Peter Agre was one of the recipients of the 2003 Nobel chemistry prize for clarifying how water is transported into and out of the cells of the body. It was long suspected that cells must contain specific water channels, but it was not until 1988 that Agre isolated a membrane protein that he later realised was the channel. A decade later, Roderick MacKinnon earned the second 2003 Nobel chemistry award by using X-ray crystallography to examine the structure of ion (salt) channels and how they work. Agre’s discovery explains, for example, how kidneys recover water from primary urine. It also has implications in animal, bacterial and plant studies.
He was born in 1949 in Northfield, Minnesota, 40 miles south of Minneapolis. Like many Minnesotans, he came from ‘Viking’ Norwegian stock. His father was a chemistry professor and double Nobel laureate, Linus Pauling, was often a guest and the family hero. Peter attended Theodore Roosevelt High School and was an Eagle Scout but a school camping trip through Russia brought out a teenage rebellious streak and when his chemistry grades slipped to ‘D’, he quit school in 1967 and continued at night school, while learning Russian during the day. Finally, he enrolled at Augsburg College and majored in chemistry. After graduating in 1970, he took a year off to tour Asia and the Middle East before entering Johns Hopkins University School of Medicine, where he became fascinated by biomedical research. He also met his future wife, Mary Macgill, there. They got married in 1975 and have three daughters and a son.
After receiving his MD in 1974, Agre trained at Case Western Reserve University Hospital, Hospitals of Cleveland, and in 1978 accepted a clinical fellowship in haematology and oncology at the University of North Carolina. In 1981 Agre returned to Johns Hopkins, becoming an assistant professor in 1983. Working on the blood group antigen Rh, Agre’s team isolated two new membrane proteins (approx. 30 kDa) in red cells. After spending 1988–89 on sabbatical to learn DNA technology, Agre decided to explore one further protein. The protein was abundant in kidney tubules and was related to proteins from diverse sources – lens of a cow’s eye, fruit fly brain, bacteria, and plants. These clues intrigued Agre but it was John Parker, his former professor at UNC, who suggested it might be the long sought-after water channel. Together with Greg Preston, Agre performed a simple test by doctoring six frog eggs with the protein. Immersing six normal eggs in water had no effect, but the doctored eggs “exploded like popcorn”. Presenting their discovery in 1992 the scientists dubbed the protein ‘aquaporin’ or AQP1. At the last count, biochemists in this field had reached AQP12 in humans, but hundreds of aquaporins are now known in plants and micro-organisms.
This text and the picture of the Nobel Laureate were taken from the book: "NOBELS. Nobel Laureates photographed by Peter Badge" (WILEY-VCH, 2008).
Picture: © Peter Badge/ Lindau Nobel Laureate Meetings
By Volker Steger
This is a sportsman in sneakers. He sketches a beautiful picture of his
discovery, the aquaporin channels in the cell membrane.
During the shoot, he gives me a demonstration of some rather cool ski
moves – while holding the sketch with his Nobel discovery!
Er ist ein echter Sportler: Seine Füße stecken in Turnschuhen.
Und er zeichnet ein wunderschönes Bild von seiner Entdeckung,
den Aquaporinkanälen in der Zellmembran.
Während des Fotoshootings demonstriert er mir einige ziemlich
rasante Skibewegungen – während er gleichzeitig die Zeichnung
seiner preisgekrönten Entdeckung in die Kamera hält!
Regulating the Flow
by Adam Smith
You’re looking at a sketch of an aquaporin channel, the route by which water travels across our membranes. Some of our membrane epithelia are pretty impermeable. You can soak in a hot tub for literally hours, and while your toes may get a little squishy you don’t absorb a lot of water. But think of Pavlov’s dog. The dog hears the bell and within seconds its saliva is flowing. There must be a mechanism to allow water to cross membranes that fast when needed, and that mechanism turns out to be the aquaporin family of water channels.
The representation shows a single subunit of the channel, with a pore running through the centre and a space where water (H-O-H) can fit through but nothing else will pass. The notion that there should be channels to explain the movement of water through membranes had been around for a century. But despite many sophisticated experiments that all pointed to the idea that there there must be a proteinaceous pore allowing water to pass through the membranes, none of the logical approaches revealed its identity. There was no culprit.
And then came Peter Agre’s observation of the first aquaporin channel. “We came upon this protein by chance observation” he says. Having purified a new protein, and knowing that it existed in great abundance, Agre checked for water transport, and found it! And while normally in science there are sceptics, his first reports of the findings in 1992 were greeted with virtually no disagreement. Now known to be a family of proteins, the aquaporins allow osmosis to occur across cell membranes (the plasma membranes mentioned in the drawing),water flowing through the channels in the direction of an osmotic gradient. And this happens fast, with thousands of millions of water molecules travelling through a single channel each second!
Agre was awarded his Nobel Prize together with Roderick MacKinnon, who demonstrated what ion channels look like at the atomic level. He describes good scientists as “those people who are total junkies for discovery.” Then he goes on to describe the scientific life: “You don’t know for sure what’s going to happen, and most of the time nothing interesting happens. And once in a while you find something that was totally unforeseen and it’s fascinating, and that happened to us. It was very dramatic, very simple. We are still celebrating.”