Thinkers50 in collaboration with Deloitte presents:

The Provocateurs:

podcast series

EPISODE 6

ABOUT THIS EPISODE

Robert Lefkowitz: Adventures of an accidental scientist

Trained at Columbia, the National Institute of Health and Harvard before joining the faculty at Duke University in 1973, Bob Lefkowitz is a Nobel Prize winning scientist who is best known for showing how adrenaline works via stimulation of specific receptors. He is also a cardiologist and the author of the memoir, A Funny Thing Happened on the Way to Stockholm: The Adrenaline Fueled Adventures of an Accidental Scientist.

In this wide ranging conversation with Deloitte’s Steve Goldbach and Stuart Crainer of Thinkers50, Bob Lefkowitz looks back on his amazing career and the lessons he has learned along the way.  Filled with inspiring anecdotes, this episode travels far and wide featuring the inside take on mentoring, how to lead brilliant people, the power of enthusiasm and storytelling, the role of humour and how a refusal to be compartmentalized led eventually to a Nobel Prize for research which has touched the lives of tens of millions of people worldwide.

#TheProvocateurs

Guest starring:

Bob Lefkowitz

Robert Lefkowitz
Howard Hughes Medical Institute investigator

Q

About Our Guest

Robert Lefkowitz

Dr. Robert Lefkowitz is a Howard Hughes Medical Institute investigator who has spent most of his 50+ -year research career at the Duke University Medical Center. He and Brian Kobilka, a post-doctoral fellow in Lefkowitz’s lab in the 1980s, were awarded the Nobel Prize in Chemistry in 2012. Lefkowitz is a Professor of Biochemistry and Chemistry, and a Chancellor’s Distinguished Professor of Medicine. He is also a basic research cardiologist at the Duke Heart Center. He has been an Investigator at the Howard Hughes Medical Institute since 1976, and is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. Other awards include the National Medal of Science, the Shaw Prize in Life Science and Medicine, and the Canada Gairdner International Award.

Hosts:

Steve GoldbachSteve Goldbach
Chief Strategy Officer, Deloitte

Stuart CrainerStuart Crainer
Co-founder, Thinkers50

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Inspired by the book Provoke: How Leaders Shape the Future by Overcoming Fatal Human Flaws; Wiley, 2021.

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EPISODE 6

Podcast Transcript

Stuart Crainer:

Hello, I’m Stuart Crainer, I’m the co-founder of Thinkers50, and I’d like to welcome you to the monthly podcast series Provocateurs, in which we explore the experiences, insights, and perspectives of inspiring leaders. Our aim is to provoke you to think and act differently through conversations with some brilliant and inspiring people. This is a collaboration between Thinkers50 and Deloitte. So my co-host today is Steve Goldbach. Steve is the Chief Strategy Officer for Deloitte and co-author of the bestselling book, Provoke. Steve and I are very excited to welcome a fantastic guest for today’s conversation, Robert Lefkowitz. He is a Nobel Prize winning scientist, who is best known for showing how adrenaline works via stimulation of specific receptors. He was trained at Columbia, the National Institute of Health and Harvard, before joining the faculty at Duke University in 1973. He’s also a cardiologist and the author of the memoir, A Funny Thing Happened on the Way to Stockholm, the Adrenaline Fueled Adventures of an Accidental Scientist.

Steve Goldbach:

And he is showing that for those of you who are listening, but not watching, Bob is showing the title of the book. And I’m really excited, Bob, for this particular conversation. It’s a great book. I’ve got some very specific questions from the lines of the book, but I wanted to start with a thank you. And I’ll get to my first question because my eight-year-old daughter right now is dealing with a specific phobia that she’s developed over time.

And so, it’s really helped me. I was telling her this morning, driving her to camp that, “I’m interviewing the person who has developed an understanding of why it is that your heart starts to beat and what’s the chemistry behind when your heart starts to beat when you see the wind. I am going to talk with the gentleman who is part of the team who discovered why that’s happening in your body.” Because she likes to understand what it’s doing. So, it’s really obviously a long way from the Bronx High School of Science to receiving the Nobel Prize in Stockholm. But looking back, how you make sense of that journey – are you really an accidental scientist?

