CERN Course

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

2
What Are the Problems Associatedwith Human
Radiation Exposure?

• Acute (High Intensity-Short DurationDeterministic
  Effects)
• 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 lt3 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)

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 bodys
  ability to replace (blood-loss) and repair
  (radiation damage) in cases of such insults

4
The General Problem

• NASA needs to be able to PREDICT DOSES or at
  least estimate conservative maximums
• GCRSolar Modulation Fluctuations
• (OR any Interstellar Spectral fluctuations???)
• Solar Particle Events
• CMEs lower flux events
• In LEO, Trapped Radiation fluxes are significant
  in low shielding situations

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• For Dose D, the Rad (100 ergs/gm) has been
  replaced by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

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 radiations 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• For CHRONIC Doses, the Rem has been replaced by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

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 ChronicStochastic
  Effects)
• E S WT HT ST WT SR ò WR DRT dT

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 lt 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
  TransferEnergy deposited per unit track-length
  by ionizing radiation) exposure such as Heavy
  Ions are UNKNOWN
• Acute Dose Limits are NOT related to Chronic
  Limits

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
• AccidentsSporadic and low statistics.
• Clinical ExposuresLow 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

10
Energy Loss by Heavy Ions in Tissue
From NASA SPP
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 103 mm2
• 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

12
DNA-Double Strand BreaksComplex 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

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
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 leukemias 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
15
Current Model- continued

• q(a) probability to die for age a and a1 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
  (ntransfer model weight)
• Excess Lifetime Risk (ELR)
• Risk of Exposure Induced-Death (REID)

Slide Courtesy of F. Cucinotta, NASA/JSC
16
Transfer ModelsAvailable data? Populations ?
Individuals

• Cohort baseline BJ (unexposed group)
• US Baseline BA
• aA linear coefficient fit to exposed cohort
• Additive Transfer
• RiskA BA aJ x Dose
• Multiplicative Transfer
• RiskM BA/ BJ x aJ x Dose
• Accuracy?
• large variations for specific tissue sites
• healthy workers or individuals
• genetic background
• dietary/environmental
• untested for space radiation non-cancer risks

Additive Transfer radiation acts independent
of spontaneous cancer risks Multiplicative
Transfer radiation risk depends on spontaneous
cancer risks
LSS Transfer to US (NCRP Report 126)
Slide Courtesy of F. Cucinotta, NASA/JSC
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
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
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 GSD1.8

• Space missions-trial Q convoluted with trial LET
  spectra to form sample rate

Slide Courtesy of F. Cucinotta, NASA/JSC
20
Accuracy of Physics Models 20(environments,
transport, shielding)
ISS Mission
Slide Courtesy of F. Cucinotta, NASA/JSC
21
PDF for Physics Uncertainties- GCR
Slide Courtesy of F. Cucinotta, NASA/JSC
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
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, SNPs-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
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
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
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.

27
Possible Strategies

• Classical Solutions Time, Shielding Distance
• Distancewe can do nothing about
• TimeMore powerful rockets to reduce mission
  durations and thus exposure time
• ShieldingDoable from the physics standpoint but
  Expensive from the standpoint of weight ( )
• Long Surface StaysUse local soil overburden as
  shielding material