The Next Green Revolution

Cocktail Party

At first glance, it was just another cocktail party at the John R. Brown Convention Center in Houston, indistinguishable from the thousand that had preceded it in the large, nondescript room. Two hundred or so mid-level executives, a tiny fraction of the thousands who were attending the 1996 convention of the Biotechnology Industrial Organization (BIO), milled about, trying to balance a plastic wine glass in one hand and a paper plate piled with food in the other. One could barely hear the classical guitar music over the din. But, despite outward appearances, the event held extraordinary meaning. This was, quite possibly, the world's first genetically engineered cocktail party! Virtually all the hors d'oeuvres in the room had been prepared from genetically modified organisms (GMOs)! I resolved to sample each of these wonders of molecular biology.

On one table was a gargantuan bowl of corn chips and a bathtub-size bowl of salsa. The chips were made from corn flour grown from seed into which had been inserted a gene that blocks the action of a herbicide with devastating killing power. Sold under the name Liberty, this poison will destroy virtually any broadleaf plant on the planet unless a gene which produces an enzyme that deactivates it is in the plant's genome. If they sow corn seed with the protective gene, farmers can harvest more bushels per acre at lower cost. Why? A single application of Liberty will kill virtually all the weeds on that acre. The corn chips looked, felt, and tasted like every other corn chip I have ever eaten. The salsa was too spicy.

At another table was a metal serving dish holding a mountain of new potatoes that had been roasted with garlic. These NewLeaf potatoes, a product of Monsanto, have been genetically engineered to resist one of the banes of potato farming, the Colorado potato beetle. The protein pro duced by the single gene that Monsanto scientists cleverly slipped into the potato genome renders the leaves of the potato plants, which the beetle normally finds delicious, to be extremely distasteful to the insect. The roasted new potatoes tasted great.

By the time I had threaded my way through the crowd to the third food table, the bruschetta, a round Italian bread with tomatoes, red peppers, and olives baked into it, was almost gone. This dish was made with Endless Summer tomatoes, the product of a company called DNAP. The company scientists had developed a method to insert a gene into the tomato genome that slows the action of a key fruit-ripening enzyme. This greatly extends the shelf life of the tomato, making it easier and less expensive to keep ripe tomatoes in the grocery bins. Since the genetic system that controls the way fruits ripen is the same in many species, including pineapples and bananas, the benefits of this extended shelf life will be vast. My last dish was vegetable tempura. The yellow squash that was coated in the delicate crust had not had any foreign genes inserted into it, but the canola oil in which the tempura was cooked had been harvested from plants that had been genetically engineered to have increased yield (more oil per plant) and vigor (more resistant to a virus). I was elbowed away from the table by a herd of sales reps before I had eaten my fill.

Transgenic Crops

During the last five years, genetic engineering—the controlled transfer of a gene or genes from one organism to the germ plasm of another—has immensely transformed American agriculture. Almost overnight, a sizable percentage of the tens of millions of acres committed to the production of soy beans, corn, and cotton have been planted with seeds that have one or more "foreign" genes incorporated into their genomes. The giant companies that dominate agribusiness (Monsanto, Cargill, DuPont, and Novar-tis are among the leaders) claim that such genetically engineered seed promises the next green revolution—an extraordinary increase in crop yields that will deliver humanity more food at much lower cost.

First in Europe and now in the United States, however, an increasing number of scientists, environmentalists, bioethicists, consumer groups, and small farmers have forged coalitions to challenge the wisdom of transforming world agriculture so rapidly. Their two most important concerns are that there has not been enough attention to food safety and that some GMO plants may carry genes that if transferred into closely related, but wild species, could create superweeds. In the United States, public awareness, relatively small until 1999, is rising rapidly. Consider, for example, the potential impact of a full-page ad created by a consortium of 60 public interest groups including Greenpeace and Friends of the Earth that appeared in the New York Times in October of that year. Under the large point question: "Who Shall Play God in the Twenty-first Century?," the ad asks who gave permission to the biotech industry "to put human genes into pigs, fish, and plants?... to put fish genes into tomatoes? to create plants that can't reproduce? to redesign and clone animals (and, soon, humans) to fit a market function? to take over Nature's work?... When did we approve all this?... Have we lost our sanity?"

