Dna: The Secret of Life

by Watson, James

  All three Agrobacterium groups – Chilton's, van Montagu and Schell's, and Monsanto's – saw the bacterium's strategy as an invitation to manipulate the genetics of plants. By then it wasn't hard to imagine using the standard cut-and-paste tools of molecular biology to perform the relatively simple act of inserting into. Agrobacterium's plasmid a gene of one's choice to be transferred to the plant cell. Thereafter, when the genetically modified bacterium infected a host, it would insert the chosen gene into the plant cell's chromosome. Agrobacterium is a ready-made delivery system for getting foreign DNA into plants; it is a natural genetic engineer. In January 1983, at a watershed conference in Miami, Chilton, Horsch (for Monsanto), and Schell all presented independent results confirming that Agrobacterium was up to the task. And by this time, each of the three groups had also applied for patents on Agrobacterium-based methods of genetic alteration. Schell's was recognized in Europe, but in the United States, a falling-out between Chilton and Monsanto would rumble through the courts until 2000, when a patent was finally awarded to Chilton and her new employer, Syngenta. But having now seen a bit of the Wild West show that is intellectual property patents, one shouldn't be surprised to hear that the story does not end so neatly there: as I write, Syngenta is in court suing Monsanto for patent infringement.

  At first Agrobacterium was thought to work its devious magic only on certain plants. Among these, we could not, alas, count the agriculturally important group that includes cereals such as corn, wheat, and rice. However, in the years since it gave birth to plant genetic engineering, Agrobacterium has itself been the focus of genetic engineers, and technical advances have extended its empire to even the most recalcitrant crop species. Before these innovations, we had to rely upon a rather more haphazard, but no less effective, way of getting our DNA selection into a corn, wheat, or rice cell. The desired gene is affixed to tiny gold or tungsten pellets, which are literally fired like bullets into the cell. The trick is to fire the pellets with enough force to enter the cell, but not so much that they will exit the other side! The method lacks Agrobacterium's finesse, but it does get the job done.

  This "gene gun" was developed during the early 1980s by John Sanford at Cornell's Agricultural Research Station. Sanford chose to experiment with onions because of their conveniently large cells; he recalls that the combination of blasted onions and gunpowder made his lab smell like a McDonald's franchise on a firing range. Initial reactions to his concept were incredulous, but in 1987 Sanford unveiled his botanical firearm in the pages of Nature. By 1990, scientists had succeeded in using the gun to shoot new genes into corn, America's most important food crop, worth $19 billion in 2001 alone.

  Corn is not only a valuable food crop; unique among major American crops, it also has long been a valuable seed crop. The seed business has traditionally been something of a financial dead-end: a farmer buys your seed, but then for subsequent plantings he can take seed from the crop he has just grown, so he never needs to buy your seed again. American corn seed companies solved the problem of nonrepeat business in the twenties by marketing hybrid corn, each hybrid the product of a cross between two particular genetic lines of corn. The hybrid's characteristic high yield makes it attractive to farmers. Because of the Mendelian mechanics of breeding, the strategy of using seed from the crop itself (i.e., the product of a hybrid X hybrid cross) fails because most of the seed will lack those high-yield characteristics of the original hybrid. Farmers therefore must return to the seed company every year for a new batch of high-yield hybrid seed.

  America's biggest hybrid corn seed company, Pioneer Hi-Bred International (now owned by Du Pont), has long been a mid-Western institution. Today it controls about 40 percent of the U.S. corn seed market, with $1 billion in annual sales. Founded in 1926 by Henry Wallace, who went on to become Franklin D. Roosevelt's vice president, the company used to hire as many as forty thousand high-schoolers every summer to ensure the hybridity of its hybrid corn. The two parental strains were grown in neighboring stands, and then these "detasselers" removed by hand the male pollen-producing flowers (tassels) before they became mature from one of the two strains. Therefore, only the other strain could serve as a possible source of pollen, so all the seed produced by the detasseled strain was sure to be hybrid. Even today, detasseling provides summer work for thousands: in July 2002, Pioneer hired thirty-five thousand temps for the job.

  One of Pioneer's earliest customers was Roswell Garst, an Iowa farmer who, impressed by Wallace's hybrids, bought a license to sell Pioneer seed corn. On September 23, 1959, in one of the less frigid moments of the Cold War, the Soviet leader Nikita Khrushchev visited Garst's farm to learn more about the American agricultural miracle and the hybrid corn behind it. The nation Khrushchev had inherited from Stalin had neglected agriculture in the drive toward industrialization, and the new premier was keen to make amends. In 1961, the incoming Kennedy administration approved the sale to the Soviets of corn seed, agricultural equipment, and fertilizer, all of which contributed to the doubling of Soviet corn production in just two years.

