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Biological Issues and Research Strategies Task Group on the Biological Effects of Space Radiation Space Studies Board Commission on Physical Sciences, Mathematics, and Applications National Research Council NATIONAL ACADEMY PRESS Washington, D.C., © 1996 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committees responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is interim president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce Alberts and Dr. William A. Wulf are chairman and interim vice chairman, respectively, of the National Research Council. Support for this project was provided by Contract NASW 4627 and Contract NASW 96013 between the National Academy of Sciences and the National Aeronautics and Space Administration. Copyright 1996 by the National Academy of Sciences. All rights reserved. Copies of this report are available from Space Studies Board National Research Council 2101 Constitution Avenue, N.W. Washington, D.C. 20418 Printed in the United States of America RICHARD SETLOW, Brookhaven National Laboratory, Chair JOHN F. DICELLO, Johns Hopkins University School of Medicine R.J. MICHAEL FRY, Oak Ridge National Laboratory JOHN B. LITTLE, Harvard University School of Public Health R. JULIAN PRESTON, Chemical Industry Institute of Toxicology JAMES B. SMATHERS, University of California, Los Angeles ROBERT L. ULLRICH, University of Texas Medical Branch, Galveston SANDRA J. GRAHAM, Study Director SHOBITA PARTHASARATHY, Research Assistant VICTORIA P. FRIEDENSEN, Former Senior Program Assistant CATHY GRUBER, Senior Program Assistant CLAUDE R. CANIZARES, Massachusetts Institute of Technology, Chair MARK R. ABBOTT, Oregon State University JOHN A. ARMSTRONG,* IBM Corporation (retired) JAMES P. BAGIAN, Environmental Protection Agency DANIEL N. BAKER, University of Colorado LAWRENCE BOGORAD, Harvard University DONALD E. BROWNLEE, University of Washington JOHN J. DONEGAN, John Donegan Associates, Inc. GERARD W. ELVERUM, JR., TRW Space and Technology Group ANTHONY W. ENGLAND, University of Michigan DANIEL J. FINK,* D.J. Fink Associates, Inc. MARTIN E. GLICKSMAN, Rensselaer Polytechnic Institute RONALD GREELEY, Arizona State University BILL GREEN, former member, U.S. House of Representatives NOEL W. HINNERS,* Lockheed Martin Astronautics Company ANDREW H. KNOLL, Harvard University JANET G. LUHMANN, University of California, Berkeley JOHN H. McELROY,* University of Texas, Arlington ROBERTA BALSTAD MILLER, CIESIN BERRIEN MOORE III, University of New Hampshire KENNETH H. NEALSON, University of Wisconsin MARY JANE OSBORN, University of Connecticut Health Center SIMON OSTRACH, Case Western Reserve University MORTON B. PANISH, AT&T Bell Laboratories (retired) CARLÉ M. PIETERS, Brown University MARCIA J. RIEKE, University of Arizona JOHN A. SIMPSON, Enrico Fermi Institute ROBERT E. WILLIAMS, Space Telescope Science Institute MARC S. ALLEN, Director * Former member ROBERT J. HERMANN, United Technologies Corporation, Co-chair W. CARL LINEBERGER, University of Colorado, Co-chair PETER M. BANKS, Environmental Research Institute of Michigan LAWRENCE D. BROWN, University of Pennsylvania RONALD G. DOUGLAS, Texas A&M University JOHN E. ESTES, University of California, Santa Barbara L. LOUIS HEGEDUS, Elf Atochem North America, Inc. JOHN E. HOPCROFT, Cornell University RHONDA J. HUGHES, Bryn Mawr College SHIRLEY A. JACKSON, U.S. Nuclear Regulatory Commission KENNETH H. KELLER, University of Minnesota KENNETH I. KELLERMANN, National Radio Astronomy Observatory MARGARET G. KIVELSON, University of California, Los Angeles DANIEL KLEPPNER, Massachusetts Institute of Technology JOHN KREICK, Sanders, a Lockheed Martin Company MARSHA I. LESTER, University of Pennsylvania THOMAS A. PRINCE, California Institute of Technology NICHOLAS P. SAMIOS, Brookhaven National Laboratory L.E. SCRIVEN, University of Minnesota SHMUEL WINOGRAD, IBM T.J. Watson Research Center CHARLES A. ZRAKET, MITRE Corporation (retired) NORMAN METZGER, Executive Director Astronauts who venture beyond the protection of Earth's atmosphere and magnetosphere risk exposure to levels of radiation far exceeding those on Earth. Of all the risks they face, this one is probably the most straightforward to control-by providing adequate