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