Dr. Lefkowitz won the Nobel Prize for Chemistry last year for his studies of G-protein-coupled receptors, which are crucial to cellular communication. He was an apt choice as the speaker for the inaugural Wylie Vale Memorial Lecture

in Physiology, because his discoveries, like Wylie's, show how basic research can lead to breakthroughs in drug development. 

Wylie, who passed away last year, worked in a similar area of research as Lefkowitz. He discovered a group of neuropeptides and their receptors that mediate the body's responses to stress and stress-related disorders. His work led to new methods for the diagnosis of pituitary disease and opened new possibilities for the development of drugs aimed at treating anxiety, depression and even drug abuse.

On June18, Nobel Laureate Robert J. Lefkowitz delivered the Inaugural Wylie Vale Memorial Lecture in Physiology, an annual lecture devoted to the memory of late Salk professor Wylie Vale. "When they called me to give this talk, I was getting three to four invitations a day," Lefkowitz said afterwards. "Even if you say no to 90 percent of them, you're still left with an impossible schedule, but I couldn't say no. Like everyone else in science, I was shocked by Wylie's passing."

Lefkowitz, a Howard Hughes Medical Investigator at the Duke University Medical Center, and Brian K. Kobilka of the Stanford University School of Medicine, jointly won the Nobel Prize for their work on G-protein-coupled receptors, also known as seven-transmembrane domain receptors. "There isn't an aspect of human physiology that isn't controlled by these seven membrane receptors," said Inder Verma, in his introduction. "Well over 50 percent of the drugs we use today have something to do with these receptors."

Cells preserve their structural integrity through a double-layered wall of fat molecules, but hormones and other chemical signals need to pass instructions into cells. There are two major ways: ion channels, which act as cellular gates, and receptors, which act more like locks and keys. Many drugs, such as beta blockers, act by jamming the locks----breaking the signaling relay. Because of Lefkowitz and Kobilka, the role of receptors in that mechanism is now precisely understood.

Going from abstract concepts to uncovering cellular mechanisms is at the very heart of basic biomedical research. Once you know a mechanism, you can know where to target a drug----and just as important, why a drug could be safe in one instance, but dangerous in others.

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