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Anatomy of a Breakthrough Nobel Prize winner Peter Agre describes his discovery of aquaporins. Photos by john kish iv Peter Agre, M.D., winner of the 2003 Nobel Prize in Chemistry, visited Moravian College October 2 to speak about the “Joys and Tears of Life in Medical Science.” Before the talk, Dr. Agre met with Moravian medical science alumni, pre-medical science students, and faculty members at a reception in Collier Hall of Science. Dr. Agre is president of the Board of the American Association for the Advancement of Science, the nation’s largest scientific organization. He was awarded the Nobel Prize for his discovery of aquaporins, proteins in cell membranes that regulate the flow of water. He currently serves as the director of the Johns Hopkins Malaria Research Institute, where his research focuses on the structural and functional characterization of aquaporins in relation to malaria. He holds two U.S. patents on the isolation, cloning, and expression of aquaporins, and is the principal investigator on four National Institutes of Health grants. Aquaporins, which are found in red blood cells, renal tubules, the epithelium of the brain, and various structures of the eye, are being investigated for their potential role in the prevention or treatment of glaucoma, nephrogenic diabetes, cystic fibrosis, brain edema, congestive heart failure, and more. Dr. Agre described his discovery of aquaporins and the significance of the Nobel Prize during his talk at Moravian: “I was very fortunate. Dr. Victor McKusick at Johns Hopkins offered me a tenured assistant professorship and the focus of my work changed to diseases affecting the newborn. I worked on the basis of the Rh blood group antigen, which was then unknown at the molecular level. This was just twentysome years ago. We [Dr. Agre and his lab team] figured out a way to identify it and purify it. It was a big, confidence-building activity, and we published our work in prominent journals. We later co-purified it, and by total accident, there was a contaminating molecule unrelated to Rh, but about the same size. “This protein was fascinating. It didn’t stain well. No one had ever seen it before. And when we were able to quantify it, we found it was one of the most abundant proteins in the membranes of cells. We were able to obtain enough protein to get the sequence. And the sequence was similar to some proteins identified in the roots of plants, and the brains of insects—none of them functionally defined. I was curious. What could this be “I talked to dozens of scientific friends and colleagues about this new protein, which was also found in red cells and renal tubules in mammalian tissues. But we had no progress.” While returning home from a Florida vacation with his family, Dr. Agre stopped in Chapel Hill, North Carolina. “I called ahead to my friend and mentor, John Parker, a clinical hematologist at UNC. In addition to being a fine physician, John had a small but excellent lab where he studied the physiology of red cells. I told him about this protein, which seemed to be membrane-spanning and channel-like in structure. “John thought for a minute, leaned forward, and said, ‘Peter—red cells, renal tubules, tissues in plants. 14 MORAVIAN COLLEGE MAGAZINE FALL 2010
These are highly permeable tissues. Have you considered this might be the long-sought water channel’ Apparently physiologists for more than a hundred years had been trying to explain why some tissues like renal tubules could be freely permeated, and other tissues like our skin are rather impermeable. So it was his suggestion that led to the breakthrough. “I returned to the lab and teamed up with another scientist at Hopkins, Bill Guggino, a physiologist. We injected the complementary RNA of this protein into frogs’ eggs, which are waterproof. When we transferred the oocytes to distilled water, they exploded like popcorn. The control eggs just sat there dormant. We knew then we had discovered the longsought water channel, but did not have a clue this could be of significant interest to others. “Within weeks we began receiving calls from around the world asking us to share the plasma. We hustled to get our first report out, fearful we’d be scooped. As a small lab shares information, the big labs often jump on it. But we published first. [The 1992 paper by Peter Agre and Bill Guggino, Ph.D., was published in Science.] This led to the discovery of related proteins—cousins in different tissues with similar but not identical functions. “. . . It is important that there be a Nobel Prize but it’s more important for the world to know about science than about any of us individually. The Nobel Prize is a footnote for the individual. But when they announce the winners, it focuses the world on what we are doing, whether in a research lab, or in a classroom, or in a clinic. It is all the same enterprise. It’s about trying to make the world a better place. I can’t imagine doing anything else.” W Nobel Prize winner Peter Agre, M.D. visited Moravian October 2 to speak about his life in medical science and the discovery of aquaporins. A reception for medical alumni and students (Nicole Hadeed ’11, center photo) was held in Collier Hall. Top: Joseph Merola, M.D. ’64, Mike Genel, M.D. ’57, Peter Agre, and President Thomforde toasted the occasion with test tubes of squash soup. FALL 2010 MORAVIAN COLLEGE MAGAZINE 15
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