Bob Lefkovitz has reached the pinnacle of scientific achievement. But he defines himself not by his Nobel prize but by the failures that got him there and the people he’s been able to connect with and support along the way. This week, we get his insightful and hilarious Perspective from the Top.
A Funny Thing Happened on the Way to Stockholm (ft. Bob Lefkowitz)
Nobel Prize-winner Bob Lefkowitz on the power of failing
OPENING QUOTE:
“It was through serendipity and really almost accidental circumstances that I became a scientist.”
—Bob Lefkowitz
GUEST BIO:
Bob Lefkowitz is best known for his groundbreaking discoveries that reveal the inner workings of an important family of cell receptors inside our bodies which essentially makes 30% to 50% of prescription drugs work, for which he was awarded the Nobel Prize for chemistry. He's currently James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at Duke University, and an investigator with the Howard Hughes Medical Institute.
CORE TOPICS + DETAILS:
[15:09] - Embracing Failure on the Path to Success
Nobody fails like a scientist
What do all the great scientists have in common? They all have failed badly at times early in their careers. Failure after failure after failure, and then success. It’s simply part of the experience— and not just in the world of science. We would all do well to embrace the role of failure in a successful life.
[25:50] - The Power of Humor
It’s about more than just levity
Why does Bob include humor in everything he does? It helps encourage a spirit of creativity. Humor is about seeing relationships between things you might not ordinarily put together. That’s also a large part of what science is all about.
[31:24] - The Importance of Authenticity
Why Robert holds authenticity in such high esteem
There’s no right way to be a scientist, a mentor, or a person— except the way that’s most true to who you are. Authenticity is often in short supply, but Robert says that when we embrace our authentic selves, it empowers us to achieve far more than we ever thought possible.
[46:35] - Robert on Mentoring
Principles anyone can put to use
The key to mentoring is individualization. What that means is understanding that mentoring isn’t about molding little versions of yourself— it’s about helping people become the best versions of who they are. Mentoring too often becomes an exercise in ego, but it should be an exercise in empathy.
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CREDITS:
Bob Lefkowitz:
... because it was through serendipity and really almost accidental circumstances that I became a scientist.
Chris Roebuck:
Welcome To Perspectives from the Top. I'm Chris Roebuck, global keynote speaker with unique leadership experience from military, business, and government; bestselling author; and your guide to greater success. Together we'll discover powerful insights from the world's leading thinkers, doers, and trailblazers; the must-know trends, thought-provoking revelations, and practical actions you can use immediately. This is your exclusive and personal shop of insight and inspiration to help you get to the top.
Chris Roebuck:
Welcome to you and all of our Perspectives from the Top community of listeners around the world. It's great to share the insights of such successful people with you to help you get to where you want to be. My guest today is Bob Lefkowitz, best known for his groundbreaking discoveries that reveal the inner workings of an important family of cell receptors inside our bodies which essentially makes 30% to 50% of prescription drugs work, for which he was awarded the Nobel Prize for chemistry. He's currently James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at Duke University, and an investigator with the Howard Hughes Medical Institute.
Chris Roebuck:
In his early career, he worked as a physician, spending time in the Public health core with Dr. Anthony Fauci, followed by work as a cardiologist, and he then made his extraordinary transition into biochemistry, which would lead to his Nobel Prize. Bob shared the prize with Brian Kobilka, who he had previously mentored. When he received the Nobel Prize, the press corps in Sweden covered him intensively, describing him as "the happiest laureate". Bob has been conducting his research and his mentoring of research trainees for nearly 50 years.
Chris Roebuck:
Bob, thanks so much for joining us on Perspectives on the Top, taking some time out of your valuable time to give our listeners some insights into your career and what you've achieved. Your career focus was initially being a physician, and we've interviewed many people on Perspectives from the Top, and they do jobs they're passionate about; but from my experience, being a physician to some degree isn't actually a job, it's more of vocation, and a lot of people don't quite understand that vocational clinical world in relation to what they do in an office. And I was reading your book and you were talking about that it all revolves actually around standard operating procedures; if this happens, we then do that. But it must be stressful, so can you give us some insights into that world that is vocational and focused on making people better?
Bob Lefkowitz:
Well, I think vocation is a good word. A synonym for that in my mind, and it's the one that I always think about when I think about how I came to go into medicine, is the word a calling, to have a calling, experience a calling. We generally associate that term with clergy having a calling to the cloth or to the church, but you can really have a calling to almost any particular occupation. And for me, the concept of a calling means a... I don't like the word mystical, but it probably obtains a feeling that you are meant or destined to do a certain thing.
Bob Lefkowitz:
And I experienced that at a very, very young age, I would say seven or eight. And the impetus to that was my family physician, a guy named Dr. Joseph Feibusch, a general practice physician in the Bronx, New York City, who made house calls. And he would come to the house if somebody was ill, myself or my parents. He would lay on hands. He carried with him this black bag from which he could produce any number of magical objects; a reflex hammer, a stethoscope, an otoscope, prescription pad. And he knew all this stuff that other people didn't know. And I was just taken with that. And it seemed to me at an early age that there was no higher purpose that one could devote oneself than to be like Dr. Feibusch, because he knew all this stuff and he could use it to make people feel better.
