LA JOLLA, CALIFORNIA – Back in June 2000, when the draft human-genome sequence was announced, US President Bill Clinton proclaimed, “It will revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases.” A decade later, hope has given way to disappointment, reflected in headlines like “Gene Map Yields Few New Cures.”
But pessimism about the potential of human-genome research to yield medical breakthroughs has arisen from unrealistic expectations. Indeed, while “silver bullets” that can cure our most feared diseases have not been found, progress in the area of gene-drug interactions, known as pharmacogenomics, has been extraordinary.
The ability to determine the principal genes that account for our variable response to prescription drugs has been advanced by a technique known as a genome-wide association study (GWAS). The whole human genome has approximately six billion bases, but a window into its composition can be probed using approximately one million bases (0.01% of the genome) via a gene chip. The bases on the chip are selected because they are informative, tagging bins of the genome, like a post-code directory. Using GWAS methodology, we have learned the biological basis for responses to many drugs – both their effectiveness and important side-effects.