Introduction 



The Office of Health and Environmental Research (OHER) manages the Human 

 Genome Program within DOE. as a focused program of resource and technology 

 development. The general objective is to advance, as economically and efficiently as 

 possible, the U.S. effort in human genome research. Other OHER responsibilities, such 

 as assessing the effects of energy by-products on our population and environment, will 

 benefit from applications of the new biological and computational resources and the 

 innovative technologies developed within the genome program. Moreover, the resources 

 and technologies being developed are of broad and continuing value: many facets of 

 biomedical research, modem agriculture, and the growing biotechnology industries will 

 be advanced. 



Knowledge of principles guiding the three-dimensional structure-function relationships 

 of cellular macromolecules is essential for the interpretation and application of the 

 linear DNA sequence that is being elucidated in the Human Genome Program. Special 

 facilities in DOE laboratories are being used (see table on p. 3) to determine the three- 

 dimensional structure of macromolecules. DOE is planning for the greatly increased 

 demand that will be placed on these facilities as a result of the Human Genome 

 Program. 



Development of the Human Genome Initiative 



In 1984 DOE and the International Commission for Protection Against Environmental 

 Mutagens and Carcinogens cosponsored a workshop in Alta, Utah. A specific charge to 

 the participants was to evaluate the present state of and project future directions for 

 mutation detection and characterization. The growing roles of novel DNA technologies 

 in diagnostics were highlighted. There, in the excitement of the meeting, some core 

 techniques of current genomic analysis were conceived (see "The Alta Summit. 

 December 1984," in Appendix B). These new approaches increasingly included gene 

 cloning and sequencing. Although the isolation of genes from libraries of clones had 

 been an integral component of biomedical research for many years, the one-gene-at-a- 

 time procedures being employed were wasteful of scientists" time and research 

 resources. 



The small genomes of several viruses were the targets of the first genome projects in the 

 1960s. These projects initiated the development of some of the current important 

 techniques in molecular genetics. (A molecular genetics primer is included as Appendix 

 A of this report. ) With the advent of molecular cloning techniques in the 1 970s. a 

 library of manageable cloned DNAs could be produced for any species. Genome studies 

 on many viruses, the bacterium Escherichia coli, two yeast species, and a nematode (a 

 minute worm) were subsequently implemented. With the skills already demonstrated, a 

 human genome program could then be considered. However, it would be a task far more 

 vast than any previously implemented in biological research. 



In 1985 DOE began to consider whether its expertise with high-technology projects 

 could facilitate and sustain a human genome program. To as.sess the desirability and 



