Dna: The Secret of Life

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by Watson, James


  One ingenious set of chemical defenses in plants involves furanocoumarins, a group of chemicals that become toxic only when directly exposed to ultraviolet light. By this natural adaptation, the toxins are activated only when a herbivore starts munching on the plants, breaking open the cells and exposing their contents to sunlight. Furanocoumarins present in the peel of limes were responsible for a bizarre plague that struck a Club Med resort in the Caribbean. The guests who found themselves afflicted with ugly rashes on their thighs had all participated in a game that involved passing a lime from one person to the next without using hands, feet, arms, or head. In the bright Caribbean sunlight the activated furanocoumarins in the humiliated lime had wreaked a terrible revenge on numerous thighs.

  Plants and herbivores are involved in an evolutionary arms race: nature selects plants to be ever more toxic, and herbivores to be ever more efficient at detoxifying the plant's defensive substances while metabolizing the nutritious ones. In the face of furanocoumarins, some herbivores have evolved clever countermeasures. Some caterpillars, for example, roll up a leaf before starting to munch. Sunlight does not penetrate the shady confines of their leaf roll, and thus the furanocoumarins are not activated.

  Adding a particular Bt gene to crop plants is merely one way the human species as an interested party can give plants a leg up in this evolutionary arms race. We should not be surprised, however, to see pest insects eventually evolve resistance to that particular toxin. Such a response, after all, is the next stage in the ancient conflict. When it happens, farmers will likely find that the multiplicity of available Bt toxin strains can furnish them yet another exit from the vicious evolutionary cycle: as resistance to one type becomes common, they can simply plant crops with an alternative strain of Bt toxin onboard.

  In addition to defending a plant against its enemies, biotechnology can also help bring a more desirable product to market. Unfortunately, however, sometimes the cleverest biotechnologists can fail to see the forest for the trees (or the crop for the fruits). So it was with Calgene, an innovative California-based company. In 1994 Calgene earned the distinction of producing the very first GM product to reach supermarket shelves. Calgene had solved a major problem of tomato growing: how to bring ripe fruit to market instead of picking them when green, as is customary. But in their technical triumph they forgot fundamentals: their rather unfortunately named "Flavr-Savr" tomato was neither tasty nor cheap enough to succeed. And so it was that the tomato had the added distinction of being one of the first GM products to disappear from supermarket shelves.

  Still, the technology was ingenious. Tomato ripening is naturally accompanied by softening, thanks to the gene encoding an enzyme called polygalacturonase (PG), which softens the fruit by breaking down the cell walls. Because soft tomatoes do not travel well, the fruit are typically picked when they are still green (and firm) and then reddened using ethene gas, a ripening agent. Calgene researchers figured that knocking out the PG gene would result in fruit that stayed firm longer, even after ripening on the vine. They inserted an inverted copy of the PG gene, which, owing to the affinities between complementary base pairs, had the effect of causing the RNA produced by the PG gene proper to become "bound up" with the RNA produced by the inverted gene, thus neutralizing the former's capacity to create the softening enzyme. The lack of PG function meant that the tomato stayed firmer, and so it was now possible in principle to deliver fresher, riper tomatoes to supermarket shelves. But Calgene, triumphant in its molecular wizardry, underestimated the trickiness of basic tomato farming. (As one grower hired by the company commented, "Put a molecular biologist out on a farm, and he'd starve to death.") The strain of tomato Calgene had chosen to enhance was a particularly bland and tasteless one: there simply was not much "flavr" to save, let alone savor. The tomato was a technological triumph but a commercial failure.

  Overall, plant technology's most potentially important contribution to human well-being may involve enhancing the nutrient profile of crop plants, compensating for their natural shortcomings as sources of nourishment. Because plants are typically low in amino acids essential for human life, those who eat a purely vegetarian diet, among whom we may count most of the developing world, may suffer from amino acid deficiencies. Genetic engineering can ensure that crops contain a fuller array of nutrients, including amino acids, than the unmodified versions that would otherwise be grown and eaten in these parts of the world.

