Published on Sunday, June 11, 2000 in the Manchester Guardian
They've Got Your Number
In a few days, scientists will reveal humanity's genetic blueprint. But is it a triumph for pure science or a goldmine for big business?
by Robin McKie
Above the dark green reception desk and easy chairs in the entrance hall of Cambridge's Sanger Centre, a large electronic ticker displays a series of endlessly changing figures. The glowing green numerals look like fluctuating share prices - until you notice the absence of numbers, and the presence of only four letters.
Over and over again, different permutations of As, Cs, Gs and Ts scurry across the screen, a new letter appearing every few seconds. Every minute of the day, every day of the week, for the past five years, this ceaseless alphabetical outpouring - from the centre's hundreds of automatic DNA sequencers - has been displayed this way.
What is being uncovered, before visitors' eyes, is nothing less than the genetic blueprint of humanity. Each A,C, G and T is a unit of DNA, and in a few days, having spewed out several hundred million such letters, that ticker will approach its first major milestone: the first working draft of the entire human genome.
In collaboration with US government researchers, scientists at the Sanger Centre, backed by the Wellcome Trust, will announce they have decoded more than 90 per cent of the 3 billion units of DNA that determine our physical and mental characteristics. They will, in effect, have made the first biological blueprint of our species.
'Think of the human genome as the Book of Life,' says John Sulston, director of the Sanger Centre. 'We are about to read the first proof copy, as important an understanding as learning the Earth goes round the Sun or we are descended from apes.'
It is an astonishing achievement, one that reveals how life's mysteries are now succumbing to the onslaught of science. At this rate, scientists will produce their second, final, full draft of the human genome next year, or by early 2002, at least three years ahead of schedule.
'We know we have now decoded between 88 and 92 per cent of human DNA,' Dr Michael Morgan, head of the Wellcome Trust's genome endeavours. 'We just have to run the figures through our computers to make sure we have pased the 90 per cent milestone mark.'
It is certainly a dramatic achievement, though it has not been made without casualties. Indeed, the human genome project has become one of the most controversial scientific endeavours ever undertaken, riddled - as it now is - with exchanges of abuse, accusations that scientists are privatising the human soul.
This hostility has been triggered, virtually single-handedly, by Craig Venter, the abrasive, ambitious geneticist whose intervention into the genome project turned a cosy academic enterprise into a bitter race that has provoked the consternation of Bill Clinton and Tony Blair.
It was Venter - backed by a vast pyramid of venture capital - who launched his private company Celera, based in Rockville, Maryland, as a straight competitor to the public international effort and claimed he would unravel the human genome's 3 billion DNA units quicker than they would, and at a profit. Give up now, he told genome scientists in 1998, and save your efforts for simpler creatures like the mouse.
Now, two years later, Celera has produced its own working draft - or first assembly, as Venter calls it - of the human genome, and this weekend, like the scientists at the Sanger centre, its researchers will put their final, frantic touches to their first folio of the Book of Life. In the next few days, the world will find which team got there first.
But the battle between Celera and the public Human Genome Project - a collective enterprise involving 16 different world institutes, with the Sanger Centre taking on by far the greatest workload - is not just a business of two outfits seeking precious scientific priority for a major discovery. They are divided by a far greater gulf: the very ownership of the genes of the human race.
Venter aims to recoup his investment by selling his data to pharmaceutical companies and by taking out patents on the most promising genes he finds. These would form the basis of new medicines - for heart disease, diabetes, mental illness and cancers - in the next decade, he believes.
But the idea that human genes can be patented this way, thus restricting their use to only a select few, is anathema to the Wellcome Trust, the Sanger Centre, and their US publicly funded counterparts. Indeed, the British Cabinet's chief scientific adviser, Sir Robert May, believes it would be a 'screaming disaster' if such patents were granted.
Yet this is exactly what Venter expects. 'One hundred to 300 of the most promising genes - out of the tens of thousands in the whole human genome - that we find should be enough to give us a tidy return,' he says.
But to do that, he will have to do more than just isolate a gene, which is typically made up of a few thousand DNA units. He will have to find out what protein that gene makes in the human body, and also work out how to interfere with its biological activity. Only then can he claim he has the right to hold a patent on it. Many scientists doubt if Venter has the resources to do that. Just working out the basic make-up of the human genome will keep him busy for the next year or so. He remains confident, nevertheless.
The dispute is therefore about how medical science will proceed in the 21st century, with Venter, the research raptor who hunts genes for cash, encapsulating the approach of the ultimate capitalist, while John Sulston fulfils the part of the committed public servant. Certainly, the comparison is stark.
