Effects of ionizing radiation in spaceflight

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Effects_of_ionizing_radiation_in_spaceflight

The Phantom Torso, as seen here in the Destiny laboratory on the International Space Station (ISS), is designed to measure the effects of radiation on organs inside the body by using a torso that is similar to those used to train radiologists on Earth. The torso is equivalent in height and weight to an average adult male. It contains radiation detectors that will measure, in real-time, how much radiation the brain, thyroid, stomach, colon, and heart and lung area receive on a daily basis. The data will be used to determine how the body reacts to and shields its internal organs from radiation, which will be important for longer duration space flights.

Astronauts are exposed to approximately 72 millisieverts (mSv) while on six-month-duration missions to the International Space Station (ISS). Longer 3-year missions to Mars, however, have the potential to expose astronauts to radiation in excess of 1,000 mSv. Without the protection provided by Earth's magnetic field, the rate of exposure is dramatically increased. The risk of cancer caused by ionizing radiation is well documented at radiation doses beginning at 100 mSv and above.

Related radiological effect studies have shown that survivors of the atomic bomb explosions in Hiroshima and Nagasaki, nuclear reactor workers and patients who have undergone therapeutic radiation treatments have received low-linear energy transfer (LET) radiation (x-rays and gamma rays) doses in the same 50-2,000 mSv range.

Composition of space radiation

While in space, astronauts are exposed to radiation which is mostly composed of high-energy protons, helium nuclei (alpha particles), and high-atomic-number ions (HZE ions), as well as secondary radiation from nuclear reactions from spacecraft parts or tissue.

The ionization patterns in molecules, cells, tissues and the resulting biological effects are distinct from typical terrestrial radiation (x-rays and gamma rays, which are low-LET radiation). Galactic cosmic rays (GCRs) from outside the Milky Way galaxy consist mostly of highly energetic protons with a small component of HZE ions.

Prominent HZE ions:

• Carbon (C)
• Oxygen (O)
• Magnesium (Mg)
• Silicon (Si)
• Iron (Fe)

GCR energy spectra peaks (with median energy peaks up to 1,000 MeV/amu) and nuclei (energies up to 10,000 MeV/amu) are important contributors to the dose equivalent.

Uncertainties in cancer projections

One of the main roadblocks to interplanetary travel is the risk of cancer caused by radiation exposure. The largest contributors to this roadblock are: (1) The large uncertainties associated with cancer risk estimates, (2) The unavailability of simple and effective countermeasures and (3) The inability to determine the effectiveness of countermeasures. Operational parameters that need to be optimized to help mitigate these risks include:

• length of space missions
• crew age
• crew sex
• shielding
• biological countermeasures

Major uncertainties

• effects on biological damage related to differences between space radiation and x-rays
• dependence of risk on dose-rates in space related to the biology of DNA repair, cell regulation and tissue responses
• predicting solar particle events (SPEs)
• extrapolation from experimental data to humans and between human populations
• individual radiation sensitivity factors (genetic, epigenetic, dietary or "healthy worker" effects)

Minor uncertainties

• data on galactic cosmic ray environments
• physics of shielding assessments related to transmission properties of radiation through materials and tissue
• microgravity effects on biological responses to radiation
• errors in human data (statistical, dosimetry or recording inaccuracies)

Quantitative methods have been developed to propagate uncertainties that contribute to cancer risk estimates. The contribution of microgravity effects on space radiation has not yet been estimated, but it is expected to be small. However as microgravity has been shown to modulate cancer progression, more research is needed into the combined effects of microgravity and radiation on carcinogenesis. The effects of changes in oxygen levels or in immune dysfunction on cancer risks are largely unknown and are of great concern during space flight.

Types of cancer caused by radiation exposure

Studies are being conducted on populations accidentally exposed to radiation (such as Chernobyl, production sites, and Hiroshima and Nagasaki). These studies show strong evidence for cancer morbidity as well as mortality risks at more than 12 tissue sites. The largest risks for adults who have been studied include several types of leukemia, including myeloid leukemia and acute lymphatic lymphoma as well as tumors of the lung, breast, stomach, colon, bladder and liver. Inter-sex variations are very likely due to the differences in the natural incidence of cancer in males and females. Another variable is the additional risk for cancer of the breast, ovaries and lungs in females. There is also evidence of a declining risk of cancer caused by radiation with increasing age, but the magnitude of this reduction above the age of 30 is uncertain.

It is unknown whether high-LET radiation could cause the same types of tumors as low-LET radiation, but differences should be expected.

The ratio of a dose of high-LET radiation to a dose of x-rays or gamma rays that produce the same biological effect are called relative biological effectiveness (RBE) factors. The types of tumors in humans who are exposed to space radiation will be different from those who are exposed to low-LET radiation. This is evidenced by a study that observed mice with neutrons and have RBEs that vary with the tissue type and strain.

Measured rate of cancer among astronauts

The measured change rate of cancer is restricted by limited statistics. A study published in Scientific Reports looked over 301 U.S. astronauts and 117 Soviet and Russian cosmonauts, and found no measurable increase in cancer mortality compared to the general population, as reported by LiveScience.

An earlier 1998 study came to similar conclusions, with no statistically significant increase in cancer among astronauts compared to the reference group.

Approaches for setting acceptable risk levels

The various approaches to setting acceptable levels of radiation risk are summarized below:

Comparison of radiation doses - includes the amount detected on the trip from Earth to Mars by the RAD on the MSL (2011 - 2013).

• Unlimited Radiation Risk - NASA management, the families of loved ones of astronauts, and taxpayers would find this approach unacceptable.
• Comparison to Occupational Fatalities in Less-safe Industries - The life-loss from attributable radiation cancer death is less than that from most other occupational deaths. At this time, this comparison would also be very restrictive on ISS operations because of continued improvements in ground-based occupational safety over the last 20 years.
• Comparison to Cancer Rates in General Population - The number of years of life-loss from radiation-induced cancer deaths can be significantly larger than from cancer deaths in the general population, which often occur late in life (> age 70 years) and with significantly less numbers of years of life-loss.
• Doubling Dose for 20 Years Following Exposure - Provides a roughly equivalent comparison based on life-loss from other occupational risks or background cancer fatalities during a worker's career, however, this approach negates the role of mortality effects later in life.
• Use of Ground-based Worker Limits - Provides a reference point equivalent to the standard that is set on Earth, and recognizes that astronauts face other risks. However, ground workers remain well below dose limits, and are largely exposed to low-LET radiation where the uncertainties of biological effects are much smaller than for space radiation.

NCRP Report No. 153 provides a more recent review of cancer and other radiation risks. This report also identifies and describes the information needed to make radiation protection recommendations beyond LEO, contains a comprehensive summary of the current body of evidence for radiation-induced health risks and also makes recommendations on areas requiring future experimentation.

Current permissible exposure limits

Career cancer risk limits

Astronauts' radiation exposure limit is not to exceed 3% of the risk of exposure-induced death (REID) from fatal cancer over their career. It is NASA's policy to ensure a 95% confidence level (CL) that this limit is not exceeded. These limits are applicable to all missions in low Earth orbit (LEO) as well as lunar missions that are less than 180 days in duration. In the United States, the legal occupational exposure limits for adult workers is set at an effective dose of 50 mSv annually.

Cancer risk to dose relationship

The relationship between radiation exposure and risk is both age- and sex-specific due to latency effects and differences in tissue types, sensitivities, and life spans between sexes. These relationships are estimated using the methods that are recommended by the NCRP and more recent radiation epidemiology information 

The principle of As Low As Reasonably Achievable

The as low as reasonably achievable (ALARA) principle is a legal requirement intended to ensure astronaut safety. An important function of ALARA is to ensure that astronauts do not approach radiation limits and that such limits are not considered as "tolerance values." ALARA is especially important for space missions in view of the large uncertainties in cancer and other risk projection models. Mission programs and terrestrial occupational procedures resulting in radiation exposures to astronauts are required to find cost-effective approaches to implement ALARA.

Evaluating career limits

Organ (T)	Tissue weighting factor (wT)
Gonads	0.20
Bone Marrow (red)	0.12
Colon	0.12
Lung	0.12
Stomach	0.12
Bladder	0.05
Breast	0.05
Liver	0.05
Esophagus	0.05
Thyroid	0.05
Skin	0.01
Bone Surface	0.01
Remainder*	0.05
*Adrenals, brain, upper intestine, small intestine, kidney, muscle, pancreas, spleen, thymus and uterus.

The risk of cancer is calculated by using radiation dosimetry and physics methods.

For the purpose of determining radiation exposure limits at NASA, the probability of fatal cancer is calculated as shown below:

1. The body is divided into a set of sensitive tissues, and each tissue, T, is assigned a weight, w_T, according to its estimated contribution to cancer risk.
2. The absorbed dose, D_γ, that is delivered to each tissue is determined from measured dosimetry. For the purpose of estimating radiation risk to an organ, the quantity characterizing the ionization density is the LET (keV/μm).
3. For a given interval of LET, between L and ΔL, the dose-equivalent risk (in units of sievert) to a tissue, T, H_γ(L) is calculated as
   ${\displaystyle H_{\gamma }(L)=Q(L)D_{\gamma }(L)}$
   where the quality factor, Q(L), is obtained according to the International Commission on Radiological Protection (ICRP).
4. The average risk to a tissue, T, due to all types of radiation contributing to the dose is given by
   ${\displaystyle H_{\gamma }=\int D_{\gamma }(L)Q(L)dL}$
   or, since ${\displaystyle D_{\gamma }(L)=L{F}_{\gamma }(L)}$, where F_γ(L) is the fluence of particles with LET=L, traversing the organ,
   ${\displaystyle H_{\gamma }=\int dLQ(L)F_{\gamma }(L)L}$
5. The effective dose is used as a summation over radiation type and tissue using the tissue weighting factors, w_γ
   ${\displaystyle E=\sum _{\gamma }{w}_{\gamma }{H}_{\gamma }}$
6. For a mission of duration t, the effective dose will be a function of time, E(t), and the effective dose for mission i will be
   ${\displaystyle E_i=\int E(t)dt}$
7. The effective dose is used to scale the mortality rate for radiation-induced death from the Japanese survivor data, applying the average of the multiplicative and additive transfer models for solid cancers and the additive transfer model for leukemia by applying life-table methodologies that are based on U.S. population data for background cancer and all causes of death mortality rates. A dose-dose rate effectiveness factor (DDREF) of 2 is assumed.

