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NS 6 jul 02

Drug genes could enter food chain

Loopholes in US regulations raise fears that food crops will be contaminated with pharmaceuticals

PHILIP COHEN, SAN FRANCISCO

THE rules the US government is proposing for field tests of crops that have been genetically modified to produce pharmaceutical products are not strict enough to prevent the contamination of food crops, experts have told New Scientist. They say the proposed rules are based on flawed science, that there are loopholes allowing them to be bypassed, and that companies do not even have to disclose what genles have been added. And they warn of severe environmental consequences if a drug-laced plant were to breed with other crops or wild relatives. Biotech companies plan to produce a vast range of products, from drugs to vaccines, in plants. "These plants have the potential for more benefit than any other agribiotech product," says Jane Rissler of the Union of Concerned Scientists in Washington DC. "But to realise those benefits we have to be very careful about the risks." The US Department of Agriculture's (USDA) plans don't come close, she says. What scares Rissler and others is that there could be a rerun of the Starlink debacle, in which GM corn strictly not intended for human consumption ended up on grocery shelves. If any contamination involved a crop producing a potent drug, the consequences could be far more serious, she says. The proposed rules require the pharmed" plants to be separated from other crops in time as well as space. For example, pharmed maize must be grown at least 400 metres away from other maize. It must also be planted two weeks before or after nearby crops, so that it isn't fertile at the same time. Similar regulations have been outlined for other plants that have been engineered to make drugs, including barley, corn, rice and sugar cane. But when it comes to keeping harvested products separate, the rules are vague, talking only of "adequate identification, packaging and segregation". Companies that violate these procedures can be fined $250,000, and individuals could face jail sentences of up to five years. James White, the USDA's branch chief for biotech evaluations, is confident the rules will do their job: "The chance of gene flow is essentially zero." . "These rules are more stringent than prior recommendations, and I applaud that," says Norman Ellstrana of the University of California, Riverside, who sat on a National Academy of Sciences committee that reviewed the regulations for GM crops. "But there are big holes in the system." The NAS report points out that some of the USDA's rules have no clear scientific rationale. For instance, the isolation distance for com is simply double the 200 metres it recommends for the production of GM seeds. The assumption is that this spacing will reduce contamination to o.1 per cent, but there is no evidence that the contamination risk drops off with this increase in distance. Only last week, Australian researchers reported that pollen from oilseed rape had contaminated fields uP tO 3 kilometres away, and that there was no obvious drop-off with distance (Science, VOI 296, p 2386). Another serious concern is that the USDA focuses on the intended use of a crop product and ignores its other possible impacts. For instance, the Texas-based company Prodigene applied to grow maize that produces a chicken-egg protein called avidin, which is known to kill or harm 26 species of insects. But because avidin is not classed as a drug, the crop doesn't come under the pharming regulations. Nor did the USDA look at the maize's environmental impact because the crop wasn't being grown in order to kill insects. "if they had used the same protein as an insecticide, they would have called in the Environmental Protection Agency to regulate it," says Ellstrand. WhileAvidin's properties are well known, that is not the case with every drug that might end up being grown in crops. Ellstrand and his colleagues were disturbed to discover that the publicly available descriptions of genes spliced into some plants are incredibly vague. White says the USDA will start posting fact sheets on genes in transgenic plants later this month. When a company wants to keep the identity of a gene secret, it will give it a code name and a general description, such as "Gene S is a hormone in humans. It is harmless to invertebrates," and so on. ' . He also says the only drugs so far being grown in crops are proteins that would simply be digested if accidentally eaten by humans or animals. "The risks are minimal," White says. "No one is making Viagra in a field : " But there's nothing to stop companies producing a Viagra crop if they want to. "It's a disaster waiting to happen," says Doreen Stabinsky, a science adviser for Greenpeace. "Grow this stuff in a greenhouse or a cave, not in an open field where animals can grab the seeds." Ellstrand agrees that stricter containment is needed. Pharmed plants could be genetically engineered to prevent gene flow using methods such as the infamous Terminator technique, which makes seeds sterile, or a newly proposed one dubbed the Exorcist (see page 32). And to be absolutely certain the food supply is safe, he argues that only plants that aren't grown for food should be used to make drugs. White points out that when the long-awaited regulations are finally published, the public will have 120 daystorespond."Iwouldn'tbe surprised if we got thousands of letters telling us: not in food."

