Dr. Agre
While Nobel Laureate Peter Agre, MD, only started performing malaria research about 3 years ago, he explains that this new direction is the fulfillment of “a life‐long ambition.” Inspired by the medical missionaries he knew during his childhood in Minnesota, Dr. Agre was always determined to work on thirdworld diseases. However, only in the past few years has he been able to experience what he calls the “true joy” of working in malaria research, first as the recipient of a grant from the Johns Hopkins Malaria Research Institute in Baltimore, Maryland (JHMRI, http://malaria.jhsph.edu) and now as the institute's director.
In the intervening decades, Dr. Agre has left his mark on a few other areas of biomedical research. A graduate of the School of Medicine at Johns Hopkins, Dr. Agre pursued research in hemolytic anemias After a residency in internal medicine and a clinical fellowship in hematology and oncology. After his return to Johns Hopkins, he says his continued studies in spherocytosis led him and his fellow researchers to “the first biochemical purifi cation of the Rh complex,” which in turn led—serendipitously, Dr. Agre insists—to the identifi cation of “the first molecular water channel, aquaporin 1.” That breakthrough resulted in his sharing the Nobel Prize in Chemistry in 2003 for discoveries concerning channels in cell membranes. After that, Dr. Agre served as the vice chancellor for science and technology at Duke University Medical Center in Durham, North Carolina for 3 years before returning to Johns Hopkins in 2008.
In his role as JHMRI director, Dr. Agre oversees an institute that brings together 25 scientists, including medical doctors and insect biologists, who work on novel approaches to malaria. He also continues to lead his own small, scaled‐down lab of 2 scientists at Duke and a handful of researchers at Johns Hopkins. Although he characterizes the water channels research as “in some ways a great and glorious distraction from [his] original life plan,” in fact that research provided Dr. Agre with a means to move into his malaria work. He explains that “the aquaporins are one of these gene families that are present in all life forms … and so, when the malaria [Plasmodium]falciparum genome was solved, one of our colleagues quickly checked it out.” Having identified that aquaglyceroporins, channels permeable by both water and glycerol, play a role in the efficiency with which malaria can invade its host, Dr. Agre says his lab is continuing to research membrane transport in the malaria organism.
Unconventional Research Experiments Under Way
Within the institute at large, there are other interesting and unconventional experiments under way. As Dr. Agre points out, “the usual approach to developing a [malaria] vaccine starts with the red cell stage” in the human body during which the malaria parasite invades blood cells and reproduces exponentially. With such a complex organism—Dr. Agre notes that the malaria parasite has 5,300 genes and millions of years of evolution to defend it—scientists are now looking at different stages in the parasite's life cycle for possible ways to inhibit the disease's movement from human to mosquito host and back. Dr. Agre enthuses about the creative approaches of JHMRI scientists who are “looking to develop vaccines against specific antigens in the malaria parasite—and also antigens in the gut of the mosquitoes—that may prevent mosquitoes from becoming infected” when they ingest parasite gametocytes through infected human blood.
The institute's research may one day save many lives. “The estimates [for malaria] run between 1 and 3 million deaths per year in the continent of Africa alone,” Dr. Agre notes, and a majority of those who die or are left severely impaired as a result of the disease are “youngsters under the age of 5.” There are, however, many intermediate steps between a research discovery and the development of a practical application, and Dr. Agre is aware of the institute's distance from malaria's painful realities. While the institute does basic research, it does not provide humanitarian aid in the more traditional sense—activities, he explains, that are more eff ectively executed by the World Health Organization or the Bill and Melinda Gates Foundation. “We do have a fi eld station in Zambia, and we’re starting a new program in Bangladesh, but we’re not out there distributing bed nets and spraying living quarters with DDT.” Likening JHMRI scientists to the basic researchers who laid the groundwork for Jonas Salk's development of the polio vaccine, Dr. Agre says, “We sincerely hope that [our basic science] discoveries will be translated into practical clinical applications to prevent or treat disease.”
Translation and Collaboration
A prestigious award in chemistry notwithstanding, Dr. Agre declares that he “never dreamed of becoming a successful basic scientist.” He explains, “I came to this by the clinical side… But things became more and more basic, and we succeeded because of a combination of good luck, hard work, and the generous collaboration of numerous scientists … who really carried the torch.” Dr. Agre has from the beginning worked with a translational perspective, and he has a clear vision of himself “as a medical doctor with an interest in developing science that Dr. Agre will lead to the improvement of health.” He is pleased to see translational work now becoming a priority. “Frankly,” he remarks, “I think this is overdue.”
