Peter Agre

Return of the Laureate

Peter Agre sets his sights on a new challenge—malaria

Interview by Brian W. Simpson

Peter Agre's phone rang at 5:30 a.m. on October 8, 2003, and his life has never been the same. The Royal Swedish Academy of Sciences was calling to tell him that he had been awarded the 2003 Nobel Prize in Chemistry for his pioneering research into aquaporins. (The proteins form small water channels in cell membranes necessary for many physiological processes and cellular functions.) The news unleashed a blizzard of congratulations, media interviews, opportunities and demands that has yet to abate.

Not long after the Stockholm ceremonies, Agre received some more life-changing news. He was awarded a pilot grant in early 2004 from the Johns Hopkins Malaria Research Institute (JHMRI). Founded in 2001, the Institute has 19 faculty members who concentrate on advancing basic science to develop new methods in malaria prevention and treatment. The grant allowed Agre to shift his research in a new direction: Could aquaporins be exploited as a means of treating or preventing malaria? Encouraging results have led to an NIH grant and a second career of sorts for Agre, MD, who spent most of his professional life at Hopkins' School of Medicine, leaving in 2005 to go to Duke University. On January 1, 2008, he becomes JHMRI's new leader, succeeding founding director Diane E. Griffin, MD, PhD, who remains chair of Molecular Microbiology and Immunology. "Peter Agre is a great scientist and a great human being," says Dean Michael J. Klag, MD, MPH '87. "His innovative research on the molecular biology of malaria parasites and his ability to lead collaborations make him an ideal candidate to direct the Malaria Research Institute."

Agre, who will continue an affiliation with Duke University, is perhaps the most unassuming Nobel laureate you're likely to meet. Quick-witted and perpetually pleasant, Agre has spent his career supporting others' research efforts and downplaying his own contributions. During an afternoon telephone interview with Brian W. Simpson, editor of Johns Hopkins Public Health magazine, Agre, 58, discussed his malaria research, his plans for JHMRI and the need to nurture young scientists.


Why malaria?

Sometimes in a career, there are pathways you never fully get to explore. I always felt an interest in diseases affecting the developing world. As a student, I worked on cholera, which is still prevalent in parts of Asia and kills many infants and children. Malaria is a scourge of even greater magnitude... A major part [of the parasite's lifecycle] is in red blood cells. So my background as a hematologist and red-blood-cell membrane biochemist will be very useful.

What made you want to apply for a JHMRI pilot grant in 2003?

We knew aquaporins were present in virtually all life forms. I thought that since Plasmodium [the malaria parasite] had aquaporins, maybe they were important to its virulence. My colleagues Landon King, Dominique Promeneur and I together put in the pilot project grant. We could not have done the studies without the Institute's support.

What have you found thus far?

We just published our first two papers. We've concentrated on Plasmodium berghei, which gives mice an infection equivalent to malaria. By knocking out the gene that codes for the parasite's aquaporins, we were able to slow down by half the rate at which red cells become infected, the first step toward showing this pathway is important for the virulence of the organism. The mice lived longer, but they weren't cured.

Could this discovery eventually lead to a cure?

Realistically, this work will probably not lead to a cure because the parasite is complicated and devious. Nevertheless, our studies have identified a new pathway that could possibly yield a secondary approach to treatment... I am not a lifelong malariologist, and I do not come to this with great malaria expertise. Sometimes I even feel like a fan who's been asked to play with the band. But that will not stop me from thinking in big terms.

What's JHMRI's role in fighting malaria?

There are other groups who provide bed nets and DDT. Our job is to look creatively as scientists and ask, "Are there things that we have never thought of or never tried?"

What do you hope to achieve as the new JHMRI director?

My goal is to do all that I can to contribute to the continued success of the Institute. JHMRI scientists have the potential to make discoveries that may reduce or eradicate one of the world's worst diseases. My job will be to facilitate their efforts. For me, that is what leadership is about. I have been named director, but my job is to serve, not to command.

Do you see this position as a major shift for you?

Yes—this is a major shift for me. On one level, I strongly feel it is time to give back. A leadership position is one way to do good things for younger scientists. I hope to do this by increasing the visibility of their work, connecting them with other scientists around the world, and reducing barriers to their achievement of success—whether it is a need for more funding, improvement of scientific environment, or even personal encouragement.

Is there another Nobel in your future?

I don't want people to have unrealistic expectations. I'm just another scientist—albeit at a senior level—who still hopes to make new discoveries but who also wants to contribute in an organizational way to Johns Hopkins, a very special institution that has always been first in my heart. Honestly, the 2003 Nobel has been a mixed blessing, and I look forward to returning to the life of a faculty member and research scientist.

Any advice for young researchers out there who would like to cap their careers with an awards ceremony in Stockholm?

Number one: Don't even think about Stockholm. My advice to young scientists is to find a lab with exciting science and a research project that's so interesting it wakes you up at night because you want to go back to work... And think creatively.