Market forces 'are the way to save the planet'

WHATam lbid forthe atmosphere? Or would you like to put in an offer for the oceans? Privatisation of these global "com?hons" might just be the future of conservation. In a reajor publication later this month from Britain's Royal Society, environmental economists will argue that traditional methods of goverrunent-run conservation have failed: protected areas, gene banks and intemational aid have been found wanting. The economists say it's time for capitalism to take charge. They want the environment parcelled out to the private sector, with market forces influencing everything from cleaning up our rivers and atmosphere to protecting forests and soils. "We can create and manage our environment as a business and make sustainability pay for itself," says Ian Swingland of the University of Kent, who compiled the study to be published in the Philosophical Transactions of the Royal Society A. Next month the US and other nations at the World Summit on Sustainable Development in johannesburg are also expected to call for conservation to be privatised. But many environmentalists say this will simply steal the planet's resources from the poor and worsen poverty.

The model for market-based conservation is the US's success in curbing acid rain by creating a market in permits to emit sulphur dioxide, the main culprit. The strategy cut the expected costs by go per cent. The Kyoto Protocol envisages doing the same for greenhouse gases. The economists see this process going much further. For one thing, the Kyoto Protocol proposes allowing foresters to sell the carbonabsorbing capacity of their trees. if they could make money from keeping trees standing, that would also help protect the world's biodiversity, the economists argue. And extending the rules to cover carbon in soils could trigger a farming revolution by encouraging farmers not to plough, which produces CO2. That would benefit both farmers and the atmosphere. Meanwhile, you could expand markets in trading water if polluters get to make money out of cleaning up their pollution. That should mean dirty rivers can once again be used for drinking or irrigation. But to succeed, "ownership of the environment is fundamental," says Richard sandor, chairman of a leading US-based envirorunent financial products company. And critics fear this is just the beginning of problems for the poor. Natasha Landell-Mills of the London-based international Institute for Environment and Development warns that the rules of trading will, in practice, often be skewed to suit the most powerful interests. Hundreds of millions of poor people live in forests that provide many of their daily needs, without having formal ownership. If the process of privatisation excluded them, they would undoubtedly be worse off. Fred Pearce *

Light turns liquid Computers could send information drop by drop

EUGENIE SAMUEL

LIGHT can be turned into a glowing stream of liquid that splits into droplets and splatters off surfaces just like water. The researchers who've worked out how to do this say "liquid light" would be the ideal lifeblood for optical computing, where chips send light around optical "circuits" to process data. Liquid light sounds like a contradiction, since the three phases gas, liquid and solid usually only apply to atomic matter. Although researchers sometimes talk about a light beam as if it's a gas, because the photons move around randomly within the beam and can exert pressure due to their momentum, they don't usually mean it literally until now.