Robert Lefkowitz:

Very much so in the sense that I never intended to be a scientist. My dream from the time I was just a little boy was to be a practicing physician. I was inspired by my general physician who made house calls in the Bronx and I was just totally taken with this man. He would come to the house, he made house calls, somebody was sick. He’d come to the house with that black bag from which he would produce all manner of magical instruments, reflex hammer, stethoscope, otoscope, prescription pad. And he knew all this stuff that other people didn’t know. And he could leverage that information to make you feel better. So I would say by the time I was seven or eight, I was absolutely intending nothing other than to become a doctor.

And I was steadfast and highly focused on that, right through the special high school you mentioned, the Bronx High School of Science, Columbia College and Medical School, house staff training at Columbia and Harvard. It never occurred to me to do research, even though I loved science. The only reason, and in fact, by the time I graduated medical school, I had never done any research at all. My lab today is filled with undergraduates, doing research electives. I never did anything like that because I had no interest in being a scientist. So how did it happen? Well, the Vietnam War was going on in the sixties and there was a doctor draft, unlike the general draft for men over 18, which was a lottery. There was no lottery for physicians.

You had to go in and you were drafted into either the army, the Navy, the Air Force or the public health service. And you went to Vietnam for one of your two years of conscripted service. But if you were lucky enough to get a commission in the public health service, you might be fortunate enough to be stationed at the NIH or the CDC or something like that. And that’s what happened to me. And there at the NIH, I first began to learn and be exposed to doing research at which I will point out, I did not distinguish myself. I was pretty bad at it for at least a year or a year and a half, but that was the accident. The fact that I came through medical school at the time of the Vietnam War.

Stuart Crainer:

So, how did you figure out how to be good at research then, Bob? What changed after the first couple of years?

Robert Lefkowitz:

Well, initially I was completely inexperienced and so I didn’t know what I was doing, and although I had good mentors, they didn’t micromanage, put it that way. So, I had to kind of learn a lot of the stuff on my own. Plus, I had no way of understanding it then, but as I look back on it later in my career, I realized the project I was given, was an extraordinarily difficult one, especially for a complete novice, but I had no sense of that at the time. So, it was a combination of my inexperience, a lack of really hands-on guidance and a very challenging problem.

Steve Goldbach:

Bob, one of the things that you’ve talked a lot about in our research on you, is the importance of appreciating failure and learning from it. One of the things that Geoff Tuff [Principal, Deloitte, co-author of Provoke] and I have written about is that we think that today, oftentimes in business, the notion of celebrating failure is used as a little bit of a crutch so that we can just accept not designing work well enough. But it seems like when you talk about it, it’s really about the notion of you got to learn something from it, but it strikes me that you’ve got this rare combination of humility and appreciation for learning. And so, I wonder if you could talk a little bit about how that failure caused you to learn, and how you dealt with that, and how others around you reacted with it.

Robert Lefkowitz:

So at the time I went to the NIH in 1968, 2 years out of medical school, 25 years of age, I had never failed at anything, much less in a protracted way. I was always top of my class. I was a pretty decent athlete. Whatever I put my mind to, I did well at. And now, despite the very best effort I could put out, I was failing and that went on for a year or a year and a half. That was devastating to me. So, I learned to pick up the pieces. The only way to really learn to deal with failures, like anything else, is to deal with failures. So that’s the first point. The second point is as you said, to learn from each failed experiment. You may have failed to accomplish the goal that you wanted, but you learn. Thomas Edison said he had about 300 ideas for inventions a year. One of which worked and somebody said, “Well, how can you deal with that?” He said, “Well, I don’t view those 300 inventions that didn’t work as failures. I view them as 300 discoveries of things that don’t work”. So, in other words, he’s learning what doesn’t work on the way to defining what does. But perhaps beyond that, you mentioned something which sounds counterintuitive, but which I have learned and tried to inculcate in my students and fellows, which is the idea that you really do have to learn to embrace failure. I told you that one of the major things, probably of the various things I mentioned to you, which were involved in my failure that first year and a half, my inexperience, the lack of close guidance. Yes, they contributed, but the single most important thing was just how challenging the problem was. And of course, I had no way of evaluating that since this was the only research problem I had ever engaged with. So, how do I know what to compare it with? I’ll tell you a story.