shielding. However, because shielding adds weight, cost, and complexity to space vehicles, it is very important for designers to have a good, quantitative understanding of the true risk and its degree of certainty. This report assesses our understanding of radiation hazards in space. It also considers the additional research needed to reduce the areas of uncertainty, research that must be completed prior to undertaking the detailed design of a vehicle carrying crew members into space for periods of extended exposure. The report finds that it will take more than a decade of research to answer even the narrowest set of key questions, although happily the needed studies can all be conducted on the ground rather than in space. The nation has backed away from a specific timetable for human exploration of the moon and Mars. Yet it seems plausible that such expeditions will be mounted sometime in the first quarter of the 21st century, especially given the recent resurgence of interest in possible life on Mars from the study of meteorites. It becomes clear, when the lengthy time scale of the research is also taken into account, that the present report is indeed timely and should receive prompt consideration by NASA planners. Claude R. Canizares, Chair
The study that is the subject of this report was initiated as a result of a series of discussions between the leaders of NASA's Office of Life and Microgravity Sciences and Applications (OLMSA), NASA's Life and Biomedical Sciences Division (LBSAD), and the Space Studies Board's Committee on Space Biology and Medicine (CSBM). In order to address concerns within NASA and CSBM regarding the many uncertainties in the understanding of radiation hazards to the crew of long-duration missions in space, CSBM formed an expert task group on radiation biology and physics whose members had no direct involvement with NASA's radiation programs. A CSBM member with the appropriate expertise was appointed to lead the group. The Task Group on the Biological Effects of Space Radiation (TGBESR) was asked to review current knowledge on the effects of long-term exposure to radiation in a space environment and to consider NASA radiation shielding requirements for orbital and interplanetary spacecraft. The task group was charged with assessing the adequacy of NASA planning for the protection of humans from radiation in those environments and with making recommendations regarding needed research and/or new shielding requirements. Where feasible, the task group would also provide NASA with radiation safety guidelines. Early in the study the task group was informed by NASA that plans for the international space station were at such an advanced stage that any recommendations affecting shielding of orbital craft could not be implemented by the agency. The task group therefore decided to concentrate on the radiation hazards of interplanetary missions. Further, at the urging of NASA, the task group has attempted to provide reasonable estimates of time lines for completing the radiation research it has recommended. Although the recommendations of the task group are published here as a separate and independent report of TGBESR, it is the intent of CSBM that this report will also form the basis of a section in a space life sciences strategy report being prepared by CSBM for publication at a later date. During the course of this study the task group was briefed extensively by representatives of OLMSA and LBSAD regarding NASA's planning for deep-space missions and projections for radiation shielding. The task group also received in-depth technical briefings on the status of NASA's radiation research and the agency's current understanding of radiation hazards, and it consulted a wide range of technical documentation . When verification or additional details of prior research were needed, task group members made direct queries to the pertinent investigators in the radiation research community. A number of individuals who assisted the task group by supplying information deserve special thanks for their contributions: Harry Holloway, Frank Sulzman, and Walter Schimmerling of NASA headquarters; John Wilson of NASA Langley Research Center; Amy Kronenberg of Lawrence Berkeley National Laboratory; and Gregory Nelson of the Jet Propulsion Laboratory.
Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 5
Contributions and Use of Past Radiation Research, 7 Current Understanding of Biological Effects of Radiation, 8
Effects Induced by Protons, 8 Effects Induced by Heavy Ions, 9 References, 11 2 ISSUES OF CONCERN TO NASA: DISCUSSION AND CONCLUSIONS 13
Solar Particles, 15 Secondary Particles, 18 Estimates of Uncertainty in Radiation Risk Factors, 18 Conclusions, 18
Early Systemic Effects, 20 Skin, 20 Fertility, 21 Other Organ Systems, 21 Conclusions, 21
Cancer and Uncertainty in Estimates of Its Induction, 22 Central Nervous System, 24 Cataracts, 27 Heritable Effects, 28 DNA Repair, 29
Other Studies, 30 Conclusion, 31 References, 32
Knowledge Base Development, 35 Shielding Approaches, 36 Cost of Research vs. Cost of Excess Shielding, 38 Crew Selection, 39 Optimal Time for Flight, 39 Solar Particle Event Warning System, 40
Coronal Mass Ejections/lnterplanetary Shocks, 40 Conclusions, 40
Lower-Priority Research Questions, 47 Time Scale of Research, 50 What Will Still Remain Unknown, and What Risk Does This Represent?, 54 References, 54
Experimental Techniques and New Data Required, 56 Ground- vs. Space-based Research, 56 Plants and Food Supply, 57 References, 57 A Acronyms and Abbreviations, 61 B Glossary, 63 C Beam Sources, 69 D Previous Advice of the National Research Council Regarding the BEVALAC Facility, 72 NASA's long-range plans include possible human exploratory missions to the moon and Mars within the next quarter century. Such missions beyond low Earth orbit will expose crews to transient radiation from solar particle events as well as continuous high-energy galactic cosmic rays ranging from energetic protons with low mean linear energy transfer (LET) to nuclei with high atomic numbers, high energies, and high LET. Because the radiation levels in space are high and the missions long, adequate shielding is needed to mini mize the deleterious health effects of exposure to radiation. The knowledge base needed to design shielding involves two sets of factors, each with quantitative uncertainty-the radiation spectra and doses present behind different types of shielding, and the effects of the doses on relevant biological systems. It is only prudent to design shielding that will protect the crew of spacecraft exposed to predicted high, but uncertain, levels of radiation and biological effects. Because of the uncertainties regarding the degree and type of radiation protection needed, a requirement for shielding to protect against large deleterious, but uncertain, biological effects may be imposed, which in turn could result in an unacceptable cost to a mission. It therefore is of interest to reduce these uncertainties in biological effects and shielding requirements for reasons of mission feasibility, safety, and cost. This report of the Task Group on the Biological Effects of Space Radiation summarizes current knowledge of the types and levels of radiation to which crews will be exposed in space and discusses the range of possible human health effects that need to be protected against (Chapters 1 and 2). It points out that recent reductions in facilities for radiation research raise concerns about how best to acquire needed new knowledge. The report goes on to suggest other steps to be taken and the types of experiments needed to reduce significantly the level of uncertainty regarding health risks to human crews in space (Chapter 3). In Chapter 4 the task group recommends priorities for research from which NASA can obtain the information needed to evaluate the biological risks faced by humans exposed to radiation in space and to mitigate such risks. It outlines, in general terms, the commitment of resources that NASA should make to carrying out these experiments in order to design effective shielding in time for a possible mission launch to Mars by 2018, which would allow for energetically favorable flight trajectories. Chapter 5 addresses additional issues pertinent to carrying out studies on the effects of radiation, and the appendixes provide additional details and clarification as appropriate. Summarized below are the task group's conclusions, its recommendations for future experiments, and its estimates of the time needed to carry out these experiments. The data from these experiments should permit NASA to design cost-effective shielding to protect astronauts from the deleterious effects of radiation in space. 1. The principal risks of suffering early effects as a result of exposure to radiation in space arise from solar particle events (SPEs). It is not too difficult a task to provide appropriate shielding or storm shelters to protect against exposure during SPEs, but surveillance methods to predict and detect solar particle events from both sides of the sun relative to a spacecraft must be improved. 2. The kinds of biological effects resulting from exposure to the ionizing radiation encountered in deep space do not differ from those resulting from exposure to x rays. However, the quantitative difference between the risks posed by x rays (low-LET radiation) and by heavy high-energy nuclei (high-LET radiation) may be large, and the magnitude of the human biological effects is largely unknown. An understanding of these effects-including cancer induction, central nervous system changes, cataract formation, heritable effects, and early effects on body organs and function-as well as of the shielding necessary to mitigate these effects for crew members, is essential for the rational design of space vehicles built for interplanetary missions. 