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Life Out of Bounds Chris Bright NS 7 Nov 98

ALL it takes is a beetle in a wooden packing case, a worm in an apple, or a seed in the mud on your boot when you fly off on holiday, and a new organism has leapt a continent. One in ten introduced organisms will thrive in their new environment, and one in ten of those will be a problem. We find it hard to imagine the effectiveness of the natural barriers that existed until a few centuries ago between islands, continents, lakes, rivers and seas, or lands divided by deserts and mountains. It was this isolation, in some cases enduring since the break up of the Pangaea supercontinent 240 million years ago, that gave rise to unique, distinct ecosystems. Now, millions of years of biological quarantine have come to a sudden end. What happened after that unplanned full stop is the tale told by Chris Bright of the Worldwatch Institute in Washington DC in his timely book Life Out of Bounds. His message is stark: "At a frenetic and ever-increasing pace, the global economy is merging the world's ecosystems, smearing them into each other. We are in the throes of a vast and little noticed biotic upheaval." In painstaking detail, he shows how the continents and the seas are coming together as ecological entities. And he points out that this turmoil is reaching levels of disturbance that no actual meeting of rock or water could possibly achieve. And within the landmasses, island ecologies-a mountain range within a desert, for example-are suffering. "Bioinvasion," he points out, "is perhaps the only category of environmental degradation that can corrode virtually every level of biological organisation." So just how deep is the impact of this "bioinvasion"? In the US, between 5 and 25 per cent of flora in nature reserves are exotic, and more than a third of all endangered species are under pressure from introduced exotics. Even such a diverse ecosystem as the Everglades of Florida, with between 60 and 80 plant species, has succumbed to a single invader. Dense thickets of the Australian melaleuca tree have taken over the lush region, producing a near monoculture. Then there are the arable weeds, whose seeds have been sown into soils the world over mixed with those of crops. And, as Bright reveals, the problem isn't just plants. The ecology of the Great Lakes suffered a blow, for example, when the Caspian Sea's zebra mussel arrived, carried in the bilges of ships as ballast water. It is now busily wiping out native mussels, blocking up intake pipes and filtering the lake water clean of the phytoplankton needed for many a local organism to survive. And the damage doesn't stop there: the zebra mussel also concentrates organochlorine pesticides from sediments, polluting any predators. In Lake Erie alone it may have wiped $400 million off the fish catch. This mussel also clogs up cooling water pipes in at least a dozen nuclear plants in the US, costing each plant nearly $1 million a year to keep them under control. Bright totals up the cost of the exotics' arrival to the US as a whole. In 1993, for example, the Office of Technology Assessment estimated the economic cost of 79 major bioinvasions at $97 billion. And that doesn't take into account financial immeasurables such as the loss of more than two-thirds of American fish to extinction in the past century because of the march of the exotics. And if North America is so vulnerable to alien invasion, how much more so are small islands such as Mauritius or the GalApagos? Greater landmasses such as Madagascar, New Zealand and Australia are not protected by their size. They, too, are islands under threat. Hawaii is an extreme example. The natural rate at which new insects arrive on these islands has multiplied a millionfold. Exotic predators, competitors or diseases threaten 95 per cent of the islands' endangered