Published online 24 April 2003 | Nature | doi:10.1038/news030421-5

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DNA's family tree

Tom Clarke retraces the path that led Watson and Crick to the double helix, and others to put their discovery to use.

Watson (left) and Crick built on nearly a century of research.Watson (left) and Crick built on nearly a century of research.© SPL

In 1869, the Swiss physician Friedrich Miescher was treating the wounded in the Crimean War. Studying the pus in casualties' bandages, he discovered a large molecule in the nucleus of cells, which he christened 'nuclein'. He went on to study the molecule in salmon sperm, and even suggested that it might be involved with the genetic code.

Miescher had discovered deoxyribose nucleic acid - DNA. But his belief in its importance swam against the scientific current. Most researchers thought that proteins, which are larger and more complicated than DNA, were the molecules that carried genetic information through the generations. DNA was seen as a handmaiden to its more complex cousin.

By the mid-twentieth century, this had become the prevailing wisdom. "The feeling was that DNA was too limited in diversity to carry genetic information," says biochemist Maclyn McCarty.

McCarty helped to change this feeling in 1944, while working in Oswald Avery's lab at Rockefeller University in New York. Avery's team showed that one pneumonia bacterium could be made infective by transferring DNA - and only DNA - from another. Infectiveness was known to be hereditary, so DNA must be the stuff of inheritance.

This work was the spark that lit the bonfire of molecular biology. It inspired James Watson and Francis Crick to begin looking for the structure of DNA.

Watson and Crick picked up on the work of another Avery-inspired researcher, biochemist Erwin Chargaff. He found that DNA's four chemical letters come in pairs: the amount of adenine (A) and thymine (T) are always the same, as are the amount of cytosine (C) and guanine (G).

Chargaff's work got Watson and Crick thinking about how two strands of DNA, each bearing a string of letters, could pair up to form the double helix A matching with T, and G with C.

DNA's structure is a three-dimensional jigsaw of its chemical building blocks.DNA's structure is a three-dimensional jigsaw of its chemical building blocks.Source:

Guided by the X-ray photographs taken by Rosalind Franklin and Maurice Wilkins at King's College London, Watson and Crick created models showing how the building blocks of DNA - the sugar molecules that form the backbone and the letters, or bases - could fit together in a chemically stable structure.

The structure made it obvious that the molecule encodes information. Almost as important, however, "it explained how all that information could be compacted into a cell", says Robert Olby, a science historian at the University of Pittsburgh in Pennsylvania. DNA's tight spiral showed how genetic information can be packed into chromosomes.

Yet even after the unveiling of the double helix, there was still no rush to study DNA. All but a few researchers saw it as "an interesting proposal waiting for further work", says Olby.

Most scientists were unfamiliar with the molecule. And people weren't ready to believe that heredity was based on a simple string of bases. "Watson and Crick provided the evidence that information underlies biology," says molecular biologist Walter Gilbert at Harvard University. "That took a while to sink in."

Scientists were also slow on the uptake because, like a newborn baby, DNA wasn't very useful. A mechanism for storing information is one thing, getting at that information was another.

Through the 1950s, researchers put flesh on the bones of Watson and Crick's structure. In 1955, geneticist Seymour Benzer of Purdue University, Indiana, showed that genes in bacteria consist of long stretches of DNA letters, and that just one error could render them useless.

And once researchers discovered how cells boss their genetic information about, they could really start making use of DNA. In 1956, biochemist Arthur Kornberg found the enzyme used to copy DNA, a finding that earned him a Nobel Prize. In 1957 Crick cracked the genetic code, showing how genetic information is translated into the protein molecules that do the work in cells.

In the late 1950s and '60s, researchers discovered enzymes that could split the two strands of DNA apart, stick them back together again, and even bite into DNA strands at the sites of specific sequences. These molecular tools made it possible to cut out lengths of DNA from one organism and paste them into another - genetic engineering was born.

“The double helix explained how all that information could be compacted into a cell”

Robert Olby
University of Pittsburgh

The other major step was figuring out how to read genetic sentences. DNA sequencing, as it became known, was pioneered by the British biochemist Frederick Sanger.

Sanger developed a way of marking the bases of DNA with radioactive tags that could be read using X-rays. Using this technique, he produced the first complete list of the DNA letters needed to code for the structure of a complete protein, insulin, a feat that netted him his second Nobel Prize in 1980.

Sanger's invention gave birth to the science of genomics. With it, we gained the power to compare genes - allowing us to analyse patterns of disease, the evolution of species, and the history of human groups and individuals.

With all the work that paved the way for Watson and Crick, and all the discoveries that were needed to give their insight relevance, why did they and their structure end up in the pantheon while other people, ideas and events did not?

The answer, says Olby, is that the molecule is the one thing that unites all of the theories and discoveries. And, like all of us, biologists need heroes. "Watson and Crick's structure for DNA has become part of the social structure of biology," says Olby. 

University of Pittsburgh

  • References

    1. Watson, J. D. & Crick, F. H. C. A structure for deoxyribose nucleic acid. Nature, 171, 737 - 738, (1953). | ISI |