  To take an example, in 1992 UNICEF estimated that some 124 million children around the world were dangerously deficient in vitamin A. The annual result is some half million cases of childhood blindness; many of these children will even die for want of the vitamin. Since rice does not contain vitamin A or its biochemical precursors, these deficient populations are concentrated in parts of the world where rice is the staple diet.

  An international effort, funded largely by the Rockefeller Foundation (a nonprofit organization and therefore protected from the charges of commercialism or exploitation often leveled at producers of GM foods), has developed what has come to be called "golden rice." Though this rice doesn't contain vitamin A per se, it yields a critical precursor, beta-carotene (which gives carrots their bright orange color and golden rice the fainter orange tint that inspired its name). As those involved in humanitarian relief have learned, however, malnutrition can be more complex than a single deficiency: the absorption of vitamin A precursors in the gut works best in the presence of fat, but the malnourished whom the golden rice was designed to help often have little or no fat in their diet. Nevertheless golden rice represents at least one step in the right direction. It is here that we see the broader promise of GM agriculture to diminish human suffering.

  We are merely at the beginning of a great GM plant revolution, only starting to see the astonishing range of potential applications. Apart from delivering nutrients where they are wanting, plants may also one day hold the key to distributing orally administered vaccine proteins. By simply engineering a banana that produces, say, the polio vaccine protein – which would remain intact in the fruit, which travels well and is most often eaten uncooked – we could one day distribute the vaccine to parts of the world that lack public health infrastructure. Plants may also serve less vital but still immensely helpful purposes. One company, for example, has succeeded in inducing cotton plants to produce a form of polyester, thereby creating a natural cotton – polyester blend. With such potential to reduce our dependence on chemical manufacturing processes (of which polyester fabrication is but one) and their polluting by-products, plant engineering will provide ways as yet unimagined to preserve the environment.

  Monsanto was definitely the leader of the GM food pack, but naturally its primacy was challenged. The German pharmaceutical company Hoechst developed its own Roundup equivalent, an herbicide called Basta (or Liberty in the United States), with which they marketed "LibertyLink" crops genetically engineered for resistance. Another European pharmaceutical giant, Aventis, produced a version of Bt corn called "Starlink."

  But Monsanto, aiming to capitalize on being biggest and first, aggressively lobbied the big seed companies, notably Pioneer, to license Monsanto's products. But Pioneer was still wed to its long-established hybrid corn methods so its response to the heated courtship was frustratingly lukewarm and, in deals made in 1992 and 1993, Monsanto looked inept when it was able to exact from the seed giant only a paltry $500,000 for rights to Roundup Ready soybeans and $38 million for Bt corn. When he became CEO of Monsanto in 1995, Robert Shapiro aimed to redress this defeat by positioning the company for all-out domination of the seed market. For a start, he broadened the attack on the old seed-business problem of farmers who replant using seed from last year's crop rather than paying the seed company a second time. The hybrid solution that worked so well for corn was unworkable for other crops. Shapiro, therefore, proposed that farmers using Bt seed sign a "technology agreement" with Monsanto, obliging them both to pay for use of the gene and to refrain from replanting with se
ed generated by their own crops. What Shapiro had engineered was a hugely effective way to make Monsanto anathema in the farming community.

  Shapiro was an unlikely CEO for a mid-Western agrichemical company. Working as a lawyer at the pharmaceutical outfit Searle, he had the marketing equivalent of science's "Eureka!" moment. By compelling Pepsi and Coca-Cola to put the name of Searle's brand of chemical sweetener on their diet soft drink containers, Shapiro made NutraSweet synonymous with a low-calorie lifestyle. In 1985, Monsanto acquired Searle and Shapiro started to make his way up the parent company's corporate ladder. Naturally, once he was appointed CEO, Mr. NutraSweet had to prove he was no one-trick pony.

