From Human Genome Research to Personalized Health Care: The Potential Is Widely Recognized, But Much More Knowledge Is Needed to Make the Science Clinically Useful (Genomics IN HEALTH Care) (Viewpoint Essay‪)‬

"Big Science" in the life sciences was launched in 1986 with a bold plan to develop the technologies to determine the sequence of the 3 billion nucleotide base pairs (letters of DNA code) in the human genome. The Human Genome Project declared success by 2001 and has stimulated a wealth of related research. Analyses of the genomes of many organisms have yielded powerful evidence of sequences conserved during evolution. Analyses of microorganisms set the stage for pathogen/host interaction studies. Essentially all fields of life sciences research have been transformed by knowledge of protein-coding genes, recognition of genomic variation across individuals, findings of new mechanisms of regulation of gene expression, and patterns of proteins and metabolites in generating the features of living organisms. From the beginning, there have been high expectations that such knowledge would enhance clinical and public health practice through understanding of predispositions to disease, identification of molecular signatures and biomarkers for stratification of patients with different subtypes of a disease, earlier diagnoses, and discovery of molecular targets for therapeutic and preventive interventions. There has been compelling evidence for at least 150 years that genetics plays a major role in many traits and diseases. Identical twins are much more likely to manifest similar traits and develop similar diseases than are fraternal twins (or regular siblings). Modern researchers first tested individual genes that seemed scientifically related to a particular disease. Now gene chips can probe 500,000 sequences throughout the genome for variation in single-nucleotide polymorphisms (SNPs) and segments of chromosomes. Genome-wide association studies have demonstrated genetic influence on height; glucose, cholesterol, and blood pressure levels; and risks for childhood-onset and adult-onset diabetes, macular degeneration of the retina, various cancers, coronary heart disease, mental illnesses, inflammatory bowel disease, and other diseases. Enthusiasm about these statistical associations stimulated the formation of companies to offer testing services with direct-to-consumer promotion. However, the market was leaping way ahead of the science.