NSRL Results and Future Plans for Space Research Francis A. Cucinotta

1. NSRL Results and Future Plans for Space Research Francis A. Cucinotta NASA, Lyndon B. Johnson Space Center Presented at BNL Accelerator & Collider Department Seminar May 6, 2008

2. Introduction • Within a year of creation of NASA in 1958, it was realized that cosmic rays are substantial threat to human space missions and a need for particle accelerator simulation for life science experiments was identified • The NASA Space Radiation Laboratory (NSRL) will be the main tool to enable deep space missions of the future • Currently a Mars mission is projected to exceed NASA safety guidelines for astronauts by a large margin

3. Categories of Space Radiation Risks 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 First experiments for leukemia induction with GCR

4. 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

5. Cancer Uncertainty Assessments • Uncertainties assessments use probability distribution functions (PDF) to represent range of data of different factors in risk model • NASA is Unique amongst government agencies in that Uncertainty assessments are part of radiation protection program NASA is expecting Risk per unit Dose from HZE nuclei will be assessed higher in near future: - Age, RBE, dose-rate, and latency for solid tumors

6. Major Findings from NSRL • First experiments at NSRL were in Oct, 2003 and many publications are in preparation. However findings to date include • A low RBE for Leukemia from Iron due to high efficiency of apoptosis • RBE concept appears to hold • A high RBE for solid cancer is emerging and also evidence that RBE concept fails • Major differences in signaling pathways between high and low LET and high and low dose • Evidence that CNS effects will occur at doses <0.5 Gy, however morbidity in humans still undefined. Costes et al result showing DNA damage movement to low chromatin density regions

7. Fatal Cancer Risk at Solar Minimum(20 g/cm2 Aluminum Shielding) *Parenthesis exclude Prostate cancer; **Parenthesis LSS-report 12 (others report 13)

8. Research progress shows significant increase in “Safe Days” to be within acceptable risks for a Mars mission Uncertainties are being reduced through NSRL research Table: Estimates of “Safe Days” in deep space under heavy shielding where NASA limit is not exceeded Estimates of “Safe Days” in Space for GCR

9. The Space Radiation Environment • Solar particle events (SPE) (generally associated with Coronal Mass Ejections from the Sun): • medium to high energy protons • largest doses occur during maximum solar activity • not currently predictable • MAIN PROBLEM: develop realistic forecasting and warning strategies • Trapped Radiation: • medium energy protons and electrons • effectively mitigated by shielding • mainly relevant to ISS • MAIN PROBLEM: develop accurate dynamic model • Galactic Cosmic Rays (GCR) • high energy protons • highly charged, energetic atomic nuclei (HZE particles) • not effectively shielded (break up into lighter, more penetrating pieces) • abundances and energies quite well known • MAIN PROBLEM: biological effects poorly understood but known to be most significant space radiation hazard

10. D=F x LET H=D x Q(LET)

11. Elemental Dependence of GCR Cancer Risks Tandem does not provide He(2), Ne(10), Mg(12), Ar(18), Ca(20); however EBIS will in 2011

12. LZE “cloud” about HZE Particles -Quasi equilibrium flux of high LET secondaries For Z>2 50% flux>1 GeV/u which is only available at AGS

13. NSRL Simulation of Biological Temporal and Space Scales • Biological time and spatial scales as well as linear or non-linear response modes must be known relative to GCR fluxes (type and rate) to properly simulate: • Proper understanding of correct temporal and spatial scales- for NSRL dose or future protracted exposures is essential to design • Temporal: • Initial damage and radiation chemistry per nucleus <1 sec • DNA Damage repair 10 minutes to ~1 day • Apoptosis and differentiation ~0.5 to several days • Cell turn-over rates- Tissue specific from ~1 to 30 days • Tumor latency (post initial damage) in humans 2 to 30 yrs • Tumor latency in mice 100 to 800 days • CNS Adaptation time to GCR insult?? • Lifespan in astronauts ~80 yrs • Lifespan in mice ~1000 days • Mars mission 1000 days

14. Spatial Scales- continued • Space: (GCR proton hits/day ; HZE) • DNA damage repair foci ~0.5 mm2 (0.002 per day / 1x10-6) • Chromosome cross sections ~ 2 mm2 (0.01 per day / 2x10-4) • Cell Nucleus ~200 mm2 ` (1 per day/ 0.02) • Interacting cell matrix ~1000 mm2 (>5 per day/ >0.1) • Whole Tissue>Many per day • Space radiation simulation is anchored in knowing space conditions relative to scientific question being addressed • A “low dose” for certain biological questions, may be a “high dose” for another • Most NSRL experiments to date have been performed in “track segment mode” where samples are irradiated with largely a single species with constant LET across sample