  In an $8 billion spending spree in 1997-98, Monsanto bought a number of major seed companies, including Pioneer's biggest rival, Dekalb, as Shapiro schemed to make Monsanto into the Microsoft of seeds. One of his intended purchases, the Delta and Pine Land Company, controlled 70 percent of the U.S. cottonseed market. Delta and Pine also owned the rights to an interesting biotech innovation invented in a U.S. Department of Agriculture research lab in Lubbock, Texas: a technique for preventing a crop from producing any fertile seeds. The ingenious molecular trick involves flipping a set of genetic switches in the seed before it is sold to the farmer. The crop develops normally but produces seeds incapable of germinating. Here was the real key to making money in the seed business! Farmers would have to come back every year to the seed company.

  Though it might seem in principle counterproductive and something of an oxymoron, nongerminating seed is actually of general benefit to agriculture in the long run. If farmers buy seed every year (as they do anyway, in the case of hybrid corn), then the improved economics of seed production promote the development of new (and better) varieties. Ordinary (germinating) forms would always be available for those who wished them. Farmers would buy the non-germinating kind only if it were superior in yield and other characteristics farmers care about. In short, nongerminating technology, while closing off one option, provides farmers with more and ever improved seed choices.

  For Monsanto, however, this technology precipitated a public relations disaster. Activists dubbed it the "terminator gene." They evoked visions of the downtrodden third world farmer, accustomed by tradition to relying on his last crop to provide seeds to sow for the new one. Suddenly finding his own seeds useless, he would have no choice but to return to the greedy multinational and, like Oliver Twist, beg pathetically for more. Monsanto backed off, a humiliated Shapiro publicly disavowed the technology, and the terminator gene remains out of commission to this day. Through the public relations fallout, its only real impact to date has been the termination of Monsanto's grandiose ambitions of the late 1990s.

  Much of the hostility to GM foods, as we saw in the last chapter with bovine growth hormone, has been orchestrated by professional alarmists like Jeremy Rifkin. His counterpart in the United Kingdom, Lord Peter Melchett, was equally effective until he lost credibility in the environmental movement by quitting Greenpeace to join a public relations firm that has in the past worked for Monsanto. Rifkin, the son of a self-made plastic-bag manufacturer from Chicago, may differ in style from Melchett, a former Eton boy from a grand family, but they share a vision of corporate America as conspiratorial juggernaut pitted against the helpless common man.

  Nor has the reception of GM foods been aided by the knee-jerk, politically craven attitudes and even scientific incompetence typical of governmental regulatory agencies – in the US the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) – when they have been confronted with these new technologies. Roger Beachy, who first identified the "cross-protection" phenomenon that saved Hawaii's papaya farmers from ruin, remembers how the EPA responded to his breakthrough:

  I naively thought that developing virus-resistant plants in order to reduce the use of insecticides would be viewed as a positive advance. However the EPA basically said, "If you use a gene that protects the plant from a virus, which is a pest, that gene must be considered a pesticide." Thus the EPA considered the genetically transformed plants to be pesticidal. The point of the story is that as genetic sciences and biotech developed, the federal agencies were taken somewhat by surprise. The agencies did not have the background or expertise to regulate the new varieties of crop plants that were developed, and they did not have the background to regulate the environmental impacts of transgenic crops in agriculture.

  An even more glaring instance of the government regulators' ineptitude came in the so-called Starlink episode. Starlink, a Bt corn variety produced by the European multinational Aventis, had run afoul of the EPA when its Bt protein was found not to degrade as readily as other Bt proteins in an acidic environment, one like that of the human stomach. In principle, therefore, eating Starlink corn might cause an allergic reaction, though there was never any evidence that it actually would. The EPA dithered. Eventually it decided to approve Starlink for use in cattle feed, but not for human consumption. And so under EPA "zero-tolerance" regulations, the presence of a single molecule of Starlink in a food product constituted illegal contamination. Farmers were growing Starlink and non-Starlink corn side by side, and non-Starlink crops inevitably became contaminated: even a single Starlink plant that had inadvertently found its way into the harvest from whole fields of non-Starlink was enough. Not surprisingly, Starlink began to show up in food products. The absolute quantities were tiny, but genetic testing to detect the presence of Starlink is supersensitive. In late September 2000, Kraft Foods launched a recall of taco shells deemed to be tainted with Starlink, and a week later Aventis began a buy-back program to recover Starlink seed from the farmers who had bought it. The estimated cost of this "cleanup" program: $100 million.

