Gene sequencing's industrial revolution

The International Human Genome Project and the private genomics company, Celera Cenomics, of Rockland, Md., plan to publish the first draft of the entire human gene sequence early next year. This has been a top flight engineering achievement. A single DNA sequencing machine today can produce over 330,000 bases (units of sequence information) per day, more than 100 researchers could manage in a year and a half using manual techniques less than a decade ago. Major genome centers such as the Sanger Center in the UK or the Whitehead Institute for Biomedical Research, in Cambridge, Mass., run over 100 such machines. Celera, with 300 machines, has a production capacity approaching two billion bases per month, or more bases than researchers had identified in the 16 years between 1982, when central databases began, and 1998. Moreover, the reliability and speed of the automated methods that became available in the past two years have increased to such an extent that high-powered computational approaches can be applied to the reconstitution of the human genome sequence from millions of fragments of processed DNA. At a basic level, DNA sequencing calls for the preparation and replication of relatively short segments of DNA; the creation of partial copies of the segments each one base longer than the next; the identification of the last base in each copy; and the ordering of the identified bases. At each step technological developments have accelerated the pace of discovery. Industrial robots shift genetic material from station to station with speed and accuracy. Sequencing machines using multiple capillaries filled with polymer gels have catapulted throughput to new heights and reduced a major source of sequencing error. And DNA assembly computer systems have been constructed that recently set in order a 120-million-base genome in less than a week's worth of calculations.