species. We are now in the firing line because human diseases and their carriers are also on the move. These have travelled with people and their animals for hundreds of years. Bubonic plague travelled the Silk Route from Asia to Europe in fleas on rats. Now the Asian tiger mosquito, whose bite carries dengue fever, is travelling the world in shipments of used tyres. It has reached the US, Brazil, southern Europe, Nigeria, New Zealand and Australia. But the biggest factor when it comes to disease remains humans: the wealthy make about 500 million international flights a year and the poor, the refugees and people displaced by war or famine, of whom 100 million a year may be crossing international borders. HIV, cholera, yellow fever, drug-resistant malaria and tuberculosis travel easily via infected people. And beyond that lurk other pests and pathogens of crops and livestock-70 000 and rising. Take the potato blight fungus, which is destroying about 20 per cent of the world's potato crop. Or the tiny sap-sucking tobacco whitefly, which has spread all over the world from Central Asia. It carries about 60 plant viruses, has acquired resistance to many insecticides and has led to 1 million hectares of land being abandoned South America alone. Bright g. ves a searing example: over a few days in June 1993, a complex of viruses, protozoa and bacteria wiped out nearly all of China's shrimp industry. Back in Hawaii, alien poxes from alien birds are passed on by alien mosquitoes to kill native birds, while pineapple plantations (themselves an introduction) are damaged by a wilt disease carried by South American mealybugs that are milked and tended by African ants. And on Africa's Lake Victoria, the Amazonian water hyacinth has been helped in its takeover by the Nile perch. Water hyacinths may yet be defeated by the introduction of insects from its native environ ment that eat its shoots. This ap proach may work, as it did with the South American water fern that had taken over Papua New Guinea's Sepik River bt 1990. But it may not. Bright points out the dangerous alternative in his tale of Micronesia, where monitor lizards were imported into sugar plantations to control rats eating the crop. The large lizards took a liking to domestic poultry, so someone had the bright idea of bring in cane toads to divert the lizards. It was a disaster. Poisons on the cane toad skins killed the lizards, leading to an explosion in a beetle pest of coconut trees, which the lizards had also been eating. Cats, dogs and pigs ate the toads. All were poisoned, leading to a huge increase in numbers of rats and of giant African snails. Did it stop here? No, someone introduced another biological control: a flatworm to prey on the giant snails. The flatworm spread across Oceania eating out the diverse native snails. Incredibly, the lesson that Bright makes so plain has still not been learnt. To alleviate fuel shortages in poor parts of the world, people who should know better are advocating bringing in exotic "wonder trees" with a long record as invasive pests. So they are promoting species of Prosopis, Mimosa and Acacia. So what is being done? Bright reveals that one of the barriers to action is that despite the monumental cost of bioinvasions, they are "not a conceptual category that figures in economic analysis". This means that these costs are ignored or sidelined. International law is weak: indeed, World Trade Organisation rules forbid states from taking pre-emptive measures to prevent pest invasions, if these would restrict the flow of goods. It is high time, Bright argues, that the global community began to take the problem seriously. Get accountants to count this collateral cost of growing world trade. Remind environmental activists that genetically intact organisms in the wrong place can be just as disruptive as GMOs -and often considerably more.

