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Featured Scientist: An Interview with Dr. Robert Lefkowitz

Left to Right: BSS Faculty Sponsor Dr. Jonathan Bennett, Tejas Sundaresan, Dr. Robert Lefkowitz, Emmanuel Assa, Halston Lim. Photo Credit: Brian Faircloth Dr. Robert Lefkowitz is the James B. Duke Professor of Medicine at Duke University. Having studied medicine at Columbia University, he completed his medical residency at Massachusetts General Hospital, after which he shifted his focus into medical research. For the past forty years, he has studied cell signaling mechanisms and receptors, and is most known for his pioneering studies of the molecular pathways and structure of the G-protein coupled receptor. A Howard Hughes Medical Investigator, he received the 2012 Nobel Prize in Chemistry for his work. he BSS staf met with Dr. Lefkowitz for his insight and advice for the aspiring high school scientist after his delivery of the keynote address for the 2013 North Carolina Student Academy of Science meeting hosted on the NCSSM campus. Can you think back to when you were in high school? Back then, what were your favorite activities and academic interests? Let’s see what I looked like back then [Dr. Lefkowitz shows us his yearbook photo from 55 years ago]. his should be 1959. Orchestra, Dynamo. Dynamo was the literary publication. So I was an editor for not a scientiic magazine, but a literary magazine. Swim squad. Biology Club. We had several [sports] teams. Interestingly, a couple of our teams were regularly among the best in the city. Of course, we had a math team, a chess team, etc… Did I have any extracurriculars other than those back then? Not really. Subjects, I loved chemistry really. I took AP Chemistry and that was my major actually… It’s really important to discover what your gifts are. Everyone has gifts, and it’s great to igure out what you’re really good at, because that’s what you want to emphasize. hings that come easy to you. It’s worth thinking about.

You had mentioned earlier in your talk that medical research didn’t really cross your mind until the end of your two years at the NIH, where you had initial “successes” in research. What advice do you have for individuals who are researching but who haven’t obtained similar “successes” yet in their ields? Let’s say I went of to residency, having met with nothing but unrelenting failure for two years. here’s no way – I can’t imagine- I would have gone on into a career in research. But let me tell you something that’s really important; it’s going back to those failure things. his guy Kobilka, by the way [referring to Dr. Brian Kobilka, co-recipient of the 2012 Nobel Prize in Chemistry who was previously a post-doctoral researcher under Dr. Lefkowitz]…If you would have said to me, out of the 250 or so you’ve trained, who were the best: hands down, I would have said Kobilka and this other guy. Now, Kobilka met with no success in my laboratory for two and a half years. If he had left after two years, he’d be practicing cardiology. And this is scary. What I have observed is that someone who is good at [research] will ultimately succeed. If I take a look over the people I’ve trained and made a graph, success versus how long it took them to get 72 | 2012-2013 | Volume 2


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Street Broad Scientific

something going, I would say, it’s a reverse correlation. he better people are, the longer it takes. Now it’s not in every case and I’m not saying p is less than .05, but in my mind, there is some correlation. Why might that be so? I have found that the best people are drawn to the most diicult and challenging problems. And the more challenging the problem, the longer it takes to make any headway at all. And two years of failure, in the big picture is nothing.

Many research scientists possess PhDs, while you have a medical doctorate. How has this medical background shaped your research? You’d be amazed how many people who win basic science prizes never got a PhD. … One thing, getting an MD teaches you discipline – that’s for sure. It selects for disciplined people, people who are clinically trained, like Kobilka and myself. In my day, surviving an internship in residency wasn’t a mean feat. You couldn’t even sleep. It really solidiied work ethic, etc… If you are a really good physician, [you are] learning how to interrogate a sick patient. It’s almost like being a prosecuting attorney learning how to cross-examine. Science is the cross examination of a problem: every experiment is a question. You got to ask exactly the right question. And that’s exactly what science is. You have to do the exactly the right experiment. And that’s what’s failure’s about. You ask the wrong question a hundred times. But each time, you learn that’s not the way to go. And then your question gets sharper and sharper. And inally, you ask exactly the right question, and bingo, you got it.

Can you tell us a little about the role of biology in business, based on your experiences. Do you have any advice for students who are interested working in the biotechnology industry? It’s interesting. Name of my company is Trevena…. We started this company ive years ago, and the company, the irst three scientists, the nucleus that formed the company, were three of my senior post-docs, who had been very much involved during the previous ive years in developing the body of science that formed the platform of the company- the idea you could signal down these diferent pathways. My irst piece of advice: become a scientist irst. Really get the background irst. You want to be able to yourself to decide “is this a good opportunity?”. I would say become a scientist, and maybe do a post-doc, and then do business.

Is there any important advice for an aspiring scientist in academia? Figure out what you like. here are three types of ways you can earn a living. One: you have a job, like my secretary, you work 9-5 and you take home a salary as a job. Two: you have a career. It’s not necessarily 9-5 and you do what you need to do to advance in the career. You have a skill you hone and you move up in a hierarchy. And then, the third category is a really small percentage: that’s folks like me. You have a passion. I’ve never felt I work for a living. Why am I doing this? It’s the same reason I was doing this thirty years ago. It’s my sandbox. I play. In a sense I’m always working, but it’s not. So if you can igure it out, is there something you’re just going to love? And, don’t take advice from anybody, you have to igure it out for yourself. In the end, you have to go with your heart. It’ll become obvious to you if you’re attentive. You spend your whole life doing what you do, and its much better if you enjoy doing it.

Twenty years from now, what areas in biology will be really important? here are a couple. Cancer. We got a long way to go there. Cancer is hundreds of diseases. We’re just beginning, in the last decade or so, to really make some headway in understanding some of the basic mechanisms that go awry, mutations that lead to cancer, and how to develop drugs. hat’s got to be a huge area. And neurobiology, how the brain works. We really don’t have, in my way of thinking, good drugs to treat severe mental illness. he drugs that we have are crude instruments. If you hear the side efects, sudden death, bleeding from the nose, vomiting, and cardiac arrest. It’s [drugs] a really blunt instrument. So I think neurobiology and understanding basic neuromechanisms at a molecular level and the tools are in place to do this. So those are my two areas in the next twenty years where fundamental biomedical research can impact upon disease. hese two ields are really ripe for progress.

Volume 2 | 2012-2013 | 73


An Interview with Dr. Robert Lefkowitz