So about 10, 15 years ago, a guy came up to my lab during Christmas week. This was a young man who didn’t train with me, but I had been mentoring him for a number of years. And I was sitting at my desk. It was probably around December 27th or 28th, between Christmas and New Year’s. And I had a ritual, if you will, that I used to do every year at that time. Because it was quiet, nobody else was around. And I would sit at my desk and I would review what my lab had accomplished or not accomplished over the previous year. And since I had gone through it a year before, I could look at the list and mark, “Well, what was working? What wasn’t working? What turned out to be stupid ideas? What things I never even got to, what things actually made some progress.”

And then based on that, I would draw up my plan for the next year. Anyway, he came in and he asked what I was doing. I said, “Well, I go through this ritual. I’m just trying to see what fraction of the things we’re working on are actually making progress or working.” He said, “No kidding. It doesn’t sound like a bad idea.” I said, “Well, what fraction of things that you are working on are actually working?” And he said, “Oh, I don’t know. 90, 95%. How about you?” I said, “I don’t know. 20, 25%.” He was appalled. He said, “Only a quarter of things that you’re working on or less, are actually working?” I said, “That’s about right. If it gets much above 35, 40%, I’m really unhappy with that.” He says, “Why would you be unhappy?” I said, “Because if I’m heading towards half of the things I’m trying are working, I’m not really taking on very challenging stuff. So, fortunately I never get anywhere near that.”

I said, “This year, it looks like it may be 15%.” Well, he was amazed by that. Anyway, he took it to heart. And in the years since, he’s told me that this has totally changed his perspective on his career and the work that he does. And I can tell you as somebody who continues to mentor him, the quality of his research has elevated significantly over the past number of years. So, I would have to say I embrace failure as a way of validating that I’m taking on challenging problems and I’ll tell you something else that’s interesting. I’ve had the privilege, the opportunity to listen to people who are leaders in virtually every field of human endeavor, sports, entertainment, military, law, medicine, science. And every time I hear a career talk by a really successful person, if I had to pick a single thread that runs through everyone, it’s just how much failure they dealt with early in their career. So I think that’s a real commonality.

Stuart Crainer:

Bob, could you talk a bit about mentoring. You’ve already alluded to mentoring and I read in Ruth Gotian’s book, The Success Factor, that one of your early mentors said, his  “chief job was to keep Lefkowitz out of a deep, dark depression,” which I thought was quite good. And I know that very early on in your career, you mentored Stokely Carmichael, the civil rights activist. So, mentoring has been kind of a pattern throughout your career. And I wonder who are the big mentors for you and how do you put it into practice? Even at an early age you were mentoring.

Robert Lefkowitz:

Yeah, so it’s interesting. I have formally trained about 250 people, but the number is well beyond that because that doesn’t count undergraduates who worked in my lab. That’s just graduate students and postdocs. And it’s interesting. In my book, I have a whole chapter on mentoring, but it’s kind of interesting. I’ve always enjoyed mentoring, but I didn’t even realize I was mentoring for probably the first 20 or 25 years of my career, because it’s only now that I’m in my dotage, so to speak, that I think a lot about what I was doing. But for much of my career, I didn’t think at all about what I was doing. I was just too busy doing it. I’m reminded of a story about Yogi Berra, who you probably never heard of. Yogi Berra was a catcher for the New York Yankees in the forties and fifties and early sixties.

When I was in my heyday as a New York Yankees fan growing up in the Bronx and he was one of these homespun philosophy guys and many quotes are attributed to him, most probably apocryphal. But one story that’s told about Yogi is the following. He was an amazing clutch hitter. He had a lifetime batting average of about 300 anyway, which was great. But bottom of the ninth inning, two out, the game on the line, the team down by a run or two, there was nobody you wanted at bat more than Yogi, because his average in that situation was probably 500. He was amazing. And he often hit a home run in that setting. So he was being interviewed one day and the interviewer said to him, “Yogi, you’re so amazing in the clutch, how you’re always able to come up with a hit.”

He says, “So, could you share with us when you’re at bat in that very tense situation and you know you have to get a hit. The game is on the line, what are you thinking?” And Yogi looked at the guy with amazement and he said, “Think? How you going to think and hit at the same time?” And that really sums it up. I mean, how you are going to think and hit at the same time? So I would say for the first 25 years of my career, I was so busy hitting, I never thought about what I was doing, but now I think about it a lot. And it was interesting, as I say, I never looked at it as mentoring. It’s just, I’m a very social person. I was doing science and I just loved doing it together with younger trainees. And it was just sort of, “Hey, join me in the enterprise. Kind of watch what I’m doing, but not just watch, do it with me because I can’t do this by myself.”

