1991 Lawrence Berkeley National Laboratory’s Research Review Article:

Studies at LBL's Bevalac are aimed at resolving uncertainties about radiation risks to space travelers.

By Jeffery Kahn

Midway through the 20th century, more than a decade before a human first rocketed into space, scientists at this Laboratory began exploring the biological hazards of cosmic rays. The work was an outgrowth of research that began in the 1930s, when the Laboratory became the birthplace of nuclear medicine, conducting seminal studies on the medical uses of radiation and on radiation safety. In a 1952 paper, biophysicist Cornelius Tobias outlined the spectrum of radiation to which a human space traveler would be exposed and described potential effects, including cancer, brain and nerve-tissue damage--and a remarkable, optical phenomenon. When the nuclei of heavy elements that streak through space strike a human eye, a future astronaut would perceive ghostly flashes of light, Tobias predicted. Twenty years after Tobias first described the phenomenon, the lunar crew of Apollo 11 reported seeing odd "light flashes and streaks." So did astronauts aboard six subsequent lunar missions. Yet, back on Earth, many experts scoffingly dismissed these reports.

To confirm the existence of these effects, Tobias conducted a unique experiment at the Bevalac, an accelerator that can be likened to a cosmic-ray factory. The Bevalac can generate a stream of particles akin to those that flash across interstellar space. The machine strips electrons from heavy elements such as iron, accelerating and focusing the nuclei into a beam of particles traveling at nearly the speed of light. Tobias, in a controlled experiment, was exposed to the beam from the Bevalac and observed a visual phenomenon never before seen on Earth.

"You see visual flashes," he later recalled. "It is an exhilarating sensation. It is as though you are looking into the universe itself." This visual effect remains puzzling. Scientists know what type of radiation causes the effect and what part of the eye is involved, but the physical and biological basis of the effect has been only partially explained.

While significant scientific progress has been made toward understanding cosmic rays since Tobias' 1952 prediction, much still remains to be learned. Scientists know that cosmic rays cause multiple biological effects. But the complex chain of molecular events triggered by these exposures is uncertain and the risk of cell damage, cancer, and genetic mutation unknown. Also, the best means and materials to shield astronauts, minimizing their risk, remains undecided.

Lawrence Berkeley Laboratory has proposed using its ground-based cosmic-ray factory to explore and resolve these mysteries. The Bevalac is the only facility in the country capable of simulating the spectrum of radiation native to space--from protons to highly energized particles as heavy as uranium. Under the proposal, the U.S. Departments of Energy and Defense and the National Aeronautics and Space Administration would join in dedicating LBL's Bevalac to a space radiation effects research program. The program is a prerequisite to the nation's plans for humans to eventually explore the planets.

Physicist Ben Feinberg, who heads operations at the Bevalac, is the principal investigator on the LBL proposal to operate the facility for space research. Feinberg points out that for many years NASA scientists, along with researchers from LBL and elsewhere, have used the Bevalac to study how cosmic radiation interacts with matter--everything from electronics to spacecraft shielding to human cells. Feinberg says this research would gradually increase so that by the middle of the decade a comprehensive program would be under way at the Bevalac and the facility predominantly devoted to this space initiative.

Working at the Bevalac, scientists would use cell cultures and animal models to assess the biological consequences of exposures to the different particles that are components of the space radiation environment.

In the past, risk has been estimated by dosage, a measure that gives little insight into the precise, long-term health effects when low doses are involved. Researchers say they can improve on this approach and intend to develop detailed knowledge able to pinpoint the damage that can be caused by even a single particle.

Research would also be conducted on measures to counter radiation. When the charged particles (also known as ions) of heavy elements encounter a spacecraft, they are not stopped in their tracks. Instead, they either pass through, slowed but with their energy largely intact, or hit other ions and shatter into a shower of fragments. As heavy ions and their fragments pass through humans, damaging interactions can occur.

Experiments would be conducted at the Bevalac to examine how various materials that could be used in a spacecraft wall would alter the cascade of particles that would ultimately reach an astronaut. Since it is almost impossible to totally stop these particles, biologists must deduce what is the most benign spectrum of particle radiation achievable. Then other scientists must determine what combination of shielding materials would produce this minimal radiation field inside the spacecraft.

The payoff from shielding research could add up to several billion dollars in savings on an interplanetary mission.