Despite such scary ads and what will be an intense political battle, GM foods are here to stay. During the next few years we can expect significantly more premarket testing of GM foods. Almost certainly, there will be new laws and regulations requiring many products made from such crops to be so labeled. But the benefits of this technology far exceed the risks.

What is actually going on? Monsanto, perhaps the world's most influential agricultural conglomerate, has driven much of the change, creating dozens of genetic modifications to important crops, each intended to enhance production. For example, Monsanto's genetic engineers have created a corn called YieldGard, which contains genes from a bacterium called Bacillus thuringiensis (Bt) that make the plant resistant to attack by the European corn borer beetle. Bt is a soil organism that during the course of evolution has acquired a number of genes which make proteins to kill insects that prey upon the plants which it calls home. During sporulation (reproduction), Bt produces enzymes which kill beetles that eat those plants. The bacteria's enzymes are a sort of time bomb. They are activated by enzymes in the insect's gut. Once activated, they kill the insect by destroying the cells in its digestive tract.

Farmers have been spraying crops with Bt for 40 years, but it was only after the first Bt "insecticide" gene was cloned in 1981 that botanists began to use the genes to build resistance to insects into the plant genome. Today, scientists have an arsenal of more than 100 Bt genes, cloned from a variety of bacterial strains, each of which kills a particular type of insect. By incorporating these genes into plants, the molecular biologists have rede fined insecticides. Instead of spraying millions of acres with toxic chemicals that defoliate virtually every unprotected plant they hit, farmers are now using natural, biological insecticides derived from soil organisms that humans have been ingesting with food for the entire 10,000-year history of agriculture. The use of seed genetically engineered to carry a Bt gene should be great news to those most concerned about the health and safety of our ecosystem.

GM seed is being planted at an amazing pace both in the United States and around the globe. In the United States, transgenic tomatoes are available in the grocery bins, and the Department of Agriculture has approved the production of dozens of transgenic plants in addition to soy, corn, and cotton. In China, farmers already tend vast acreages of transgenic cereals. In Japan and southeast Asia, there will soon be millions of acres committed to transgenic rice.

The dramatic change in how we produce key crops depends on two new technologies, both of which emerged in the 1980s: (1) plant regeneration (cloning) and (2) gene transfer. During the 1980s, scientists, who had been working on the problem for decades, perfected methods to remove cells from plant embryos and to turn each into a fully formed plant by culturing the cells in a broth of nutrients that included growth hormones. Thus, the embryo of one desirable plant could become the parent of billions of cloned (genetically identical) offspring.

The development of gene transfer technology allowed plant scientists to intervene in a precise manner to genetically modify individual embryo cells that could then become the parents of countless other plants, each of which would also contain the newly inserted gene. Among the first important advances was the discovery that a bacterium called Agrobacterium tumefaciens (At), a ubiquitous bug that has the natural capacity to penetrate the cell wall, was an excellent vehicle with which to transfer a desirable gene from another species. Since the 1970s, microbiologists have been able to use a family of enzymes to cut DNA molecules at precise spots as a chemical tool kit for splicing genes in bacteria. Using the same tools, it was relatively straightforward to transfer a potentially desirable gene that had been isolated from some organism into A. tumefaciens (the name comes from the fact that it causes noncancerous tumors on the roots of plants that it invades). The genetically engineered At bug could then be placed into culture with the plant cell of interest and act as a vector to deliver the gene it carried into the plant.

In 1994 Japanese scientists succeeded in using A. tumefaciens to create transgenic rice (so called because a gene from a foreign species has been transferred into it). Since then, scientists have succeeded in using a similar approach to create a variety of transgenic plants including corn and cassava (a widely consumed tropical plant with starch-rich tubers that is used to make manioc and tapioca). The At vector system has provided botanists with a way to study the impact of particular genes on the size, color, ripening time, resistance to infection, and nutritional qualities of most agriculturally important crops.