Evaluating cumulative radiation risks

The cumulative cancer fatality risk (%REID) to an astronaut for occupational radiation exposures, N, is found by applying life-table methodologies that can be approximated at small values of %REID by summing over the tissue-weighted effective dose, E_i, as

${\displaystyle Risk=\sum _{i=1}^N{E}_i{R}_0(ag{e}_i,sex)}$

where R₀ are the age- and sex- specific radiation mortality rates per unit dose.

For organ dose calculations, NASA uses the model of Billings et al. to represent the self-shielding of the human body in a water-equivalent mass approximation. Consideration of the orientation of the human body relative to vehicle shielding should be made if it is known, especially for SPEs.

Confidence levels for career cancer risks are evaluated using methods that are specified by the NPRC in Report No. 126 Archived 2014-03-08 at the Wayback Machine. These levels were modified to account for the uncertainty in quality factors and space dosimetry.

The uncertainties that were considered in evaluating the 95% confidence levels are the uncertainties in:

• Human epidemiology data, including uncertainties in
  • statistics limitations of epidemiology data
  • dosimetry of exposed cohorts
  • bias, including misclassification of cancer deaths, and
  • the transfer of risk across populations.
• The DDREF factor that is used to scale acute radiation exposure data to low-dose and dose-rate radiation exposures.
• The radiation quality factor (Q) as a function of LET.
• Space dosimetry

The so-called "unknown uncertainties" from the NCRP report No. 126 are ignored by NASA.

Models of cancer risks and uncertainties

Life-table methodology

The double-detriment life-table approach is what is recommended by the NPRC  to measure radiation cancer mortality risks. The age-specific mortality of a population is followed over its entire life span with competing risks from radiation and all other causes of death described.

For a homogenous population receiving an effective dose E at age a_E, the probability of dying in the age-interval from a to a+1 is described by the background mortality-rate for all causes of death, M(a), and the radiation cancer mortality rate, m(E,a_E,a), as:

${\displaystyle q(E,a_E,a)=\frac{M(a)+m(E,a_E,a)}{1+\frac{1}{2}\left[M(a)+m(E,a_E,a)\right]}}$

The survival probability to age, a, following an exposure, E at age a_E, is:

${\displaystyle S(E,a_E,a)=\prod _{u=a_E}^{a-1}\left[1-q(E,a_E,u)\right]}$

The excessive lifetime risk (ELR - the increased probability that an exposed individual will die from cancer) is defined by the difference in the conditional survival probabilities for the exposed and the unexposed groups as:

${\displaystyle ELR=\sum _{a=a_E}^{\mathrm{\infty }}\left[M(a)+m(E,a_E,a)\right]S(E,a_E,a)-\sum _{a=a_E}^{\mathrm{\infty }}M(a)S(0,a_E,a)}$

A minimum latency-time of 10 years is often used for low-LET radiation. Alternative assumptions should be considered for high-LET radiation. The REID (the lifetime risk that an individual in the population will die from cancer caused by radiation exposure) is defined by:

${\displaystyle REID=\sum _{a=a_E}^{\mathrm{\infty }}m(E,a_E,a)S(E,a_E,a)}$

Generally, the value of the REID exceeds the value of the ELR by 10-20%.

The average loss of life-expectancy, LLE, in the population is defined by:

${\displaystyle LLE=\sum _{a=a_E}^{\mathrm{\infty }}S(0,a_E,a)-\sum _{a=a_E}^{\mathrm{\infty }}S(E,a_E,a)}$

The loss of life-expectancy among exposure-induced-deaths (LLE-REID) is defined by:

${\displaystyle LLE-REID=\frac{LLE}{REID}}$

Uncertainties in low-LET epidemiology data

The low-LET mortality rate per sievert, m_i is written

${\displaystyle m(E,a_x,a)=\frac{m_0(E,a_x,a)}{DDREF}\frac{x_D{x}_s{x}_T{x}_B}{x_{Dr}}}$

where m₀ is the baseline mortality rate per sievert and x_α are quantiles (random variables) whose values are sampled from associated probability distribution functions (PDFs), P(X_a).

NCRP, in Report No. 126, defines the following subjective PDFs, P(X_a), for each factor that contributes to the acute low-LET risk projection:

1. P_dosimetry is the random and systematic errors in the estimation of the doses received by atomic-bomb blast survivors.
2. P_statistical is the distribution in uncertainty in the point estimate of the risk coefficient, r₀.
3. P_bias is any bias resulting for over- or under-reporting cancer deaths.
4. P_transfer is the uncertainty in the transfer of cancer risk following radiation exposure from the Japanese population to the U.S. population.
5. P_Dr is the uncertainty in the knowledge of the extrapolation of risks to low dose and dose-rates, which are embodied in the DDREF.

Risk in context of exploration mission operational scenarios

The accuracy of galactic cosmic ray environmental models, transport codes and nuclear interaction cross sections allow NASA to predict space environments and organ exposure that may be encountered on long-duration space missions. The lack of knowledge of the biological effects of radiation exposure raise major questions about risk prediction.

The cancer risk projection for space missions is found by

${\displaystyle m_J(E,a_E,a{)}_{lJ}(E,a_E,a)\int dL\frac{dF}{dL}L{Q}_{trial-J}(L)X_{L-J}}$

where ${\displaystyle \frac{dF}{dL}}$ represents the folding of predictions of tissue-weighted LET spectra behind spacecraft shielding with the radiation mortality rate to form a rate for trial J.

Alternatively, particle-specific energy spectra, F_j(E), for each ion, j, can be used

${\displaystyle m_J(E,a_E,a)=m_{lJ}(E,a_E,a)\sum _j(E)L(E)Q_{trial-J}(L(E))x_{L-J}}$.

The result of either of these equations is inserted into the expression for the REID.

Related probability distribution functions (PDFs) are grouped together into a combined probability distribution function, P_cmb(x). These PDFs are related to the risk coefficient of the normal form (dosimetry, bias and statistical uncertainties). After a sufficient number of trials have been completed (approximately 10⁵), the results for the REID estimated are binned and the median values and confidence intervals are found.

The chi-squared (χ²) test is used for determining whether two separate PDFs are significantly different (denoted p₁(R_i) and p₂(R_i), respectively). Each p(R_i) follows a Poisson distribution with variance ${\displaystyle \sqrt{p(R_i)}}$.

The χ² test for n-degrees of freedom characterizing the dispersion between the two distributions is

${\displaystyle {\chi }^2=\sum _n\frac{{\left[p_1(R_n)-p_2(R_n)\right]}^2}{\sqrt{p_1^2(R_n)+p_2^2(R_n)}}}$.

The probability, P(ņχ²), that the two distributions are the same is calculated once χ² is determined.

Radiation carcinogenesis mortality rates

Age-and sex-dependent mortality rate per unit dose, multiplied by the radiation quality factor and reduced by the DDREF is used for projecting lifetime cancer fatality risks. Acute gamma ray exposures are estimated. The additivity of effects of each component in a radiation field is also assumed.

Rates are approximated using data gathered from Japanese atomic bomb survivors. There are two different models that are considered when transferring risk from Japanese to U.S. populations.

• Multiplicative transfer model - assumes that radiation risks are proportional to spontaneous or background cancer risks.
• Additive transfer model - assumes that radiation risk acts independently of other cancer risks.

The NCRP recommends a mixture model to be used that contains fractional contributions from both methods.

The radiation mortality rate is defined as:

${\displaystyle m(E,a_E,a)=\left[ERR(a_E,a)M_c(a)+(1-v)EAR(a_E,a)\right]\frac{\sum _{L}Q(L)F(L)L}{DDREF}}$

Where:

• ERR = excess relative risk per sievert
• EAR = excess additive risk per sievert
• M_c(a) = the sex- and age-specific cancer mortality rate in the U.S. population
• F = the tissue-weighted fluence
• L = the LET
• v = the fractional division between the assumption of the multiplicative and additive risk transfer models. For solid cancer, it is assumed that v=1/2 and for leukemia, it is assumed that v=0.

Biological and physical countermeasures

Identifying effective countermeasures that reduce the risk of biological damage is still a long-term goal for space researchers. These countermeasures are probably not needed for extended duration lunar missions, but will be needed for other long-duration missions to Mars and beyond. On 31 May 2013, NASA scientists reported that a possible human mission to Mars may involve a great radiation risk based on the amount of energetic particle radiation detected by the RAD on the Mars Science Laboratory while traveling from the Earth to Mars in 2011-2012.

There are three fundamental ways to reduce exposure to ionizing radiation:

• increasing the distance from the radiation source
• reducing the exposure time
• shielding (i.e.: a physical barrier)

Shielding is a plausible option, but due to current launch mass restrictions, it is prohibitively costly. Also, the current uncertainties in risk projection prevent the actual benefit of shielding from being determined. Strategies such as drugs and dietary supplements to reduce the effects of radiation, as well as the selection of crew members are being evaluated as viable options for reducing exposure to radiation and effects of irradiation. Shielding is an effective protective measure for solar particle events. As far as shielding from GCR, high-energy radiation is very penetrating and the effectiveness of radiation shielding depends on the atomic make-up of the material used.

