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鈥檛 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鈥檚 monster, might escape their master鈥檚 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鈥檚 GM organisms aren鈥檛 worth losing sleep over. But that doesn鈥檛 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.
Advertisement
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 鈥渉orizontal gene transfer鈥, in which one species picks up fragments of DNA shed by another. We鈥檝e 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 鈥渆scaped鈥 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. 鈥淕enes are transferred back and forth all the time, I am convinced,鈥 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鈥檚 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鈥檚 been happening for hundreds of millions of years. 鈥淪ome environmental groups have convinced the public or politicians that as soon as a transgene appears, it鈥檚 a hazard. And I think that is not right,鈥 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. 鈥淭raits that are not going to persist are not worth worrying about,鈥 says Allison Snow, a plant ecologist at Ohio State University.
If she鈥檚 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 鈥済olden rice鈥 enriched with vitamin A, probably wouldn鈥檛 give a weed any extra edge. In fact, they鈥檇 most likely make it less fit by diverting the plant鈥檚 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. 鈥淭here should be no risk,鈥 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鈥檛 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鈥檛 become contaminated with unhealthy levels of the foreign molecule. 鈥淲ho wants a pharmaceutical in their cornflakes?鈥 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. 鈥淎s an ecologist, I鈥檓 not very concerned,鈥 says Bartsch. 鈥淰ery 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.鈥 That means herbicide-resistance genes aren鈥檛 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鈥檚 product.
Weedy relatives might have more to gain from genes that confer resistance to insects or diseases. Snow鈥檚 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 (快猫短视频, 17 August, p 11). The Bt gene helped the wild sunflowers oust unwanted invaders, leaving them with more energy for making seed. 鈥淲e didn鈥檛 even know it, but there were insects feeding inside the stems,鈥 says Snow. 鈥淚n a case like that, the gene would spread and have a huge advantage.鈥 The sudden increase in fitness could make wild sunflowers much more abundant, upsetting the ecosystem鈥檚 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. 鈥淪o far, we鈥檝e not seen anything that leads us to worry about the escape of these particular transgenes,鈥 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. 鈥淭he 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,鈥 says Snow. 鈥淭hese are all genes that people are working on now, and they鈥檙e 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.鈥 Such shifts could create noxious new invaders 鈥 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. 鈥淚t鈥檚 too problematic and too complicated to make a blanket statement that a trait like drought tolerance in any crop would be more risky,鈥 says Tom Nickson, who heads Monsanto鈥檚 ecological technology centre in St Louis. 鈥淚t鈥檚 too superficial an evaluation.鈥 One reason for the uncertainty is that very few experiments have addressed this issue. 鈥淚t鈥檚 very frustrating that there鈥檚 so little research,鈥 says Snow.
That鈥檚 especially true for microbes. 鈥淲e are pretty ignorant about organisms we cannot see, including bacteria,鈥 says Kaare Nielsen, a microbial geneticist at the University of Troms酶, Norway. 鈥淲hen the current state of knowledge is at that level, it鈥檚 very difficult to start predicting how transgenes will affect the community.鈥 Genes which came from bacteria in the first place, such as Bt, probably don鈥檛 confer much of an advantage. If they did, horizontal transfers among bacteria would already have spread them widely. 鈥淏ut 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,鈥 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鈥檚 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鈥檚 plan to control alien carp by releasing GM fish that produce only male offspring (快猫短视频, 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. 鈥淏ut if that fish were to be brought to China, oh man鈥,鈥 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 鈥淐urbing wanderlust鈥). 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鈥檛 know enough about the consequences of wandering transgenes to sort out any but the easiest cases with any confidence. 鈥淭he science of putting genes in is far ahead of the risk assessment research,鈥 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 (快猫短视频, 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. 鈥淪hould we regulate the other methods more, or transgenics less?鈥 asks Stewart.
Curbing wanderlust
Biotechnologists know that transgenes, like any other genes, will wander if given the chance. However, they have several ways of reining them in to slow the spread.
鈥void risky products. 鈥淭here have been crops we have chosen not to pursue at this time,鈥 says Tom Nickson of the biotech giant Monsanto. Two good examples are sunflowers and sorghum, both of which hybridise freely with relatives that are already significant weeds.
鈥on鈥檛 use GM organisms in regions where they have wild relatives. For example, the US does not allow farmers to grow GM cotton in southern Florida, where wild cotton also grows. But such restrictions will prove difficult to enforce. Mexico imports millions of pounds of whole, viable GM maize seed each year for animal feed. 鈥淭hey鈥檙e in bags marked 鈥榙o not plant鈥, but are people going to do that, especially if they speak Indian languages and can鈥檛 read Spanish?鈥 asks Norman Ellstrand, a population geneticist at the University of California at Riverside.
鈥se tricks to make hybrids less fit. Transgenes can be paired with a mitigator gene that makes weeds 鈥 but not crops 鈥 less fit, suggests Jonathan Gressel of the Weizmann Institute of Science in Israel. One mitigator might be a dwarfing gene, which can be an advantage in crops. Gressel and his colleagues paired a herbicide-resistance gene with a dwarfing gene in transgenic tobacco, then grew these plants in competition with normal tobacco plants in a greenhouse. The dwarf plants simply couldn鈥檛 compete. 鈥淭he wild type just crowds it out. The few that don鈥檛 die don鈥檛 make flowers,鈥 says Gressel. One of his students, Hani Al-Ahmad, is now working with Canadian scientists to try the same trick in rapeseed (canola). The extreme example of this approach is the notorious Terminator, a genetic modification that causes host plants to produce sterile seed (快猫短视频, 28 October 2000, p 4). Originally billed as a way of making sure farmers bought new seed each year instead of saving their own, it was attacked as an affront to poor farmers. Yet Terminator could produce real environmental benefits in reining in risky transgenes. 鈥淭he Terminator is coming back,鈥 says Gressel. 鈥淚 think it was being lambasted without thinking hard enough about the story. If the technology does work, it would be a good way of keeping transgenes from being distributed.鈥 The catch, as he hints, is that the technology has yet to be tested in real plants.
Mitigation technologies of this sort haven鈥檛 been explored much 鈥 probably for political reasons. 鈥淭he proponents [of biotechnology] don鈥檛 want to focus on the risk, and the critics don鈥檛 want to focus on the spread of the technology,鈥 says Goldburg. Perhaps it鈥檚 time to get on with it.