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INSECT-RESISTANT: Monsanto's NewLeaf potatoes, above, are genetically engineered to protect against the Colorado potato beetle, which can severely damage plans, below Controversy is stirring in the European Union (EU) over genetically engineered food crops. The EU has already demanded that genetically engineered crops imported after July 31 be labeled as products of biotechnology. In the United States also, some consumers are wary of these new "supercrops," fearing that introduced genes could prove toxic or allergenic or that genes for herbicide resistance might encourage more chemically intensive agriculture. The labeling controversy in Europe threatens to interfere with U.S.-European trade, and a similar outcry in the U.S.-and resulting increases in government regulation-could strain research budgets and employment opportunities at agricultural biotech companies. In answer to critics, companies and researchers point to the need for improved quality and increased quantity of food production to feed a skyrocketing world population. A popular example is the rice plant. The grain of this low-lying grass provides some 30 percent of the total calories consumed by the world's people. As productive as it is, the plant could be better-harsh climates, predatory insects, and invasive weeds all conspire to limit its yields. What's more, it isn't terribly high in protein and other vital nutrients. Such drawbacks have plant biologists and biotech companies scrambling to improve rice-and most other major crop plants-through genetic engineering. Some genetically engineered food crops are already on U.S. and European markets: St. Louis-based Monsanto Life Science Co. offers Roundup Ready soybeans, which are resistant to Monsanto's Roundup herbicide, allowing the farmer greater flexibility in weed control. Numerous other crops have insect and virus resistance engineered into them. For example, St. Louis-based Monsanto Life Science Co.'s NewLeaf potatoes have been genetically engineered to include a gene to express the Bacillus thuringiensis toxin, which kills susceptible insects feeding on the plant. The FlavrSavr tomato, introduced by Davis, Calif.-based Calgene Inc. in 1995, has a longer shelf life than its cousins. Consumer acceptance will drive the marketplace, both in the U.S.-where transgenic crops have met little resistance-and in Europe, where U.S. exporters will be at a distinct disadvantage if they cannot convince Europeans to accept these new crops. LOOKING FORWARD: Tufts' Sheldon Krimsky notes that biotech companies are "simply developing products and hoping the markets will be there." Tufts University urban and environmental policy analyst Sheldon Krimsky doesn't think consumer skepticism will drive agricultural biotechnology out of business. "Except for some forms of herbicide-resistant crops, companies are assuming that this opposition will go away, and they're just simply developing products and hoping the markets will be there" when they're approved, he says. Krimsky believes that acceptance may depend on the particular food product and how it was modified. Although herbicide resistance is frowned upon in many circles, Krimsky notes that when a genetically engineered enzyme was introduced into cheese production several years ago, the public did not respond at all. Public responses are "very hard to generalize," he observes. But some consumer groups take a hard-line stance against genetically engineered food. "What the public wants is a tomato that tastes good, that didn't destroy the environment while being produced, and that they don't have to worry about feeding to their kids," contends Ronnie Cummins, national director of the Pure Food Campaign, a Washington, D.C.-based activist group "dedicated to building a healthy, safe, and sustainable system of food production and consumption." Cummins and others fear that allergens and toxins may be introduced into altered foods, and that herbicide-resistant crops will just tempt farmers to use more chemicals, all the while lining biotech companies' pockets. "There is a race for commercialization, but no one is looking at the fact that our agriculture is a mess-our water is barely drinkable, the population is unhealthy. . . . The problem with genetic engineering is that it's going to prolong the life of this chemically intensive agriculture, while offering a false green solution," says Cummins. Biotech companies counter that the high yields necessary to feed a burgeoning world population can be achieved only through chemical intervention, but transgenic crops can be used to decrease the overall use of pesticides, herbicides, and fertilizers. Genetic engineering is simply an extension of the domestication process that has been going on for nearly 10,000 years and therefore carries no more risk than genes from wild plants, biotech industry representatives contend. POSITIVE RECEPTION: According to surveys by NC State's Thomas Hoban, the public is supportive of genetically engineered food crops. The companies by and