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DOE/ER-0544P uman enome 1991-92 Program Report Date Published: June 1992 U.S. Department of Energy Office of Energy Research Office of Health and Environmental Research Washington, D.C. 20585 Major Events in the Development of the DOE Human Genome Program Meeting held in Santa Fe, New Mexico, to explore Human Genome Initiative feasibility DOE Human Genome Initiative announced I Pilot projects pursued at national laboratories: physical mapping, informatics, and development of critical resources and technologies lor genomic analysis HERAC recommendations made for the Human Genome Initiative First interagency workshop held on genomic resources and informatics LBL and LANL designated as human genome centers I First management and program plans published First peer-review panel for human genome research proposals held NRC recommendations made for a national human genome proje First primary R&D awards made I First Small Business Innovative Research awards made in genome research DOE-NIH Memorandum of Understanding for human genome research signed DOE Human Genome Coordinating Committee formed Human Genome Management Information System established First issue of Human Genome Quarterly published by HGM!S DOE-NIH Five-Year Plan developed First DOE Contractor-Grantee Workshop held at Santa Fe, New Mexico First biannual meeting of NIH-DOE Joint Subcommittee on the Human Genome held I First Joint Mapping Working Group meeting held DOE-NIH Five-Year Plan for the Human Genome Project presented to Congress First DOE ELSI awards made First Joint Working Group on Ethical, Legal, and Social Issues meeting held DOE Human Genome 1989-90 Program Report published First Joint Informatics Task Force meeting held First joint DOE-NIH issue of Human Genome News published First Joint Sequencing Working Group meeting held LLNL designated as third human genome center DOE-NIH annual planning and evaluation retreat held DOE Human Genome Distinguished Postdoctoral ACRONYM LIST Fellowships initialed DOE plans announced to generate STS mapping sites ADA Americans with Disabilities Act at expressed loci DOE U.S. Department of Energy Joint NIH-DOE Five-Year Plan officially implemented Second Contractor-Grantee Workshop held a ELSI Ethical, Legal, and Social Issues Santa Fe, New Mexico HERAC Health and Environmental Research Advisory Committee First DOE Cooperative Research and Development Agreement signed HGMIS Human Genome Management Information System ADA revisions recommended by ELSI HUGO Human Genome Organization (International) Working Group Special peer-review panel held for STS LANL Los Alamos National Laboratory production from cDNAs LBL Lawrence Berkeley Laboratory First meeting of the Joint Working Group on the Mouse held LLNL Lawrence Livermore National Laboratory First DOE Human Genome Distinguished NIH National Institutes of Health Postdoctoral Fellowships awarded DOE-NIH support of Genome Data NRC National Research Council Base begun R&D Research & Development cDNAISTS technology awards made USDA U.S. Department of Agriculture NIH-DOE annual planning and I evaluation retreat held SBH Sequencing by hybridization First peer-review panel held for ELSI STS Sequence tagged site Moscow SBH Workshop sponsored by DOE, HUGO, and The Wellcome Trust 86 87 88 89 90 91 92 ii Foreword cquiring complete knowledge of the organization, structure, and function of the Ahuman genome-the master blueprint of each of us-is the broad aim of the Human Genome Project. It is a new kind of program in biology, both in its size and focus on a limited set of goals and in its dependence on the development and use of technology. The coordinated U.S. Human Genome Project was officially initiated by the Department of Energy (DOE) Office of Health and Environmental Research and the National Institutes of Health (NIH) National Center for Human Genome Research (NCHGR) in FY 1991 with the publication in April 1990 of Understanding Our Genetic Inheritance; The U.S. Human Genome Project: The First Five Years 1991-1995. The DOE effort, which began very modestly almost 4 years before, is now over 5 years old. Taking stock of what has been done and what remains to be done is particularly appropriate at this time. That the ambitious scientific goal of the Human Genome Project can now be imagined is the result of the revolution occurring in biology during the last 20 years. Modern biological science has achieved a profound but still quite incomplete level of understanding of how the diversity of all living things is determined. This insight, along with scientific and techni­ cal advances in other fields, has brought unprecedented power both in being able to analyze and manipulate genetic structures and to use and store large quantities of genetic information. DOE is uniquely positioned to bring together expertise in physics, chemistry, engineering, and computer science to help solve fundamental biological problems and to exploit exciting opportunities presented by the Human Genome Project. Genome research will also contribute to the department's role in providing the scieniific foundation for under­ standing the health effects of radiation and of chemical insults to the genome. The DOE program stresses mapping, the development of sequencing technologies and instrumentation, and informatics. Informatics refers to computational approaches in acquir­ ing, storing, distributing, analyzing, and manipulating vast amounts of mapping and sequence data that will result from the project. Another important program component studies the ethical, legal, and social issues arising from use of the generated data, partic­ ularly in the privacy and confidentiality of genetic information. Cutting across all DOE biological and environmental research programs are several science education activities. The Human Genome Project is a closely cooperative activity between NIH and DOE. NCHGR is an important and essential participant. Internationally, the formation of the Human Genome Organization and the establishment of national genome projects by an increasing number of countries indicate the fascination and promise of this effort on the collective imaginations of many nations. In addition to the inherent excitement about increased knowledge of human life, the project offers the promise of many new opportu­ nities for benefiting humanity through the development of new diagnostics, pharmaceuticals, and therapies for a multitude of human diseases; a wide range of improvements will flow from other biotechnology advances. Further expected benefits include improved risk assessment for individuals and populations exposed to agents that impact genetic mate­ rial, as well as possible applications of the data to environmental and remediation issues. To be successful, the program must continue to focus on clear objectives for mapping and sequencing and to incorporate the flow of technological developments into the efforts of all working laboratories. Strategies must be planned carefully and in a comprehensive iii Foreword fashion as the next phase begins, in which mapping and sequencing results proliferate and technologies mature. Planning must be project-wide and include interagency planning at ever-earlier stages. This report describes the status of the DO!: Human Genome Program and its accomplish­ ments to date. Research highlights are noted from the program as a whole and from the three principal DOE human genome centers at Lawrence Berkeley Laboratory, Lawrence Livermore National Laboratory, and Los Alamos National Laboratory. These national laboratory facilities of DOE have been especially successful because they are organized to focus efforts, foster interdisciplinary projects, and use advanced technologies, some developed for other purposes, toward program goals. Essential work is also reported from 41 different research universities. Remarkable progress has been made in advanced instrumentation and informatics. A further indication of the increasing development of the DOE program is the simple statis­ tic that the 1989-90 report had 157 pages and included 57 abstracts of work involving 211 scientists. The current program report contains over 240 pages and includes more than 150 abstracts of work involving over 400 investigators, essentially a doubling of DOE program size. The Human Genome Project ultimately will create scientific resources for the next wave of advances in biology and medicine. As the project is completed, accomplishments will dwarf those that have occurred in the biological sciences since the advent of recombinant DNA technologies. By the same token, the ethical and social consequences of the uses of this new knowledge must be considered as the knowledge is acquired; if this knowledge is responsibly