DURHAM - The Nobel Prize for chemistry was awarded today to Duke University professor Robert J. Lefkowitz and a Stanford University scientist he trained in the 1980s, for their trail-blazing discoveries about how the body’s cells respond to outside signals – a key to the workings of beta blockers, antihistamines and many other medicines.
Lefkowitz, 69, and Brian K. Kobilka, 57, were recognized by the Royal Swedish Academy of Sciences for their work on a class of receptors, laced through a cell’s outer membrane, that give the cell information about chemical changes in the body.
“They work as a gateway to the cell,” Lefkowitz said, speaking by phone from his Durham home to reporters in Stockholm. “As a result, they are crucial ... to regulate almost every known physiological process with humans.”
He and Kobilka will share the $1.2 million prize to be awarded in December.
Trained as a cardiologist at Columbia and Harvard, Lefkowitz came to Duke in 1973 and has spent his entire 39-year research career there. He is an investigator with the Howard Hughes Medical Institute and a professor of biochemistry, immunology and medicine in Duke’s medical school.
“Bob’s seminal discoveries ... ultimately became the basis for a great many medications that are in use today across many disease areas,” said Victor J. Dzau, CEO of the Duke University Health System. “He is an outstanding example of a physician-scientist whose impact can be seen in the lives of countless patients who have benefited from his scientific discoveries.”
Lefkowitz oversees a lab with as many as 30 scientists at a time, and he is renowned for mentoring more than 200 scientists since he came to Duke in the early 1970s.
“One of his trademarks is that he has contagious enthusiasm,” said Marc Caron, a Duke professor who was one of Lefkowitz’s first two post-doctoral fellows and now runs his own research lab. “He can get just about anybody excited about what they do. That’s a very good trademark for people in science.”
Lefkowitz appeared at a press conference with Duke University President Richard Brodhead this afternoon. Before it began, he told Brodhead that it’s not surprising that he was being recognized for work he did more than 20 years ago.
“Some things become obvious very, very quickly,” Lefkowitz said. “Others, it takes hundreds of years, and we’re all gone by the time it’s clear.”
In the 1980s, Lefkowitz discovered a class of tiny cell structures called G protein-coupled receptors and showed that they respond to chemical changes outside the cell in the same way that other receptors in the body detect smells, taste and light. About half of all medicines act on these receptors. As scientists learn how they work, they are leading to improvements in drugs.
“This looks very attractive for the future development of drugs,” Caron said. “We might eventually be able to separate the side effects from the beneficial effects of a drug, by either activating or blocking these receptors. The potential of this field is still incredibly exciting.”
This morning, Lefkowitz was fast asleep when the Nobel committee called. He sleeps with ear plugs, and he didn’t hear the phone. His wife answered.
“Right at 5 a.m. I get an elbow, and she says it’s Stockholm calling,” Lefkowitz said at the Durham press conference. “Obviously they’re not calling to find out the weather here in Durham. This must be something important.”
Kobilka, a professor at Stanford University in California, said he found out around 2:30 a.m., after the Nobel committee called his home twice. He said he didn’t get to the phone the first time, but that when he picked up the second time, he spoke to five members of the committee.
“They passed the phone around and congratulated me,” Kobilka told the Associated Press. “I guess they do that so you actually believe them. When one person calls you, it can be a joke, but when five people with convincing Swedish accents call you, then it isn’t a joke.”
The academy said it was long a mystery how cells interact with their environment and adapt to new situations, such as when they react to adrenaline by increasing blood pressure and making the heart beat faster.
Scientists suspected that cell surfaces had some type of receptor for hormones.
Using radioactivity, Lefkowitz managed to unveil receptors, including the receptor for adrenaline, and started to understand how they work.
Kobilka and his team realized that there is a whole family of receptors that look alike – a family now called G-protein-coupled receptors.
In 2011, Kobilka achieved another breakthrough when his team captured an image of the receptor for adrenaline at the moment when it is activated by a hormone and sends a signal into the cell. The academy called the image “a molecular masterpiece.”
The award is “fantastic recognition for helping us further understand the intricate details of biochemical systems in our bodies,” said Bassam Z. Shakhashiri, president of the American Chemical Society.
“They both have made great contributions to our understanding of health and disease,” Shakhashiri said. “This is going to help us a great deal to develop new pharmaceuticals, new medicines for combating disease.”
Drugs such as beta blockers, antihistamines and various psychiatric medicines have been around for some time, but before Lefkowitz and Kobilka’s discoveries, their impact on the human body wasn’t fully understood, said Sven Lidin, chairman of the prize committee.
“All we knew was that they worked, but we didn’t know why,” Lidin said. There is hope that the Nobel-winning research will lead to new medicines, he added. The Associated Press contributed to this report.