In the last few years, scientists have also found other ways to transfer genes that do not depend on using a bacterium to infect a plant cell culture. One, called electroporulation, is based on the fact that when a cell is exposed to a mild electric current, tiny holes appear in its wall through which DNA molecules can pass. Another attractive method (because the outcome may be better controlled) is to bombard plant cells with microscopic missiles that carry a payload of DNA (a gene of interest). Because in both cases the target is a cell that can be cloned, one does not need a terribly efficient success rate. When scientists find a few cells that have integrated the transgenes into their genomes, they can use them to propagate an infinite number of copies.

Botanists began creating transgenic plants with Bt genes in the mid-1980s, and by 1990 they had shown that the proteins coded by the genes protect the tobacco, tomato, and potato plants from certain pests. Since then, they have made remarkable progress by redesigning the Bt genes to produce a much larger amount of insecticide protein. Francis Rajamohan, a scientist at Ohio State University, and his colleagues were among the pioneers trying to genetically engineer Bt to become a super-killer of insects. They study insects with receptors in the cells in their gut that bind Bt toxins. They are trying to re-engineer the Bt genes to make the proteins bind even more efficiently to those receptors, thus causing more devastating injuries to the insects. Their goal is to make new Bt genes that will kill other pests such as gypsy moth larvae, mosquitoes, cabbage loopers, and cotton worms.

The development of Bt corn by no means signals the end of the havoc wrought by the corn borer beetle and other pests. In the intricate dance of evolution, struggling under the harsh conditions created by Bt corn, the beetle is likely to benefit from the appearance and spread (through reproductive success) of mutations that counter Bt. Other pests have done so.

The boll weevil which attacks cotton, and the northern and western corn root worms which devastate corn, are so far invulnerable to Bt proteins.

To feed the world efficiently, farmers will need plant scientists to come up with other weapons against pests. Attacks by root worms and cutworms are so devastating that American farmers spend $1,000,000,000 a year on chemical insecticides to repel them. Scientists are busily testing other soil bacteria to find those which have natural insecticides, and which might lead to a transgenic corn plant that is so resistant to the root worms that farmers will not need to spray millions of acres with chemical insecticides.

The boll weevil, which deposits its eggs inside the cotton flower buds, where they cannot be reached effectively by chemical sprays, does so much damage that it strongly influences the geographic distribution of U.S. cotton production. Botanists have recently discovered that a strain of the ubiquitous bacteria Streptomyces contains a protein known as a cholesterol oxidase that is acutely toxic to the larvae of boll weevils. This may lead to a product that will be among the second generation of transgenic insecticides.

The Debate over GMOs

A now defunct company called Calgene played a key early role in bringing genetically engineered crops to the American consumer. Its FlavrSavr tomato is a transgenic fruit with foreign genes that allow it to stay on the vine longer and, thus, be tastier than conventional tomatoes which are picked green and, as they are moved across America in box cars, gassed with ethylene oxide, which produces the natural red color by unnatural means. In 1989 Calgene embarked on what became a five-year dialog with the U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA), culminating in April of 1994 when an advisory panel decided that the transgenic tomato was not a new substance, that it did not have unusual levels of any toxic substances, and that it did not pose risks of food allergies. Despite their confidence in the FlavrSavr tomato's safety, the panel was concerned that so few people appreciated the magnitude of their decision. As Joan Gusow, a Columbia University professor put it, "We are changing the relationship between humans and nature on a scale of the industrial revolution." She is right.

Within eight months after Calgene got the go-ahead, five other com panies had gained approval for seven additional products, including the Monsanto potato that I ate in Houston. Another important approval that came in the mid-90s was the decision by the USDA to permit marketing of a genetically engineered strain of yellow squash called ZW-20. The transgenic squash is resistant to two plant viruses that have caused major economic losses for squash farmers in Georgia and Florida. During the late 90s there was a steadily increasing pace of government approval that was largely due to the fact that the transgenic plants are all created in roughly the same way. New technical and safety issues did not emerge with each application.