  Blame for this debacle can only be laid at the door of an overzealous and irrational EPA. Permitting the use of corn for one purpose (animal feed) and not another (human consumption), and then mandating absolute purity in food is, as is now amply apparent, absurd. Let us be clear that if "contamination" is defined as the presence of a single molecule of a foreign substance, then every morsel of our food is contaminated! With lead, with DDT, with bacterial toxins, and a host of other scary things. What matters, from the point of view of public health, is the concentration levels of these substances, which can range from the negligible to the lethal. It should also be considered a reasonable requirement in labeling something a contaminant that there be at least minimal evidence of demonstrable detriment to health. Starlink has never been shown to harm anyone, not even a laboratory rat. The only positive outcome of this whole sorry episode has been a change in EPA policy abolishing "split" permits: an agricultural product will hereafter be approved for all food-related uses or not.

  That the anti-GM food lobby is most powerful in Europe is no accident. Europeans, the British in particular, have good reason both to be suspicious about what is in their food and to distrust what they are told about it. In 1984, a farmer in the south of England first noticed that one of his cows was behaving strangely; by 1993, 100,000 British cattle had died from a new brain disease, bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. Government ministers scrambled to assure the public that the disease, probably transmitted in cow fodder derived from remnants of slaughtered animals, was not transmissible to humans. By February 2002, 106 Britons had died from the human form of BSE. They had been infected by eating BSE-contaminated meat.

  The insecurity and distrust generated by BSE has spilled over into the discussion of GM foods, dubbed by the British press "Frankenfoods." As Friends of the Earth announced in a press release in April 1997, "After BSE, you'd think the food industry would know better than to slip 'hidden' ingredients down people's throats." But that, more or less, is exactly what Monsanto was planning to do in Europe. Certain the anti-GM food campaign was merely a passing distraction, management pressed ahead with its plans to bring GM products to European supermarket shelves. It was to prove a major miscalculation: through 1998, the
consumer backlash gained momentum. Headline writers at the British tabloids had a field day: "GM Foods Are Playing Games with Nature: If Cancer Is the Only Side-Effect We Will Be Lucky"; "Astonishing Deceit of GM Food Giant"; "Mutant Crops." Prime Minister Tony Blair's halfhearted defense merely provoked tabloid scorn: "The Prime Monster; Fury As Blair Says: I Eat Frankenstein Food and It's Safe." In March 1999, the British supermarket chain Marks and Spencer announced that it would not carry GM food products, and soon Monsanto's European biotech dreams were in jeopardy. Not surprisingly other food retailers took similar actions: it made good sense to show supersensitivity to consumer concerns, and no sense at all to stick one's neck out in support of an unpopular American multinational.

  It was around this time of the Frankenfood maelstrom in Europe that news of the terminator gene and Monsanto's plans to dominate the global seed market began to circulate on the home front. With much of the opposition orchestrated by environmental groups, the company's attempts to defend itself were hamstrung by its own past. Having started out as a producer of pesticides, Monsanto was loath to incur the liability of explicitly renouncing these chemicals as environmental hazards. Yet one of the greatest virtues of both Roundup Ready and Bt technologies is the extent to which they reduce the need for herbicides and insecticides. The official industry line since the 1950s had been that proper use of the right pesticides harmed neither the environment nor the farmer applying them: Monsanto still could not now admit that Rachel Carson had been right all along. Unable to simultaneously condemn pesticides and sell them, the company could not make use of one of the most compelling of arguments in defense of the use of biotechnology on the farm.

 

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