Bob Lefkowitz:
And so without even realizing that I was experiencing a calling, by age seven or eight, I knew that I was going to grow up to be just like Dr. Feibusch. And I was totally focused on it. And unlike so many of the kids that I see today, as well as my own show of five children that I raised many years ago, who are trying to find themselves and figure out what you're going to do, there's really nothing more clarifying for a young person then to experience a calling, whether it's to medicine or the church or to law or whatever it is. I never had to worry about what I was going to do, everything fell into place.
Bob Lefkowitz:
And I must say, the early years of my career as a physician were some of the most gratifying that I've ever experienced. I loved what I was doing. And to this day, if you were to say to me, even having now spent most of my life more dedicated to research than the clinic, so I did both for 35 years; if you asked me what was the greatest privilege of your life, I would say it was to be a physician, and to for a number of years have the ability and the opportunity to use my knowledge to alleviate suffering, on occasion cure disease, and on some clear occasions to save a human life. And I just don't know that there is any higher experience you can have than that. So for me, that was and remains just an amazing experience.
Chris Roebuck:
I think you're so right, because as you say, you're saving lives, but also there are so many people out there who go to university, and even at the end of university, they've done a degree in something but they're still saying, "I'm not sure what to do." And there is a lack of clarity about what they want their life to be about. But there's a small group of people like you and other people where there is this focus on something that is a calling, and it's truly special, because it enables you to focus all your efforts passionately on what you want to achieve.
Chris Roebuck:
And that links in to your medical career as well, because as you were going through that, you were doing the clinical stuff, you were making people better, albeit as you told me in certain circumstances of exhaustion. But then you started getting this insight into perhaps there might be this little area called research where you weren't doing the standard operating procedures, but you were maybe trying a few new things, seeing if this worked; as I like to think about, a medical entrepreneur. Maybe give us some insight into the start of the medical part of your career, the clinical part, and how this research passion crept in from the side.
Bob Lefkowitz:
Well, it's an interesting story. I wrote an autobiographical essay four or five years ago, and I titled it A Serendipitous Scientist, because it was through serendipity and really almost accidental circumstances that I became a scientist. So here's the story. I was so focused on becoming a physician early on. I loved science, but the idea of actually producing original science was never part of the equation for me. I had no interest in doing research. And all the way through college and especially medical school, whenever I had elective periods where I could have done research, I never did it. In medical school, I always took clinical electives. And I would've happily, after medical school, finished my residency training and gone into practice, were it not for a cataclysmic event which was going on in the 1960s, and that was the Vietnam War.
Bob Lefkowitz:
So I graduated in 1966 from Columbia Medical School, and at that time there was a lottery draft for all men over 18. But for physicians, there was no lottery, there was just a draft, there was conscription. All physicians in training were given a deferment through medical school graduation, and then you were given a further deferment for one or two more years of postgraduate clinical training, and then you were drafted. You went into either the Army, the Navy, the Air Force, or the United States Public Health Service. And you could pretty much be guaranteed of spending one of your two conscripted years in Vietnam, which was not a popular choice. It was a very, very unpopular war.
Bob Lefkowitz:
Now, your best chance of avoiding going to Vietnam was to get a commission in the public health service, because they had a number of posts, if you will, here in the United States, especially in research institutions like the National Institutes of Health and the CDC, the Communicable Disease Center. But it was very competitive for obvious reasons to get those appointments and commissions. It was very merit based. And I was fortunate in that I had very high academic standing and strong recommendations. So I got the commission in the Public Health Service and was assigned to the National Institutes of Health, where I spent 20% of my time taking care of patients in the clinical center and 80% of my time assigned to a research laboratory where I first began doing research. Not because I was burning with desire to do research, but because I was essentially drafted and told to do research. And so that's what I did for two years.
Bob Lefkowitz:
And for the first year or even more, things did not go well. And I experienced something which I had never experienced before in my young life, and that was failure and protracted failure. Nothing worked, further convincing me that I had no interest in research. So I decided I would just finish my time there, which was a two year hitch, and then move on with my clinical training. Well, after about a year and a half or so, things did begin to work, and I got a taste of what success was like producing original new information. But I would say the passion still wasn't there. So I went off to finish my clinical training at the Massachusetts General Hospital in Boston. And for six months, next six months, I threw myself into the clinical work, loved it as I always had.
Bob Lefkowitz:
But now I began to have the feeling that something was missing, because as I've told you, in clinical medicine it's not that things are cut and dry, but there is a standard way of doing things. Of course there are variations and making the diagnosis can be challenging, but in general you follow certain procedures. But in research it's all free form. You're doing things that nobody ever did before. And somehow after six months of doing full-time clinical work, I began to really feel something was missing, and that what was missing was the challenge of day to day getting data, doing experiments, doing research. And so I found another mentor and I started sharing my time, splitting my time between doing research and finishing my clinical training. I did that for the next couple of years, and then I came to Duke in 1973, and by then I was really hooked on the research. And I guess they would say the rest is history.
Chris Roebuck:
Well, you certainly haven't looked back since then, have you?
Bob Lefkowitz:
No, I have not at all. Always looking forward.
