require them to be economists to do it. I haven't really tried the experiments yet, but we'll get to it soon.
ZIERLER: You've taught so many generations of undergraduates. How have things changed for them in terms of their interests, their talents, their motivations?
WHITESIDES: Many of the undergraduates who take organic chemistry historically have been people who are going on to be medical students. You can argue the correctness of that choice, but there's no question that having smart people involved in medicine and in appropriate ways is a very good thing for all of us, especially as you grow older. How have things changed? It's easy to understand that a course while you're taking it is difficult and takes time. But I've been struck by the fact that students that I see periodically come back and say, "Oh, you taught the organic chemistry course that I took, and I want you to know that as a result of that, the med chem course that I took in medical school has turned out to be a piece of cake because I know all about it." I think that's what chemistry can do for that group of students (and for patients). There are other students who are going to be materials scientists who need to know something about polyethylene and polystyrene and all these silicones and things of that kind, so it varies with the field. I think a good course teaches the basics of what is required to understand as a chemical and as a material what that field works with.
ZIERLER: For all of the graduate students that you've mentored, what are the rough proportions of those who have gone on to industry, to academia, and to government service? What does that breakdown look like?
WHITESIDES: I don't know. I haven't done that assessment. I've thought about doing it, but I haven't done it to this point. I would say most of them have gone to either one form of academia, or one form of company. I would guess it's roughly 50/50, but I'm not sure. Not many have gone straight to Washington to do whatever they choose to do in Washington, but some have ended up there.
ZIERLER: Of all of the successful careers that they have pursued, what have been some of the commonalities? What is the platonic ideal of a graduate student in your group who has done great things?
WHITESIDES: Well, a graduate student, remember, in most of science, is a stepping stone to being a postdoc. For many students, as an undergraduate, you learn the periodic table. As a graduate student, you learn how to be a really good technician. Then as a postdoc, you learn how to be a scientist. There's a difference between these three stages. I would say that what happens is that people go on and they evolve their own style as they go on, and you can't necessarily tell at the stage that I'm working at who is going to be good at what. People who are curious and smart and hardworking and self-directed will come up with something interesting, and people who are basically not that collection of things will have a harder time. They may change over the course of some years and become outstanding in their own way, too.
ZIERLER: What have been some of your key contributions in biotechnology or drug design or drug delivery?
WHITESIDES: In that area, I would say it's probably understanding something about why biology, why life occurs in water, so understanding the hydrophobic effect and things of this kind, which the community of biologists is not particularly interested in but I'm very interested in. Then the issues having to do with how you interfere with some forms of viruses.
ZIERLER: Have you been involved in COVID-19 research?
WHITESIDES: No. Well, the answer to that is, yes, we've been involved in viruses that are very much like COVID-19, but we don't have a program in COVID-19.
ZIERLER: Tell me about your increasing interest in origin of life. How did you get involved in that field?
WHITESIDES: That's one of the big questions in science, in my opinion. It's relatively straightforward as a consequence of work by a number of people to come up with the chemicals that are required for life, but then how they mix spontaneously and spontaneously generate structures, whatever they might be, that after 100,000 years have become alive, become us, we really don't know how that happens. I guess the most popular theory right now is somehow this mixture of chemicals becomes RNA, and then the RNA does something, and it becomes the basis for a living vesicle. But whether that's true or not, I can't tell you, because we don't have the evidence.
ZIERLER: Do you see that mystery along the same lines as the creation of the universe itself? Something from nothing?
WHITESIDES: Oh, probably not. I'm not the person to judge what the physicists do about something from nothing. But something in life from nothing is basically a chemical question, and then the nature of life is a biological question. It's a wonderfully important subject, but it also has the interesting characteristic that if we pursue the origin of life from the point of view of animals and whatever they might be, what you're getting to is self-improving matter, and if we could understand that, it would have applications all over, so it's a really interesting subject from that point of view.
Origin of Life Research
ZIERLER: Among the competing theories about how life originated on Earth, what seems most plausible to you as of now?
WHITESIDES: I don't think I could answer that question. The theory that most people accept is an RNA world of one or another fashion. You start out, and carbon monoxide and carbon dioxide and sugars and phosphates and whatever end up making something that is a copolymer, a random copolymer of these, and then that develops as we know RNA does, interesting reactions which lead to replication and lead to mutations, and the mutations eventually lead to somehow an organism that then goes ahead and replicates. You can certainly see the structure of that idea as containing the right pieces, but whether those pieces are really what went on is anybody's guess at this stage. The people who believe in the RNA world would disagree with me. They would say that we have enough evidence to say it's an RNA world. But, not to me.
ZIERLER: Has your interest in origin of life studies pulled you into astrobiology to some degree?
WHITESIDES: Not astrobiology. The subject that's to my mind more relevant is complexity. How do you get a simple system to become complex and self-regulating or self-improving or changing in some way, spontaneously? I am very interested in complexity, but it's a quite difficult subject. Unfortunately it involves a fair amount of mathematics, and many of the people who go into chemistry go in because, unlike physics, it's not a strongly mathematical field; it's a strongly empirical field. Empiricism is good, too, because if something happens, it happens, so it meets one of the criteria for science, and you have something firm to start from.
ZIERLER: If we do discover life elsewhere—Mars, the icy worlds, an exoplanet—do you think that question will clarify or at least help to arrange our understanding of how life could have originated on Earth?
WHITESIDES: It would be wonderful to see another example, yes! It would certainly help. It would also raise problems that people have raised. They call it the three-body problem. The notion of "if we find something that leads from randomness to life, and life turns out to be common in the universe, do we advertise that we are here, or do we keep quiet about it?" That's a subject which is a policy point of a very deep sort, but it's not really relevant because we don't have any examples yet to worry about.
ZIERLER: What have been some of the key advances in instrumentation over the course of your career? This could be crystallography, microscopy, or anything else that really stands out in your memory.
WHITESIDES: Spectroscopy, if you look at it now and look at it 50 years ago, it's not the same field at all. It just involves looking at various parts of the electromagnetic spectrum and seeing what you can see. But it's enormously more powerful now than it was. Techniques like high-resolution mass spectroscopy are again enormously powerful and very complicated in terms of instrumentation, and that field has gone leaps and magnitudes in that direction. Interestingly, and for reasons that I don't understand, ESR has not made as much progress. It has gone as far in terms of the technical developments in the field, but in terms of applications, there doesn't seem to be quite as much that one can do about it. Then all of the optical spectroscopies have been enormously productive in what they can do, particularly the things that go to very small scales right now. They are key elements of looking at the micro world and nano world and are doing very well, along with electron microscopy as are other forms of small-scale spectroscopy.
ZIERLER: You're a prolific author, writer of scientific papers. What have you learned in terms of efficiency to pump out papers at the volume that you have?
WHITESIDES: Well, we don't pump out papers. We actually go, I regret to say, relatively slowly with them. But I have come to believe that the ability to write clearly and to speak clearly are important parts of thinking clearly. They go along with the rest of science in being a part of the toolkit that a scientist has to have. So, we spend a lot of time learning how to write. We, being me and the students together, spend a lot of time learning how to write.
ZIERLER: What have been the most important funding agencies to support your research?
WHITESIDES: NSF has been important. DARPA has been important. DOE has been important in its way. NIH at various stages in my career has been important. That has been most of them. As a scientist, one goes where there's money, and where, for whatever reason, the peer review community seems to be at least partially on your side. That varies from field to field and time to time.
ZIERLER: What about private organizations such as corporations, individual benefactors? Has that been important to support your research?
WHITESIDES: Corporations have provided some amount of money at various times, but in the greater scheme of things, they have not been a key part of the story.
ZIERLER: George, let's go back and develop some history now. We'll go back to Louisville, Kentucky. First, tell me a little bit about your parents and where they're from.
