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Designer Crops Go to Market

As researchers make plants into `products,' controversy continues to grow over biotechnology

SINCE the late 1970s, genetic engineers have tantalized the rest of us with visions of the wonders they hope to work with crop plants down on the farm. These include coffee trees that yield flavorful beans with low caffeine, corn rich in lysine - the essential amino acid that today's maize lacks, or drought-tolerant wheat. But the genetic planners now have even larger goals. According to Howard A. Schneiderman, vice president of research for Monsanto Agricultural Company in St. Louis, plants will become ``our central way of making things.'' Genetic engineers, he says, can ``persuade'' plants to make many useful products that they don't make naturally.

Plant Genetic Systems in Ghent, Belgium, points the way with its canola (a variety of rapeseed) that can produce pharmaceuticals such as blood factors and growth hormones.

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Andrew Hiatt, Robert Cafferkey, and Katherine Bowdish of the Research Institute of Scripps Clinic in La Jolla, Calif., have reinforced this vision by showing how to make tobacco plants produce human antibodies, the proteins that counter viruses or toxic molecules. Dr. Hiatt says the genetic engineering techniques involved ``have been perfected to the point where [production of] a foreign protein can be targeted to an organ of choice,'' such as roots or leaves in a plant. He foresees an ``unparalleled capability and flexibility of agricultural production'' of valuable chemicals.

But that is a 21st-century prospect. The first genetically engineered crop you'll encounter at the local market is likely to be an ``improved'' tomato.

For example, Calgene in Davis, Calif., is field testing a tomato engineered to ripen without rotting. And Monsanto is continuing field tests of a tomato with genetic instructions that help it resist the tomato-mosaic virus. The owners of these designer vegetables may soon begin the daunting process of seeking approval to grow and sell them commercially.

This would present the United States Department of Agriculture (USDA) with its first decision on whether to release a gene-tailored plant from the strictures of regulated field tests and into unregulated commercial cultivation. USDA biotechnology official Terry Medley says the department is ready for such requests, which will ``be decided on a case by case basis.'' The Food and Drug Administration, which has not yet determined its policy, would then have to decide how to handle genetically engineered food products when it considers their safety and nutrition.

The tomato could become a symbol of the transition that research on crop genetic engineering is likely to undergo in the 1990s. It is a transition from being a wholly experimental field to being an applied science that is finding commercial use and also raising public policy issues.

Biology seems to have destined the tomato, or some other member of its botanical class, for this role. It's a dicot, meaning that its seedlings have two leaves. The bacterium Agrobacterium tumefaciens, which aggressively invades dicots, gives genetic engineers a handy tool for slipping genetic material into the plants. This is why dicots dominate the nearly 80 field trials the USDA has approved, or is considering for approval, since 1987.

There is no comparable agent to easily unlock the gene pool of the monocots, plants whose seedlings have only one leaf. The major cereals - corn, rice, wheat - belong to this class. Researchers have had much more trouble learning to manipulate the genetic instructions of monocots.

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One way to get new genes into the germ line of a grain plant is literally to shoot it in. In Ithaca, N.Y., Cornell University's John Sanford and colleagues designed the first gene gun. This device shoots tiny tungsten ``bullets'' coated with genetic material into animal and plant cells. After proving the gun's effectiveness in 1988, Cornell sold the rights to the Du Pont Company last year. Other versions of the gun may use different material for ``bullets.'' And at the University of Chicago, Laurens Mets is perfecting an aerosol device that sprays a fast- moving cloud of genetic material dissolved in chemicals, such as polyethylene glycol or ethanol, that ease entry of the material into plant cells.

Another technique, called electroporation, uses pulses of electricity to open self-repairing holes that allow plant cells, which have been stripped of their outer walls, to take up genetic material from solution.

Once plant cells have new genes, experimenters still have to grow them into complete plants. This is a tricky process. USDA scientists James Saunders and Benjamin Mathews are exploring a way to get around this problem by working directly with pollen. They germinate Nicotiana pollen in a culture to which they add genetic material when the pollen tubes develop. Using electroporation, they open pores in the pollen tubes to let in the foreign genes. These genes then are incorporated into the seed the pollen produces.

Using a variety of techniques, researchers in several countries are working with genetically altered rice. Ken Scott and his team at the University of Queensland in Australia have used a gene gun to modify genetic instructions in wheat - a technical breakthrough for that cereal. Dr. Scott says their technique ``has substantial advantages over techniques developed overseas.'' He explains that ``it produces minimal damage to the cells.''

And in what is considered a major advance with corn, Biotechnica International in Cambridge, Mass., and a joint Monsanto-USDA team have used gene guns to put new genetic material in corn. Both companies now want to field test their corn. Once it has perfected the technique, Biotechnica has said it hopes to give corn an enhanced ability to produce lysine.

While many genetic engineers are working to give plants new traits, North Carolina State University entomologist Fred Gould and his graduate-student assistant Tracy Johnson are trying to learn how to use transgenic plants in the field. They're working with tobacco that has been given the ability to produce a bacterial pesticide as part of a Rohm and Haas Company of Philadelphia field-test project.

Dr. Gould notes that it would be foolish to use such plants in a way that would encourage the rise of resistant strains of insects. Thus, he says, it may make sense to mix the resistant plants with normal plants so that the insect population is significantly reduced but not to the extent that only resistant bugs remain. Conversely, Gould says, it may be better to make only certain parts of a plant - leaves or roots - insect resistant. Strategic research into how to use improved plants has to go along with the genetic research itself, he says.

CROP genetic engineers still have much to learn in both these areas. They have only begun to identify what genes and gene combinations control various traits in different plants. Even when they have such knowledge, they have to decide what new traits are desirable and how best to introduce them. These will be political as well as technical decisions, as ``Biotechnology's Bitter Harvest,'' a report by a coalition of 18 environmental, farm, church, and other groups issued last March, illustrates.

This report criticized one of the favorite goals of industrial crop designers: making crop plants resistant to herbicides. It cited 58 projects at 27 companies and 21 universities and public research centers. The Industrial Biotechnology Association's Alan Goldhammer calls the criticism unfair. He says ``the focus of this research is on benign herbicides.''

But the groups doing the research should ``be taken to task for betrayal of their promise'' to reduce chemical farming, says Jane Rissler of the National Wildlife Federation, a co-author of the report. Sen. Patrick J. Leahy (D) of Vermont, who chairs the Senate Agriculture Committee, has said he will try to prohibit funding such research.

Whether Congress will actually cut back on that research or not, it seems likely that herbicide-resistant plants alone could set off a major biotechnology policy debate when they are ready for commercial use later in this decade. World Watch Institute food analyst John E. Young says the central issue is how best to use biotechnology to benefit the world.

He explains: ``Firmer tomatoes and herbicide-tolerant corn, not hardier rice or cassava are [present commercial] objectives. These companies are not sinking money into less-profitable plant research that might help close the widening gap between the growth in world food supplies and that in human numbers.'' He adds that plant engineering can be ``a threat to the very diversity [of species] on which it relies for raw material [if] it allows the rapid dissemination of identical plants over large areas.''

``Biotechnology,'' he warns, ``could be an important new weapon in the fight against hunger ... but only if aimed at the right targets.''