The secret of Life

Today, scientists in London, Washington and Tokyo will announce that they have cracked the genetic code of human chromosome No 22.

Pluck a single hair from your head and take a look at the small, white root of living tissue at the base of the shaft. What you have between your fingers is the complete recipe for making another you. Each one of the microscopic cells contains a book of humanity, written in the 23 chapters of the pairs of chromosomes. If this digital code could be downloaded on a CD-rom and sent to an intelligent extraterrestrial civilisation, it would contain just about all the instructions necessary for making a human being on another planet.

Pluck a single hair from your head and take a look at the small, white root of living tissue at the base of the shaft. What you have between your fingers is the complete recipe for making another you. Each one of the microscopic cells contains a book of humanity, written in the 23 chapters of the pairs of chromosomes. If this digital code could be downloaded on a CD-rom and sent to an intelligent extraterrestrial civilisation, it would contain just about all the instructions necessary for making a human being on another planet.

Sending the recipe for a man or woman into space is not, of course, the intention of the Human Genome Project, the massive international effort to decode the entire complement of 23 chromosomes. But understanding how we are made from the bare instructions of our genes is what is behind the estimated $3bn (£1.9bn) being spent on unravelling the code of our DNA. This week, a major milestone is reached in that effort with the unveiling in London, Washington and Tokyo (today) and the formal publication (tomorrow) of the complete genetic code of the smallest of the human chromosomes, number 22. The remaining chromosomes will be completely deciphered within three to five years, opening the door to a huge library of knowledge relevant to medicine, human origins and our place in the evolution of life.

"The end of the Human Genome Project is the beginning of the real genetics of mankind," says Sir Walter Bodmer, one of the architects of the project, and now master of Hertford College, Oxford.

Decoding the human chromosomes marks the dawn of a new era of unrivalled scientific achievement, says John Sulston, director of the Sanger Centre in Cambridge and leader of the team that deciphered chromosome 22. "Think of the human genome as the Book of Life. We are about to read the first chapter, as important an accomplishment as discovering that the Earth goes round the Sun, or that we are descended from apes."

Twenty years ago, the prospect of being able to read that book of life was a mere twinkle in the eye of scientists such as Bodmer and Sulston. Their vision slowly became reality during the Eighties. At a series of meetings on the east and west coasts of America - mostly at the Cold Spring Harbor Laboratory in New York and the University of California - the cognescenti met to discuss their dream. By 1986 the blueprint for how it could be done was drawn up, backed by a string of Nobel laureates, not least of whom was the American molecular biologist Jim Watson, co-discoverer of the structure of the DNA helix. In 1988 they established an international body to take charge of the effort, supported by the huge financial muscle of the US government.

Few people realise that Mikhail Gorbachev, the former Soviet leader, played a small but decisive role in instigating the genome project. As a result of Gorbachev's perestroika, and the subsequent thaw in the Cold War, the American Department of Energy began to look for alternative jobs for its immensely expensive nuclear weapons laboratories. Rather than shrink its military research operation, the department instead offered its powerful supercomputers to the molecular biologists who dreamed of unravelling the entire DNA code of man.

It is no mean feat to decipher the DNA packed into each of the 23 pairs of human chromosomes. If each molecule of DNA in the 46 chromosomes of just one cell were unravelled and placed end to end, they would stretch for 6ft.

It is this 6ft of information that constitutes the book of man. And what a book. There is enough information in the DNA of one cell to fill 5,000 conventional books, or about a dozen copies of the Encyclopaedia Britannica. Writing out the book with each letter of the genetic code taking up one centimetre would result in a text as long as the river Danube. Yet it can all sit comfortably in a single cell on the tip of a human hair.

For those scientists gathering at the interminable scientific meetings at the end of the Eighties, it seemed a daunting task. Most thought that, even with the best computers available, they would be lucky to complete the job by 2010. Some cynics even calculated that the finishing-date would neatly coincide with their retirement, guaranteeing them full employment for life. Then along came a man called Craig Venter, who upset the apple cart by setting up a rival decoding operation.