So, I’ve always been very sort of collaborative and bringing people in and just sort of showing them the way and making myself as available and transparent as I can. It’s interesting to me to talk with people like you from the world of business, because I don’t know anything about business. I remember my father was always very frustrated with me because I never gave a damn about money. He always used to say, “Yeah, Bobby rises above it.” So it’s interesting in terms of leadership styles. My idea, I guess, as I look back on it, is even though I was the leader of my group and everybody knew I was the leader and I was the senior guy – I didn’t work by giving orders. I never gave orders to anybody. I mean, the number of times in my life, in my career where I’ve actually said to somebody, “You are going to do this,” – very small. It’s happened, but it just is very rare.

In general, I work by suasion, convincing people that, “This is the overall goal. And I really think this is the way you might come in, but what do you think?” And when I say, “What do you think?” It’s not proforma. I really care what they think because I found that at least in what I do, the best way to have success is that if people are not just in tune or in sync with what’s going on, but they’re really enthusiastic about it. And in fact, one of the things I tell people, when I have a new postdoc come to my lab, we spend the first few weeks figuring out together, what they’re going to do. And I always tell them, “Look, there are two keys to success in my lab. They are necessary, but not sufficient.” That is to say they will not guarantee success, but absent either of these, success is most unlikely. So first, you need to be excited about your project. Second, I need to be excited about your project. If we’re both excited about it, it doesn’t guarantee will succeed, but it really ups the possibilities.

Steve Goldbach:

Bob, it’s interesting you go there because one of the things that we’ve been writing a lot about in business is that the most basic, we call it a sub atomic element of business is actually human behavior. Not money, not anything else, it’s human behavior. And the stories that you’re describing and one of my favorite stories from your book is the story where you gave the woman in the hospital a placebo every day. And you show the power of the human brain by overcoming her personal pain. And the story that you’re telling there is just understanding the motivations of other people is super important in getting them to do what they’re passionate about. And here you talk a lot about passion in how you talk about your work and how you feel like you’re working on important things. How did you decide what problems to tackle over the years? How did you develop the passion for the projects you pursued?

Robert Lefkowitz:

That’s a wonderful question. So, the first thing about being passionate is some people are more passionate than others. Let’s face it. There are different personalities, but some people may be passionate, but another aspect of their personality is that they’re very guarded. So, they’re not as able to display that passion. I’m fortunate in that I’m both passionate about what I do, and I like sharing that passion with others. And what you learn over the years is that there is nothing – COVID included – which is more infectious than enthusiasm and passion. And I have learned that repeatedly in my career. Another story I may tell in the book – I got too many stories. I don’t remember which ones are in there. When we finished writing the book, and as you know, I wrote it together with a former postdoc of mine.

I told them stories over a couple of years, we recorded it and then we turned it into the book. But then we had a list of, it was called Left on the Cutting Room Floor. We had close to a 100 stories that didn’t make it in. So there may be sort of a sequel, but one story was, and this was told by one of my trainees 20 years ago, when we had my 60th birthday, we had a big reunion. And some of the trainees were reminiscing about their time in my lab. And one guy who now has a name chair at Cornell, was saying that he was working late one night, and he was sort of just chatting with one of his lab mates. And he was explaining to this guy how excited he was about his project.

And in particular, the fact that he knew that I, Bob, viewed his project as the most exciting one in the laboratory. And this lab mate listened and said, “Well, that’s very nice, but I hate to burst your bubble, Bob thinks my project is the most exciting in the lab.” Well, there was another guy there. He said, “Wait a minute. I don’t know what you guys are talking about, but you can just tell by the way he talks at lab meetings, that my project is really the focal point of the whole lab.” Well, certainly had a little bit of a dust up about it. The next day or two, we had a lab meeting and these three guys confronted me. They said, “Well, what’s the story? We all think our project is the most important one. Which one is it?”

And I said, “Well, it’s all of them.” I said, “Of course in the moment that I’m talking to you, your project is the most important one to me in the entire lab. And when I’m talking to you, your project is the most important one. So they’re all the most important.” And you can’t put that on. You can’t act authentically, what I was saying was true, but they feel that passion and they feel that enthusiasm. And it always amazes me how I get these people so ginned up end up because I can’t see myself from the outside. So, I don’t know what it’s like working with me, but this has been a theme throughout my career, that the people that work with me, just get all excited about what we’re doing. And then they go on to be enthusiastic mentors in their own right.