But translating basic science discoveries into clinical practice is, Dr. Agre notes, “a major challenge,” not just with malaria but also with other diseases. He points out that, in 1949, sickle‐cell anemia became the first molecular disease to be delineated, thanks to the work of Linus Pauling (an Agre family friend). Sixty years later, the world is still waiting for a cure. Apart from the technical challenges of translation, Dr. Agre sees other potential problems that limit translational medicine's promise. As the director of JHMRI, he may think specifi cally about how to recruit young scientists to work on malaria, but, more broadly, he sees the research world as a whole competing with the clinical realm, the latter in many cases offering a more stable lifestyle. Research, he observes, “is oftentimes not the safe career.” Although Dr. Agre commends medical practitioners who care for patients, he wants to ensure that medicine does not stagnate. He emphasizes, “We need to make sure that the best and the brightest of our young people will get engaged. We need young Jonas Salks.”
For those who have chosen the research path, he worries that translational developments could be hampered by the current “constriction in the funding pipeline.” As he explains, “one fear I have, quite honestly, is that … there will be antagonistic relations between the basic scientists and those doing clinical science which is translated.” As one who has been “on both sides of the street,” Dr. Agre sees the contributions of both basic scientists and clinical investigators as essential: “We need each other.”
My challenge to scientists, every scientist who's a tenured professor at a university or an institute, [is to deliver] some fraction of his or her time to public awareness and the public well‐being.—Peter Agre, MD
The People's Laureate
In a world in which funding continues to be a problem, Dr. Agre believes there is a need for both public and private investment. JHMRI itself was founded and is sustained by funds provided by the Bloomberg Family Foundation, and Dr. Agre is quick to point out that the institute would simply not exist without this investment of private money. He says that the infrastructure that the foundation supports allows scientists who would otherwise be “scattered here and there” to work in a unifi ed institute.
At the same time, Dr. Agre observes that almost all JHMRI scientists are funded by the National Institutes of Health (NIH). In fact, Dr. Agre's own research has been supported not by the biomedical industry or by private nonprofit organizations such as the Howard Hughes Medical Institute in Chevy Chase, Maryland, but by successive, hard‐won NIH grants funded, he notes, by the taxpayers. Dr. Agre says he received “one of the greatest compliments” of his life at a Yale University lecture when he was introduced by Yale's C.N.H. Long Professor of Medicine and Professor of Cellular and Molecular Physiology, Peter S. Aronson, MD, as “Peter Agre … the people's laureate.”
Being a researcher supported by public funds, Dr. Agre is convinced of the importance of sharing biomedical research with the public. He believes that “if the public are supporting us, we owe them clear spoken explanations of what we’re doing, not to brag, not to get larger amounts of money, but to share with them why this is important.” Dr. Agre continues, “We scientists have to take personal responsibility [for] presenting our work … I think we need to take our show on the road.” He puts this belief into practice by talking to citizens’ groups and, when invited to give a Nobel lecture on his water channel research, scheduling a public lecture for the same trip. To questions about the value of scientific research, Dr. Agre has a compelling response: “We’re not just looking to grow improved fruit flies in Paris, France [as was recently suggested by a politician]; we’re actually looking for basic biological molecules and pathways which may have some significance to the diseases that are affecting our loved ones.”
Dr. Agre sees the Nobel Prize as providing “a bully pulpit” from which to speak about science and its significance to society. He is also excited about a new opportunity to represent the scientific community in an official capacity: In February 2009, he assumed the office of president of the American Association for the Advancement of Science. “My mission,” he says, “will be to bring science to the public.” He also sees other ways in which scientists like himself can become more socially involved. Having considered—and ultimately decided against—running for a U.S. Senate seat in his home state of Minnesota, Dr. Agre believes that scientists should, “when possible, consider running for office, whether it's the school board, town council, state legislature, or U.S. Senate.” He says that scientists have been undervalued and have not put in the effort to ensure a good representation of scientific perspectives in the political sphere.
There are many ways to get involved, Dr. Agre says. “My challenge to scientists, every scientist who's a tenured professor at a university or an institute, [is to deliver] some fraction of his or her time to public awareness and the public well‐being. Speaking to the public, volunteering at neighborhood schools, meeting with the PTA and other community groups, writing op‐eds to the newspaper … being part of the public debate is very important. I think if we cloister ourselves and sulk in our tents … we’re not going to improve things.”
Improving life and health, whether through basic research or public outreach, remains Dr. Agre's fundamental goal. He remembers that, at the time he won the Nobel Prize, his mother reminded him of the importance of doing something useful. “Getting prizes is not enough,” she said. He continues to hope that his work in water channels will someday be translated into concrete life‐saving techniques. “That,” he says, “is a joy I am waiting to witness.” In the meantime, Dr. Agre promises, “we’re still working hard.”