What’s New in Space Radiation Research for Exploration? Francis A. Cucinotta

1. What’s New in Space Radiation Research for Exploration? Francis A. Cucinotta NASA, Lyndon B. Johnson Space Center Presented to Future In-Space Operations (FISO) May 18, 2011

2. National Aeronautics and Space Administration The Space Radiation Problem • Space radiation is comprised of high-energy protons and heavy ions (HZE’s) and secondary protons, neutrons, and heavy ions produced in shielding • Unique damage to biomolecules, cells, and tissues occurs from HZE ions • No human data to estimate risk • Expt. models must be applied or developed to estimate cancer, and other risks • Shielding has excessive costs and will not eliminate galactic cosmic rays (GCR) Single HZE ions in cells And DNA breaks Single HZE ions in photo-emulsions Leaving visible images

3. Executive Summary • Estimating space radiation risks carries large uncertainties that preclude setting exposure limits and evaluating many mitigation measures • NASA needs to close the knowledge gap on a broad-range of biological questions before radiation protection goals can be met for exploration • The Human Research Program (HRP), Space Radiation Program Element (SRP) led by JSC is committed to solving the space radiation problem for exploration

4. Space Radiation Environments • Galactic cosmic rays (GCR) penetrating protons and heavy nuclei - a biological science challenge • shielding is not effective • large biological uncertainties limits ability to evaluate risks and effectiveness of mitigations • Solar Particle Events (SPE) largely medium energy protons – a shielding, operational, and risk assessment challenge • shielding is effective; optimization needed to reduce weight • improved understanding of radiobiology needed to perform optimization • accurate event alert and responses is essential for crew safety GCR a continuum of ionizing radiation types Solar particle events and the 11-yr solar cycle

5. Sham TGFβ  +TGFβ Fe Fe+TGFβ Space Safety Requirements • Congress has chartered the National Council on Radiation Protection (NCRP) to guide Federal agencies on radiation limits and procedures • NCRP guides NASA on astronaut dose limits • Crew safety • limit of 3% fatal cancer risk • prevent radiation sickness during mission • new exploration requirements limit brain and heart disease risks from space radiation • Mission and Vehicle Requirements • shielding, dosimetry, and countermeasures • NASA programs must follow the ALARA principle to ensure astronauts do not approach dose limits Cell fusion caused by radiation Space Radiation in breast cancer formation

6. Categories of Radiation Risk Four categories of risk of concern to NASA: • Carcinogenesis (morbidity and mortality risk) • Acute and Late Central Nervous System (CNS) risks • immediate or late functional changes • Chronic & Degenerative Tissue Risks • cataracts, heart-disease, etc. • Acute Radiation Risks – sickness or death Differences in biological damage of heavy nuclei in space with x-rays, limits Earth-based data on health effects for space applications • New knowledge on risks must be obtained Lens changes in cataracts cataracts First experiments for leukemia induction with GCR

7. Space Radiation Health Risks • NASA limits acceptable levels of risks of astronauts to a 3% Risk of Exposure Induced Death (REID) from cancer • PEL requirement to be below 95% Confidence Interval (C.I.) for cancer risk protects against uncertainties in risk projection models • Estimates of number of days to be within a 95% C.I. are used to assess: • Safe mission lengths • Crew selection criteria such as Age, Gender and Prior Exposure • Mitigations such as Shielding or Biological Countermeasure Requirements • Non-cancer risks are not well defined • Potential for late non-cancer mortality risks (Heart and CNS) on long-term exploration missions confounds assessments of Acceptable Risk, which includes only cancer at this time • Additionally, the NCRP recommends that limits for non-cancer morbidity risks be based on avoiding any clinically significant effect • Research in cells and murine models are not conclusive regarding clinical significance of space radiation exposure to the astronaut's CNS • Need appropriate animal model to assess clinical significance