Stuart Crainer:

I mean, one issue in the environment you work in, Bob, is that you are always managing and leading very smart people, which is an issue increasingly in the management and business world, that the leaders aren’t necessarily the smartest people in the room anymore.

Robert Lefkowitz:

I’ve never been the smartest person in the room. I mean, I’d dare say, I probably couldn’t get into medical school today. I mean, the kids that come through my lab are so effing smart. I can’t believe it. And I love surrounding myself with really smart people. The smarter, the better.

Steve Goldbach:

Are you still learning from them? I’d just be curious. You strike me as a type of person that is just, you’re never done learning from the folks around you.

Robert Lefkowitz:

Absolutely. In fact, let me open the dedication of my book. It says, “For all those who have taught and inspired me, especially my parents, my wife Lynn, and my children, and my students.” Absolutely. And everybody who works with me knows that one of my maxims is that at lab meetings, when we’re all together, I don’t care who’s got the best idea. I don’t care whether it’s some amazingly junior undergraduate or whether it’s a visiting full professor, who’s on sabbatical. I really don’t care who’s got the best idea. I just want the best idea wherever it comes from. And they know that I’m the kind of leader that I like to be called Bob. Some people can’t handle it. And I understand that. I’ve learned that it’s inappropriate for the undergrads, et cetera. And especially, you get older and then you win a Nobel Prize.

I mean, people have trouble calling me Bob, but I don’t want any special… What’s the word I’m looking for? I don’t want any special weight given to my opinion, just cause I’m Bob Lefkowitz. In fact, I think my ideas, the older I get, should be given even less credit, but yeah, absolutely. Who’s ever got the idea, we want it. And I love smart people and I’m never embarrassed by not knowing something. And I love being taught by my students and I am taught every day. God help us when it comes to technical stuff, but it’s so great. I mean, if something got screwed up right now on the screen, I’d open the door, I’d wave down the first student who’s coming by. I’d say, “Get in here and fix this,” it would take them five seconds. So absolutely, I love having all these people around.

Steve Goldbach:

Well, I want to maybe explore for a second, a topic, and maybe we can geek out a bit on the science aspect of your discoveries. And one of the things that when we’re talking about business, we talk about business leaders being able to spot trends as they’re moving from a matter of, if they’ll come to fruition, to a matter of when they’ll come to fruition. What were you seeing in your discoveries around the receptors or the receptas as you like to say, as I remember. Were you able to see something there, that the people who had been researching in that field before, hadn’t seen, and that led you down the path. I know it wasn’t just a Eureka moment where the light bulb went off, and there’s a lot of work that goes into an overnight success. So, talk us through a little bit about what were the things you started to see that led you to believe that there was something more to discover there?

Robert Lefkowitz:

So, let me try to talk about a few general principles about creativity and science, which come into bear here, because there are these amazing lineages in science, where if you look at outstanding scientists, Nobel laureates, for example, and you ask who do they train with, almost invariably, they trained with really accomplished scientists. And if you look at who they trained with, same story. And I’ve actually written about this, especially amongst Nobel laureates, there are amazing family trees of one Nobel Laureate training another. Sometimes it skips a generation, but it’s really pretty amazing. And I think the reason for that is that there are transferable elements in learning how to pick good problems, but a good problem has several characteristics. One is that if you solved it, it would really be important. And the other is that you have some realistic chance of solving it, at least in science.

So there’s a spectrum. On one side are problems, which you could solve. In fact, almost any competent scientist could solve, but nobody’s going to give a damn because they’re just not that important. At the other end are problems of cataclysmic importance. But frankly, the chances of you solving it are next to zero. And in fact, for some of them, there’s no chance anybody could solve it right now because the techniques or ideas that would be necessary to do that, aren’t coming down the pike for years to come. So the secret in our game is to work as far over toward really important problems as possible. But without going over that cliff of what you can’t do. Now, how do you find that spot? Nobody can tell you. If anybody can answer that question, boy, I can’t imagine, but that’s like everything else that I want to teach about how to do science.

