Pioneers in a new age of discovery

The story behind yesterday's discovery goes back to 1953, when two young scientists at Cambridge University worked out that DNA came in the beautiful three-dimensional structure of a double helix.

With that insight, Jim Watson and Francis Crick opened the way to explaining two of the most important features of the DNA molecule of inheritance: how it stored the information of the genes, and how it replicated this information for the benefit of subsequent generations.

The second half of the 20th century was the age of the new biology, when molecular genetics began to explain many of the distinguishing features of humanity, from inherited diseases to the origins of man.

Fred Sanger, one of the many Nobel laureates at the Laboratory of Molecular Biology in Cambridge - in fact Sanger won two - laid the groundwork for the modern techniques of DNA sequencing, the unravelling of the individual letters of the genetic code.

In the 1980s, scientists began to talk about achieving the ultimate goal, the complete sequencing of the human genome. Jim Watson, who was appointed head of the American government's genome effort, said in 1990 that unravelling the full sequence of the human genome could be likened to the goal set by President John F Kennedy in 1961 to land a man on the Moon.

"The implications of the human genome project for human life are likely to be far greater. A more important set of instruction books will never be found," Dr Watson said.

Huge teams of scientists were assembled to begin the project on both sides of the Atlantic. The Wellcome Trust, the world's biggest medical research charity, led the effort in Britain, setting up the Sanger Centre in Cambridge to lead the work.

Meanwhile, a private organisation led by Craig Venter, a former beach bum and Vietnam veteran, began a sequencing effort using a different approach. The two efforts were not supposed to be rivals, but everyone knew they were . Dr Venter denied that he was trying to privatise the human genome, which was being made publicly available by the public effort funded by the British and the American governments.

"People were making distorted claims, saying I would patent the entire genome. But we're not in the business to own the human genome. We're in the information business, and this only works if our data are widely used," Dr Venter said in 1999.

Meanwhile, the British effort was led by John Sulston, who was to win a Nobel Prize for his previous work in genetics. Sulston - who lists his hobbies as gardening and avoiding people - appeared the antithesis of the brash Venter.

Dr Sulston promised he would do everything in his power to keep the human genome freely available to all. "Craig has gone morally wrong. Celera Genomics [Venter's company] wants to establish a monopoly on the human sequence," Dr Sulston once said.

But what no one anticipated after the full sequence was finally published was just how complicated the genetic landscape would become. Instead of carrying just two copies of each gene - one from each parent - it now appears that we have several copies of certain key genes.

On top of the variation in the DNA sequence between people, there seems now to be an added layer of complexity. Some people appear to have many more copies of certain genes than otherwise healthy people. Why we have this variation and how it has come about is unanswered.

Scientists now believe this unexpected genetic variation may explain why some people are prone to illnesses ranging from inflammatory bowel disease to schizophrenia.

"As we study more healthy individuals... we uncover completely new human DNA sequences," said Charles Lee, of the Brigham and Women's Hospital in Boston, Massachusetts."

"The copy number variations and the biological implications of these novel DNA sequences can now be fully explored," Dr Lee added.

The genome explained

DNA

Deoxyribonucleic acid is the blueprint of life. It is the chemical substance of genes that creates the variations that dictate the development of every form of cellular life, from amoeba to human beings.

The information which DNA contains passes on all inherited traits such as hair colour. Biochemists isolated DNA in the late 19th century but its structure was unravelled only in 1953 by British scientists including James Watson and Francis Crick.

Chromosome

This is the part of a cell that contains the DNA. Its rod-shaped structure contains the genes or individual units that are built from DNA. Every species has a specific number of chromosomes - humans have 23 pairs while a fruit fly has eight. Chromosomes are key to cell division, providing the DNA sequence for each new entity.

Genes

Anchored within chromosomes, genes are the unit of heredity. They consist of strings of DNA and direct the physical development or behaviour of an organism. It is the arrangement of nitrogen-based molecules on a strand of DNA which determines the genetic code. Biologists rarely use the term "gene" to apply to a single cause of a disease because it is unlikely that a single gene is responsible.

Genome

The entire hereditary information of an organism as encoded within its DNA. The human genome consists of three billion separate units of information which together describe the genes that make up the 23 pairs of chromosomes. It does not express the genetic diversity of a species, which would require the comparison of the DNA of each individual.

Cahal Milmo