  As the GM food debate swirls around us, it is important to appreciate that our custom of eating food that has been genetically modified is actually thousands of years old. In fact, both our domesticated animals, the source of our meat, and the crop plants that furnish our grains, fruits, and vegetables, are very far removed genetically from their wild forebears (see Plate 36).

  Agriculture did not suddenly arise, fully fledged, ten thousand years ago. Many of the wild ancestors of crop plants, for example, offered relatively little to the early farmers: they were low-yield and hard to grow. Modification was necessary if agriculture was to succeed. Early farmers understood that modification must be bred in ("genetic," we would say) if desirable characteristics were to be maintained from generation to generation. Thus began our agrarian ancestors' enormous program of genetic modification. And in the absence of gene guns and the like, this activity depended on some form of artificial selection, whereby farmers bred only those individuals exhibiting the desired traits – the cows with the highest milk yield, for example. In effect, the farmers were doing what nature does in the course of natural selection: picking and choosing from among the range of available genetic variants to ensure that the next generation would be enriched with those best adapted for consumption, in the case of farmers; for survival, in the case of nature. Biotechnology has given us a way to generate the desired variants, so that we do not have to wait for them to arise naturally; as such, it is but the latest in a long line of methods that have been used to genetically modify our food.

  Weeds are difficult to eliminate. Like the crop whose growth they inhibit, they are plants too. How do you kill weeds without killing your crop? Ideally, there would be some kind of pass-over system whereby every plant lacking a "protective mark" – the weeds, in this case – would be killed, while those possessing the mark – the crop – would be spared. Genetic engineering has furnished farmers and gardeners just such a system in the form of Monsanto's "Roundup Ready" technology. "Roundup" is a broad-spectrum herbicide that can kill almost any plant. But through genetic alteration Monsanto scientists have also produced "Roundup Ready" crops that possess built-in resistance to the herbicide, and do just fine as all the weeds around them are biting the dust. Of course, it suits the company's commercial interests that farmers who buy Monsanto's adapted seed will buy Monsanto's herbicide as well. But such an approach is also actually beneficial to the environment. Normally a farmer must use a range of different weed killers, each one toxic to a particular group of weeds but safe for the crop. There are many potential weed groups to guard against. Using a single herbicide for all the weeds in creation actually reduces the environmental levels of such chemicals, and Roundup itself is rapidly degraded in the soil.

  Unfortunately, the rise of agriculture was a boon not only to our ancestors but to herbivorous insects as well. Imagine being an insect that eats wheat and related wild grasses. Once upon a time, thousands of year
s ago, you had to forage far and wide for your dinner. Then along came agriculture, and humans conveniently started laying out dinner in enormous stands. It is not surprising that crops have to be defended against insect attack. From the elimination point of view at least, insects pose less of a problem than weeds because it is possible to devise poisons that target animals, not plants. The trouble is that humans and other creatures we value are animals as well.

  The full extent of the risks involved with the use of pesticides was not widely apparent until Rachel Carson first documented them. The impact on the environment of long-lived chlorine-containing pesticides like DDT (banned in Europe and North America since 1972) has been devastating. In addition, there is a danger that residues from these pesticides will wind up in our food. While these chemicals at low dosage may not be lethal – they were, after all, designed to kill animals at a considerable evolutionary remove from us – there remain concerns about possible mutagenic effects, resulting in human cancers and birth defects. An alternative to DDT came in the form of a group of organophosphate pesticides, like parathion. In their favor, they decompose rapidly once applied and do not linger in the environment. On the other hand, they are even more acutely toxic than DDT; the sarin nerve gas used in the terrorist attack on the Tokyo subway system in 1995, for instance, is a member of the organophosphate group.

  Even solutions using nature's own chemicals have produced a backlash. In the mid-1960s, chemical companies began developing synthetic versions of a natural insecticide, pyrethrin, derived from a small daisylike chrysanthemum. These helped keep farm pests in check for more than a decade until, not surprisingly, their widespread use led to the emergence of resistant insect populations. Even more troubling, however, pyrethrin, though natural, is not necessarily good for humans; in fact, like many plant-derived substances it can be quite toxic. Pyrethrin experiments with rats have produced Parkinson-like symptoms, and epidemiologists have noted that this disease has a higher incidence in rural environments than in urban ones. Overall – and there is a dearth of reliable data – the Environmental Protection Agency estimates that there may be as many as 300,000 pesticide-related illnesses among U.S. farmworkers every year.

  Organic farmers have always had their tricks for avoiding pesticides. One ingenious organic method relies on a toxin derived from a bacterium – or, often, the bacterium itself – to protect plants from insect attack. Bacillus thuringiensis (Bt) naturally assaults the cells of insect intestines, feasting upon the nutrients released by the damaged cells. The guts of the insects exposed to the bacterium are paralyzed, causing the creatures to die from the combined effects of starvation and tissue damage. Originally identified in 1901, when it decimated Japan's silkworm population, Bacillus thuringiensis was not so named until 1911, during an outbreak among flour moths in the German province of Thuringia. First used as a pesticide in France in 1938, the bacterium was originally thought to work only against lepidopteran (moth/butterfly) caterpillars, but different strains have subsequently proved effective against the larvae of beetles and flies. Best of all, the bacterium is insect-specific: most animal intestines are acidic – that is, low pH – but the insect larval gut is highly alkaline – high pH – just the environment in which the pernicious Bt toxin is activated.

