The Forever Enemy
August 27, 2009 |  by Michael Anft

Malaria kills more than one million people worldwide each year, most of them young children. Backed by new money and renewed interest in stopping this eternal killer, researchers at Johns Hopkins are working on several fronts to stop it. Their main experimental subject: the bloodthirsty mosquito.

She comes out at night, flying out of woods and swamps in search of a suitable landing spot. When she finds one, she plants all six legs on uncovered flesh and bends her body forward. She hunkers down and maneuvers her spike of a snout into position. She bores that spike, a complex package of micro-machines—serrated tools for cutting, pumps for moving liquids—through the epidermis, then punches it through a thin layer of fat. In short order, she drills the tip down into tiny capillaries, then taps them, sucking blood in the name of future generations.

If she’s not interrupted, the female of the mosquito genus Anopheles will draw in the lifeblood that will nourish her eggs for up to 10 minutes, taking in more than twice her body weight. While she engorges herself, the Anopheles will dribble some saliva into the hole she’s made to keep the flow of blood from clotting. In the case of millions of African mosquitoes called Anopheles gambiae, the blob of spit isn’t the only thing left under the skin. A. gambiae serves as a “vector”—an organism that transmits dangerous germs and diseases—for Plasmodium falciparum, the most deadly of the handful of parasites that cause malaria. What means life for mosquitoes and parasites too often adds up to death and debilitation for the humans who take part in the three-way transmission cycle—a devil’s trinity that leads to up to half a billion malaria infections annually and between 1 million and 2 million deaths worldwide.

As the expectant mosquito feeds on human blood, Plasmodium cells living in her salivary glands leak into the human bloodstream. It takes tens of thousands of these cells to cover the head of a pin, but only five or so to infect a human. Once inside the body, the parasites spend 10 days or more encamped in the liver, then begin infecting red blood cells, their population exploding before the human immune system gets wind of them. They cause chills, high fevers, draining fatigue. In the worst case—in a disease commonly called cerebral malaria—parasites destroy so many red blood cells that there aren’t enough left to run the body’s functions, and they attack the brain. Neurological damage, coma, and death often follow.

During the past century, medical researchers have approached malaria with the same combination of exigency and diligence as they did when they took on the specters of polio, smallpox, and tuberculosis—but with decidedly less in the way of results. It continues to vex, even during an age marked by the relentless march of medical discoveries. As major infectious diseases go, malaria has been the trickiest for the longest. Some scientific historians theorize that animals that predate humans, including dinosaurs, may have suffered from the disease. Others contend that half of all humans who have ever lived died from malaria—and that it may always be part of the disease landscape. Efforts to wipe it out by spraying pesticides, including DDT, or by developing better and cheaper drugs and vaccines have been thwarted by the wiliness of mosquitoes and the parasite’s rapid reproductive cycle, which allows Plasmodium to mutate beyond the ability of the drugs that would fight it.

An infusion of fresh money has bolstered science’s arsenal for fighting the disease—and yet many observers still consider malaria hopeless. Others are merely amazed by its many, ever-changing faces. “The disease is one thousand times more complicated than I had thought,” says Peter Agre, Med ’74, director of the Johns Hopkins Malaria Research Institute and a Nobel laureate in chemistry. “I’m humbled by my ignorance of it.”

Deep-pocketed businesspeople, including Bill Gates, have lavished more than a billion dollars on the cause in the past few years, hoping to put an end to that ignorance and stop malaria at ground zero: sub-Saharan Africa. Gates’ foundation has given more than $200 million to Johns Hopkins strictly for malaria research. And a $100 million gift made eight years ago by New York Mayor Michael Bloomberg, Engr ’64, to the School of Public Health that bears his name led to the creation of the Malaria Research Institute.

A new cadre of scientists there has fanned out across disciplines to unlock the timeless secrets of a hardy affliction. They have worked to develop less dangerous and less expensive diagnostic tests for malaria, built a field station in rural Zambia where they can study the disease close up, and laid the groundwork for a deeper, yet more basic scientific approach to “malariology.” By painstakingly assembling pieces of the puzzle surrounding the basic biology of mosquitoes and parasites, Johns Hopkins scientists hope to find new ways to battle the disease, including genetically engineering a cure into the mosquito itself.