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The newspaper of The Johns Hopkins University October 13, 2003 | Vol. 33 No. 7
JHU Prof Awarded Nobel Prize

Capping off the big day: Peter Agre dons a descriptive hat at a luncheon held in his honor shortly after the announcement of his Nobel Prize in chemistry.

Peter Agre is recognized for lab's 1991 discovery of 'water pores' in cells

By Joanna Downer
School of Medicine

Peter Agre, a professor of biological chemistry at the School of Medicine, on Oct. 8 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.

Not bad for someone who earned a "D" in high school chemistry. (His classmates nonetheless voted him Most Likely to Succeed.)

"If my high school chemistry teacher is still with us, he probably has aspirated his morning coffee," said Agre during a press conference held in Tilghman Auditorium just hours after the prize was announced. In attendance were university President William R. Brody; Chi Dang, vice dean for research at the School of Medicine; and various members of the Johns Hopkins community, among them colleagues and students from Agre's laboratory.

Agre, the son of a college professor, told those gathered of a person who learned at a relatively young age how "fun" science could be. After netting that "D," Agre said, he buckled down and got serious. He said he was fortunate enough to eventually wind up at Johns Hopkins.

In the Biological Chemistry departmental library, Agre, center, is applauded by Susan Michaelis, Stephen Gould, Ann Hubbard and Chi Dang.

In his typically humble manner, Agre gave the lion's share of credit to his colleagues and the "many young people in the laboratory who did the work."

"This is really our reward," he said. "In all sincerity, I'm delighted this happened, but I feel that at Hopkins this could have happened to several of our colleagues. I like to think I was just the guy lucky enough to be up at bat when a fastball was thrown right down the middle of the plate."

He certainly knocked this pitch out of the park.

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," said Agre, a member of Johns Hopkins' Institute for Basic Biomedical Sciences, upon learning of the award. "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."

Edward D. Miller, dean of the medical faculty and CEO of Johns Hopkins Medicine, missed the press conference because he was out of town but said, "This is a great day for the School of Medicine and the university at large. There are few happier occasions to celebrate at an academic medical center."

Chi Dang said, "This is a terrific day for Peter and a tremendous day for the Hopkins community. The prize is not only a recognition of the important discoveries on how materials are transferred into and out of cells, but it also symbolic — in the case of Peter Agre — of being rewarded for a job superbly done with great depth, without fanfare. This should be an encouragement for the young scientists that persistence and dedication will yield the joy of discoveries and, occasionally, fringe benefits. It also highlights that the prepared mind can turn serendipity, as in the case of the discovery of water channels, into a paradigm-breaking moment."

Since a 1992 paper in Science by Agre and Hopkins physiologist Bill Guggino that 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.

"I am so pleased that Peter has been recognized for his outstanding work on aquaporins," said Gerald Hart, director of Biological Chemistry, the division housing Agre's laboratory. "He has been part of the Johns Hopkins family for more than 20 years, and we just couldn't be prouder."

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-doc Gregory Preston, 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," Agre said. "We still have much to learn, and the possibilities of where aquaporins will take us are unlimited."

Born in Northfield, Minn., 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 degree from Johns Hopkins in 1974. In 1981, after postgraduate 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 to become a professor in the Department of Biological Chemistry, a position he still holds, by then department director Daniel Lane.

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.

It has been 25 years since a current Johns Hopkins School of Medicine faculty member was awarded a Nobel Prize. In 1978, scientists Hamilton Smith and Daniel Nathans shared the prize with Werner Arber for development and application of restriction enzymes — molecular scissors that cut DNA in predictable places.

Most recently, Riccardo Giacconi, research professor of physics and astronomy in the Krieger School of Arts and Sciences, was awarded the Nobel Prize in physics in 2002. J.M. Coetzee, named Oct. 2 as winner of the 2003 Nobel Prize in Literature, was the Hinkley Visiting Professor in the Writing Seminars at Johns Hopkins in spring 1989.

Greg Rienzi of The Gazette contributed to this article.

Related Web sites
The Royal Swedish Academy of Sciences
Johns Hopkins Nobel laureates


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