There is concern that the radiations encountered during long-term space exploration missions may result in significant damage to the central nervous system (CNS) of astronauts. SC 1-24 Phase 1 Committee evaluated the available information and concluded that there is sufficient evidence to justify a more detailed study of the potential damage and its implications for long-term space missions, the phase 2 activity proposed to National Aeronautics and Space Administration (NASA). NASA accepted this recommendation and the Phase 2 Committee, with expanded membership, was formed.
There is abundant evidence that humans exposed to large doses of low linear energy transfer (LET) radiation experience cognitive and behavioral changes which are often persistent and can have significant effects on normal activities. Animal experiments using charged particles show biochemical and behavioral changes at the lower doses relevant to long-term space missions, but it is difficult to relate these changes to risk of damage to the human CNS. Furthermore, it is likely that the cognitive reserve of the human will compensate for small amounts of damage without adverse effects on spacecraft crew function. However, many characteristics of the environment in spacecraft, microgravity, variable CO2 levels, irregular sleep schedules, job related stress, cramped quarters, separation from family, and communications lag time, produce stress which can lead to cognitive impairment and personality changes which may mask radiation effects or perhaps interact with radiation in a synergistic fashion.
The goals of the Phase 2 Committee include:
- evaluation of what constitutes a “significant impairment” in the context of actual spacecraft operation;
- can existing schemes for evaluation of chemical neurotoxicity be used as a guide for evaluating CNS effects of radiation;
- can key events related to behavior or performance impairment and/or late effects such as dementia be identified;
- are nonhuman primate experiments necessary for the extrapolation from animal effects to risk of impaired human performance;
- are there radiation exposure levels below which the risk of significant impairment is minimal;
- how might space radiation “interact” with other aspects of a mission that would impair performance, both for the individual and the team;
- what is the relative balance between the likelihood of neurobehavioral effects that would impair operational performance and the likelihood that serious neurodegenerative disease develop such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis (ALS), and dementia; and
- does the human CNS have compensation mechanisms that would influence the likelihood of getting to a level of impairment that would adversely affect performance and the mission?
An initial planning teleconference involving Committee members was held on January 19, 2016. The first face-to-face Committee meeting was held February 11–12, 2016, in Galveston, Texas, conjunction with the NASA Human Research Program annual workshop. Committee expertise was shared and key questions to be addressed were assigned to Committee members for overview presentations at the next meeting, to be held May 25–26, 2016, in Bethesda, Maryland. The key questions to be addressed involve:
- Animal Behavior Effects, Dose and Ion Dependent [Raber (Rosi, O’Banion, Krull)]
- Cellular and Biochemical Issues [O’Banion (Rosi, Chang, Raber, Goodhead)]
- Medical Side Effects [Krull (Root, Hopewell)]
- Other Stressors [Dinges t(Qin)]
- Quantifying Effects in Crew [Qin (Dinges)]
- Potential Countermeasures [Winhauser (Dinges, others)]
- Mechanistic Approach [postponed to the Bethesda meeting (Herr as the potential lead)]
- Animal Behavior Effects, Dose and Ion Dependent [Raber (Rosi, O’Banion, Krull)]
- Extrapolation to Humans (also postponed until the Bethesda meeting)
NCRP is grateful to the National Aeronautics and Space Administration for financial support for this work.
The membership of SC 1-24 Phase 2 is:
LESLIE A. BRABY
has been a Research Professor at Texas A&M University since 1996. His previous experience includes Biology and Chemistry Department Staff Scientist from 1971 to 1991 and Radiation Physics and Chemistry Section Manager from 1991 to 1995 at Battelle, Pacific Northwest National Laboratory. He received his BA degree from Linfield College and PhD from Oregon State University in 1972.
Dr. Braby is a former member of the NCRP Board of Directors and a member of several NCRP scientific committees (SC) including SC 88 on Fluence as a Basis of a System of Radiation Protection for Astronauts, SC 1-7 on Research Needs for Deep Space Missions, chair of SC 1-11 on Safety Considerations for Pulsed Fast Neutron Surveillance Systems, SC 6-1 on Uncertainties in Measuring External Beam Irradiation, SC 1-20 on the biological effects of low energy x rays, and Chairman of SC 6-5 on Safety of Cargo Inspection Systems Using High Energy Photons. He was also Chair of the International Commission on Radiation Units and Measurements (ICRU) working committee on characterizing low level radiation exposure, and member of ICRU working committee to prepare a report on microdosimetry.
