these things, whether we should, and why, on the brink of doing so, our courage seems to be failing us and we are strongly tempted to throw away the whole word processor and insist that the text remains sacrosanct. This chapter is about genetic manipulation.
For most laymen, the obvious destination towards which genetic research is headed, the ultimate prize if you like, is a genetically engineered human being. One day, centuries hence, that might mean a human being with newly invented genes. For the moment it means a human being with an existing gene borrowed from another human being, or from an animal or plant. Is such a thing possible? And, if it is possible, is it ethical?
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Consider a gene on chromosome 18 that suppresses colon cancer.
We have already met it briefly in the last chapter: a tumour suppressor whose location has not quite been determined for sure. It was thought to be a gene called
guides the growth of nerves in the spinal column and has nothing to do with tumour suppression. The tumour- suppressor gene is close to
I am just old enough to have begun my career in journalism cutting paper with real scissors and pasting with real glue. Nowadays, to move paragraphs around I use little software icons suitably decor-ated by the kind folk at Microsoft to indicate that they do the same job. (I have just moved this paragraph to here from the next page.) But the principle is the same: to move text, I cut it out and paste it back in somewhere else.
To do the same for the text of genes also requires scissors and glue. In both cases, fortunately nature had already invented them for her own purposes. The glue is an enzyme called ligase, which stitches together loose sentences of D N A whenever it comes across them. The scissors, called restriction enzymes, were discovered in bacteria in 1968. Their role in the bacterial cell is to defeat viruses by chopping up their genes. But it soon emerged that, unlike real scissors, a restriction enzyme is fussy: it only cuts a strand of D N A where it encounters a particular sequence of letters. We now know of 400 different kinds of restriction enzymes, each of which recognises a different sequence of D N A letters and cuts there, like a pair of scissors that cuts the paper only where it finds the word 'restriction'.
In 1972, Paul Berg of Stanford University used restriction enzymes in a test tube to chop two bits of viral D N A in half, then used ligases to stick them together again in new combinations. He thus produced the first man-made 'recombinant' D N A . Humanity could now do what retroviruses had long been doing: insert a gene into a C U R E S 245
chromosome. Within a year, the first genetically engineered bacterium existed: a gut bacterium infected with a gene taken out of a toad.
There was an immediate surge of public concern and it was not confined to lay people. Scientists themselves thought it right to pause before rushing to exploit the new technology. They called a moratorium on all genetic engineering in 1974, which only fanned the flames of public worry: if the scientists were worried enough to stop, then there really must be something to worry about. Nature placed bacterial genes in bacteria and toad genes in toads; who were we to swap them? Might the consequences not be terrible? A conference, held at Asilomar in 1975, thrashed out the safety arguments and led to a cautious resumption of genetic engineering in America under the supervision of a federal committee. Science was policing itself. The public anxiety seemed gradually to die down, though it was to revive quite suddenly in the mid-1990s, this time focusing not on safety but on ethics.
Biotechnology was born. First Genentech, then Cetus and Biogen, then other companies sprang up to exploit the new technique. A world of possibilities lay before the nascent businesses. Bacteria could now be induced to make human proteins for medicine, food or industrial use. Only gradually did disappointment dawn, when it emerged that bacteria were not very good at making most human proteins and that human proteins were too little known to be in great demand as medicines. Despite immense venture-capital investment, the only companies that made profits for their shareholders were the ones, such as Applied Biosystems, that made equipment for the others to use. Still, there were products. By the late 1980s, human growth hormone, made by bacteria, had replaced the expensive and dangerous equivalent extracted from the brains of cadavers.
The ethical and safety fears proved so far groundless: in thirty years of genetic engineering no environmental or public health accident big or small has resulted from a genetic engineering experiment. So far, so good.
Meanwhile, genetic engineering had a greater impact on science than it had on business. It was now possible to 'clone' genes (in 2 4 6 G E N O M E
this context the word has a different meaning from the popular one): to isolate a 'needle' of a human gene in the 'haystack' that is the genome, put it in a bacterium and grow millions of copies of it so that they can be purified and the sequence of letters in the gene read. By this means, vast libraries of human D N A have been created containing thousands of overlapping fragments of the human genome, each present in sufficient quantity to study.
It is from such libraries that the people behind the Human Genome Project are piecing together the complete text. The scale of their task is immense. Three billion letters of text would fill a stack of books 150 feet high. The Wellcome Trust's Sanger Centre near Cambridge, which leads the effort, is reading the genome at the rate of 100 million letters a year.
There are, of course, short cuts. One is to ignore the ninety-seven per cent of the text that is silent - the selfish D N A , the introns, repetitious minisatellites and rusting pseudogenes - and concentrate on the genes alone. The quickest way to find such genes is to clone a different sort of library, called a cDNA library. First, sieve out all fragments of R N A in the cell. Many of them will be messengers —
edited and abridged copies of genes in the process of being translated. Make D N A copies of those messengers and you will have, in theory, copies of the texts of the original genes with none of the junk D N A that lies in between. The main difficulty with this approach is that it gives no hint of the order or position of the genes on the chromosomes. By the late 1990s there was a marked difference of opinion between those who wanted to pursue this
'shotgun' method to the human genome with commercial patenting along the way, and those who wanted to be slow, thorough and public. On one side was a high-school drop-out, former professional surfer, Vietnam veteran and biotechnology millionaire named Craig Venter, backed by his own company Celera; on the other a studious, bearded, methodical Cambridge-educated scientist, John Sulston, backed by the medical charity Wellcome Trust. No prizes for guessing which camp is which.
But back to manipulation. Engineering a gene into a bacterium C U R E S 2 4 7
is one thing; inserting a gene into a human being is quite another.