Despite the enthusiasm of American agribusiness, transgenic crops provoked concern almost immediately upon their arrival in Europe. The reaction in Europe was in part due to the traditionally much stronger influence of environmental issues on political discourse and in part due to the deeply felt unease about "mad cow disease" in Britain at that time. During the mid-90s the environmentalist Green Party, led by Euro-Parliamentarian, Hiltrud Breyer, repeatedly raised questions about the safety of GMOs and argued that such products are unnatural.

In 1996 a simmering debate boiled over when the European Commission granted Monsanto permission to sell 200,000 tons of genetically engineered soybeans to food manufacturers in Europe. The EC made its decision after advisors concluded that there was no safety issue significant enough to require that the final products (ranging from baby food to ice cream) using the transgenic soy beans be labeled. Nevertheless, in October, EuroCommerce, the industry association for wholesalers and retailers, insisted that member companies must label products to inform consumers if GMOs were present.

In November, 1996, a shipload of genetically engineered soybeans arrived in Hamburg, but the dockworkers refused to unload them, and several major European supermarket chains announced that they would not carry products made with the soybeans, labeled or not. These events were widely reported and had much influence on the public. During 1997 and 1998, the importation of other transgenic products such as genetically engineered corn produced by Ciba-Geigy declined dramatically. By 1998, despite the fact that there had never been an incident in which an individual was harmed by consuming transgenic food, the battle was over. In Britain, GMOs became known as "Frankenstein foods," and many major food re tailers publicly promised not to knowingly carry products made with them. In Europe, at least for now, society has voted overwhelmingly against genetically modified food.

During 1999 controversy over GMOs erupted in the United States. The major arguments are (1) that GMOs are unnatural, (2) that moving some genes into food plants creates an unknown risk of food allergies, (3) that transgenic foods may violate certain food purity laws that are part of the Orthodox Jewish and Islamic religions, (4) that transgenic crops may pose harm to particular species, (5) that transgenic crops may upset existing ecological balances, and (6) that GMOs will be used by agribusiness to the economic disadvantage of the third world.

GMOs are unnatural—in the sense that they exist only because humans are capable of creating them. But this is also the case for virtually every other agricultural product used by humans. All our crops and livestock have arisen from an intensive campaign of forced breeding that has been under way for hundreds of generations. As for concerns about allergens, there is a small risk of creating transgenic organisms that will provoke allergic reactions. For example, if genes from peanuts were moved into corn, corn might become a dangerous food for those people with a severe peanut allergy. I know of only one occasion in which it was proposed to move a nut gene into a cereal, and that was abandoned when such concerns were raised. The number of transgenic food products that have been engineered in a way that eating them would violate a religious law is van-ishingly small. Fortunately, both the danger of allergic reactions and the risk of causing people to violate their religious obligations can be solved by labeling, a topic to which we will return.

In the United States, concern for GMOs burgeoned in May of 1999 when researchers at Cornell University reported that in laboratory experiments they had found evidence that the pollen from Bt corn killed monarch butterflies, one of America's favorite insects. Monarchs dine exclusively on milkweed, a plant that is found throughout the midwest, frequently adjacent to corn fields. The Cornell scientists surmised that Bt corn pollen must frequently be blown onto milkweed. In the laboratory, about half the monarchs that dined on milkweed dusted with Bt pollen died, while none of the monarchs that ate milkweed without Bt pollen died. Given that more than 20,000,000 acres of American soil is planted with Bt corn, the experiment suggested that the transgenic corn threatened the butterflies.

The study, which was reported on the front page of the New York Times, brought the issue of how little we have studied the ecological impact of GMOs squarely before the public. Dr. Margaret Mellon, director of the agriculture and biotechnology program at the Union of Concerned Scientists, opined, "This should serve as a warning that there are more unpleasant surprises ahead." Overlooked in public discussions about the threat that Bt corn may pose to the monarch butterfly is the fact that unusually severe storms in the Mexican mountains where most of the species spends the winter have occasionally decimated the population, but it repeatedly bounces back. Deforestation of that environment is a far more real threat to the monarch than is Bt corn. Without a protective forest canopy, the monarchs cannot survive severe winters. During 1999 botanists and molecular biologists hotly debated the implications of the butterfly research, with most asserting that Bt corn poses no significant threat to monarchs in the field. Nevertheless, the debate focused attention on the limited review that currently precedes government approval of transgenic crops. Also lost in the rush to criticize GMOs was the fact that by planting GM seed, farmers have sharply reduced their use of chemical pesticides.

