Contemplating the End of the Beginning

On February 12, 2001, an unprecedented collection of papers describing the initial sequencing and analysis of the human genome was published in Nature and Science(International Human Genome Sequencing Consortium 2001; Venter et al. 2001). Although much celebration and press attention had surrounded the earlier announcement in June 2000 of the coverage of the vast majority of the human genome sequence in working draft form, the publications in February 2001 carried with them the kind of satisfying scientific significance that laborers in the genome fields had longed for—the full description of the methods used to determine the letters of over 90% of the human instruction book, and a host of surprising revelations from the analysis of its contents. This brief essay represents a personal reflection on how we got here, and where we are going.

The achievement of these landmarks, coming years ahead of the original schedule, was only possible because of the advances begun early in the preceding decade, reflecting the polyphonic set of interconnected goals that the planners of the Human Genome Project (HGP) wisely included as part of the original master plan. Science traditionally operates by the process of researchers standing on the shoulders of those who came before, and that has certainly been true for the HGP. Building detailed genetic and physical maps, developing better, cheaper, and faster technologies for handling DNA, and mapping and sequencing the more modest-sized genomes of model organisms were all critical stepping stones on the path to initiating the large-scale sequencing of the human genome.

Pilot efforts to sequence the human genome began in the mid-1990s. When the International Human Genome Sequencing Consortium met for the first time in Bermuda in 1996, there was a sense of excitement, but the magnitude of the task at hand was sobering–throughput was too …