Matt Ridley

These are early days in gene therapy. Some think it will one day be as routine as heart transplants are today. But it is too early to tell if gene therapy will be the strategy that defeats cancer, or whether some treatment based on blocking angiogenesis, telomerase or p53 wins that particular race. Whichever, never in history has cancer treatment looked so hopeful - thanks almost entirely to the new genetics.1

Somatic gene therapy of this kind is no longer very controversial.

Concerns about safety still remain, of course, but almost nobody can think of an ethical objection. It is just another form of therapy and nobody who has watched a friend or relative go through chemotherapy or radiotherapy for cancer would begrudge them, on far-fetched safety grounds, the comparatively painless possibility of gene therapy instead. The added genes go nowhere near the germ cells that will form the next generation; that worry has been firmly laid to rest. Yet germline gene therapy - changing genes in places where they would be passed on to future generations, which remains C U R E S 2 5 1

a total taboo in human beings - would in one sense be much, much easier to do. It is germline gene therapy, in the form of genetically modified soya beans and mice, that has caused a resurgence of protest in the 1990s. This is, to borrow a term from its detractors, Frankenstein technology.

The genetic engineering of plants took off rapidly for several reasons. The first was commercial: farmers have for many years provided an eager market for new seed varieties. In ancient pre-history, conventional breeding had turned wheat, rice and maize from wild grasses to productive crops entirely by manipulating their genes, though these early farmers did not of course know that this is what they were doing. In modern times, the same techniques have trebled yields and increased per-capita food production by more than twenty per cent even as world population doubled between 1960 and 1990. The 'green revolution' in tropical agriculture was largely a genetic phenomenon. Yet all this had been done blindly: how much more could be achieved by targeted, careful gene manipulation? The second reason for the genetic engineering of plants is the ease with which plants can be cloned or propagated. You cannot take a cutting from a mouse and grow a new mouse as you can from many plants. But the third reason was a lucky accident. A bacterium called Agrobacterium had already been discovered, which had the unusual property of infecting plants with small loops of D N A called Ti plasmids that incorporated themselves into plant chromosomes. Agrobacterium was a ready-made vector: simply add some genes to the plasmid, rub it on a leaf, wait for the infection to take hold and grow a new plant from the leaf cells. The plant would now pass on the new gene in its seeds. So in 1983, first a tobacco plant, then a petunia and then a cotton plant were genetically modified in this way.

The cereals, which are resistant to Agrobacterium infection, had to wait until the invention of a rather more crude method: the genes are literally shot into the cell on board tiny particles of gold using gunpowder or particle accelerators. This technique has now become standard for all plant genetic engineering. It has led to the creation 2 5 2 G E N O M E

of tomatoes less likely to rot on the shelf, cotton resistant to boll weevils, potatoes resistant to Colorado beetles, maize resistant to corn borers and many other genetically modified plants.

The plants progressed from laboratory to field trial to commercial sale with relatively few hiccoughs. Sometimes the experiments did not work - boll weevils devastated the supposedly resistant cotton crop in 1996 - and sometimes they attracted protest from environmentalists. But there was never an 'accident'. When the genetically modified crops were brought across the Atlantic, they encountered stronger environmental resistance. In Britain in particular, where food safety regulators had lost public confidence after the 'mad-cow'

epidemic, genetically modified food was suddenly a big issue in 1999, three years after it had become routine in the United States.

Moreover, in Europe Monsanto made the mistake of starting with crops rendered resistant to its own indiscriminate herbicide, Roundup. This enabled the farmer to use Roundup to kill weeds.

Such a combination of manipulating nature, encouraging use of herbicides and making profits infuriated many environmentalists.

Eco-terrorists began tearing up experimental plots of genetically manipulated oilseed crop and paraded around in Frankenstein suits.

The issue became one of Greenpeace's top three concerns, a sure sign of populism.

The media, as usual, rapidly polarised the debate with shouting matches between extremists on late-night television and interviews that forced people into simplistic answers: are you for or against genetic engineering? The issue reached its nadir when a scientist was forced to take early retirement over claims made in a hysterical television programme that he had proved that potatoes into which lectin genes had been inserted were bad for rats; he was later 'vindicated' by a group of colleagues assembled by Friends of the Earth.

The result proved less about the safety of genetic engineering than it did about the safety of lectins - known animal poisons. The medium had become confused with the message. Putting arsenic in a cauldron makes the stew poisonous, but it does not mean all cooking is dangerous.

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In the same way, genetic engineering is as safe and as dangerous as the genes that are engineered. Some are safe, some are dangerous.

Some are green, some are bad for the environment. Roundup-resistant rape may be eco-unfriendly to the extent that it encourages herbicide use or spreads its resistance to weeds. Insect-resistant potatoes are eco- friendly to the extent that they require fewer insecticide applications, less diesel for the tractors applying the insecticides, less road use by the trucks delivering the insecticides and so on.

The opposition to genetically modified crops, motivated more by hatred of new technology than love of the environment, largely chooses to ignore the fact that tens of thousands of safety trials have been done with no nasty surprises; that gene swapping between different species, especially microbes, is now known to be far more common than was once believed, so there is nothing 'unnatural'

about the principle; that before genetic modification, plant breeding consisted of deliberate and random irradiation of seeds with gamma rays to induce mutations; that the main effect of genetic modification will be to reduce dependence on chemical sprays by improving resistance to diseases and pests; and that fast increases in yields are good for the environment, because they take the pressure off the cultivation of wild land.

The politicisation of the issue has had absurd results. In 1992, Pioneer, the world's biggest seed company, introduced a gene from brazil nuts into soya beans. The purpose was to make soya beans more healthy for those for whom they are a staple food by correcting soya beans' natural deficiency in a chemical called methionine. However, it soon emerged that a very few people in the world develop an allergy to brazil nuts, so Pioneer tested its transgenic soya beans and they proved allergenic, too, to such people. At this point, Pioneer alerted the authorities, published the results and abandoned the project. This was despite the fact that calculations showed that the new soya-bean allergy would probably kill no more than two Americans a year and could save hundreds of thousands worldwide from malnutrition. Yet instead of becoming an example of extreme corporate caution, the story was