The major ecological worry about transgenic crops is whether there is a risk that transgenes that confer resistance to herbicides could (via windblown pollen) cross into closely related species in the wild and create new strains of weeds that spread rapidly, creating a menace to the environment as, for example, occurred with the importation of kudzu, which covers much of the South, and purple loosestrife, a beautiful aquatic weed which is almost impossible to kill and which is choking the ponds of New England. Unfortunately, researchers cannot design experiments that assess such risks, so the environmental concerns cannot be laid to rest. We will have to work with indirect assessment methods and make the most of experience.

As public awareness of GMOs rises and opponents stoke the debate, the public will want to be more informed about the methods used to create the food which makes its way onto supermarket shelves. They will claim a right to know and demand labeling of GMOs. Of course, labeling adds to the price of food in the marketplace, which raises the question of whether the price of disclosure may deprive some people of having the option of consuming these products.

It is likely that over the next few years the USDA will require that there be more extensive field tests of transgenic plants aimed at assessing ecological concerns, and it is possible that foods derived from at least some transgenic crops will be permitted to market only if they carry a label informing the public of their origin. Given the extensive manipulations that humans have performed on our food chain for centuries, I doubt that GMOs carry any more risk than the foods that preceded them. On balance, given the significant reduction in the use of chemical pesticides that they permit, I think it likely that they will be an ecological blessing. Given the immense benefits they promise and the paucity of data suggesting health or environmental risks, GMOs are here to stay. Nevertheless, the public anxiety over GMOs offers an important lesson about the need for advance dialogue with society when technocrats begin to contemplate tampering with something as fundamental as the food supply.

Plant Factories

The emergence of transgenic plant technology raises the fascinating possibility that plants could be designed as factories to produce at low cost otherwise extremely expensive medicines and other crucial products. The first signs of future success are emerging. In 1996 CropTech, a tiny biotech company in Virginia, announced that, using Agrobacterium tumefaciens as a vector, it had successfully spliced a gene that codes for an enzyme called human glucocerebrosidase into the genome of tobacco plants. This enzyme is the only effective treatment for Gaucher disease, a rare genetic disorder that severely affects about 30,000 persons in the world. Some children who are born without the ability to make proper glucocerebrosidase grow poorly, develop big spleens, and have severe anemia. Genzyme, one of the largest biotech companies, currently derives much more than half of its revenues from sales of Ceredase, a genetically engineered form of the enzyme. The cost to treat a single patient with this drug ranges from $100,000 to $300,000 a year, making it a contender as the world's most expensive medicine.

During the late 1980s and early 1990s, Genzyme manufactured Ceredase by extracting it from the cells of thousands of human placentas collected for it by a company in Belgium. It now has a better way to make the drug. Genzyme scientists transferred the human glucocerebrosidase gene into bacteria, which are grown in vast numbers in gigantic fermenta tion tanks. The new product, Cerezyme, is extracted from the gleaming steel tanks in a "factory" in Allston, Massachusetts. The company no longer depends on a large supply of human placentas, but the huge costs in product development mean that it will not lower the price of the medicine any time soon.

Carol Cramer, CropTech's vice president for research, claims that a single genetically engineered tobacco plant produces about one milligram of enzyme per gram of fresh leaf. This means that a single plant could produce enough enzyme to provide the medicines to treat one person for one year. Theoretically, the reduction in production costs from using plants as factories could be dramatic and would greatly benefit persons with Gaucher disease. We are years away from knowing whether CropTech's vision will be realized.