A Question of Breeding GE and the environment NS 27 Feb 99 4

Oliver Tickell writes on the environment

IT LOOKS just like an ordinary oilseed rape plant, but farmers in Canada know it as "Smart Canola". Because it carries genes for resistance to two families of herbicides, the farmers can kill off every weed in sight, without fear of damaging their harvest. The prospect of plants that could in effect conspire with farmers to produce chemically sterilised fields has sent Europe's conservationists into a flat spin. They have issued dire warnings about the perils of agricultural biotechnology and call for moratoriums on GM plantings. But Smart Canola is not quite what it seems. While European officials agonise over the pros and cons of growing GM crops, they could do little to stop farmers planting this oilseed rape. The reason: Smart Canola is not genetically engineered. Scientists at Pioneer Hi-Bred in Des Moines, Iowa, used normal breeding and selection techniques to create Smart Canola. This involved screening thousands of naturally occurring variants for strains resistant to herbicides. The company rejects any suggestion that its crops will encourage farmers to sterilise their fields and thiis harm wildlife. "You don't just go out there and apply these chemicals randomly," says company spokesman Tim Martin. But because the crop is not genetically engineered, Martin's assertion would not need to be put to the test before the rape could be grown in Europe. The only trials required would be experimental plantings designed to evaluate its performance to confirm that it really is a novel variety. In fact, Pioneer has already made one application to market Smart Canola in Britain. This was turned down, but only because the yield was too low-a problem the company is confident it can solve. Smart Canola is just one of several conventionally bred crops that could in theory pose the same environmental hazards as GM plants. And yet these crops would bypass rules compelling companies to show that their GM crops are unlikely to create environmental problems. Other plants that could slip through the net include maize and soya beans designed to resist the same herbicides as Smart Canola, also from Pioneer Hi-Bred. David Robinson of the Scottish Crop Research Institute near Dundee, a member of the British government's Advisory Committee on Releases to the Environment (ACRE), says existing legislation is plagued by a "double standard" that defies reason. "The idea that herbicide resistant crops produced by genetic engineering are inherently more hazardous than ones produced by conventional techniques is simply nonsense," he says. This point is reiterated in a report from ACRE on GM crops and wildlife that was released last week. Headlines claimed that the document detailed a catalogue of environmental disasters waiting to happen, from genes escaping from GM crops to create superweeds to insect and bird populations already decimated by intensive farming being killed off by genetic engineering. In fact, the report is an even-handed analysis of the risks and benefits of introducing the crops onto Britain's farmland. It's true that the conservation watchdog English Nature has called for a ban on commercial plantings of GM crops that are resistant to broad spectrum herbicides. It is worried that more farmland would be wiped clean of wild plants as a result. The ACRE report acknowledges these fears but also lists possible advantages. These include less need to till soil to control weeds, which could help stem erosion. One of the document's more alarming observations has nothing to do with GM crops, however. "Potential adverse effects," it notes, "may be just as likely to occur as a result of conventional plant breeding programmes." Martin takes a more positive view of ACRE's statements on the similarity between GM and conventional crops. "I see it as affirmation that conventional breeding can work just as well," he says. But for environmentalists, the ACRE report carries as a sobering message. While they concentrate on attacking GM crops, the plants' conventionally bred cousins could sneak into Europe through the back door. David Concar and Andy Coghlan

For comprehensive international GM coverage, see hftp://gmworld.newscientist.com

Dispatches from the Killing Fields NS 27 Feb 99 5

PERHAPS the most serious charge levelled against crops engineered to produce insecticidal toxins is that they will poison beneficial insects as well as wiping out pests. The latest findings will fuel the debate over the environmental safety of these crops by giving both sides more ammunition. One unpublished study, which looks at the impact on insects of a bacterial toxin engineered into maize, suggests the toxin's effects mysteriously increase as it passes along the food chain. But another team is disputing earlier claims that ladybirds are harmed by plants that produce a protein toxic to aphids and other sap-sucking pests. Experts can't agree on exactly what the two studies mean-particularly since any harmful effects of insecticidal GM crops must be balanced against the probable benefits of reduced pesticide use in fields where the plants grow. Everybody accepts that plants producing insecticidal toxins will reduce the number and nutritional value of the pests that beneficial insects feed on, but confusion surrounds the extent to which the toxins poison predatory insects directly. At the Swiss Federal Research Station for Agroecology and Agriculture near Zurich, Angelika Hilbeck and her colleagues say they have found evidence confirming that lacewings, which eat caterpillars and aphids, can be poisoned by an insecticidal toxin engineered into maize. The gene for this toxin, called Bt, comes from the bacterium Bacillus thuringiensis. Hilbeck raised a red flag about the effects of Bt toxin on lacewings last year (This Week, 2 May 1998, p 21). In later experiments, her team fed identical quantities of purified Bt toxin directly to lacewing larvae or via caterpillars that had consumed the toxin. Fifty per cent more lacewings died after eating the caterpillars. Hilbeck believes that the toxin became more potent, perhaps because its chemical structure was altered. Her results may require changes in the way that biotech firms test for any "collateral damage" their crops might cause. They tend to feed the engineered toxins directly to beneficial predators, rather than through their prey. "You need to use a realistic route of exposure," says Hilbeck. Meanwhile, researchers led by John and Angharad Gatehouse at the University of Durham have studied what happens to ladybird larvae fed aphids that had eaten a purified lectin protein from a snowdrop. This is the same protein that was engineered into the potatoes that sparked Britain's current GM food scare. Fears for the safety of beneficial insects surfaced in 1997, when a team led by Nick Birch of the Scottish Crop Research Institute found evidence that eating aphids reared on transgenic potatoes reduced the lifespans and egg production of ladybirds (This Week, 1 November 1997, p 4). Now the Durham team suggests the lectin is not acutely toxic to ladybirds. The lectin stunted the growth of aphids, but when the ladybird larvae were given more aphids to compensate for the aphids' small size, they developed normally to the pupal stage. David Concar

