It’s been 20 years since Johns Hopkins’ Peter Agre won the Nobel Prize in Chemistry for his game-changing discovery of aquaporin water channels. Known as “the plumbing system of cells,” aquaporins facilitate the movement of water across cell membranes and are now known to have a vital role in processes ranging from brain function to male fertility to hearing and vision.
At a recent CIM Seminar, dozens of CIM supporters and clinician-scientists gathered online with Agre, now director of the Johns Hopkins Malaria Institute and a Bloomberg Distinguished Professor, to reminisce about the exciting swirl of activity surrounding his Nobel honor and to learn insights he’s gained over the last two decades.
On the Months Leading Up to the October 2003 Announcement of his Nobel Prize
“I had been invited to lecture several times in Sweden over the previous few years,” Agre recalls. “Then out of the blue, I got an email from Bengt Nordén from Sweden asking if he could come visit me in the laboratory. This was unexpected. I didn’t know who he was, so I called a colleague, who told me: ‘You might be interested that he is chair of the Nobel Chemistry Committee.’
“His visit was very pleasant. He never talked about the Nobel Prize, and I didn’t ask him about it,” Agre says. CIM Scholar Landon King, a key member of Agre’s lab team at the time and today executive vice dean for the school of medicine, recalls that Nordén and Agre spent much of the day examining old lab notebooks, “looking for evidence of the primacy of the discovery.”
“It all became even more tantalizing when a Swedish television crew showed up in our lab on pretty short notice, with no explanation.” – Peter Agre
“It all became even more tantalizing when a Swedish television crew showed up in our lab on pretty short notice, with no explanation,” Agre says.
King adds, “We imagined it. To the point that I went out and bought bagels and balloons the night before the announcement was to come out.”
On the 5:30 am Call That Changed Everything
“On Wednesday of that first week in October, about 5:30 in the morning, the phone rang. I was ready,” Agre says. “I answered, and a pleasant voice with a Swedish accent said, ‘This is an important telephone call from Stockholm for Professor Peter Agre. Are you Professor Agre?’ I replied, ‘I sure am!’ Then they connected me with the Nobel Chemistry committee.”
Agre learned that he shared the prize in chemistry with Rockefeller University’s Roderick MacKinnon, for his work on the structural and mechanistic study of ion channels.
“I was instructed there would be a press conference in 20 minutes. I sprinted for the shower,” Agre says. “Mary, my dear wife, called my mother in Minnesota. My mother was a farm girl who was very wise in the ways of humanity. She listened to Mary and said, ‘Tell Peter that’s very nice, but don’t let this go to his head.’”
“Then Landon appeared at the door with balloons, and the New York Times was in the front yard. Johns Hopkins President William Brody called. I made my way into the lab, and by 10 o’clock in the morning, there was already a party going and champagne ripping open, and the day only got crazier.”
On Nobel Week in Stockholm, December 6–12
“It’s a very compact week with multiple events every day — lectures by the Laureates and receptions. The ceremony itself is held in Symphony Hall in downtown Stockholm. Everyone is in formal wear: white tie and tails for men. They don’t trust the Laureates to know how to receive the award, so they actually have a practice session earlier in the day. They instruct you where to sit, where to stand, how to approach the king, how to bow.
“Following the awards ceremony, there’s a sit-down dinner for 1,100 people, served simultaneously by waiters, some of whom are opera singers, so it’s a musical performance. There’s really a lot of fanfare. During the banquet, one member of each prize is asked to give a three-minute talk. I gave a talk on science education for small children,” he says.
The celebration lasts well into the night with dancing and parties. “Then early the next morning, we had to get up for more Nobel interviews and visits.”
On Science as a Tool in Diplomacy
“Early in my career, I was very interested in international affairs and world events. I never thought I’d be a research scientist. In fact, I came to Hopkins with the idea of becoming a global health worker. When things started working in the lab so well, I stuck with it, but I thought that [eventually] I wanted to get more involved with bringing science to the public.
“I was elected president of the American Association for the Advancement of Science in 2008, which had a new Center for Science Diplomacy. When I became president, we had the first trips to Cuba, to North Korea and Iran. I made six trips with the AAAS. I even met with Fidel Castro himself, who was in his 80s. He was quite frail, but he had a very sharp mind.”
Agre also served as chair of the Committee on Human Rights of the U.S. National Academies of Sciences, Engineering, and Medicine from 2005–2007. “We were involved with seeking pardons and the release from captivity of scientists, engineers and health professionals from around the world. Between these two activities, I was really very busy.”
On the Importance of Cross-Training for Young Clinician-Scientists
“As a medical student, you learn a lot of information, but as a house officer, you really learn the diseases. I was a medical resident at Case Western Reserve, and program leaders there had adopted the Osler Medical Resident training model. That training really helped us anticipate what clinical defects would be caused by aquaporins. Clinical training also helps an individual develop good discipline. As an intern or resident, you’ve got to know the facts. There are no excuses.”
“Of course, every serendipitous observation is not going to turn out with an important answer. The challenge when you are sorting through the unexpected is to know when to pursue something and when to drop it.” – Peter Agre
On the Value of Serendipity
“The aquaporins were a clear serendipitous discovery,” Agre says. His lab had been focused on red cell membranes when his team came upon a protein fragment they couldn’t explain. “We were very interested in it because it appeared to have a shape suggesting it was a membrane channel, but red cells were not believed to have membrane channels.”
Agre consulted dozens of scientists about the mysterious protein (“It appeared to be a contaminant and had no clear functional role”) when hematologist John Parker at the University of North Carolina at Chapel Hill suggested that perhaps it could be a water channel. Agre and his team collaborated with Bill Guggino at Johns Hopkins to investigate the idea — which ultimately bore out.
“There was jubilation!” Agre says. “That experiment changed the focus of our laboratory entirely and my career as well.
“Of course, every serendipitous observation is not going to turn out with an important answer. The challenge when you are sorting through the unexpected is to know when to pursue something and when to drop it. If we had not figured out the function of the protein, we would have dropped it.”