Peter Agre, M.D., was awarded the 2003 Nobel Prize in Chemistry by the Royal Swedish Academy of Sciences. The Academy recognized him for his laboratory’s 1991 discovery of the long-sought “channels” that regulate and facilitate water molecule transport through cell membranes, a process essential to all living organisms.
Agre (pronounced AHG-ray) shares this year’s prize with Roderick MacKinnon, a Rockefeller University scientist who determined the spatial structure of cell membrane channels that control passage of salts.
The discovery of the water channel, dubbed “water pore” or aquaporin, ushered in a golden age of biochemical, physiological and genetic studies of these proteins in bacteria, plants and mammals, and fundamental understanding — at the molecular level — of malfunctioning channels associated with many diseases of the kidneys, skeletal muscle and other organs. Working from this basic knowledge, scientists are searching for drugs that can specifically target water channel defects.
“It is a remarkable honor to receive a Nobel Prize, because it not only recognizes discoveries, but also their usefulness to the advancement of fundamental science,” says Agre. “It is amazing and gratifying that the Nobel committee feels our work has accomplished that milestone in just 12 years.”
Since a 1992 paper in Science by Agre and Hopkins physiologist Bill Guggino, Ph.D., which documented the discovery of the very first water channel protein, 10 more have been found in mammals, and hundreds more in plants, bacteria and other forms of life. In Agre’s lab alone, aquaporins have been discovered to be part of the blood-brain barrier and also associated with critical water transport in skeletal muscle, lung and kidney. Members of Agre’s lab also have found aquaporins in the eye and in salivary and tear glands. Researchers around the world now study aquaporins in many species of plants, bacteria and animals, and have linked aberrant water transport to a multitude of human diseases and conditions.
The discovery of aquaporin is an example of luck favoring the well-prepared. Beginning in the mid-1980s, he and his colleagues, including technician Barbara Smith and then post-doc Gregory Preston, Ph.D., were searching for proteins that are part of the Rh-factor when they happened across an abundant and much smaller protein. The researchers pursued the unexpected protein visitor — they isolated it and discovered that it was widely expressed — and within a year had cloned its complementary DNA. In dramatic experiments with frogs’ eggs, the scientists next proved that the unknown protein was in fact biology’s elusive cellular regulator of water transport.
Although Agre started his career in medicine, he gradually shifted to laboratory research so that he could investigate fundamental biological questions whose answers would have clinical relevance. “I am certain that in the future, we will be able to capitalize on our understanding of aquaporins to benefit medicine, biotechnology and even agriculture,” says Agre. “We still have much to learn, and the possibilities of where aquaporins will take us are unlimited. ”
Born in Northfield, Minnesota, in 1949, Agre went to Theodore Roosevelt High School in Minneapolis, and in 1970 earned his bachelor’s degree in chemistry from Augsburg College in that city. He received his medical doctorate from Johns Hopkins in 1974. In 1981, after post-graduate medical training and then a fellowship at the University of North Carolina at Chapel Hill, Agre returned to Hopkins, where he progressed through the ranks of the departments of medicine and cell biology. In 1993, he was recruited by then-department director Daniel Lane, Ph.D., to become a professor in the department of biological chemistry, a position he still holds.
Agre was elected to membership in the National Academy of Sciences in 2000 and to the American Academy of Arts and Sciences in 2003. He holds two U.S. patents on the isolation, cloning and expression of aquaporins 1 and 5 and is the principal investigator on four current National Institutes of Health grants.
Also visit www.nobelprize.org for more information on Peter Agre.