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FEATURES: Rational Exuberance
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YOUR LAB STILL PRODUCES A SLEW OF RESEARCH PAPERS. HOW DO YOU MAINTAIN ENTHUSIASM FOR THE WORK AFTER SO MANY YEARS?
A lot of being successful is leveraging your gifts to the maximum extent possible and protecting yourself from inevitable failures. Gifts cannot be explained or fundamentally changed—though you can tinker around the edges.
For example, throughout my life I was a long-distance jogger. I’m totally devoid of athletic talent, but with hard training I could get to seven minutes a mile. I have a friend, Alton Steiner, who was once a champion swimmer and runner, a real athlete. Then he had some back problems, and he didn’t run a speck for two years. One day he called me up, and I mentioned that I was running a 15K race the next day. He decided to join me. It was a miserable, humid day. The first mile we do at about a seven-and-a-half-minute pace. In the second mile I slow down a bit, and by the third mile I’m down to 8:30. He looks fine. Eventually he looks over sheepishly and says, “Do you mind if I go up ahead?”
Duke’s Robert Lefkowitz shares in chemistry Nobel Prize Reactions to Lefkowitz’s Nobel Prize.
I finished the race, but it was not pretty. And he’s there sipping a lemonade, having finished at an average pace better than my fastest pace. You can tinker around the edges. But at my best, I can’t eat his dust. That’s what a gift is. After all these years, I haven’t a clue how I still have this exuberance for science. I guess it’s a gift.
WHAT’S THE NEXT FRONTIER FOR YOUR LAB?
Lately we’ve been focused on beta arrestins, a class of molecules we discovered about 20 years ago that we still don’t fully understand. They interact with receptors when they’re stimulated, thereby turning off signaling, hence the name. But in the last few years we’ve discovered that beta arrestins can act as signaling molecules in their own right. That suggested the possibility of developing a new class of therapeutic that stimulates the biological pathways with desirable results and arrests the pathways with less desirable results.
Still, my job is to look at the big picture. Every experiment’s results suggest five different things you could do next. They’re all interesting. That’s the problem. But we want to go from here to there, and my job is to keep us on the trail.
I often tell people there are four keys to success in science. The first is focus, the second is focus, the third is focus, and you can figure out the fourth. If anybody learned that lesson from me it was Brian Kobilka. After he left my lab, he became obsessed with getting a crystal structure of the receptor. It took him about 15 years. In 2007, he solved the structure of the beta-adrenergic receptor [the G-protein-coupled receptor that responds to adrenaline] and later the structure of the receptor interacting with its G protein. That’s a remarkable accomplishment.
One of the things I learned by running races is you don’t look up. You don’t look ahead. You look down. You put one foot in front of the other, and you just look at the road in front of you. You don’t worry about what’s out there. Before you know it, you get to the end.