How to Price what we put on our Plate NS 27 Feb 99 6

FOR most people, the main question about GM food is: do I have to eat it or not? If we are to have that choice, GM crops will have to be segregated from plough to plate and all products containing GM food labelled as such. The US government claims that this would impose heavy costs on its food suppliers. It threatens a trade war if the European Union responds to public pressure by demanding segregation of GM crops within US exports. But a new analysis suggests that the costs of segregation and labelling are manageable, and could even enhance trade. "This could be the only key to easing public acceptance of biotechnology," says Allan Buckwell, an agricultural economist at Wye College near Ashford, Kent. Buckwell presented his findings in Brussels earlier this month. He says that similarly stringent segregation-although not on the basis of genetic modification-is already widespread. "Different varieties of wheat, for bread or pasta, are already strictly separated from farm gate to production plant," he says. And in the US, soya growers already distinguish beans used in different kinds of tofu for export to Japan. The cost of such segregation is not prohibitive, say Buckwell and his colleague Graham Brookes. For example, soya growers and processors in the US separate and label beans with different protein and oil contents for an extra cost of just 6 to 9 per cent compared with unsegregated beans. Soya growers in Brazil distinguish GM from non-modified soya for a premium of 10 to 15 per cent. European dealers separate maize with a high oil content for 17 per cent extra cost, while US producers do it for 6 per cent. Canadian farmers distinguish GM from normal oilseed rape, or canola, for an 8 per cent premium. And costs will come down, says Buckwell, if segregation becomes widespread. The organisation that commissioned the Wye College study remains sceptical, however. The Food Biotech Communications Initiative, which represents companies such as Monsanto, CocaCola and Nestl6, concludes that segregation will increase food costs by "as much as 150 per cent". But this interpretation assumes that food labelled as non-GM has to be absolutely pure. In practice, regulators are likely to allow food to carry such a label if contamination with GM materials is below a certain level. The EU, which is currently debating its labelling criteria, is considering tolerances for GM contamination for individual ingredients of around I per cent. Debora MacKenzie, Brussels

Unknown Quantity NS 27 Feb 99 18

IN 1794, a Royal Navy squadron set sail with enough raw lemon juice to last a 23-week voyage. The Admiralty had finally got round to testing the ideas of the Scottish surgeon James Lind, who had discovered in 1747 that citrus fruits can stave off scurvy. The experiment proved so successful that the Admiralty made its ships carry supplies of citrus fruit, and British sailors quickly became known as "limeys" because of their lime juice ration. Scientists realised for the first time that the body needed essential trace nutrients that later came to be called vitamins. Two hundred years later, just about the only thing scientists know for sure about vitamin C is that 60 milligrams a day will prevent scurvy. Nevertheless, many people pop pills containing thousands of milligrams, hoping to prevent cancers or ward off the common cold. Linus Pauling, the Nobel prizewinner who in his old age extolled the benefits of vitamin C, reportedly stirred 18 grams into his daily orange juice. He lived to the ripe old age of 93. Last April, however, researchers at the University of Leicester reported that a supplement of as little as 500 milligrams of vitamin C a day may produce free radicals, which can damage DNA and cause cancer (Nature, vol 392, p 559). Although this study was widely criticised for being flawed, it highlights a growing worry about high doses of vitamins. Long regarded as worthless but harmless, megadoses have come under heightened scrutiny after two large studies showed that beta-carotene can increase the risk of cancer. Many European countries have already laid down maximum limits for vitamin tablets that are sold to the public and last year the European Commission issued a discussion document on the maximum safe levels. But what should be the maximum limit? There is a lack of hard data. The studies that have been carried out frequently contradict each other. And the public likes its vitamins. In Britain last year the government proposed limiting the intake of vitamin B6 by banning the sale of tablets containing more than 10 milligrams, because of worries that high doses could cause nerve damage. But women who take up to 200 milligrams as a diuretic to relieve premenstrual syndrome reacted with dismay and forced the goverranent to back down in July last year. The Ministry of Agriculture, Fisheries and Food's advisory group on vitamins and minerals is now considering whether to recommend maximum doses for vitamin supplements. The US Institute of Medicine is due to issue a report this autumn recommending intakes of antioxidants, including vitamin C, vitamin E and betacarotene. Antioxidants can neutralise free radicals and they have been touted as cure-alls for a whole range of diseases.