Chris Roebuck:
Absolutely. Looking forward, moving forward, all the time. So when you are doing research, obviously not everything goes right, and I think you get these patches of things going wrong where it never rains but it pours and everything seems to go wrong. But how do you respond to that to at least try and keep your sanity and try to keep your motivation?
Bob Lefkowitz:
This is one of the most difficult things that one has to deal with in research, because basically most of what we do fails, the overwhelming majority does. And for young people, when they're first starting out, as I was back in the '60s, they're not used to that. In life, much of what you do, whatever it is, is working. But here, most of what you're doing doesn't work. And it takes a great deal of experience to come to grips with that. And one of the important things about mentoring, which is a subject near and dear to my heart, is teaching people first of all that that's the reality and that you have to expect that.
Bob Lefkowitz:
But the other part of that is that you have to look at failure, you have to sort somehow change the way you frame it so that the failure is really part of your ultimate success, because it's a matter of learning smart, as they say. Every experiment that fails teaches you. I'm reminded by this famous quote by Thomas Edison, the very famous inventor, who said that he comes up with 300 ideas a year for inventions and only one of them actually ever works. And they say, "Well, that must be awful frustrating." He says, "No, no, no, no. It means that there are 299 times a year I have figured out something which won't work. In other words, I've learned something that doesn't work, and so that gets me to the point that the one that does work." So you can kind of reframe things.
Bob Lefkowitz:
But I've been fortunate in my career to listen to talks, as you have probably more than I, from all manner of people who have been extremely successful, whether in science or legal profession or entertainment or the military, whatever. And if there is a single common thing that they have to say, they all talk about how badly they failed early in their careers, failure after failure after failure, and then success. And so I often tell that to my trainees, that the failure is just part of the experience. In fact, I give a talk to the research fellows at Duke University I'd say at least every year, sometimes more than that, different groups, called "How to Deal with Failure and Rejection in Research". In fact, the title is "How to Deal with Failure and Rejection". That's just the title. Then my opening line is always, "This is not about your sex life. This is about your career." Anyway, failure is ever present, but looked at in the correct way or in good way, it's just something you have to accept.
Chris Roebuck:
Well, what I think is really interesting about your research world is that to some degree, all the other professions that you quoted, the military, legal and all the rest of it, the failure level is nowhere near the figures that you are talking about. I think for our listeners, it's really instructive that if you are in a legal job or something, you might get something like 80% success, 85% success and 15% failure. If people in the legal profession were getting a 2% success rate, they'd either be out of a job or they'd be throwing themselves off window ledges in their offices.
Chris Roebuck:
The reason I asked you the question is that it's so instructive because I knew that your success rate was so much lower. The point for our listeners is that if you in the scientific research world can get through that level of failure, then all of us sitting out here in the normal world where we are freaking out because we've had one failure out of 20, then we just need to put it in perspective and listen to what you guys in the research world are saying that if you have the right mindset, it's not as bad. The failure is a learning experience to ensure more success in the future.
Bob Lefkowitz:
Very well put. Let me tell you a little illustrative story, which is in my book by the way, A Funny Thing Happened on the Way to Stockholm, a memoir that I've written, which tells a lot of my stories. But I have a ritual that I go through every year during the week between Christmas Day and New Year, which is very quiet here at the university. I come into my office and I review the previous year's work in my laboratory. The starting point for that is a sheaf of handwritten notes, maybe three or four pages long, which I prepared exactly a year before. I've been doing this for my whole career.
Bob Lefkowitz:
On that list are all the projects I envisioned that we would work on over the subsequent year, ideas, et cetera. Then I put letters next to them, A, B, C, with the letters refer to how exciting I think the project would be. I try to work on only the most exciting A projects. Now, a year later when I come back to these, I go through and I see what's working, what didn't work, what turned out to be totally stupid, what turned out to be so stupid that we realized we're not even going to work, et cetera.
Bob Lefkowitz:
I was working on that exercise when a young colleague of mine, not a mentee, but a more junior professor came by and said, "Hey, what are you doing?" I explained it to him. He said, "Well, how are things going?" I said, "Well, I'm having a pretty good year." I said, "How about you?" He said, "Oh, yeah. Everything's going great." I said, "Well, what fraction of your projects that you're working on your lab would you say are working?" He said, "I don't know. 80%, 90%, something like that."
Bob Lefkowitz:
I said, "That's great." He said, "How about you?" I said, "Well, I'd say about 15% or 20%." He said, "What? The great Bob Lefkowitz has only a 20% success rate in terms of projects that are working." I said, "Yeah." He says, "Well, how do you feel about that?" I said, "Great." He said, "Really?" He said, "Why?" I said, "Well, every once in a while my success rate drifts up in maybe 40%. One year," I said, "50% of the things we were trying to do were working and I got very unhappy about that." He said, "Why would you be unhappy?" I said, "Look," I said, "If half of what I'm trying to do is working, I'm not challenging myself very much. I must just be picking off low-hanging fruit and starting to work on projects which weren't all that important." I said, "If I'm really challenging myself and working on important things, there is no way that the majority of what I'm working on could work." Well, he was chastened and we ended the conversation.
