part because of time constraints. Among the more important areas that are not fully covered or not addressed at all are:

Studies on high incapacitating level exposures at high dose

(This research area is supported largely by the

Department of Defense.)

The modification of procedures and development of new methods
and equipment for reducing diagnostic exposures in medical
and dental practices. (Programs within the National Cancer
Institute and the Bureau of Radiobiological Health of the Food
and Drug Administration address these problem areas.)

The development of new radiopharmaceuticals and radioisotope applications for diagnostic purposes and equipment designed to reduce radiation doses to patients while maintaining or improving the information obtained. (This area finds support from several Federal agencies and private sources.)

Issues of social science such as problems in decisionmaking, psychological effects of perceptions of risk, legal issues deriving from allocation of risks, and risk assessment procedures.

Further, this document does not deal with the issue of acceptable risk, which is perceived by the drafters of this document to be more a political issue than a scientific one.

B. Objectives

This strategy for Federal research into the biological effects of ionizing radiation has been designed to ensure a comprehensive program of

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research, within which special attention will be given to research which has the potential to:

(a) Reduce the uncertainties associated with assessment of the

doses and associated health effects resulting from exposure

to manmade or enhanced natural radiation;

(b)

Improve the ability to assess the benefit-to-risk ratio ass0ciated with the use of ionizing radiation;

(c) Provide the fundamental knowledge required to attain the objectives and goals listed in (a) and (b). It is recognized that advancement in basic radiation biology has the potential to make valuable contributions to the field of biology in general and to carcinogenesis in particular.

The objectives to be served by the development of this strategy are:

To advance fundamental knowledge and to maintain expertise in radiation biology;

To safeguard the public health by providing regulatory agencies with the knowledge required to set appropriate standards for protecting occupationally exposed workers and the general public;

To minimize adverse impacts on the environment;

To ensure that the development of radiation sources and their use for beneficial purposes are performed in an orderly and safe fashion;

• To ensure the relevancy and cost efficiency of governmental
research activities related to ionizing radiation;

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L

To increase public confidence in Federal radiation research and
regulatory programs.

In the development of the agenda, the guiding philosophy was the need for achieving the following:

Obtaining a better quantitative understanding of the relation-
ship between doses which might be encountered in the work place
or in the general environment and attendant biological effects;

Improvement in the ability to predict the physical doses which
might be received from activities involving the use of radio-
nuclides and other sources of radiation;

• Developing procedures and technology to reduce either exposures
to ionizing radiation (from both manmade and enhanced natural
sources) or the impact from unavoidable exposures.

A proper Federal research program on the health effects of ionizing radiation must be a balanced program that provides appropriate support to a number of reasonable research approaches to achieve these goals and obtain related supporting knowledge.

Some approaches involve direct studies of exposed human populations and others address the problems indirectly through studies of laboratory animals, isolated cell systems, or other simple chemical or physical systems. Each of these approaches can provide useful solutions to elements of the overall problem, but no one research approach is likely to answer all of the important scientific questions. Therefore, it is appropriate to review

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the general characteristics of the individual approaches and their relative roles in reaching the objectives and goals listed above.

The required diversity of these approaches makes research into the biological effects of ionizing radiation an interdisciplinary field in which the planning, execution, and analysis of experiments and the subsequent modeling and application of the results require the active collaboration of biologists, physicists, chemists, mathematicians, and others.

It is highly desirable that appropriate use be made of existing human populations that have been exposed to external or internal sources of ionizing radiation as a result of nuclear weapons explosions, occupational activities, medical applications, or other activities. Epidemiological investigations of these populations can contribute essential information on radiation dose-response relationships although it must not be expected that by themselves they will provide either accurate estimates of risk in the low-dose region or reliable information on the shape of doseresponse curves for low LET radiation.

Epidemiological studies have produced most of the available information on the effects of ionizing radiation in humans. Once a suitable population of potentially exposed people has been identified, it can be observed for the remaining lifespans of the subjects if appropriate levels of cooperation and long-term research support are available. Because of the emphasis on the study of individuals, some of these studies involve periodic physical examinations that can provide a much more accurate and detailed knowledge of the health status of each subject. There are unique end-points which have to be studied in humans because there are no appropriate animal models.

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1

Most

The number of human subjects appropriate for study is limited. of those identified and studied to date have been exposed to intermediate or relatively high levels of radiation. Estimates of possible effects at low doses must be obtained by fitting a dose-response relationship to these data and extrapolating to other dose regions of interest. Such extrapolations involve a number of uncertainties arising from the generally small numbers of people in the study groups, appropriateness of selected control groups, uncertainties relating to the doses received by individual subjects, completeness of followup, possible exposures to other environmental pollutants, and other complicating factors. In spite of these difficulties, the need of information obtained from direct observation of human subjects requires that there be a continuing effort to collect, analyze, and use human data whenever possible.

(b) Studies in laboratory animals

Because the number of exposed people and the range of their exposure levels are quite restricted, our understanding of dose-response relationships in people is augmented substantially by studies in different species of laboratory animals. Observations of people and studies in laboratory animals both deal with integrated patterns of dose and response that reflect complex interactions in the individual due to immune responses, hormonal control, interactions among cells, etc.

There is a vital interplay between studies in laboratory animals and human studies. Many animal studies have examined dose-response relationships for internal or external exposure regimens for which there are no

1As used in this document, "low dose" means doses below the occupational exposure limit, i.e., 5 rem/year; "intermediate dose" means doses that do not produce any immediately apparent biological effects, i.e., below 50 rem delivered in a short period (days); and "high dose" anything above that. "Low dose rate" means below 1 rem/day.

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