You really can think of light as a gas, says Humberto Michinel's team at the University of Vigo in Ourense. And like any gas, it can be made to condense into a liquid. The researchers have been working on "non-linear" materials, which slow light down by an amount that depends on the intensity of the beam rather than simply a fixed amount, as happens in water or glass. In most non-linear materials, the more intense the light, the more it is slowed down. That means the inside of a beam slows more than the outside, as if it were passing through a convex lens, and the beam is focused to a point, rather than transmitted as you'd want in an optical computer. But this doesn't have to happen, Michinel realised. if you have a material in which the light slows less when the intensity of the beam gets very high, then a high-energy laser beam could be concentrated into a tight column instead. This column behaves just like a liquid, says group member lose Ramon Salguiero at the University of Santiago de Compostela in Spain. The researchers carried out computer simulations of what would happen to a light pulse concentrated in this way. They showed that the pulse had a kind of surface tension, making it stretchy on the outside, and that it would shatter into smaller drops when it bounced off a surface, just like a liquid (see Graphic). They have published their results in Physical Review E (vol 65, p o66604). Other researchers aren't convinced, however. "The name is catchy and it's a clever idea, but I'm not sure it's really going to change things," says Demetrios Christodoulides at Lehigh University in Bethlehem, Pennsylvania, part of a competing team also working on non-linear materials. One problem is whether the material that Michinel wants to use to test his predictions will be up to the task. Michinel reckons a "chalcogenide" glass made by Fr6d6ric Smektala and colleagues at the University of Rennes in France is just right for making liquid light. But Christodoulides says that the material would have to interact so strongly with the light that the droplets would probably be absorbed before they could get anywhere. But if the researchers can make liquid light, blobs of the stuff could form the heart of an optical computer. The speed of silicon-based processors is limited by the rate at which electrons move round circuits. An optical computer based on photons would be much faster, but it's tough to bounce light around without the beam spreading out and information disappearing. "Liquid drops are optimal candidates to be information bits," says Michinel. But Christodoulides believes his own approach is a better bet: adjusting the design of optical pathways so that they handle pulses of ordinary light better. "Pulses are discrete things and you can do digital operations with them," he says. "A liquid can end up anywhere and be quite unpredictable."

DARK MAtteR It's an echo from the fifth dimension

THERE'VE been some pretty strange theories to explain the identity of the missing mass that must exist to make the Universe behave the way it does. Now there's another one: the lost mass is made of echoes from the hidden dimensions of space. One reason physicists seriously contemplate the possibility that higher dimensions exist is because of superstring theory. This is the best candidate for a "theory of everything", and it says that there are six extra space dimensions in addition to the three of space and one of time that we know. We can't see or move in these extra dimensions. And they must be minuscule. If they were any more than a fraction of the size of an atom, we would have detected signs of them already. But if they exist, physicists say there must be a whole load of extra particles out there too. These are known as Kaluza-Klein particles, and were first suggested in the 192os. They would arise when force fields such as the electromagnetic field and the gravitational field bounce around in small, hidden dimensions, rather like the sound of a voice bouncing around in a small room. This would create "echoes" or distortions in the fields, which would manifest themselves as particles. If there are higher dimensions, then quarks, electrons and all the other familiar particles would have a whole family of heavier cousins. No Kaluza-Klein particles have been observed in collisions at any particle accelerator, so the lightest must require an enormous amount of energy to create. They would have been created in abundance in the energetic conditions that existed in the first split second of the Universe. But physicists have always assumed they would have been much too short-lived to survive until now. Two physicists now say that assumption may be wrong. Tim Tait of the Argonne National Laboratory in Illinois and G6raldine Servant of the University of Chicago have calculated that the lightest KaluzaKlein particle the first echo of the photon or neutrino could be stable after all. "it could have survived to the present day," says Tait The particle would probably interact with normal matter only very rarely. So if is still around today, it could explain why there seems to be a lot more mass in the Universe than astronomers can actually see. Tait and Servant worked out that if Particles would arise when force fields bounce around in small, hidden dimensions, like the sound of a voice bouncing around in a small room"

The Kaluza-Klein photon or neutrino is 800 to 1000 times as massive as a proton, then the mass of the particles they'd expect to have survived since the big bang would be just about right to explain the amount of dark matter in the Universe. They have submitted their findings to NuclearPhysics B. "Such things are possible," admits Joseph Silk of the University of Oxford. If Tait and Servant are right, the super-heavy photon or neutrino could show up in the next generation of particle accelerators as they smash particles together at higher and higher energy. More intriguingly, because the KaluzaKlein particles are so heavy, they'd be drawn by gravity towards the centre of the Sun and of our Milky Way. Matter and antimatter versions of the particles would then be likely to meet and annihilate each other, possibly creating a characteristic signature of gamma rays and high-energy electrons that physicists could look for to prove the existence of the Kaluza-Klein particles. Marcus Chovvn

