Past research conducted under this program has elucidated the

sulfur cycle in forested ecosystems and is now providing crucial information on acid rain. Information on carbon cycling developed

with support of this program is now a central part of the

evaluation of CO2 buildup.

Research in physiologic ecology includes studies on a basic understanding of the mechanisms of stress and tolerance in marine organisms exposed to contaminants. Our research has shown that in response to heavy metal contaminants, animals synthesize specific proteins (metallothioneins) which bind and sequester metals in the animal, thus, decreasing metal mobility and effects. Companion studies with host-specific intracellular pathogens are being used to investigate the effects of heavy metals on the synthesis of immune proteins which mitigate disease processes. The results of these studies are being used to predict the ecological effects of energy-related contaminants on valued marine species.

The FY 1987 Operating Expenses request for the Health Effects research area is $65.9 million. Recent information indicates that the potential exposures to radon gas and its daughter products in residential structures, and the number of people so exposed, may be substantial. The formulation of a rational strategy for the abatement of the risk, requires the entire spectrum of activities sponsored by the BER program. Thus, fully addressing the issue of radon health effects will not only require the development and testing of models of radon transport through the environment, but also carefully controlled epidemiological studies and fundamental studies of the mechanisms by which radon produces injury.

The epidemiologic research program comprises studies that provide needed scientific data and, at the same time, provide information of important practical significance. These studies include investigations of human populations with occupational or

environmental exposure to energy-related pollutants.

Among the

major populations which have been under study for several years are DOE Workers/DOE contractor workers, Japanese atomic-bomb survivors, nuclear shipyard workers, and New Mexico uranium miners. These population studies will be supplemented by studies of lung cancer cases in communities located near DOE facilities.

During FY 1987, the results of the nuclear shipyard study will come available. These results will greatly refine our confidence in low-level radiation risk estimates which have been developed through extrapolation from populations exposed at high doses and dose rates. The intensive effort to characterize the industrial hygiene aspects of these facilities in order to identify chemical hazards which may be responsible for some apparently deleterious health effects that have been discovered in previous epidemiologic investigations will continue.

The experimental health effects research program uses laboratorybased studies and a multispecies approach to make predictive correlations between cellular/molecular events and whole animal responses, and between laboratory animals and humans. The discovery that DNA damaged by radiation and chemicals could be repaired was a landmark achievement. High priority will be given to the molecular biology of the enzymes that repair damaged DNA and to the genes that control these enzymes. More generally, increased emphasis will be placed on molecular epidemiology including identification of molecular markers for susceptibility and resistance to chemical and radiation damage. Studies will also be made to identify populations that may be especially susceptible to energy byproducts so their needs and concerns can be met early. Research on cancer-related genes, oncogenes, that are activated by radiation and other energy-related materials, will be expanded, and relations will be sought to link them to current DOE-supported epidemiologic studies of cancer in human and animal populations.

The majority of exposures of people to hazardous material is not to single materials but to complex mixtures of chemicals and perhaps even to radiation and chemicals together. Studies of complex mixtures show that their health effects cannot always be predicted by adding the effects of isolated components. То understand this problem a complex mixture program has been

initiated to develop predictive principles of toxicity and mutagenicity.

Another major problem is to determine the extent to which radiation and chemical damage to genetic material is transmitted to future generations. This problem is of extraordinary

importance since it bears directly on the question of whether decisions made today will effect the burden of disease of future generations. To develop a basis for answering these questions, new molecular approaches will be developed for studying the hereditibility of certain types of molecular, chromosomal and

genomic damage.

Research in General Life Sciences, for which $29.9 million in Operating Expenses is requested in FY 1987, provides the fundamental basis of the entire BER program. This research extends our base of biological information and develops concepts to allow the fullest understanding of the health effects of various energy options.

Research in cell biology will be supported to understand the normal processes of cells, their functions and their regulation. An important problem is to understand the factors influencing cell stability and malignant transformation.

Research in molecular biology will focus on the structure and

function of the gene at the molecular and chromosomal levels, the

arrangement of genes in chromosomes, and how this arrangement

affects the way genes are expressed and regulated.

Studies in structural biology will use the special facilities developed by the Department for the analysis of macromolecular structure. Use of the intense neutron beams produced by nuclear reactors and accelerators and the synchrotron light produced by its electron storage rings will permit information to be obtained faster and under more realistic conditions than was previously possible. These experimental capabilities, the Department's powerful computer network, and its unique breadth and depth in the mathematical sciences will lead to new and far more rapid approaches to determining and predicting molecular structure. Progress in this area will have a major impact on the future of biotechnology including protein engineering, and drug and vaccine design.

The second major goal of the BER program is the utilization of the Department's unique scientific and technological capabilities to address major problems in medicine and biology. The development of applications in the field of nuclear medicine has historically been the major program associated with this goal.

The budget request for the FY 1987 Nuclear Medicine Applications program is $22.1 million. Its objective is to continue the development of new nuclear medicine procedures through the production of new radionuclides, the radiolabeling of new biologically active agents, and advancements in instrumentation. Efforts to develop other medical applications using reactors, accelerators and other related nuclear technologies for the treatment of cancer will be maintained.

Recent developments in the BER nuclear medicine program have produced new radiopharmaceuticals labeled with short-lived

radionuclides.

In syntheses involving the most important positron emitting radionuclides (oxygen-15, 2 minute half life; nitrogen-13 10 minute half life, carbon-11, 20 minute half life, and fluorine18, 110 minute half life), one cannot use standard techniques.

Rather, innovative rapid organo- and biosynthetic techniques must

be developed using the technologies or molecular biology,

biochemistry, organic chemistry, hot atom chemistry and radiochemistry.

The new short-lived radionuclide labeled radiopharmaceuticals are proving to be useful in studies of the metabolic functions of the brain and heart. Major advances have been made to date in quantitating hysiology and pathophysiology in the human brain and heart utilizing Positron Emission Tomography. Continued development of advanced tomographic systems will have immediate medical implications in evaluation of stroke patients and diagnosis of degenerative brain disorders such as Alzheimer's, Huntington's and Parkinson's disease.

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In FY 1987, research and development will be maintained and devoted to identifying and optimizing techniques for attaching radionuclides to monoclonal antibodies. These homogeneous populations of molecules recognize characteristics which are peculiar to cancer cells. They, therefore, offer the potential for early detection of cancer, for following the response of patients to treatment, and for general cancer therapy. substantial research and development effort will be required to perfect and evaluate techniques for using labeled monoclonal antibodies. It is anticipated that by FY 1987 work on monoclonal antibodies for cancer therapy will have progressed to the point that one or more of these agents will have been identified as having sufficient potential for clinical trials. In addition, the monoclonal antibody work will be extended to labeling with radionuclides suitable for positron tomographic diagnostic imaging.

The use of magnetic resonance imaging (MRI) spectroscopy to detect carbon-13 and nitrogen-15 labeled metabolic products within intact