Globe-trotting insects spread resistance.

Much to the frustration of scientists, some fruit flies scamper around on insecticide crystals designed to kill them. But now entomologists have identified and described the genetic mutation that appears to make the insects resistant to cyclodiene insecticides.

That mutation, consisting of a single change in the chain of nucleotide bases that make up the flies' DNA, may be responsible for up to BO percent of all insecticide resistance, says Richard H. ffrench-Constant, an entomologist at the University of Wisconsin-Madison. Furthermore, because scientists found the identical mutation in 158 different strains of fruit flies collected from five continents, ffrench-Constant suggests that it arose in one location and then rapidly spread worldwide.

This genetic change alters the structure of the GABA receptor, an important protein that prevents nerve cells from firing, ffrench-Constant and colleagues report in the June 3 NATURE. Cyclodienes normally bind to this receptor, blocking the passage of inhibiting messages; as a result, the overexcited insect goes into convulsions.

The mutation prevents the cyclodienes from attaching, so the receptor functions normally - even when the fly is doused with the insecticides.

The theory that the mutation spread globally from one population is proving controversial. Such dispersal would entail not only transporting the fruit flies, but also their ability to establish themselves and to predominate over local species, argues entomologist George P. Georghiou at the University of California, Riverside. Insecticide resistance could give alien insects a selective advantage over nonresistant natives, he adds.

Precedence exists for this. Scientists reported in 1991 that a nonmalarial, insecticide-resistant mosquito had migrated worldwide from its African home. Although insects have been transported in ship cargoes in the past, "we are more concerned today because of greater traffic and the phenomenon of resistance:' says Georghiou. The prospect of global pest migration may call for stricter quarantine measures in world commerce, says Richard T. Roush, an entomologist at Cornell University

A single origin is indicated by the mutation itself and by the noncoding genetic material surrounding the mutation, both of which are remarkably similar in all resistant strains, ffrench-Constant says. However, Roush, who uses a different genetic technique to examine the mutation, asserts that there are insufficient data to determine whether the resistance mutation has one origin. In addition, the receptor probably has a limited number of ways it can mutate to become resistant without also killing the insect, making the possibility of multiple origins more likely, Roush says.

Regardless of the mutations beginnings, its identification should help in insecticide development, the report notes. Since insecticides were first used in the 1940s, over 600 insect species have developed resistance, leading chemists to constantly search for new products. Insecticide resistance now costs an estimated $1.4 billion a year in crop losses in the United States alone.

Cyclodienes are widely used in the developing world, and even though U.S. farmers have not used them in 30 years, resistant insects still inhabit fields and orchards. New insecticides that target the same genetic site as cyclodienes could be automatically impotent in these insects. Now, by understanding the GABA receptor mutation, chemists can avoid developing compounds that bind to this site, says coauthor Alison E. Chalmers, a geneticist with the Rhone-Poulenc Ag Company in Research Triangle Park, N.C. This approach might have avoided the problems of insect resistance to pyrethroids, newer chemicals that target the same genetic site as the U.S.-banned insecticide DDT. Cotton crops today suffer huge losses because of DDT-resistant caterpillars, which also proved pyethroid resistant.

In the long run, ffrench-Constantwould like to transfer the insecticide-resistant gene into beneficial insects, such as bumblebees. Such transgenic bees could then survive insecticide exposure. Georghiou notes that evidence of the mutations rapid spread should further "stimulate interest in alternative methods, the integration of chemical with nonchemical controls." This would reduce insecticide use, thereby delaying the onset of resistance in additional species.

In the near term, ffrench-Constant plans to clone the GABA receptor gene in pest insects, where he expects to find the same mutation that popped up in the fruit fly.