Venter is a maverick. He left school in California at 17, with few qualifications apart from the surfboard skills learnt as a teenage beach bum. He was drafted to Vietnam in 1967 and served as a medical orderly in Da Nang, which saw some of the most horrific casualties in the war. The experience changed his life, and on his return to America he set about qualifying in medical science. He completed his two degrees in just six years. By 1990 he, too, was involved in the genome project, having devised a "quick and dirty" way of deciphering the hugely long human DNA code.

One of the problems scientists have faced with DNA is that most of it - more than 90 per cent - is apparently meaningless. Only a small fraction has useful information in the form of the 80,000 or so human genes. The rest is "junk" DNA that just gets in the way of the decoders. Venter used nature's own way of editing out this junk to get to the real meat of the genetic story.

In the early Nineties, Venter fell out with the official genome project after he applied to patent the fragments of genes he was discovering - and as a result he left to set up his own rival, private operation. Suddenly the comfortable world of the genome masters turned into an unseemly race; on the one hand was the leviathan might of the US government and the Wellcome Trust (the world's biggest research charity, and funder of the Sanger Centre), aided by the ageing doyens of molecular biology; and on the other was a bunch of privateers epitomised by Venter, whose quick and dirty approach using highly specialised skills threatened to beat the DNA dinosaurs to the finishing line.

In public, everyone involved denies that there is a race. "That our work is so often portrayed as a race to get the human genome sequenced is very sad. The real point is to get to that new starting-line," says Venter, referring to the future opportunities the genome offers for medicine in the 21st century and beyond. Nevertheless, he accepts that he has ruffled a few feathers. "We're changing the rules, and that upsets people," he says. Jim Watson, a man not noted for his tact, has meanwhile dismissed Venter's approach as work that "any monkey" could do.

Yet the fact remains that there is more to the human genome project than the pure pursuit of knowledge. Drug companies in particular see the venture as a vital element in their continuing battle to develop new medicines, and to keep ahead of the competition. Bodmer, a former head of the Imperial Cancer Research Fund, says that deciphering the genes will have an enormous impact on understanding and treating common, currently incurable diseases, notably cancer, as well as more obvious inherited disorders such as cystic fibrosis. Knowing the genetic mechanism behind a disease such as cancer allows pharmaceutical companies to design drugs specifically targeted against that gene defect, he says.

Another growth area will be in so-called "personalised medicine", which envisages a day when doctors are able to investigate a patient's genetic make-up and compare it against the standard genome in order to offer specific advice or treatment to lessen the risk attached to an inherited predisposition, such as heart disease or even alcoholism. Drug companies see the genome as an opportunity for designing drugs tailored to specific patients, which might avoid the side-effects experienced by people with a certain genetic constitution.

In a neat twist to the genome race, a consortium of some of the world's best-known drug companies and gene-research institutes announced earlier this year that they intend to co-operate on a type of genetic mapping involving the discovery of the smallest DNA mutations. The co-operation, however, is not entirely philanthropic. The aim is to publish the information on the Internet as soon as it is found, thereby frustrating small fry such as Venter who would be unable subsequently to claim a patent on data that is freely available in the public domain.

Publication of the genetic code of chromosome 22 by the official genome project marks a defining moment that many scientists believe will revolutionise almost every aspect of medicine and human biology. "Being able to read the genome will tell us more about our origins, our evolution, our nature and our minds than all the efforts of science to date," says Matt Ridley, the British science writer. "I truly believe we are living through the greatest intellectual moment in history. Bar none."

Chromosome 22 marks the start, and the rest of the genome will soon follow. The ultimate mystery of our DNA will then begin to unfold in the language of the genes. And the entire book is there, on the tip of that single shaft of hair.

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