The following history is taken from the U.S. Department of Energy 1991-91 Human Genome Program Report (June 1992). This is an archived item.
A brief history of the U.S. Department of Energy (DOE) Human Genome Program will be useful in a discussion of the objectives of the DOE program as well as those of the collaborative U.S. Human Genome Project. The Office of Health and Environmental Research (OHER) of DOE and its predecessor agencies--the Atomic Energy Commission and the Energy Research and Development Administration--have long sponsored research into genetics, both in microbial systems and in mammals, including basic studies on genome structure, replication, damage, and repair and the consequences of genetic mutations.
In 1984, OHER and the International Commission on Protection Against Environmental Mutagens and Carcinogens cosponsored a conference in Alta, Utah, which highlighted the growing roles of recombinant DNA technologies. Substantial portions of the meeting's proceedings were incorporated into the Congressional Office of Technology Assessment report, Technologies for Detecting Heritable Mutations in Humans, in which the value of a reference sequence of the human genome was recognized.
Acquisition of such a reference sequence was, however, far beyond the capabilities of biomedical research resources and infrastructure existing at that time. Although the small genomes of several microbes had been mapped or partially sequenced, the detailed mapping and eventual sequencing of 24 distinct human chromosomes (22 autosomes and the sex chromosomes X and Y) that together comprise an estimated 3 billion subunits was a task some thousandsfold larger.
DOE OHER was already engaged in several multidisciplinary projects contributing to the nation's biomedical capabilities, including the GenBank® DNA sequence repository, which was initiated and sustained by DOE computer and data-management expertise. Several major user facilities supporting microstructure research were developed and are maintained by DOE. Unique chromosome-processing resources and capabilities were in place at Los Alamos National Laboratory and Lawrence Livermore National Laboratory. Among these were the fluorescence-activated cell sorter (FACS) systems to purify human chromosomes within the National Laboratory Gene Library Project for the production of libraries of DNA clones. The availability of these monochromosomal libraries opened an important path--a practical means of subdividing the huge total genome into 24 much more manageable components.
With these capabilities, OHER began in 1986 to consider the feasibility of a dedicated human genome program. Leading scientists were invited to the March 1986 international conference at Santa Fe, New Mexico, to assess the desirability and feasibility of implementing such a project. With virtual unanimity, participants agreed that ordering and eventually sequencing DNA clones representing the human genome were desirable and feasible goals. With the receipt of this enthusiastic response, OHER initiated several pilot projects. Program guidance was further sought from the DOE Health Effects Research Advisory Committee.
The HERAC Recommendation. The April 1987 HERAC report recommended that DOE and the nation commit to a large, multidisciplinary, scientific, and technological undertaking to map and sequence the human genome. DOE was particularly well suited to focus on resource and technology development, the report noted; HERAC further recommended a leadership role for DOE because of its demonstrated expertise in managing complex and long-term multidisciplinary projects involving both the development of new technologies and the coordination of efforts in industries, universities, and its own laboratories. Evolution of the nation's Human Genome Project further benefited from a 1988 study by the National Research Council (NRC) entitled Mapping and Sequencing the Human Genome, which recommended that the United States support this research effort and presented an outline for a multiphase plan.
The National Institutes of Health (NIH) was a necessary participant in the large-scale effort to map and sequence the human genome because of its long history of support for biomedical research and its vast community of scientists. This was confirmed by the NRC report, which recommended a major role for NIH. In 1987, under the leadership of Director James Wyngaarden, NIH established the Office of Genome Research in the Director's Office. In 1989 this office became the National Center for Human Genome Research (NCHGR), directed by James D. Watson. After Watson's resignation in April 1992, Michael Gottesman was appointed NCHGR Acting Director. In 1997 NCHGR became the National Human Genome Research Institute (NHGRI).
In addition to extramural support for research projects in physical mapping and the development of index linkage markers and technology, NIH also provides support for genetic mapping based on family studies and, following NRC recommendations, for studies on several relevant model organisms. DOE-supported genome research is focused almost exclusively on the human genome through support of large-scale physical mapping, resource and instrumentation technology development, and improvements in computational and database capabilities and research infrastructure. A significant portion of the DOE Human Genome Program is allocated to the DOE national laboratories.
In several important areas, DOE and NIH cooperate to support critical resources such as the Genome Data Base (GDB) at Johns Hopkins University. Cofunded since 1991 as the central international repository of human chromosome mapping data, GDB is expected to receive supporting funds from other nations. DOE and NIH also cooperate to support joint workshops; a number of ethical, legal, and social issues projects; and the Human Genome News newsletter.
Joint task groups under the DOE-NIH Joint Subcommittee on the Human Genome meet periodically to define program needs and develop recommendations for their parent DOE and NIH committees. OHER and NCHGR cosponsor workshops and meetings of the task groups on mapping; sequencing; informatics; the use of the mouse as a mammalian model; and--in a departure from most scientific programs--ethical, legal, and social issues related to data produced in the project.