Bob Lefkowitz:
Over the years, he has told me repeatedly what a profound effect that conversation had on him and how it has reshaped the way he approached his own research program, which I can attest. I have seen myself. I'll tell you the truth, this conversation was 15 or 20 years ago. He has become a much better scientist and is making much more substantive and significant contributions in his area than he did before. He always comes back to that conversation that he realized that if he was going to really challenge himself, he had to accept that the success rate is going to be a lot lower.
Chris Roebuck:
Bob, that's a really, really powerful comment, but I think that's not just true about the world you're in with research. That comment about challenge, and unless you are challenging yourself and you are challenging the people around you, and sometimes things go wrong, then you are not pushing things. You're just doing what you've always done.
Bob Lefkowitz:
I think that to some extent that's what moved the bulk of my effort from clinical medicine to research because I just felt that after you treat your 100th case of hypertension or your 200th case of heart failure or whatever it is, it becomes too routine. I didn't want routine. I often tell people no two days for me are the same. Every day when I come in, I don't know what's coming at me in the way of data and what problems will be with our experiments. That's what I like. I think that's one of the reasons that I have avoided various other types of careers is that I really do like to be challenged and to see new things every day. In science, you do. You just never know what curve balls are coming.
Chris Roebuck:
That's such a good point for listeners, I think, to think about that do you want a completely predictable every day being the same or do you want some element of challenge? But from the strategic organizational perspective, the fundamental point has to be that unless the organization is challenging itself, unless things are sometimes going wrong, it cannot possibly be changing and developing and improving because if it's not experiencing the occasional failure, it can't be challenging itself, which means it's not going anywhere.
Bob Lefkowitz:
Absolutely. I couldn't agree more. Of course, my experience is in science, not in business or large organizations. I've never run anything larger than my laboratory. That's by choice. I never wanted to be a department chair or a dean. I had many opportunities in my career. The largest my laboratory ever got was pretty big, was about 30 people, but that's very big for a lab. Now it's about half that.
Bob Lefkowitz:
But yeah, I love the challenge. I love the surprises. There's nothing that makes me happier than, and I have this experience all the time, than one of my trainees coming in with a long face saying, "Hey, Bob. The experiment didn't turn out the way we thought." My initial reaction to that is, "Great, tell me what happened," because if it turns out the way I expected, then I probably didn't learn much. I mean, because I knew enough to already predict how the experiment would turn out. But if it turns out different than I predicted, then I'm going to learn something by definition. But, the trainees it takes a while until they understand that.
Chris Roebuck:
You have to teach them to insulate themselves from failure.
Bob Lefkowitz:
Absolutely.
Chris Roebuck:
But the beauty of it is that you are leading a lab and the beauty of it is that how you do that to pick people up off the ground is with humor. Give our listeners some insight into how when you are leading those trainees and collaborating with them in the lab, how you do that and how you use humor just to keep everybody optimistic and going in the right direction.
Bob Lefkowitz:
I think humor is a very, very important part of what we do. I think in science it's particularly important. At my lab meetings, which I hold weekly, I use a liberal amount of humor. I find if I can get people laughing, which I often do, it seems to encourage or foster or nurture a spirit of creativity because, I mean, let's think for a minute about what is the process of saying something funny? What is humor? I mean, basically it involves seeing relationships between things that you might not ordinarily put together. It often involves juxtaposing things which seem totally not in the same frame.
Bob Lefkowitz:
In the moment that somebody appreciates what you're doing, if you're telling a funny story or a joke, in the moment that they see the joke, they're making a little discovery. That's what seeing the joke is. You're making a little discovery about what was just said. In the first instant, you don't get it. There's a pause. Then you get it and there's laughter. That's a little discovery. You're seeing putting things together that you might not ordinarily see. Of course, that's exactly what making discoveries in the laboratory is. It's a matter of looking at things, data, where somebody might not see anything but somebody else does see something, they're putting things together.
Bob Lefkowitz:
That's why I think the process of humor ... I'll give you an example, which one of my kids reminded me about just the other day. At each of my five children's weddings, I always made remarks, I mean, it was a toast, et cetera. I always would tell a few stories. When my youngest got married about 12 or 13 years ago, I came up to the microphone. He's the fifth now of my five children getting married. This joke is probably not meant to be offensive in any way, but the first thing I said was something along the lines of, "Well, you know, Josh, when your mother told me that she was pregnant for the fifth time, I wasn't immediately all that excited about it." I said, "Because I had just read a couple of days before that every fifth child born in the world is Chinese."
Bob Lefkowitz:
Now, what happened was the following. After a brief period of quiet, there was a burst of laughter. Then a few microseconds later, another burst and then another burst. You had different groups of people who got the joke at different points in time. I'll never forget it. It went on for four or five seconds. Some people got it like that. Others, it took another second until they put together these two completely crazy things that have nothing to do with each other.
Bob Lefkowitz:
Often, to me, that's what making the scientific discovery is all about. You're looking at two sets of data or whatever and they seem to be tied, and then all of a sudden, you see that these two seemingly unrelated things really have a common basis and that there's something in common, even though they seem totally unrelated to each other. That's why I think the process of humor is very important.