WHITESIDES: They were both Midwesterners. My father, in particular, was a chemical engineer. He started a small company during the Depression. This company basically worked in polymers during a period in which the chemical industry was producing an explosion of new amines and new epoxides. He would buy the ones that were I guess out of date and mix them together and figure out what they were good for. He made coatings that went on the insides of silos and went on billiard balls, and billiard pins. Wherever there was a lot of hard impact, he made polymers to resist corrosion and to resist impact. He was a very classical inventor.
ZIERLER: What was his academic training?
WHITESIDES: He went to college at Cornell. I think that was pretty much it, so what he learned, he learned on the job mostly.
ZIERLER: Did he involve you in his work when you were a boy? Did you understand what it meant to be a working chemist?
WHITESIDES: Well, when I was a teenager, I would work in summers as a technician in his company, in the laboratory. I was involved in measuring pour-point viscosities and producing lots and lots of glassware that was covered with black slime at the end of a day, and then I would wash it off, so I learned very well how to wash dishes. Then I learned the virtues of keeping clean records and record books and all the things that a scientist is supposed to do. I'm very grateful—he didn't teach me these things; he was off and running the company. But the guy who was the head of the laboratory was pretty strict about it, and I have found it very useful over the course of time.
ZIERLER: You would have been very young, but do you have any memories of World War II?
WHITESIDES: I have some very fragmented memories. I remember when the bomb was dropped, my parents were very excited. I didn't understand any of the context beyond that.
From Kentucky to Harvard
ZIERLER: What neighborhood did you grow up in? Was it urban, rural?
WHITESIDES: It was sort of a mixture. It was a suburb of Louisville, Kentucky, and so we had a perfectly pleasant house. The neighborhood was quiet, and not difficult to live in at all.
ZIERLER: Was it segregated?
WHITESIDES: I don't think it was segregated by law. It was primarily a white neighborhood.
ZIERLER: Growing up, did you have interactions with African Americans? Were they at your schools?
WHITESIDES: Some, but not many.
ZIERLER: Tell me about the decision to go to Phillips Andover.
WHITESIDES: That was a very interesting phenomenon. What happened at one point was that I had started attending something called the Anchorage Public School. It was in the town of Anchorage. Then at some point in that, I went to a country day school in Louisville. One of the teachers in that school, who I had never had as a teacher in class, called up my parents and said, "My name is"—whatever his name was—"and I need to come and talk to you." And, you know, a parent's heart goes pump-pump, pump-pump, flutter-flutter, when somebody wants to talk about a child. But he came out in due course, and what he said is, "You've got to get your kid out of here"—"your kid" meaning me. He had arranged for me to be admitted to Andover. It was just a question of whether I would go or not. I was happy to go, and my parents were willing to let me go, and so off I went, and that's how I ended up going to Andover. It was a wonderful time. I loved being alone. I loved having a room to myself. I loved working on courses and many things about that particular environment. It was all in all a very good experience.
ZIERLER: Were you oriented toward science even then? In other words, entering Harvard, did you know that's what you wanted to focus on?
WHITESIDES: No. I thought, in fact, that I wanted to be a mathematician. But we were required at that point to go to the department chairman of the department we wanted to major in and explain that we wanted to be in X, whatever X was. So, I went to the department chairman and said that I wanted to be a mathematician. He said, "Fine. May I ask you a couple of questions?" I said, "Of course, sir." The questions were, "Do you like your exams? Do you work hard in them? Do you get good grades? Do you like your homework? Do you work hard?" The usual sort of questions. My answers were what you would expect, which was that I found the questions hard, but I enjoyed working on them, and I got basically good grades, and so it was all fine. He looked at me and he said, "Forget it." I said, "Forgive me." He said, "The best that can happen to you is that you end up as an applied mathematician, and you have better things to do with your life than that." But what he meant was I really didn't have the wherewithal that is required to be a mathematician, and he was right. I mean, I like empiricism. I like facts that are based on something I can see and touch and feel and, in principle, taste. I still love mathematics but I can't say that I've ever regretted not becoming a mathematician.
ZIERLER: Was it a professor or a particular course at Harvard that turned you on to chemistry?
WHITESIDES: No, chemistry was always very easy for me. I have a visual memory, so I remember things by looking at them. Then washing dishes and stuff like that, I liked doing. I tell my wife periodically that I enjoy washing dishes and I've washed far more dishes than she ever has. And she tells me, in a polite way, to fuck off. We get along very well on that basis.
ZIERLER: [laughs] George, were there any professors as an undergraduate at Harvard that you considered a mentor or you became close with?
ZIERLER: That wasn't the culture?
WHITESIDES: I don't know whether it was the culture or not; it wasn't for me. I took a standard array of courses, and enjoyed some, and didn't enjoy others, and it was all fine.
ZIERLER: What were some of the lab courses that proved formative in your development?
WHITESIDES: I don't think any were really formative. Probably the most important lab course I took was the physical chemistry laboratory course, because that was involved in understanding the limits to how closely you can know a number, and that's always a good thing for a scientist to know. Then the organic laboratory course was right next to reality. We made compounds, and we crystallized them, and we did things like that, and they caught fire. It sort of simulated what people do as graduate students. So, when I went from Harvard to Caltech, I was pretty well familiar with the standard techniques that you use for chemistry. That is, I was a good technician at that point. Then I learned something different as a graduate student.
ZIERLER: As an undergraduate, what did you do during the summers? Did you have lab work?
WHITESIDES: I had a working relationship with one of the guys who was an electrochemist, and so I would work in his lab over the summer. At least some of the time I did. That was interesting, because he sort of didn't know what I was doing, and you learn a lot by doing it yourself.
ZIERLER: Was there a particular moment where you felt confident that you wanted to go on to graduate school or did that seem like a foregone conclusion from the beginning for you?
WHITESIDES: A foregone conclusion.
ZIERLER: Where were you considering? What kind of advice did you get about people to work with or programs to apply to?
WHITESIDES: Oh, I got such a range of advice that it didn't form any sort of pattern in my mind. I thought I wanted to get away from the East Coast; that meant the West Coast. I originally applied to Berkeley. They lost my application, I think. I never heard back from them. As time went on, I would write them letters saying, "I applied in September, and I haven't heard anything from you since. Am I admitted or not admitted?" The letters were never answered. Eventually I just wrote to Caltech and said, "Look, I have a fellowship, and I have no place to go. Can I come?" Caltech said "yes," more or less immediately, so that's how I ended up at Caltech.
ZIERLER: Did you know of John Roberts before you got to Caltech?
WHITESIDES: No. It was a name that I had seen, but I didn't know anything about him.
ZIERLER: What about reputationally? Did you know about Chemistry at Caltech at all?
ZIERLER: What were your impressions when you first arrived in Pasadena? What sticks out in your memory?
WHITESIDES: Smog. I got off the airplane, and by the time I finished taking a taxi cab, my eyes were streaming tears, and that was just the smog of that day. This was in 1960.
ZIERLER: Do you remember thinking at all perhaps that chemists might have a solution?
WHITESIDES: No. I was primarily concerned with finding someplace to sleep.
WHITESIDES: I don't know how I did that, but I did it.
John Roberts and Caltech
ZIERLER: How well prepared were you in terms of the kind of chemistry you wanted to pursue at Caltech?
WHITESIDES: I didn't have any kind of chemistry I wanted to pursue. I wanted to join a research group, and I assumed that I would figure out what was going to happen then, when it happened, which is pretty much the way it happened.
ZIERLER: What was the process whereby you joined Roberts' research group?
WHITESIDES: Because of the delay in getting admission, I arrived late, and basically the groups were all filled up. I went to Roberts and said, "Look, the groups are all filled up. Can I at least have a bench to work on and sit at while we're trying to straighten this out?" He said, "Okay." Or I guess maybe Marjorie Caserio did. I don't remember who it actually was. I did that for a while. Eventually, I settled into that group. There wasn't anything very formal about it. It was just that Roberts had a bench, and I was doing research on things that were interesting to him, and he was interested in them, and so we just kept on going. It wasn't very formal.
