91av

IN THE long-running debate over the safety of genetically modified organisms, one fear stands head and shoulders above the rest: what if the genes we insert don’t stay where we put them, but instead escape into other species? One of the panicky subtexts behind the tabloid references to Frankenfoods is the possibility that engineered genes, like Mary Shelley’s monster, might escape their master’s control and turn nasty. Is this a legitimate concern or empty scaremongering that can only muddy the waters over the future of genetic engineering?

The answer is an unsettling one. In the real world, organisms of different species toss genes back and forth all the time. They always have, and they always will. Occasionally, even before the advent of transgenics, this genetic shuffling created a weedier weed, or drove a wild species toward extinction. The real question, then, is not whether transgenes might move: they will. But is this any more dangerous than the high jinks ordinary genes get up to? So far, at least, the answer is clear.

The latest evidence, including results of the first-ever experimental tests, suggests that today’s GM organisms aren’t worth losing sleep over. But that doesn’t mean we can sit back with a sigh of relief: new transgenes that may hit the market within the next 10 years could carry a much greater potential for harm.

Even though gene transfer is common in nature, little of it involves genes taking great evolutionary leaps between unrelated species. Sure, bacteria are experts at “horizontal gene transfer”, in which one species picks up fragments of DNA shed by another. We’ve seen it in the explosion of antibiotic resistance over the past 50 years as a wide range of species swap resistance genes like business cards. But horizontal transfer between plants and animals, or between these organisms and bacteria, is very rare. The draft sequence of the human genome, for example, contains no genes unequivocally acquired from bacteria in the past few hundred million years.

Instead, the overwhelming majority of “escaped” transgenes, especially among plants and animals, will spread through good, old-fashioned sex. Almost every major crop hybridises with wild relatives somewhere in the world, and so do many animals. Often the amount of hybridisation can be staggering, especially when crop plants vastly outnumber their weedy relatives. For example, Neal Stewart, a plant molecular geneticist at the University of Tennessee in Knoxville, tracked the spread of a jellyfish fluorescence gene from rapeseed (canola) to its wild relative, wild turnip. Around the periphery of a rapeseed field, he found that more than 10 per cent of wild turnip plants gave off a telltale glow. “Genes are transferred back and forth all the time, I am convinced,” says Stewart.

Other researchers have found up to 42 per cent of the seed produced by wild sunflowers growing at the margin of a commercial sunflower field were hybrid. Some rapeseed hybrids have been found up to 3 kilometres from the nearest transgenic crop, and hybrids of beets and their wild relatives have been a problem for years. Hybrids are common among animals, too, most notoriously among fish such as trout and minnows.

Genes will wander, then, and there’s no reason to suspect that transgenes are any more or less footloose than the rest. But a little gene flow is not necessarily a problem. After all, it’s been happening for hundreds of millions of years. “Some environmental groups have convinced the public or politicians that as soon as a transgene appears, it’s a hazard. And I think that is not right,” says Detlef Bartsch, a plant ecologist at Aachen University of Technology in Germany.

Instead, the real issue is what effect the gene will have on its new owner. For the most part, that boils down to the question of whether a transgene will make hybrids more likely to survive than their wild kin. If it does, the gene will spread throughout the wild population. If not, then the hybrids are an ecological and genetic dead end, a minor sideline we can safely ignore. “Traits that are not going to persist are not worth worrying about,” says Allison Snow, a plant ecologist at Ohio State University.

If she’s right, and most experts think she is, we can strike several sorts of GM organism off our escaped-transgene worry list straight away. Engineered genes that boost the nutritional value of a crop, such as “golden rice” enriched with vitamin A, probably wouldn’t give a weed any extra edge. In fact, they’d most likely make it less fit by diverting the plant’s energy into producing molecules irrelevant to life in the wild. The same would apply to microbes modified to break down toxic waste: once the waste is gone, the specialised enzymes become an unnecessary burden, and the engineered microbes should fade away. “There should be no risk,” says James Tiedje, a leading microbial ecologist at Michigan State University in East Lansing. Of course, developers would have to check that the transgenes didn’t help the microbes use some other, natural foodstuff, but that should be relatively easy to do.

For similar reasons, transgenes that turn crop plants such as maize into factories for churning out vaccines, drugs or industrial molecules are unlikely to spread widely. But if these GM crops cross-pollinate with nearby food crops, regulators will need to keep checking on them to ensure they don’t become contaminated with unhealthy levels of the foreign molecule. “Who wants a pharmaceutical in their cornflakes?” says Rebecca Goldburg, a senior scientist at Environmental Defense, an advocacy group in New York.

Nor do herbicide-resistance genes pose much of a threat of spreading into natural ecosystems. “As an ecologist, I’m not very concerned,” says Bartsch. “Very often, resistance is achieved at some physiological cost. A person can protect himself against rain with a big plastic raincoat, but it makes him less able to run.” That means herbicide-resistance genes aren’t likely to spread much beyond the edges of cultivated, sprayed fields. The biggest threat is to the agrochemicals company that makes the herbicide. In the end if too many resistant weeds appear, no one will buy the firm’s product.