Bob Lefkowitz:
Now, I always tell people there's a caveat. I believe that everybody is born with the inherent ability to appreciate humor, but not everybody is able to be funny. There's a bimodal distribution. People are either funny or they're not funny. The important thing is self-awareness. If you are not funny, then it's important not to try to be funny because there's nothing more cringe-inducing, and you know what I'm talking about, then an unfunny person trying to be funny. It really makes your skin crawl and you want to go under the desk. That's the caveat. If you're not funny, that's fine, just don't try to be funny.
Chris Roebuck:
But the point is that it goes back to the emotional stuff, and it goes back to the fundamental principle that you need to be you and don't try and be somebody who you are not. Because whenever people try to do that in any way, if I try to be a scientist or you are a leader and you try and do something which isn't naturally you, other human beings have a very, very good antenna that detects that you are not being genuine. When I'm talking to leaders about, don't just think that people are listening to your words. Their mind is reading thousands and thousands of body language signals second by second. A human mind can work out if there is a contradiction between the words and the body language extremely quickly.
Bob Lefkowitz:
I could not agree with you more, Chris. I mean if you were to ask me, because I ask myself this increasingly as I get older, what are my core values? What values do I most appreciate in people and in myself? Way up on that list would be authenticity. I like people to be authentic. I try to be as authentic as I can in virtually every circumstance that I'm in. People often ask me for advice about mentoring and this and that, which I do have a lot of experience with. I have a lot of ideas about mentoring, but probably the most important one is that there's no one exact right way to be a mentor because each of us is a different human being. And you have to mentor, there are certain principles that everybody can use, but you need to mentor in your way. And your personality may be very different than mine, and you mentor differently.
Bob Lefkowitz:
I shared the Nobel Prize with one of my former trainees, Brian Kobilka, who's a professor at Stanford. And like myself, he has a reputation, and I think very well deserved in his case, of being an outstanding mentor. You couldn't have two more different personalities than Brian and myself. I am extroverted. I enjoy conversation, etc. Brian is painfully shy, which he's overcome to some extent and just has a totally different personality. And yet we're both very good at mentoring. But I can guarantee you, we can't mentor in the same way because we're so different as people. So I think the key to mentoring is, first of all, you got to be you. You got to be yourself and do it your way.
Chris Roebuck:
And so indeed, you mentioned Brian, so we're in the interview, and maybe it's time for you to tell our listeners a little bit about what your work has been focusing on to some degree for 30, 40 years.
Bob Lefkowitz:
50 and counting.
Chris Roebuck:
50 by now. Just a simple explanation about what you've been working on and how receptors work in our bodies and what your discoveries have done.
Bob Lefkowitz:
So basically, when I started my work, which is, golly, almost 55 years ago, there was an idea which was very controversial, that there might be specific binding sites on cells that hormones and drugs could bind to and thereby initiate their actions. And they were referred to as receptors, but frankly, it was a controversial idea, and there was really no proof that they existed. But the idea seemed very compelling to me. So I set out to try to prove that-
Chris Roebuck:
Sorry, sorry. So basically, for our listeners, so obviously within all the cells in our body, if we want a drug to work, somehow the cell has to get a message of what it's supposed to do for the drug. Because unless that message is passed to the cell, the drug is useless.
Bob Lefkowitz:
Exactly right. So to give an example, let's take adrenaline. Now, adrenaline also known as epinephrine, our body makes that, but we also use it as a drug. And it does many wonderful things to be sure. But so, for example, one of the things adrenaline does is it makes your airways dilate. So if somebody's having an asthma attack, and they're wheezing because their airway is constricted, you give them adrenaline, and it dilates.
Bob Lefkowitz:
Well, how does the adrenaline know to work on your airway and not on your eyeball or on a thyroid gland? And so the idea would be that, well, maybe there are special sites on the airway cells that adrenaline can fit into. And that's the concept of a receptor. So you can see it as the receptor being a lock and the drug or hormone, like adrenaline, being a key. Okay? And there has to be a complementary, an exact complementary in shape of some site on that receptor, the lock, in order for the key to fit in. And if it does, then it can turn and do something.
Bob Lefkowitz:
Alternatively, a drug might fit into that site and not do anything, but it would still block the ability of the adrenaline to work. So for example, picture that you put a key in and then broke it off. Okay, nothing's happened. But now the guy with the real key comes. He can't get in there because there's something jammed in there. That's what we call a blocker. So when you hear about beta blockers, for example, these are drugs which block adrenaline receptors.
Bob Lefkowitz:
Anyway, so what my work has been and was to develop a whole raft of new techniques and technologies to, first of all, prove that there was such things, to then isolate them, purify them, figure out what they were, how they were regulated, and then realize, by essentially what we call cloning the genes for the receptors, to figure out what their molecular structure was. And from that, to figure out that there was really a huge family of these receptors, which included the receptors for adrenaline, which is what I was initially working on, but including a thousand different kind of receptors for all kinds of hormones and drugs and figure out how they are regulated.
Bob Lefkowitz:
Bottom line, now, many years later, people in the drug industry have used this information to develop drugs, and in fact drugs which target receptors in this family, which includes not just receptors for adrenaline, but receptors for dopamine, serotonin, parathyroidoma, all manner of things. And also in this family of receptors, and when I say family, I mean they all have very similar structure, receptors, it's how we smell. Smell receptors are in this family. Taste receptors, vision receptors, something called rhodopsin. That's how we perceive light.