Antioxidants are effectively used to prevent the damage caused by radiation injury and oxygen poisoning (the formation of reactive oxygen species), but since antioxidants work by rescuing cells from a particular form of cell death (apoptosis), they may not protect against damaged cells that can initiate tumor growth.

Evidence sub-pages

The evidence and updates to projection models for cancer risk from low-LET radiation are reviewed periodically by several bodies, which include the following organizations:

• The NAS Committee on the Biological Effects of Ionizing Radiation
• The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)
• The ICRP
• The NCRP

These committees release new reports about every 10 years on cancer risks that are applicable to low-LET radiation exposures. Overall, the estimates of cancer risks among the different reports of these panels will agree within a factor of two or less. There is continued controversy for doses that are below 5 mSv, however, and for low dose-rate radiation because of debate over the linear no-threshold hypothesis that is often used in statistical analysis of these data. The BEIR VII report, which is the most recent of the major reports is used in the following sub-pages. Evidence for low-LET cancer effects must be augmented by information on protons, neutrons, and HZE nuclei that is only available in experimental models. Such data have been reviewed by NASA several times in the past and by the NCRP.

• Epidemiology data for low linear energy transfer radiation
• Radiobiology evidence for protons and HZE nuclei

Central nervous system effects from radiation exposure during spaceflight

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Central_nervous_system_effects_from_radiation_exposure_during_spaceflight

Travel outside the Earth's protective atmosphere, magnetosphere, and in free fall can harm human health, and understanding such harm is essential for successful crewed spaceflight. Potential effects on the central nervous system (CNS) are particularly important. A vigorous ground-based cellular and animal model research program will help quantify the risk to the CNS from space radiation exposure on future long distance space missions and promote the development of optimized countermeasures.

Possible acute and late risks to the CNS from galactic cosmic rays (GCRs) and solar proton events (SPEs) are a documented concern for human exploration of the Solar System. In the past, the risks to the CNS of adults who were exposed to low to moderate doses of ionizing radiation (0 to 2 Gy (Gray) (Gy = 100 rad)) have not been a major consideration. However, the heavy ion component of space radiation presents distinct biophysical challenges to cells and tissues as compared to the physical challenges that are presented by terrestrial forms of radiation. Soon after the discovery of cosmic rays, the concern for CNS risks originated with the prediction of the light flash phenomenon from single HZE nuclei traversals of the retina; this phenomenon was confirmed by the Apollo astronauts in 1970 and 1973. HZE nuclei are capable of producing a column of heavily damaged cells, or a microlesion, along their path through tissues, thereby raising concern over serious impacts on the CNS. In recent years, other concerns have arisen with the discovery of neurogenesis and its impact by HZE nuclei, which have been observed in experimental models of the CNS.

Human epidemiology is used as a basis for risk estimation for cancer, acute radiation risks, and cataracts. This approach is not viable for estimating CNS risks from space radiation, however. At doses above a few Gy, detrimental CNS changes occur in humans who are treated with radiation (e.g., gamma rays and protons) for cancer. Treatment doses of 50 Gy are typical, which is well above the exposures in space even if a large SPE were to occur. Thus, of the four categories of space radiation risks (cancer, CNS, degenerative, and acute radiation syndromes), the CNS risk relies most extensively on experimental data with animals for its evidence base. Understanding and mitigating CNS risks requires a vigorous research program that will draw on the basic understanding that is gained from cellular and animal models, and on the development of approaches to extrapolate risks and the potential benefits of countermeasures for astronauts.

Several experimental studies, which use heavy ion beams simulating space radiation, provide constructive evidence of the CNS risks from space radiation. First, exposure to HZE nuclei at low doses (<50 cGy) significantly induces neurocognitive deficits, such as learning and behavioral changes as well as operant reactions in the mouse and rat. Exposures to equal or higher doses of low-LET radiation (e.g., gamma or X rays) do not show similar effects. The threshold of performance deficit following exposure to HZE nuclei depends on both the physical characteristics of the particles, such as linear energy transfer (LET), and the animal age at exposure. A performance deficit has been shown to occur at doses that are similar to the ones that will occur on a Mars mission (<0.5 Gy). The neurocognitive deficits with the dopaminergic nervous system are similar to aging and appear to be unique to space radiation. Second, exposure to HZE disrupts neurogenesis in mice at low doses (<1 Gy), showing a significant dose-related reduction of new neurons and oligodendrocytes in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Third, reactive oxygen species (ROS) in neuronal precursor cells arise following exposure to HZE nuclei and protons at low dose, and can persist for several months. Antioxidants and anti-inflammatory agents can possibly reduce these changes. Fourth, neuroinflammation arises from the CNS following exposure to HZE nuclei and protons. In addition, age-related genetic changes increase the sensitivity of the CNS to radiation.

Research with animal models that are irradiated with HZE nuclei has shown that important changes to the CNS occur with the dose levels that are of concern to NASA. However, the significance of these results on the morbidity to astronauts has not been elucidated. One model of late tissue effects suggests that significant effects will occur at lower doses, but with increased latency. It is to be noted that the studies that have been conducted to date have been carried out with relatively small numbers of animals (<10 per dose group); therefore, testing of dose threshold effects at lower doses (< 0.5 Gy) has not been carried out sufficiently at this time. As the problem of extrapolating space radiation effects in animals to humans will be a challenge for space radiation research, such research could become limited by the population size that is used in animal studies. Furthermore, the role of dose protraction has not been studied to date. An approach to extrapolate existing observations to possible cognitive changes, performance degradation, or late CNS effects in astronauts has not been discovered. New approaches in systems biology offer an exciting tool to tackle this challenge. Recently, eight gaps were identified for projecting CNS risks. Research on new approaches to risk assessment may be needed to provide the necessary data and knowledge to develop risk projection models of the CNS from space radiation.

Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior or neurological disorders. Radiation and synergistic effects of radiation with other space flight factors may affect neural tissues, which in turn may lead to changes in function or behavior. Data specific to the spaceflight environment must be compiled to quantify the magnitude of this risk. If this is identified as a risk of high enough magnitude then appropriate protection strategies should be employed.

— Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009.

Introduction

Both GCRs and SPEs are of concern for CNS risks. The major GCRs are composed of protons, α-particles, and particles of HZE nuclei with a broad energy spectrum ranging from a few tens to above 10 000 MeV/u. In interplanetary space, GCR organ dose and dose-equivalent of more than 0.2 Gy or 0.6 Sv per year, respectively, are expected. The high energies of GCRs allow them to penetrate to hundreds of centimeters of any material, thus precluding radiation shielding as a plausible mitigation measure to GCR risks on the CNS. For SPEs, the possibility exists for an absorbed dose of over 1 Gy from an SPE if crew members are in a thinly shielded spacecraft or performing a spacewalk. The energies of SPEs, although substantial (tens to hundreds of MeV), do not preclude radiation shielding as a potential countermeasure. However, the costs of shielding may be high to protect against the largest events.

The fluence of charged particles hitting the brain of an astronaut has been estimated several times in the past. One estimate is that during a 3-year mission to Mars at solar minimum (assuming the 1972 spectrum of GCR), 20 million out of 43 million hippocampus cells and 230 thousand out of 1.3 million thalamus cell nuclei will be directly hit by one or more particles with charge Z> 15. These numbers do not include the additional cell hits by energetic electrons (delta rays) that are produced along the track of HZE nuclei  or correlated cellular damage. The contributions of delta rays from GCR and correlated cellular damage increase the number of damaged cells two- to three-fold from estimates of the primary track alone and present the possibility of heterogeneously damaged regions, respectively. The importance of such additional damage is poorly understood.

At this time, the possible detrimental effects to an astronaut's CNS from the HZE component of GCR have yet to be identified. This is largely due to the lack of a human epidemiological basis with which to estimate risks and the relatively small number of published experimental studies with animals. RBE factors are combined with human data to estimate cancer risks for low-LET radiation exposure. Since this approach is not possible for CNS risks, new approaches to risk estimation will be needed. Thus, biological research is required to establish risk levels and risk projection models and, if the risk levels are found to be significant, to design countermeasures.

Description of central nervous system risks of concern to NASA

Acute and late CNS risks from space radiation are of concern for Exploration missions to the moon or Mars. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks are possible neurological disorders such as Alzheimer's disease, dementia, or premature aging. The effect of the protracted exposure of the CNS to the low dose-rate (< 50 mGy h–1) of proton, HZE particles, and neutrons of the relevant energies for doses up to 2 Gy is of concern.

Current NASA permissible exposure limits

PELs for short-term and career astronaut exposure to space radiation have been approved by the NASA Chief Health and Medical Officer. The PELs set requirements and standards for mission design and crew selection as recommended in NASA-STD-3001, Volume 1. NASA has used dose limits for cancer risks and the non-cancer risks to the BFOs, skin, and lens since 1970. For Exploration mission planning, preliminary dose limits for the CNS risks are based largely on experimental results with animal models. Further research is needed to validate and quantify these risks, however, and to refine the values for dose limits. The CNS PELs, which correspond to the doses at the region of the brain called the hippocampus, are set for time periods of 30 days or 1 year, or for a career with values of 500, 1,000, and 1,500 mGy-Eq, respectively. Although the unit mGy-Eq is used, the RBE for CNS effects is largely unknown; therefore, the use of the quality factor function for cancer risk estimates is advocated. For particles with charge Z>10, an addition PEL requirement limits the physical dose (mGy) for 1 year and the career to 100 and 250 mGy, respectively. NASA uses computerized anatomical geometry models to estimate the body self-shielding at the hippocampus.