15. Linear energy transfer (LET) does not adequately describe energy deposition at biomolecular or cellular scales Full characterization of HZE nuclei- Charge, Z defines density of ionization along track (Z2 dependence) Kinetic energy of b defines width of track corresponding to maximum distance of energy deposition laterally from track Track Structure of Space Radiation Nuclei of LET = 150 keV/mm Monte-Carlo simulation of ionization patterns (He 0.45 MeV/u; C (10 MeV/u), Si (90 MeV/u) and Fe (1 GeV/u)

17. NSRL Beam Selection • NASA guides beam selection to provide full range of Z and LET for GCR to PIs, while allowing for future retrospective inter-comparison between experiments • Protons 250, 1000, 2500 MeV • Solar Proton Events (1972, TBD) • Carbon (250 MeV/u) • Oxygen (600, 1000 MeV/u) • Silicon (300, 600, 1000 MeV/u) • Chlorine (500, 1000 MeV/u) • Titanium (1100 MeV/u) • Iron (300, 600, 750, 1000 MeV/u) • Mixed Proton+Iron at 1 GeV/u • Future capabilities (~2009) with addition of jointly DOE-NASA funded EBIS source will allow for He, Ne, and Ca as well as improved mixed-field capabilities

18. Space Radiation Research- The Next 20-yrs Contributions to National Priorities Agency Mission 2008–2014 2015–2023 2024–2030 Perform research on dose-rate effects of protons, develop shielding design tools; apply probabilistic risk assessment to lunar missions Develop and deploy operational strategies for managing SPE risks; Apply biomarker methods to samples from lunar crews • Contribute to increased understanding of solar physics; Apply biomarker technologies to problems on Earth Validate radiation environment and transport models using lunar data; Validate models of proton dose-rate effects Lunar Sortie Missions by 2020 Design exploration missions; Apply new knowledge of radiation effects and NASA computational biology models to human diseases on Earth Continue NSRL research on risks; perform research on biological countermeasures; optimize shielding designs for Mars missions Finish NSRL research on countermeasures; Develop diagnostics of radio-sensitivity and gene therapy for prevention and/or treatment of radiation damage Use NSRL to simulate space radiation to understand their biological effects; Compete radiation transport codes and design tools Lunar outpost Missions up to 240 days Reduce uncertainties in risk projections to less than 2-fold; Determine if CNS and degenerative risks from GCR will occur Reduce uncertainties in risk projections to less than 50%; lunar- instruments to measure Mars surface environment at solar minimum Apply knowledge on individual risk assessments and biomarkers; develop accurate long-term solar weather predictions • Apply countermeasure knowledge to diagnosis, prevention and treatment of diseases on Earth Mars Exploration Missions by 2030

19. Countermeasures Research • The Space Radiation program envisions a large research program on biological and shielding materials counter-measures in 2015-2025 timeframe • It will be impractical to test a large number of drug types and concentrations in a sufficient number of biological models to demonstrate efficacy using track-segment approach with multiple HZE nuclei types and energies • NSRL will need to develop a small number of Design Reference fields for GCR and SPEs to support SRP Countermeasure research programs • Mixed field capabilities will be essential for optimal Design fields

20. Significance Tests of Shielding Effectiveness Test of Shielding effectiveness can be made with transport codes such as HZETRN and a small number of measurements; however Drug testing will not be able to rely on a theoretical approach for basic data

21. Future Goals for NSRL Capabilities • Solar particle event simulation • Major peak of SPE’s is over a 5-15 hour window • Dose-rates ~1-100 rad/hr • Mixed-energies corresponding to primary spectrum and slowing down spectrum in tissues • Small secondary neutron and recoil ion component • Proton energy spectra at select animal tissues matched to energy spectra at human tissues of interest • Requires Transport code modeling of translation • To control costs NASA will work with BNL to group PI’s into multiple Group extended exposure experiments

22. Historically Large Solar Proton Events Recent Era (1550-2000) McKracken et al Modern Era (1956-2005)

23. August 1972 Solar Particle Event Dose-rates at deep tissues Oct./Nov. 2003 Solar Particle Event

24. Simulating SPE’s in Small animals to represent Human tissue spectra

25. Future NSRL Capabilities- GCR • Dose-rate from GCR • There should be no dose-rate effect from GCR for most biological time scales; a limiting low dose-rate has been reached • However, there is the possibility of tissue adaptation including roles for cell turnover, re-population, etc. • Mixed- Z and E exposures • Each shielding configuration of spacecraft leads to a varying Z and E composition. • There is a need to use the EBIS facility to define a “GCR simulation field representative of LET and Z composition of GCR • Several “GCR reference fields” will be needed: • Earth-Mars transit field • Mars surface representative field • Mixed fields must be reproducible • Because of the upper E-limit of NSRL GCR simulation must rely on well defined degrader approach with 2 to 3 sources

27. Nuclear Fragmentation-GCR composition is defined by same cross sections as would be observed at NSRL Mean free path for event 5-20 g/cm2 (energy, projectile and Target dependent