Bob Lefkowitz:
And the bottom line is 30% to 50% of all the drugs that are sold today, therapeutic drugs, are drugs would target members of this family. So even though I was always working at a very basic or fundamental level, the work has had a tremendous impact on clinical medicine and therapeutics.
Chris Roebuck:
You quote the fact that perhaps 30% to 50% of prescription drugs that our listeners are taking have been enabled by the work you've done then.
Bob Lefkowitz:
I think, in a sense, that's really true, although it boggles my own mind. I mean, so many common drugs, I mean, for example, ones that people would immediately come to mind would be things like beta blockers or adrenaline or antihistamines, I mean, just to name a few. In the United States there are 700 FDA-approved drugs which target these receptors. And that's, as I said, about a third to a half of all drugs.
Chris Roebuck:
As a result of all of that work over all of those years, bob, on the 10th of October, 2012, early in the morning, you got a telephone call from somebody. And tell us what that telephone call was, and tell us what happened when you had your week away as a result of that telephone call.
Bob Lefkowitz:
Okay, so what Chris is referring to is a call from Stockholm telling me that I had won the Nobel Prize in chemistry and that I was sharing it with my former trainee Brian Kobilka. The backdrop to this is that as my career had progressed, people began to talk about the fact that I might be a potential Nobel laureate. I would say that started about the time I was maybe 50 or in my early 50s.
Bob Lefkowitz:
Now the Nobel Prizes, as you may or may not know, are announced the first week in October, so we're coming up on it. And they're announced in as set order, one prize each day. Monday is Medicine or Physiology. Tuesday is Physics. Wednesday is Chemistry, etc., etc.
Bob Lefkowitz:
So I started thinking about it, and during that week, first week of October, I kind of wonder when I went to bed Sunday night, was I going to get a call? Never happened. Almost 20 years passed, and people were always saying, Bob, when are you going to get the prize? It's got to happen this year. And always expectation, it didn't happen.
Bob Lefkowitz:
So I finally kind of had given up on it. So here it was in 2012, not on Monday, which is Medicine or Physiology price, but on Wednesday, Chemistry. And at 5:00 AM, I feel my wife poking me in the ribs and waking me. And the reason she was waking me is because I sleep with ear plugs, and so I don't hear the phone, but she does, fortunately. And she said, there's somebody calling for you with a Swedish accent? That was interesting. So I pick up the phone, and they didn't keep me waiting. Very quickly, a female voice with a thick Swedish accent said, Professor Lefkowitz? I said, yes. She says, I'm going to put Dr. so and so on. He's the chairman of the Nobel Prize Committee in Chemistry. So I realized what was up. And he told me that I had won the Nobel Prize. I asked him, was I sharing it with anybody? And he told me, Brian. And of course, that was even more fulfilling and exciting.
Bob Lefkowitz:
People say, how did it feel? Did you jump up and down? And the answer is no. It was more a quiet sense of satisfaction and almost like the monkey is off my back. People have said to me over the years, what was the best thing about winning the Nobel Prize? And I say, kind of tongue in cheek, but there's an element of truth in it, well, the best thing was knowing that, for a fact, I would never again in my life have to answer the question, Bob, when are you going to win the Nobel Prize? And that was a good feeling.
Bob Lefkowitz:
And the experience of going to Stockholm to receive the prize is just beyond. It's over the top. And as I say in my memoir, The Funny Thing Happened on the Way to Stockholm. I have a whole chapter dealing with this experience. But it's not just one day, but it's really more like about a 10 day journey. It starts, interestingly, by visiting with the president of the United States, who for the last 60 years has had a tradition of meeting with all the American Nobel laureates as they are on their way over to Stockholm to get the prize in December. In this case, it was President Obama, and there were five of us that year. We got to meet with him in the Oval Office, which was amazing.
Bob Lefkowitz:
I would point out that the only president, you won't be surprised to hear, who never met with any Nobel laureate during the four years he was president was President Trump. For some reason, he opted not to do that. Once you're over there, they treat you like royalty from the moment you step off the plane. You have an attache that they assign to you, like a minder who gets you everywhere. You have a BMW 7 Series limousine devoted just to you and your spouse and family with an assigned chauffeur. It's all absolutely amazing. There are banquets with the King and the Queen. It just goes on and on.
Bob Lefkowitz:
And then the Nobel Prize ceremony, of course, is remarkable. And yeah, it's just incredible. And it was like I was taking adrenaline the whole week, and it was wonderful. It was like being in a fairy tale because it was a very cold winter over there. So it snowed every day. It was really like being in a fairy tale. It really was.
Chris Roebuck:
It's interesting. One of the things that I sort of read in your book was a comment that actually one of the things that is important to scientists, to some degree, is not specifically the prize itself, but the fact that the prize is validation for your work and the fact that it's made a difference.
