How has he transformed the scene?
Dr. Peter Agre’s best-known contribution to science is undoubtedly the 1991 discovery of the first functionally defined water channel protein, or “aquaporin.” This discovery—the outcome of research directed by Agre in his Johns Hopkins laboratory—provided the world with critical insight into the mechanism by which living organisms regulate and facilitate the transport of water molecules through cell membranes. Subsequent work revealed that this first protein (dubbed AQP1) was in fact only one of a family of aquaporins that together make up what Agre calls “the plumbing system for cells.”
Agre has been called an ambassador, a diplomat for American science, the “people’s laureate.” Whether speaking before elementary kids or kings, Agre gives science not only a human face, but a wise and generous heart.
Agre, with characteristic humility, attributes the discovery to “sheer blind luck.” If so, others have countered, it is a variety of luck that only favors the well prepared. In 1985 when the protein was first noted, Agre’s lab was not,in fact, engaged in a search for the water channel but in hematological studies focused on Rh blood group antigens. The protein later understood by Agre to be the long-sought water channel protein was originally viewed as something of a nuisance, in that it represented a contaminant in their purified Rh preparations. Only upon reflection, with further investigations undertaken in Agre’s lab and after consulting with mentor Dr. John C. Parker at the University of North Carolina, did Agre realize the significance of this rascal protein.
In 2003, at the age of 54, Agre was awarded the Nobel Prize in Chemistry for this groundbreaking work. The research endeavor he’d led would revolutionize the field of membrane transport. In 2004, the magazine of the Johns Hopkins Hospital and School of Medicine, Hopkins Medicine, described the tremendous implications of Agre’s findings:
“Since the paper proving the existence of the water channel appeared in 1992 in Science, Agre and others have identified 11 mammalian aquaporins. The channels have turned up, not surprisingly, in the more water-permeable parts of the body: salivary, tear and sweat glands, kidney tubules, the choroid plexus of the brain where spinal fluid is produced, the ciliary epithelium of the eye where aqueous humor is formed, the moist surface tissues of the alveoli in the lungs.
What most excites physicians, though, is that aquaporin research has shifted from merely finding where else the proteins are expressed to exploring how this knowledge can be harnessed to prevent or treat disease (among the current targets: glaucoma, nephrogenic diabetes insipidus, asthma, cystic fibrosis, brain edema and congestive heart failure).”
To date, in Agre’s lab and elsewhere, the focus has been largely on basic research to lay groundwork for what is hoped will be a new chapter in medicine, with drugs or therapies to repair or circumvent disease related to water channel defects. But great as this work is, the story of Peter Agre—the scientist and the man—is not a story of aquaporins alone.
Born in Northfield, MN to devoted parents, Agre says he knew as a boy that he would follow in the footsteps of his greatest hero—his father, Courtland Agre, a chemist on the faculty of nearby St. Olaf College. Despite a 9th grade chemistry demonstration gone dramatically awry (young Peter’s eyebrows eventually grew back, and the school ceiling was repainted after the giant fireball), Agre did indeed set off in the career direction his father had pursued. He earned an undergraduate degree in chemistry at Augsburg College on a pre-med track and was thrilled to be accepted at prestigious Johns Hopkins Medical School in Maryland. But before he made his way to Baltimore, he took the better part of a year to travel by foot, “thumb,” and motorcycle to Japan and Taiwan, to Laos and up the Mekong River, to Cambodia and the Malay highlands, to Ceylon, India, Pakistan, Afghanistan, Iran.
His experiences deepened his compassion for people dealing with Third World diseases; people whose lives are not what they deserve or would wish. When Agre entered Johns Hopkins as a first year med student in September of 1970, he knew that his interest lay in tropical diseases and world health problems. At Johns Hopkins, he would come to learn the arena in which he would make his greatest contribution: bio-medical research.
Agre completed his medical degree at Johns Hopkins in 1974, remaining for a year as a postdoc fellow in the Department of Pharmacology. He then undertook post-graduate residency training in Internal Medicine at Case Western Reserve University in Ohio, and completed a second postdoc fellowship in Hematology/Oncology at the University of North Carolina at Chapel Hill, which included work as a physician in a clinical setting. Still, Agre never strayed far from a research lab. He supplemented his UNC work by taking a position as Senior Clinical Research Scientist at nearby Wellcome Laboratories, where a number of his former “Hopkins” colleagues were engaged in research.
By 1981 he was back at Johns Hopkins School of Medicine, which would remain his professional home for the better part of the next three decades. It was here that he would establish his first independent lab and lead the research that would result in discovery of aquaporins. He rose through the ranks to professor in the Departments of Biological Chemistry and Medicine and in 1996 he was appointed Director of the school’s Graduate Program in Cellular and Molecular Medicine. After a brief departure to serve in various capacities at Duke University’s School of Medicine in the years 2005-2007, Agre was lured back to Johns Hopkins once again in 2008 by the opportunity to direct the Malaria Institute in the Johns Hopkins Bloomberg School of Public Health, a position he continues to hold.
In addition to the work on aquaporins, Agre’s other “firsts” in bio-medical research have included purifying the E. coli toxin, isolation of the Rh blood group antigens, and spherocytosis studies contributing to the understanding of membrane defects related to congenital hemolytic anemias. Over the course of his career he has published widely and is represented in the scientific literature by 155 original scientific reports, 40 review articles, three books, and many contributed works. He holds two patents—on isolation, cloning and expression of Aquaporins 1 and 5—and has served the scientific community through an array of international communities, scientific advisory boards, and editorial boards of medical journals.
Remarkably, Peter Agre’s professional stature as a researcher and accomplishments within the scientific community are matched—even bettered—by his tireless advocacy work in the broader community promoting the value of science. He maintains a wildly busy schedule, criss-crossing the globe speaking and writing about the role of science—and scientists—in public life. He has been outspoken on humanitarian issues, on the need for equity in access to education, on the role of research in addressing the critical issues of our time. He reminds us all, in particular young scholars, of the ongoing need to find solutions to the problems of malaria and other Third World diseases.
Although it has been more than 30 years since he lived in Minnesota, in speeches and interviews Agre often finds reason to raise the name of his home state where, as he notes, four generations of his father’s people are buried. Speaking recently in his role as President of the American Association for the Advancement of Science, he offered a glimpse into his guiding philosophy: “A native of Minnesota, I often like to share the wisdom of our Native Americans, the Ojibwe tribe of Minnesota included, who would make policy decisions for the tribe only after considering how these would affect the tribe seven generations in the future.” Thanks to Peter Agre, the long view is looking better every day.