3. The task group members generally agreed that the potential late effects of radiation are the major concern in estimating risks to crew members. Of the known late effects, cancer is currently considered to be the most important. However, experimental data suggest that exposure to high-atomic-number and high-energy (HZE) particles may also pose a risk of damage to the central nervous system (CNS). Since it is estimated that during a 1-year interplanetary flight each 100-µm2; cell nucleus will be traversed by a primary energetic particle of atomic number greater than 4,1 further experimentation is essential to determine if CNS damage is a significant risk. 4. To estimate the cancer risk posed by exposure of humans to radiation such as HZE particles, for which no human data are available, it is necessary to use data on the Japanese atomic bomb survivors exposed to acute low-LET radiation and then extrapolate, based on experimental data, to estimate the risks posed by high-LET radiation. At present, the only comparative data for cancer are for studies on the induction of Harderian gland tumors in mice. Additional research is required to reduce the uncertainties of the assumptions inherent in this approach. To calculate risks associated with exposure to low-fluence-rate HZE par ticles, it is assumed, based on cell and animal studies, that there is not a large dose-rate effect. 5. Biophysical models and data for cell killing and mutagenesis indicate that as the LET increases, the biological effect of the radiation increases to a maximum near a LET of 100 keV/µm and then decreases at higher LET. (See, for example, NCRP Report No.98.2) However, no such decrease was observed in the one animal tumor for which data were obtained using a number of heavy ions with increasing LET.3 This discrepancy creates uncertainties in estimates of risks associated with exposure to particles at these higher LETs. To resolve these uncertainties, additional systematic studies are needed on the induction in animals of other radiobiologically well characterized cancers, such as leukemia and breast cancer. From a practical point of view, sufficiently accurate data can only be obtained from ground-based experiments using acute doses. 6. The background frequencies of the heritable changes in humans, which might be increased by exposure to radiation, range from ~ 10-5 to 3 x 10-3 per genetic locus.4 The minimum chronic dose that would double these values is ~ 4 Sv,5 a value greater than that given in NASA's current lifetime exposure guidelines. Hence, the genetic risk-the absolute increase in the frequencies of heritable changes-to an astronaut will be low. The risk to the gene pool of the overall human population will of course be far lower due to the relatively small number of space-faring humans. 7. The doses of radiation to which crews are exposed in space are not expected to induce early deterministic effects, with the possible exception of skin damage and a temporary reduction in fertility. Skin damage is likely only following exposure at high doses outside the spacecraft. Experimental studies in dogs indicate that any reduction in fertility per unit dose of radiation may be greater for low-dose-rate, protracted exposure than for acute exposure.6 8. The space vehicles used for missions of short duration in low Earth orbit have required minimal optimization of radiation shielding for crew protection purposes. In contrast, optimization of shielding for prolonged interplanetary trips will be a major factor in the design and cost of space vehicles. It will be necessary to know, for protons and HZE particles, the basic nuclear cross sections for interactions and fragmentation in shielding. Such data will be used to calculate the particle distributions and energies present behind different types of shielding as a result of the incident radiation passing through the shield material. Such transport calculations must be verified by ground-based experiments. 9. A knowledge of the particle types and energies present behind types of shielding should be used, with appropriate risk models, to calculate biological effects-cell killing, mutations, chromosomal changes, and tumor induction-in animals exposed to radiation. NASA investigators should also obtain parallel experimental data for the same radiation types and energies and compare these to the results calculated with models. This research is best accomplished at ground-based facilities. 10. Microgravity has little effect on the responses of simple cellular systems to radiation,7 and uncertain ties about the effects of microgravity seem negligible compared with the other uncertainties regarding risk (see 11 below). Doing cell biology and cancer induction experiments in space is costly and difficult and would require that a source of radiation be carried in the spacecraft. Because only a limited number of animals could be investigated, the results would not be statistically significant. Hence, for the study of living systems, radiation experiments in space should have a very low priority compared with ground-based research. 