Terminator Genes

When you park in downtown Scott, Mississippi, population 200, you can leave your keys in your unlocked car and still expect to drive home. Outside of Scott, people don't know much about the town's primary employer, the Delta and Pine Land Company, a seed company that specializes in cotton. But that will probably change, because Delta and Pine Land is working on something of a time bomb in the world of farming—a terminator gene. More than 70 percent of the acreage of soybeans and cotton in the United States supports genetically modified varieties. The first genetically engineered crop plant, the Flavr-Savr tomato, had a fish gene that extended its shelf life. But the innovation failed in the marketplace. Plants equipped with a terminator gene grow up just like other plants, with one crucial exception -farmers can't grow anything from the seed they produce. This feat of genetic engineering has caused a world-class ruckus, and renewed commercial interest in the trait is sure to put the town in the spotlight. ¦ Depending on whom you talk to, the terminator gene—known by its makers as the Technology Protection System—is either a great safeguard against possible hazards in the brave new world of biotechnology or a threat to the world food supply. Ever since Homo sapiens began farming about 12,000 years ago, people have relied on seed saved from one crop to sow the next season's bounty. Yet since World War II, that practice practically disappeared in developed countries as seed companies offered new and improved varieties to farmers every year. These new varieties were created by selectively crossing, or hybridizing, plants to maximize traits such as seed production and pest resistance. Now seed scientists can do better than hybridize—they can plug new genes, even those from other organisms, straight into plants. And many biologists and consumers fear that these imported traits could spread unintentionally to other plants. What if, for example, a truly obnoxious weed developed the pest-fighting traits of a genetically modified corn plant? Would it take over fields across the world? Melvin Oliver thinks the terminator is the solution. He is the plant biologist who spearheaded the gene's development at a U.S. Department of Agriculture research station in Lubbock, Texas, in the mid-1990s. Oliver points out that any genetically modified plant that also carries the terminator would be unable to beget any progeny—either through its seed or its pollen. "We thought we were doing the right thing at the time," he says, "and I still think it's the right thing." But joint patenting of the terminator technology by Delta and Pine Land and the U.S. Department of Agriculture in 1998 sowed international rancor. Advocates of subsistence farmers, who depend on harvested seed for the next season's planting, said the system would force even the poorest farmers in developing countries to buy new seed each season. The scope of the problem is unimaginably vast: More than 1 billion people rely on saved seed in developing countries each year. Two-thirds of the population of sub-Saharan Africa subsist on small, low-production farms. Critics contend that once terminator technology takes hold, it will become tied to every other improvement in plant development, so farmers who are unwilling or unable to pay for new seed will be stuck with outdated, inferior varieties. "It's climb on the terminator platform, or stay on the sidelines with your old technology and hope you survive," says Pat Mooney, executive director of the ETC Group, an advocacy organization in Winnipeg, Manitoba. Even if terminator-seed purchases are subsidized, he says, dependence on them could become devastating. "When the foreign aid dries up, terminator companies back out, leaving no grain." Persuaded by such arguments, India has banned terminator genes. The world's largest network of agricultural research institutes—the Consultative Group of International Agricultural Research—recommended not using the system in their programs. The biotech giant Monsanto backed off a proposed purchase of Delta and Pine Land and publicly vowed it would never market any genetic plant-sterilization method. But activists say terminator-like applications from big seed companies are descending on the U.S. Patent and Trademark Office like a plague of locusts. And Delta and Pine Land is pressing ahead with plans to put terminator genes in cotton. "We're still working toward commercialization of the technology," says Harry Collins, vice president of technology transfer. "We never stopped." Oliver and his colleagues began brainstorming the terminator project in the mid-1990s, before most genetically modified seed had even been marketed. Even then it was clear that the possibility of unintended genetic drift could create image problems for engineered crops. "Most plants don't outcross very effectively, but we wanted to make sure it didn't happen at all," says Oliver, who keeps a poster of the namesake Arnold Schwarzenegger hero on his office wall. There was also a need to recoup the millions of dollars spent on engineering genes that would improve the pest resistance and herbicide tolerance of major crops such as corn and soybeans. Sterilizing the plants that bore these traits would guarantee seed suppliers repeat sales. Seed saving isn't just a third world custom: The practice persists even among wheat farmers in the American heartland. Curbing a plant's reproductive power proved to be a far more complicated prospect than other genetic modifications. Creating new traits typically involves coaxing the desired gene—along with the snip of DNA that controls it—into cultured leaf, stem, or root fragments. The transformed plant tissue then regenerates into whole plants that