8. CNS Risks from Galactic Cosmic Rays (GCR) • Retinal flashes observed by astronauts suggests single heavy nuclei can disrupt brain function. • Central nervous system (CNS) damage by x-rays is not observed except at very high doses • In-flight cognitive changes and late effects similar to Alzheimer’s disease are a concern for GCR. • NASA research in cells and mouse/rat models has increased concern for CNS Risks • Over 90 CNS journal publications supported by NASA since 2000 • Studies have quantified rate of neuronal degeneration, oxidative stress, apoptosis, inflammation, and changes in dopamine function related to late CNS risks • Cognitive tests in rats/mice show detriments at doses as low as 10 mGy (1 rad) • Large hurdle remains to establish significance in humans Reduction in number of neurons (neurodegeneration) for increasing Iron doses in mouse hippocampus

9. Control Iron Nuclei Radiation and Non-Cancer Effects Vasculature Damage by GCR • Early Acute risks are very unlikely: • Low or modest dose-rates for SPE’s insufficient for risk of early death • SPE doses are greatly reduced by tissue or vehicle shielding • Radiation induced Late Non-Cancer risks are well known at high doses and recently a concern at doses below 1 Sv (100 rem) • Significant Heart disease in Japanese Survivors and several patient and Reactor Worker Studies • Dose threshold is possible making risk unlikely for ISS Missions(<0.2 Sv) ; however a concern for Mars or lunar missions due to higher GCR and SPE dose • Qualitative differences between GCR and gamma-rays are a major concern

10. NASA Space Radiation Lab (NSRL) at DOE’s Brookhaven National Laboratory Medical Dept. Biology Dept.

11. EBIS SC solenoid Beam port Dipoles – preparing RFQ Linac National Aeronautics and Space Administration NASA Space Radiation Laboratory • A $34-million facility, is located at DOE’s Brookhaven National Laboratory is managed by NASA’s Johnson Space Center. It is one of the few places in the world that can simulate heavy ions in space. • New joint DoE-NASA Electron beam injector source (EBIS) for 2009 increases space simulation capability • $9 M Annual operations cost EBIS Construction

12. National Aeronautics and Space Administration Major Sources of Uncertainty • Radiation quality effects on biological damage • Qualitative and quantitative differences between space radiation compared to x-rays or gamma-rays • Dependence of risk on dose-rates in space • Biology of repair, cell & tissue regulation • Predicting solar events • Temporal and size predictions • Extrapolation from experimental data to humans • Individual radiation-sensitivity • Genetic, dietary and “healthy worker” effects Durante & Cucinotta, Nature Rev. Cancer (2008) Cucinotta et al Radiat Meas (2006)

13. Space Radiation Shielding is Well Understood Radiation Shielding Materials • NASA has invested in shielding technologies for many years and understanding is nearly complete • Over 1,000 research publications since 1980 • Solar events can be shielded • GCR requires enormous mass to shield because of high energies and secondary radiation • Highly accurate predictive codes exist with +15% errors for organ exposure projections • Transport codes • Environmental models • Optimal materials • Topology Design methods • Knowledge missing is accurate understanding of radiobiology for Exposure to Risk conversion August 1972 SPE and GCR Solar Min

14. Value Of Uncertainty Reduction Research: Cost of research to reduce uncertainties much less than cost of shielding in space or reducing mission length

15. What’s New in Space Radiation Research? • New Epidemiology data suggests much weaker age dependence on radiation cancer risks • Number 1 Trade variable (Astronaut age) is negated • Probabilistic risk assessments replace “rads and rem” • New Quality factors and uncertainty assessments • Galactic cosmic rays (GCR) are much higher concern than Solar particle events • Shielding plays only a small role for GCR • New health risks of concern from radiation • Heart disease, and Central nervous system (CNS) risks • Risks estimated to be much smaller for “Never-smokers”

16. Roles of Select Committees and Radiation Projection Councils National Aeronautics and Space Administration • Select expert panels from the National Academy of Sciences (NAS) and United Nations (UN) update human radio-epidemiology based estimates of radiation cancer risks each decade • These reports form the basis for revised radiation protection standards and policy as recommended by the US National Council on Radiation Protection and Measurements (NCRP) and International Commission on Radiological Protection (ICRP) • The most recent reports from NAS (BEIR VII) and the UN (UNSCEAR 2006) make important changes to the description of the age dependence of cancer risks, and cancer risks at low dose-rates • BEIR VII: Linear dose response with no age at exposure dependence above age 30-yr • UNSCEAR model shows similar age dependence for cancer incidence • These changes will increase risk projections if accepted by NASA 16