ZIERLER: What was Roberts working on when you connected with him? What was the research of the group at the time?
WHITESIDES: He was working on a number of things, and I don't remember what they all were. There were some projects in Grignard reagents. There was work in the Diels-Alder reaction, which was a hot topic at that point. There were several mechanistic problems of different sorts. He also worked on a range of different projects at a time, so it was a cross-section of topics that were interesting to physical organic chemists at that point.
ZIERLER: Was this your first introduction to NMR spectroscopy, or you were aware of this back at Harvard?
WHITESIDES: It was my first contact with NMR spectroscopy.
ZIERLER: What were your impressions? Did you immediately understand how relevant and valuable it could be?
WHITESIDES: I thought it was very, very interesting, but I didn't understand anything about broader implications.
ZIERLER: How did you go about developing your thesis topic?
WHITESIDES: I did what I was curious about. One of Roberts' great advantages was that he didn't really tell me what to do. We would interact in major part through papers, so that I would do some piece of research, and I would write a paper, and I would submit it to him, and then he would go over it in detail and write notes and ask questions. We would go through that process a couple of times. At the end of that, we'd have a paper and we'd submit it.
ZIERLER: When did you have enough to defend?
WHITESIDES: Three and a half years, I guess, or three years. I've forgotten what it was.
ZIERLER: What were the principal conclusions of your thesis?
WHITESIDES: That I could explain how in certain Grignard reagents, the NMR spectra, adopted the shapes that they had. If you take NMR samples that have the characteristic that there are multiple compounds in them, and they're exchanging with one another somehow, they're becoming one another, then the lines that characterize each of the ones that is exchanging becomes broad in a characteristic way, and NMR is very good at explaining that broadening. The way I did it, I wrote a thesis, and when I got all finished with the thesis—this was a time when there were not much in the way of computers—we would type it up ourselves and use White-Out and correction type and all the rest of it. When my thesis was done, I recognized it was wrong; I had come to the wrong conclusion. So, I started over. In starting over, I went down to see some of Harden McConnell's graduate students and postdocs, and said, "I've got to understand more about the broader mechanics of NMR spectra, and can you please help?" One of the postdocs decided this would be amusing to do, and so he helped me understand. Part of what he helped me understand was, in some weird papers from Israel in the physics literature on time-dependent Schrödinger equations, density matrix approximations, to solutions for Schrödinger equations for fast interchanging systems in NMR spectroscopy. I got a grip on that subject and rewrote the thesis, and that was fine.
The thesis exam was sort of interesting. I remember that pretty clearly. I walked in and there was the usual exchange of pleasantries. Then the person who was the chairman, whoever that was, turned to the group of faculty and said, "Are there any questions?" Harden McConnell, who has been one of the smartest people I've ever met, was there, and he said, "Well, let me ask one question. Imagine, George, that you have a glass of water in front of you, and I tell you that just before you walked in, the water contained either pieces of cubic ice or spherical ice, and they had melted. How would you know which one it was just by looking?" We talked about that for about 15 minutes, and I couldn't come up with an answer. I can do a better job of it now, but I couldn't, at that point, come up with an answer. He didn't know what the answer was, either. He was just asking because this was a time where he was very interested in time reversal phenomena. After a while, somebody got up and left because they had another appointment, and then somebody else got up and left because they had another appointment, and that was the end of the exam. We never did talk about the thesis.
ZIERLER: [laughs] What were you considering at that point? Did you have faculty offers, postdoc appointments? What were your options at that point?
WHITESIDES: I had a faculty offer from MIT, and I trundled off to there. I got that, I think, by having Roberts call up Art Cope, who was the department chairman, and say, "Don't ask too many questions; just hire him." And that was the way it went.
ZIERLER: Were postdocs not that common back then?
WHITESIDES: I think they were not that common. I don't know, for sure. I never really considered a postdoc. There didn't seem to be as many of them in Roberts' group. My group now is essentially all postdocs. I think at that point, Roberts had very few—a couple, but they were sort of peripheral to the main function of the group. I think it was a perfectly legitimate way of going about things. Many people went that way, but I didn't.
ZIERLER: You really didn't go out on the job market? You didn't apply for multiple positions?
WHITESIDES: I applied for multiple positions, and I got a couple of offers, but one was to MIT, and I had wanted to go to Boston, anyway. My girlfriend (now my wife) was there. I thought that was a neat place to go. So off I went.
ZIERLER: That was enough of the West Coast for you.
WHITESIDES: It was enough of the West Coast, that's right. Also I didn't get any offers, I don't think, from the West Coast. I've sort of forgotten this part of my life, but it's a while ago.
Setting up Shop at MIT
ZIERLER: Tell me about setting up the lab at MIT, 1963. What was that like?
WHITESIDES: Something that turned out very well—at the time, it seemed peculiar—I got there, and they didn't have any space for me. After a while, this resolved in such a fashion that I shared a large laboratory that had been an undergraduate laboratory and had been converted into a research laboratory for a guy named House. He very kindly said I could use unused benches in this laboratory. What was wonderful about that was that he had a bunch of senior students, and I think a couple of postdocs, and they were very good at teaching my initial students beginning stuff about chemistry as well. So I sort of shared first-year graduate students with Herb House, and his students were as active as mine and teaching the beginning students how to do things. It was all in all a very effective way of doing things. They had lots of instruments, they let me use them, and they maintained them. It was very generous on Herb's part and very effective from my point of view in getting the group started.
ZIERLER: Was your lab initially narrowly focused? When did you begin to have such a broadly conceived research agenda?
WHITESIDES: It began when I had a larger group. Of course you can't have 20 projects if you have five students. The group started at maybe five people—I don't remember—and then went on from there. It was not really until I got to Harvard that I started working on a lot of different things at the same time.
ZIERLER: What were the key things that you worked on at MIT, the major areas of research?
WHITESIDES: Organometallic chemistry, and that was pretty much it. We did a whole batch of stuff on using enzymes to do organic synthesis. That also worked out quite well.
ZIERLER: Was this mostly fundamental research? Did you see any opportunities for application?
WHITESIDES: Certainly in the biochemistry, there was. We could, in principle, make things that other people couldn't make, and do it in a reasonably efficient way. But if you compare it with the way things are done now in synthesis, there were nothing. There's very little trace of this work left. People do still use some of the enzymatic methods. The pharmaceutical industry in particular has become very accepting of any method that works. The people who really, really understand pharmaceutical chemistry, putting together complex molecules, are the chemical engineers in the pharmaceutical industry, because they use any technique from any field to accomplish what they want to do, and they do it very well.
ZIERLER: You mentioned all of the advances in spectroscopy over the course of your career. What about in those first few decades when you became a faculty member? What were some of the advances then?
WHITESIDES: I don't remember. We were mostly focused on NMR spectroscopy, so we didn't use a wide variety of different methods.
ZIERLER: When did computers enter the scene? Do you have a memory of when the first computer landed in your laboratory?
WHITESIDES: I think the first real computer was bought by one of my secretaries, who wanted to use it for writing letters and things like that. I remember when I hired her, one of the letters for recommendation said, "She is the best secretary you will ever have." And she was. She at one point came and said she wanted to buy whatever kind of computer she wanted to buy, for instrumentation. I didn't think about it too much except that the bill was quite high. It was $20,000 or $25,000. In those days, that was a fair amount of money. But she put it to good use. It was a fairly big operation. She could get things done very efficiently, and that started me off in the right direction.
ZIERLER: Was it at MIT that you got involved in polymer research?
WHITESIDES: It was more at Harvard, but also at MIT. The general issue was that the most common polymer used everywhere is polyethylene. My question was, it's also the simplest polymer from a chemical point of view, so why not just focus on that? That's where we began to work by changing the surface chemistry of the polyethylene film so that you could buy polyethylene film for almost nothing in gigantic quantities, and explored what the relationship was between the surface chemistry and the surface properties, and that was a very good introduction to the materials science of surface polymers, surface-modified polymers.