SEX Bigger is better when it comes to the G-spot

NICOLA JONES

DRUGS such as Viagra should work for some women especially if they have a big G spot. This spot, famed for producing spectacular orgasms, tums out to be awash with the enzymes that these drugs act on. The term G spot, coined by Emest Grifenberg in 1950, refers to an area a few centimetres up inside the vagina on the side closest to a woman's stomach (see above). Buried in the flesh here are the Skene's glands, the female equivalent of the prostate gland. In men, the prostate produces the watery component of semen. In women, Skene's glands are also thought to produce a watery substance that may explain female "ejaculation". The tissue surrounding these glands, which includes the part of the clitoris that reaches up inside the vagina, swells with blood during sexual arousal.

"It's great for women that understanding of the clitoral and vaginal structure and function is developing"

And there's some evidence that nerves in the area produce an orgasm different to one produced by clitoral stimulation. Nevertheless, there is still debate about whether the G spot even exists. "Not everyone has accepted this yet," says Beverly Vifhipple, a neurophysiologist who co-wrote a book about the G spot in the 1980s. So Emmanuele Jannini of the University of Aquila, Italy, and his team decided to look for biochemical markers of sexual function in the area where the G spot is meant to be. They picked PDE5, an enzyme that chews up the nitric oxide that triggers erections. Viagra works by blocking PDE5. Researchers had seen evidence of nitric oxide activity in the clitoris before, but no one had actually looked for PDE5 enzymes or knew exactly where they might be. "It's ridiculous but true that we've waited till now to really know the female anatomy," says Jannini. He found PDE5 in the vagina of five volunteers, he will report in Adult Urology. Dissections Of 14 cadavers revealed that the enzymes were mostly clustered in the G spot. But in two of the subjects with much lower concentrations of PDES, he couldn't find any Skene's glands at all. "For such women, having a vaginal orgasm is anatomically impossible," he says. Whipple and others suspect the glands may have been there but were too small to spot. Even so, the small size of the area should make a "G-spot orgasm" unlikely. The findings suggest that Viagra and related drugs like tadalafil and vardenafil, set to hit the market in a few months, should have the greatest effect on women who have large Skene's glands and heaps of PDE5. Trials of Viagra in women have so far had mixed results. Some researchers speculate that this is because the women tested had too broad a range of sexual problems, from not reaching orgasm to not wanting sex at all. Jannini's work suggests that a woman's anatomy might also make a difference. "Research in women using these drugs has been hampered by a lack of a framework demonstrating the biochemical processes governing the female sexual response," says Helen O'Connell of the Royal Melbourne Hospital, Australia, who showed in i998 that the clitoris is far bigger than anyone thought (New Scientist, 1 August 1998, p 34). "That understanding of the clitoral and vaginal structure and function is developing is great for women.' So how do you tell if you've got a G spot? Sadly, because Skene's glands are so wen hidden by the surrounding tissue, no visual examination can reveal if a women has them or not. Only personal experience can do the trick. But even for those with a small G spot or none at all, Viagra-type drugs might still have some effect, as PDE5 is found in the clitoris too. And other drugs that stimulate arousal via the brain could soon become available (New Scientist, 3 November 2001, p 11). But Jannini and Whipple both agree that the female orgasm is so complex that drugs alone won't work for everyone.