pass along the foreign elements in their seed. A: The tufted bits of green are tissue from the stems of very young cotton plants. To create plants with the plant-sterilizing "terminator" trait, researchers put the required genes into a bacterium that will then infect this developing tissue. The next step is to select plant cells that carry the desired genes and cultivate them. B: The resulting seedlings grow up to be plants that bear seed carrying the terminator trait. But the terminator trait is dormant until the seed is exposed to an activating agent, tetracycline. To implement this system commercially, the seed companies would cultivate plants bearing the terminator trait normally and harvest their seed. The plant-sterilizing trait, however, would be activated only in seed that is sold to farmers. Oliver's terminator system follows this protocol, with a few twist. Instead of one foreign gene, it uses three from three different organisms to yield plants that produce seed with the terminator trait. But the terminator system is dormant until this seed is soaked in the antibiotic tetracycline. Tetracycline exposure triggers a byzantine sequence of molecular events that allow the treated seed to flourish yet halt the germination of seed in the next generation. In other words, the treated seed can produce seed, but this new seed, while preserving its nutritive value and other commercially relevant attributes, can't produce new plants. Likewise, any seed derived from plants fertilized by terminator pollen won't germinate. "The whole system is a dead end," Oliver declares. "The seed goes nowhere." In 2000 Oliver showed that his system worked in tobacco plants, a less complicated test bed than cotton. He says that the terminator blocked germination in 100 percent of his tobacco seed. Last year Delta and Pine Land took over the research with the aim of adapting it to cotton, the company's specialty. The adaptation hasn't been easy, Collins admits, especially since Delta and Pine Land is trying to develop induction schemes that don't involve tetracycline. Collins says Delta and Pine Land also plans to license the system to other companies for use in wheat, rice, and soybeans. He claims the terminator trait could inspire more effort to improve these species as well as third world "orphan" crops such as cassava and pearl millet that don't have much commercial allure. "We sincerely believe that this could be good for farmers in the Southern Hemisphere," says Collins. "We think this would help them to become production farmers rather than subsistence farmers." With nearly 150 million acres worldwide already given over to genetically modified crops, even some critics have conceded a need for a method that prevents possible genetic contamination, says Marshall Martin, associate director of agricultural research programs at Purdue University. In the latest figures from the USDA, he notes, 34 percent of corn acreage, 71 percent of cotton acreage, and 75 percent of soybean acreage is planted in genetically modified varieties. The risk these crops pose to neighboring crops and the natural environment has yet to be ascertained. Last year, claims that transgenic corn had spread its germ plasm to native Mexican maize devolved into a partisan tussle with no objective resolution in sight. Groups like ETC and the Environmental Defense Fund, however, oppose the terminator system. In addition to their concerns about subsistence farmers, environmentalists worry that the terminator gene could castrate wild relatives of cultivated plants by spreading through pollen. Oliver points out that contaminated plants wouldn't survive past a single generation, so the problem would be nipped in the bud. But to environmentalists, the prospect of even a single generation of terminator victims is noxious, and with repeated plantings, they fear, the cycle of thwarted propagation would continue, with unknown consequences. Beyond the fertile plains of North America, even the terminator's ability to block unintended genetic drift holds no weight, because acceptance of any genetically modified crop is still far from a given. Resistance to transgenic plants remains high in Europe, and production farmers in sub-Saharan Africa are avoiding engineered varieties so as not to jeopardize their chances in the European market. Last year many countries in the famine-gripped region refused to accept genetically modified grain as food aid unless it was milled to prevent planting. China has embraced genetically modified crops, but India, while approving genetically modified cotton, eschews genetically modified foods as well as the terminator system. Three years ago, the U.N. Convention on Biological Diversity chartered a panel to consider the impact of the terminator trait on smallholding farmers, indigenous peoples, and local communities. Results of the meeting, which was held in February and included industry, government, and advocacy representatives, have yet to be released. But even if the terminator prompts yet another backlash, it seems unlikely that any new method could stuff the genie back into its lamp, Mooney laments. "It's just too commercially attractive to set aside." To see how the U.S. Department of Agriculture describes terminator technology, visit www.ars.usda.gov/is/br/tps. For a general overview from those who oppose the terminator technology, visit www.globalissues.org/EnvIssues/GEFood/Terminator.asp. To see how two distinguished scientists describe—and oppose—the terminator technology, read an article that appeared in a 1998 issue of the French newspaper Le Monde Diplomatique: mondediplo.com/1998/12/02gen.

Terminator Genes

Here's another fine mess biotechnology has gotten us into

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