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Master Disclaimer Program Director's Report for the Office of Health and Environmental Research August 1996 Prepared for Office of Health and Environmental Research Office of Energy Research U.S. Department of Energy Prepared by Ernest Orlando Lawrence Berkeley National Laboratory Berkeley, California 94720 operated by University of California for U.S. Department of Energy under Contract No. DE-AC03-76SF00098 PUB-778 MASTER DISCLAIMER This report was prepared as an account of work sponsored by an agency of the United States Government Neither the United States Government nor any agency thereof, nor any of their employees, make any warranty, express or implied, or assumes any legal liabili- ty or responsibility for the accuracy, completeness, or usefulness of any information, appa- ratus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessar- ily state or reflect those of the United States Government or any agency thereof. DISCLAIMER Portions of this document may be illegible in electronic image products. Images are produced from the best available original document. Ill 1.0 OHER Program Summary 1.1 Director's Overview 1 Program Integration 5 Center for Environmental Biotechnology 6 2.0 Program Organization, Facilities, and Resources ... 9 2.1 Organization and Management of OHER Programs Figure l.-LBNL and Division Org, Charts 9 2.2 Budget Information Table 1&2: Budget Data & Staff 12 Figure 2: Sponsoring Agencies Pie Chart 12 2.3 Personnel OHER Investigator List 13 2.4 Table 3: Facilities and Resources 15 Advanced Light Source 15 Imaging Facilities 16 National Tritium Labeling Facility 16 Biomedical Isotope Facility 16 Resource for Molecular Cytogenetics 17 Transgenic Resource 17 Life Sciences Microscope Resource 17 Yeast Genetic Stock Center 17 3.0 Research Management Practices 19 3.1 Advisory Committees and Program Reviews 19 President's Council on the National Laboratories— 20 3.2 Institutional Program Development Funds 22 Table 5: Summary of Major Discretionary Funding Investements (OHER-related LDRD) 22 3.3 Compliance with Animal Welfare and Human Subjects 23 Waste Minimization and Pollution Prevention... 23 Safety Committees 23 4.0 Research in Progress & Major Accomplishments .. 25 Analytical Technology 25 New Instrumentation & Detection Methods 25 iv Health Effects 26 Tumor Biology 26 Radiation Damage and Genetic Toxicology 27 Stem Cell Biology 28 General Life Sciences 28 Structural Biology—Proteins 28 Structural Biology—Nucleic Acids 29 Structural Biology—Uses of the ALS 29 Modeling Human Pathology in Transgenic Mice30 Human Genome Center 30 DNA Repair 30 Medical Applications 32 The Center for Functional Imaging 32 Imaging of Apolipoprotein E-Binding Receptors In Vivo 32 Table 6: Significant Science and Technology Achievements 33 Table 7: Major Examples of Collaborative Research 47 Table 8: Patents, Licenses, CRADAs (FY 95-96) 49 Work for Others 51 Table 9: Summary of Work for Others 55 5.0 Program Orientation/Future Directions (FY97-99) 63 Analytical Technology 63 Health Effects 65 General Life Sciences 67 Medical Applications 73 Table 10: Facility Construction and Modification 74 Table 11: Major Equipment Requirements 75 6.0 Contemporary Issues 78 7.0 Appendices 82 7.1 Information Transfer 82 7.2 Conferences. Workshops, & Training Programs . 92 7.3 Extramural Activities 92 7.4 OHER-Supported Publications 102 7.5 Selected Research Highlights 114 I am very grateful for the assistance I received in pre- paring this document. In particular, I would like to Acknowledgments thank the following people for their extraordinary contributions: Huber Warner, Assistant Deputy Director; Adele Sylar; Kati Markowitz; Tony Linard; of Life Sciences Division... ...as well as all of the fine scientists and engineers at "Berkeley Lab" whose research provided the inspi- ration for this document. David Gilbert—Editor (please call 510-486-6096 with your questions or comments, or contact me through the Internet at degilbert @ Ibl. gov) OVERVIEW • 1 Since its establishment, the Department of Energy's Office of Health and Environmental Research (OHER) 1. OHER Program Summary has had responsibility for conducting biological research to develop the knowledge needed to identify, under- 1.1 Director's Overview: stand, and anticipate the long-term health consequences of energy use and development, including the potential health impacts of radiation. The Health Effects Research Program has established the basis for understanding the health consequences of radiation for humans, devel- oped radiation dosimetry methodology, characterized and evaluated the health