DOE Human Genome Program:
Early History, Enabling Legislation
Energy Reorganization Act of 1974 (P.L. 93438): Provided that responsibilities of ERDA should include "engaging in and supporting environmental, biomedical, physical, and safety research related to the development of energy resources and utilization technologies."
In 1984, OBER [then named Office of Health and Environmental Research (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 chromosomeprocessing resources and capabilities were in place at Los Alamos National Laboratory and Lawrence Livermore National Laboratory. Among these were the fluorescenceactivated cell sorter (called 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 mono-chromosomal libraries opened an important patha 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 (HERAC).
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 longterm 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.
DOE and NIH Coordination
The National Institutes of Health (NIH) was a necessary participant in the largescale 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 1988, DOE and NIH signed a Memorandum of Understanding in which the agencies agreed to work together, coordinate technical research and activities, and share results. In 1990, DOE and NIH submitted a joint research plan outlining short- and long-term goals of the project.