Duke professor asks the big questions, gets big answers

STAFF WRITEROctober 10, 2012 

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Dr. Robert Lefkowitz of Duke University.

CHRIS HILDRETH — Duke Photography

  • ROBERT JOSEPH LEFKOWITZ BORN: April 15, 1943, in the Bronx, New York City FAMILY: Wife, Lynn Lefkowitz; five grown children, David, Larry, Cheryl, Mara and Joshua; and three grandchildren. JOB: Howard Hughes Medical Institute investigator. James B. Duke Professor of Medicine and Professor of Biochemistry, Duke University Medical Center. HEROES: As a teenager, Woody Allen, Mickey Mantle and Ian Fleming (author of James Bond novels). More recently, Michael Brown and Joseph Goldstein, Nobel laureates who discovered the way the body regulates cholesterol. SUMMER READING 2003: Harry Potter, volumes one through five. MOST NAGGING SCIENTIFIC QUESTION: Three-dimensional structure of the subset of seven- membrane spanning receptors he discovered. They are too small to be seen. GOALS FOR NEXT DECADE: "To stay at the top of my game for as long as possible ... turning out good science and turning young people on to the satisfaction of a career in biomedical research."

Editor's note: This story was first published Aug. 24, 2003

DURHAM -- Inside a medical center office wallpapered with scientific awards, Duke University biologist Robert Lefkowitz launches his weekly lab meeting with an announcement.

"We'll begin casting soon for the spring show, so pick your parts," Lefkowitz jokes as 16 weary-looking American, Korean, Chinese, Indian and French scientists carry in page after page of experiment results. "I've taken the role of Dumbledore."

That would be Albus Dumbledore, wizard-extraordinaire from the Harry Potter books, a make-believe world of magic where Lefkowitz finds major inspiration these days.

Such is life in one of the world's top research laboratories. Everyone works hard on important puzzles; but work must feel like play sometimes, too.

Lefkowitz, 60, has long been considered one of the Triangle's likely Nobel Prize candidates. In the 1980s he discovered a giant class of tiny cell structures that enable many medicines to work. That launched a new field of research that he continues to lead. In recognition of that, this summer he was awarded the $560,000 Grand Prix de Science, to be presented in Paris at the Institut de France this fall.

But the cardiologist-turned-scientist isn't celebrated only for early breakthroughs. From 1992 to 2002, biologists and biochemists quoted new findings from Lefkowitz's lab in their scientific papers more frequently than any other published research.

"A lot of people can make discoveries that are important. But sometimes discoveries take on such a huge scale that they become one of the very top discoveries in the biomedical field," says Pascal Goldschmidt, chairman of medicine at Duke, who first heard of Lefkowitz while studying medicine 20 years ago in Belgium.

A high-energy, wiry guy raised in the Bronx, Lefkowitz didn't always envision this life. His plan from childhood was to become a doctor. He started that path, whipping through undergraduate training at Columbia University in three years and attending medical school there, graduating first in his class.

Lefkowitz fancied academic medicine . That, and a desire to stay out of Vietnam, propelled him in 1968 to spend two years in the Public Health Service in a National Institutes of Health lab in Maryland. From the beginning, big questions grabbed him.

"If you select something trivial, your results will be trivial," Lefkowitz says. "I thought if I could get under the hood and figure out how the engine worked, I could understand some important things."

Lefkowitz went hunting inside cells for structures theorists assumed must be there to receive orders from important hormones, such as adrenaline. When a person gets scared or stressed, adrenaline floods the body to make the heart beat quicker and blood flow faster. No one had found what carried its messages into individual cells.

Using blunt microbiology tools available then, Lefkowitz searched for more than a decade. Eventually, he detected molecules called "seven-membrane spanning receptors." Threaded over and under the surface of cells, the receptors act like doormen in hot city nightclubs: Nothing gets in unless they like the fit.

Finding the chemical gatekeepers was only part of the breakthrough . Lefkowitz quickly saw that similar biological hardware plays comparable roles all over the body, enabling hearts to beat, eyes and noses to function and all sorts of medicines to work. That launched a new research field and gave pharmaceutical companies countless new targets for drugs.

"That is really a colossal achievement," says Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Disease, who has collaborated with Lefkowitz.

Duke recruited Lefkowitz in 1973, when he was just 30. In Durham he has done some doctoring, but mostly he works with younger scientists in a sizable lab next to Duke Hospital. Funding from the Howard Hughes Medical Institute, which gives top laboratories about $1 million a year, lets him pursue whatever interests him most.

Talented apprentice scientists from all over the world compete to work with the guy who sits in a chair marked "TurboBob" and preaches that science is play. Every day, Lefkowitz prowls their research stations clamoring for data to advance his cause. Former students, many accomplished scientists, remember his ability to motivate.

"When you were in Bob's lab, you felt a big hand on your back," says Sheila Collins, now a pharmacology researcher at Duke. "You heard him saying: 'Go for it. Where's the answer? What are you waiting for?' "

Lefkowitz has influence outside his lab. His best friend is Ralph Snyderman, who has run Duke Medical Center for more than a decade. The scientist sits on editorial boards of scientific journals and is active in the National Academy of Sciences and other prestigious societies. With a former student, he helped found the local biotech company Norak Biosciences Inc.

But Lefkowitz credits his ability to stay at the forefront of his field, in part, to what he does not do. He limits travel as much as he can. He won't be chairman of a department or top editor at a journal. He keeps studying the ways receptors and related cell parts function and can be manipulated to treat disease.

Before a roomful of young cardiology residents at Duke Hospital one day recently, he talks about how to find excellent mentors. He advises that they find people talented at staying on task.

"There are four keys to success in science," he says, as his audience munches on turkey sandwiches and chips. "One is focus, two is focus, three is focus and four is focus."

The young doctors laugh. Lefkowitz fields their questions. He takes 15 minutes to help a younger faculty member improve a scientific paper. Then he hurries back to his domain.

"What's going on?" he calls out as he reaches his lab. "What did I miss?"

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