# Presentation: 690054

## 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**

## 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

## 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

**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*

## 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

- 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*

## Cancer Uncertainty Assessments

**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

## 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

##  Fatal Cancer Risk at Solar Minimum(20 g/cm2 Aluminum Shielding)

| Mission | D, Gy | E, Sv | %REID | 95% CI |
| --- | --- | --- | --- | --- |
|  |  | Males |  |  |
| Lunar (180 d) | 0.06 | 0.14 | 0.56 | [0.19,1.92] |
| Mars (600 d) | 0.36 | 0.87 | 3.2 | [1.0,10.5] |
| Mars (1000 d) | 0.41 | 0.96 | 3.4 (3.2)* | [1.1,11.0] |
|  |  | Females |  |  |
| Lunar (90 d) | 0.06 | 0.14 | 0.68 | [0.21,2.4] |
| Mars (600 d) | 0.36 | 0.87 | 3.9 | [1.2, 12.8] |
| Mars (1000 d) | 0.41 | 0.96 | 4.1 (4.5)** | [1.4, 14.4] |

- *Parenthesis exclude Prostate cancer; **Parenthesis LSS-report 12 (others report 13)

## 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

- 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**

| Age, yr | Females |  | Males |  |
| --- | --- | --- | --- | --- |
|  | Previous
(2001) | Current
(2006) | Previous
(2001) | Current
(2006) |
| 30 | 54 | 112 | 91 | 142 |
| 35 | 62 | 132 | 104 | 166 |
| 40 | 73 | 150 | 122 | 186 |
| 45 | 89 | 182 | 148 | 224 |
| 50 | 115 | 224 | 191 | 273 |

## 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

**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

**The Space Radiation Environment**

**Trapped Radiation**:
- medium energy protons and electrons
- effectively mitigated by shielding
- mainly relevant to ISS
- MAIN PROBLEM: develop accurate dynamic model

## D=F x LET

- H=D x Q(LET)

## 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**

## 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

## 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

## Spatial Scales- continued

- Space:				   _(GCR proton hits/day__ ; __HZE)_
- DNA damage repair foci ~0.5 m2                 (0.002 per day /  1x10-6)
- Chromosome cross sections ~ 2 m2          (0.01 per day /  2x10-4)
- Cell Nucleus ~200 m2    `		           (1 per day/ 0.02)
- Interacting cell matrix ~1000 m2                    (>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

## Track Structure of Space Radiation

- 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 defines width of track corresponding to maximum distance of energy deposition laterally from track

- Nuclei of LET = 150 keV/m

- Monte-Carlo simulation of ionization patterns (He 0.45 MeV/u; C (10 MeV/u), Si (90 MeV/u) and Fe (1 GeV/u)

## Slide 16

## 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

## Space Radiation Research- The Next 20-yrs

**Mars Exploration**
**Missions**
**by 2030**

**Lunar outpost **
**Missions up to 240 days**

**Lunar Sortie**
**Missions**
**by 2020**

**2008–2014**

**2015–2023**

**2024–2030**

**Contributions**
**to National**
**Priorities**

-   Contribute to increased understanding of solar physics; Apply biomarker technologies to problems on Earth

- Perform research on dose-rate effects of protons, develop shielding design tools; apply probabilistic risk assessment to lunar missions

- Validate radiation environment and transport models using lunar data; Validate models of proton dose-rate effects

- Develop and deploy operational strategies for managing SPE risks; Apply biomarker methods to samples from lunar crews

- Use NSRL to simulate space radiation to understand their biological effects; Compete radiation transport codes and design tools

- Continue NSRL research on risks; perform research on biological countermeasures;
- optimize shielding designs for Mars missions

- 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

- Finish NSRL research on countermeasures;
- Develop diagnostics of radio-sensitivity and gene therapy for prevention and/or treatment of radiation damage

-    Design exploration missions; Apply new knowledge of
-    radiation effects and  NASA computational biology models to human diseases on Earth

- 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

**Agency**
**Mission**

## 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

## Significance Tests of Shielding Effectiveness

**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*

## 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

## Historically Large Solar Proton Events

- Modern Era (1956-2005)