The genes of the much maligned tobacco plant are among the most studied in the world. Because we know it so well, it may emerge as the key plant in which to design protein factories. In 1997 French scientists announced that they had successfully completed a three-year project to transfer the human gene that codes for hemoglobin, the protein that carries oxygen through the body and makes blood red, into the tobacco genome and to extract tiny amounts of human hemoglobin from its leaves. The main impetus to produce hemoglobin from plants is to produce a blood substitute that carries no risk of threatening patients with lethal human viruses such as happened with HIV in the 1980s. For reasons relating to the cost of production and yield per plant, tobacco does not appear to be the best choice for hemoglobin, but it provided a wonderful test system. The French scientists are now trying to do this work in corn.

Even more exciting is the prospect that within a decade we may be able to give children their immunizations simply by having them eat specially engineered, uncooked vegetables. More than a decade ago, Hilary Ko-prowski, a biologist at Thomas Jefferson University in Philadelphia, developed a genetically engineered rabies vaccine in edible plants. In 1997, working with immunologists, he created a double vaccine by infecting plants with viruses with genes from both the rabies and HIV-1 virus. He fused genes from the two lethal viruses with the gene for the coat protein of the benign alfalfa mosaic virus, and then put the resulting "construct" under the genetic control of the tobacco mosaic virus. Tobacco plants infected with the modified virus produced large quantities of viral-like par ticles that comprised the outer coat of the alfalfa virus which enclosed the proteins from the dangerous viruses. When these particles were purified and injected into mice, they made them immune to rabies.

Currently, there is great interest in turning the banana into a vector for vaccines. Given the dismal poverty that engulfs much of Africa, it will be years before there will be a public health infrastructure to deliver traditional vaccines to rural areas, even allowing for the massive ($700 million) gift that the Gates Foundation made in 1999 to overcome this problem. If one could grow bananas and other plants that had been genetically engineered to make vaccines, one could reach most of the population within a few years.

Genetic engineering may someday solve the energy problem by unlocking the virtually inexhaustible energy supplies stored in growing plants. The world runs on oil, vast underground lakes of hydrocarbons created over millions of years as the earth's crust pulverized decaying plants. Rather than exhausting the planet's oil supplies (which at current rates probably will last a couple of centuries), it is not unreasonable to hope that we may someday derive fuel directly from the hydrocarbons that make up much of the biomass in plants. Genetically engineered bugs may be the answer, permitting us to grow our fuel which they will ferment for us.

Xylose, a five-carbon sugar, constitutes nearly 30% of the world's biomass. If it could be inexpensively converted to ethanol, it could greatly ease demand for fuel. In Brazil, for example, a substantial fraction of the trucks and cars run on alcohol fermented from sugar cane. The key to success here is a bug called Zymomonas mobilis, which is best known because it ferments the sugary sap in the century plant (A. tequilana) to make tequila. But Z. mobilis, which is really good at breaking down six-carbon sugars, cannot ferment five-carbon sugars. In 1994 Stephen Picataggio of the Department of Energy's National Renewable Energy Laboratory (NREL) in Golden, Colorado, used gene transfer techniques to create a strain of Z. mobilis that can break down xylose. He isolated (cloned) four genes from E. coli, a bug found in the human gut, which together produce proteins that catalyze the chemical steps to turn xylose into ethanol. He then inserted them into the Z. mobilis genome. The new strain could be used to ferment anything from corn cobs to municipal garbage into ethanol. The NREL is investigating whether a tough weed called switch-

grass that covers hundreds of thousands of acres on the American prairie might be genetically engineered to produce massive amounts of ethanol at acceptable cost.

Wine Sleuths

Genetic engineering may soon be used to create even better grape cultivars than man has developed through centuries of trial and error. In 1997 biologists answered one important question: What is the origin of the prized Cabernet Sauvignon grape, source of a wine renown for its pigments, tannins, and aroma? Sometime in the 18th century, this dark grape appeared in southeastern France. Within a few decades, viticulturists had adapted it to the climate around Bordeaux to produce an immensely popular wine. As its popularity grew, so did speculation about its origin. Some guessed that it was the long-lost Biturica cultivar praised in Roman times, others guessed it originated in Spain, still others along the Adriatic coast.