impacts of fossil fuels, and developed and conducted research to determine the health impacts of inhaled toxicants. The results of this research have provided input for setting genetic stan- dards for radiation and chemical exposure. During the ensuing years the Ernest Orlando Lawrence Berkeley National Laboratory ("Berkeley Lab" or "LBNL") has emerged as one of the premier Biosciences research venues in the national laboratory system. LBNL performs unclassified basic and applied research and develops technologies in support of OHER. OHER's mission is to explore and mitigate the long-term health and environmental consequences of energy use and to advance solutions to major medical challenges. The ability of the Laboratory to engage in this mission de- pends upon the strength of its core competencies. In addition, there are several key capabilities that are cross- cutting, or underlie, many of the core competencies. We refer to these as foundations in order to distinguish them from the core competencies. COKE COMPETENCIES Bioscience and Biotechnology: Structural biology; Ge- nome research; Bioinstrumentation; Cell and molecular biology, Molecular cytogenetics; Medical imaging; Biol- ogy of human diseases; Radiation biology and; Biomolecular design. 2 • PROGRAM DIRECTOR'S OVERVIEW STATEMENT Environmental Assessment and Remediation: Ad- sertion devices for synchrotron radiation; Large-vol- vanced instrumentation and methods for environmen- ume semiconductor-detector technology; Laboratory tal characterization and monitoring; Human health and automation; Advanced CAD/CAM facilities for large ecological risk assessment; Indoor air quality; Subsur- systems; Facilities for materials processing and fabri- face remediation of contaminants; Geologic isolation of cation. high-level nuclear waste; Actinide chemistry. Education of Future Scientists and Engineers: Under- Advanced Detector Systems: Major detectors for high- graduate, graduate, postdoctoral, and faculty involve- energy physics, nuclear science, and astrophysics; ment in scientific and engineering research through Scientific conception and project leadership; Ad- close ties with the University of California (UC) sys- vances in particle and photon detection; Implemen- tem; Educational programs for elementary schools, tation of new concepts in detector technology. high schools, and colleges. Materials Characterization and Synthesis: Advanced The following areas bear most significantly on the role spectroscopies and microscopies based on photons, that LBNL plays in furthering the mission of OHER. electrons, and scanning probes; Ceramics; Alloys; Heterostructures; Superconducting, magnetic, and atomically structured materials; Bio-organic synthe- BlOSCIENCES AND BIOTECHNOLOGY sis. Chemical Dynamics, Catalysis, and Surface Science: LBNL's bioscience and biotechnology competency fo- Reaction dynamics; Photochemistry of molecules and cuses on structural biology; genome research; bioinstru- free radicals; Surface structures and functions; Het- mentation; molecular cytogenetics; medical imaging; erogeneous, homogeneous, and enzymatic catalysis. the biology of human diseases; and biomolecular de- sign. New recruits in the areas of genomic instability Advanced Technologies for Energy Supply and and chromatin structure will provide added cohesive- Energy Efficiency: Subsurface resources and pro- ness to the on-going studies under the newly established cesses; Building technologies; Electrochemistry; Fos- Department of Cancer Biology. In the area of Radiation sil-fuel technologies; Energy analysis. Biology, radiation is used as a probe to delineate the structure of DNA in chromatin and chromosomes. Also, Particle and Photon Beams: Analysis and design of fundamental research is conducted from molecules to accelerators; Beam dynamics; High-brightness ion cells, animals and humans, to develop better methods and photon sources; Advanced magnet design and for radiation risk asessment. LBNL has pioneered the R&D; High-frequency RF technology; X-ray optics use of such techniques as electron crystallography, and and lithography; Induction linacs and neutral beams has strong programs in x-ray crystallography, NMR for fusion energy. spectroscopy, and chemical probe analysis to study biological problems. Recent programs have accelerated LBNL has identified four foundations; they are listed the capability to evaluate molecular complexes and the below together with descriptive subheadings. function of biological molecules, particularly proteins and DNA, from the perspective of their specific three- FOUNDATIONS
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