Surviving in space: the challenges of a manned mission to Mars

1. Surviving in space: the challenges of a manned mission to Mars Lecture 2 Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

2. What Are the Problems Associatedwith Human Radiation Exposure? • Acute (High Intensity-Short Duration—DeterministicEffects) • Serious Debilitation and Death (within Hours to Months) • NOT GENERALLY THE BIGGEST PROBLEM FACED in Long Term Human Space Travel (Because the potential sources of this kind of threat are easier to mitigate). • Chronic (Low Intensity-Long Duration— Stochastic Effects) • Increased Risk of Cancer in the Future (Acceptable = <3% Increase) • Potential Increased Risk of Other Diseases (Coronary, Brain Cell Loss) • Increased Risk of Debilitations Like Cataracts… • THE REAL HURDLE (Due to “Bureaucratic” Career Dose Limits) Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

3. Contrasting Acute v. Chronic • Imagine having to set limits on blood-loss • For Acute loss situations over a few hours, the amount of loss (without replacement) before serious health effects may occur is perhaps as much as a few liters… • …On the other hand, for Chronic loss situations like blood-donors, one might safely donate one liter every 6 weeks, or almost 350 liters over a 40 year “career.” • The reason for the difference is the human body’s ability to replace (blood-loss) and repair (radiation damage) in cases of such “insults”… Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

4. The General Problem • NASA needs to be able to PREDICT DOSESor at least estimate conservative maximums • GCR—Solar Modulation Fluctuations • (OR— + any Interstellar Spectral fluctuations???) • Solar Particle Events • CME’s + lower flux events • In LEO, Trapped Radiation fluxes are significant in low shielding situations… Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

5. A Short Primer on Dose • Radiation Dose: • Energy deposited per gm (~cm3) of tissue by Ionizing Radiation • For Dose D, the Rad (100 ergs/gm) has been replaced by: • …the Gray (Gy) = J/kg = 100 Rad, • …or more commonly: 1 cGy = 1 Rad Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

6. Acute v. Chronic Equivalent Dose • Equivalent Dose — Dose Modified by Effect in “Generic” Human Tissue • Quality Factor Modifiers, WR (RBE) with respect to gamma radiation’s effect for each kind of radiation R, summed over all tissues, T… HTR = SR WR DRT • For CHRONIC Doses, the Rem has been replaced by the Sievert (Sv) = 100 Rem • For ACUTE Doses, the Dose is given in Gray-Equivalent (Gy-Eq) = 100 Rads of X-Rays Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

7. “Effective Dose Equivalent” • Effective Dose Equivalent — Uses a Different Weighting Factor for EACH kind of tissue, WT, summed over EACH “Organ” and then over the whole body… • Also quoted in Sieverts (for Chronic—Stochastic Effects)… • E =S WT HT =ST WT [ SRò WR DRT dT] Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

8. Effects of Dose • ACCUTE DOSES (High Short Time Exposures) • 4.5 Gy = LD 50/60 (50% Lethal in 60 Days) [without medical intervention…] • 1.0 Gy = “Radiation Sickness” (Nausea, Diarrhea) • No Macroscopically Observable effects < 0.1 Gy… • CHRONIC DOSES (Low Continual Exposure) • Increased Cancer and other risks (Coronary, Eye…) • No Observable Short-Term effects… • Long-Term Effects from High LET (Linear Energy Transfer—Energy deposited per unit track-length by ionizing radiation) exposure such as Heavy Ions are UNKNOWN… • Acute Dose Limits are NOT related to Chronic Limits Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

9. Where do we get Data on the Effects of Doses? • Actual Human Exposures • Hiroshima Survivors represent the best extant cohort for long term effects… • Accidents—Sporadic and low statistics…. • Clinical Exposures—Low Doses or in Radiation Therapy exposures, localized high doses… No Controls… • Existing Astronaut “cohort”… • Animal Exposures • Inter-species extrapolation uncertainties… • Isolated Cell Culture Exposures • In Vitro cells do not behave like there conterparts In Vivo Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

10. Energy Loss by Heavy Ions in Tissue From NASA SPP Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

11. On The Baseline Mars Mission~ 1 Fe Traversal PER CELL • The “Deep Space” GCR Fe ~ 1 per m2 Ster Sec… • Human Body ~ 1 m2 * 4p Ster or ~10 Fe/sec • Baseline Mission = 3 Years ~ 108 sec • So, there will be 109 Fe traversals per mission • 1 m2 = 1012 mm2 & each human cell ~ 103mm2 • …Or, ~109 cells in a typical cross section view • …Thus, ~ 1 Fe traversal PER CELL !!! • The Mission Volunteer Sign-Up Sheet will be Available After My Talk… Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

12. DNA-Double Strand Breaks“Complex Lesions” & “Biological Dose • The latest idea is that multiple breaks within 30 base pairs on a DNA strand is a better measure of the likelihood of causing a cancer to form than other measures of dose. • We cannot yet calculate that liklihood from “first principles.” • We can estimate it from empirical radiation exposure data… Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

