MALCOLM RITTER and KARL RITTER
NEW YORK —
Two Americans won the Nobel Prize in chemistry Wednesday for studies of how the cells in our bodies pick up signals as diverse as hormones, smells, flavors and light — work that is key to developing better medicines.
Those signals are received by specialized proteins on cell surfaces. Dr. Robert Lefkowitz and Dr. Brian Kobilka made groundbreaking discoveries about the inner workings of those proteins, mainly in the 1980s, the Royal Swedish Academy of Sciences said.
The proteins are called G-protein-coupled receptors. Many of today’s drugs — maybe about half — act on these receptors, including beta blockers and antihistamines. Experts say the prize-winning work and subsequent research is helping scientists as they try to improve current drugs and develop new ones.
The receptors pick up signals outside a cell and relay a message to the interior.
“They work as a gateway to the cell,” Lefkowitz told a news conference in Stockholm by phone. “As a result, they are crucial ... to regulate almost every known physiological process with humans.”
Lefkowitz, 69, is an investigator at the Howard Hughes Medical Institute and professor at Duke University Medical Center in Durham, N.C.
Kobilka, 57, worked for Lefkowitz at Duke before transferring to Stanford University School of Medicine in California, where he is now a professor.
Lefkowitz said he was fast asleep when the Nobel committee called, but he didn’t hear the phone because he was wearing ear plugs. So his wife picked up.
“She said, ‘There’s a call here for you from Stockholm,”’ Lefkowitz told The Associated Press. “I knew they ain’t calling to find out what the weather is like in Durham today.”
He said he didn’t have any “inkling” that he was being considered for the Nobel Prize.
“Initially, I expected I’d have this huge burst of excitement. But I didn’t. I was comfortably numb,” Lefkowitz said.
Kobilka 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 AP. “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.”
He said he would put his half of the 8 million kronor ($1.2 million) award toward retirement or “pass it on to my kids.”
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 cells had some type of receptor for hormones and other substances, but they couldn’t find any.
Lefkowitz managed to reveal receptors, such as one for adrenaline, and started to understand how that one works.
Kobilka, working with Lefkowitz, found the gene that tells the body how to make the adrenaline receptor, and it soon became clear that there was a whole family of receptors that look alike — a family that is now called G-protein-coupled receptors.
Since then, scientists have built up detailed knowledge about how those receptors work and how they are regulated. The two prize winners “have been at the forefront of this entire scientific journey,” the Nobel committee said.
Kobilka moved on to Stanford after the gene discovery, and just last year he and his team there captured an image of a receptor at the moment it transferred the signal from a hormone to the interior of the cell. The academy called that “a molecular masterpiece.”
Awarding the Nobel to Lefkowitz and Kobilka is “a fantastic decision,” said Roger Sunahara, who studies how hormones activate the receptors at the University of Michigan. With detailed knowledge about the receptors, scientists can better understand how drugs work, which in turn helps them improve current medications and look for new ones, he said.
Drugs such as beta blockers, antihistamines and various psychiatric medicines have been around for some time, but before Lefkowitz and Kobilka’s discoveries, their interaction with 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.
Mark Downs, chief executive of Britain’s Society of Biology, said the critical role receptors play is now taken for granted.
“This groundbreaking work spanning genetics and biochemistry has laid the basis for much of our understanding of modern pharmacology as well as how cells in different parts of living organisms can react differently to external stimulation, such as light and smell, or the internal systems which control our bodies such as hormones,” Downs said in a statement.
The U.S. has dominated the Nobel chemistry prize in recent years, with American scientists being included among the winners of 17 of the past 20 awards.
This year’s Nobel announcements started Monday with the medicine prize going to John Gurdon of Britain and Japan’s Shinya Yamanaka for their work on reprogramming cells. Frenchman Serge Haroche and American David Wineland won the physics prize Tuesday for work on quantum particles.
The Nobel Prizes were established in the will of 19th-century Swedish industrialist Alfred Nobel, the inventor of dynamite. The awards are always handed out on Dec. 10, the anniversary of Nobel’s death in 1896.