I always tell people if it’s important, you can’t look it up in a book. You have to learn in my view, by lived experience. And learning how to do science, as I suspect is true in most walks of life, whether it’s business or law or whatever, it’s an apprenticeship. So people come to my lab, they live with me in the lab for a number of years and they have a chance to watch me over and over and over again, make decisions about, “Well, are we going to work on that or are we not going to work on that? Are we going to keep working on this? Or is it time to give it up?” In all manner of other such things, that they learn. It’s essentially a matter of developing value judgements. “Is that a really amazing piece of art or is it dribble?” Well, you’d have to train with somebody who’s an art critic to try to learn a certain sense of taste.

So that’s one thing. So then the question is, “Well, how do I choose problems?” Well, again, I can’t really tell you the rules. I just mention some things, but for me, one thing, one criterion has dominated everything else. “How interested am I in the answer to that question?” So, I’m relying not on an intellectual process – it’s almost an emotional process. Do I find that interesting? Simple as that. Well, what the last 50 years have shown, is that my interests seem to lead to important discoveries. So lucky for me. It suggests that the things that interest me are inherently important. So, I make that decision based on that. Now, when I look back on my original decision to try to figure out about these receptors, again, without going into the scientific details, it was within the context of what was known at the time.

And there was this question about, “Was there such a thing as a receptor? Was this a real idea?” I mean, the idea that there might be receptors in cells for specific hormones and drugs, like adrenaline, had been around for many decades, but there was no proof that they existed. And when I lecture about this, I spend a fair bit of time showing quotes from famous scientists, arguing against the fact that they were receptors. But intuitively it seemed to me, there had to be. That was my vision. There had to be these receptors. And it just seemed obvious on its face that assuming that there were these receptors, and since we still had no proof that they existed, and there were no techniques for studying them, if you could develop ways of studying these alleged receptors. And in fact, isolate them, find out what they were, how they were regulated. And again, the postulate was, these receptors were a gateway to the cell. This is how all manner of hormones and drugs actually got cells to do their thing. How could that not be important? Now, I didn’t really know much more beyond that. I figured, “Well, I’ll start with that.” And I was 30-years-old, well actually 28 when I went to the NIH. And that’s a place to start. I had no vision for where the field would go for the next 25 years. I was thinking maybe five years ahead. And then one thing led to another. And that’s another thing about choosing really great problems. They seem to be forever self-renewing.

In other words, as quickly as you answer one question, it’s that old trivial thing about, you have to climb one mountain to see the next mountain range, but it’s really true. It’s really true. And I often tell people that 50 years on from opening my lab at Duke, you could take any experiment going on in my lab today and connect it back to the experiment done a day or two ago, which led to this experiment. And back to the one before that and that, back through tens of thousands of experiments to July 1st, 1973, and there would never be a discontinuity. There was no break. Every experiment was based on an experiment that came before, but of course, it’s continuously expanding. Every time you make a discovery, it opens up many subfields. Many of them, you have to just sort of leave for others to do.

Steve Goldbach:

And Bob, because you’re a humble guy and Stuart, I’ll let you jump in with your question in a second. I feel like it’s really important for our listeners to realize that the high likelihood is if you’re listening to this and have ever taken medication, you’ve taken a prescription medication whose mechanism of action has been founded on Bob’s discovery. So 30 to 50% of all prescription drugs today, work on the principles of these receptors that Bob and his collaborators have discovered. Whether it’s ulcer drugs, antihistamines, beta blockers, cardiac, almost every category of medicine works on something like this. So to say you’re working on an important problem, and a problem that you’re interested in, is a very humble way of saying the degree of impact that you’ve had on literally billions of people around the world, Bob. So I just don’t want our listeners to think that we’re talking to a guy who’s thought about niche science. It’s really important discoveries. Because we didn’t get into the details of it so much.

Robert Lefkowitz:

Thank you so much for saying that, Steve, but another interesting principle there is, in the early years, as I said to you, I felt this was an important problem, but I never dreamed that it would have the breadth of implications and ramifications that it did. And in the early years of the work, it was never my intention to develop new drugs. It was just this faith that this is important. And if we figure this out, good things will follow. But then as the years went by, it was increasingly clear that this was the case. But thank you for saying that. To this day, I pinch myself when I look at what has come from all of that.