ZIERLER: What about biology? Was it at MIT that you started to interact with biologists?
WHITESIDES: It was more at Harvard. We got involved in it because it was an adjunct of polymer chemistry. A lot of biology is polymers. There was another (and very distinguished professor) named Don Wiley who was a very good virologist who was interested in some of this stuff, and so we started to collaborate with him. That evolved into a project on flu virus, which was where we focused much of our attention at the beginning.
ZIERLER: Tell me about the origins of the so-called Corey-House-Posner-Whitesides Reaction.
WHITESIDES: When I was deciding what I would do when I got out of Caltech, one of the things that attracted me was catalysis. A lot of catalysis in industry is done using metals as catalysts. I thought that probably an organic molecule adsorbed on a metal surface was like an organic molecule with a coordinated metal in solution, so I would study those and see what they did instead, which we did at great length, with platinum. The underlying idea was to look at the soluble organometallic chemistry and see if they did the same sort of chemistry that you see in heterogeneous catalysis and then draw appropriate conclusions from that. We found all sorts of interesting things about chemical reactivity this way, but not very close connections between the surface reactions and the solution reactions.
ZIERLER: Was it polymer research that got you more thinking about applications, even commercial applications?
WHITESIDES: No, I don't think so. I think it was just a general feeling that coming from the Midwest, you pay your debts, and if people are going to pay for your research, you ought to give them something back in return. Also I have to say that applications of things lead to lots and lots of opportunities and new problems to think about, so one of the best ways of going off in new directions is often to think about what you do with the old directions. Thinking about applications has been very stimulating scientifically as well as being practically useful.
ZIERLER: You mentioned that, of course, you need a larger research group to have a more broadly conceived research agenda. Did that happen for you at MIT? Was the group quite large by the time you decided to leave for Harvard?
WHITESIDES: It was pretty big. It was probably 20 people or something like that. They all moved to Harvard, so I had the same group to start with there.
Returning to Harvard
ZIERLER: What was the decision? Why move to Harvard?
WHITESIDES: Oh, you could say it was partially change of scenery. I still love MIT, and I love it primarily because it manages to integrate engineering and science, in many areas—not all areas, but many areas—almost seamlessly. But I thought in my naivete that at Harvard I wouldn't find that everyone was learning how to do solutions to Maxwell's equations in their head, and that there would be some increased stimulation that would come from working with people who were in the humanities and things of this sort. That is probably true but I have never managed to find it myself.
ZIERLER: You thought that Harvard encouraged more interdisciplinary research?
WHITESIDES: No, I thought that Harvard encouraged more humanities research. Which is true.
ZIERLER: You moved the entire group?
WHITESIDES: I moved the entire group, yeah.
ZIERLER: What was that like, going back to your alma mater? Were any of your old professors there, still?
WHITESIDES: Many of them were. They had not known me as an undergraduate, and they didn't know me as an assistant professor, and that was fine. The general assumption was I was just a postdoc for Herb House.
ZIERLER: [laughs] You said Harvard was really when you got more involved in a broader area of research.
ZIERLER: In what way? What caused that?
WHITESIDES: The problems just got to be broader. As you do research, more problems crop up. Rather than fewer problems, more problems get solved, so your range of problems to work on goes up rather than down. A big research group with smart students working on a lot of different problems produced even more problems to work on, which meant even more people working on more different areas and more different applications.
ZIERLER: Tell me about your decision to become chair of the Chemistry Department.
WHITESIDES: Oh, there wasn't really much of a decision. Somebody came to me at some point and said, "Will you be chair?" and I said, "Yes." I had learned enough in Washington about how to run committees and how to do things of that sort that it was never a particularly difficult job.
ZIERLER: Already, even in the 1980s, you were involved in things in Washington D.C.?
WHITESIDES: Yes. Washington at that point was very involved in the Cold War, and so they needed people who thought about materials in new ways and thought about new structures and thought about new propulsion methods and whatever. There was a fair appetite for young people who had a technical background, and I was just one of many such people. I did most of my work with DARPA. DARPA was very welcoming. They had a number of other bright young people and we all got together and taught one another various things, and it was a good arrangement.
ZIERLER: This was not JASON, though? This was a different group?
WHITESIDES: JASON is mostly physics. This was something called the DSRC, which was the Defense Science Research Council. JASON I think is primarily about problems in physics, Washington has made a decision that it is going to eliminate most of these advisory groups, which I think in the long term is a terrible idea for Washington, because it was a very good method of training young people in thinking about things as Washington does and thinking about problems as Washington does. If you look around, and you're thoughtful, you're going to find a remarkable number of young people in materials science who learned their materials science in advisory groups in Washington.
ZIERLER: Was it at Harvard that you got involved in microfluidics, or that goes back farther?
WHITESIDES: That was at Harvard, because we learned how to make microstructures. The obvious question is, "What do you do with microstructure?" One thing you do is you run fluids through them, so it's a natural thing to look at. The rules of microfluidic science—rheology—apply over a very broad range of sizes, so that much of the theoretical work in microfluidics had been done already by people who had done fluidics in oil pipelines and things of that kind. So it was possible to get a lot done in a short period of time. And there were many surprises in that area, so that's a good thing as well.
ZIERLER: What about surface chemistry, surface physics? Was that also at Harvard when you got involved?
WHITESIDES: Yeah, mostly, although we had started on polyethylene earlier, looking at that. Adhesion, lubrication, friction, all these sorts of areas, are all surface areas of one or another sort. It also turns out that if you look at a carbonated beverage can or something like that, or a bottle, most of the function, the gas resistance, comes from the interfaces in various ways. So it's full of neat stuff to think about. We got involved in trying to understand if we could make this rational rather than empirical, and years later, the answer is yes, you can. Surface science is now not pure empiricism. But companies like 3M did lots and lots of surface chemistry, and were very good at surface science, so they were also there.
ZIERLER: You mentioned it was really at Harvard that you got involved more with biologists. How did that come about?
WHITESIDES: I don't remember. I just know that at a certain point we were not involved with Don Wiley, and then at some later point, we were working with Don Wiley to try to find things that would inhibit the propagation of influenza virus. That never got to the point where it made it into the clinic, that particular project, but it taught me an enormous amount of biochemistry which I had never known before. It was also the case that somewhere in that period, I taught my first biochemistry course, and that was with a guy named Wally Gilbert, who subsequently went on to win the Nobel Prize in biology. Very, very smart guy, and very nice, very pleasant person. I would go to all his lectures, and I don't know what the students learned, but I learned a staggering amount of biology from Wally.
ZIERLER: Did you get involved with consulting as the biotech revolution was underway?
WHITESIDES: Yes, I did a number of biotech companies, or big companies with biotech companies. It was a good thing to do. I learned from that as well.
The Primacy of Simple Research
ZIERLER: As your research agenda broadened, what are the decision-making techniques about what to hang on to, and what to leave behind completely? How do you do that?
WHITESIDES: Different people have philosophies. The one that I have is that what one wants research to be primarily is simple. If you can make it simple, then other people have a relatively low barrier to entry when they think about incorporating one of your techniques. So what we look at is, if we get something done but it requires a massive effort to do it, then we don't spend too much time in that. But if we find some way of doing something that is really, really easy to do, then that's a good thing to focus on. So, a lot of what we have done tends to be things that were really easy to do, because you could make rapid progress that way.
ZIERLER: Was it at Harvard that you got involved in soft lithography?
ZIERLER: How did that come about?
WHITESIDES: That's part of the story that I was just saying. It turns out to be very simple to do lithography using soft methods. Since it's really simple, why not do more things and see what can be done? One of the things, for example, you could do, is make the microchannel systems that are used in microfluidics as just a natural extension. You do that, and once you've developed the techniques, the application is right there, in microfluidics, and off we went.
ZIERLER: Were there startups that sprung out of this research in particular?
