by Steve Jones
Agriculture itself began with some mild infringements of sexual convention. Farmers ameliorated nature by clearing trees to allow vegetation to flourish. Plants that never normally meet came together and, from time to time, hybrids appeared. They contained combinations of genes never seen before. The process goes on. Many mudflats around Britain are covered by a tough grass, a hybrid between a local species and one introduced from America. The new mixture of genes does better in a harsh environment than does either parent, and has become a pest.
Chromosomes show that modern wheat began when two species of grass (each of which is still used for food in the Middle East) hybridized. As on the mudflats, the new cross was more productive than either parent. Soon, another grass crossed with the new recombinant, improving it further. This was the predecessor of every one of the billions of wheat plants grown today. The early farmers had moved chromosomes, genes and DNA from one species to another. They were the first genetic engineers.
Now, science has made sex universal. Molecular biology allows genes to be shifted among lineages which were once quite alien to one another; to make recombinant DNA not by the joint efforts of male and female, but by bypassing the inconvenience of reproduction altogether. Genes can be moved from more or less anywhere to anywhere else. At last, DNA can be used where it is needed, wherever it comes from. The biological rules have been broken and a new era of agriculture is at hand.
Genetic engineering began in bacteria, which have a commendable range of sexual interests. They exchange information in many ways; by taking up naked DNA, by a process of mating rather like that of higher animals and by the use of a range of third parties or viruses. This 'infectious heredity' (which suggests that venereal disease evolved before sex) has been subverted by science. The gene to be engineered (which may be from a bacterium, a plant or a human) is put into a piece of viral DNA with the help of various technical tricks. The manipulated virus plus its fellow-traveller is then used to infect a new host. With luck, the recipient will treat the immigrant DNA as its own and make a copy every time its divides. It can be persuaded to generate vast numbers of duplicates of the engineered gene — and large amounts of whatever it manufactures; pure human proteins, drugs, or other materials.
To cross the sexual divide, deep as it is, between bacteria and the rest of life proved unexpectedly easy. Insulin was once extracted from the pancreas of pigs. The human gene was moved to bacteria and large quantities of the pure protein can now be made. Human growth hormone, too — once extracted with much controversy from the pituitary glands of the dead — is now made in the same way. This avoids a macabre and unexpected problem. A few patients caught a nervous degenerative disease from corpses that carried a virus. Now, the factor VIII gene, too, has been inserted into bacteria and patients are treated with its product.
Genetic engineering can also be used against infectious disease. Jenner could use the cowpox virus to vaccinate against smallpox (an experiment which would fall foul of the most lenient Ethics Committee today) because the viruses share antigens, cues of identity recognised by the immune system as the basis of its response. As a result, antibodies against cowpox protect against smallpox. Cow-pox itself can cause problems and even modern vaccines have a small risk of a reaction to the foreign protein. In any case, many diseases {such as leprosy) cannot be helped by vaccination because it is hard to grow their agents in the laboratory.
Some clever engineering gets round the problem. Antigen genes from an agent of disease are inserted into a harmless bacterium, avoiding the risk of infection as the genes for virulence have been left out. Antigens from several sources can be put into the same host to give a single vaccine against many infections. A modified strain of Salmonella {which in its native state can cause food poisoning) is used. The bacterium, with its added antigens, flourishes for a short time in the gut and, by persuading the recipient that he has been infected, ensures that antibodies are made.
Some of the tricks are simple. Plants can make copies of themselves from a few cells so that many can be produced from one without sex. It is hard to improve trees by breeding from the best, because it takes so long. Instead, a superior specimen has its tissues broken into single cells. Copies of that super-tree can then be grown to give, within a single generation, a super-forest. In the same way, natural vanilla, once extracted at great expense from a tropical orchid, has been replaced with the same chemical made by cultures of cells grown in the botanical equivalent of a factory farm.
The real promise for farming comes from inserting genes from one species into another. A certain virus causes what is almost a plant cancer: tissues lose their identity and the plant grows up distorted. This crown gall virus is good at picking up foreign genes and has been used to move them into new hosts. The first transformed plant, a strain of tobacco, was made in 1984, to great lack of public interest. A dozen years later, tomato puree made from engineered plants was on sale without much controversy. Then, though, public alarm began; and the 'Frankenstein Food' label was invented, gathering around itself a variety of cranks who claimed, with no evidence, that such foods were harmful to health.
Part of the problem is the word 'engineering', which sounds more of a threat than does the 'domestication' used of the first genetic manipulators. Part comes from the caution of biologists themselves. Thirty years ago they declared a moratorium (soon abandoned) on new experiments until safety rules were worked out. Most important, people are always suspicious of technical fixes; the idea that science can overcome all problems. From nuclear power to Concorde the optimism of engineers has often turned out to be short-lived. For the companies involved, public concern (helped by their own bland assurances about safety and by simple arrogance in refusing to label engineered food) has proved a real problem. Monsanto makes many things (although it has now changed its name to disguise that faci); but became synonymous with a supposed attempt to poison the public. So alarmed is industry that it has set absurd standards of safety. One project used genes from Brazil nuts put into soybeans to provide a certain amino acid. As this is in short supply in the third world it might have saved thousands of children. Instead the project was abandoned as a very few people are allergic to the nut itself. The new plant might have killed one or two Americans a year. The end of the research was greeted as a triumph by the Greens. Other false accusations turn on the supposed dangers of resistance to an antibiotic, kannamycin, used to help pick out which engineered plants have incorporated foreign DNA. Kannamycin is not used in medicine, is widespread in nature, and its use in genetic manipulation is in any case becoming obsolete. Even so, kannamycin has been used as a stick with which to beat those keen to improve food production.