Evidence

Review of human data

Evidence of the effects of terrestrial forms of ionizing radiation on the CNS has been documented from radiotherapy patients, although the dose is higher for these patients than would be experienced by astronauts in the space environment. CNS behavioral changes such as chronic fatigue and depression occur in patients who are undergoing irradiation for cancer therapy. Neurocognitive effects, especially in children, are observed at lower radiation doses. A recent review on intelligence and the academic achievement of children after treatment for brain tumors indicates that radiation exposure is related to a decline in intelligence and academic achievement, including low intelligence quotient (IQ) scores, verbal abilities, and performance IQ; academic achievement in reading, spelling, and mathematics; and attention functioning. Mental retardation was observed in the children of the atomic-bomb survivors in Japan who were exposed to radiation prenatally at moderate doses (<2 Gy) at 8 to 15 weeks post-conception, but not at earlier or later prenatal times.

Radiotherapy for the treatment of several tumors with protons and other charged particle beams provides ancillary data for considering radiation effects for the CNS. NCRP Report No. 153 notes charge particle usage “for treatment of pituitary tumors, hormone-responsive metastatic mammary carcinoma, brain tumors, and intracranial arteriovenous malformations and other cerebrovascular diseases.” In these studies are found associations with neurological complications such as impairments in cognitive functioning, language acquisition, visual spatial ability, and memory and executive functioning, as well as changes in social behaviors. Similar effects did not appear in patients who were treated with chemotherapy. In all of these examples, the patients were treated with extremely high doses that were below the threshold for necrosis. Since cognitive functioning and memory are closely associated with the cerebral white volume of the prefrontal/frontal lobe and cingulate gyrus, defects in neurogenesis may play a critical role in neurocognitive problems in irradiated patients.

Review of space flight issues

The first proposal concerning the effect of space radiation on the CNS was made by Cornelius Tobias in his 1952 description of light flash phenomenon caused by single HZE nuclei traversals of the retina. Light flashes, such as those described by Tobias, were observed by the astronauts during the early Apollo missions as well as in dedicated experiments that were subsequently performed on Apollo and Skylab missions. More recently, studies of light flashes were made on the Russian Mir space station and the ISS. A 1973 report by the NAS considered these effects in detail. This phenomenon, which is known as a Phosphene, is the visual perception of flickering light. It is considered a subjective sensation of light since it can be caused by simply applying pressure on the eyeball. The traversal of a single, highly charged particle through the occipital cortex or the retina was estimated to be able to cause a light flash. Possible mechanisms for HZE-induced light flashes include direction ionization and Cherenkov radiation within the retina.

The observation of light flashes by the astronauts brought attention to the possible effects of HZE nuclei on brain function. The microlesion concept, which considered the effects of the column of damaged cells surrounding the path of an HZE nucleus traversing critical regions of the brain, originated at this time. An important task that still remains is to determine whether and to what extent such particle traversals contribute to functional degradation within the CNS.

The possible observation of CNS effects in astronauts who were participating in past NASA missions is highly unlikely for several reasons. First, the lengths of past missions are relatively short and the population sizes of astronauts are small. Second, when astronauts are traveling in LEO, they are partially protected by the magnetic field and the solid body of the Earth, which together reduce the GCR dose-rate by about two-thirds from its free space values. Furthermore, the GCR in LEO has lower LET components compared to the GCR that will be encountered in transit to Mars or on the lunar surface because the magnetic field of the Earth repels nuclei with energies that are below about 1,000 MeV/u, which are of higher LET. For these reasons, the CNS risks are a greater concern for long-duration lunar missions or for a Mars mission than for missions on the ISS.

Radiobiology studies of central nervous system risks for protons, neutrons, and high-Z high-energy nuclei

Both GCR and SPE could possibly contribute to acute and late CNS risks to astronaut health and performance. This section presents a description of the studies that have been performed on the effects of space radiation in cell, tissue, and animal models.

Effects in neuronal cells and the central nervous system

Neurogenesis

The CNS consists of neurons, astrocytes, and oligodendrocytes that are generated from multipotent stem cells. NCRP Report No. 153 provides the following excellent and short introduction to the composition and cell types of interest for radiation studies of the CNS: “The CNS consists of neurons differing markedly in size and number per unit area. There are several nuclei or centers that consist of closely packed neuron cell bodies (e.g., the respiratory and cardiac centers in the floor of the fourth ventricle). In the cerebral cortex the large neuron cell bodies, such as Betz cells, are separated by a considerable distance. Of additional importance are the neuroglia which are the supporting cells and consist of astrocytes, oligodendroglia, and microglia. These cells permeate and support the nervous tissue of the CNS, binding it together like a scaffold that also supports the vasculature. The most numerous of the neuroglia are Type I astrocytes, which make up about half the brain, greatly outnumbering the neurons. Neuroglia retain the capability of cell division in contrast to neurons and, therefore, the responses to radiation differ between the cell types. A third type of tissue in the brain is the vasculature which exhibits a comparable vulnerability for radiation damage to that found elsewhere in the body. Radiation-induced damage to oligodendrocytes and endothelial cells of the vasculature accounts for major aspects of the pathogenesis of brain damage that can occur after high doses of low-LET radiation.” Based on studies with low-LET radiation, the CNS is considered a radioresistant tissue. For example: in radiotherapy, early brain complications in adults usually do not develop if daily fractions of 2 Gy or less are administered with a total dose of up to 50 Gy. The tolerance dose in the CNS, as with other tissues, depends on the volume and the specific anatomical location in the human brain that is irradiated.

In recent years, studies with stem cells uncovered that neurogenesis still occurs in the adult hippocampus, where cognitive actions such as memory and learning are determined. This discovery provides an approach to understand mechanistically the CNS risk of space radiation. Accumulating data indicate that radiation not only affects differentiated neural cells, but also the proliferation and differentiation of neuronal precursor cells and even adult stem cells. Recent evidence points out that neuronal progenitor cells are sensitive to radiation. Studies on low-LET radiation show that radiation stops not only the generation of neuronal progenitor cells, but also their differentiation into neurons and other neural cells. NCRP Report No. 153  notes that cells in the SGZ of the dentate gyrus undergo dose-dependent apoptosis above 2 Gy of X-ray irradiation, and the production of new neurons in young adult male mice is significantly reduced by relatively low (>2 Gy) doses of X rays. NCRP Report No. 153  also notes that: “These changes are observed to be dose dependent. In contrast there were no apparent effects on the production of new astrocytes or oligodendrocytes. Measurements of activated microglia indicated that changes in neurogenesis were associated with a significant dose-dependent inflammatory response even 2 months after irradiation. This suggests that the pathogenesis of long-recognized radiation-induced cognitive injury may involve loss of neural precursor cells from the SGZ of the hippocampal dentate gyrus and alterations in neurogenesis.”

Recent studies provide evidence of the pathogenesis of HZE nuclei in the CNS. The authors of one of these studies  were the first to suggest neurodegeneration with HZE nuclei, as shown in figure 6-1(a). These studies demonstrate that HZE radiation led to the progressive loss of neuronal progenitor cells in the SGZ at doses of 1 to 3 Gy in a dose-dependent manner. NCRP Report No. 153 notes that “Mice were irradiated with 1 to 3 Gy of 12C or 56Fe-ions and 9 months later proliferating cells and immature neurons in the dentate SGZ were quantified. The results showed that reductions in these cells were dependent on the dose and LET. Loss of precursor cells was also associated with altered neurogenesis and a robust inflammatory response, as shown in figures 6-1(a) and 6-1(b). These results indicate that high-LET radiation has a significant and long-lasting effect on the neurogenic population in the hippocampus that involves cell loss and changes in the microenvironment. The work has been confirmed by other studies. These investigators noted that these changes are consistent with those found in aged subjects, indicating that heavy-particle irradiation is a possible model for the study of aging.”

Figure 6-1(a). (Panel A) Expression of polysialic acid form of neural cell adhesion molecule (PSA-NCAM) in the hippocampus of rats that were irradiated (IR) with 2.5 Gy of 56Fe high-energy radiation and control subjects as measured by % density/field area measured. (Panel B) PSA-NCAM staining in the dentate gyrus of representative irradiated (IR) and control (C) subjects at 5x magnification.

Figure 6-1(b). Numbers of proliferating cells (left panel) and immature neurons (right panel) in the dentate SGZ are significantly decreased 48 hours after irradiation. Antibodies against Ki-67 and doublecortin (Dcx) were used to detect proliferating cells and immature neurons, respectively. Doses from 2 to 10 Gy significantly (p < 0.05) reduced the numbers of proliferating cells. Immature neurons were also reduced in a dose-dependent fashion (p<0.001). Each bar represents an average of four animals; error bars, and standard error.

Oxidative damage

Recent studies indicate that adult rat neural precursor cells from the hippocampus show an acute, dose-dependent apoptotic response that was accompanied by an increase in ROS. Low-LET protons are also used in clinical proton beam radiation therapy, at an RBE of 1.1 relative to megavoltage X rays at a high dose. NCRP Report No. 153 notes that: “Relative ROS levels were increased at nearly all doses (1 to 10 Gy) of Bragg-peak 250 MeV protons at post-irradiation times (6 to 24 hours) compared to unirradiated controls. The increase in ROS after proton irradiation was more rapid than that observed with X rays and showed a well-defined dose response at 6 and 24 hours, increasing about 10-fold over controls at a rate of 3% per Gy. However, by 48 hours post-irradiation, ROS levels fell below controls and coincided with minor reductions in mitochondrial content. Use of the antioxidant alpha-lipoic acid (before or after irradiation) was shown to eliminate the radiation-induced rise in ROS levels. These results corroborate the earlier studies using X rays and provide further evidence that elevated ROS are integral to the radioresponse of neural precursor cells.” Furthermore, high-LET radiation led to significantly higher levels of oxidative stress in hippocampal precursor cells as compared to lower-LET radiations (X rays, protons) at lower doses (≤1 Gy) (figure 6-2). The use of the antioxidant lipoic acid was able to reduce ROS levels below background levels when added before or after 56Fe-ion irradiation. These results conclusively show that low doses of 56Fe-ions can elicit significant levels of oxidative stress in neural precursor cells at a low dose.

