The human genome project, chronologically, is at the halfway point in its execution. It was conceived as a 15 year project, with an estimated cost of US $3 billion, with the object of mapping and sequencing the haploid human genome, abou 3 billion base pairs of DNA sequence in 22 somatic chromosomes together with the X and chromosomes. The target date for cmpletion was the year 2005. Incorporated in the project were the sequence determinations of genetically less complex organisms, a bacterium, a yeast, a rematode. In addition, it was anticipated that technological developments would provide new approaches to sequence determination.

1998 brings us to the point where many of the introductory objectives have been achieved. The outstanding and most dernanding objective is the determination of the DNA sequence itself, of which only about 2% is presently complete, and to do that on time and on budget.

The talk will discuss the present state of DNA sequence methodology. It will discuss the basic strategy of large scale DNA determinations and describe some of the problems which are encountered. Finally, it will describe progress on sequencing part of the human genome, including the quality of the sequence that can be achieved with present technology and the biological lessons that can be learned.