Bob Lefkowitz:
I think that's very, very true. Nobel, in his will, when he established the prizes more than well over a hundred years ago, said that the prize in each field should go to that set of discoveries, I forget his exact wording, but which have brought the greatest benefit to mankind. And actually, the way he said it was those discoveries, which over the preceding year have made the greatest benefit to mankind.
Bob Lefkowitz:
Now, by and large, the prize almost never goes to somebody whose work was just over the last year. Typically, my case turns out to be very, very typical in the sense that the most salient discoveries I made were probably made 20 to 25 years before I got the prize. And in fact, that's typical. There have been studies of this. And I think the reason for the long delay is the committees. It takes time to see what the impact of discovery is.
Bob Lefkowitz:
Now, sometimes that's not the case. Something which hasn't won the Nobel Prize, for example, was the underlying discoveries which made Covid vaccines possible. I would've given the prize for that last year. And I still think they will get the prize. They should get the prize. But that's the rare exception where the discoveries have had that immediate an impact. Typically, it is 20 or 25 years.
Chris Roebuck:
So you talked earlier about the importance of mentoring, and linked to that within the mentoring relationship, the whole concept of storytelling. Many, many of our guests have mentioned that either they are mentors or that, and they've mentioned that a mentor had a significant impact on the way they have been successful. So just sort of give our listeners an insight into couple of your thoughts on mentoring.
Bob Lefkowitz:
Yes, this is a subject I would gladly spend the full hour talking about. And again, in my book, A Funny Thing Happened on the Way to Stockholm, I have a whole chapter on mentoring. And I think there are some principles that everybody can use, but for me, one of the most important things about mentoring is that you have to individualize what you do. There's no one size fits all. Some people are absolutely brilliant. Others are less so. Some are very independent. Some are more dependent. Each of them has to be dealt with in a different way. And for any given mentee, at different stages in their training, they have to be handled differently. So when you're first starting with them on day one, you handle them differently than you do three years in when they've got a lot of experience, but to me, one of the most important things, and the biggest challenge is empowering trainees so that as they go forth into their own... Again, I'm talking from the perspective and now of course of professional scientists, but what I want them to do is I want them when they leave to have the appropriate expertise that they need and knowledge, but I want them to have the confidence to be able to take on important problems and solve them. Now, the challenge for the mentor in my business is this, and there are two diametrically opposite ways to fail here. One is you can micromanage the trainee throughout their time in your lab, basically treat them almost like a technician, meet with them very frequently telling them what to do.
Bob Lefkowitz:
The problem with doing that is when you finally meet with success, the trainee does not have sufficient intellectual ownership of what you've discovered because in their back of their mind, or even the front of their mind is, "Well, if Bob wasn't directing me like that, who knows if I could have done it?" On the other extreme, if you stand back too far, they get nothing from you, and even if they do pretty well, you've missed an opportunity to share with them all the things you've learned in your career. The key is to walk that line, manage them enough so that they have a higher chance of succeeding and learning from you, but not so much that you rob them of the intellectual ownership that is necessary to go forward with confidence to do your own thing later on. That to me is the single biggest challenge.
Chris Roebuck:
And that I think is absolutely true for mentoring in any environment, in that there will be no learning if the mentor is over directive. And also to some degree within the commercial world, there is that interesting balance because often in the commercial world, the mentor is not the boss or leader of the individual. They have their own boss, but the mentor is someone separate who is giving, to some degree, not on-the-job advice, but longer term personal development advice on how they can deal with the here and now, but also turn that into the future.
Bob Lefkowitz:
Mm-hmm. Yeah, I see what you're saying. It's a very different situation.
Chris Roebuck:
But the same applies in both of the situations because I think your comments about mentoring and how you do mentoring absolutely apply to the fundamentals of leadership if you are leading somebody in a team, because somebody who joins your team at this point in time, you can lead in a certain way, you can delegate to in a certain way, but in three years time when they're significantly more experienced, you have to change the equation because if you start micromanaging them once they've been doing the job for three years, they're not going to be too happy.
Bob Lefkowitz:
Absolutely correct. Couldn't agree more.
Chris Roebuck:
It's your beautiful point about above all, it's not about you who is the mentor, it is about the person that you are mentoring and matching their needs as much as you can. But so many mentors get it wrong. So many mentors think that this is my opportunity to download all of my experience on this poor unsuspecting person and that it will make them a better person.
Bob Lefkowitz:
I can tell you as well that I know some scientists, outstanding scientists, Nobel Laureates, who are terrible mentors for just this reason. They're completely overbearing. I know one guy, I won't mention his name, he's deceased, brilliant scientist, Nobel Prize winner, not a single one of his trainees ever went on to a career of great acclaim. Not one, which is unusual. Typically, people who win Nobel Prizes, if you look at their scientific lineages and the people who trained with them, it's usually many superstars, but I know of Nobel Prize-winning scientists who have essentially produced few, or in this case virtually nobody who went on to a distinguished career. And the reason is, and I know it because I knew this person very well, is he was so overbearing and basically micromanaged everybody, so they got a lot of great science done, because he was brilliant, but nobody was able to develop sufficiently to go on and carry that tradition on their own.
Chris Roebuck:
Effectively there was no empowerment, but one of the things I definitely want to mention too, to listeners, is your book, A Funny Thing Happened on the Way to Stockholm, listeners, you have to read the book. It has got some really great insights into leadership, into life, it's funny, there's some great stories because Bob is an amazing storyteller. What next for you?
