Steve Jones - The Language of the Genes

After rhe conquest of the louse, DDT was sprayed onto malarial mosquitoes. Victory soon seemed imminent. The number of infections fell, in Ceylon from millions to scores. The rot set in as genes for resistance spread. The counterattack has been so effective that malaria is raging at levels greater than before and the World Health Organisation admits that 'the history of anti-malaria campaigns is a record of exaggerated expectations followed sooner or later by disappointment 1. The parasites, too, have subverted attempts to engineer them out of existence and in many places malaria treatments are now useless as the disease organism has evolved means of coping with them. Mutation and natural selection helped both parties survive.

The parasites have a variety of tactics. Chloroquine was developed in the 1940s. Forty years ago it worked almost everywhere. In the 1960s resistance appeared in south-east Asia and South America and has now spread over the tropical world. One defence resembles the mechanism used by cancer to combat drugs. Massive amounts of a transporter protein are made and pump the drugs out of the cell at fifty times the normal rate. Genes that give resistance to other drugs — sometimes several at a time — have also turned up. The Walter Reed Army Institute in the USA screened more than a quarter of a million compounds in the search for a new anti-malarial drug. Only two proved suitable. One was mefloquine, and in Thailand almost all the parasites are now resistant. Medicine is now down to the last remedy, with nothing new in sight. As a result doctors are returning to quinine and to an extract of wormwood (first used in China a thousand years ago), treatments that are toxic and not very effective.

The history of genetic engineering may, when it is written, turn out not to be too different from that of the war against the insects, in which evolution prevailed after initial setbacks. All is not gloom. For some targets, insecticides have worked well and continue to do so. Without them, there would have been no Green Revolution, lice might still be carrying typhus through the poorer parts of Hurope and malaria killing even more than it does today. In rime, no doubt, economics will prevail over hysteria when it comes to genetically manipulated plants as well. The triumph of ingenuity will not be unalloyed. Only one thing is certain about the new attempts to engineer nature; that nature will respond in unexpected ways. Because living organisms deal with new challenges by evolving to cope, genetic engineers, unlike those who build bridges, must face the prospect that their new toys will fight back.

Geneticists never use the F-word but often have it turned against them. This chapter takes the subtitle of Mary Shelley's great work. Her monster has been used again and again to berate the efforts of scientists. Frankenstein's creation almost gained a Scottish mate, for his maker journeyed to the Orkneys to manufacture a female for his fierce original. He destroyed it at the last moment: 'Even if they were to leave Europe, and inhabit the deserts of the New World, yet one of the first results of those sympathies for which the daemon thirsted would be children, and a race of devils would be propagated upon the earth who might make the very existence of the species of man a condition precarious and full of terror. Had I the right, for my own benefit, to inflict this curse upon everlasting generations?'

Two centuries later, and two hundred miles south, in the Scottish Borders, was born a lamb which, according to the report in one New World newspaper, at once turned carnivore and devoured her flock-mates. She became the most famous sheep in history. Dolly is not a curse, but has a sweet nature (although, like some biologists — her makers not included — she rushes bleating to the front whenever she sees a camera). Reproduction without sex had hit the headlines. It had in fact been around for some time, but the public was not much interested; even when, in 1985, the genes from a sheep embryo cell were put into a different egg and made a cloned lamb.

Dolly was different. Her birth in 1997 amazed researchers because her genes came from an adult cell that had been persuaded to take a leap back into infancy and to start again. Since then, there have been many more cloned mammals — sheep, mice, cattle and goats — with yet more on the way. The egg that made the sheep Tracy was engineered to make valuable drugs in her milk and there may soon be cows that make human breast milk. Dolly herself has a daughter, Bonnie, made in the traditional sexual way, and the descendants of Tracy and her fellows may grow into factory flocks, worth millions.

And what about the ultimate clone? People have long chosen partners, but now, for the first time, comes the chance of the most perfect choice of all, that of a child in one's image. Quite what that implies is not clear — would a cloned Mozart have written Don Giovanni? — and quite why anyone would want to do so is uncertain; but the chorus is against it. The World Health Organisation calls the procedure 'contrary to human integrity and morality', the European Parliament is convinced that cloning '. cannot under any circumstances be justified or tolerated by any society, because it is a serious violation of fundamental human rights and is contrary to the principle of equality of human beings as it permits a eugenic and racist selection of the human race, it offends against human dignity and it requires experimentation on humans' and the Vatican is certain that it is 'contrary to moral law' as it is 'in opposition to the dignity both of human procreation and the conjugal union 1. Political knees jerk as one when they see the chance for a headline, but Dolly's own progenitor — whose views deserve respect — calls human cloning 'an ugly diversion; superfluous and in general repugnant' (which does not inhibit the seven per cent of Americans who, according to one poll, would be happy to clone themselves).

Cloning, though, is but the latest stage in the manipulation of our reproductive machinery. Most people are ready to accept pregnancy termination on genetic grounds; and, in spite of the concerns about modified plants and animals, have no complaints about gene therapy, should that ever come to fruition. However, to interfere with the next generation, by engineering eggs or sperm or by cloning is, it seems, a step too far.

Even before Dolly, sexual technology had begun to explode. The demand is high. One married couple in six suffers from some failure of fertility, and miscarriages take place in about the same proportion of all pregnancies. At least a million people have been born by artificial insemination, and by 2005 there may be almost as many who trace their origins to a test-tube. Indeed, the chances of reproductive success in such a vessel are higher than those when trying to have a baby by more traditional means. Now, such methods are beginning to change the practice of genetics.

Many inborn illnesses, from PKU to cystic fibrosis, can be treated with some success. Such treatments deal with symptoms, rather than putting right the fundamental flaw — which is no more that what medicine does for most illnesses. Gene therapy gives hope of a cure. In its purest form, it offers the hope of replacing a faulty section of DNA with a normal equivalent, and putting right the problem at source. The idea is a powerful one: and nobody who accepts the necessity of inserting a new heart and lung can quarrel with the idea of replacing a piece of nucleic acid. Whatever its promise, gene therapy has, unfortunately, failed to live up to its headlines.

In principle, the job ought to be if not easy, at least feasible. DNA can be inserted into cells in culture in many ways. Copies made in a laboratory are infiltrated with the help of a virus or wrapped in envelopes of fat that are accepted by the cell as its own. Working genes can even be shot into cells by firing gold spheres coated with DNA from a tiny gun. Twenty years ago there were great hopes that such technology would revolutionise medicine. There have been many claims of success, but only one has much weight. Severe combined immunodeficiency is an inherited failure of the immune system that arises from the absence of a certain enzyme. Children with the condition are kept in a plastic bubble to reduce the chances of infection, and are given bone marrow transplants and injections of the enzyme to help their defences. Cells which lack the crucial protein have been 'cured 1with the appropriate DNA. Several children have been treated with such engineered cells- They are still alive and even go to school. As most of them were also given extracts of the enzyme it is not yet certain that their improved health is due to the gene manipulation.