WHITESIDES: Not so much out of microfluidics, but there were companies that have used microfluidics. Actually microfluidics is quite well used, and was used based in part on stuff that came along before we were involved in the field. It turns out that it is a field that existed, and was scattered, and it benefited from having an academic focus on the subject as such. We were working at that time with a professor named Howard Stone who has subsequently moved to Princeton, but he was one of the pioneers of microfluidics and a very, very good microfluids person. We learned an enormous amount from him.
ZIERLER: In thinking about your service in Washington D.C., when did you start thinking about pedagogy, education, and American competitiveness? How did that come about?
WHITESIDES: They're different subjects. We have not thought much about pedagogy. It's an enormously important subject, but the point of view that I take is that you've got to find ways of getting people to do things; then they become good at it. It's not a question of the pedagogy, teaching them how to do something they wouldn't do otherwise. I'll tell you a little story about that in the moment. The underlying subject of, when did we talk about that, that has been a subject that has come up periodically but most of what I have done in Washington has been—we have rocket throw nozzles that burn out in one launch, so what do we do to make better rocket throw nozzles. It was that sort of question. I remember in the vein of learning by doing, at one point in this period, I was giving a talk to—I guess it was the incoming MD/PhD students at Harvard Medical School. It just happened that by coincidence, a couple of nights before I was to give this talk, I was having with a dinner with a bunch of people who were Boston biotech experts. I said to them, "Look, guys, I have to give this talk. What would be the one lesson that you think I should pass on about what the students should learn if they want to become biotech entrepreneurs?" It was interesting that everyone there, myself included, had essentially the same answer, which was that if you're going to become a biotech entrepreneur, the way to do it is not to take courses in being a biotech entrepreneur, but rather to apprentice yourself—without salary, if necessary—to somebody who is a biotech CEO and just follow them around and see what they (he/she) do. Because the only way you'll learn how to deal with the time where your company is running out of money and you've got an offering lined up and the money is just there waiting for you, but just at the point that you are about to announce this offering, the market collapses, what do you do, then? You learn how to deal with that by watching somebody who deals with it, who has to deal with it and does deal with it. It has been very effective. That particular question is to me one of the more interesting questions in pedagogy. Do you actually have courses in things or do you set up ways for people to learn by doing? I'm in the learn-by-doing school.
ZIERLER: The original concerns that prompted you to get involved in the idea of American competitiveness, how did that come about?
WHITESIDES: What do we have to offer as a country? We've got very bright people, and a range of applications of things, problems that need to be solved. So, we have a clear opportunity, and we have demonstrated repeatedly that we're really pretty good at this kind of thing, or we can be pretty good at it. So we need to learn how to do it. That's the origin of the interest. It's something which you can do, which we know we are good at, and it's simple enough that you can see what needs to be done. So, how can you most efficiently make it happen? People who are in business have a point of view. People who are in universities have a different point of view. Nobody, even now, is in very firm agreement as to how to do this kind of thing. It's one of the issues the country has to solve as it goes on, one I will say I'm very interested in.
ZIERLER: Because you've been involved in this for some time, what is the current state of play? Has the United States become more or less competitive, overall?
WHITESIDES: The United States has probably become less competitive because other countries have become more competitive. That is, they have put more effort and money into it. The Chinese, for all their real and maybe imagined faults, have put an astonishing amount of money into getting an industrial complex up and running, which is very good in some parts, and really very good. There's nothing intrinsically different about the Chinese way of thinking about things than the American way. There are differences, but there's nothing that is going to dominate whether one is better than the other in the long-term competition. But we have to work on it. If the country develops the point of view that it no longer believes that science is important, and it doesn't believe science anyway, then we've got a problem.
ZIERLER: I wonder if your vantage point from Harvard, which is in many ways the global beacon of higher education, if that's a useful barometer in terms of the kinds of students who are motivated to come to the United States for their education as opposed to staying home?
WHITESIDES: It's a good question. My postdocs often want to do startups. They want to be involved in small companies, which is fine. But the problem there is that all this involves having people and families that have to be paid for, and money for materials and supplies. Research is actually a fairly expensive operation. The country has to decide that it's important to do and then pay for it, or we have to find some other way of doing it. I think that most of the efforts to get industry involved have not been very successful for a variety of reasons.
ZIERLER: Have your graduate students and postdocs become more international over the years?
WHITESIDES: Yes. When I was starting, most of the graduate students came from the Midwest and had repaired tractors in their childhood. Now, the people who want to come here in droves are mostly Chinese. A very large number of Chinese want to come. Sometimes they're very, very good students, and sometimes they're not so good students. Maybe it's not a difference; maybe it's a question of learning how to deal with these differences. But there is a difference that the Americans tend to want to be left alone to do what they want to do, and students from some other countries want to be told what they need to do to succeed. Those are different. The question of do you succeed by doing what you want to do, or do you succeed by doing what somebody tells you to do, is a real difference in science and technology.
ZIERLER: Beyond the American context of service in support of science policy, where have you had opportunity to serve in an international context, thinking about science across countries, not within them?
WHITESIDES: Not so much. I have been on advisory groups that are German and Swiss and Indian and to an extent Japanese, but these have all been fairly casual. They may have taken a fair amount of time but they were not deeply involved in deciding where the money came from and where the money went. With policy, you have to make a distinction between those who think about policy and those who do policy. I haven't been involved in doing policy in foreign countries. Oh, and Taiwan; I had forgotten about.
ZIERLER: What about the so-called Whitesides Report? Was that exclusive to the U.K. or that was more general?
WHITESIDES: It was intended for the U.K. and I think many of the conclusions apply elsewhere. The basic idea of how should science be organized, and does simplicity count, and all those sorts of things, I think it does. The university has the tendency to become self-referential. You sign up to be at a university, and then you work hard to get a Nobel Prize or something. Basically, who cares? Your next-door neighbor doesn't care. You need to decide what standards you're working for and will you cure a disease or make a better cell phone? Are there going to be jobs created, or academic awards that you've won, or what is it going to be? I have my view of that, and other people have different views, and you can take your choice from the menu of ideas that are out there. But I strongly believe that if my neighbor next door can't understand what I am doing, then probably I should think of something else to do, at least in part.
ZIERLER: Because in recent years particularly you've been a leading voice in ensuring, as you mentioned, that science really should be more relevant to people's lived realities, what debates has that sparked within academia, particularly among professors who might bristle at the notion that fundamental research should have those motivations?
WHITESIDES: I don't think much. People do what they do because they think they know what the answer is. The underlying idea in that is fairly deep-seated, and there are some examples. One that constantly comes up is quantum mechanics. It works very well, because Schrödinger did quantum theory for his own reasons, and we'll never know what they were because he didn't write them down, and everyone around him disappeared. You can find examples of things, but chemistry is an area which is pretty strongly dominated by this idea that you do things because other chemists tell you that it's a good idea to do them. They determine how much money you get and they determine a whole bunch of other things. So it's a little bit countercultural to think of things in terms of how directly is it related to something that goes on outside of the academic laboratory.
ZIERLER: Have your ideas gained traction? Have you seen more scientists in academic institutions become more willing to take on applied research?
WHITESIDES: I don't know. How would one ever judge that? I think you find more schools now that are interested in doing applied research (solar power or circular economy, or cancer, are examples). If you want to put it that way. That is, research that is stimulated by solving a problem, as opposed to research that is stimulated by the curiosity of the investigator. I think that's a better way of doing it than saying fundamental and applied, since that has sort of a value judgment already built into it. So, "problem-solving research" or "curiosity-driven research". When you ask is the current situation better or worse than it was, what is your criterion for better or worse? How do you judge? I don't think you can, right now.
ZIERLER: For you personally, what were the scientific areas of opportunity that inspired you to think about becoming more applied, becoming more relevant?