17. National Aeronautics and Space Administration NASA 2010 Cancer Projection Model • NASA is developing new approaches to radiation risk assessment: • Probabilistic risk assessment framework • Tissue specific estimates • Research focus is on uncertainty reduction • Smaller tolerances are needed as risk increases, with <50% uncertainty required for Mars mission • NASA 2010 Model • Updates to Low LET Risk coefficients • Risks for Never-Smokers • Track Structure and Fluence based approach to radiation quality factors • Leukemia Q lower than Solid cancer Q GCR doses on Mars

18. Radiation Risks for Never-Smokers Lung cancer in Unexposed Thun et al., PLoS Med (2008) • More than 90% of Astronauts are never-smokers and remainder are former smokers • Smoking effects on Risk projections: • Epidemiology data confounded by possible radiation-smoking interactions, and errors documenting tobacco use • Average U.S. Population used by NCRP Reports 98 and 132 • NASA Model projects a 20 to 40-% risk reduction for never-smokers compared to U.S. Ave. • Larger decreases are possible if more were known on Risk Transfer models • Balance between Small Cell and Non-Small Cell Lung Cancer a critical question including high LET effects

19. National Aeronautics and Space Administration CDC Estimates of Smoking Attributable Cancers *Other cancers being considered Colon, leukemia, and liver

20. National Aeronautics and Space Administration Point Estimates: Risk of Exposure Induced Death (REID) %REID per Sv

21. National Aeronautics and Space Administration Fatal lung cancer risks per Sv (per 100 rem)Transfer model impact much larger change than >100 cm of GCR shielding– the 100 Billion Dollar question?

22. National Aeronautics and Space Administration “Safe” days in Space: Uncertainties estimated using subjective PDFs propagated using Monte-Carlo techniques %REID predictions and 95% CI for never-smokers and average U.S. population for 1-year in deep space at solar minimum with 20 g/cm2 aluminum shielding: Maximum Days in Deep Space with 95% Confidence to be below Limits (alternative quality factor errors in parenthesis):

23. National Aeronautics and Space Administration New Quality Factors: Comparison NASA Q’s to ICRP Q

24. Solar Min and Max Comparison with Proposed NASA Quality Factor (Q) and Tissue Weights (Wt) vs ICRP Quality Factor Definition

25. National Aeronautics and Space Administration Shielding Materials play little role for GCR Annual effective dose. Solar max calculations include 1972 Solar Particle Event.

26. Future risk assessments-New Approaches are needed Inherent uncertainties in “Standard’” model points to the need for new approaches Systems biology for disease modeling is most viable approach NASA has selected 7 NASA Specialized Centers of Research (NSCORs) and several related Grants using mouse models of colorectal, liver, leukemia, and lung cancer from space radiation. The NASA Lung Consortium is a $28 M effort to focus on risks of non-small lung cancer (NSCLC) and small-cell lung cancer (SCLC) from space radiation. CNS and Circulatory disease risks from space radiation are a major concern for space exploration with 12 Grants funded by NASA and the CNS NSCOR.

27. Summary Space radiation is a major challenge to exploration: • Risks are high limiting mission length or crew selection • Large mission cost to protect against risks and uncertainties • New findings may change current assumptions NASA approach to solve these problems: • Probabilistic risk assessment framework for ISS and Exploration Trade Studies • Ground-based research focused on uncertainty reduction at NASA Space Radiation Laboratory (NSRL) • Collaborative research with DoE, and ESA • Ongoing external reviews by authoritative bodies

28. National Aeronautics and Space Administration Solar Particle Event (SPE) Risks • Research studies show that risks of acute death from large SPEs has been over-estimated in the past: • Proper evaluation of dose-rates, tissue shielding, and proton biological effectiveness show risk is very small • SPE risk remain important for lunar EVA • Radiation sickness if unprotected > 2 hour EVA • Cancer risk is priority for both EVA and IVA • Proper resource management through research: • Probabilistic risk assessment tools for Lunar and Mars Architecture studies • Optimize shielding requirements by improved understanding of proton radiobiology & shielding design tools • ESMD and SMD collaborations on research to improve SPE alert, monitoring and forecasting • Biological countermeasure development for proton cancer, and Acute radiation syndromes (if needed)

