On his way to the moon in July 1968, Apollo 11 astronaut Buzz Aldrin noticed tiny, intermittent flashes of white light in his field of vision. They occurred as often as once per minute, and Aldrin noticed them even when his eyes were closed. Eventually he mentioned the flashes to his crewmates, Neil Armstrong and Michael Collins, and they admitted having seen them too. Other astronauts on subsequent Apollo and Skylab missions would report similar visual phenomena.
NASA scientists concluded that the flashes were caused by impacts on astronauts’ eyes or optic nerves by cosmic radiation. This flux of high-speed charged particles, emitted by the sun and other stars, is normally kept to low levels on Earth by the planetary magnetic field; Moon-bound astronauts were the first humans to venture beyond that protective barrier. Researchers found microscopic cosmic-ray tracks in the astronauts’ plastic helmets, and even reproduced the light-flash phenomenon in the laboratory by placing their own eyes in the path of low-dose particle beams.
Each Apollo mission exposed its astronauts to interplanetary cosmic radiation levels for less than a week and a half. With the shielding available on modern spacecraft, such brief exposures are not considered very dangerous. But NASA now envisions human missions lasting up to several years, for example to Mars and back, and over these lengthy periods the accumulated dose of cosmic radiation could be enough to cause serious harm. Such harm wouldn’t necessarily be restricted to slow-developing conditions such as cancer and cataracts. Researchers are now looking into the possibility that Mars-bound astronauts would suffer acute brain damage that might affect how well they could perform their mission.
“For a long time, the adult central nervous system was considered relatively insensitive to radiation, because radiation has strong effects on fast-dividing cells, and mature neurons don’t divide at all; but we now know that the brain is quite vulnerable,” says Marcelo Vazquez, a researcher at Brookhaven National Laboratory who is part of a network of scientists now doing radiation-effects research for NASA.
Fast, heavy metal
Not all cosmic radiation is of equal concern. Charged particles from the sun are usually simple protons—hydrogen atoms stripped of electrons—and even the thin metal or plastic shielding available on spacecraft can block them effectively. NASA is much more worried about the heavier atomic nuclei emitted by other stars and accelerated to near-light-speed, over millions of years, by galactic magnetic fields. These high charge, high energy (HZE) particles, among which iron nuclei are particularly abundant, either go straight through thin spacecraft shielding or create showers of secondary radiation. “Secondary particles from these collisions can be even more damaging than the primary particles,” says Vazquez, who has determined that large fractions of the cells in astronauts’ brains would be hit at least once by HZE particles on a three-year Mars mission.
HZE particles seem inherently more damaging than lighter nuclei or gamma rays when they strike living tissue. Cells exposed to them naturally or in laboratory particle-beam experiments show relatively broad areas of damage around the tracks the heavy, speeding particles have followed. “Even a particle that doesn’t directly hit a cell’s DNA can affect its function and viability,” says Vazquez. Particle radiation also can cause a “bystander effect,” in which particle-struck cells undergo changes that somehow trigger damage or death in neighboring cells.
Neural stem cells – the weakest link?
A few years’ worth of such hits, affecting a significant fraction of brain cells, could have serious consequences for cognitive functioning. Over the past decade, researchers using a NASA particle beam facility at Brookhaven have shown that HZE bombardment of lab rodents’ brains reliably impairs certain kinds of memory-dependent behavior—in a manner similar to that seen in ordinary aging.
A growing body of evidence suggests that such impairments are due largely to damage to stem cells in the hippocampus—a key memory region and one of the only places in the brain where stem cells normally exist and replenish neurons throughout adult life. In a paper in Experimental Neurology in 2008, researchers reported that “quiescent,” infrequently-dividing stem cells in the hippocampus are particularly sensitive to HZE radiation. “In our tests in mice, around half of the quiescent hippocampal stem cells were killed, under particle radiation conditions where we didn’t see much cell death elsewhere in the brain,” says Grigori Enikolopov, a scientist at Cold Spring Harbor Laboratory in New York who was a senior author of the study.
Enikolopov notes that the result was “surprising and counter-intuitive”—given that slow-dividing cells are normally considered more resistant to radiation, and fast-dividing cells more vulnerable. (An attempt at division, by a cell with heavily damaged DNA, is relatively likely to end in the cell’s self-destruction.) Gamma-ray bombardment of the brain in cancer therapy has been known to impair stem-cell-driven “neurogenesis” and thereby cause delayed cognitive impairments—but it seems to do so by affecting faster-dividing neural stem cells, rather than quiescent ones.
Why HZE would have its greatest impact on quiescent stem cells remains a mystery. But the fact that it can relatively easily impact the hippocampal stem cell population is ominous, given the hippocampus’s role in memory as well as in mood regulation. “Astronauts with severely impaired neurogenesis could, in the worst case scenario, experience certain kinds of memory impairment and also become depressed,” Enikolopov says.
Mechanisms and mitigation
If spacecraft shielding can’t protect Mars-bound astronauts from HZE radiation, what can? Since radiation is known to increase the levels of damaging oxygen molecules within cells, anti-oxidant drugs might be somewhat protective. “Antioxidants are very popular now in terms of possible radioprotection options,” says Martha Sanchez, a NASA-funded researcher at Loma Linda University. Therapies that enhance neural stem cell activity, such as physical exercise and serotonin-boosting antidepressant drugs, are also potentially useful. “Unfortunately we can’t really pinpoint optimal radioprotective strategies because we don’t yet understand the precise [damage-causing] mechanisms,” adds Sanchez.
Coming to grips with those mechanisms is a major goal of NASA’s current research efforts, and at Loma Linda, Sanchez is one of several scientists working in this area under NASA grants. She studies the effects of gamma, proton, and HZE radiation on key cellular signaling pathways, and already has reported that such radiation can cause sustained changes in the way that a major neurotransmitter, glutamate, is processed by brain cells. “In general, something is happening over a certain period of time that’s changing the cells’ environment and thereby causing damage,” she says.
Another question that Sanchez and other NASA-funded researchers intend to explore is how such effects change when the same radiation dose is delivered over a longer period. For practical reasons, most experimenters to date have exposed cells or lab animals to one or a few relatively intense bursts of particle radiation, rather than the low-intensity but years-long radiation of interplanetary space. “For future grants, we’re designing experiments with low-dose chronic exposure, to better reflect what goes on in space,” says Sanchez.