Stuart Crainer:

Yeah. Bob your career’s been called, A Tale of Two Callings. The kind of practice of medicine as a cardiologist and your research, but that was a dangerous thing to do at the start. You thought you were going to be thrown out of medical school when you were doing the research project on the side. And I wonder how important that has been, that you refuse to go down one particular route. You wanted to broaden that. And I wonder if that has helped keep you fresh.

Robert Lefkowitz:

Yeah, I think so. I mean, I really can’t imagine a more rewarding career than a career as what we call a physician scientist, that is both a physician and a scientist. I experienced each as a true calling. Although at very different times in my life, the research came as you heard, significantly later. But it really was a calling in the sense of this just almost mystical sense that you’re destined to do this. I mean, this is what you’re supposed to do and you don’t question it, but what has made it so gratifying is that what I get from the two things is so very different. The practice of medicine, which I no longer do. To my dying day, I will think of myself as a physician, but I haven’t practiced for about 15 years.

To my wife’s amazement, I can’t really say annoyance, I still carry an active medical license and an active narcotics license. And she says, “Why do you pay several hundred dollars a year for these licenses when you haven’t seen a patient for 15 years?” And kind of shrug and I say, “What can I tell you? I’m a doc. I should be licensed.” But the gratification of medicine is that I still feel the way I did right at the beginning in the sense that what could be more gratifying than to be able to relieve suffering on occasion, really heal somebody, cure somebody. And on an even rarer occasion, even save a human life. I mean, I just don’t know of a greater privilege a human being could have, than to be able to do those things. But I don’t know if irony is the right word, but when I think of the lives I would’ve touched, if I had become the full-time practicing physician that I dreamed of.

Maybe it would’ve been in the thousands, but as you mentioned before, the way it’s worked out, it’s in the tens of millions, if not more, hundreds of millions. So it’s on a much grander scale. None of that ever entered my mind in making the decisions. I mean, when I came to Duke, which was my first and as it turned out, my only job once I finished training at the Mass General. I would say the first year I probably spent about 40% of my time doing clinical work, clinical teaching, going to clinics and about 60% of my time setting up the lab. And maybe that mix was for a couple of years, but then increasingly, I started spending more and more time in the laboratory, 80, 85, 90%. And then that became the pattern for the next 35 years or so, which is that the overwhelming bulk of my time was in the laboratory and a small fraction was involved in clinical work.

Now, I maintain that none of that was based on conscious decisions. That is to say it just happened. In fact, I view a lot of my life that way. It just happened. I just started spending more and more time. It was like I was drawn irresistibly away from what had been the passion of my whole early life, just because I was so sucked in. On the way home in the car or in the shower, I found I wasn’t really thinking about the interesting patient that I saw in clinic that afternoon. I was thinking about why I couldn’t purify the damn protein and what other approach I would need to take on that. It was just happening. So, I mean, really kind of interesting. So the gratifications that I got from the two different aspects of my career, I think they appealed to also different aspects of my personality.

Steve Goldbach:

Bob, I’ve got one last question then and I think Stuart has one more too. And it’s at that intersection of the role of being both a clinician and a researcher. In fact, you tell a story about an interview that you were having with Jesse Roth at the NIH. And he said to you, that “It was bullshit that you could never be the triple threat that you wanted to be a great physician, a great researcher, and a great administrator.” Do you now reject Roth’s premise that you can be both and in fact, maybe being a great physician helps you be a better researcher and vice versa?

Robert Lefkowitz:

I don’t reject it. He was right. You can be a good physician and a great researcher or a great physician and a good researcher, but there are a rare few who can do it. But the level of focus and intensity that I brought to my research over many years, was really not consistent with being at the top of my game, in the other fields. And when I finally retired from clinical medicine, more than any other reason, it was because I knew that after 35, almost 40 years, that I was not right up to the minute anymore on the latest advances, because there just aren’t enough hours in the day. And what I was reading was the Journal of Biological Chemistry or the Journal of Molecular Biology, not the New England Journal of Medicine or the Annals of Internal Medicine. So, I think Roth was right in his typically overstated kind of a way. So, I would say I’ve sort of come around to his way of thinking.

Stuart Crainer:

I mean, Bob, you’ve received the greatest of plaudits in that you were an answer to a question on Jeopardy.

Robert Lefkowitz:

Yes, indeed. You want to hear that story?

Stuart Crainer:

Yes, please.