Exorcist the Phoenix of Terminator Tech

A NICKNAME can sometimes be the kiss of death. It wasn't so long ago that scientists at the US Department of Agriculture were crowing over a bit of genetic engineering they called the Technology Protection System, a way to make crop seeds sterile and so stop genetically engineered genes from spreading. But anti-GM groups gave it a more sinister name: Terminator. They pointed out that the technology would put an end to the age-old tradition of saving seed from this year's crop to plant next year, forcing poor farmers to buy new seed every year. Soon companies and researchers couldn't move fast enough to distance themselves from the technology. But Pim Stemmer doesn't seem too worried by the label an anti-GM group recently gave his new idea. "They call it Exorcist?" he laughs. "Now that's good. I like it.' Exorcist is also a genetic trick, but it's more cunning than Terminator. Rather than killing the seeds of GM plants, Exorcist splices out and destroys every bit of foreign DNA inside the seeds and fruit before the crop is harvested. The crop benefits from a GM trait but the food it yields is, in theory, GM free. Stemmer bets that for a lot of people the stigma of GM food would vanish along with those foreign genes. And as vice-president of research at the biotech company Maxygen in Redwood City, California, he is confident he could turn that bit of molecular magic into reality. "I think this is a compromise between two reasonable policies," says Stemmer. "Farmers get to use GM plants and consumers get GM-free food ' " And he says the benefits would go way beyond making food more palatable to people simply spooked by the thought of GM. Consumer concems over allergic or toxic reactions to proteins from the newly introduced genes will evaporate. Farmers could plant their crops without worrying that some errant gene will escape via pollen into other crops or plants. And since the valuable genes would vanish at the end of the crop's life cycle, companies would get extra protection against theft of the GM crops they created. And while Exorcist already has its foes, it has fans as well. "This is revolutionary in a lot of ways," says William Muir, a geneticist at Purdue University who studies gene flow between GM and non-GM organisms. "In one fell swoop it seems to address a lot of concems people have about GM plants." And according to Stemmer, giving all sides new benefits is the perfect way to bring the GM food debate to a close. Stemmer and his Maxygen colleague, Robert Keenan, first floated their idea a few months ago in a commentary in the journal Nature Biotechnology (VOI 20, p 215). They point out that in GM agriculture as it is currently practised, genetic changes are wholesale and permanent. Engineers insert DNA containing a foreign gene into a plant cell, where it finds a home by slipping into a chromosome. If that cell gets used to make a new plant, the gene and the protein it produces will be in every tissue of that plant. And once it is there, the foreign gene is in every descendant that inherits the altered chromosome. Critics say that those genes and proteins could trigger nightmarish disasters such as toxic side effects or allergies in people who eat them. And those fears have been fed by reports like those from Arpad Pusztai, a plant researcher in Scotland who announced four years ago that rats who dined on GM potatoes suffered irregularities in their immune system and changes in their internal organs. However, other researchers found serious flaws in Pusztai's experiments and few now believe his claims. More recently, another furors erupted when StarLink, a type of GM corn only approved for animal feed, turned up in grocery stores in taco shells and other products intended for human consumption. The worry was that the gene introduced into the corn, for an insecticidal protein called Crygc, might trigger allergies in some people. Again, there was no evidence that anyone had been hurt. But the incidents weren't good publicity for GM food safety. Exorcist, by banishing all foreign DNA from the plant or just its fruit or seed, would make those fears moot, says Stemmer. "I personally believe GM foods are very safe, so this would be a cosmetic change," he adds. "But if it made people more comfortable with GM products, it would be worth it." A much more serious concern to Stemmer is the potential negative environmental and commercial impact of gene leakage from transgenic plants into unmodified crops or even wild plants. The most recent fiasco involved a report in Nature that claimed transgenic genes had infiltrated traditional maize