Venter turns up at meetings in hired Jaguars, snappy clothes and a gold Rolex watch. When not checking the soaring price of share options, he sails his own yacht. Sulston runs a second-hand car, reads The Observer , and is opposed to global capitalism. Their only common denominator is science.
However, it would be wrong to underestimate Venter, despite his upstart ways. He was a former medical orderly during the Tet offensive in the Vietnam War, where he started to ask himself 'big, naive questions', as he recalls. 'What is life in the first place? What makes it work?', he demanded. On his return to the US, he determined to find the answer and studied biochemistry, establishing a reputation as an innovative researcher, albeit one for whom the lure of lucre has been a prime motivation.
By contrast, Sulston - the son of a vicar and a teacher - was a committed opponent of the Vietnam War and remains modest to the last, describing his work as nothing more than 'solid, middle-of-the-road science'. Money appears to have little appeal. In their different ways both have had a considerable impact on science, of course: Sulston in his quiet determined way, Venter in his role as a brash stimulator of genetic research - though scientists on either side of the Atlantic dispute his claims that his intervention was responsible for galvanising the human genome project, and bringing forward its completion date.
'Competition is always good for efforts like ours,' says Dr Morgan. 'But the truth is that there were other, far more telling factors.
'The development of new generation DNA analysers in the late Nineties dramatically improved sequencing rates, both for us and for Craig Venter. Similarly, we have come under increasing pressure from scientists to speed up our work. They have found our information so valuable they have pushed and pushed us to increase our output, and we have obliged.'
For his part, Venter retains his main ire for British researchers. It was Morgan and Sulston, after all, who flew to the USA in 1998 immediately after Venter had announced his bid to privatise the project. There they pledged that they would double the United Kingdom's investment in unravelling the human genome, a move that restored US government researchers' dented morale, and raised the Sanger centre to the role of being the public project's prime opponent to Celera, much to Venter's annoyance.
According to him, the Wellcome Trust - which has bankrolled Britain's entire £240 million involvement in the project - has merely involved itself in human genomics to try to cover up massive losses. It is not a point that impresses Dr Morgan. 'We are a charity. We can't hide our losses. In any case, if Venter had decided to co-operate with us, if he had decided to share the workload, instead of going into this thing as straight, competitive battle, we would be completing the full final draft, not the 90 per cent first draft, by now.
'We would be a couple of years further down the path towards understanding our genes and their role in determining our health. That's why this stressing of a race is so harmful.'
Life's building blocks
Our bodies are made up of billions of cells, and each of these cells has a central core called a nucleus. Inside this nucleus are found the chromosomes. Each of us has 46 chromosomes in each one of our cells.
Chromosomes are carriers of our genes, the units of information that direct our bodies to manufacture the various proteins that make up our bodies. Our total complement of chromosomes is known as the genome.
We have about 100,000 genes parcelled up inside these 46 chromosomes and these are made of the chemical deoxyribonucleic acid: DNA.
A total of about 3 billion units of DNA coil up inside the nucleus to form our chromosomes. These units of DNA are known as 'bases' and they come in four varieties: adenine (A), cytosine (C), guanine (G) and thymine (T). Our genes are made up of different combinations of As, Cs, Gs, and Ts, a typical gene consisting of several thousand bases.
Not every piece of DNA goes to make up a gene, however. Along our chromosomes, there are gaps between our genes - stretches of As, Cs, Gs, and Ts that have no obvious function. These are known as junk DNA, and their role in human biology remains a mystery.
DNA holds key to beating disease
No two people on Earth have the same genetic make-up, apart from identical twins who are essentially human clones.
On average each person on the planet has about one million bases of DNA different from the next individual. Put another way, this means that each of us share 999 out of every 1,000 units of DNA. The remaining thousandth accounts for the myriad differences that separate each member of our species.
These mutations are spread along the genome and are known as single nucleotide polymorphisms (SNPs).
These are the genetic roots of individual differences and they hold the secret of medicine in the future.
Scientists want to study these SNPs because they believe they will allow them to pinpoint individual susceptibilities to disease. By correlating particular SNP mutations with individuals prone to certain illnesses they will be able to pinpoint versions of genes that leave people vulnerable to specific diseases.
'SNPs will allow disease associations to be determined for common disorders so drugs can be tailor-prescribed for the patient's particular mutation,' says geneticist Professor Kay Davies, of Oxford University. 'This will be very important in many disorders, but particularly in cancer and neural degenerative disorders like Alzheimer's Disease. The impact is some way off, but it will be enormous.'
© Guardian Newspapers Limited 2000