For 30 years or more, farmers have been spraying bacterialtoxins synthesized by Bacillus thuringiensis (Bt) as theirinsecticide of choice to protect crop plants.

Now, several biotechnology companies are on the verge ofbringing to market plants genetically transformed to carry thegene for the bug-killing Bt toxin. This "organic" approach topest control should further reduce the need for expensive,polluting chemical insecticides, and Bt's wide spectrum of toxinvarieties targeted at specific insects should solve the pestproblem once and for all, right?

Wrong.

In 1985, USDA entomologist William H. McGaughey discoveredthe first insect resistant to Bt, the Indian mealworm Plodiainterpunctella, which infests granaries and bins where driedfoods, from grain to nuts, are stored. "Insect resistance to thespore-crystal protein complex of B. thuringiensis, the mostwidely used and intensively studied microbial insecticide, hasbeen presumed to be unlikely to occur," he said.

More recently, entomologist Mark E. Whalon, who heads thePesticide Research Center laboratory at Michigan StateUniversity, found that the Colorado potato beetle, for whichthere is no chemical control whatsoever, developed "more than200-fold resistance to Bt by its 20-something generation"under laboratory selection conditions. This ominous report, hetold BioWorld, has not yet been published. Many other croppests are also showing Bt resistance.

Whalon and McGaughey are co-authors of a paper in lastFriday's Science, "Managing Insect Resistance to Bacillusthuringiensis Toxins." It warns: "Although Bt genes arecurrently used to transform plants in order to impart pestresistance in several major crops, the value of this approachcould be seriously diminished by widespread development ofresistance to Bt toxins."

Their report is the result of a three-day conference convenedlast January by the USDA's research services to evaluate thescientific potential for pest resistance to Bt delta-endotoxins,and explore resistance management strategies. That council ofwar against insect crop pests made several recommendations togovernment, academia and industry, but so far, saidMcGaughey, "industry, from my perspective, has beensomewhat slow to respond to this resistance thing. I thinkmuch of the scientific community just did not want to believethat resistance was a problem."

Michael Dimock, manager of entomology at Crop GeneticsInternational Corp. in Hanover, Md., "begs to differ." Dimockchairs the Bt Management Working Group, a consortium of 13companies formed in 1988 to plot countermeasures againstinsect resistance (see list). "Our group is having a workshopnext February," he told BioWorld, "to attack the issue fromindustry's standpoint." Dimock noted that "scientific work isflourishing, but as far as any kind of coordinated attack orrecommendations, Monsanto is pretty vocal in putting forwardtheir plans for resistance strategy, to coincide with theircommercial release of transgenic cotton, potato and cornproducts." Monsanto research entomologist Steven R. Simsconfirmed this strategy to BioWorld.

Dimock's group will invite academic experts to its Februaryconclave "to help us draw a circle around the problem -- whatwe're able and willing to do, and whose responsibility it is to dowhat in this arena."

Among the resistance-confronting strategies and tactics thatMcGaughey and Whalon suggested in Friday's Science:

-- Deploy mixtures or sequences of unrelated Bt toxins (thebacterium puts out at least 34 varieties) either by multiplecloning into transgenic crop plants, or mixtures of separatelycloned seed lines;

-- cultivate a reserve supply of Bt-susceptible (non-resistant)insect cohorts to slow the evolution of resistance in pestpopulations. These vulnerable reserves might be billeted inrefuges, such as rows, fields or entire regions of untreatedcrops. Susceptibles mating with the relatively rare homozygousresistant individuals could dilute or limit the resistantpopulations.

"Transgenic plants," Whalon emphasized, "must be deployedwisely or else lose genes to this insect-resistance phenomenon.The plants should be modified to release their Bt only at statedtimes."

Once insects acquire resistance, he told BioWorld, "that's not theend of the game. Because many insect resistance genes arerecessively inherited, we may be able to restore susceptibility."

And a final upbeat note: Bt toxin is also sprayed to controlmosquitoes, the Science paper reports. "Resistance levels in twomosquito species, Aedes aegypti (which transmits the virus ofyellow fever and dengue) and Culex quinquefasciatus (a non-pathogenic nuisance) ... were relatively low."

Is it time for the crop toxicologists to look beyond Bacillusthuringiensis to some new source of insecticidal toxin genes?Some researchers are beginning to consider scorpions or blackwidow spiders, whose venom kills insects. Most stick with Btbecause its genes lie on plasmids, and therefore are readilymanipulated.

What's in it for the bacterium itself, said McGaughey "no oneknows." People have speculated, he added, that Bacillusthuringiensis employs its arsenal of crystal-protein toxins toslay the insects in which it resides and grows, "to allow it tocomplete its life cycle."

BT MANAGEMENT WORKING GROUP

These 13 companies constitute the Bt Management WorkingGroup, (BMWG) to resist insect resistance to Bt toxin:

Abbott Laboratories of ChicagoBacTec Corp. of HoustonCiba-Geigy of Research Triangle Park, N.C.Crop Genetics International of Hanover, Md.E I. du Pont de Nemours of Wilmington, Del.Ecogen of Langhorne, Pa.Entotech, Inc. of Davis, Calif.ICI Agrochemicals/ICI Seeds of Bracknell, Berkshire, EnglandMonsanto Agricultural Co. of Chesterfield, Mo.Mycogen Corp. of San DiegoPioneer HiBred International of Johnston, IowaPlant Genetics Systems of Ghent, BelgiumSandoz Agro, Inc. of Palo Alto, Calif.Michael Dimock, manager of entomology at Crop GeneticsInternational Corp. also cites the following non-members whoare conducting insect resistance research:Agracetus of Middleton, Wisc.Agrigenetics of Eastlake, OhioAsgrow Seed of Kalamazoo, Mich.DowElanco of IndianapolisNorthrup King of Golden Valley, Minn.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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