11. The estimated overall uncertainty in the risks of radiation-induced biological effects ranges from a factor of 4- to 15-fold greater to a factor of 4- to 15-fold smaller than our present estimates because of uncertainties both in the way HZE particles and their spallation products penetrate shielding (particle transport) and in the quantitative way in which these types of radiation affect biological functions.8 In the absence of precise data and calculations, the shielding would have to protect crew members against the higher, but uncertain, estimated risk. The cost of this possibly unnecessary shielding has been estimated by NASA researchers to be in the range of $10 billion to $30 billion.9 In comparison, the cost of a ground-based, dedicated HZE particle research accelerator is estimated (in 1996) to be $18.7 million, with an annual operating cost of about $4 million for 2000 operating hours per year.10,11 The disparity between the excess cost of additional shielding and the annual NASA budget for biology and space radiation physics indicates the need for a significant increase in the research budget for these areas. 12. Major radiation facilities-including both specialized radiation sources and animal colonies-have been shut down in recent years. At present, there are severe limits on the availability of radiation particle types and particle energies for HZE particle research. NASA can no longer rely on the Department of Energy and the Department of Defense for expertise, research, and facilities. If the necessary facilities, expertise, and funding were available now, it would take approximately 10 years to provide data that NASA needs to assess the best way to provide appropriate safeguards for its spaceflight crews. 13. Unless NASA obtains access to a reliable source of HZE particles with an appropriate support staff for a significant fraction of each year, it will take well over 10 years, perhaps over 20 years, depending on the level of effort, to reduce the present large uncertainties in particle transport behavior and in the biological response functions for cancer induction. Such a delay will postpone the design of necessary shielding or may result in the use of excess shielding (at a higher cost) and possibly delay any planned Mars mission beyond the next quarter century. 14. In Chapter 4, the task group outlines its recommendations for research priorities that NASA should follow to obtain the information needed to evaluate the biological risks faced by humans exposed to radiation in space and to mitigate such risks. The research priorities recommended by the task group include extensive physical and biological experiments, including animal studies using light and heavy nuclei up to 1 GeV/ nucleon. Such experiments could take more than 20 years at NASA's present utilization rate of approximately 100 hr/yr of accelerator time at Brookhaven National Laboratory's Alternating Gradient Synchrotron (AGS), the only source for HZE particles supported by NASA.
15. To carry out needed research expeditiously, NASA should explore a number of possibilities, including international collaborations, so as to increase the research time available for experiments with HZE particles and protons at energies over 250 MeV. Such possibilities include a combination of more running time at the AGS and at lower-energy accelerators, expansion of existing facilities (see Appendix C), the commissioning of new beam lines at existing facilities, and the construction of a new facility. A 1992 National Research Council letter report (Appendix D) emphasized the need for a dedicated HZE particle facility. REFERENCES 1. Curtis, S.B., and Letaw, J.R. 1989. Galactic cosmic rays and cell-hit frequencies outside the magnetosphere. Adv. Space Res. 9: 293-298. See also Curtis, S.B. 1992. Relating space radiation environments to risk estimates. In: Biological Effects and Physics of Solar and Galactic Radiation (C.E. Swenberg, G. Horneck, and E.G. Starsinopoulos, eds.). Plenum Press, New York. 2. National Council on Radiation Protection and Measurements (NCRP). 1989. Guidance on Radiation Received in Space Activities ties. Recommendations of the National Council on Radiation Protection and Measurements. NCRP Report No. 98. National Council on Radiation Protection and Measurements, Bethesda, Md. 3. NCRP, 1989, Guidance on Radiation Received in Space Activities. 4. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 1993. Sources and Effects of Ionizing Radiation: United Nations Committee on the Effects of Atomic Radiation: UNSCEAR 1993 Report to the General Assembly, with scientific annexes. United Nations, New York. Pp. 754-757. 5. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). 1993. Annex F: Influence of dose and dose rate on stochastic effects of radiation. Pp. 619-728 in: Sources and Effects of Ionizing Radiation, UNSCEAR. 6. Lushbaugh, C.C., and Cassarett, G.W. 1976. Effects of gonadal irradiation in clinical radiation therapy: A review. Cancer 37: 1111-1125. 7. Horneck, G. 1992. Radiobiological experiments in space: A review. Int. J. Radiat. Appl. Instrum. 20: 82-205. 8. Curtis, S.B., Nealy, J.E., and Wilson, J.W. 1995. Risk cross sections and their application to risk estimation in the galactic cosmic-ray environment. Radiat. Res. 141: 57-65. 9. Wilson, J.W., Cucinotta, F.A., Shinn, J.L., Kim, M.H., and Badavi, F.F. 1997. Shielding strategies for human space exploration: Introduction. Chapter 1 in: Shielding Strategies for Human Space Exploration: A Workshop (John W. Wilson, Jack Miller, and Andrei Konradi, eds.). NASA, Washington, D.C., forthcoming. 10. Brookhaven National Laboratory. 1991. Booster Applications Facility Report - Phase II. BNL-52291. Brookhaven National Laboratory, Upton, N.Y. 11. Alternating Gradient Synchrotron estimates transmitted to NASA by the chairman of the Alternating Gradient Synchrotron Department of Brookhaven National Laboratory, 1996. 12. NCRP, 1989, Guidance on Radiation Received in Space Activities. |