Figure 6-2. Dose response for oxidative stress after 56Fe-ion irradiation. Hippocampal precursors that are subjected to 56Fe-ion irradiation were analyzed for oxidative stress 6 hours after exposure. At doses ≤1 Gy a linear dose response for the induction of oxidative stress was observed. At higher 56Fe doses, oxidative stress fell to values that were found using lower-LET irradiations (X rays, protons). Experiments, which represent a minimum of three independent measurements (±SE), were normalized against unirradiated controls set to unity. ROS levels induced after 56Fe irradiation were significantly (P < 0.05) higher than controls.

Neuroinflammation

Neuroinflammation, which is a fundamental reaction to brain injury, is characterized by the activation of resident microglia and astrocytes and local expression of a wide range of inflammatory mediators. Acute and chronic neuroinflammation has been studied in the mouse brain following exposure to HZE. The acute effect of HZE is detectable at 6 and 9 Gy; no studies are available at lower doses. Myeloid cell recruitment appears by 6 months following exposure. The estimated RBE value of HZE irradiation for induction of an acute neuroinflammatory response is three compared to that of gamma irradiation. COX-2 pathways are implicated in neuroinflammatory processes that are caused by low-LET radiation. COX-2 up-regulation in irradiated microglia cells leads to prostaglandin E2 production, which appears to be responsible for radiation-induced gliosis (overproliferation of astrocytes in damaged areas of the CNS).

Behavioral effects

As behavioral effects are difficult to quantitate, they consequently are one of the most uncertain of the space radiation risks. NCRP Report No. 153 notes that: “The behavioral neurosciences literature is replete with examples of major differences in behavioral outcome depending on the animal species, strain, or measurement method used. For example, compared to unirradiated controls, X-irradiated mice show hippocampal-dependent spatial learning and memory impairments in the Barnes maze, but not in the Morris water maze which, however, can be used to demonstrate deficits in rats. Particle radiation studies of behavior have been accomplished with rats and mice, but with some differences in the outcome depending on the endpoint measured.”

The following studies provide evidence that space radiation affects the CNS behavior of animals in a somewhat dose- and LET-dependent manner.

Sensorimotor effects

Sensorimotor deficits and neurochemical changes were observed in rats that were exposed to low doses of 56Fe-ions. Doses that are below 1 Gy reduce performance, as tested by the wire suspension test. Behavioral changes were observed as early as 3 days after radiation exposure and lasted up to 8 months. Biochemical studies showed that the K+-evoked release of dopamine was significantly reduced in the irradiated group, together with an alteration of the nerve signaling pathways. A negative result was reported by Pecaut et al., in which no behavioral effects were seen in female C57/BL6 mice in a 2- to 8-week period following their exposure to 0, 0.1, 0.5 or 2 Gy accelerated 56Fe-ions (1 GeV/u56Fe) as measured by open-field, rotorod, or acoustic startle habituation.

Radiation-induced changes in conditioned taste aversion

There is evidence that deficits in conditioned taste aversion (CTA) are induced by low doses of heavy ions. The CTA test is a classical conditioning paradigm that assesses the avoidance behavior that occurs when the ingestion of a normally acceptable food item is associated with illness. This is considered a standard behavioral test of drug toxicity. NCRP Report No. 153 notes that: “The role of the dopaminergic system in radiation-induced changes in CTA is suggested by the fact that amphetamine-induced CTA, which depends on the dopaminergic system, is affected by radiation, whereas lithium chloride-induced CTA, which does not involve the dopaminergic system, is not affected by radiation. It was established that the degree of CTA due to radiation is LET-dependent ([figure 6-3]) and that 56Fe-ions are the most effective of the various low and high LET radiation types that have been tested. Doses as low as ~0.2 Gy of 56Fe-ions appear to have an effect on CTA.”

The RBE of different types of heavy particles on CNS function and cognitive/behavioral performance was studied in Sprague-Dawley rats. The relationship between the thresholds for the HZE particle-induced disruption of amphetamine-induced CTA learning is shown in figure 6-4; and for the disruption of operant responding is shown in figure 6-5. These figures show a similar pattern of responsiveness to the disruptive effects of exposure to either 56Fe or 28Si particles on both CTA learning and operant responding. These results suggest that the RBE of different particles for neurobehavioral dysfunction cannot be predicted solely on the basis of the LET of the specific particle.

Figure 6-3. ED₅₀ for CTA as a function of LET for the following radiation sources: ⁴⁰Ar = argon ions, ⁶⁰Co = Cobalt-60 gamma rays, e⁻ = electrons, ⁵⁶FE = iron ions, ⁴He = helium ions, n⁰ = neutrons, ²⁰Ne = neon ions.

Figure 6-4. Radiation-induced disruption in CTA. This figure shows the relationship between exposure to different energies of ⁵⁶FE and ²⁸Si particles and the threshold dose for the disruption of amphetamine-induced CTA learning. Only a single energy of ⁴⁸Ti particles was tested. The threshold dose (cGy) for the disruption of the response is plotted against particle LET (keV/μm).

Figure 6-5.jpg High-LET radiation effects on operant response. This figure shows the relationship between the exposure to different energies of ⁵⁶Fe and ²⁸Si particles and the threshold dose for the disruption of performance on a food-reinforced operant response. Only a single energy of ⁴⁸Ti particles was tested. The threshold dose (cGy) for the disruption of the response is plotted against particle LET (keV/μm).

Radiation effect on operant conditioning

Operant conditioning uses several consequences to modify a voluntary behavior. Recent studies by Rabin et al. have examined the ability of rats to perform an operant order to obtain food reinforcement using an ascending fixed ratio (FR) schedule. They found that ⁵⁶Fe-ion doses that are above 2 Gy affect the appropriate responses of rats to increasing work requirements. NCRP Report No. 153 notes that "The disruption of operant response in rats was tested 5 and 8 months after exposure, but maintaining the rats on a diet containing strawberry, but not blueberry, extract were shown to prevent the disruption. When tested 13 and 18 months after irradiation, there were no differences in performance between the irradiated rats maintained on control, strawberry or blueberry diets. These observations suggest that the beneficial effects of antioxidant diets may be age dependent."

Spatial learning and memory

The effects of exposure to HZE nuclei on spatial learning, memory behavior, and neuronal signaling have been tested, and threshold doses have also been considered for such effects. It will be important to understand the mechanisms that are involved in these deficits to extrapolate the results to other dose regimes, particle types, and, eventually, astronauts. Studies on rats were performed using the Morris water maze test 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/u ⁵⁶Fe-ions. Irradiated rats demonstrated cognitive impairment that was similar to that seen in aged rats. This leads to the possibility that an increase in the amount of ROS may be responsible for the induction of both radiation- and age-related cognitive deficits.

NCRP Report No. 153  notes that: “Denisova et al. exposed rats to 1.5 Gy of 1 GeV/u56Feions and tested their spatial memory in an eight-arm radial maze. Radiation exposure impaired the rats’ cognitive behavior, since they committed more errors than control rats in the radial maze and were unable to adopt a spatial strategy to solve the maze. To determine whether these findings related to brain-region specific alterations in sensitivity to oxidative stress, inflammation or neuronal plasticity, three regions of the brain, the striatum, hippocampus and frontal cortex that are linked to behavior, were isolated and compared to controls. Those that were irradiated were adversely affected as reflected through the levels of dichlorofluorescein, heat shock, and synaptic proteins (for example, synaptobrevin and synaptophysin). Changes in these factors consequently altered cellular signaling (for example, calcium-dependent protein kinase C and protein kinase A). These changes in brain responses significantly correlated with working memory errors in the radial maze. The results show differential brain-region-specific sensitivity induced by 56Fe irradiation ([figure 6-6]). These findings are similar to those seen in aged rats, suggesting that increased oxidative stress and inflammation may be responsible for the induction of both radiation and age-related cognitive deficits.”

Figure 6-6. Brain-region-specific calcium-dependent protein kinase C expression was assessed in control and irradiated rats using standard Western blotting procedures. Values are means ± SEM (standard error of mean).

Acute central nervous system risks

In addition to the possible in-flight performance and motor skill changes that were described above, the immediate CNS effects (i.e., within 24 hours following exposure to low-LET radiation) are anorexia and nausea. These prodromal risks are dose-dependent and, as such, can provide an indicator of the exposure dose. Estimates are ED50 = 1.08 Gy for anorexia, ED50 = 1.58 Gy for nausea, and ED50=2.40 Gy for emesis. The relative effectiveness of different radiation types in producing emesis was studied in ferrets and is illustrated in figure 6-7. High-LET radiation at doses that are below 0.5 Gy show greater relative biological effectiveness compared to low-LET radiation. The acute effects on the CNS, which are associated with increases in cytokines and chemokines, may lead to disruption in the proliferation of stem cells or memory loss that may contribute to other degenerative diseases.

Figure 6-7. LET dependence of RBE of radiation in producing emesis or retching in a ferret. B = bremsstrahlung; e⁻ = electrons; P = protons; ⁶⁰Co = cobalt gamma rays; n⁰ = neutrons; and ⁵⁶Fe = iron.

Computer models and systems biology analysis of central nervous system risks

Since human epidemiology and experimental data for CNS risks from space radiation are limited, mammalian models are essential tools for understanding the uncertainties of human risks. Cellular, tissue, and genetic animal models have been used in biological studies on the CNS using simulated space radiation. New technologies, such as three-dimensional cell cultures, microarrays, proteomics, and brain imaging, are used in systematic studies on CNS risks from different radiation types. According to biological data, mathematical models can be used to estimate the risks from space radiation.