- Recent Era (1550-2000)
*McKracken et al*

## August 1972 Solar Particle Event

**August 1972 Solar Particle Event**

**Oct./Nov. 2003 Solar Particle Event**

- Dose-rates
- at deep
-  tissues

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

## 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

## Slide 26

## 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

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

## GCR Spectra on Mars Surface

**GCR Spectra on Mars Surface**

- Flux (Z)

## Mars surface neutron environment- 

**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

## NASA Space Research Laboratory (NSRL) at BNL

- 0.10287 g/cm2

**NASA Space Research Laboratory (NSRL) at BNL**
- Mars Simulation Configuration

**IC2**
- 0.08288 g/cm2

**IC1**
- 0.08288 g/cm2

**Ion Chamber/SWIC (RW302)**
- 0.09827 g/cm2

**Binary Filter**
- 0 ~ 24.225 g/cm2

- Air
- 0.05379 ~ 0.08604 g/cm2

- Air
- 0.4257 g/cm2

- Air
- 0.12281 g/cm2

- Air
- 0.01471 g/cm2

**IC3**
- 0.08288 g/cm2

- Air
- 0.03482 g/cm2

- Air
- 0.08274 g/cm2

**Biological**
**Target**** **

- beam

- CO2
- (16 g/cm2)

- Mars Regolith (0.5 meter)

## 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

## Backup material

## Research Major Deliverables 

- 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

**Research Major Deliverables**

## LET vs. Range, Energy

**LET vs. Range, Energy**

## Improving Cancer Projections

**Dose & Dose-Rate**
** ****Effectiveness factor,**
**DDREF**

**Radiation Quality**
** ****(Q/RBE)**

**Space particle **
**spectra, F(L=LET)**

**Human epidemiology**
**data (age/gender)**

_**Focus?**_

**Double Detriment Life Table**
**(US Population – age/gender)**

**Mission/Astronaut**
**Specific Cancer Risk**
**Uncertainties**

- No. Studied
- by NCI, BEIR,   etc.

- Smallest
- uncertainty

- Yes, 2nd
- Largest uncertainty

- Yes, Largest
- uncertainty

**Improving Cancer Projections**

**Tissue Specific Cancer Rate**
**(Mortality/Incidence)**

**Tissue specific risk **
**transfer, ******

- Yes, 3rd
- Largest uncertainty

**Excess Relative or **
**Additive Risk (ERR/EAR)**

**Assumption: **
**Heavy ion effects**
** ****can be scaled **
**to Gamma-rays?**

**Assumption: **
**Risk is linear &**
** ****additive over mixed high-**
**& low-LET env.?**

**Assumptions: **
**Sensitivity to radiation **
**does not change in Ave. US**
**Population and does not vary **
**with radiation quality?**

## 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 (****transfer model weight**)*
- Excess lifetime risk (ELR)
- Risk of exposure induced-death (REID)

## http://srhp.jsc.nasa.gov/ 

- _[http://srhp.jsc.nasa.gov/](http://srhp.jsc.nasa.gov/)__ _

- Saganti/Cucinotta: Space Science Reviews 2004

## Solar Min and Solar Max

## NASA Space Radiation Lab (NSRL)

**NASA Space Radiation Lab (NSRL)**
** ****at DOE’s Brookhaven National Laboratory**** **

**Medical Dept**.

**Biology Dept.**

## Approaches to Human Risk Assessment

**Human Risk from Space Radiation**

**Animal model: **
**Molecular/Cell **
**event by space **
**radiation**

**Human Cells:**
**Molecular/**
**Cell event by**
**Space Radiation**

**Nature and relative **
**sensitivity to HZE ions**

**Approaches to Human Risk Assessment**

**Experiments/**
**Theory**

**Relative value of **
**Initiating event**

**Experiments/**
**Theory**

**Nature and relative **
**sensitivity to HZE ions**

**Experiments/**
**Theory**

**Animal Cells:**
**Molecular/Cell event by**
**Space Radiation**

## Carcinogenesis: Targeted vs Non-Targeted Effects

**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**

## GCR and SPE Dose: Materials & Tissue- GCR higher energy producing secondary radiation

- No Tissue Shielding

- With Tissue Shielding

- August 1972 SPE

## Slide 44