Weedy relatives might have more to gain from genes that confer resistance to insects or diseases. Snow’s team studied sunflowers engineered to express a gene for the insecticidal toxin, Bt. When the experimental GM crop hybridised with wild sunflowers, the hybrids produced 50 per cent more seeds than ordinary wild sunflowers (91av, 17 August, p 11). The Bt gene helped the wild sunflowers oust unwanted invaders, leaving them with more energy for making seed. “We didn’t even know it, but there were insects feeding inside the stems,” says Snow. “In a case like that, the gene would spread and have a huge advantage.” The sudden increase in fitness could make wild sunflowers much more abundant, upsetting the ecosystem’s normal balance. It could also drive insects toward extinction if their larvae feed exclusively on the sunflowers.

Nothing to worry about

In contrast, wild squash plants bearing a transgene that makes them resistant to mosaic viruses show little or no advantage over their kin without the gene, probably because the virus only rarely causes significant damage except in the crowded conditions of cultivated fields. “So far, we’ve not seen anything that leads us to worry about the escape of these particular transgenes,” says Hector Quemada, a plant pathologist at Western Michigan University in Kalamazoo, who led the work.

No one knows which of these two scenarios will be more common, but most experts agree that the riskiest transgenic traits are still to come. “The genes that catch my attention as an ecologist are anything that makes the plants bigger and healthier, or anything that would allow them to expand their range, like cold tolerance or drought tolerance or salt tolerance,” says Snow. “These are all genes that people are working on now, and they’re going to be available in five or ten years. Those could have some major ecological effects if they get into wild relatives and suddenly those plants could grow where they never grew before.” Such shifts could create noxious new invaders – the transgenic equivalents of scourges such as kudzu and strawberry guava, which crowd out native species and drive them towards extinction.

Not everyone is comfortable with such sweeping generalisations. “It’s too problematic and too complicated to make a blanket statement that a trait like drought tolerance in any crop would be more risky,” says Tom Nickson, who heads Monsanto’s ecological technology centre in St Louis. “It’s too superficial an evaluation.” One reason for the uncertainty is that very few experiments have addressed this issue. “It’s very frustrating that there’s so little research,” says Snow.

That’s especially true for microbes. “We are pretty ignorant about organisms we cannot see, including bacteria,” says Kaare Nielsen, a microbial geneticist at the University of Tromsø, Norway. “When the current state of knowledge is at that level, it’s very difficult to start predicting how transgenes will affect the community.” Genes which came from bacteria in the first place, such as Bt, probably don’t confer much of an advantage. If they did, horizontal transfers among bacteria would already have spread them widely. “But at the point where you start to engineer your own genes and make things which deviate substantially from natural counterparts, it will become increasingly difficult to predict what the outcome would be,” says Nielsen. One especially risky area might be engineering pathogenic microbes for biocontrol, where an escaped virulence gene could create new diseases in other organisms.

Similar considerations apply to the fledgling field of GM animals. Livestock rarely interbreed with wild relatives, so there’s little chance of gene leakage. But plying fish with growth-enhancing genes is more worrying, because fish hybridise so readily. Bigger, faster-growing fish could certainly upset the competitive balance in lakes, rivers and oceans.

Or take the Australian government’s plan to control alien carp by releasing GM fish that produce only male offspring (91av, 11 May, p 6). Such a gene would make females scarcer and scarcer with each generation until the carp pest vanished altogether. Australia has no native species in the carp family, so the gene poses no risk of escape there. “But if that fish were to be brought to China, oh man…,” says Eric Hallerman, a population geneticist at Virginia Tech in Blacksburg. China is the centre of diversity for carp.

The biotech industry, and government regulators, may find ways to reduce the likelihood of troublesome transgenes making their bid for freedom (see “Curbing wanderlust”). However, it seems clear that in the end, there will be no substitute for a case-by-case assessment of the risks. Some transgenes clearly pose negligible risk, while others may well prove far too dangerous to play with. But so far, scientists just don’t know enough about the consequences of wandering transgenes to sort out any but the easiest cases with any confidence. “The science of putting genes in is far ahead of the risk assessment research,” says Marjorie Hoy, an insect geneticist at the University of Florida. Governments, not biotech companies with their obvious conflicts of interest, must ramp up research if they expect the public to trust their safety calls in the future.

But one more twist bedevils those who fear the spread of transgenes into natural populations: any risks apply just as much to traits acquired through conventional breeding. For example, both conventional breeders and genetic engineers have now created salt-tolerant tomato plants (91av, 18 May, p 47). Either one could spread to wild relatives, potentially creating a new weedy invader of saline habitats. Yet while governments and NGOs tightly regulate the planting of GM varieties, they put no restrictions on the products of conventional breeding. “Should we regulate the other methods more, or transgenics less?” asks Stewart.