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Last Updated: Friday, 25 April 2003, 07:55 GMT 08:55 UK
DNA: 50 years in the open
1953 DNA model section
Watson and Crick's 1953 model
Courtesy Science Museum, London
Carina Dennis of the science journal Nature explains the significance and consequences of Watson and Crick's landmark 1953 discovery.

DNA is, in every sense, a modern icon. For decades, it has enthralled scientists striving to understand its molecular meaning, provided an aesthetic template for artists, and challenged society with all sorts of ethical conundrums.

The defining moment for DNA was the discovery of its structure.

Published in the science journal Nature 50 years ago this month, James Watson and Francis Crick described how two strands of DNA embrace to form a double helix, and sparked a scientific revolution.

Watson and Crick published their landmark paper in Nature
Watson and Crick published their discovery 50 years ago in Nature
To convince the sceptics that DNA truly was the material of inheritance - the so-called "stuff of life" - it was necessary to show how it could be copied and passed on from one generation to the next. Watson and Crick's model immediately hinted as to how DNA might be copied - each strand of the helix could act as a template to replicate the other.

This turned out to be true and a couple of years later Arthur Kornberg and his co-workers isolated the DNA-copying enzyme, DNA polymerase, which was later recruited for many kinds of DNA technologies.

Another quandary for contemporaries of Watson and Crick was how DNA with its 4-letter alphabet could encrypt the 20 kinds of protein building blocks, called amino acids.

Dawn of biotech

The genetic code was cracked in the 1960s, when Marshall Nirenberg, Har Khorana, and Severo Ochoa figured out that three letters of DNA encodes a particular amino acid. A three-letter word made of four possible letters could have more than enough permutations to encode the 20 amino acids.

The sun rose for biotechnology in the 1970s, with some ingenious tricks for manipulating DNA.

The rate of progress has been breathtaking
Paul Berg and Herbert Boyer devised a way of cutting and pasting together different pieces of DNA.

Boyer, together with Stanley Cohen, then discovered how to clone DNA - by piecing together fragments of DNA from different species and popping them into bacteria, where they could be copied in limitless quantities, like a biological photocopier.

In 1983, in a flash of inspiration while driving on a Californian highway, Kary Mullis figured out how to churn out millions of copies of a DNA segment in a test-tube by a process known as polymerase chain reaction.

These DNA techniques, and others, soon became essential components of the modern genetic engineer's toolkit.

Industrialising biology

If landing a man on the Moon has an equivalent in biology, it would have to be the sequencing of the human genome.

And this lofty goal would not have been conceivable without moments of exceptional scientific insight, like the discovery of the double helix, plus years of refining sequencing technologies.

Not to mention a cast of thousands - of both human and robotic sequencers - doggedly transforming the process into production-line efficiency.

The rate of progress has been breathtaking. In the 1970s, scientists first figured out how to sequence the letters along a strand of DNA.

Genomic milestones

The first genome - that of a bacterial virus - was a mere 5,400 bases and it took years to sequence. Only a decade later, an international collaboration of scientists embarked on an endeavour to sequence the 3 billion bases of our genome.

The draft version of the human genome sequence was unveiled in 2001, amidst much fanfare. And this month the International Human Genome Sequencing Consortium reached their summit, unveiling a polished complete version of the human genome, bar a few gaps that still remain beyond the reach of current sequencing technology.

One reason that many of us take DNA personally - more so than say, discoveries of superconductors, cold fusion or dark matter - is because it constitutes the enigmatic core around which much of our behaviour, desires, fears, as well as our health, revolve.

Genes and medicine

Not much is known about how DNA controls the former but some progress is being made on the medical front.

With the aid of genetic maps - where sequence landmarks help to navigate around the vast landscape of the human genome - scientists have been able to pinpoint the genetic mishaps that underpin some human diseases without any prior knowledge of the cause.

In 1986, the first gene for an inherited disease - the gene defective in chronic granulomatous disease - was identified using only genetic mapping strategies. Gene hunters have since collected an impressive range of trophies, with the genes for hundreds and hundreds of inherited diseases identified.

Many DNA-based cures for human disease... are still a long way off
Meanwhile, triumphs in finding genes that influence common diseases and human behaviour are far fewer, in part because the hunt is complicated by the influence of multiple genes as well as environmental factors thrown in. Nonetheless, genes that influence mood, eating habits, heart disease and diabetes have surfaced.

DNA has influenced medicine in other ways.

The advent of DNA recombinant technology has made it possible to manufacture important human proteins, like insulin and growth hormone, for treating disease.

It started with the first cloning of a human gene - the gene encoding somatostatin, an inhibitor of human growth hormone - by the company Genentech in 1977 followed by the human insulin gene the following year which, when marketed in 1982, became the first recombinant-DNA drug.

More recently, doctors have been able to look at the profile of gene activity in some cancers to make more accurate diagnoses and decide on the most effective treatments.

But many DNA-based cures for human disease - such as gene therapy strategies to replace a defective gene with a healthy version - are still a long way off.

DNA in the courtroom

DNA technology has revolutionised forensic science.

The next revolution will be in the hands of educators and lawmakers
In the mid-1980s, Alec Jeffreys developed DNA fingerprinting methods for identifying individuals.

DNA has since become a key "witness" in numerous cases, pointing the finger at the guilty and exonerating the innocent. It has also been used in paternity cases, such as that between Liz Hurley and her former beau, and to identify victims of accidents and crimes, including those who perished in the World Trade Center terrorist attack.

But, as with other great scientific advances, progress comes with some perils.

Like gazing into a crystal ball, we are transfixed by the potential of DNA to open windows into our past, present and future. But it may reveal more than we would like to know and there are concerns about genetic discrimination by employers, health insurers or society generally.

While some laws have already been implemented to protect against such abuses of genetic information, the next revolution will be in the hands of educators and lawmakers to ensure the public understands and benefits from the promise embedded within the DNA double helix.

© Carina Dennis 2003

Carina Dennis is co-author and editor of the book 'The Human Genome', published by Palgrave, 2001, co-editor of '50 years of DNA', published by Palgrave, 2003, editor of the publication of the human genome in Nature, 15 February 2001 and commissioning editor of the 'The Double Helix - 50 years' supplement in Nature, 23 January 2003.




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