Mentor and Data Junkie

The mid-1970s found Bob Lefkowitz playing mentor to postdoc (and future HHMI investigator) Marc Caron.

Just about everywhere you look in receptor biology—indeed, biomedical research—you find someone who trained with Bob Lefkowitz. They total some 160 so far.

Walter Koch, a former Lefkowitz postdoc and now close collaborator at Duke University Medical Center, once picked up Lefkowitz at the airport in Ohio when Koch was a still a graduate student at the University of Cincinnati. "I had read all his papers," Koch recalls. "He'd been publishing so long, I was expecting somebody 65, and here he was only 45. I was amazed."

Lefkowitz's most enduring contribution to biology may, in fact, be his dedication to mentoring and his unflagging devotion to his students. When asked how he thinks he will be remembered, he replies that he hopes he'll be remembered as someone who made a contribution to science and as "somebody who trained a helluva lot of people."

Talk to his former students and a consensus emerges that Lefkowitz has a gift for helping students succeed. Virtually all of the alumni of his laboratory, including four current or former HHMI investigators, have gone on to establish independent research careers.

"He has succeeded as a mentor because he has made a decision to resist the things that distract too many scientists," says Henrik Dohlman, a Yale pharmacologist and former graduate student in Lefkowitz's lab from 1982 to 1988. "He rarely travels, never chaired a department, doesn't own a biotech company, doesn't edit a journal. His important and noble focus has been on the education of his students. I always tell my students a mentor should do three things: inspire, instruct and inform. He does all these very well."

But there's one thing you'd better have if you want his attention: Data. "Bob is sort of a data junkie," says Rick Cerione, professor of molecular medicine at Cornell University and former Lefkowitz postdoc.

Koch concurs, "He'll talk to you about anything—rock music, movies, whatever—but if you really want his attention, you'd better have some data. He really, truly gets genuinely excited when you have a good result, and the beauty of it is he gets excited every time you show it to him. I've shown him a result in the lab and then presented it at a lab meeting, and he gets excited all over again.... It's contagious. He really motivates you."

Lefkowitz himself has divined the secret for success in science. "I always tell my trainees there are four secrets to success in science: the first is focus; the second is focus; the third is: You get the idea."

He tells the story of a microscope he bought in medical school. It had been passed down through several generations of students and was showing its age. Lefkowitz would be studying his histology slides and he'd look away to his notes. When he looked back, the microscope would be slightly out of focus.

"I learned after a while just the right amount of pressure to put on that fine-tuning knob to hold it in focus, look away, and—when I looked back—it was still in focus. That's what I have to do with the fellows—exert just this little pressure. I find I go out of town for a week, I don't talk to a fellow, I come back, they're losing their focus! Every experiment suggests an infinite number of possibilities. The magic is to see the path through, to see where there is a clear space. That's what I do."

Lefkowitz makes sure his students not only stay focused but also focus on big questions."Bob has a way of taking complicated situations and reducing them to the simplest forms," says Dohlman. "His attention is always focused on one question ahead of the game. He taught me how to think big. But the most important thing is that he helps people so eventually they won't need him. He has a way of asking questions instead of dictating answers, so that any success I've enjoyed is my own."

Says Lefkowitz, "There is no way to develop a person's independent creativity unless they have some room, both to make mistakes and to develop their own ideas. Nothing gives more confidence than having an idea and showing it's true. In order to let that happen, you have to let go some."

But make no mistake, says Lee Limbird, Lefkowitz's first postdoc and now associate vice chancellor for research at Vanderbilt University Medical Center, he's the kind of guy who you go to with data. What you learn from him very quickly is that data are the currency of research. If you go to a scientific meeting and don't have data, you may as well not be there, she adds.

"The biggest thing Bob taught me was that sometimes your data look like garbage, but if the same result comes up a couple of times the data are telling you something and you'd better listen," says Sheila Collins, a former Lefkowitz trainee and now associate professor of psychology and pharmacology at Duke.

Lefkowitz has had a large lab almost since the beginning. Today he has 30 people working in it, including students, postdoctoral fellows and technical and administrative staff. With that many people, he has to be judicious with his time. Without data, it can take a while before you see him. "If I couldn't get an audience with him because I was data-less, I would sometimes call him from next room to get his advice," Limbird recalls, laughing.

Of course, everyone has an Achilles' heel, and former graduate student Rusty Williams, now at Chiron Corp., says Lefkowitz's is lab work: The guy was not meant for the lab bench.

"Bob took great pride in doing things himself, but he wasn't very good in the lab," Williams says. One day Williams was working in the lab trying to isolate a substance he'd been working on for a week. He had a homogenate of tissue and had spun down the solid, trying to get supernatant, the liquid portion of the sample. "At this point Bob strode into the lab and said 'Here, let me show you how to decant the sup [supernatant],'" says Williams. He then proceeded to dump the liquid right down the drain. "My jaw just dropped," says Williams. "After that I learned to stay clear if he came into the lab."