Benign by design

U researchers look for new, less toxic mosquito repellents

New research will look at approaches to combating mosquitoes that are less toxic than DEET and less severe than calling in the SWAT team.

By Pauline Oo

Published June 19, 2004; updated on June 22, 2004

In a mosquito's eyes, I am a breakfast, lunch, and dinner. There is something in my blood that draws these pesky little buggers to me like bees to honey. I couldn't live without DEET. And apparently, neither can around 97 million other people in this country. According to the U.S. Environmental Protection Agency (EPA), about one-third of the U.S. population is expected to use DEET every year.

Currently nearly 70 different companies produce roughly 230 EPA-registered products containing DEET (N,N-diethyl-meta-toluamide). Formulations for topical applications--like insect repellent--range from 4 to 100 percent DEET. The EPA says that the insect repellent "will not pose unreasonable risks to human health or the environment" as long as we "follow label directions." Yet, there is room for improvement--perhaps healthier alternatives--as evidenced by the $1.4 million grant from the U.S. Department of Agriculture to University researchers to find new synthetic repellents through computational chemistry.

Basak and his team know that an overdose of what attracts mosquitoes is the best way to keep them away. At low concentrations DEET attracts mosquitoes, but in higher doses it repels them; and in even higher quantities, it kills them.

"We are interested in developing a new generation of chemicals that will be less toxic but more effective--what we call 'benign by design' chemicals," explains Subhash Basak, project leader and a mathematical chemist with the Natural Resources Research Institute (NRRI) at the University of Minnesota, Duluth. "To do this, we must understand the biological mechanisms of how these chemicals work."

What Basak and his team know is that an overdose of what attracts mosquitoes is the best way to keep them away. And that's exactly what DEET provides, says Basak. At low concentrations it attracts mosquitoes, but in higher doses it repels them; and in even higher quantities, it kills them.

What the researchers are hoping to do is to find something as effective as DEET, but not as potentially harmful to humans. They must sieve through tens of millions of possible chemicals and chemical combinations to locate a substance similar to DEET in repellent quality. And they will do this "in silico," or in the computer.

Basak has created a software program that can scan a virtual chemical library for chemicals with the right structures and narrow the number of possibilities to something manageable for the researchers to test in the lab.

"We're looking for a chemical like DEET, only better, so we screen the DEET neighborhood of chemicals and look for dissimilar derivatives of the same class," explains Basak. "Then we have chemicals that are similar but dissimilar enough to be better." Multi-national companies like Glaxo and Upjohn (now part of the Pfizer Corporation) have successfully used his program to simplify the process of finding new drugs and chemicals.

"When DEET was first discovered, the scientists were only able to sample a limited number of compounds along with it," says Basak. "Today we can do a computational evaluation of 100 million chemical structures--very quickly and inexpensively."

Basak and his fellow researchers will work with BASF Corporation, one of the largest chemical companies in the world, on this five-year project. Other collaborators are the USDA, the Uniformed Services University of the Health Sciences, the Walter Reed Army Institute of Research, and the Kasetsart University of Thailand.