Systems biology approaches to Alzheimer's disease that consider the biochemical pathways that are important in CNS disease evolution have been developed by research that was funded outside NASA. Figure 6-8 shows a schematic of the biochemical pathways that are important in the development of Alzheimer's disease. The description of the interaction of space radiation within these pathways would be one approach to developing predictive models of space radiation risks. For example, if the pathways that were studied in animal models could be correlated with studies in humans who are suffering from Alzheimer's disease, an approach to describe risk that uses biochemical degrees-of-freedom could be pursued. Edelstein-Keshet and Spiros have developed an in silico model of senile plaques that are related to Alzheimer's disease. In this model, the biochemical interactions among TNF, IL-1B, and IL-6 are described within several important cell populations, including astrocytes, microglia, and neurons. Further, in this model soluble amyloid causes microglial chemotaxis and activates IL-1B secretion. Figure 6-9 shows the results of the Edelstein-Keshet and Spiros model simulating plaque formation and neuronal death. Establishing links between space radiation-induced changes to the changes that are described in this approach can be pursued to develop an in silico model of Alzheimer's disease that results from space radiation.

Figure 6-8.Molecular pathways important in Alzheimer's disease. From Kyoto Encyclopedia of Genes and Genomes. Copyrighted image located at http://www.genome.jp/kegg/pathway/hsa/hsa05010.html

Figure 6-9. Model of plaque formation and neuronal death in Alzheimer's disease. From Edelstein-Keshet and Spiros, 2002: Top row: Formation of a plaque and death of neurons in the absence of glial cells, when fibrous amyloid is the only injurious influence. The simulation was run with no astrocytes or microglia, and the health of neurons was determined solely by the local fibrous amyloid. Shown above is a time sequence (left to right) of three stages in plaque development, at early, intermediate, and advanced stages. Density of fibrous deposit is represented by small dots and neuronal health by shading from white (healthy) to black (dead). Note radial symmetry due to simple diffusion. Bottom row: Effect of microglial removal of amyloid on plaque morphology. Note that microglia (small star-like shapes) are seen approaching the plaque (via chemotaxis to soluble amyloid, not shown). At a later stage, they have congregated at the plaque center, where they adhere to fibers. As a result of the removal of soluble and fibrous amyloid, the microglia lead to irregular plaque morphology. Size scale: In this figure, the distance between the small single dots (representing low-fiber deposits) is 10 mm. Similar results were obtained for a 10-fold scaling in the time scale of neuronal health dynamics.

Other interesting candidate pathways that may be important in the regulation of radiation-induced degenerative CNS changes are signal transduction pathways that are regulated by Cdk5. Cdk5 is a kinase that plays a key role in neural development; its aberrant expression and activation are associated with neurodegenerative processes, including Alzheimer's disease. This kinase is up-regulated in neural cells following ionizing radiation exposure.

Risks in context of exploration mission operational scenarios

Projections for space missions

Reliable projections of CNS risks for space missions cannot be made from the available data. Animal behavior studies indicate that high-HZE radiation has a high RBE, but the data are not consistent. Other uncertainties include: age at exposure, radiation quality, and dose-rate effects, as well as issues regarding genetic susceptibility to CNS risk from space radiation exposure. More research is required before CNS risk can be estimated.

Potential for biological countermeasures

The goal of space radiation research is to estimate and reduce uncertainties in risk projection models and, if necessary, develop countermeasures and technologies to monitor and treat adverse outcomes to human health and performance that are relevant to space radiation for short-term and career exposures, including acute or late CNS effects from radiation exposure. The need for the development of countermeasures to CNS risks is dependent on further understanding of CNS risks, especially issues that are related to a possible dose threshold, and if so, which NASA missions would likely exceed threshold doses. As a result of animal experimental studies, antioxidant and anti-inflammation are expected to be effective countermeasures for CNS risks from space radiation. Diets of blueberries and strawberries were shown to reduce CNS risks after heavy-ion exposure. Estimating the effects of diet and nutritional supplementation will be a primary goal of CNS research on countermeasures.

A diet that is rich in fruit and vegetables significantly reduces the risk of several diseases. Retinoids and vitamins A, C, and E are probably the most well-known and studied natural radioprotectors, but hormones (e.g., melatonin), glutathione, superoxide dismutase, and phytochemicals from plant extracts (including green tea and cruciferous vegetables), as well as metals (especially selenium, zinc, and copper salts) are also under study as dietary supplements for individuals, including astronauts, who have been overexposed to radiation. Antioxidants should provide reduced or no protection against the initial damage from densely ionizing radiation such as HZE nuclei, because the direct effect is more important than the free-radical-mediated indirect radiation damage at high LET. However, there is an expectation that some benefits should occur for persistent oxidative damage that is related to inflammation and immune responses. Some recent experiments suggest that, at least for acute high-dose irradiation, an efficient radioprotection by dietary supplements can be achieved, even in the case of exposure to high-LET radiation. Although there is evidence that dietary antioxidants (especially strawberries) can protect the CNS from the deleterious effects of high doses of HZE particles, because the mechanisms of biological effects are different at low dose-rates compared to those of acute irradiation, new studies for protracted exposures will be needed to understand the potential benefits of biological countermeasures.

Concern about the potential detrimental effects of antioxidants was raised by a recent meta-study of the effects of antioxidant supplements in the diet of normal subjects. The authors of this study did not find statistically significant evidence that antioxidant supplements have beneficial effects on mortality. On the contrary, they concluded that β-carotene, vitamin A, and vitamin E seem to increase the risk of death. Concerns are that the antioxidants may allow rescue of cells that still sustain DNA mutations or altered genomic methylation patterns following radiation damage to DNA, which can result in genomic instability. An approach to target damaged cells for apoptosis may be advantageous for chronic exposures to GCR.

Individual risk factors

Individual factors of potential importance are genetic factors, prior radiation exposure, and previous head injury, such as concussion. Apolipoprotein E (ApoE) has been shown to be an important and common factor in CNS responses. ApoE controls the redistribution of lipids among cells and is expressed at high levels in the brain. New studies are considering the effects of space radiation for the major isoforms of ApoE, which are encoded by distinct alleles (ε2, ε3, and ε4). The isoform ApoE ε4 has been shown to increase the risk of cognitive impairments and to lower the age for Alzheimer's disease. It is not known whether the interaction of radiation sensitivity or other individual risks factors is the same for high- and low-LET radiation. Other isoforms of ApoE confer a higher risk for other diseases. People who carry at least one copy of the ApoE ε4 allele are at increased risk for atherosclerosis, which is also suspected to be a risk increased by radiation. People who carry two copies of the ApoE ε2 allele are at risk for a condition that is known as hyperlipoproteinemia type III. It will therefore be extremely challenging to consider genetic factors in a multipleradiation-risk paradigm.

Conclusion

Reliable projections for CNS risks from space radiation exposure cannot be made at this time due to a paucity of data on the subject. Existing animal and cellular data do suggest that space radiation can produce neurological and behavioral effects; therefore, it is possible that mission operations will be impacted. The significance of these results on the morbidity to astronauts has not been elucidated, however. It is to be noted that studies, to date, have been carried out with relatively small numbers of animals (<10 per dose group); this means that testing of dose threshold effects at lower doses (<0.5 Gy) has not yet been carried out to a sufficient extent. As the problem of extrapolating space radiation effects in animals to humans will be a challenge for space radiation research, such research could become limited by the population size that is typically used in animal studies. Furthermore, the role of dose protraction has not been studied to date. An approach has not been discovered to extrapolate existing observations to possible cognitive changes, performance degradation, or late CNS effects in astronauts. Research on new approaches to risk assessment may be needed to provide the data and knowledge that will be necessary to develop risk projection models of the CNS from space radiation. A vigorous research program, which will be required to solve these problems, must rely on new approaches to risk assessment and countermeasure validation because of the absence of useful human radio-epidemiology data in this area.

Health threat from cosmic rays

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Health_threat_from_cosmic_rays

Health threats from cosmic rays are the dangers posed by cosmic rays to astronauts on interplanetary missions or any missions that venture through the Van-Allen Belts or outside the Earth's magnetosphere. They are one of the greatest barriers standing in the way of plans for interplanetary travel by crewed spacecraft, but space radiation health risks also occur for missions in low Earth orbit such as the International Space Station (ISS).

In October 2015, the NASA Office of Inspector General issued a health hazards report related to space exploration, including a human mission to Mars.

The deep-space radiation environment

Sources of ionizing radiation in interplanetary space.

The radiation environment of deep space is different from that on the Earth's surface or in low Earth orbit, due to the much larger flux of high-energy galactic cosmic rays (GCRs), along with radiation from solar proton events (SPEs) and the radiation belts.

Galactic cosmic rays (GCRs) consist of high energy protons (85%), alpha particles (14%) and other high energy nuclei (HZE ions). Solar energetic particles consist primarily of protons accelerated by the Sun to high energies via proximity to solar flares and coronal mass ejections. Heavy ions and low energy protons and helium particles are highly ionizing forms of radiation, which produce distinct biological damage compared to X-rays and gamma-rays.

Microscopic energy deposition from highly ionizing particles consists of a core radiation track due to direct ionizations by the particle and low energy electrons produced in ionization, and a penumbra of higher energy electrons that may extend hundreds of microns from the particles path in tissue. The core track produces extremely large clusters of ionizations within a few nanometres, which is qualitatively distinct from energy deposition by X-rays and gamma rays; hence human epidemiology data which only exists for these latter forms of radiation is limited in predicting the health risks from space radiation to astronauts.

The radiation belts are within Earth's magnetosphere and do not occur in deep space, while organ dose equivalents on the International Space Station are dominated by GCR not trapped radiation. Microscopic energy deposition in cells and tissues is distinct for GCR compared to X-rays on Earth, leading to both qualitative and quantitative differences in biological effects, while there is no human epidemiology data for GCR for cancer and other fatal risks.