Other complaints, with more weight than all this pseudo-science, are based on fears about the future of the landscape or of farming itself. Many people do not like modern industrial agriculture (in spite of its productivity) and genetically manipulated foods will, without doubt, help it to prevail. It also, say the opponents, makes little sense to manipulate wheat to add to the grain mountain; or to drive peasants from the land to the cities. The Green Revolution itself forced Indian farmers from the land as large companies gained control of seed production.
Much the same happened half a century ago in the American mid-West. In the 1930s new strains of hybrid corn were made by crossing two lineages together. Their sale was controlled by combines who manipulated the price and put small farmers out of business. Another commercial trick played a part. No longer could a producer use his own seed for the following year because a hybrid plant produces new and unfavourable mixtures among its offspring. Engineered seeds pose the same danger of a harvest of the grapes of economic wrath. Few farmers can bargain with an organisation with a monopoly on the sale of a herbicide-tolerant plant — and the herbicide involved. The companies have threatened ro sue those who plant the new seeds in a subsequent year without a new purchase (and have been sued in their turn by clients disappointed by its yield and by others whose own cro
ps are polluted by manipulated pollen). New 'terminator technology' prevents engineered plants from setting seed and — as in the mid-West — forces those who use them to buy new stocks for every harvest.
As is often the case in genetics, much more has been promised by biotechnology than has been achieved (particularly in the third world, where few profits are to be made). Some GM crops have lower yields than others, which has led some farmers to give them up. Such is the storm generated by their use that their potential may be long delayed. Thirty million hectares of land were planted with GM crops in 1998; and a million Chinese farmers used engineered cotton. So alarmed is the public (and so over-priced the seeds) that in the west at least the acreage has been reduced since then.
Most of the brouhaha turns on economics and emotion rather than science. Science, indeed, has got rather lost in the fuss. What might genetic manipulation of plants do, given the chance?
Some of the technology aims to increase the range of places in which particular crops can live, with genes that make them tolerant to salty soil, or high temperature, or shortage of water, or allow growth for a larger portion of the year. The Green Revolution turned on a natural mutation that caused plants to grow less tall than normal. Now the gene involved (which prevents the plant from responding to growth hormones) has been cloned and could be introduced into other crops, to give an instant revolution in unexpected places.
Other genes might fight biological enemies. Many creatures produce natural pesticides as they are at constant risk of attack. Such genes from one species can be shifted into another, to cut down the use of chemical sprays. A pesticide much used by organic farmers is taken from a bacterium, Bacillus thuringiensis, which is lethal to many insects. The toxin genes have now been introduced into cotton, reducing the chemicals used on the fields. A related trick inserts a gene that makes the plant resistant to artificial weedkillers. 'Round-Up' is much used by soya-bean farmers. 'Round-Up Ready' plants (which represent about three quarters of all genetically modified crops) have a gene that breaks down the chemical, so that the field can be sprayed to kill the weeds but leave the harvest untouched. Plants can even be 'vaccinated' by introducing a few genes from their viral enemies. When the virus strikes it uses the plant's machinery to make copies of itself. If parts of its own structure are already there, the mechanism is disrupted and the attack fails. Virus resistance has been introduced into rice and peppers, and genes that resist parasitic worms into potatoes and bananas, although none has yet been used on farms.
We grow plants because they make useful things; food, for example. As most plants lack certain amino acids it is hard to stay healthy on a strict vegetarian diet. Much could be done by moving the right genes in and many hopes are pinned on 'golden rice', which has within it a new gene for vitamin A (whose deficiency causes half a million third-world children to go blind each year). Some foodstuffs, such as broccoli, contain anti-cancer substances and the DNA responsible might be introduced to other species. Plants could even be used as biological factories, with the prospect of using potatoes to make antibodies or other blood proteins. Already, rice can make a human protein used to treat cystic fibrosis and other lung diseases.
Other species might be persuaded to make natural oils for use in plastics or fuel. Another option is to interfere with the DNA of trees to reduce the toughness of the wood and to cut down the amount of energy needed when it is converted into paper. Blue cotton and black carnations are on the horizon. The great hope for agricultural engineers is to introduce genes that allow crops to make their own fertiliser. Clover has evolved an arrangement with certain bacteria. The bugs take nitrogen from the air and turn it into a form which can be used by the plant. In return they gain food and protection. Farmers have long used mixtures of grass and clover that are more productive than either grown alone. To put nitrogen-fixing genes into crops would much reduce the need for fertilizers. The potential rewards are huge. All this may mean that plants may rule and that animals will fade in importance as — perhaps — the salmon-flavoured banana takes over.