|Jacob Raber, Co-Chair|
David F. Dinges
is a tenured Professor of Psychology in Psychiatry, Director of the Unit for Experimental Psychiatry, and Chief of the Division of Sleep and Chronobiology, at the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania. For the past two decades he has conducted both laboratory and field research for the National Aeronautics and Space Administration (NASA) on ways to predict, prevent, detect and mitigate neurobehavioral health risks to astronauts, including research on the International Space Station and in numerous space analogs. He is Team Lead of the Neurobehavioral and Psychosocial Factors Team for the National Space Biomedical Research Institute (NSBRI). Dr. Dinges has published 207 peer-reviewed and 140 other papers. He has been a recipient of numerous awards, including the NASA Distinguished Public Service Medal and the NSBRI Pioneer Award. He is an elected member of the International Academy of Astronautics, and he has served on a number of committees for the National Academies of Science.
Dudley T. Goodhead
is Emeritus Director of the Medical Research Council (MRC) Radiation and Genome Stability Unit, Harwell, United Kingdom. His Unit carried out basic research on the relationship of genome stability to human health, including how DNA may be damaged by radiation and the cellular repair systems act to restore normality. He is now an independent consultant and assists agencies in evaluating and guiding their radiation research programs in the European Union and the United States. His personal research has been mainly on the biophysics of radiation effects, with particular emphasis on microscopic features of radiation track structure at the atomic, molecular, and cellular levels and their consequent radiobiological and health effects. He gained his PhD in particle physics at the University of Oxford. Early career positions were at the Universities of California, London and Natal and at the MRC Radiobiology Unit. He has served on a variety of national and international committees on evaluation of radiation risks, including the Committee on Medical Aspects of Radiation in the Environment in the United Kingdom, two National Research Council committees [on health risks of exposure to radon (BEIR VI) and evaluation of the National Aeronautics and Space Administration’s (NASA) space radiation cancer risk model] and working groups of the International Agency for Research on Cancer (on carcinogenic risk of gamma rays, neutrons, and internally deposited radionuclides) and the Royal Society (on risks from depleted uranium) and consultancies to the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Atomic Energy Agency. He was chair of the Committee Examining Radiation Risks of Internal Emitters in the United Kingdom and is currently acting chair of the Advisory Group on Ionizing Radiation of Public Health England. In the 2002 Queen’s Birthday Honours List, he was awarded the Order of the British Empire for services to medical research. His other awards include the Weiss Medal from the Association for Radiation Research, Failla Medal from the Radiation Research Society, Douglas Lea Lecturer from the Institute of Physics and Engineering in Medicine and Biology, Bacq and Alexander Award from the European Society of Radiation Biology, Honorary Fellowship from the Society of Radiological Protection, Warren K. Sinclair Lecturer from NCRP, and Gray Medal from the International Committee on Radiation Units and Measurements. For the past 3 y he has directed the NASA Space Radiation Summer School at Brookhaven National Laboratory.
|Richard M. Linnehan|
Thomas J. MacVittie
a professor of radiation oncology and pathology at the University of Maryland, School of Medicine in Baltimore, is recognized internationally as an expert on the effects of radiation on the hematopoietic and gastrointestinal systems in large animal models and their treatment, in vivo, with supportive care and selected organ-specific medical countermeasures against acute and delayed effects of acute radiation exposure.
He earned MS and PhD degrees in radiation biology at the State University of New York at Buffalo and has more than 40 y of experience as a radiobiologist in the field of experimental hematology and the effects of acute radiation exposure. He has published 184 peer-reviewed manuscripts and 47 chapters in books or proceedings. He has co-edited five books published from international meetings organized on radiation effects and treatment.
Dr. MacVittie has served as an advisor to the World Health Organization Collaborating Centers in Radiation Emergency Medical Preparedness and Assistance and as a member of North Atlantic Treaty Organization Radiation Research Study groups and the Task Group for the International Council on Radiation Protection entitled “Radiation Effects on Normal Tissue.” Dr. MacVittie also served on the inaugural National Biodefense Science Board Federal Advisory Committee.
The MacVittie laboratory has developed an Animal Model Research Platform that positions the research team to carry the lead in an integrated effort to develop the most effective products to treat the acute radiation syndrome and the delayed effects of acute radiation exposure to include a strategic focus on MCM efficacy against multiple organ injury.
