The Genom of Homo sapiens.pdf

52 COLLINSFigure 2. A public-sector small-molecule initiative is made possible by four convergent developments in biology and chemistry.effect on phenotype or its impact on the protein productof a specific gene (Stockwell 2000).Although major organizational and funding challengesare associated with any novel science effort of this scale,a public-sector initiative in chemical genomics is nowwithin our reach because of convergent developments inbiology and chemistry: the essential completion of thehuman genome sequence, advances in combinatorialchemistry, the wide availability of small-molecule compounds,and the development of high-throughput robotictechnology for high-throughput screening (Fig. 2).Although it will build upon what has been learned insimilar efforts within the pharmaceutical industry, a publicchemical genomics initiative should not be viewed asan effort to turn academic researchers into drug developers.Instead, we consider it an opportunity for academicand government biologists to contribute in a much moreempowered way to the earliest stages of the drug developmentpipeline where there is reasonable certainty ofsuccess, namely the identification of biological targets,the development of biologically relevant assays, thescreening of small-molecule libraries, and initial medicinalchemistry to convert screening hits into useful biologicalprobes (Fig. 3). To realize this vision, we anticipatethe establishment of centralized facilities forhigh-throughput screening of small molecules, as well asthe creation of public-sector capacity to advise researcherson the development of assays and to provide assistancein medicinal chemistry to render the initial “hits”more useful. As has been the case with sequence datagenerated by the Human Genome Project, these resourceswould be freely and readily accessible to the entire scientificcommunity, and a central database would allow potentiallypowerful inferences to be drawn about biologicalpathways and networks.Catalyze Development of LargeHuman CohortsIf we are to fully discern genotype–phenotype correlationsand environmental contributions to common illnesses,it is imperative that we assemble large cross-sectionalhuman cohorts that encompass multiplepopulations. Given the time and expense needed to pulltogether such studies, we must embark on this effort verysoon or else face the risk of not having such large cohortsin place when we need them to understand genotype–environment–phenotypecorrelations in an unbiased way. Inaddition to furnishing valuable clues about major causesof morbidity and mortality, large cohorts may also provepriceless in efforts to find alleles that protect against diseaseand help to promote health and longevity.Elucidate the Role That GenomicsCan Play to Reduce Health Disparities andImprove Health in the Developing WorldDisparities in health status constitute a significantproblem in the United States and throughout the world.Although socioeconomic and other nongenetic factors aremajor contributors to such disparities, genomics may beable to contribute to the reduction of disparities by sheddinglight on the effects of disease-associated gene variantson the health status of certain populations. Likewise,many efforts to improve health in developing nations mayseem to lie outside the direct realm of genomics. But genomicscan offer significant contributions by improvingunderstanding of the genetic factors that influence susceptibilityand response to infectious diseases, as well asby reducing research and development costs of vaccinesand pharmaceuticals.