In Pursuit of the Gene

EPILOGUE © 285
characterization of the disease. In 1986 the invention of PCR (polymerase
chain reaction) by Kary Mullis, a biochemist at Cetus Corporation, made it
possible to make millions of copies of DNA fragments in a few hours, radically
simplifying the process of DNA sequencing. As a result of PCR and the
development of automated sequencing technology, the idea of sequencing
the human genome in its entirety began to take off. By the end of 1986, human
genome sequencing had been the focus of five major biological conferences
throughout the country and an independent initiative by scientists at
the Department of Energy. At an estimated cost of one dollar per base pair,
the total cost of sequencing the entire human genome was projected to exceed
three billion dollars.
Initially many highly respected scientists, including David Botstein,
questioned the value of getting a full genome sequence, arguing that money
was better spent on mapping and other smaller-scale initiatives. In 1987 the
National Academy of Science convened a committee on the genome project
to study the problem. In their report, issued in the spring of 1988, the
committee advised focusing first on genetic and physical maps (made from
DNA markers). The result would be a collection of well-ordered, overlapping
DNA fragments, each about 40,000 base pairs in length, spanning the
complete set of chromosomes. James Watson, a strong advocate of genome
sequencing from the start, argued that the project ought to be run by a
prominent scientist who could advocate effectively for the project and
make sure that the money was well spent, and that fall the director of the
National Institutes of Health (NIH) created the Office of Human Genome
Research and appointed Watson himself as its first director. 20 Still associated
with the glory of the double helix, Watson would prove to be the perfect
advocate for the Human Genome Project.
Over the next decade, the project unfolded very much according to
plan, turning out increasingly detailed maps and sequences of smaller
genomes ahead of schedule. In 1998 former NIH researcher-turned-biotechentrepreneur
Craig Venter announced the formation of a privately funded
company to sequence the human genome four years ahead of the NIH-led
effort at a fraction of the cost. Venter’s idea was to sequence fragments selected
at random from a pool of sheared whole genomic DNA and to as-