large support the Food and Drug Administration's (FDA's) policy, which requires labeling only when the nutrient quality or safety of a food has been altered. Since there is no strong evidence that any of the transgenic crops on the market affect the food's nutrition or safety, they remain unlabeled on U.S. produce shelves. "How the seed was developed will-and should-be of little consequence," states Thomas Hoban, an associate professor in the departments of anthropology and sociology at North Carolina State University. Hoban has conducted a number of surveys to determine public opinion of genetically engineered food crops, most of which he says find the public supportive of the new plants. One danger that companies must look out for is the introduction of new genes disrupting a plant's metabolism, according to Peter Day, director of the Center for Agricultural Molecular Biology at Rutgers University in New Brunswick, N.J. Companies must be sure that "the exercise of introducing a new gene has not upset what's already there," perhaps causing a toxin that is present naturally to be produced in much higher levels. He points to the example of Calgene's FlavrSavr. The stems and leaves of tomatoes naturally contain low concentrations of tomatine, a toxic alkaloid that is used commercially as a plant fungicide. In premarket testing, Calgene determined that levels in the transgenic variety were the same as in unaltered tomatoes. DEFENSIVE MANEUVERS: BIO Chairman Jerry Caulder points out that R&D funding often is diverted to satisfy government funding. Most companies seem frustrated by the short-term problems these controversies present, but they expect public acceptance to eventually prevail. "You have to divert money that should go into inventing new products [in order] to defend yourself, when you shouldn't have to from a scientific standpoint," says Jerry Caulder, chairman of the Washington, D.C.-based Biotechnology Industry Organization's (BIO's) committee for food and agriculture and a former president and CEO at San Diego-based Mycogen Corp. Money spent on satisfying regulations that are believed to be excessive could potentially total 30 percent to 50 percent of a company's research budget, limiting funds for research and development and new hires, Caulder notes. Genetic engineering may have its hazards, but so does traditional breeding, since genes bred in from wild relatives could also pose a danger, Caulder maintains. "There is no way [one] can live in a no-risk society," he points out. Henry I. Miller, former director of FDA's Office of Biotechnology and currently a senior research fellow at the Hoover Institution and a consulting professor at Stanford University's Institute for International Studies, is more direct in his criticism of biotech opponents. "Increasing the costs of 'undesirable' technologies or products is . . . a hidden part of the activist agenda," he says. Labeling could put a stigma on products, turning off consumers, producers, and even researchers. Such costs hit businesses hard, especially industries such as food production, whose profit margins are low, he contends. Caulder agrees that labeling could seriously damage the agricultural biotech industry: "I grew up in the South, where most people label Southerners as bigots and racists. . . . That was a social prejudice. I think labeling [products] that don't need to be labeled is a technological prejudice, and that will have far-reaching implications." He worries about what effect consumer pressure will have on government spending that is already under tight fiscal restraint. He expects the support for academic research will likely come from industry instead. "I think that's a terrible direction for it to be going in, because when industry sponsors something there [often] are strings attached. Universities should be doing basic research with taxpayers' money, so that the [benefit] goes to everybody," he maintains. CALCULATED RISKS: Companies must be careful that introducing new genes does not disrupt a plant's metabolism, cautions Rutgers' Peter Day. Hoban is confident that consumer reluctance will die down. Surveys he has conducted over the past few years (T. Hoban, Nature Biotechnology, 15:232-4, 1997) indicate that "most consumers still recognize the benefits of biotechnology and remain willing to buy food developed through biotechnology." If so, that's good news for research. Ag biotech researchers are a diverse bunch. "I usually look for somebody who is well-grounded in the basic science itself-biology, molecular biology, genetics, agronomy, plant pathology, horticulture, biochemistry, or food science. . . . I also look for people who can connect divergent pieces of information," reports Rob Horsch, director of technology at Agracetus Inc. a Monsanto subsidiary in Middleton, Wis. Mycogen's researchers come from "all over the board. . . .Most people are well-founded in some phase of biochemistry, though," states Caulder. He estimates that 80 percent to 90 percent of the tasks, such as growing, harvesting, and routine analyses, "could