But the evidence for the beneficial effects of antioxidants is ambiguous. One study, conducted by the National Cancer Institute in the US and Finland's National Public Health Institute, tested the hypothesis that antioxidants would help to prevent cancer in smokers. The researchers recruited 29 000 male Finnish smokers, dividing them into four groups. From 1985 to 1993, one group was given a daily pill with 50 milligrams of alpha-tocopherol (a form of vitamin E), one group took 20 milligrams of beta-carotene, one group took both vitamins, and the rest took a placebo.

To the researchers' horror, the risk of cancer among the group on the beta-carotene supplement increased by 16 per cent (The New England Journal of Medicine, vol 330, p 1029). "It was a huge shocker to the whole field," says Susan Taylor Mayne of Yale University. Further analysis of the data showed that heavy smokers and people who drank alcohol seemed worst affected. This theory gained support from a second long-term trial, led by Gilbert Omenn of the Fred Hutchinson Cancer Research Center in Seattle. Omenn and his colleagues looked at 18 000 American men and women at risk of lung cancer (The New England Journal of Medicine, vol 334, p 1150). Smokers, former smokers and workers exposed to asbestos took either a placebo or sup plements of vitamin A and beta-carotene for an average of four years. The researchers stopped the study in January 1996 because the group on supplements had a 28 per cent higher incidence of lung can cer (see Diagram). The inves tigators could not explain the findings, which they described as "troubling". Mayne believes that oxidising gases in cigarette smoke may degrade betacarotene and produce harmful byproducts in the lung. "I'm concerned about all of these nutrients that people go out and take in massive doses. These nutrients may have adverse effects," she says.

Supplementary risks

But John Hathcock of the Council for Responsible Nutrition in Washington DC, which represents the manufacturers of supplements, argues that "Beta-carotene is safe for everyone except long-term smokers who smoke while they are taking betacarotene." He says: "If we had taken that policy thirty years ago, we would have missed out on vitamin E," he argues. Several large studies have recently suggested that large doses of vitamin E can prevent deaths from cardiovascular disease. In one study, researchers at the Harvard School of Public Health in Boston asked around 40 000 male doctors about their usual daily intake of nutrients. After four years of follow-up, they found fewer instances of coronary disease in those taking vitamin E supplements of between 60 and 100 milligrams (The New England Journal of Medicine, vol 328, p 1450). Scientists think that vitamin E prevents free radicals from oxidising low-density lipoprotein (LDL), which contributes to . But too much vitamin E can also promote bleeding. "Some of the large studies have seen a modest increase in haemorrhagic stroke,' says Manfred Steiner of the East Carolina University School of Medicine in Greenville, North Carolina. "I feel uncomfortable that people can go to a drug store and get free access to vitamin E in any dosage they want." Some doctors prescribe as much as 400 milligrams to prevent a second heart attack. But experts advising the French government recommend a maximum limit for vitamin E of 40 milligrams a day, because of the risk of strokes among people taking more than 50 milligrams a day. Often the very medical condition that seems to require a supplement can make a vitamin dangerous. Alcoholics suffer from a deficiency of vitamin A, for example. So Charles Lieber of the Mount Sinal School of Medicine in New York considered supplementing their diet with beta-carotene, a precursor of vitamin A. But his studies showed that alcohol also hinders the conversion of beta-carotene to vitamin A, and high blood levels of beta-carotene can damage the liver. Lieber believes it is time to set maximum limits for supplements. "It's useful in the sense that people will be more aware that they can't just take these things," he says. "In our society, we have a lot of problems with excess." Nell Boyce, Washington DC

