Breaking the Cycle

By Michael Leahy
Sunday, October 8, 2006

TO REACH THE SPECIAL MOSQUITOES, an Army researcher like Gray Heppner must walk through seven heavy doors off a corridor at Walter Reed Army Institute of Research in Silver Spring. The mosquitoes, called Anopheles gambiae , are behind that last door, in meshed cartons. They don't fly much in their confined space and appear quite benign in this room where everything feels unremarkable, even the high heat and humidity, which are meant to mimic the sweltering environs in which the anopheles thrives.

Only the unusual routines of the area, known as the insectary, belie the air of ordinariness. No two doors out of these seven are ever to be opened at the same time -- this to guard against the escape of any mosquitoes, which have been infected with malaria parasites by Army lab technicians. Just in case, small plastic bags, illuminated by an icy-blue light, hang between all the doors -- mosquito traps guarding against the remote chance that an anopheles gets loose. If a fugitive mosquito ever made it beyond all seven doors, it would be an unprecedented event, an entomological feat akin to an escape from Alcatraz.

By conservative estimates, malaria claims more than 1 million lives globally each year, 90 percent of them in sub-Saharan Africa, the vast majority children. Young survivors are frequently left with cognitive damage that can cause them to fail at school and work. African adults, while having lived long enough to gain some immunity against malaria's worst effects, often lose weeks of work while recovering from the disease. Western economists estimate that malaria results in an economic loss of $12 billion annually in Africa, the continent least able to foot the bill for fighting the disease.

But in the consciousness of the average Westerner or in the official discourse of a governmental body such as the U.S. Congress, the scourge hardly registers -- a relic, like polio. Although affecting regions that make up about 40 percent of the planet, malaria is overshadowed by diseases that directly touch the West, such as AIDS, and worries about possible pandemics, such as bird flu. With U.S. government funds scarce, Heppner is vying with rival malaria vaccine researchers -- and rival approaches to fighting the disease -- for public attention and private research dollars, most of which come from philanthropic organizations with deep pockets, such as the Bill and Melinda Gates Foundation. As a colonel and the chief of Walter Reed's department of immunology and its malaria vaccine research program, Heppner's ultimate ambition is simple: Create a vaccine that will prevent infection and eradicate malaria in the way that Jonas Salk's vaccine wiped out polio in most places.

But malaria vaccine research must always compete for funding against more conventional methods for battling the disease, such as antimalarial drugs and insecticide-treated bed nets, as well as methods still in development -- including dreams of sterilizing mosquitoes and of making a vaccine to stop the transmission of parasites from an infected human to a healthy mosquito, thereby breaking the cycle of disease.

This particular summer day marks the launch of what Heppner estimates to be the 30th clinical trial of a malaria vaccine since the Walter Reed program began in 1983. There have been a lot of colossal failures. In the early '90s, not long after he accepted a position in the malaria program, an eager Heppner volunteered to take a shot of a prospective vaccine and allow himself to be bitten by an infected mosquito, as part of a clinical trial. The vaccine failed, and Heppner contracted malaria, after which an antimalarial drug treatment left him disoriented and suffering from nightmares for a couple of days.

But vaccine makers, like oil men and gold diggers, never stop dreaming. Sixteen years after he started at Walter Reed, Heppner's hopes are higher than ever in the wake of promising test results from a vaccine called RTS,S, which Walter Reed helped develop with a prominent pharmaceutical company, GlaxoSmithKline Biologicals.

In this latest clinical trial, Heppner and other Walter Reed researchers will evaluate another vaccine candidate, different from RTS,S and not yet publicly identified. Its potency in mice has fueled confidence at Walter Reed and brought 28 visitors to the insectary. They are the clinical trial's volunteers, drawn in some cases by newspaper advertisements. Others were recruited by Walter Reed personnel or heard about the trial from friends. According to Walter Reed staff members, 22 of the 28 participants have already received two doses of the vaccine.

The vaccine's inventor, David Lanar, is an Army researcher who has worked for years with others at Walter Reed to make the vaccine ready for clinical trials. Their efforts have cost several million dollars, in a field where government funding is hard to come by; one contributor, the Department of Defense, annually allocates $8 million (about .002 percent of the Defense budget) for malaria vaccine research, equally divided between Heppner's Army unit and a similar Navy group. The stakes of this trial feel high to Lanar. "There are only so many chances that [a researcher] will get in a career to make a vaccine," he says.

He has been in this position before. In the early '90s, he created another vaccine, NYVAC-7, whose possibilities thrilled Heppner and others during early testing. Lanar fleetingly pondered the possibility that he might become famous: The Man Who Cured Malaria. "I could see myself on the cover of Science [magazine]," Lanar remembers, smiling. But then the vaccine failed. "It was pretty devastating."

Now waiting on the test of his new vaccine, Lanar is no less daunted by the challenge. "The parasites have learned how to withstand desperate attempts to eradicate them for thousands of years," he says. "They've survived the attempts of the body's [immune system] to wipe them out for millions of years."

Nearly all the volunteers know that human beings can be infected by four species of malaria parasites, the most dangerous of which, the one responsible for virtually all malaria deaths around the world, Plasmodium falciparum , is the parasite carried by the mosquitoes behind door seven. The volunteers understand that if the vaccine doesn't work, even those treated quickly are likely to experience a few days of nasty flu-like symptoms that could include screaming headaches, high fever, chills and vomiting fits. Some admit to feeling spooked ever since they volunteered to be bitten by an infected anopheles.

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