WHITESIDES: I mentioned one, that being robotics. I think that the question of what people have jobs, how many people are there, how will people and machines and computers interact? How will the younger generation pay for the aging elderly? China is running out of people now. It's an interesting thing. You think of the Chinese population as being uncontrollably large, but it's not as large as the country needs to pay for all the obligations that it is accumulating. Different countries are different that way, and you need to think about them in those terms. I just had a bunch of students go over to the U.K., and they're working in robotics, and they're doing it because they find it interesting, but also because they in due course are probably going to establish their own companies and get things going in that direction. That may well be at least superficially motivated by money, but I think it's mostly motivated by curiosity.
Mentorship and Being First
ZIERLER: To return to the topic of taking on new areas of research, what are the calculations in terms of making sure that you're serving your students well, that a graduate student who comes to you can be confident that they're going to do well because you're knowledgeable, you're an expert in this area? How do you have expertise when, by definition, you're moving into new areas?
WHITESIDES: You don't. That's one of charming characteristics of science. You actually have to put skin in the game. The great virtue of being first in something—as everyone says, if you're first, everyone thereafter works for you, but if you're not first, then you work for them. You're going off to do something new; you don't know it's going to work. What you know is that nature is very kind, and if you are intelligent and you watch carefully and you try to behave in a way that's really devoted to dealing with the problem you're working on, then your chances are not bad of coming up with something interesting. It may not be what you were looking for, but something interesting. I think overall the odds are much better for young people to work in things that are curiosity-driven problems in which other people are not working and have not worked than to do it the other way around.
ZIERLER: Is it important to communicate to the students that you're a novice in these areas and there's a certain risk involved?
WHITESIDES: No, I don't think that serves a major function. If you pick out a problem like origin of life, you have to be really almost resistant to new ideas to think that that's something in which the answers were already known. It's clear that it is a topic in which the answer is not known. Whether I think it's soluble or not soluble doesn't make any difference. Probably the best answer is that I think it's not soluble but it's really important. Then you have the motivation to go and do it, because it's obviously not going to be trivial for someone else to come and do it for you, or do it instead of you. Instead you get the entire field with all of its ramifications to be your own, provided that you get there first, which means a lot depends upon your own creativity and perseverance.
ZIERLER: To turn the nature of the question around, when have students—postdocs, graduate students—been a source of inspiration for you to pursue new areas? When do you look to them for new ideas?
WHITESIDES: They come up with stuff all the time that is new. Sometimes the new things are worthwhile pursuing. For example, we were talking about soft lithography. Soft lithography was invented by a pair of Chinese students, Dong Qin and Younan Xia. They did so because that was something that came naturally out of the research that they had agreed to work on, but their solutions were their own, and the solutions were better than the problem was. If you followed Dong's idea of doing nano lithography using a high-resolution printer rather than using a chrome mask maker or something like that, you could get enormously farther in a short period of time. She was just very good at coming up with creative solutions to things that were, in retrospect, very straightforward. They involved equipment that you could buy off the shelf, and wasn't expensive, and techniques that were not complicated, and with which anyone could get involved and do it. I think it is my responsibility to suggest areas that I genuinely think are important and worthwhile doing and doable, but it is their responsibility to come up with innovative solutions to lead to fundamentally new things to do.
ZIERLER: You mentioned the importance of being able to communicate so that your neighbor understands what you're doing. More broadly, what opportunities have you had in being a science communicator, talking about science generally for an audience who is not experts but are interested?
WHITESIDES: This hasn't been a major part of what I've done, but one thing we have done is we've—I have—written collaboratively with Felice Frankel a book on interesting phenomena. That book was driven by her selecting pictures and then me coming up with statements of what the problem was that the pictures represent, and what the solution was, if there was one. But that's interesting to do, and I've done some of that. Then I've done a lot of stuff which involves writing reviews for the scientific public, if you can put it that way, which does as best I can do explaining what problems there are to be done at a given time, or why an area is interesting, or things of that sort. This contributes, I think, to the general noise of the background between different areas of science and society, but nonetheless it probably leads to something worthwhile in the long term.
Reflecting on Science and Society
ZIERLER: Have you been surprised in recent years the disconnect between science and society, between conspiracy theories, misunderstanding, even misinformation? Do you see these as new developments or have they always been present?
WHITESIDES: That's a really interesting question. I don't know. Obviously finding conspiracy theories that seem to violate laws of thermodynamics really sets my teeth on edge. I'm a thermodynamics person. I really believe in thermodynamics. But things that basically contravene established scientific fact strike me as a bad idea. It's okay to come up with those, but you better have a reason for doing it, and you better have very strong empirical evidence to support your point of view. Having said that, there's an entire industry of trying to come up with good ideas about how to do pedagogy and things of this kind. How do students learn how to do science or how to look at nature or how to look at phenomena? They don't do it in general from courses. They do it by doing it. What I would say is that science education should involve more opportunities for creative play, if I can put it that way. Much of what goes on in an academic laboratory is creative play. You do it because you're curious, and the problems are hard and interesting, and when you come out, there may be something else you can do with it. But it's definitely a kind of exercise that doesn't lend itself to learning the way a multiplication table does.
ZIERLER: What have been some of the big takeaways for you in terms of science communication, for better or worse, during the COVID-19 pandemic, about what scientists understand and what they don't, and how they should communicate that?
WHITESIDES: One of the positives is that I think there are far fewer people now that are opposed to vaccination than before. I don't think people have any better idea of what vaccination does or is about than they did before. In fact, vaccination is a hard area. One of the things that to me is a little bit frustrating is that, if you go to different areas, humanity has always been plagued by pandemics of one or another sort. You would think that this would provide a counterexample of a technology, the RNA methods, which makes it possible actually to make a vaccine by design as opposed to doing it by randomly throwing compounds at it. And it doesn't seem to be doing that. It doesn't seem to have done that. The anti-science movements of various sorts are still pretty firmly of the opinion that vaccination is bad for you. Now, how do we get over that hump? It's an interesting question. I would prefer to think that the way you're going to do it is not to have repeated pandemics followed by vaccination is stepping in at the last moment to save the day. But I don't see any evidence of it so far. But maybe in Washington, people are—there's a lot of money in Washington, so you can get a lot of stuff done in a very short time if you've got a good leader to do it.
ZIERLER: More recently, tell me about your decision to give up the University Professorship. Is that just a matter of there's other people that should have this honor?
WHITESIDES: Yeah. The president thought it was a good idea to do. It's something which is okay with me. If it provides other advantages, greater flexibility to the president, and more things that can be done, I'm all for it.
ZIERLER: Obviously that doesn't change your day to day?
WHITESIDES: Not so far. We'll see in due course.
ZIERLER: This is a recent change?
WHITESIDES: It's a recent change. After all, I'm 83 now. At some point I'm going to be run over by a bus or struck by a heart attack or something, and the time is growing closer and closer, and I need to think about what happens to these students that are in the group and how you pay for things, and how you provide exit supervision and all the rest of these kinds of things. This is just part of that whole story.
ZIERLER: What is the timescale for that in terms of committing to students and making sure that they're properly funded?
WHITESIDES: A postdoc comes and usually spends two or three years in the group. It may be two to four depending on the student, but most people spend two to three years and then they move. Graduate students take usually five years, something like that. I don't take very many graduate students now for at least in part this reason. But the postdocs are definitely people you want to pay attention to. They to me are one of the creams of society, of the scientific society, because they've already been through most of the process of training, and now it's just a question of, how do you stir the sense of curiosity and help them to understand what a good problem is, and a bad problem, and are you even right in your own view of this, or is it obsolete now that you've gotten old and atherosclerotic? There are lots of interesting problems there that have to be dealt with. I think there is an obligation for the people who are getting older to think about the students. I'm fortunate that I have a family that consists of two sons and one wife, all of whom are very concerned with the students, and they keep reminding me to pay attention to this problem.
ZIERLER: Where you see time as an increasingly valuable resource, is it the students, that challenge, that seems most precious?
