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The glow worm of self-destruction

UCR Entomologist Thomas Miller works against the odds on a technique to make a pest exterminate itself.

by: Lisa Dunlap   (February 2000)

Scientists at UCR are working on a discovery that could change pest control in the 21st century.
By changing the genetic characteristics of crop pests so that they self-destruct, the need to use costly and often controversial chemical pesticides, baiting methods or disease-resistant plants could be eliminated.

Entomologist Thomas A. Miller (‘62, ‘67 Ph.D.) is working on the autocidal biological control (ABC) technique, termed the new frontier of pest management by scientists, government officials and growers alike. The revolutionary idea came a step closer to fruition when he and his colleagues broke new ground in spring 1998 by proving that they had altered the genetic composition of the targeted pest, the pink bollworm.

Miller, post-doctoral researcher John Peloquin and graduate student Steven Thibault were able to insert a gene derived from jellyfish that causes the pink bollworm to glow green when viewed at a certain illumination. While the gene itself is useful as a marker, of even greater importance was discovering a method for inserting the gene and turning it on once incorporated in the insect genome (genetic structure).

“This is the first confirmed report of the genetic transformation of a Lepidopteran insect,” said Miller, adding that his laboratory’s breakthrough preceded a similar result achieved by a large research team working with the silkworm in France and Japan.

Lepidopterans are butterflies and moths. The pink bollworm starts life as a pink caterpillar, which bores into cotton and related plants to feed on the seeds. After feeding, it emerges to complete development and then continues its life cycle as a small, brown moth, which then mates and lays eggs on the host plants again.

The pest is also one of the world’s most destructive insects to cotton.

Believed to have originated in Asia, the insect was first observed in the United States in 1917, when it began to infest cotton crops in Texas. Since then, it has spread throughout the South and is also present in Mexico. While the pink bollworm prefers to feed on cotton, it also will host on okra, kenaf and hibiscus buds. According to USDA estimates, some Asian countries with less developed pest management methods suffer as much as 20 percent loss of their cotton crops due to pink bollworm infestations.

“I’m really excited about (Miller’s) work. I’m about as high on this as I could possibly be because he has the best lab data I’ve seen,” said Robert T. Staten, (‘66 M.S., ‘70 Ph.D.) director of the Phoenix Plant Protection Center of the USDA Animal and Plant Health Inspection Service. “We hope to not only keep our collaboration strong and healthy, but to expand it.”

Staten received the first federal permit allowing interstate movement of a transgenic insect so that his facility can raise pink bollworms mutated by Miller and his colleagues. Currently the mutated insects at the Phoenix site are the source of research to determine if they can be used for biomedical purposes, including the production of a protein that is given to heart attack or stroke victims as an anti-coagulant.

But Staten envisions a day soon when Miller will have identified a “lethal gene,” or a gene that is mutated so that it causes the death of the insect. Then the Phoenix center plans to raise and release up to 7 million mutated pink bollworms each day into infested fields to spread the mutated gene throughout the pest population.

Staten presented statistics at a December 1999 meeting that estimates that the cost to eradicate the pest from 500,000 acres will be reduced from $31 million to $14 million if the ABC technique is implemented.

The savings include a drop in expenses associated with pesticides; genetically mutated crops, including Bt cotton; pheromone traps and other current control methods that include additional post-harvest handling of plants. In addition, the genetic mutation will reduce by at least a factor of four the mortality of pink bollworms at the Phoenix center, which now sterilizes the pink bollworm using an often-damaging cobalt irradiation procedure.

Releasing sterilized insects currently is the primary method for area-wide suppression in California and Arizona.

“These are only speculations, but they are speculations based on years of experience as well as existing data,” said Staten.

An insect physiologist and toxicologist who receives the majority of his funding from the California Cotton Research Board, Miller developed the idea of the ABC technique about five years ago after working for two decades with farmers to measure insecticide resistance and to develop new control methods for the bollworm. He invented a method of measuring insecticide resistance in the field that is used for resistance monitoring, especially in whiteflies.

Another innovation was the discovery that the pink bollworm produces a unique protein as it entered its inactive period, known as diapause. A test developed by postdoctoral researcher Mohamed Salama from Egypt could then be used by farmers in the field to test if the insects were entering diapause rather than pupating, an indication that there will be a significant infestation problem by early spring.

“That revolutionized the diapause measurement,” said Miller. “Before our discovery, the traditional method was to hold the insects for a month and wait and see if they would pupate or not.”

Miller also invented a combination weather station and automated pheromone trap, which used sex hormones to attract males. The weather data showed that “trap catch” was entirely determined by wind speed and temperature in the middle of the night. His research, conducted in commercial cotton fields near Blythe, explained a phenomenon that had bewildered pest control advisors: why the daily number of male adult moths varied widely when monitoring pheromone traps for infestations.

While studying the insect, Miller was asked by Staten to improve the sterile insect technique used on the pink bollworm. This called for finding a conditional lethal gene, developing a genetic transformation system and finding a marker gene that could be used to breed true lines of conditional lethal insects. At the time of Staten’s request, none of these three elements were known or had been done.

After being unable to find or develop a lethal gene from the diapause protein gene, Miller followed a suggestion from UCR Biology Professor Karl Fryxell to investigate the use of Notch genes, which are present in all animals and serve to regulate an organism’s development. Soon after, Miller’s associate Leo Schouest (‘84 Ph.D.) demonstrated that mutant Notch genes in the vinegar fly could cause a temperature-sensitive lethal condition.

The struggle to improve the sterile insect technique switched into high gear, with the critical breakthrough occurring when Thibault invented a functional transposable element, a promoter and a marker gene combination that allowed genes to be inserted into the pink bollworm.

“The research he’s working on is the best chance we have of eradicating -- not just controlling or suppressing but eradicating -- this pest,” said John R. Benson, a farmer in Brawley.

Benson said Miller has impressed him as an academic willing to meet with farmers to develop useful technologies and solutions to their problems.

“The Imperial Valley seems to have things pretty much under control, but we’re only 30 miles from a disaster,” he said. “What do we do if a problem develops in Mexico?”

Benson shares Staten’s belief that mutating the pink bollworm will dramatically improve life for growers battling cotton’s worst pest.

“Some people have complaints about pesticides and others have worries about transgenic crops like Bt cotton, but what could they have against an insect designed to kill itself?” asked Benson.

The transgenic procedures developed by Miller’s laboratories are now used by the Phoenix center for its research with both the pink bollworm and the Mexican fruit fly. The breakthroughs have led to the first steps in obtaining patents and letters of intent regarding possible biomedical applications for the work.

“Genetic transformation is incredibly risky work, and not everybody can do it,” said Miller. “We began five years ago, and we’re just getting started.”

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