Two U.S. scientists won the Nobel Prize in Chemistry for discovering receptors, proteins that receive and transmit messages to cells, and are the basis for as much as half of all today’s medicines.
Robert J. Lefkowitz, 69, of Duke University Medical Center in Durham, North Carolina, and Brian K. Kobilka, 57, of Stanford University School of Medicine in Palo Alto, California, will share the 8 million-krona ($1.2 million) award, the Royal Swedish Academy of Sciences said at a news conference today in Stockholm.
They received the prize for their work on “cells and sensibility,” the academy said. The men showed receptors are used to relay information about adrenaline, histamine and other molecules to cells, and showed the inner workings of the largest family of such switches known as G-protein-coupled receptors.
Lodged in the fatty envelope that surrounds cells, they are the body’s mechanism to read its environment. Uncovering them paved the way for more effective treatments against afflictions ranging from allergies and heart disease to mental disorders, and helped reveal why the impact of some drugs wanes over time.
“This speaks of how far we have come in chemistry that we can see the intricate details of mechanisms in our bodies,” said Bassam Shakhashiri, the president of the American Chemical Society and professor of chemistry at the University of Wisconsin, in a telephone interview. “It’s just fantastic.”
Lefkowitz, a professor of medicine at Duke and an investigator at the Howard Hughes Medical Institute, said he “didn’t have a clue” he would be in the running for the prize, the first for Duke.
“I did not go to sleep last night waiting for this call,” he said by telephone at the news conference. “I’m feeling very, very excited. I was fast asleep and the phone rang and I didn’t hear it. I wear earplugs when I sleep and my wife gave me an elbow.”
Lefkowitz, an only child who grew up in the Bronx, New York, isolated eight out of nine subtypes of the most common G-protein-coupled receptors, which regulate the body’s fight-or-flight response. He also discovered two families of proteins that desensitize the receptors, helping scientists understand how drugs such as beta blockers work.
In his early research, he used radioactive material to track the receptors, a bit of sleight of hand that allowed him to find the whole family of receptors. His lab then revealed the receptors’ genetic blueprint.
Portrait of Receptors
Kobilka, who was introduced to the receptors while doing post-doctoral research in Lefkowitz’s lab, worked for more than 20 years to create a portrait of a key cell receptor in action.
“What the structure reveals is important details about how they transmit information from outside the cell to inside the cell,” Kobilka said on a conference call. “Structure tells how the drugs will bind. Knowing that, it may be possible to make drugs bind more selectively,” potentially making them more potent with fewer side effects, he said.
Kobilka said he was shocked by the news of his Nobel Prize, the 27th for Stanford, and initially “wasn’t exactly sure if it was real.” The researcher, who doesn’t have a secretary and generally answers his own phone, was swamped by phone calls of congratulations that quickly overwhelmed his voice mail.
The initial discovery allowed scientists to screen thousands of compounds in test tubes to see if they interacted with receptors, changing the fundamental approach to drug discovery. Kobilka’s three-dimensional imaging work has the potential to take the technique to another level, Lefkowitz said. Once the atomic structures are known, a computer may be able to determine how well drugs fit into the receptor, leading to virtual libraries that could screen millions of compounds.
Drugs that target the molecular transmitters include the Zantac antacid, Novartis AG’s Toprol-XL blood-pressure drug and Bristol-Myers Squibb Co.’s Abilify for schizophrenia.
“Knowing how they work helps us to make better drugs with fewer side effects,” Sven Lidin, a member of the Nobel committee for chemistry, said at the news conference.
Kobilka graduated from Yale University School of Medicine in New Haven, Connecticut. Lefkowitz holds a bachelor’s degree from Columbia College and a master’s degree from Columbia University’s College of Physicians and Surgeons in New York.
Annual prizes for achievements in physics, chemistry, medicine, peace and literature were established in the will of Alfred Nobel, the Swedish inventor of dynamite, who died in 1896. The Nobel Foundation was established in 1900 and the prizes were first handed out the following year. The Swedish science academy chooses the chemistry and physics winners.