Four decades of scientific pursuit led Dr. Robert Lefkowitz down the East Coast to a Nobel Prize in chemistry.
Lefkowitz, James B. Duke professor of medicine and professor of biochemistry and immunology, is the first standing faculty member to receive a Nobel Prize. The Royal Swedish Academy of Science awarded the Nobel Prize in chemistry early Wednesday morning to Lefkowitz and his colleague, Dr. Brian Kobilka—a former postdoctoral fellow at Duke who worked under Lefkowitz—for “studies of G protein-coupled receptors.”
Their research on these receptors has led to major advancements in the development of prescription drugs for a variety of issues, ranging from allergies to coronary disease.
Prior to his research, few scientists believed in the existence of G protein-coupled receptors, Lefkowitz said. But despite the scientific community’s skepticism, Lefkowitz decided to pursue his research, allowing him to isolate these receptors, clone their genes and learn about their structures.
“In a very real sense, this is our accomplishment,” Lefkowitz said, referring to the Duke community. “I came here in 1973 and Duke was not the powerhouse in ’73 that it is today, but throughout every stage, I couldn’t imagine leaving.”
G protein-coupled receptors are embedded in the cell membrane. They catch external chemical signals that provide information to the cell about changes in the body.
About 30 to 50 percent of pharmaceutical drugs on the market attach onto these receptors like a “lock and key,” Lefkowitz said. In doing so, the drugs are able to manipulate the cells in a way that treats the patient’s condition. The hope is that this research will allow for the development of increasingly effective drug therapies.
A long journey
As a student at the Bronx High School of Science, Lefkowitz grew up with science as a prominent aspect of his life. He noted that his high school alma mater had seven Nobel laureates prior to him, all of whom received the award in the field of physics.
He commended the academic rigor of his high school for producing alumni with such significant roles in the field of science. To get into Bronx Science, prospective students must take a general knowledge exam and get one of the highest scores in the city.
Lefkowitz later went on to serve as a clinical and research associate at the National Institutes of Health from 1968 to 1970, where he began looking into the possible existence of G protein-coupled receptors.
“I was the schlepper in the room—I was the only guy who didn’t win a Nobel Prize,” he said. “It was a nascent field, nothing was known, but I got some kudos for what I had done and it kind of whetted my appetite. I got interested in pursuing receptors more.”
Lefkowitz became a fellow at Massachusetts General Hospital in 1970, where he considered staying until Andrew Wallace, who was the chief of Duke’s division of cardiology at the time, offered him a position at Duke in 1973. Lefkowitz, however, was initially reluctant to take the job.
“I talked it over with my wife and put together a list of demands that were far beyond reasonable for someone at my stage of the career, figuring that that would be the end of it,” he said. “I didn’t hear back for a month and then they called back and said they’d give me everything.”
From that point on, Lefkowitz remained at Duke, continuing his research as a Howard Hughes Medical Institute investigator.
A researcher and a mentor
Members of the Duke community lauded Lefkowitz for his contributions as both a scientist and a mentor. Dr. Nancy Andrews, dean of the School of Medicine and vice chancellor for academic affairs, noted that his role as both a researcher and a professor is what makes Lefkowitz a great scientist.
“There are three ways that medical scientists can be great—by making discoveries that immediately transform patient care, by making scientific contributions that stand the test of time and by mentoring the next generation of scientists,” she said. “Bob has accomplished all three and he has done it over and over again.”
Kobilka, now a professor at the Stanford University School of Medicine, said that even though he came into Lefkowitz’s lab with less experience than other people, Lefkowitz always encouraged him in scientific pursuits.
“I never felt like I was a second-class citizen,” he said. “I made my share of mistakes early on, but he always gave me freedom to do what I want and supported me in my research.”
Helen Yao, a senior staff scientist in Lefkowitz’s lab who previously worked with Kobilka for eight years at Stanford, also commended Lefkowitz for being a strong mentor, noting that he leaves his office door half-open at all times in case anybody needs advice on a specific project.
Lefkowitz’s constant enthusiasm inside and outside the classroom also makes him an excellent mentor, said Makoto Hara, a postdoctoral fellow who has spent six years working with the Nobel laureate. When Lefkowitz is walking around the lab, everyone notices his presence because of his strong voice, Hara added.
“A lot of our experiments end in failure because we don’t get any data, but he tries to cheer you up and find something good in the mess,” Hara said. “He’s really enthusiastic about everything.”
Sophomore Frank Cai, who worked in the lab next to Lefkowitz’s this summer, said Lefkowitz’s unyielding enthusiasm for science sets him apart from other researchers. Lefkowitz does not stop talking about science, even when he is on the way to the bathroom.
“One thing that distinguishes him from other people is he never takes a break from science—it’s always on his mind, it’s literally all he thinks about and he’s dedicated to his work,” Cai said.
Andrews predicted that Lefkowitz’s scientific influence will last for decades and should leave a mark on the Duke community.
“We have had, for some time now, a Coach K, and from now on we should recognize Bob’s tremendous contribution by calling him Coach L,” she said.
Life as a Nobel laureate
Those close to Lefkowitz said they expected him to receive a Nobel Prize and were simply waiting for the day to come.
Dr. Sanders Williams, former dean of the medical school and senior vice chancellor for academic affairs, made the prediction to President Richard Brodhead that Lefkowitz would be the first Duke faculty member to receive a Nobel Prize, Brodhead said.
Andrews said she—along with most of Lefkowitz’s colleagues—expected him to win the Nobel Prize for his work.
Lefkowitz, however, does not want this achievement to define him. Although many scientists will use their status as Nobel laureate to promote themselves for the rest of their careers, Lefkowitz said, he would be content if people did not know he was a Nobel Prize recipient a couple years down the road.
“You make these decisions for yourself—how much of the hoopla you want to do,” he said. “If people know I won the prize, great. If not, I’m not going to tell anyone. I can’t imagine it would change me.”
Lauren Carroll and Andrew Luo contributed reporting.