The MacVittie research team and its accumulated data base served as the focal point for recent efforts to design the initial “pivotal” trials in nonhuman primates to determine the treatment efficacy of neupogen and neulasta to treat potentially lethally irradiated personnel. These are the first two MCM approved by the U.S. Food and Drug Administration (March and October 2015) under the ”animal rule” to treat the hematopoietic acute radiation syndrome.
|M. Kerry O’Banion|
is a neuropsychologist in the Department of Psychiatry and Behavioral Sciences at Memorial Sloan-Kettering Cancer Center and an Assistant Professor of Psychology in the Department of Psychiatry and the Department of Anesthesiology at Weill Cornell Medical College. His neuroimaging research focuses on the cognitive effects of cancer diagnosis and treatment, including surgery, anesthesia, chemotherapy, radiotherapy and endocrine therapy, utilizing structural and functional techniques, as well as neurocognitive measures. His clinical expertise is in the assessment of cognitive abilities in adults following cancer treatment. He completed his postdoctoral training in clinical neuropsychology at Columbia University College of Physicians and Surgeons, a second fellowship in neuroimaging at Weill Cornell Medical College, and completed a predoctoral residency in neuropsychology at Yale University School of Medicine. He holds secondary appointments as Lecturer at Harvard Medical School and as Faculty Lecturer at the New School for Social Research.
GREGORY A. NELSON
earned his BS in chemistry from Caltech and his PhD in Cell and Developmental Biology at Harvard Medical School in 1979 where his thesis work was on the genetics of sex determination and spermatogenesis in the nematode C. elegans. During a postdoctoral fellowship at Harvard he investigated regulation of cell surface distribution of immunoglobulin on lymphocytes and its control by the calcium regulator, calmodulin. He joined the Jet Propulsion Laboratory in 1982 where he became interested in the space radiation environment and developed C. elegans as a biodosimetry system for spaceflight applications. As principal investigator, he flew the nematode experiments using the European Space Agency's Biorack facility on shuttle missions STS-42 (1992) and STS-76 (1996). He has since participated in shuttle missions STS-108, -118 and -135 examining effects of spaceflight on the immune and nervous systems of mice as part of the commercial biotechnology technology mission experiments 1-3.
The spaceflight experiences led him to participate in a number of National Aeronautics and Space Administration (NASA) programmatic activities, including the design of a dedicated biological satellite (LifeSat) system. He joined Loma Linda University (LLU) in 1996 to direct its new radiobiology program and to develop the infrastructure needed to do space research with proton beams. As the LLU radiobiology program grew, he was able to maintain a modest research activity with C. elegans, and later began collaborations on projects that have investigated the effects of protons and charged particles on immune responses, thyroid cells in three-dimensional tissue models, microvasculature, and rodent behavior. More recently he served as principal investigator on two NASA program projects (NSCOR) team involving nine institutions that investigate how space-like radiation exposures produce time- and dose-dependent changes in the mouse brain.
He was a founding director of NASA's Space Radiation Summer School held at the Brookhaven National Laboratory and serves as a member of NCRP. He recently completed a NASA-funded study investigating genes regulating bystander effects in C. elegans in a study involving RNA interference screening and microbeam-based experiments in collaboration with Professors Leslie Braby and John Ford of Texas A&M University and was appointed Adjunct Professor of Nuclear Engineering at TAMU in 2008. Another ongoing study funded by the U.S. Department of Energy investigates the effects of low doses of gamma rays on adaptive immunity in the mouse. Dr. Nelson is currently Professor of Basic Sciences and Radiation Medicine at Loma Linda University.
Lawrence W. Townsend
is the Chancellor's Professor and Robert M. Condra Professor of Nuclear Engineering, University of Tennessee, Knoxville. He has a BS in Physics from the U.S. Naval Academy, and an MS in Physics (experimental nuclear) from the Naval Postgraduate School. After obtaining his MS, he served for 7 y as a nuclear submarine engineer. After leaving the Navy, he obtained a PhD in Physics (theoretical nuclear) from the University of Idaho. After a short stint as a Research Assistant Professor of Physics at Old Dominion University, he became a National Aeronautics and Space Administration (NASA) Research Scientist and Senior Research Scientist where his research has focused on nuclear interactions of cosmic rays and their implications for space radiation shielding and crew protection. For these efforts, he was awarded a NASA Scientific Achievement Medal. In 1995 he retired from NASA and entered academia at the University of Tennessee where he continues to do research on space radiation interactions, transport, and their effects. In 1998 he served as the Organizing Committee Chair for the NCRP Annual Meeting and was elected a Member of Council and was appointed as a Distinguished Emeritus Member of Council in 2010. He has served as a member of Scientific Committee 75, chair of Scientific Committee 1-7, and consultant for Scientific Committee 1-24 (phase I).