29. SPE Probabilistic Risk Assessment SPE Hazard Rate in Space Era • Using detailed data base of all SPE’s in space age (1955-current) and historical data on Ice-core nitrate samples (15th-century to current), SRP has developed a probabilistic model of SPE occurrence, size, and frequency • Hazard rate model using Survival analysis • Non-uniform Poisson process provides high quality fit of all SPE data • Probabilistic model supports shielding design and resource management goals for Exploration missions • Department of Defense model estimates various acute risks Non-Uniform Poisson Process

30. National Aeronautics and Space Administration Blood Forming Organ (BFO) Dose on Lunar Surface • SPEs readily mitigated with proper alert, dosimetry, and shielding below 25 cGy-Eq acute limit; however cancer risk a concern • SRP probabilistic models account for variability in event frequency, size and proton energies 5 g/cm2 Shielding 10 g/cm2 Shielding Predictions for peak hazard rate in solar cycle

31. Acceptable Risk Levels for Exploration Missions • The NASA Standard of 3% Risk of Exposure Induced Death was set in 1989 by NASA Administrator with OSHA Concurrence under Code of Federal Regulation (CFR 1960) • NASA has set an identical acceptable risk level for Exploration missions under the OCHMO’s 2006 Permissible Exposure Limits (PEL) • OSHA concurrences on NASA Health policy in Spaceflight dropped in 2004 after discussion with OCHMO • The NCRP recommendation of 3% Limit based on 3 rationales: • Comparison of fatality rates in less-safe Industries made in 1989 • Comparison to risk limits for ground-based workers • Recognition of other spaceflight risks • Fatality rates in less-safe industries have improved more than 2-fold since 1989 and therefore no longer valid basis; however other 2 rationale from NCRP in 1989 are still valid

32. Acceptable Levels of Risk - continued • A discussion of higher or lower Acceptable Risk Levels would consider • Over arching Ethical and Safety standards at NASA and in the U.S. • Benefits to Human-kind from Exploration missions • Emerging information on possible radiation mortality risks from non-cancer diseases, notably Heart (Stroke and Coronary Heart Disease) and Central Nervous System risks • The resulting burden for morbidity risks including cancer, cataracts, aging, and other diseases that entail pain, suffering, and economic impacts • Radiation cancer incidence probability approximately Two times higher than cancer death probability • Improvements in other areas of safety at NASA, other government agencies and work places since 1989 • Balance between other space flight risks and space radiation risks • NCRP Recommendation is the high risk nature of space missions precludes allowing an overly large radiation risk to Astronauts • Impacts on finding solutions through research programs and mission design architectures that result from Acceptable Risk Standards

33. 3% and 6% Cancer Mortality Risks at 90% to 95% Confidence Levels (CL) (Solar Min at 20 g/cm2 Aluminum) Number of Days in Deep Space At Solar minimum with a 95% or 90% CL to be below 3% or 6% Risk of Cancer Death from Space Radiation (Avg US pop) 33

34. Risk of Exposure Induced Cancer (REIC) for 1-year in Deep Space at Solar Minimum with 20 g/cm2 Al shield Females Males

35. Foundations of SRP Research Plans • External review by NCRP, National Academy of Sciences, and standing Radiation Discipline Working Group (RDWG) • Simulate space radiation at the NASA Space Radiation Laboratory (NSRL) • Located at DoE’s Brookhaven National Lab (Long Island NY) • Five NASA Specialized Centers of Research (NSCOR’s) studying the biology of space radiation risks • Broad program of directed research including collaborative research with DoE • NASA directed NSBRI research on acute risks and EVA dosimetry thru co-operative agreement • Collaborate with SMD on advanced SPE alert & Mars robotic missions • Long-term goal to improve knowledge to develop individual risk assessments, countermeasures