Monday, April 9, 2001

Splicing the Sting Out of Bugs
Health: Genetic altering of insects and bacteria could prevent them from transmitting diseases such as malaria. But ultimate effects are unpredictable.

By AARON ZITNER, LA Times Staff Writer

     ATLANTA--Charles Beard's recipe for stopping the kissing bug, a tropical pest that kills 50,000 people each year, calls for ammonia, ink and guar gum. The result is an odorous goop that resembles the bug dung that, unpleasant as it may seem, happens to be a vital meal for young kissing bugs.
     But Beard adds something else to his faux feces that could prove to be even more noxious. It is genetically engineered bacteria that, once ingested, render the kissing bug unable to pass along its deadly disease.
     Now, a world that is already debating the safety of gene-spliced foods is about to meet a new class of genetically engineered organisms: modified bugs. Beard's creation is just one in a series of plans to turn insects and bacteria into warriors against disease and crop pests.
     This summer, scientists hope to start the first U.S. field tests on a gene-spliced insect--a version of a moth that chews through $24 million worth of U.S. cotton plants each year. Researchers are also trying to create mosquitoes that cannot carry malaria, which still kills 1 million a year, or West Nile fever, which is spreading across the United States. On the drawing board are ticks that cannot carry Lyme disease or Rocky Mountain spotted fever. Although the work is advancing quickly, questions remain about which U.S. agencies would monitor the new organisms.
     If released in the wild, scientists say, a properly engineered bug would spread its disease-defusing trait to its wild cousins, protecting a whole community or region. Public health officials say the bugs could be a crucial new weapon against often-deadly diseases such as malaria, which has built resistance to drugs and pesticides and has reemerged in places where it was once defeated.
     "The situation is awfully bleak out there," said Barry Beaty, an insect specialist at Colorado State University. "A lot of people are dying. We need new ways to respond to the problem."
     But if much of the world is anxious about genetically engineered foods, then modified bugs are sure to set off alarms as well. "Once you release an insect, it flies, and you can't control its distribution in the environment," cautioned Svata Louda, a University of Nebraska plant ecologist. "That's just one of the things that makes ecologists apprehensive about new versions of an insect."
     Critics also ask whether an engineered bug gene might mutate over time into something dangerous, or whether it would jump to an unintended insect species. Another question: Given that bugs travel freely, how many people in an area would have to give consent before gene-spliced bugs were released?
     Scientists say they have kept these questions well in mind over the last decade. But it is only now, thanks to funding from such heavyweights as the U.S. government and the World Health Organization, that they have accomplished enough in the lab to start thinking about conducting field tests that would produce some answers.
     In London this June, researchers from around the world will hash out basic scientific questions about field trials--where they might be conducted, what data should be collected and how they should be monitored. The meeting is sponsored by the WHO, the National Institutes of Health and London's Imperial College.
     At the same time, U.S. officials say they are taking some early, tentative steps to sort out which agency should make sure that the new bugs pose no harm to people or the environment.
     In some cases, jurisdiction seems clear. In July, for example, scientists from the U.S. Department of Agriculture and UC Riverside hope to start the first field test of a gene-spliced insect, the pink bollworm moth, a bane to cotton growers. Because the Agriculture Department itself has authority over plant pests, it has claimed jurisdiction over the field trial.
     The scientists want to place 2,350 gene-altered moths in a large mesh cage in an Arizona cotton field. Their long-term plan is to insert a lethal gene into the moth that would be passed to their offspring, wiping out the next generation of insects. But in their first field trial, the scientists will use only a marker gene and watch how it affects moth behavior.
     Robert Rose, a USDA official charged with assessing the scientists' plan, said he is considering the stability of the mesh cage and the fitness of altered moths to survive in the wild. Only sterile moths would be put into the cage, he said, a step that aims to diminish their effect on the environment if they escape.
     Federal jurisdiction is less clear over other bugs now being developed. A "talking points" document by the NIH says "there are gaps" in the existing law covering field tests.
     An antimalaria mosquito, for example, would not be considered a plant pest and therefore would probably not fall under USDA jurisdiction, Rose said. But officials at the Environmental Protection Agency say it is not clear that they would oversee the mosquitoes, either.
     Beard, a parasitic-disease specialist with the Centers for Disease Control and Prevention, says he consulted the CDC's own biosafety committee about his plans for the kissing bug. The bug has infected 14 million people in Central and South America with Chagas disease, which causes heart and digestive problems that kill 50,000 a year.
     Kissing bugs hide in the thatch huts common in the developing world, and they feed on the blood of people and animals. But the bugs cannot live on blood alone. They must also consume bacteria, Rhodococcus rhodnii, which they pick up from the dung of their parents.
     Beard has produced a gene-altered version of the bacteria and loaded it into his fake dung. Once the bug eats the dung, the bacteria attack and kill any Chagas disease agent that the bug is also carrying.
     "We've tested this concept in jars. Now we want to test it in a place that's more like the field," Beard said recently near his CDC office outside Atlanta.
     He swept open the door to a greenhouse to show his plan. Inside, he had built a protective mesh tent, and then a second mesh tent inside the first. Within that, he had built a small thatch hut, the kind that might be found in Honduras or Guatemala.
     Within weeks, Beard and his research partner, Dr. Ravi Durvasula of Yale University, plan to seed the hut with the fake dung, then release a handful of kissing bugs. They want to study how the altered bacteria flow through the kissing bug population. Like the moth researchers, Beard is using bacteria that carry only a marker gene, not the gene designed to attack Chagas disease. The tents are meant to stop the kissing bugs from escaping.
     Agriculture officials in California also have high hopes for gene-altered insects, as they continue the battle against the Mediterranean fruit fly.
     State and federal officials control the crop-eating pest by flooding the environment with sterile males, which crowd out wild males in the competition for females and yet produce no offspring. Officials release about 500 million sterile flies each week in Southern California, at an annual cost of $15.8 million. A similar program in Florida costs nearly $3 million.
     To sterilize the flies, officials use radiation, which also leaves the insects weak and diminishes their ability to mate in the wild. Researchers think they would have a more robust fly if they accomplished the sterilization through a genetic flaw. "If we could release, say, 75,000 flies per square mile instead of 250,000, that would save money," said Patrick Minyard, an official with the state Agriculture Department.
     Several researchers said bug scientists should take heed of the past problems with introducing new insects to the environment.
     A fly released in 1906 and for decades afterward to control the gypsy moth has also caused damage to 200 other butterflies and moths in the Northeast, said Jeff Boettner, an insect specialist at the University of Massachusetts in Amherst. The fly's wide appetite was known at the time, but researchers believed that was a good trait.
     Now, they want to preserve many of the targeted butterflies. "We change our views over time about what risk is and what is proper," Boettner said.
     Louda, the Nebraska researcher, said weevils released in the state to control an invasive, foreign thistle plant have also attacked a native thistle more than expected. This suggests that the present tools are "not sufficient" for evaluating what effect a new insect species will have on plants, she said.
     But Rebecca Goldburg of Environmental Defense, which questions the safety of bioengineered foods, suggested that people might find a certain amount of risk acceptable if it helped stop disease.
     "People have been more reluctant to take on environmental risk when we see the benefit of a product going to big biotech and chemical companies," she said. "Consumers in general are less concerned if sick people are getting the benefit."