||Introduction A genie, on being released from its bottle is empowered to grant wishes. What might we as geneticists and you as society ask of the gene genie? Make no mistake the power of this genie is real, rooted firmly in the spectacular successes of biomedical research over the last two decades that have fueled the genetics revolution. And the power is being multiplied geometrically by the fruits of the Human Genome Project. We have only just begun to understand the human genome. The next few years promise to be a wild ride - a singular time in history. This year marks the fifth anniversary of the Human Genome Project, a good time to take stock. How far have we come? Has it been worth the investment? Where are we going? Is this the right direction? The national, and international, project is at a crucial turning point. Its goals for the first five years have in general been met, although their design was clever enough that victory could be declared within quite wide margins. What is the Genome Project? Merely a $3 billion, fifteen year commitment to determine the human blueprint -unthinkable a decade ago. This project will create an encyclopedic data resource containing the complete 3 billion-nucleotide sequence of the human DN A that is in each of our cells, as well as complete sequences for five model organisms (mouse, C. elegans [a worm], Drosophila [fruit fly], yeast and E. coli [bacterium]). Remember that chromosomes consist of very long DN A molecules made up of sub-unit bases, or nucleotides: A, G, C and T. This is the DNA alphabet, only four letters in a linear order (it makes for boring reading, reminiscent of a Phillip Glass composition). However, in this sequence is hidden the complete set of instructions for making an organism. New technologies and an increasing understanding of molecular biology allows us to recognize genes, sets of 10,000-30,000 bases that, three at a time, encode the linear order of amino acids that make up proteins - the gene products. Genome complexity increases with complexity of the organism, from the human with 3 billion bases comprising some 100,000 genes to the bacterium E. coli with 4 million bases and 4,000 genes. The 3 billion-base human genome is one meter long, but when typed in letters it would fill a large set of encyclopedias. The DNA, AGGATCCCT, etc., typed out on one line would reach from here to Tierra del Fuego. The genome of E. coli would reach from here to the Jordan Temple. Human DNA, one meter long is folded up into chromosomes in the nucleus of each cell.