WHITESIDES: The students are beginning, and the directions they go make a big difference. Let's hypothesize that you're going into an academic job, and you manage to get a starter grant. Is your primary objective to get another starter grant? What are you trying to do? Or is your objective to use the starter grant to start something and then go into finding other bigger problems to work on? This whole question of how you design your own career can only be done by you. It makes a difference what you decide to do, because if you decide to work on new problems, that's quite different from working on problems that are just designed to show that you can exercise a skill that someone else has developed. It's much more interesting to work on your own problems, I think.
ZIERLER: Is the emeritus designation something that makes sense for you personally?
ZIERLER: How come?
WHITESIDES: For one thing, I plan to keep on running my research group. In general terms, one of the things that happens at my age is that I feel an obligation to do for the university what I can to benefit it. It's probably more beneficial to have me operating just as a professor than to have me operating as a retired something. Retired suggests that I've lost all my skill and the usual scientific things and I'm just retaining a title. I'll leave it up to history to decide whether that turned out to be true or not, but I don't intend it to.
ZIERLER: At this point, you don't have any particular timescale, what it would look like to wind down the lab?
WHITESIDES: Oh, it will have to be done in the next five years, or a little bit more than that, but it's that period of time. Yes, there is a time that you have to get out. One of the things is to make space for younger people.
ZIERLER: In those five years, do you have a game plan? What's most important to accomplish?
WHITESIDES: I can just walk out. The things that I'm working on as problems, like the origin of life, I don't know that I'm going to be finished in five years, and the way things are going right now, I'm not. Some of the others are the same way, so they will keep going. But if I'm not making progress and not coming up with new ideas, I'm actually quite qualified to judge that myself.
ZIERLER: That's probably always been true in your career, making those decisions?
WHITESIDES: Yes, but it's a difference of whether I can look backwards over five years and then look forward over 20, or whether I can look backwards over five years and look forward over five. There is a real difference in what demography tells you, and what's why demography is fundamentally an empirical art. You see what has happened to other people.
ZIERLER: We're right up to the present. For the last part of our discussion, if I may, some overall retrospective questions about your career, and then we can end looking to the future. I certainly wouldn't want to burden you with the discussion of all of the awards and honors that you have experienced over your career. But what, if any, have been most meaningful, either as an opportunity for you to talk about science, or that have been just most personally satisfactory to you?
WHITESIDES: We're not going to do that because I can't actually answer the question. It's not the case that one has been particularly relevant and another has been particularly irrelevant. Some have been irrelevant and some have been—I'm happy to get them, but there's no point in—all are well intended, and there's no point in trying to make distinctions between them. So, you have to come up with another question.
ZIERLER: [laughs] What about the opportunity? For example the Priestley Medal comes with an opportunity to give an address. Have you found utility in being reflective and to communicate what you have tried to do, when you get an award like that?
WHITESIDES: Utility only happens when you look in retrospect at what other people have done. Have people who heard the Priestley address, would they necessarily go off and do something different than what they had done before? I don't know how you judge that, even if you could get that information. I think I'm one of a number of people who make the point that science should pay its own bills, by thinking at least in part about issues like climate change and global warming and whatever. What can we contribute to this? There are a lot of clever people doing that, so, more power to them. But the underlying notion of just an award—I think it's an open question as to whether awards serve a useful function. What they do do, without question, is to show the person who gets the award and shows the community that they are somehow picked out for having done something of notice. That's good because we don't have the kind of thing that a corporation has, of having an identified list of fast movers and things of that sort. But the other question of whether it actually influences the course of research or not, I don't know.
ZIERLER: Do you think that there is validity to a cynical perspective that it does motivate people because they want the recognition?
WHITESIDES: Oh, you know that that's true. I don't think it's anything cynical, and I don't think it's even a bad idea, because after all, you work for an A in freshman chemistry or first-year mathematics or whatever it is that you're doing. Some form of recognition—in a corporation, you do it in terms of P&L statements. How do you do it in a university? How do you even tell whether you're doing the right kind of thing? At least in part it's are you making an impression on the world. If you are impressing the scientific community, that doesn't really mean very much, but it's a step toward impressing the broader world, because if the scientific community is impressed, then they go off and do some of what you've done, and maybe they'll do something that changes the world. I think it all ties together in a way, but I don't know that the awards are a critical part of that.
ZIERLER: What scientific societies have been most important for you professionally, within chemistry?
WHITESIDES: I guess the answer is that the ACS provides a sort of core skeleton for thinking about chemistry in a variety of ways. The National Academy has assorted committees on various subjects, some of which write reports that are quite interesting and influential. Things like DARPA have made a very big impression on me as I've gone along. They are with a different function altogether. But I think the key issue is that the society or whatever should have as its primary objective to promote the flow of knowledge or the development of new knowledge in the field. IEEE has done a very good job of this, as far as I can tell. ACS has done maybe a less good job, because it has got an enormously broad spectrum of stuff to work on. You can make your way through the others, picking and choosing, but the picking and choosing is based on idiosyncratic information and may not be of much use.
ZIERLER: Of all of your service in a public policy context, you've mentioned already it's difficult to measure impact. Have you seen the way that some of your ideas have changed policy for the better?
WHITESIDES: Changed policy—I'm not actually even sure what that means. There are, for example, a lot of people who do soft lithography, and SAMs (self-assembled monolayers), and things of this sort. The agencies have responded by funding some of these activities. Is that changing policy? I mean, it's changing the peer review system. You can make an argument that the peer review system needs to be reexamined, but there's no point in examining it unless you have a better idea. The peer review system has its faults, but it also serves a function of putting the decisions about scientific priorities in the hands of scientists rather than in the hands of Congress, which is I think a good idea. You can make prolonged disquisitions on the subject of who should decide what, for what, in what field, but I don't know that that's very helpful to do. Vannevar Bush made a big contribution with Endless Frontier, but I don't know anything that has made a bigger impression, except for, I will say, materials science. Materials science is an odd field, and it's the only academic field that I know that has been made up in real time. It was made up by the government agencies, so it was a public policy thing. I give DARPA a lot of credit for that. There's the example. The way they did it was to pay for research which they thought would lead to solutions to problems that they had. If somebody would come up with good ideas as to what the scientific community should do to deal with climate change, I'm sure that scientists would go and do it, because scientists are constantly looking for things to do that are worthwhile problems. But I don't think anyone has come up with a good idea.
ZIERLER: In recent years, there has been such an emphasis on increasing diversity and inclusivity in the sciences. I wonder what your perspective on this is—where that came from, and what its impact has been so far.
WHITESIDES: I think I'm completely for it, and I think that part of the trick in that is to understand this issue of what do people want to do. Because if your idea for inclusivity is to sweep in Black, Hispanic, whatever it is, students, and have them write academic papers that get published in Phys. Rev. Letters, it's not clear they want to do that. Why would you want to do that? If the idea is to start companies and sell things and make money and do whatever, that may be closer. I think a lot of the idea of people getting together and deciding for others what they want to do and should want to do is misdirected. What may be good for me as a member of one sector of society may not at all be good for somebody who is from a different sector of society. We need to find ways not so much of providing opportunities for people as providing a sympathetic understanding that people are different and have different things in mind, and see different problems, when they're doing things. What I would do with inclusivity is to provide opportunities for people to go off in a variety of directions which led to better jobs and more interesting lives. That's not necessarily being a technician for a pharmaceutical company or something of that sort. That's not necessarily what I want to do if I'm with some backgrounds. We have a group of people in society who are trying very hard to solve a problem, which I think is a good and legitimate thing to do. Whether they've got the most efficient way of doing it, or whether they're trying to reimpose on the problem their point of view if they were the problem, is another question that I'm less certain of.
ZIERLER: What about the specific issue of providing access to underrepresented groups, to make sure that they have the opportunities to succeed in the kind of environment like your lab at Harvard?
WHITESIDES: I'm completely for it. How are you going to do it without money? People are beginning to pay attention to that, but the underlying idea that you just say, "We need to provide access and you figure out the details and money and time and attention of how to do that," is not going to work.
