Target: mosquitoes

A mosquito can start tracking its victim from more than 100 feet away. Even at this distance, the insect can detect individual molecules of human sweat wafting through the air. Then the mosquito flies in and makes its annoying -- and potentially dangerous -- probe for blood.

To fight back, people have relied for decades on the chemical DEET , which is reasonably effective but has a sharp smell, feels sticky, and, especially at higher concentrations, has an unfortunate tendency to melt plastic, such as tents and plastic watches.

Now, as mosquito-borne diseases such as West Nile and Eastern equine encephalitis are threatening New Englanders, the science of insect repellents is experiencing something of a renaissance.

Just last year the federal Centers for Disease Control and Prevention declared that two additional products are effective repellents, including an odorless one on shelves now. Researchers are identifying other candidates. And an international group of scientists has begun a five-year, $8.5 million effort to find new repellents by unraveling the mysterious workings of mosquitoes' exquisite sense of smell.

The progress offers the promise of better protection for Americans, but scientists say that their more ambitious goal is to help in the global fight against diseases such as malaria, which kills 1 million people, mostly children, every year.

``It is a problem of just staggering dimensions," said John Carlson , a professor of biology at Yale University who is part of the effort, sponsored primarily by the Bill and Melinda Gates Foundation , to find new repellents by studying mosquitoes.

Making a repellent is a challenging problem. Researchers are looking for substances that a wide range of insects find repulsive but that don't smell foul to humans. The ideal repellent also needs to be low cost and safe and last for hours on sweaty skin.

DEET, the reigning king of repellents, was developed during World War II by the Army and the Department of Agriculture as a response to the ravages of malaria and other diseases in the Pacific theater. No one knows precisely how it works.

Many people still resist using DEET because of its smell or because of fears that it is toxic. (The scientific consensus is that it is safe for everyone over 2 months old.) A Harvard School of Public Health study released in 2003 found that only about half of people in high-mosquito areas had used a DEET repellent, despite the risk of potentially fatal diseases such as West Nile and Eastern equine encephalitis.

One of the new repellants, picaridin, is widely used in the rest of the world and hit US shelves last year, according to Mark Bauman , senior director of household products at Spectrum Brands , which markets several picaridin repellents. Picaridin, a synthetic chemical, does not have the sharp smell of DEET.

The other, oil of lemon eucalyptus, is only available commercially in the United States as Repel. Bauman said Spectrum Brands also offers a DEET product that uses a new manufacturing technique to temper the strong smell.

Picaridin is about as effective as DEET at repelling mosquitoes and, like DEET, repels a broad range of insects. Oil of lemon eucalyptus repels mosquitoes and deer ticks, but not other insects.

Even as these products become available, researchers are looking for new compounds that could perform better -- repelling more or different insects, lasting longer, or lowering costs. Some mosquitoes, for example, are not deterred by DEET.

The Agriculture Department has patented a compound after undertaking a project inspired by folk wisdom. A USDA botanist remembered how his grandfather had used leaves from a shrub, American beautyberry , to keep flies off of his animals. Based on this lead, researchers have found a number of botanical compounds that repel mosquitoes and have patented one of them, according to Jerome A. Klun , a research entomologist with the government's Agricultural Research Service .

Klun also has been involved with developing another compound, called SS220 , which is an effective repellent, he said, but has not yet undergone expensive toxicological tests.

At his New Haven laboratory, Carlson has developed a way of testing compounds using fruit flies, which are easier to work with than mosquitoes. His lab has identified the genes that allow both fruit flies and mosquitoes to smell. Each of these genes makes a different protein, called a receptor, that sits on the surface of a nerve cell in the insect's antenna. If a molecule in the air fits into a particular receptor, like a key into a lock, then that nerve delivers a signal, and the insect senses -- or smells -- it.

Carlson can genetically engineer fruit flies with a nerve cell that makes a mosquito receptor and then monitor that cell with a tiny electrode. Now he is working through a large library of compounds to see how each affects each mosquito receptor. He said he is interested in compounds that cause more activity, which could serve as lures in traps, and in compounds that dampen activity, which could serve as repellents.

Eventually, Carlson said, he hopes to generate a kind of smell map, which would show how each of the mosquito's receptors responds to a large number of chemicals.

He is sending promising compounds to collaborators who test them on mosquitoes in a laboratory, and, eventually, on mosquitoes in Africa. The five-year effort was started last year and is funded by the Grand Challenges in Global Health initiative, which gets most of its funding from the Gates Foundation.

If the effort is successful, the same technique could be applied more broadly. Agricultural pests also rely on their sense of smell to navigate the world. Perhaps, he said, it will be possible to develop new pest traps or repellents that will reduce the need for traditional pesticides. The more we know about how insects smell, he said, the more we can use this knowledge against them.

Gareth Cook can be reached at cook@globe.com.