We Can Rebuild NS 27 Feb 99 52

IT'S like a Woody Allen script run backwards. In Allen's 1973 film Sleeper, attempts are made to clone Hitler from his preserved nose. Now, instead of cloning people from spare parts, scientists hope to derive those parts-cells, tissues, organs-by cloning people. In the two years since the world first leamt about the cloning of Dolly the sheep, this area of science has made huge progress. Not just sheep, but mice and cows have now been cloned from adult cells. The talk now, however, is not about cloning to reproduce a later-born "identical twin". The focus of ethics and public policy has shifted from an alarmist and rather fanciful preoccupation with human reproductive cloning to an emphasis on "therapeutic cloning" for cell and tissue replacement and repair. To be sure, discussion of the so-called "spare parts" potential of human cloning has not escaped sensationalist treatment. Tales of organ farms and headless clones stuffed into cupboards-awaiting the need of their forebears for new hearts, livers or kidneys-have provoked some anxiety. But the real story is every bit as fascinating and far less alarming. We may, for example, be able to produce cells and tissue for therapeutic use by a technique known as somatic cell nuclear transfer: taking the nucleus from a differentiated cell, such as a skin cell, and inserting it into an egg cell that has had its nucleus removed. Even without cloning, appropriate growth factors can be used on isolated embryo stem cells to produce immunologically compatible cells or tissues for treating, say, degenerative diseases of the heart, liver, kidney or brain and damaged bone. Legislators were quick to appreciate the huge potential of human cloning at the cellular level. In Britain, the House of Commons Select Committee on Science and Technology issued a report on 18 March 1997, barely a month after the announcement of Dolly's birth. Ian Wilmut, who leads the team that produced Dolly, and Harold Varmus, director of the US National Institutes of Health, were asked to describe the promise of therapeutic cloning to a Senate subcommittee. Three months later, the US National Bioethics Advisory Conu-nission issued a report recommending a five-year ban on human reproductive cloning by somatic cell nuclear transfer that would result in the birth of a cloned child. It did not seek to regulate private-sector research into human cloning at the cellular level (This Week, 7 June 1997, p 13). The most thorough and impressive public policy examination of cloning has come from Britain. In December 1998, a joint working group representing the Human Fertilisation and Embryology Authority and the Human Genetics Advisory Commission issued its report Cloning Issues in Reproduction, Science and Medicine (This Week, 12 December 1998, p 5). After a three-month public consultation, the group recommended that human reproductive cloning should be prohibited. And it said that regulations would have to be changed in order to allow human embryo research involving cell nuclear transfer technology that does not result in the birth of a human clone. The joint committee decided that therapeutic cloning, with its potentially beneficial applications, should be allowed to go ahead. But because the consultation process had revealed widespread public unease with the term "cloning", the working group thought it wise not to use the term "therapeutic cloning" but to refer instead to cell nuclear replacement. In the early days of public discussion on cloning, when the emphasis was still on human reproductive cloning, the tone in the US was mainly religious. Theologians were everywhere in the media, and their call "not to play God" was echoed in Congress. In Britain the discussions were largely secular. When scientists speak of the benefits that cloning or any other novel technology offers, they are using the language of "consequentialist" ethics, weighing the benefits and the harms. Such language is now far more prevalent in both the US and Britain than the "thou shalt not..." kind of pronouncement. The change of focus from reproductive cloning to therapeutic or spare-part cloning has brought a return to consequentialist ways among ethicists and policy makers. This in no way diminishes the moral anxiety of those who disapprove of cloning humans and using the resulting embryos to derive tissues and organs. With thinking now directed towards the promise of medical benefits, the consequentialist arguments seem to be coming up trumps.

Arlene Judith Klotzko is a healthcare lawyer and bioethicist. She writes and edits books on cloning for Oxford University Press