The 2003 Nobel Prize in Chemistry goes to two researchers for pioneering work on proteins that control which molecules pass into and out of cells. These gatekeepers are the basis of many vital functions, including the generation of nerve impulses and the ability to regulate the excretion of urine.
Peter Agre, 54, of Johns Hopkins University in Baltimore claims half of the prize for his discovery of water channels. These tiny protein pores escort water in and out of cells much faster that it could diffuse through their fatty outer membranes. This speed is particularly critical in the kidney, which reclaims water from the urine to prevent dehydration. "You'd pee out 50 gallons of water a day if these channels didn't filter the water back into the body," says Robert Stroud, a biophysicist at the University of California, San Francisco.
Agre isolated the first water channel, which he termed aquaporin, from red blood cells in the early 1990s (Science, 17 April 1992, p. 385). His team identified the amino acid sequence of the protein and from that, the DNA sequence of the aquaporin gene. Combing genome databases for similar sequences, they and others have subsequently identified 11 human aquaporins--some of which are suspected to play a role in diseases--and many more in bacteria and plants. "I think [Agre's discovery] is really one of the big breakthroughs in physiology," says Robert Schrier, a nephrologist at the University of Colorado Health Sciences Center in Denver.
The other half of this year's prize goes to Roderick MacKinnon, 47, of Rockefeller University in New York City for his work on ion channels. These proteins are essential for, among other things, nerve cell communication and muscle contraction. For decades, researchers tried to infer the structure of ion channels and understand their workings from indirect physiological evidence. But MacKinnon and colleagues sent a jolt through the field in 1998 with the first ever high-resolution picture of an ion channel, derived from x-ray crystallography (Science, 3 April 1998, p. 69).
Based on the crystal structure, MacKinnon's team presented an elegant model of how ions--in this case potassium ions--pass through the core of the channel and explained the channel's most remarkable feature: its ability to let potassium ions through while excluding much smaller and identically charged sodium ions. MacKinnon's colleagues describe him as a tireless worker who's made many key contributions to the field in a remarkably short time. "He certainly deserves this," says Clay Armstrong of the University of Pennsylvania. "He's packed two or three careers into 10 years."