crops in Mexico and were causing genetic havoc (New Scientist, 15 June, P 14). This research has been questioned, but plant companies concede that their transgenes may have inadvertently slipped into crops, even in their own greenhouses. Here too, Exorcist-would solve that problem by removing foreign ge-ties from pollen before it matured. Indeed, Exorcist incorporates three features that were at the heart of a 2ooo report by the Advisory Committee on Releases to the Environment (ACRE), which advises the British government (New Scientist, 28 OCt 2000, P 4). It recommended that companies engineer plants to limit gene flow, switch genes on only where they are needed and incorporate as little foreign DNA as possible. "If you can excise all the DNA that may cause the problems, so much the better," says Brian Johnson, biotechnology adviser with English Nature and an adviser to ACRE. "It's encouraging that people are beginning to think this way." Here's how Exorcist works. At its heart is a little protein called Cre, borrowed from a virus that usually infects bacteria. Cre is an enzyme called a "recombinase", a pair of molecular scissors that can snip out any DNA that lies between two copies of a short marker sequence called loxp. Cre and enzymes like it are already widely used to manipulate DNA in plants and animal cells. But it was Stemmer's insight that it could be used to excise all the genes that plant biologists were splicing into crops. He suggested that alongside the gene for a trait you want to engineer in, say, herbicide resistance, you also insert a gene for Cre and flank the entire piece with loxp markers. Finally you insert a regulatory DNA site, or promoter, to tum Exorcist on exactly where and when it's needed (see Diagram, left). In the edible part of the crop that usually means at the early stage of development, while in the reproductive organs it might be before the pollen starts to ripen. To achieve such exquisite control over the timing and location of the exorcism, Stemmer suggests using a tissue-specific promoter. These are naturally-occurring sequences which switch genes on only in a particular tissue at a particular time. For example, to delete a foreign gene from fruit, you could choose a promoter that normally activates genes involved in the fruit's early development. As those first few cells start to differentiate into fruit cells, the Exorcist system also springs into action, excising all the DNA between the recognition sites. All that's left in the fruit cell chromosome is a tiny footprint 34 DNA letters long a loxp site but no active genes making foreign proteins. The excised DNA forms a loop that usually breaks down and disappears in a few days, or is simply diluted into insignificance by cen division. By the time it's harvested the fruit is GM-free. Tissue-specific promoters aren't the only option. If you prefer more hands-on control, you can use a promoter that is inactivated by an externally-applied chemical such as ethanol. Under normal conditions, the promoter switches on the Cre gene and Exorcist does its work in every tissue of the crop plant. But spray the field with ethanol and you shut down the system and the foreign genes stay in place. That way, farmers could remove foreign genes from plants destined for the dinner table, but hang onto them in plants they want to use for seed crop. And if those genes should escape from that seed crop in pollen, they would simply splice themselves out of their new host and disappear. Stemmer suggests that labs could even evolve the Cre recombinase to recognise native plant DNA sequences instead of loxp. That would mean you could even remove that tiny DNA footprint, leaving nothing but natural DNA. "It really surprises me that no one had proposed this before," says Stemmer. On paper the system looks fairly simple. The necessary components, such as Cre, all exist as research tools, or, like the tissue-specific promoters, are something plant biotech companies are eager to develop. But will it really work? Stemmer cites the work of Nam-Hai Chua of New York's Rockefeller University who showed the Cre excision is already almost loo per cent successful in plant cells (Nature Biotechnology, vol 19, P 157). But Chua is sceptical about Exorcist. He points out that in his research, excision from plant tissues was very efficient. But in the seeds it was incomplete, ranging from 22 to 69 per cent. "And out in the field, the plant is going to be subjected to all sorts of unpredictable insults," he says. "In the lab, they are taken care of like babies. I'm not saying it's not going to work, but they have to prove it does."

