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An Overview of the Human Genome Project

A Brief History of the Human Genome Project

In February 2001, the Human Genome Project (HGP) published its results to that date: a 90 percent complete sequence of all three billion base pairs in the human genome. (The HGP consortium published its data in the February 15, 2001, issue of the journal Nature.

The project had its ideological origins in the mid-1980s, but its intellectual roots stretch back further. Alfred Sturtevant created the first Drosophila gene map in 1911.

The crucial first step in molecular genome analysis, and in much of the molecular biological research of the last half-century, was the discovery of the double helical structure of the DNA molecule in 1953 by Francis Crick and James Watson. The two researchers shared the 1962 Nobel Prize (along with Maurice Wilkins) in the category of "physiology or medicine."

In the mid-1970s, Frederick Sanger developed techniques to sequence DNA, for which he received his second Nobel Prize in chemistry in 1980. (His first, in 1958, was for studies of protein structure). With the automation of DNA sequencing in the 1980s, the idea of analyzing the entire human genome was first proposed by a few academic biologists.

The United States Department of Energy, seeking data on protecting the genome from the mutagenic (gene-mutating) effects of radiation, became involved in 1986, and established an early genome project in 1987.

In 1988, Congress funded both the NIH and the DOE to embark on further exploration of this concept, and the two government agencies formalized an agreement by signing a Memorandum of Understanding to "coordinate research and technical activities related to the human genome."

James Watson was appointed to lead the NIH component, which was dubbed the Office of Human Genome Research. The following year, the Office of Human Genome Research evolved into the National Center for Human Genome Research (NCHGR).

In 1990, the initial planning stage was completed with the publication of a joint research plan, "Understanding Our Genetic Inheritance: The Human Genome Project, The First Five Years, FY 1991-1995." This initial research plan set out specific goals for the first five years of what was then projected to be a 15-year research effort.

In 1992, Watson resigned, and Michael Gottesman was appointed acting director of the center. The following year, Francis S. Collins was named director.

The advent and employment of improved research techniques, including the use of restriction fragment-length polymorphisms, the polymerase chain reaction, bacterial and yeast artificial chromosomes and pulsed-field gel electrophoresis, enabled rapid early progress. Therefore, the 1990 plan was updated with a new five-year plan announced in 1993 in the journal Science (262: 43-46; 1993).

Indeed, a large part of the early work of the HGP was devoted to the development of improved technologies for accelerating the elucidation of the genome. In a 2001 article in the journal Genome Research, Collins wrote, "Building detailed genetic and physical maps, developing better, cheaper and faster technologies for handling DNA, and mapping and sequencing the more modest-sized genomes of model organisms were all critical stepping stones on the path to initiating the large-scale sequencing of the human genome."

Also in 1993, the NCHGR established a Division of Intramural Research (DIR), in which genome technology is developed and used to study specific diseases. By 1996, eight NIH institutes and centers had also collaborated to create the Center for Inherited Disease Research (CIDR), for study of the genetics of complex diseases.

In 1997, the NCHGR received full institute status at NIH, becoming the National Human Genome Research Institute in 1997, with Collins remaining as the director for the new institute. A third five-year plan was announced in 1998, again in Science, (282: 682-689; 1998).

In June 2000 came the announcement that the majority of the human genome had in fact been sequenced, which was followed by the publication of 90 percent of the sequence of the genome's three billion base-pairs in the journal Nature, in February 2001.

Surprises accompanying the sequence publication included: the relatively small number of human genes, perhaps as few as 30,000; the complex architecture of human proteins compared to their homologs - similar genes with the same functions - in, for example, roundworms and fruit flies; and the lessons to be taught by repeat sequences of DNA.

For more information on how this story unfolded, see News About the HGP.

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Last Reviewed: December 13, 2011