28. Geometry Factors on Mars:Transport of GCR through Mars atmosphere and neutron backscatter off of surface

29. Solar Minimum (Phi = 428 MV) 10 5 Top of Mars Atmosphere 10 4 Surface (all angles) Surface (65 Deg Cone for RAD) 10 3 10 2 1 10 0 10 -1 10 10 -2 0 4 8 12 16 20 24 28 Charge, Z GCR Spectra on Mars Surface Flux (Z)

30. Mars surface neutron environment- above 10 MeV neutron seasonal variation. NASA LaRC Model (p.o.c. John W. Wilson) Forward and Backward Neutron components and soil dependence

31. NASA Space Research Laboratory (NSRL) at BNL Mars Simulation Configuration Mars Regolith (0.5 meter) IC3 0.08288 g/cm2 Binary Filter 0 ~ 24.225 g/cm2 IC2 0.08288 g/cm2 IC1 0.08288 g/cm2 Ion Chamber/SWIC (RW302) 0.09827 g/cm2 Booster Window 0.10287 g/cm2 Biological Target beam CO2 (16 g/cm2) Air 0.03482 g/cm2 Air 0.01471 g/cm2 Air 0.4257 g/cm2 Air 0.12281 g/cm2 Air 0.08274 g/cm2 Air 0.05379 ~ 0.08604 g/cm2

32. Summary • NSRL capabilities need to evolve from early work on track segment irradiations for a few select HZE nuclei and protons towards validation and counter-measure design studies with realistic SPE and GCR simulations • Challenges include • Better understanding of temporal dependence of biological models for extended duration or fractionated exposures • Mixed-field design using energy switching, multiple ion sources, and complex degrader (shielding) configurations • Dosimetry needs for mixed fields including secondary neutrons for a Mars surface simulation • NASA expects to utilize NSRL beyond original 15-to-20 year plan, which may require unforeseen upgrades and replacements to facility over its lifetime

33. Backup material

34. Research Major Deliverables • Develop the Knowledge to Accurately Estimate andReduce Risk: • Understand radiation effects on health and performance through ground-based research • Achieve accuracy required for cost effective risk  prediction    • Develop approaches to prevent acute risks and reduce chronic risks • Evaluate mitigation approaches (shielding or biological) for reducing risks   • Utilize data from precursor robotic missions to characterize crew exposure • Operate and maintain the NSRL to facilitate this research • Develop Recommendations and Requirements for: • Risk projection models for NASA programs • Acceptable levels of risk (acute & chronic dose limits) • Crew constraints, mission length and operations • Provide Capabilities: • Crew risk projection and analysis • Concept evaluation • Architectural and mission assessment

35. 0.05 1000 GeV/nucleon 0.1 0.2 0.6 1 2 Fe 100 Ca Ar Si Ne O LET, keV/µm 10 N RBE C 1 He H 0.1 1 10 100 1000 Range, cm Shielding Spacesuit Test Tube Mouse Person Atmosphere LET vs. Range, Energy

36. Improving Cancer Projections Focus? Human epidemiology data (age/gender) No. Studied by NCI, BEIR, etc. Excess Relative or Additive Risk (ERR/EAR) Assumption: Heavy ion effects can be scaled to Gamma-rays? Tissue specific risk transfer, n Yes, 3rd Largest uncertainty Tissue Specific Cancer Rate (Mortality/Incidence) Yes, 2nd Largest uncertainty Dose & Dose-Rate Effectiveness factor, DDREF Assumption: Risk is linear & additive over mixed high- & low-LET env.? Radiation Quality (Q/RBE) Yes, Largest uncertainty Double Detriment Life Table (US Population – age/gender) Space particle spectra, F(L=LET) Assumptions: Sensitivity to radiation does not change in Ave. US Population and does not vary with radiation quality? Smallest uncertainty Mission/Astronaut Specific Cancer Risk Uncertainties

37. Current Model- continued • q(a) = probability to die for age a and a+1 based on US mortality rate, M (all causes) and exposure dependent cancer rate, m • Probability to survive to age ‘a’ • Mortality rate for ion fluence F, of LET, L (n=transfer model weight) • Excess lifetime risk (ELR) • Risk of exposure induced-death (REID)

38. http://srhp.jsc.nasa.gov/ Saganti/Cucinotta: Space Science Reviews 2004

39. Solar Min and Solar Max

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

41. Approaches to Human Risk Assessment Theory Animal model: Molecular/Cell event by space radiation Experiments/ Theory Human Risk from Space Radiation Nature and relative sensitivity to HZE ions Relative value of Initiating event Human Cells: Molecular/ Cell event by Space Radiation Animal Cells: Molecular/Cell event by Space Radiation Experiments/ Theory Experiments/ Theory Nature and relative sensitivity to HZE ions

42. Carcinogenesis: Targeted vs Non-Targeted Effects Radiation interacts with DNA causing genetic changes leading to cancer: Radiation causes aberrant signals between cells leading to cancer

43. GCR and SPE Dose: Materials & Tissue- GCR higher energy producing secondary radiation No Tissue Shielding With Tissue Shielding August 1972 SPE