GENOMICS: REVOLUTIONIZING MEDICINE

DNA: The Genetic Blueprint

It seems almost a miracle to me that fifty years ago we could have been so ignorant of the nature of the genetic material and now we can imagine that we will have the genetic blueprint of man.
-James Watson, 1992

In 1953, James Watson and Francis Crick electrified the scientific world with their now-famous model of the structure of deoxyribonucleic acid (DNA), the molecule that carries genetic information in coded form. Their double-helix formulation precipitated a rash of discoveries that has changed science — and provided a new way of seeing, studying, and knowing the biological world.

Left: James Watson and Francis Crick with their model, 1953.

Right: Original base pair templates, made of brass, from the Watson and Crick model. These templates represent the paired nucleotide bases that appear as horizontal links in the DNA model. This version represents an earlier incorrect modeling.

In the 46 years since the model was unveiled, the genetic "code" has been broken — and recombinant DNA technologies now allow us to splice, manipulate, and alter the all-important sequences of nucleotide bases within DNA. We are presently in the midst of a concerted effort to assemble comprehensive maps and atlases of genomes (the genetic material in any organism).

Left: X-ray crystallography image of DNA, 1952. This image, seen and studied by Watson and Crick, provided tantalizing clues to DNA's helical structure.

Right: Deoxyribonucleic acid (DNA) is identified as the genetic substance, 1944.

This grand enterprise is currently a central focus of genomics. The vast genomic databases that are being assembled will serve as road maps that will allow present and future generations to navigate through a biomolecular universe that is now being revealed for the first time — in much the same way that a microbiological universe was revealed centuries earlier.

An organism base by base
In 1995, Haemophilus influenzae was completely sequenced, meaning that the identity and location of every one of its more than 3 million base pairs (A, G, C, and/or T) was resolved. It was the first bacterial genome to be sequenced completely. What do these seemingly endless sequences of letters matter? Ultimately scientists are trying to find out how organisms are created, protein by protein and nucleic acid by nucleic acid. They would like to use DNA sequences to predict complex outcomes, and they would like to fill in "unknown" genomic territories.

Left: H. influenzae — genome map. Colored areas indicate genes whose function is more or less known. White bars indicate genes of unknown function. The map is round because the genome is essentially circular-composed of a single fused length of DNA. It is now more common to depict a circular chromosome as two rings, each representing one DNA strand.

Right: H. influenzae — pathogen. Despite its name, this bacterium is unrelated to the disease known as influenza. Rather, it can produce meningitis and other infectious diseases.