Hopkins scientist wins Nobel Prize

Biochemist discovered `water channel' protein

Shares award in chemistry

October 09, 2003|By Scott Shane | Scott Shane,SUN STAFF

Dr. Peter C. Agre, a self-effacing Johns Hopkins School of Medicine biochemist who delights in telling colleagues that he earned a D in chemistry before dropping out of high school, was awarded the Nobel Prize in chemistry yesterday for his breakthrough discovery of the proteins that govern the movement of water in and out of cells.

Agre's identification of aquaporins, which he stumbled upon while doing unrelated blood experiments more than 10 years ago, opened avenues for promising research in areas as diverse as anti-malaria drugs, kidney ailments, brain swelling after strokes, lung problems in premature babies and even the mechanisms of root systems in plants.

A 54-year-old professor of biological chemistry, Agre will share the $1.3 million prize with Dr. Roderick MacKinnon, 47, a biophysicist at Rockefeller University in New York. MacKinnon helped unravel the operation of ion channels, electricity-generating molecules that stud the outer surface of cells and play an essential role in everything from the creation of thoughts to the tick of the heart.

Yesterday morning at his home in the Baltimore County neighborhood of Stoneleigh, where someone had tied balloons to the dogwood out front, Agre fended off congratulations with jokes and patiently spelled aquaporin for reporters calling from Denmark, Brazil, Germany, Argentina and Colombia.

"Life is interesting," Agre said, between pouring coffee for visitors and hugging a neighbor who dropped off a handmade card. "Most of your hypotheses in science turn out to be wrong. This one was right, and I guess that's why Stockholm called."

There had been some hints over the past few years - invitations to speak at the Nobel-awarding Karolinska Institute in Sweden, mysterious visitors to his cluttered lab in East Baltimore. But the 5:30 a.m. telephone call still came as a surprise, Agre and his wife, Mary, recalled a couple hours later.

"They said it was the Nobel Committee," he said. "I wondered if it might be some kind of a joke, but they sounded very convincing."

His memory of the next few moments is a little fuzzy. "What did I say?" he wondered. "I think I said, `Yes!'"

His wife, meanwhile, was hoping the call was from Sweden. "We knew chemistry was today. So I heard the phone and I was like, `God, could this be it?'" said his wife of 28 years, a preschool teacher.

Carly, 14, the youngest of the Agres' four children and the only one still at home, said she figured something good had happened when her father began behaving strangely.

"I heard him jumping up and down and giggling," she said. "I thought either he won the lottery or the Nobel Prize."

When Mary Agre reached her husband's mother in Minnesota, Ellen Agre expressed pleasure but quickly added an admonition: "Tell him not to let it go to his head."

There was little danger of that. A swimmer, bicyclist, Scouting leader and walker of the family's black lab, Jinx, Agre seemed determined to remain a regular guy. When Hopkins President William R. Brody called to congratulate him on the Nobel - the first for a sitting Hopkins faculty member in 25 years - Agre was taking out the trash.

As he and others tell it, Agre's great discovery was a classic piece of scientific serendipity, a dead-on illustration of Louis Pasteur's adage that chance favors the prepared mind.

"The humbling truth is we bumbled along and bumped into this," Agre said.

A physician specializing in blood disorders, Agre was working at Hopkins in the late 1980s on Rh incompatibility in pregnancy, a dangerous condition in which a mother with Rh-negative blood has a fetus with Rh-positive blood.

As Agre and his colleagues purified the Rh protein they needed for the blood studies, they noticed a "contaminant" - a different protein found in red blood cells.

"The smart thing to do would have been to discard it and go back to the important work," Agre said. But he was intrigued that the mysterious substance resembled proteins found in the human kidney and in plants. He couldn't resist following the byway.

When he realized that the protein might be the long-sought "water channel," Agre helped design a series of elegant experiments to test the idea.

"My approach to science might be described as the Huck Finn approach," he said at a news conference at the Hopkins medical school. "If it looks fun and it's doable, we're going to do it. ... The greatest element of all in this discovery is luck."

Dr. Landon S. King, a pulmonologist who collaborates with Agre on aquaporins, said his colleague's self-deprecation disguises an uncanny sense of which research paths will prove fruitful and a formidable capacity for grueling scientific labor.

"There's a certain element of chance in the discovery of the protein," said King, who arrived at Agre's house before 7 a.m. with another colleague, Dr. Masato Yasui, bearing bagels and champagne. "But the elucidation of its function and the rest of the biology were not at all chance. They were the result of hard work and rigorous study.

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