The Story of a Nobel Prize
|Peter Agre, M.D., 54, professor of biological
chemistry at the Johns Hopkins University School of Medicine, was awarded
the 2003 Nobel Prize in Chemistry by the Royal Swedish Academy of Sciences.
TheHYI 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) shared the 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, a member of Hopkins' Institute for Basic Biomedical Sciences. "It is amazing and gratifying that the Nobel committee feels our work has accomplished that milestone in just 12 years. That's warp speed in molecular chemistry and it could never have happened as fast as it did without the wonderful resources and collaborators available at Johns Hopkins. This is an honor for the entire Hopkins family." Since a 1992 paper in the journal 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, Agre and his colleagues, including technician Barbara Smith and then post-doctoral fellow 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.
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.
Agre joins other Johns Hopkins faculty who have been honored with
the Nobel Prize, notably scientists Hamilton Smith and Daniel Nathans,
who shared the 1978 prize with Werner Arber for the discovery of restriction
enzymes, the molecular scissors that cut DNA. Their discovery gave birth
to the field of genetic engineering.