Robert Lefkowitz:

So, this was years before I had won the Nobel Prize and my wife and I were having dinner here in North Carolina. And I had an uncle Henry, who spoke with a thick Yiddish accent, which I won’t try to imitate. And he was about 90 at the time and was a devotee of a quiz show called Jeopardy, which I think is probably known around the world. We’re eating dinner, my wife and I, and he calls and he says, “Bobby, I’m so excited. You were just a question on Jeopardy.” I said, “Uncle Henry, what are you talking about?” He said, “You were the answer to a question.” He says, “I was so proud of you.” I said, “Well, what was the question?” He said, “Well, it was something like, how does the sperm sense the egg and the answer turned out to be smell. And this was discovered by Dr. Robert Lefkowitz at Duke. And when I saw your name, I was so excited. You know, Bobby,” he says, “when you go to Scotland, I’m going with you.” I said, “Scotland? Uncle Henry, why in the world would I go to Scotland?” He says, “You know, Scotland.” I said, “What are you talking about? Why would I go to Scotland?” He says, “You know, when you win that big prize? “Oh, I said, “You mean Stockholm?” He says, “Stockholm, Scotland. What’s the difference?” So that was uncle Henry, who was quite a guy, but telling that funny story and as you know, there are a lot of funny stories in my book. I want to put in one other point, we were talking before about creativity and let’s face it. I mean, some people are more creative than others.

But I think everybody has a certain inherent level of creativity, but there are certain things that you can do to, I think, enhance the creativity of individuals. And for me, one of the main things that you can do is encourage a sense of humor, because I find that humor is a big prod to creativity. And in fact, humor is an inherently creative process. One of you mentioned before, the idea of pattern recognition. Yeah, pattern recognition and seeing patterns, that’s the classic thing that scientists are supposed to do. See something that others haven’t seen in the data. I mean, that’s the essential of discovery. And when you think about it, that’s really the core of humor. I mean, humor is seeing relationships between things that might not seem related at all and making a bridge or a connection where others don’t really see that connection.

And in fact, in the moment that you make a joke or say something funny, and people say, “Oh, I saw the joke, or I got the joke.” In the moment that you get the joke, what you’re doing is making a little discovery. You’re saying, “Oh, now I see the double entendre. Now, I see the relationship that I didn’t see before.” And that is essentially the core of making discoveries. So I find at my lab meetings, I use a lot of humor, telling stories and this and that. And I find the more I get my people laughing, the more creative ideas that just seem to flow. And so, I think that cultivating a humorous perspective on everything is a good way to develop creativity, but there is one caveat – everybody has the ability, I’m convinced, to appreciate humor.

But not everybody has the inherent ability to be funny. And herein lies the conundrum, because it’s important to know if you’re funny or not funny. And there are only two people, I mean, it’s a bimodal distribution. People are either funny or they’re not funny. And if you’re not funny, the key is don’t try to be funny, because there’s nothing more cringe inducing than an unfunny person, trying to be funny. You know what I’m talking about. And you just want to crawl under the table, because they’re just a little bit off and it’s just not funny. And you really wish they hadn’t tried. So that’s the caveat. No sin in being an unfunny person, just don’t try to be funny.

Steve Goldbach:

Well, Bob, it has been an absolute pleasure to spend time with you today. And I’ll end with maybe just a few quick observations. So one is, fun fact, my wife, Michelle was a contestant on Jeopardy. And so, it’s always nice to make connections. So, I will test her to see whether she would’ve got that answer. And I will say that you are one of those apex people, and the apex I’m going to put you on is you are at the apex of empathy and brilliance. So there may be some people who are more brilliant than you, but they’re definitely not more empathetic than you.

And there may be some people who are more empathetic than you, but they’re probably not as brilliant as you. And so, it has been an absolute pleasure to spend time with such an interesting and humble person and to learn from you and learn with your stories. And so, I guess as our favorite 18 time, all star, 10 time world series champion, and 285 career batting average, he didn’t quite make it to 300 batting average. It ain’t over till it’s over. But I think at this point, we’re going to have to call it a day and we would love to have a part two with you sometime if you’re interested, but Stuart, I’ll let you have at it.

Robert Lefkowitz:

Very much, I enjoyed chatting with you guys.

Stuart Crainer:

Bob, thank you very much. A real pleasure talking to you.

Steve Goldbach:

Bob, thank you very much.

Robert Lefkowitz:

My pleasure. It was fun.