SILVER SPRING -- Once each week, Wesley McCardell steps into a humid, brightly lighted room at Walter Reed Army Institute of Research and bares his legs to be bitten by dozens of mosquitoes -- the same type that transmits diseases and kills millions of people worldwide.
There is no danger that McCardell or the other volunteers will be infected with malaria, which kills 3 million people each year. Walter Reed's swarms are raised in laboratories and are disease-free.
But bites from these anopheles stephensi can still cause itchy skin.
"You can feel it biting, but it's not really that bad," said McCardell, a technician for the U.S. Agricultural Research Service in Beltsville.
Researchers at Walter Reed and ARS have been working together since 1997 to come up with an insect repellent that will be easier to sell than the DEET-based products now on the market.
But more than marketing is at stake. Researchers say that with increases in the spread of diseases transmitted by mosquitoes -- such as malaria and West Nile virus -- the work is about saving lives.
"Anything we can find that can protect a human being is a plus," said Lt. Col. Mustapha Debboun, program manager of the Department of Defense's repellants and personal protection program at Walter Reed.
DEET, or diethyl-meta-toluamide, is a key ingredient in most of the insect repellents sold in what is a $1 billion industry worldwide.
Commercially available since 1957, DEET is sold in 230 products made by 70 companies and is used by about one-third of the U.S. population each year to repel biting pests such as mosquitoes and ticks, according to the Environmental Protection Agency.
But there are concerns about its safety. Although most studies say DEET is safe, some recommend using it only in low doses because of evidence that high doses may cause health problems, particularly when used with other medications or insecticides.
In high concentrations, it also is a plasticizer -- meaning that if applied to the skin, it will soften plastic surfaces touched by those using it.
Jerome A. Klun, an ARS research entomologist working with Debboun, said they began work five years ago when they saw a need for a replacement for DEET. The chemical has been linked to eye irritations, skin rashes, skin swelling and, in a few cases, slurred speech, confusion and seizures.
"DEET fell out of favor," Klun said. "And with that, there developed a need for a new product that people would readily use."
Klun began examining a compound that contains piperidine -- found in trace amounts in black pepper -- that Beltsville scientists found in 1978 could repel mosquitoes.
As a first step, Klun said, researchers synthesized the original compound's four optical isomers -- molecules with the same chemical compositions that have different spatial arrangements.
They then applied each of the four synthesized compounds in liquid form to the legs of volunteers, who were then exposed to mosquitoes in a series of lab tests.
The repellent developed by the team's research -- a clear liquid with a slightly fruity scent -- was shown to be three to four times more effective than the original compound, the researchers say. The compound, known as SS220, is just as effective as DEET and probably safer, they say.
Klun hopes to publish a paper on the results in the Journal of Medical Entomology.
The Agricultural Research Service and the Army have worked together since World War II on insect repellents and other measures to keep troops healthy in overseas climates. But the researchers are aware their search for a new repellent is timely.
Malaria was diagnosed in two Virginia teen-agers this summer. In what were rare cases of infection originating in the United States, malaria-infected mosquitoes also were found this fall in Montgomery County, a first in Maryland in more than 20 years.
West Nile virus, which arrived in the United States in 1999, caused 201 deaths nationwide and two confirmed deaths in Maryland this year, according to state and federal health officials. Another five Maryland patients with West Nile died of causes that have yet to be determined, state health officials say.
Although DEET is effective at preventing insect bites, studies have questioned its safety.
A 1996 study of Persian Gulf war veterans published in the Journal of Toxicology and Environmental Health concluded that DEET, combined with other chemicals soldiers used, may have contributed to the diverse group of physical complaints -- mood changes, muscle and joint pain, skin rashes and diarrhea -- that became known as Gulf War Syndrome.
Mohamed B. Abou-Donia, a professor of pharmacology at Duke University and co-author of the study, said he believes DEET should be used only occasionally, in low concentrations and not in combination with any other form of repellent or treatments. He also wouldn't recommend it for pregnant women or young children because too little is known about its effects on the unborn and the young.
"Obviously, when used occasionally, it probably is safe," Abou-Donia said. "But there is much about it that we don't know."
But most studies, along with the EPA, say that DEET is safe if used as directed.
A study published in the July issue of the New England Journal of Medicine reported that DEET is both safe and effective, noting that the EPA reviewed the accumulated data on DEET and found that it "does not present a health concern."
Klun said toxicology tests on SS220 being conducted at Aberdeen Proving Ground indicate their compound is safe. He said Army scientists have completed about half of the tests needed to win EPA approval for commercial use.
Klun and Debboun say they hope to form a partnership with a private firm and help develop a repellent that will replace DEET by 2006.
"There's a great deal of potential there," Klun said.
The mosquito-biting research at Walter Reed is a follow-up to verify the initial lab work Debboun and Klun did in a controlled experiment.
McCardell and the other volunteers in the study arrive each Tuesday morning and use markers with washable ink to draw a series of rectangles, each about an inch in diameter, on their bare thighs.
Then they coat portions of each marked-off area with the experimental repellent or other repellents currently on the market.
Each group of rectangles on the volunteers' legs is then covered by a Plexiglas module about the size of a breadbox, which is made up of six smaller cells, each containing five mosquitoes. The mosquitoes are released through a trap door in each cell, giving them access to the volunteer's skin.
The effectiveness of each repellent is determined by comparing the number of bites on the treated skin with those on a control patch of skin with no repellent.
"If the repellent works, the insects just won't feed," Klun said.
McCardell doesn't mind serving as an unpaid guinea pig for the study. He said that he is no stranger to insect bites, having been raised in Brewster, Ohio, a city on the Ohio River that he recalls as being a haven for mosquitoes in the summer.
McCardell says that he has become something of an expert when it comes to mosquito bites.
"Different mosquitoes feel different when they bite," he said. "These mosquitoes aren't so bad."