The solar cycle is an approximately 11-year period of varying solar activity including solar maximum where the solar wind is strongest and solar minimum where the solar wind is weakest. Galactic cosmic rays create a continuous radiation dose throughout the Solar System that increases during solar minimum and decreases during solar maximum (solar activity). The inner and outer radiation belts are two regions of trapped particles from the solar wind that are later accelerated by dynamic interaction with the Earth's magnetic field. While always high, the radiation dose in these belts can increase dramatically during geomagnetic storms and substorms. Solar proton events (SPEs) are bursts of energetic protons accelerated by the Sun. They occur relatively rarely and can produce extremely high radiation levels. Without thick shielding, SPEs are sufficiently strong to cause acute radiation poisoning and death.

Life on the Earth's surface is protected from galactic cosmic rays by a number of factors:

1. The Earth's atmosphere is opaque to primary cosmic rays with energies below about 1 gigaelectron volt (GeV), so only secondary radiation can reach the surface. The secondary radiation is also attenuated by absorption in the atmosphere, as well as by radioactive decay in flight of some particles, such as muons. Particles entering from a direction far from the zenith are especially attenuated. The world's population receives an average of 0.4 millisieverts (mSv) of cosmic radiation annually (separate from other sources of radiation exposure like inhaled radon) due to atmospheric shielding. At 12 km altitude, above most of the atmosphere's protection, radiation as an annual rate rises to 20 mSv at the equator to 50–120 mSv at the poles, varying between solar maximum and minimum conditions.
2. Missions beyond low Earth orbit transit the Van Allen radiation belts. Thus they may need to be shielded against exposure to cosmic rays, Van Allen radiation, or solar flares. The region between two and four Earth radii lies between the two radiation belts and is sometimes referred to as the "safe zone". See the implications of the Van Allen belts for space travel for more information.
3. The interplanetary magnetic field, embedded in the solar wind, also deflects cosmic rays. As a result, cosmic ray fluxes within the heliopause are inversely correlated with the solar cycle.
4. Electromagnetic radiation created by lightning in clouds only a few miles high can create a safe zone in the Van Allen radiation belts that surround the Earth. This zone, known as the "Van Allen Belt slot", may be a safe haven for satellites in medium Earth orbits (MEOs), protecting them from the Sun's intense radiation.

As a result, the energy input of GCRs to the atmosphere is negligible – about 10⁻⁹ of solar radiation – roughly the same as starlight.

Of the above factors, all but the first one apply to low Earth orbit craft, such as the Space Shuttle and the International Space Station. Exposures on the ISS average 150 mSv per year, although frequent crew rotations minimize individual risk. Astronauts on Skylab missions received on average 1.4 mSv/day. Since the durations of the Skylab missions were days and months, respectively, rather than years, the doses involved were smaller than would be expected on future long-term missions such as to a near-Earth asteroid or to Mars (unless far more shielding could be provided).

On 31 May 2013, NASA scientists reported that a possible human mission to Mars may involve a great radiation risk based on the amount of energetic particle radiation detected by the radiation assessment detector (RAD) on the Mars Science Laboratory while traveling from the Earth to Mars in 2011–2012. However, the absorbed dose and dose equivalent for a Mars mission were predicted in the early 1990s by Badhwar, Cucinotta, and others (see for example Badhwar, Cucinotta et al., Radiation Research vol. 138, 201–208, 1994) and the result of the MSL experiment are to a large extent consistent with these earlier predictions.

Human health effects

Comparison of radiation doses, includes the amount detected on the trip from Earth to Mars by the RAD on the MSL (2011–2013). The y-axis scale is in logarithmic scale. For example, the exposure from 6 months aboard the ISS is roughly a factor of 10 greater than that from an abdominal CT scan.

The potential acute and chronic health effects of space radiation, as with other ionizing radiation exposures, involve both direct damage to DNA, indirect effects due to generation of reactive oxygen species, and changes to the biochemistry of cells and tissues, which can alter gene transcription and the tissue microenvironment along with producing DNA mutations. Acute (or early radiation) effects result from high radiation doses, and these are most likely to occur after solar particle events (SPEs). Likely chronic effects of space radiation exposure include both stochastic events such as radiation carcinogenesis and deterministic degenerative tissue effects. To date, however, the only pathology associated with space radiation exposure is a higher risk for radiation cataract among the astronaut corps.

The health threat depends on the flux, energy spectrum, and nuclear composition of the radiation. The flux and energy spectrum depend on a variety of factors: short-term solar weather, long-term trends (such as an apparent increase since the 1950s), and position in the Sun's magnetic field. These factors are incompletely understood. The Mars Radiation Environment Experiment (MARIE) was launched in 2001 in order to collect more data. Estimates are that humans unshielded in interplanetary space would receive annually roughly 400 to 900 mSv (compared to 2.4 mSv on Earth) and that a Mars mission (12 months in flight and 18 months on Mars) might expose shielded astronauts to roughly 500 to 1000 mSv. These doses approach the 1 to 4 Sv career limits advised by the National Council on Radiation Protection and Measurements (NCRP) for low Earth orbit activities in 1989, and the more recent NCRP recommendations of 0.5 to 2 Sv in 2000 based on updated information on dose to risk conversion factors. Dose limits depend on age at exposure and sex due to difference in susceptibility with age, the added risks of breast and ovarian cancers to women, and the variability of cancer risks such as lung cancer between men and women. A 2017 laboratory study on mice, estimates that the risk of developing cancer due to galactic cosmic rays (GCR) radiation exposure after a Mars mission could be two times greater than what scientists previously thought.

The quantitative biological effects of cosmic rays are poorly known, and are the subject of ongoing research. Several experiments, both in space and on Earth, are being carried out to evaluate the exact degree of danger. Additionally, the impact of the space microgravity environment on DNA repair has in part confounded the interpretation of some results. Experiments over the last 10 years have shown results both higher and lower than predicted by current quality factors used in radiation protection, indicating large uncertainties exist.

Experiments in 2007 at Brookhaven National Laboratory's NASA Space Radiation Laboratory (NSRL) suggest that biological damage due to a given exposure is actually about half what was previously estimated: specifically, it suggested that low energy protons cause more damage than high energy ones. This was explained by the fact that slower particles have more time to interact with molecules in the body. This may be interpreted as an acceptable result for space travel as the cells affected end up with greater energy deposition and are more likely to die without proliferating into tumors. This is in contrast to the current dogma on radiation exposure to human cells which considers lower energy radiation of higher weighting factor for tumor formation. Relative biological effectiveness (RBE) depends on radiation type described by particle charge number, Z, and kinetic energy per amu, E, and varies with tumor type with limited experimental data suggesting leukemia's having the lowest RBE, liver tumors the highest RBE, and limited or no experimental data on RBE available for cancers that dominate human cancer risks including lung, stomach, breast, and bladder cancers. Studies of Harderian gland tumors in a single strain of female mice with several heavy ions have been made, however it is not clear how well the RBE for this tumor type represents the RBE for human cancers such as lung, stomach, breast and bladder cancers nor how RBE changes with sex and genetic background.

Part of the ISS year long mission is to determine the health impacts of cosmic ray exposure over the course of one year spent aboard the International Space Station. However, sample sizes for accurately estimating health risks directly from crew observations for the risks of concern (cancer, cataracts, cognitive and memory changes, late CNS risks, circulatory diseases, etc.) are large (typically >>10 persons) and necessarily involve long post-mission observation times (>10 years). The small number of astronauts on the ISS and the limited length of missions puts statistical limits on how accurate risk predictions can be. Hence the need for ground-based research to predict cosmic ray health risks. In addition, radiation safety requirements mandate that risks should be adequately understood prior to astronauts incurring significant risks, and methods developed to mitigate the risks if necessary.

Noting these limitations, a study published in Scientific Reports looked over 301 U.S. astronauts and 117 Soviet and Russian cosmonauts, and found no measurable increase in cancer mortality compared to the general population over time. An earlier 1998 study came to similar conclusions, with no statistically significant increase in cancer among astronauts compared to the reference group. See spaceflight radiation carcinogenesis for further details on cancer risks.

Central nervous system

See also: Central nervous system effects from radiation exposure during spaceflight

Hypothetical early and late effects on the central nervous system are of great concern to NASA and an area of active current research interest. It is postulated short- and long-term effects of CNS exposure to galactic cosmic radiation are likely to pose significant neurological health risks to human long-term space travel. Estimates suggest considerable exposure to high energy heavy (HZE) ions as well as protons and secondary radiation during Mars or prolonged Lunar missions with estimates of whole body effective doses ranging from 0.17 to greater than 1.0 Sv. Given the high linear energy transfer potential of such particles, a considerable proportion of those cells exposed to HZE radiation are likely to die. Based on calculations of heavy ion fluences during space flight as well as various experimental cell models, as many as 5% of an astronaut's cells might be killed during such missions. With respect to cells in critical brain regions, as many as 13% of such cells may be traversed at least once by an iron ion during a three-year Mars mission. Several Apollo astronauts reported seeing light flashes, although the precise biological mechanisms responsible are unclear. Likely pathways include heavy ion interactions with retinal photoreceptors and Cherenkov radiation resulting from particle interactions within the vitreous humor. This phenomenon has been replicated on Earth by scientists at various institutions. As the duration of the longest Apollo flights was less than two weeks, the astronauts had limited cumulative exposures and a corresponding low risk for radiation carcinogenesis. In addition, there were only 24 such astronauts, making statistical analysis of any potential health effects problematic.

In the above discussion dose equivalents is units of Sievert (Sv) are noted, however the Sv is a unit for comparing cancer risks for different types of ionizing radiation. For CNS effects absorbed doses in Gy are more useful, while the RBE for CNS effects is poorly understood. Furthermore, stating "hypothetical" risk is problematic, while space radiation CNS risk estimates have largely focused on early and late detriments to memory and cognition (e.g. Cucinotta, Alp, Sulzman, and Wang, Life Sciences in Space Research, 2014).

On 31 December 2012, a NASA-supported study reported that human spaceflight may harm the brains of astronauts and accelerate the onset of Alzheimer's disease. This research is problematic due to many factors, inclusive of the intensity of which mice were exposed to radiation which far exceeds normal mission rates.

