The Human Genome Project: a player's perspective.

The Human Genome Project was a natural culmination of one of the great scientific triumphs of the 20th century—the elucidation of the means by which biological organisms store, replicate, and process information. Specifically, the discovery at mid-century that biological information is stored as a linear, digital code led directly to the concept of a genome sequence. Technical advances in DNA analysis during the second half of the 20th century made the determination of genome sequences a practical goal. The achievement of this goal, at the end of the century, occurred during an extraordinary confluence of rapid scientific progress, rampant technological optimism, and exuberant entrepreneurial capitalism. The resultant strains on basic scientific values are exemplified by the public–private competition that arose during the sequencing of the human genome. While this competition accelerated initial availability of the genome sequence, it did so at considerable cost to the health of the interface between science and society. Analysis of this episode may reveal important lessons since the human future will continue to be shaped by the same forces that were at play during the endgame of the Human Genome Project. There are two stories of the Human Genome Project. One describes a century of scientific progress that began with the rediscovery of Mendel’s laws in 1900 and ended in a frenzy of genome sequencing. The other is a story about contemporary societal values—particularly, those that framed the project’s endgame and continue to shape public perceptions toward this defining event of our time. Both stories deserve attention. The first will help counter the illusion that the Human Genome Project was a sudden inspiration of the 1990s, while the second offers a sobering look at the forces that shape the current interface between science and society. We should pay attention to the ethic of this frontier since—like that of the American West—its influence will linger long after the present exuberance has faded. I will start with the scientific story of the first triumphant century of genetics. In this narrative, the Human Genome Project will emerge as a natural step in the scientific quest to understand one of nature’s deepest mysteries: How can a fertilized egg cell, an object too small to see with the unaided eye, contain all the information required to guide the development of a unique human being? Within a few years of the rediscovery of Mendel’s laws, an initial synthesis emerged that linked Mendel’s probabilistic rules of inheritance to the internal structure of cells. This synthesis placed the material basis of Mendelian traits on the chromosomes, tiny bodies within cells that are readily stained with colored dyes. Chromosomes are duplicated every time a cell divides and are distributed with extraordinary precision to the two progeny cells. Through the life cycle of an organism, as it builds itself through successive divisions of a fertilized egg and ultimately produces new egg or sperm cells, chromosomes obey precisely the same rules of transmission as those that govern the inheritance of Mendelian traits. Hence, early geneticists quickly inferred that chromosomes must mediate the transmission of Mendelian inheritance. But how? Within the scientific worldview of the early 20th century there was simply no plausible explanation. Chromosomes, as then known to cell biologists, were tiny, uniformly staining objects comprised of a featureless material referred to as “chromatin.” This monotonous substance seemed an unpromising carrier of the rich universe of biological traits displayed by elephants, orchids, and human beings. William Bateson, an early geneticist, expressed this perspective in a 1916 review of the classic book The Mechanism of Mendelian Heredity: