Fashionable Omics

In Benet Street, Cambridge, stands a rather ordinary pub which on Saturday, February 28, 1953, enjoyed 15 minutes of fame far beyond Andy Warhol -wildest dreams. Two young men arrived for lunch and, as James Watson watched, Francis Crick announced to the regulars in the bar that "we have found the secret of life." The more formal announcement of the structure of DNA appeared in Nature on April 2 in a commendably brief paper of two pages with six references. Watson and Crick shared a Nobel prize with Maurice Wilkins, whose work with Rosalind Franklin at King -s College, London had laid the groundwork. Sadly, Franklin' s early death robbed her of a share of the prize, which is never awarded posthumously.

Over the next two decades a large number of researchers teased out the details of the genetic control of cells, and by 1972 a team at the Laboratory of Molecular Biology of the University of Ghent, led by Walter Fiers, were the first to determine the sequence of a gene (a coat protein from a bacterio-phage). The same team followed up in 1976 by publishing the complete RNA nucleotide sequence of the bacteriophage. The first DNA-based genome to be sequenced in its entirety was the 5368-base-pair sequence of bacteriophage

0-X174 elucidated by Frederick Sanger in 1977. The science of genomics had been born.

Although the rush to sequence the genomes of ever more complex species (including humans in 2001) initially held out considerable hope of yielding new biomarkers, focus gradually shifted to the protein products of the genes. This process is dated by many to the introduction in 1977 by Patrick O'Farrell at the University of Colorado in Boulder of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The subject really took off in the 1990s, however, with technical improvements in mass spectrometers combined with computing hardware and software to support the extremely complex analyses involved.

The next "omics" to become fashionable was metabolomics, based on the realization that the quantitative and qualitative pattern of metabolites in body fluids reflects the functional status of an organism. The concept is by no means new, the first paper addressing the idea (but not using the word) having been "Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography" by Robinson and Pauling in 1971. The word metabolomics, however, was not coined until the 1990s.

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