  In the age of recombinant DNA technology the success of Bacillus thuringiensis as a pesticide has inspired genetic engineers. What if, instead of applying the bacterium scattershot to crops, the gene for the Bt toxin were engineered into the genome of crop plants? The farmer would never again need to dust his crops because every mouthful of the plant would be lethal to the insect ingesting it (and harmless to us). The method has at least two clear advantages over the traditional dumping of pesticides on crops. First, only insects that actually eat the crop will be exposed to the pesticide; non-pests are not harmed, as they would be with external application. Second, implanting the Bt toxin gene into the plant genome causes it to be produced by every cell of the plant; traditional pesticides are typically applied only to the leaf and stem. And so bugs that feed on the roots or that bore inside plant tissues, formerly immune to externally applied pesticides, are now also condemned to a Bt death.

  Today we have a whole range of Bt designer crops, including "Bt corn," "Bt potato," "Bt cotton," and "Bt soybean," and the net effect has been a massive reduction in the use of pesticides. In 1995 cotton farmers in the Mississippi Delta sprayed their fields an average of 4.5 times per season. Just one year later, as Bt cotton caught on, that average – for all farms, including those planting non-Bt cotton varieties – dropped to 2.5 times. It is estimated that since 1996 the use of Bt crops has resulted in an annual reduction of 2 million gallons of pesticides in the United States. I have not visited cotton country lately but I would wager that billboards there are no longer hawking chemical insect-killers; in fact, I suspect that Burma-Shave ads are more likely to make a comeback than ones for pesticides. And other countries are starting to benefit as well: in China in 1999 the planting of Bt cotton reduced pesticide use by an estimated 1,300 tons (see Plate 37).

  Biotechnology has also fortified plants against other traditional enemies in a surprising form of disease prevention superficially similar to vaccination. We inject our children with mild forms of various pathogens to induce an immune response that will protect them against infection when they are subsequently exposed to the disease. Remarkably when a plant, which has no immune system properly speaking, has been exposed to a particular virus, it often becomes resistant to other strains of the same virus. Roger Beachy at Washington University, in St. Louis, realized that this phenomenon of "cross-protection" might allow genetic engineers to "immunize" plants against threatening diseases. He tried inserting the gene for the virus's protein coat into the plants to see whether this might induce cross-protection without exposure to the virus itself. It did indeed. Somehow the presence in the cell of the viral coat protein prevents the cell from being taken over by invading viruses.

  Beachy's method saved the Hawaiian papaya business. Between 1993 and 1997, production declined by 40 percent thanks to an invasion of the papaya ringspot virus; one of the islands' major industries was thus threatened with extinction. By inserting a gene for just part of the virus's coat protein into the papaya's genome, scientists were able to create plants resistant to attacks by the virus. Hawaii's papayas lived to fight another day.

  Scientists at Monsanto later applied the same harmless method to combat a common disease caused by potato virus X. (Potato viruses are unimaginatively named. There is also a potato virus Y.) Unfortunately, McDonald's and other major players in the burger business feared the use of such modified spuds would lead to boycotts organized by the anti-GM food partisans. Consequently, the fries they now serve cost more than they should.

  Nature conceived onboard defense systems hundreds of millions of years before human genetic engineers started inserting Bt genes into crop plants. Biochemists recognize a whole class of plant substances, so-called secondary products, that are not involved in the general metabolism of the plant. Rather, they are produced to protect against herbivores and other would-be attackers. The average plant is, in fact, stuffed full of chemical toxins developed by evolution. Over the ages, natural selection has understandably favored those plants containing the nastiest range of secondary products because they are less vulnerable to damage by herbivores. In fact, many of the substances that humans have learned to extract from plants for use as medicine (digitalis from the foxglove plant, used in precise doses, can treat heart patients), stimulants (cocaine from the coca plant), or pesticides (pyrethrin from chrysanthemums) belong to this class of secondary products. Poisonous to the plant's natural enemies, these substances constitute the plant's meticulously evolved defensive response.

  Bruce Ames, who devised the Ames test, a procedure widely relied upon for determining whether or not a particular substance is carcinogenic, has noted that the natural chemicals in our food are every bit as lethal as the noxious chemicals we
worry about. Referring to tests on rats, he takes coffee as an example:

  There are more rodent carcinogens in one cup of coffee than pesticide residues you get in a year. And there's still a thousand chemicals left to test in a cup of coffee. So it just shows our double standard: If it's synthetic we really freak out, and if it's natural we forget about it.