Bob Lefkowitz:
Well, that's a good question. I'm approaching my 80th birthday in a few months and I'm still fully at it. Today is actually a bit of a big day for me. I have literally an hour ago finished three months of work writing what's called the competitive renewal of my NIH grant, which I've had for 51 years, which funds part of the effort in my laboratory. I went at it with the same drive and focus as I have, and I have to do this every four or five years, and it's competitive, it'll be reviewed by a study section, etc., and I just finished that, the very final readthrough.
Chris Roebuck:
Congratulations.
Bob Lefkowitz:
Thank you. And it feels good, and so I'm taking a deep breath and I'm saying to myself, "Well, what now?" Now back to the writing papers, because for the last few months people have been clamoring at Bob, we've got to get this manuscript submitted to a journal. And I say, "Well, I'm totally focused on the grant." Now I've finished that, moving on, I will have to face the reality as I move into my 80s that I guess I won't be doing this forever, so I'll have to be thinking about the next stage, but... And these grants are for four or five years, so maybe I'll revisit that in four or five years.
Chris Roebuck:
That's absolutely amazing, although I do know sometimes you do take the opportunity to slip away to the beach.
Bob Lefkowitz:
Absolutely. I've just come back from a wonderful beach trip with my wife and mother-in-law and sister-in-law earlier in the summer. I have five children, as I mentioned, all married with [inaudible 00:55:33] I have six grandchildren, and very devoted to all of them. Every summer we have a family tradition, there are 20 of us in all, we go to a beach and we all stay in one house, typically 10 or 11 bedrooms, and we just enjoy each other's company. That was just a month ago, so yeah, family's very, very important to me.
Chris Roebuck:
And it should be to everybody. Finally, how can people learn more about what you do? I suppose it's just read the book.
Bob Lefkowitz:
I think so. Filet people. Obviously I don't expect them to go to the scientific journals and read the Journal of Molecular Biology or the Journal of Biological Chemistry, but in my book, A Funny Thing Happened on the Way to Stockholm, which you were kind enough to mention, woven throughout that is the story of my research, and in fact, to make it easy on people, a lot of the science is put in a separate section so that you can dip into it as much as you want, but it's written at a lay level. It's not written for scientists, so I think if they want to learn more about receptors, which is a fascinating topic, I think the best way in is the book.
Chris Roebuck:
I absolutely agree. Having dived into various medical scientific papers over my life, I think we'll stick to your book because more than five lines of a medical scientific paper, most of us will be completely lost. Bob, thank you so much for your time. It's been great fun, it's been insightful. There's some amazing both insights, and actually picking up on what you said, ideas for action that our listeners can use, so all I can say is just thank you. It's been absolutely amazing. Congratulations on your achievement with the prize, and to be blunt, from all of us who take prescription drugs, thank you for your work.
Bob Lefkowitz:
Well, thank you very much, Chris. I've enjoyed with you.
Chris Roebuck:
Well listeners, there certainly is a lot to reflect on there, and a lot that you can do something about tomorrow. Amazing story. I think one of the most interesting points was about the level of failure within scientific research. Bob quoting that even in his best years, he probably only had 30% success, which meant that essentially 70% of things he tried failed. Now, there are a couple of really powerful points there to pick up on. Firstly, that being in an environment where you have that level of failure means you have to have the right mindset to keep going with determination to achieve your vision, and that that vision is motivating you to do so. But on a wider point, for all of us, if you want to move forwards, if you want to grow and develop yourself, your team, your organization, you have to try new things, and that inevitably involves both risk and potential failure.
Chris Roebuck:
But as Bob expressed, failure isn't necessarily as bad as you might think, because naturally it then enables you to more accurately focus in on potential successful options for action, and if you don't try new things, you'll just do what you've always done and the world will move on anyway, leaving you behind. Certainly the fact that Bob has been doing this research for nearly 50 years and his work has benefited all of us listeners in our daily lives, plus the fact he's also developed scientists who have then gone on to make further discoveries which have benefited us all, is just simply amazing. Maybe identify one idea for action you've heard from Bob and go and start to make it happen between now and our next episode. Don't forget that in a week I'll be giving a more in-depth view of my key takeaways from Bob, my insights and ideas for action in reflections on the top.
Chris Roebuck:
If you've used any of the insights you've got from previous Perspectives from the Top guests and they've helped you, I'd be delighted to hear your success stories. And don't forget to sign up on the website so you don't miss any of the great future guests coming out. Thanks for tuning in. Check out the show notes from today's episodes at perspectivesfromthetop.com, where you cannot only enjoy additional resources from today's show, but all previous ones. If you haven't already, subscribe to the show on Spotify, Apple, or wherever you get your favorite podcasts so you don't miss any, and if you really enjoyed the show, please give us a five star rating and review. Have a question or comment? Let's discuss it. Message me on LinkedIn. Perspectives from the Top is produced in collaboration with Detroit Podcast Studios, so have a successful week, use today's new learnings and actions, and remember, it's onwards and upwards. See you next time on Perspectives from the Top.