When Carole Meredith, an ecologist at the University of California at Davis, was asked by a group of California wine growers to use molecular genetics to verify the identity of key stock plants (a science known as am-pelography), she had no idea she would solve one of oenology's favorite puzzles. To develop a reference base, she and her colleague, John Bowers, performed DNA fingerprinting on about 50 cultivars by studying variation in microsatellite DNA (short, highly repetitive stretches of DNA that vary hugely in size among varieties), including all of the common, and most of the obscure, varietals used worldwide in the industry. Analysis of the various stocks showed that all the microsatellites in Cabernet Sauvi-gnon derived from the Cabernet franc or the Sauvignon blanc plants, both native to Bordeaux! All along the name had correctly depicted the parentage, but no one had been sure. Cabernet Sauvignon probably arose accidentally, for even 200 years ago grape growers would probably not have attempted a cross of those particular strains because experience taught them that it would not be expected to retain its all-important disease resistance.

More recently, Dr. Meredith and her colleagues have used DNA analysis to show that all 16 types of wine grapes grown in northeastern France (including Chardonnay, Gamay noir, Aligote, and Melon) derive from a single pair of parents, the Pinot and Gouais blanc, both of which have been cultivated since the Middle Ages! The attribution of parentage to the Pinot came as no surprise, but the historical importance of Gouais blanc will shock the grape growers. Gouais is widely thought to be an inferior grape and is today rarely cultivated in France. We may soon be drinking genetically engineered wine. The creation of transgenic grapes may prove to be the most efficient way to create strains with better disease resistance. It is, however, much more difficult for me to imagine the use of transgenes to enhance taste, which is as much a product of the subtilties of soil and sunlight as it is of genes.

Nutritional Genomics

What will be the most important development in plant genetics in the next 10 to 20 years? I would place my bet on nutritional genomics, an infant science that is already commanding substantial resources of giant companies like Du Pont. The vision of nutritional genomics is that scientists will use molecular biology to define those chemicals in foods that really confer health benefits. Next they will engineer plants to contain more of the really helpful compounds and less of those that may be harmful. Finally, they will develop a composite picture of how humans vary in their ability to absorb and metabolize those compounds and develop foods to match the varieties of human need. Indeed, one can imagine a day in which foods are chosen for consumption based on a genetically influenced wellness strategy. In its most advanced form, nutritional genomics will reshape preventive medicine, keying it to the construction of individual diets that will sharply reduce or delay the onset of disease.

This a grand vision, and even the most optimistic nutritional scientist would agree that it will take decades to realize if fully. But the impact that nutritional genomics will ultimately have is so vast that it is not yet possible to perceive its limits. For starters, molecular biologists and nutritionists will be able to provide a much more accurate picture of the benefits of the food we eat. Indeed, they will in time redefine how we think of food. Breakfast cereals may, for example, be manufactured in a manner that counters one or more genetic predispositions to heart disease. Fruits may be genetically engineered to attenuate a known genetic risk for colon cancer. There may come a day when food manufacturers market directly to consumers based on wellness claims that tie the genetic status of the consumer to the genetic profile of constituents in the food. One biotech com pany is already developing an assay to screen the impact of key food ingredients on the body's inflammatory response. If foods could be designed to modulate such systems, they could open up new approaches to managing chronic disorders like arthritis and treating less common disorders like lupus. Designer foods will become a reality.

Nutritional genomics could come to occupy a middle ground between the pharmaceutical industry, which will be the source of many new medicines based on genomic research, and the alternative medicine movement that is robust today. Millions of Americans today consume St. John's wort, echinacea, ginko, and hundreds of other relatively unstudied substances to ward off diseases or retain health. There is, no doubt, real medicinal value in some compounds contained in these substances. The tools of nutritional genomics will allow us to isolate them and understand their benefits and their modes of action. Nutritional genomics may provide a much-needed bridge between traditional medicine and holistic health care.

A transgenic goat which carries a gene that produces an important human protein that can be harvested from her milk. (Courtesy ofGenzyme Transgenics Corporation.)

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