"This is revolutionary in a lot of ways. In one fell swoop it seems to address a lot of concems people have about genetically modified plants"

David Ow of the US Department of Agriculture's Plant Gene Expression Center in Albany, Califomia, one of the pioneers in using the Cre/loxP system in plants, adds an even more bizarre twist. He says that in some of his experiments the excised DNA doesn't disappear but mysteriously persists inside plant cells in a form Ow hasn't yet been able to figure out. "You are going to need some elegant and fine genetic engineering to make this really reliable," he says. "But if it does work, it could have real benefits for people who are anti-GM. Someone is going to give ft a trY." Stemmer is undeterred. He points out that many of the components of Exorcist are already being worked on for other reasons, such as controlling expression of genes in different parts of plants. He also points out there are other recombinases more likely to leave the DNA in a form that is more amenable to breaking down. While he agrees that nothing can be guaranteed at ioo per cent, he thinks some GM residue, offending genes in less than 1 per cent of cells, for example, could be tolerated in much the way as some trace of pesticide or dirt is tolerated now. in fact, there is hardly a technical problem that Stemmer hasn't got a fix for. For instance, you might think that removing the genes from the seeds or fruit might rule out improving their nutritional content, a fundamental goal of so-called "second-generation" GM technology. Not so, says Stemmer. Because seeds draw most of their nutrients from elsewhere in the plant, it would still be possible to boost vitamins and other nutrients. What about genes you want to stay in the seed during growth such as those that might protect it from insects? He would put those under a "desiccation-inducible" promoter so the gene would be exorcised as the grain dries after harvest.

"People who continue to reject GM will be shown for what they are, non-rational and anti-technology and it will make them look stupid. That's really good"

"The technical part of this is will be the simplest part," he says. The hardest part will be convincing GM's biggest critics. "It's an attempt to'greenwash'the issui , rather deceptive," says Sue Mayer of Genewatch UK. To her, the technology is really just Terminator 2, an attempt to pass off a technology that protects intellectual property as a food and environmental safety tool. "I just had to laugh when I saw it." And she doesn't trust Exorcist to behave as advertised. She points out that engineering plants has already had some unintended consequences. Recently, for instance, GM potatoes designed to be resistant to sap-sucking bugs became more susceptible to other types of insects (New Scientist, i June, P 17). Putting more genes and clever switches into plants is only going to increase the range of unforeseeable consequences, she says. "Why should society accept a new, unproven technology to fix a defective one?" agrees Hope Shand of action group ETC (formerly the Rural Advancement Foundation International), whose team coined the term Exorcist and were among the most vocal opponents of Terminator. She feels that Stemmer's offer to banish the evil spirit of spliced genes is a tacit admission that transgenics are dangerous in the first place. But Stemmer is convinced that if he can remove every detectable trace of engineered genes from food, he will convert "reasonable" people to GM. "If we go all this way to address their concerns, the people who continue to reject it will be shown for what they are, non-rational and anti-technology and it will make them look stupid. That's really good." It would be Exorcist's best trick if it could split the GM opposition as effectively as it snips out foreign DNA. But there are still some major hurdles to overcome. As both Shand and Mayer point out, it's a mistake to define the GM debate in purely technical terms. One of the most powerful objections to GM technology is that it makes farmers increasingly dependent on large seed companies. That's something the Exorcist system which Maxygen has filed a patent on cannot solve. Stemmer may have an even tougher sell when it comes to the agribusiness giants. If the big companies aren't willing to put their money down to develop the technology, Exorcist will remain exactly where it is now: a clever idea on a piece of paper. So far the big companies aren't beating a path to Stemmer's door. "This approach is astronomically unfeasible right now. Id rather take the money and perfect golden rice [vitamin A-enriched rice]," says Mary-Dell Chilton of the crop biotechnology giant Syngenta. Her company feels that by simply educating the public more about GM food, consumer support for these products will grow. Exorcist's creator says he often encounters a similar attitude among other plant scientists. "Companies think if they can get over this current hump of opposition, the crops they have right now are going to win over the public," says Stemmer. "But what if they don't get over that hump? They [email protected]'t got an altemative." For that reason, he prefers a different name for Exorcist. He calls it "Plan B".