A review of CNS space radiobiology by Cucinotta, Alp, Sulzman, and Wang (Life Sciences in Space Research, 2014) summarizes research studies in small animals of changes to cognition and memory, neuro-inflammation, neuron morphology, and impaired neurogenesis in the hippocampus. Studies using simulated space radiation in small animals suggest temporary or long-term cognitive detriments could occur during a long-term space mission. Changes to neuron morphology in mouse hippocampus and pre-frontal cortex occur for heavy ions at low doses (<0.3 Gy). Studies in mice and rats of chronic neuro-inflammation and behavioral changes show variable results at low doses (~0.1 Gy or lower). Further research is needed to understand if such cognitive detriments induced by space radiation would occur in astronauts and whether they would negatively impact a Mars mission.

The cumulative heavy ion doses in space are low such that critical cells and cell components will receive only 0 or 1 particle traversal. The cumulative heavy ion dose for a Mars mission near solar minimum would be ~0.05 Gy and lower for missions at other times in the solar cycle. This suggests dose-rate effects will not occur for heavy ions as long as the total doses used in experimental studies in reasonably small (<~0.1 Gy). At larger doses (>~0.1 Gy) critical cells and cell components could receive more than one particle traversal, which is not reflective of the deep space environment for extended duration missions such as a mission to Mars. An alternative assumption would be if a tissue's micro-environment is modified by a long-range signaling effect or change to biochemistry, whereby a particle traversal to some cells modifies the response of other cells not traversed by particles. There is limited experimental evidence, especially for central nervous system effects, available to evaluate this alternative assumption.

Prevention

Spacecraft shielding

Standard spacecraft shielding, integrated into hull design, is strong protection from most solar radiation, but defeats this purpose with high-energy cosmic rays, as it simply splits this into showers of secondary particles. This shower of secondary and fragmented particles may be reduced by the use of hydrogen or light elements for shielding.

Material shielding can be effective against galactic cosmic rays, but thin shielding may actually make the problem worse for some of the higher energy rays, because more shielding causes an increased amount of secondary radiation, although thick shielding could counter such too. The aluminium walls of the ISS, for example, are believed to produce a net reduction in radiation exposure. In interplanetary space, however, it is believed that thin aluminium shielding would give a net increase in radiation exposure but would gradually decrease as more shielding is added to capture generated secondary radiation.

Studies of space radiation shielding should include tissue or water equivalent shielding along with the shielding material under study. This observation is readily understood by noting that the average tissue self-shielding of sensitive organs is about 10 cm, and that secondary radiation produced in tissue such as low energy protons, helium and heavy ions are of high linear energy transfer (LET) and make significant contributions (>25%) to the overall biological damage from GCR. Studies of aluminum, polyethylene, liquid hydrogen, or other shielding materials, will involve secondary radiation not reflective of secondary radiation produced in tissue, hence the need to include tissue equivalent shielding in studies of space radiation shielding effectiveness.

Several strategies are being studied for ameliorating the effects of this radiation hazard for planned human interplanetary spaceflight:

• Spacecraft can be constructed out of hydrogen-rich plastics, rather than aluminium.
• Material shielding has been considered:
  • Liquid hydrogen, often used as fuel, tends to give relatively good shielding, while producing relatively low levels of secondary radiation. Therefore, the fuel could be placed so as to act as a form of shielding around the crew. However, as fuel is consumed by the craft, the crew's shielding decreases.
  • Water, which is necessary to sustain life, could also contribute to shielding. But it too is consumed during the journey unless waste products are utilized.
  • Asteroids could serve to provide shielding.
• Light active radiation shields based on the charged graphene against gamma rays, where the absorption parameters can be controlled by the negative charge accumulation.
• Magnetic deflection of charged radiation particles and/or electrostatic repulsion is a hypothetical alternative to pure conventional mass shielding under investigation. In theory, power requirements for a 5-meter torus drop from an excessive 10 GW for a simple pure electrostatic shield (too discharged by space electrons) to a moderate 10 kilowatts (kW) by using a hybrid design. However, such complex active shielding is untried, with workability and practicalities more uncertain than material shielding.

Special provisions would also be necessary to protect against a solar proton event, which could increase fluxes to levels that would kill a crew in hours or days rather than months or years. Potential mitigation strategies include providing a small habitable space behind a spacecraft's water supply or with particularly thick walls or providing an option to abort to the protective environment provided by the Earth's magnetosphere. The Apollo mission used a combination of both strategies. Upon receiving confirmation of an SPE, astronauts would move to the Command Module, which had thicker aluminium walls than the Lunar Module, then return to Earth. It was later determined from measurements taken by instruments flown on Apollo that the Command Module would have provided sufficient shielding to prevent significant crew harm.

None of these strategies currently provide a method of protection that would be known to be sufficient while conforming to likely limitations on the mass of the payload at present (around $10,000/kg) launch prices. Scientists such as University of Chicago professor emeritus Eugene Parker are not optimistic it can be solved anytime soon. For passive mass shielding, the required amount could be too heavy to be affordably lifted into space without changes in economics (like hypothetical non-rocket spacelaunch or usage of extraterrestrial resources) — many hundreds of metric tons for a reasonably-sized crew compartment. For instance, a NASA design study for an ambitious large space station envisioned 4 metric tons per square meter of shielding to drop radiation exposure to 2.5 mSv annually (± a factor of 2 uncertainty), less than the tens of milli sieverts or more in some populated high natural background radiation areas on Earth, but the sheer mass for that level of mitigation was considered practical only because it involved first building a lunar mass driver to launch material.

Several active shielding methods have been considered that might be less massive than passive shielding, but they remain speculative. Since the type of radiation penetrating farthest through thick material shielding, deep in interplanetary space, is GeV positively charged nuclei, a repulsive electrostatic field has been proposed, but this has problems including plasma instabilities and the power needed for an accelerator constantly keeping the charge from being neutralized by deep-space electrons. A more common proposal is magnetic shielding generated by superconductors (or plasma currents). Among the difficulties with this proposal is that, for a compact system, magnetic fields up to 10–20 teslas could be required around a crewed spacecraft, higher than the several teslas in MRI machines. Such high fields can produce headaches and migraines in MRI patients, and long-duration exposure to such fields has not been studied. Opposing-electromagnet designs might cancel the field in the crew sections of the spacecraft, but would require more mass. It is also possible to use a combination of a magnetic field with an electrostatic field, with the spacecraft having zero total charge. The hybrid design would theoretically ameliorate the problems, but would be complex and possibly infeasible.

Part of the uncertainty is that the effect of human exposure to galactic cosmic rays is poorly known in quantitative terms. The NASA Space Radiation Laboratory is currently studying the effects of radiation in living organisms as well as protective shielding.

Wearable radiation shielding

Apart from passive and active radiation shielding methods, which focus on protecting the spacecraft from harmful space radiation, there has been much interest in designing personalized radiation protective suits for astronauts. The reason behind choosing such methods of radiation shielding is that in passive shielding, adding a certain thickness to the spacecraft can increase the mass of the spacecraft by several thousands of kilograms. This mass can surpass the launch constraints and costs several millions of dollars.

On the other hand, active radiation shielding methods is an emerging technology which is still far away in terms of testing and implementation. Even with the simultaneous use of active and passive shielding, wearable protective shielding may be useful, especially in reducing the health effects of SPEs, which generally are composed of particles that have a lower penetrating force than GCR particles. The materials suggested for this type of protective equipment is often polyethylene or other hydrogen rich polymers. Water has also been suggested as a shielding material. The limitation with wearable protective solutions is that they need to be ergonomically compatible with crew needs such as movement inside crew volume. One attempt at creating wearable protection for space radiation was done by the Italian Space Agency, where a garment was proposed that could be filled with recycled water on the signal of incoming SPE.

A collaborative effort between the Israeli Space Agency, StemRad and Lockheed Martin was AstroRad, tested aboard the ISS. The product is designed as an ergonomically suitable protective vest, which can minimize the effective dose by SPE to an extent similar to onboard storm shelters. It also has potential to mildly reduce the effective dose of GCR through extensive use during the mission during such routine activities such as sleeping. This radiation protective garment uses selective shielding methods to protect most radiation-sensitive organs such as BFO, stomach, lungs, and other internal organs, thereby reducing the mass penalty and launch cost.

Drugs and medicine

Another line of research is the development of drugs that enhance the body's natural capacity to repair damage caused by radiation. Some of the drugs that are being considered are retinoids, which are vitamins with antioxidant properties, and molecules that retard cell division, giving the body time to fix damage before harmful mutations can be duplicated.

Transhumanism

Main article: Transhumanism

It has also been suggested that only through substantial improvements and modifications could the human body endure the conditions of space travel. While not constrained by basic laws of nature in the way technical solutions are, this is far beyond current science of medicine.

Timing of missions

Due to the potential negative effects of astronaut exposure to cosmic rays, solar activity may play a role in future space travel. Because galactic cosmic ray fluxes within the Solar System are lower during periods of strong solar activity, interplanetary travel during solar maximum should minimize the average dose to astronauts.

Although the Forbush decrease effect during coronal mass ejections can temporarily lower the flux of galactic cosmic rays, the short duration of the effect (1–3 days) and the approximately 1% chance that a CME generates a dangerous solar proton event limits the utility of timing missions to coincide with CMEs.

Orbital selection

Radiation dosage from the Earth's radiation belts is typically mitigated by selecting orbits that avoid the belts or pass through them relatively quickly. For example, a low Earth orbit, with low inclination, will generally be below the inner belt.

The orbits of the Earth-Moon system Lagrange points L₂ - L₅ take them out of the protection of the Earth's magnetosphere for approximately two-thirds of the time.

The orbits of Earth-Sun system Lagrange Points L₁ and L₃ - L₅ are always outside the protection of the Earth's magnetosphere.