To develop such new crops is expensive and the research is, of course, done with profit in mind. It must, like the transistor or the vacuum cleaner, be protected. The first known patent was granted in 1421 in Florence to the architect Filippo Brunelleschi for his invention of a barge with hoisting gear used to transport marble. The idea that inventions need protection spread, and — in spite of attempts to do without in places such as China — is now universal. The law works; and without it capitalism would not have developed.
But what about the idea of patenting life (or, at least, genes)? It seems somehow wrong, but the pass was sold long before the days of DNA technology. In the 1970s it possible to protect agricultural varieties and in 1980, the US Supreme Court gave the green light to a patent for a bug whose genes had been altered to chew up oil spills. Such creatures were the products of years of work by those who sold them, with a real claim to be inventions, in the legal sense, rather than mere discoveries that cannot be patented.
With life, the boundary between the natural and the invented is soon blurred. Can genes themselves be patented? After all, they evolved and are not products of human ingenuity. In spite of much argument thousands of genes are now under legal protection. The law is still dubious about just how far this should be allowed, and an aggressive attempt to patent segments of DNA without even knowing what they do has failed. Patenting, though, is here to stay. It can, like capitalism itself, be unfair; but, like that economic system, seems unavoidable.
The interesting question is not about ethics, but about who owns the patents. 'Biopiracy' is the theft of genes from the third world. The sums involved are large. Seven of the globe's twenty-five top drugs are derived from natural products; aspirin from willow-bark, a cholesterol-lowering medicine from a Japanese fungus, and cyclosporin, a powerful anti-cancer agent, from a Norwegian equivalent. Those nations have gained from such drugs; but vincristine and vinblastine, developed in the 1960s as a treatment for leukaemia, came from the Madagascan rosy periwinkle. That impoverished land has gained nothing from a trade worth millions (although had it obtained patent cover it might have done so). And what about the anti-cancer chemicals found in Asian corals or the material two thousand times sweeter than sugar made by a West African tree? Those genes will be worth millions when cloned — but who owns them? Some companies are quite blatant in their attempts to cull profit from ancient expertise. Basmati rice is an aromatic (and expensive) variety that has long been used in India and Pakistan. Both governments were outraged to find that, in 1998, the Ricetec Corporation of Texas had filed a patent application for its seeds — and, to add insult to injury, that they had been collected by American scientists invited in to search for new genes that might help feed the third world.
The West itself is dubious about the actions of its citizens. In 1997 the United States Patent Office overturned an attempt to patent the active ingredient of turmeric as an aid to wound-healing as this had long been used as a folk remedy in India. Indeed, the nation's own fingers have been burned. The enzyme used in the polymerase chain reaction comes from a bacterium collected in a hot spring in Yellowstone National Park. The Swiss company that owns the patent makes a hundred million dollars a year in royalties, while the Federal Government (the owner of the spring and presumably of the bacteria) gets not a cent. Now, the Parks Service charges a hundred thousand dollars a go (plus a guaranteed share in profits) for any company that wants to prospect for DNA on its land. Although the claims of wealth from tropical nature may be exaggerated — after all, only one of fifty thousand plants tested by the US National Cancer Institute gave a usable drug — the third world is understandably enraged. Now it is fighting back. Amazonian tribes use the skin of certain frogs as a source of poison for their darts. That substance is a pain-killer if used in minute amounts, and an American company is keen to patent it. But, counter the governments of Ecuador and Venezuela, was not the discovery made by their own people and shoul
d not at least some the profits come back to them? The Americans disagree (and are annoyed by the Venezuelans, who have put a stop to the collection of frogs by outsiders).
All this is the stuff of commerce and is as familiar to students of the history of gold-prospecting as much as to those of gene-mining. Like most of the fuss about manipulated crops, it lies outside science. However, science itself has something to say about the implications of the new technology. Not all of it is reassuring.
The most widespread fear is of the escape of engineered forms and of a new plague unleashed upon the world. Biologists have some standard defences against this concern. Manipulated creatures are likely to be less fit than those which have not been interfered with. After ail, if the gene gives its carriers an advantage it might be expected already to have evolved. Most farm animals and plants cannot survive outside farms, which is why the streets are not full of marauding sheep or potatoes. The same is true of bacteria and viruses. Children are injected with a live polio virus that has been 'attenuated' to make it less dangerous. Surveys of sewage show that this live virus is constantly escaping. That is the key to its success: even children whose parents do not allow them to be vaccinated are exposed to the viruses excreted by their treated friends. The attenuated virus has never survived in the wild, but depends on a supply of newly treated children. If all engineered organisms are as feeble there is not much to worry about.
Even so, it is worth remembering that every domestic animal is a pest somewhere. Cats wiped out many of New Zealand's birds. Goats have done worse in many places, feral pigs are everywhere in the subtropics and even horses can be a nuisance in California deserts. Plants are even more destructive. Everyone knows about the prickly pear in Australia, but a pretty yellow South African garden plant, the sour-sop, has done even more damage there.
