repackaged by environmentalists 2 5 4 G E N O M E
and told as a tale of the dangers of genetic engineering and reckless corporate greed.
None the less, and even allowing for the cautious cancellation of many projects, it is a safe estimate that by the year 2000, fifty to sixty per cent of the crop seed sold in the United States will be genetically modified. For better or for worse, genetically modified crops are here to stay.
So are genetically modified animals. Putting a gene into an animal so that it and its offspring are permanently altered is now simple in animals as well as plants. You just stick it in. Suck your gene into the mouth of a very fine glass pipette, jab the tip of the pipette into a single-celled mouse embryo, extracted from a mouse twelve hours after mating, make sure the tip of the pipette is inside one of the cell's two nuclei, and press gently. The technique is far from perfect: only about five per cent of the resulting mice will have the desired gene switched on, and in other animals such as cows, success is even rarer. But in those five per cent the result is a 'transgenic'
mouse with the gene incorporated in a random position on one of its chromosomes.
Transgenic mice are scientific gold dust. They enable scientists to find out what genes are for and why. The inserted gene need not be derived from a mouse, but could be from a person: unlike in computers, virtually all biological bodies can run any kind of software. For instance, a mouse that is abnormally susceptible to cancer can be made normal again by the introduction of a human chromosome 18, which formed part of the early evidence for a tumour-suppressor gene on chromosome 18. But rather than inserting whole chromosomes, it is more usual to add a single gene.
Micro-injection is giving way to a subtler technique, which has one distinct advantage: it can enable the gene to be inserted in a precise location. At three days of age, the embryo of a mouse contains cells known as embryonic stem cells or ES cells. If one of these is extracted and injected with a gene, as Mario Capecchi was the first to discover in 1988, the cell will splice that gene in at precisely the point where the gene belongs, replacing the existing C U R E S 2 5 5
version of the gene. Capecchi took a cloned mouse oncogene called
mouse - a mouse in which some of the cells contain the new gene.3
Homologous recombination allows the genetic engineer not only to repair genes but to do the opposite: deliberately to break working genes, by inserting faulty versions in their place. The result is a so-called knockout mouse, reared with a single gene silenced, the better to reveal that gene's true purpose. The discovery of memory mechanisms (see the chapter on chromosome 16) owes much to knockout mice, as do other fields of modern biology.
Transgenic animals are useful not only to scientists. Transgenic sheep, cattle, pigs and chickens have commercial applications. Sheep have already been given the gene for a human clotting factor in the hope that it can be harvested from their milk and used to treat haemophiliacs. (Almost incidentally, the scientists who performed this procedure cloned the sheep Dolly and displayed her to an amazed world in early 1997.) A company in Quebec has taken the gene that enables spiders to make silk webs and inserted it into goats, hoping to extract raw silk protein from the goats' milk and spin it into silk. Another company is pinning its hope on hens' eggs, which it hopes to turn into factories for all sorts of valuable human products, from pharmaceuticals to food additives. But even if these semi-industrial applications fail, transgenic technology will transform animal breeding, as it is transforming plant breeding, generating beef cattle that put on more muscle, dairy cattle that give more milk or chickens that lay tastier eggs.4
It all sounds rather easy. The technical obstacles to breeding a transgenic or a knockout human being are becoming trivial for a 256 G E N O M E
good team at a well-equipped laboratory. In a few years from now you probably could, in principle, take a complete cell from your own body, insert a gene into a particular location on a particular chromosome, transfer the nucleus to an egg cell from which the nucleus had been removed, and grow a new human being from the embryo. The person would be a transgenic clone of yourself, identical in every way except, say, in having an altered version of the gene that made you go bald. You could alternatively use ES cells from such a clone to grow a spare liver to replace the one you sacrificed to the bottle. Or you could grow human neurons in the laboratory to test new drugs on, thus sparing the lives of laboratory animals.
Or, if you were barking mad, you could leave your property to your clone and commit suicide secure in the knowledge that something of you still existed, but slightly improved. Nobody need know that this person is your clone. If the increasing resemblance to you later became apparent as he grew older, the non-receding hairline would soon lay suspicions to rest.
None of this is yet possible - human ES cells have only just been found — but it is very unlikely to remain impossible for much longer. When human cloning is possible, will it be ethical? As a free individual, you own your own genome and no government can nationalise it, nor company purchase it, but does that give you the right to inflict it on another individual? (A clone is another individual.) Or to tamper with it? For the moment society seems keen to bind itself against such temptations, to place a moratorium on cloning or germline gene therapy and strict limits on embryonic research, to forego the medical possibilities in exchange for not risking the horrors of the unknown. We have drummed into our skulls with every science fiction film the Faustian sermon that to tamper with nature is to invite diabolic revenge. We have grown cautious. Or at least we have as voters. As consumers, we may well act differently. Cloning may well happen not because the majority approves, but because the minority acts. That, after all, was roughly what happened in the case of test-tube babies. Society never decided C U R E S 257
to allow them; it just got used to the idea that those who desperately wanted such babies were able to have them.
Meanwhile, in one of those ironies which modern biology supplies in abundance, if you have a faulty tumour- suppressor gene on chromosome 18, forget gene therapy. A much simpler preventive treatment may be at hand. New research suggests that for those with genes that increase their susceptibility to bowel cancer, a diet rich in aspirin and unripe bananas offers the promise of protection against the cancer. The diagnosis is genetic, but the cure is not.
Genetic diagnosis followed by conventional cure is probably the genome's greatest boon to medicine.
C H R O M O S O M E 1 9
P r e v e n t i o n
Ninety-nine per cent of people don't have an inkling about how fast this revolution is coming.