ZIERLER: If you can think about all the students that you've mentored, all the great things that they've gone on to do, what stands out in your memory? I don't know if "proud" is the right word, but when you look at what one or more of your students have done and you feel really good about whatever role you played, I wonder if you can reflect on that?
WHITESIDES: It's difficult to reflect in something that is going to be a public document, but one of my students who was a young Black man has become one of the best venture guys I know, and is doing an excellent job in running his venture firm. I hope that he eventually makes a lot of money and gets ahead in the world and changes things. He finds it very interesting to do this. Another one was the CTO of DuPont for a while. It was a woman, in fact. You can find others who have gone off and done interesting jobs. Then I'm pretty much a radical feminist, so I am a big admirer of having women do all sorts of things because I think they make for better research groups and better research and better ideas and just all sorts of other stuff. When you have a bunch of high-testosterone young males looming for a while in the laboratory, there tend to be tensions. Better off not to do that. I think there's lots that can be done, so I think it's a doable problem with money and with effort, but I think it requires both money and effort, and sympathetic reading of people's intentions and what they really want to do. The fact that we want inclusion doesn't necessarily mean that people who want to be included want our view of what inclusion is.
The Long Perspective in Measuring Value
ZIERLER: For all of the new research areas that you ventured into where you embraced being a novice, do you regret any of those research turns? Or even if a particular one didn't work out, there's value in that experience as well?
WHITESIDES: The value in any experience may not crop up for 10 or 20 years. An interesting area that we have worked in recently has been magnetic levitation. How do we use a magnetic field gradient to lift, or not lift, heavy weights or light weights? You can do some really interesting things. For example, we can separate fentanyl crystals from meth crystals in very small quantities to enable their identification. That's an example of something you can do. But that's a very specialized example.
ZIERLER: Only a few more questions to wrap up. What are you most proud of in terms of fundamental discovery in chemistry? Where do you see your most important legacy in what you've accomplished?
WHITESIDES: You still used "fundamental." What do you mean?
ZIERLER: Understanding how nature works.
WHITESIDES: Is that curiosity-driven?
ZIERLER: Yes. What have you discovered? Simple as that.
WHITESIDES: Probably the self-assembled monolayer work (SAMs) is the most widely used. It's part of the democratization of science, because anyone can do nanotechnology with self-assembled monolayers and come up with really good results that way with almost no effort. That's interesting. That was done in collaboration with Ralph Nuzzo at the University of Illinois, who is a very good scientist, who has also worked on the problem. I put him as number two in the line of people who discovered and rediscovered self-assembled monolayers. Number one was the engineers at 3M.
ZIERLER: What about on the applications side or the translational side? What are you most proud of there?
WHITESIDES: That's again a complicated question. The one area or the one company that has produced stuff that is widely used—it was originally GelTex, and it became whatever it was—the name will come to me in a moment; I've forgotten it. It makes material for kidney failure, and it is widely used today as a substitute for more extreme procedures. The reason it works is that it simply is a simply polymeric method of sopping up phosphate from the urine and preventing it from being excreted in the wrong fashion. Soft robotics is also doing well, and it has served a real need, and is serving a real need in food manipulation, or manipulation of soft objects in general. We are working on others right now for memory—secure memory for computers and things of that kind. At any given time, there are three or four of these that are going, and I can only really tell you after 20 years and see what has finally happened to them. That's not a very satisfying answer, but the lifetime of a small company is typically that it is founded, it goes through a troublesome period when it's growing, and then at some point it gets sold to a big company which does the delicate arts of manufacturing and applications to immediate problems, which is more difficult than people think it is, and more important than people think it is. It's best done in big companies with scads of good engineers who really know how to think about manufacturing and related subjects. I would say that we have a couple going now. This particular one, I'm wearing a sweater from Arsenal Medical, which is going to be doing stents for nasal infections. That probably looks like it's going to work well, and is a relief for people who have nasal infections, sinus infections as well. Each one is different. It's like saying, "Which of your children do you like best?" The answer is, "I can't answer that question because they're all different." For some things, some are better than others.
ZIERLER: Is there anything that you've learned from your time at Caltech, either institutionally or from John Roberts specifically, that really has stayed with you, that has informed the kind of scientist you went on to be?
WHITESIDES: I learned all sorts of things from Roberts. Starting at the beginning, he had the skill—and I actually have become more and more convinced it is a skill—to leave me relatively alone. So I set my own course. He was very helpful during it, in this process of writing papers, but it was not directive. It was more assistive. Then the underlying idea that if you work with smart people, good things come of that, sometimes by accident. My ability to solve the problem of line shape in NMR spectroscopy came from talking to one of Harden McConnell's postdocs. He was a smart guy. He was a very smart guy and he taught me what I needed to know in a very efficient way. The mere fact he put up with me was a good thing to do. The underlying issue of trying to understand what's important enough to do in retrospect, which is I think what you're really asking, is a tricky question to answer, because it varies with the subject, with your age, with the number of students, with their point of view. I think one of the major things that I learned as a research director really came from, of all people, my secretaries, who at one point sat me down and said, "Look, the thing you need to understand more clearly than you do is that running a research group—a research group is a social organization. It's not a scientific organization. So, what you need to understand is what the people want, and what the people do, and how they think about things, and then you try to help them, and things will work out at that point fairly well. You've got to do it that way rather than doing it from the point of view of your view just of what the best science is." I think it's largely correct, and I think the university is not very good at teaching that particular point of view.
ZIERLER: But it's one that you came to appreciate, from secretaries, of all people.
WHITESIDES: From secretaries, yeah. When people go off to get university jobs, I tell them that the one group of people they must get to know and must get to be sympathetic with and learn to operate with are the staff in the department, whoever that turns out to be—the secretaries, the machine shop operators, all the rest of those people—because those know how to really make things run. They're the good engineers of an academic environment.
ZIERLER: Finally, looking to the future, I want to ask a question about technology. What are some of the technologies that you're most excited about? In that same vein, what are some developments, either in simulation, artificial intelligence, that might give you pause, that might take science in a way that might be troublesome for you?
WHITESIDES: We're interested in and have been interested in, for a number of years, AI. The underlying notion of this, you're more than familiar with, but that question of the mere fact that it's easier to ask a machine questions than it is to think it through yourself, what does that do to the process of self-training that leads to creativity? I'm not so sure about that. I'm not so sure that that's a helpful idea. We're going to have to see how that works. But I think we're going to go have another—we had our initial flurry into AI in the mid 1990s, actually in the early 1990s, and at that point, we couldn't find what we needed in the way of data sets, so we abandoned the subject. But I think now one can do it a little bit differently. I don't know whether it's really going to end up being good for science or not. I know it's going to be good for technology, and exactly how one makes something of that is an interesting question which users will have to figure out as they have figured out what to do with the internet and the web and things of that kind. What else is there? The neurological sciences are obviously extremely important in understanding how the brain works, but I don't see a lot of life in those areas yet. It may well be my fault, not their fault, but I don't see a revolution occurring in that subject, in those subjects. But then the question of "Can you manipulate matter to make something that's fundamentally new?"—I think the chances are we're going to be pretty good at doing that. What we do with it, I'm not sure, but we're going to be doing that. Finally, the military, for better or for worse, has been a very strong contributor to the development of new technology, and what does the military need? I don't know right now. What does one do with a hypersonic weapon other than owning a hypersonic weapon? I don't know the answer to that question. That isn't really an answer; it's just sort of a ramble.
ZIERLER: It's useful indeed, that these are the things that you think about. George, it has been a great pleasure spending this time with you. I want to thank you so much for doing this.
- Melding Translational and Basic Science
- Chemistry and National Policy
- Origin of Life Research
- From Kentucky to Harvard
- John Roberts and Caltech
- Setting up Shop at MIT
- Returning to Harvard
- The Primacy of Simple Research
- Mentorship and Being First
- Reflecting on Science and Society
- The Long Perspective in Measuring Value