be done by people straight out of high school. . . . The really good [researchers] say, 'How do I look at [an obvious result] and observe something different about it?'" Such scientists can observe subtle, even unexpected, changes in a plant's physical characteristics and pursue those advantageous traits. Investigations fall into two broad categories: output research and input research. The output approach concentrates on improving the yield or nutritional content of the crop-or even its shelf life. Others see plants as miniature factories that can produce therapeutic proteins, spider's silk, or even biodegradable plastics. HIDDEN COST: The cost of labeling genetically altered crops would hit biotech businesses hard, maintains Stanford's Henry Miller. Input research yields plants that are more tolerant of harsh climates or resistant to viruses or pests. Bestowing herbicide resistance also is a common tactic. Though activists often parade herbicide-resistant plants as a sin of biotechnology, the trait is not a simple "go" signal to farmers to dump more herbicide onto their land, asserts Caulder. Herbicides are the farmer's best alternative to plowing, he insists, and plowing is a far harsher treatment of the land: Churning the topsoil brings erosion, run-off, and pollution in the form of diesel fuel spills and exhaust fumes. Common practice is to plow before the crop is planted, then treat with herbicide after the crop begins to grow, when it is in greatest competition with surrounding weeds. But farmers who use Monsanto's Roundup Ready soybeans and similar products have an alternative: The farmer can treat with herbicide before and after planting, limiting use of the plow. The weeds are still controlled, claims Caulder. With a low enough plowing frequency, the soil may sequester carbon from the atmosphere, actually increasing the richness of the soil. Caulder's former company, Mycogen, is hard at work engineering soybean varieties to produce a greater percentage of monounsaturated oils and reduce the plant's complement of the less healthy polyunsaturated oils. "It's the first time we've really been able to affect the quality of foods," he says, adding that "for the first 10,000 years" of agriculture, researchers were working on increasing production. TOUGH OUTLOOK: Plant geneticists have "hugely difficult biological problems" to tack in developing next-generation seeds, contends Agracetus's Rob Horsch. Monsanto-"the 200-pound gorilla" of the agricultural biotech companies, according to one industry observer-has already produced a first wave of products, including Roundup Ready soybeans, NewLeaf potatoes, and insect-resistant cotton and corn. According to Agracetus's Horsch, the company will soon have cotton and corn varieties with the dual punch of Roundup and insect resistance. Fungi and nematodes are also on Monsanto's hit list, with resistance genes in the discovery stage. On the output side of things, Calgene (a Monsanto partner) is fiddling with oil contents, in this case in canola, while Monsanto is mulling over the starch content of tomatoes and potatoes. Starch forces processing plants to cook the vegetables longer, which reduces the energy efficiency of the process. Plant geneticists still have much to do. Horsch sees the accomplishments so far as having tackled the simpler problems-the traits have mostly been the result of single-gene substitution. But multiple-gene traits provide a challenge that should occupy researchers for years to come. "Some traits that would be really beneficial, like stress tolerance and the ability to fix atmospheric nitrogen [reducing the need for fertilizer], are hugely difficult biological problems," he remarks. "In some cases we don't even have a clue where to start." Horsch also touts the "nutraceutical" approach to improving crop varieties (K.S. Brown, The Scientist, March 4, 1996, page 1): Many of the antioxidants that protect against cancer and other diseases are present only in low amounts in staples like rice, corn, and wheat. Researchers foresee new and improved plants that provide greater protection against cancer, heart disease, and nutrient deficiencies. In a recent report in the Plant Journal, Peter Burkhardt and Ingo Potrykus of the Swiss Federal Institute of Technology in Zurich described their modification of rice to produce beta-carotene (P.K. Burkhardt et al., 11:1071-8, 1997). Although rice doesn't produce beta-carotene naturally, it does contain a distant precursor; geranyl geranyl diphosphate (GGPP), a 20-carbon isoprenoid molecule. Two of these condense to form phytoene, the first precursor in the biosynthetic pathway that leads to beta-carotene, and eventually to the sought-after vitamin A. The team engineered the rice to produce an enzyme from daffodil that converts GGPP to phytoene. Calgene Inc. http://www.calgene.com Monsanto Life Science Co. http://www.monsanto.com/ Mycogen Corp. http://www.mycogen.com/ Pure Food Campaign

Political Controversy Puts Ag Biotech In Spotlight

Sep 28, 1997

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