Evidentia

Malaria afflicts between 300 and 500 million people each year, killing up to one million children, mostly in sub-Saharan Africa. In 2003, Peter Agre won the Nobel Prize for Chemistry for his discovery of aquaporins –  what he calls “the plumbing system in cells” – water channels that conduct water molecules in and out of the cell. A Minnesota native, Peter is now director of the Johns Hopkins Malaria Research Institute, in Baltimore. He says aquaporin research is providing new insights into the virulence – the disease-causing capacity – of malaria parasites. Peter is also the current president of the American Association for the Advancement of Science, and was a science advisor to the Barack Obama presidential campaign.

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George Tombs: Before getting to malaria, let’s talk first about water and aquaporins. Could you tell me why you’ve said in one of your writings that water is the solvent of life?

Peter Agre: Well, the statement actually was first made by a wonderful biochemist back in the 1930s, Albert Szent-Györgyi and it was recognized at that time that the mass of our bodies is primarily water - about two-thirds of our body mass is water. That’s something we share with all life forms – plants, micro-organisms. So I think it’s a fairly safe statement – without water, there is no life….

Clarke and Peter Agre (Photo courtesy of Peter Agre)

George: Do all organisms – from mammals to malarial parasites – have aquaporins?

Peter: Most organ systems include aquaporins of one kind or another. Now humans have thirteen different genes encoding aquaporins, of which eleven have been worked out functionally. That’s a significant number. Plants have more. The rice genome contains 50 different aquaporins and each is expressed at a specific site. So in the human body we have sometimes sets of aquaporins, and in the brain aquaporin 4 appears to be particularly important, in movement of water into and out of the brain branchioma – and it’s involved in brain edema, which happens after closed-head injuries. Aquaporin 1 is involved in the release of spinal fluid. Aquaporin 9 is there. We don’t know what it does. The eye has several different aquaporins – each at a precise location. The kidney has several. It’s not like one system will have only one aquaporin.

George: To what extent is the proper management of water related to one’s health?

Peter: There are so many physiological pathways that are ongoing in our life that we don’t even think about them. And many of these involve aquaporins. While we’re just sitting here, each of us is releasing cerebral spinal fluid, bathing the surface of our brains, protecting our brains, we are absorbing cerebral spinal fluid, and those are both mediated by aquaporins. We are filling the orbits of our eyes with aqueous liquid, the surface of our eyes with a thin film of tears. These are again aquaporin-mediated fluid transports. Any time you can think of a fluid transport in the body, whether it’s humidification of airways, concentration of urine, or release of sweat, aquaporins are involved. They’re not involved in every physiological event of course. Contractions of our hearts are an electrical issue. They are not aquaporin-mediated. Neural transmission is not aquaporin-mediated. But they’re there in virtually every organ system…. We sometimes wonder if these proteins are always good to have around. By and large they are. In our brains, the fourth member of the family – aquaporin 4 – appears to be important in moving water which carries potassium after activation of neurons. Mice that have defects in that protein, or mislocalization, are actually vulnerable to epileptic seizures. So it seems to be important to the brain, in a basal state. On the other hand, after head injury, some individuals will sustain swelling of a damaged part of the brain, and since our skulls are fixed, there’s no room for swelling. Other areas of the brain will be compressed. So aquaporins mediate the movement of fluid into the brain. Defects in the aquaporins in kidneys will lead to defective water reabsorption, thereby causing release of large volumes of dilute urine – polyuria – bedwetting in children is an example of that.

George: What bearing does your aquaporin research have on malaria parasites?

Peter: Aquaporins and aquaglyceroporins are present in all life forms – even in Plasmodium falciparum and Plasmodium vivax, two parasitical organisms that cause malaria. We found that the aquaglyceroporin is necessary for full virulence of the parasite. “Full virulence” refers to the level of clinical stress. Half of mice infected with wild type Plasmodium berghei are dead in 11 days. Half of those infected with parasite lacking PbAQP – that is, the kind of aquaglyceroporin present in the malarial parasite Plasmodium berghei – are dead in 22 days. I do not expect this lead will produce new therapies, since all mice eventually die of malaria. But the approach may reveal pathways for potential therapeutic intervention. By the way, this research was published in our paper by Promeneur et al. Proc Natl Acad Sci 104: 2211, 2007.

George: Whether as a scientist or an outdoorsman, you seem to be fascinated by water.

Peter: Those who paddle the great rivers in Canada and explore the lakes of the Quetico Wilderness west of Lake Superior on the US-Canada border – all are curious about the natural world, and find it quite beautiful. Scientists who see something for the first time will usually do so because they are curious and notice things that other people don’t…. I think it’s so interesting to see different species in the wilderness – particularly mammalian species, the polar bears, which we were able to observe… My son and I with the assistance of a ranger from the York Factory were able to observe a mother and cub polar bear. And yeah, I guess we think what it takes to survive there, but just observing them was beautiful. I felt sort of like a mother bear myself, standing there with my son, who was eighteen years old at the time. Probably the bear, the cub, my son and I all bonded – we were sharing some sort of fundamental life bonding. I am planning a kayaking trip on Lake Superior this summer and off the coast of Labrador in 2010. By the way the photographs on this page are from Deaf Rapids – the final and most exciting cataract on the Seal River. It flows into Hudson Bay, north of Churchill, Manitoba.  My son Clarke is now 24 years old and is a sculptor working here in Baltimore.

Clarke and Peter Agre (Photo courtesy of Peter Agre)

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/agre-lecture.html
http://www.aaas.org/aboutaaas/

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This Q&A inaugurates two new features on Evidentia. First is the Health category – Evidentia will be returning to Health every third blog. And second is “Five Questions for …” – a short interview with an expert on a particular issue related to the environment, health or justice.