13. Current Cancer Risk Model (NCRP-132) 1) Estimates of radiation induced cancer mortality are based on the atomic-bomb death certificate data for 1950 through 1990. • Other human data (reactor workers, patients) used as checks for consistency 2) A minimum latency period following exposure for radiation induced cancers of 10-years for solid cancers is assumed. For leukemia, minimum latency of 2-years, however risks are multiplied by 0.1, 0.25, 0.5, 0.75, 0.9, and 1 for years 3, 4, 5, 7, and 8 or more years after exposure, respectively. 3) The excess relative risk for solid cancer is assumed to be constant over time following exposure. For leukemia a decline in excess risk with time after exposure is assumed. 4) The baseline survival and cancer rates for astronauts are assumed as those of the US population (SEER, 2000). Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

14. Current Cancer Risk Model (NCRP-132)(Continued) 5) The transfer of risk from the Japanese to the US population for solid cancers is made using the average of the multiplicative and additive transfer models, and for leukemia’s using the additive transfer model. 6) The dose response for the acute exposures of the Japanese survivors is assumed to be a linear function of dose. For leukemia a linear-quadratic dose response function is used. 7) For chronic exposures a dose and dose-rate reduction factors of two is assumed. The quadratic term in the leukemia response model is set to zero. 8) For high-LET radiation, an LET dependent radiation quality factor, Q(L) recommended by the ICRP is used to scale the doses (No other factors in the model are assumed to depend on radiation quality). Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

15. 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) Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

16. Transfer ModelsAvailable data Populations  Individuals* Additive Transfer: radiation acts independent of spontaneous cancer risks Multiplicative Transfer: radiation risk depends on spontaneous cancer risks • Cohort baseline BJ (unexposed group) • US Baseline BA • aA linear coefficient fit to exposed cohort Additive Transfer: RiskA = BA + aJx Dose Multiplicative Transfer: RiskM = BA/ BJ x aJx Dose • Accuracy? • large variations for specific tissue sites • healthy workers or individuals • genetic background • dietary/environmental • untested for space radiation non-cancer risks LSS Transfer to US (NCRP Report 126) Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

17. Methods for Uncertainty Estimates • Method: Monte Carlo sampling over each factor in model based on current knowledge to form Probability Distribution Function (PDF) • PDF defined to bound values of each factor (quantile) x: • Cancer mortality rate for ions • Physics PDF based on comparisons to flight data • Use of REID corrects for competing risks (important for Mars mission) Factors (NCRP 126): xD = DS86 (dosimetry of A-bombs) xS = Statistical errors xT = pop. transfer xP = Bias xDr = Dose-rate effects xQ = Quality factors xL = physics (transport/dosimetry) Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

18. Radiation Quality Effects • Tradition- Effects increase to about 100-200 keV/mm and then decline due to “overkill” • Mechanisms: • Energy deposition in Biomolecules • Cluster DNA damage site • Gene deletion/mutation • Chromosomal aberrations • Sterilization term in dose-response • Genomic instability • LET or dose thresholds in activating molecular pathways (epigenetic effects) Cell Death is good Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

19. Uncertainties in Biological Effectiveness • Trial Function, Q(L) • Sampling: • L0 [1, 15] (flat 5 to 10) • Lm [50, 250] (flat 80 to 150) • Declining slope, p [0,2] • Qp = 30 log-normal with GSD=1.8 • Space missions-trial Q convoluted with trial LET spectra to form sample rate Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

20. Accuracy of Physics Models: + 20%(environments, transport, shielding) ISS Mission Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

21. PDF for Physics Uncertainties- GCR Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

22. Fatal Cancer Risk per Rad vs. LET • Average Life-loss from radiation cancer death • (40-yr at exposure) low LET: • Leukemia 20 yr • Solid Cancers • Multiplicative Transfer 12-yr • Additive Transfer 20-yr • HIGH LET??? Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

23. Uncertainties not Included • Deviation from linear-additivity models • Radiation quality and latency or progression • Models assume a constant ERR (Equivalent Relative Risk) for solid cancers with no time-dependence on radiation quality • Animal and cellular models suggest decreased latency with increasing LET and ERR declines after saturation • Possible uncertainties for mixed fields and progression not modeled • Radiation quality and susceptibility • Population averaged values do not account for dispersion due to genetic factors (familial, high and low penetrance genes, SNP’s-Single Nucleotide Polymorphisms) • Neutron carcinogenesis studies show RBE variations across mouse strains for same tissue • Non-cancer mortality • Dose limits need to consider life-loss per death across each cause • For Mars mission non-cancer risks may be a significant competing risk to radiation carcinogenesis Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

24. High LET- Protraction Effects Pulmonary Tumors - fission neutrons in B6CF1 mice (Fry et al., Env. Int. 1, (1972)) Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

25. Radiation “Risqué”- transgender estimates*(M(a) = Net Mortality & MC(a) = Cancer Mortality) *Differences between males and females are approximate level of change for calendar year changes Slide Courtesy of F. Cucinotta, NASA/JSC Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

26. Summary of Issues • Acute effects are more predictable than Chronic effects for Space Radiation Exposures… • Cancer Risk is the Primary Chronic Effect. • Big uncertainties exist in estimating risks because: • Effects from high LET radiation are poorly known • Cancer causes themselves are not well understood. • Current Policies Require Limiting Risks to the same values as for Earth-based workers. Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation

27. Possible Strategies • Classical Solutions: Time, Shielding & Distance… • Distance—we can do nothing about… • Time—More powerful rockets to reduce mission durations and thus exposure time… • Shielding—Doable from the physics standpoint… but Expensive from the standpoint of weight (& $$$) • Long Surface Stays—Use local soil overburden as shielding material… Dosimetry and the Effects of the Exposure of Humans to Heavily Ionizing Radiation