As currently envisioned, an interplanetary spacecraft would weigh some 300 tons and include 30 tons of shielding material. According to Tom Ward, scientific and technical advisor to the Department of Energy's Office of Space, "With research, it may be possible to redesign more effective, lighter-weight shielding using new composite materials. Conceivably, shielding could be reduced in weight down to between two and five tons. In terms of the cost of an interplanetary mission, we estimate that there will be a $50,000 savings for every pound of shielding weight that can be eliminated."

The studies at the Bevalac not only can reduce the costs of an interplanetary mission, but are vital to the well-being of the astronauts. Besides the extended duration of exposures on an interplanetary mission, the spectrum of radiation differs from past missions ****near Earth, and overall exposures and biological risks increase.

Stanley Curtis, a physicist with LBL's Cell and Molecular Biology Division, helped write the book on radiation exposures for astronauts and currently is busy rewriting the book on how to gauge the biological effects of cosmic rays. Since 1965, he has worked on understanding what happens to heavy ions as they travel through matter. Curtis is a member of the National Council on Radiation Protection and Measurements which, in 1968, published guidelines that today govern astronauts' exposures in low Earth orbit. A committee on which he currently sits is revising these guidelines incorporating what has been learned during the continuing analysis of epidemiological data from the Japanese A-bomb survivors. Curtis notes that up until now human space travel has been confined to the proximity of Earth. Within this domain, astronauts are exposed to radiation from the trapped radiation belts but are largely protected by the Earth's magnetic field from galactic cosmic rays emanating from outside the solar system. Astronauts on a planetary exploration will be exposed to these galactic cosmic rays which consist of a different spectrum of energies. Estimates by Curtis and the National Council on Radiation Protection and Measurements indicate that during a three-year Mars mission, astronauts would be exposed to roughly one sievert (100 rem) of radiation to their blood-forming organs. This is more than six times the maximum ****allowable**** dose equivalent over three years for nuclear workers in the U.S. By way of contrast, astronauts in low Earth orbit typically receive less than 1/1000th of the dose of a Mars voyage during their seven to 10-day missions. The components that comprise solar and galactic cosmic rays include protons (85 to 95 percent), helium ions (five to 14 percent), and the more hazardous high-energy heavy ions. Importantly, up to one percent of galactic cosmic rays consist of heavy ions, whereas particulate radiation from the sun generally contains less than one-tenth this number. Both protons and heavy ions can cause cell damage that results in tumors. However, because of the greater charge and ionizing power carried by a heavy ion, the likelihood of its causing a tumor may be roughly 10,000 times that of a proton, says Curtis. Curtis has quantified the radiation that astronauts would be exposed to during a three-year Mars mission by each of its constituent elements. His calculations assume that astronauts are protected by relatively heavy spacecraft shielding but that no solar particle event occurs during the voyage. (On rare, sporadic occasions, certain types of solar flares generate extraordinary storms of radiation. Since this radiation consists of predominantly low-energy protons, astronauts can effectively protect themselves with emergency "storm shelters.")

"Once a spacecraft is outside the Earth's magnetosphere," says Curtis, "the probability is that any given cell nucleus within an astronaut will be hit once every three days by a proton and once a month by a helium ion. The heavier ions will hit less frequently. That same cell, for instance, will be hit once every six years both by a carbon and oxygen ion and once every 100 years by an iron ion. When the full spectrum of particle radiation is included, over a three-year mission a heavy ion with charge between 10 (neon) and 26 (iron) would hit one in every three cell nuclei."

Curtis' precise calculations are a state-of-the-art demonstration of contemporary space physics. Curtis is even able to predict that six percent of all cell nuclei will be hit two or more times by heavy ions with charges between 10 and 26 during this hypothetical mission. But deducing the biological effects of these hits is another matter altogether. Whether a given hit will be benign or perhaps result in a tumor, a cataract, or damage to neural tissue is unresolved.

The proliferation of standard measures used to quantify ionizing radiation and exposures--including roentgen, rad, gray, absorbed dose, rem, sievert, and dose equivalent--testifies to the complexity of gauging the biological effects. Curtis believes he has a better way to assess and pinpoint risk, at least to astronauts traveling outside the Earth's magnetosphere.

"Galactic cosmic rays are unusual in that they are highly penetrating and will traverse virtually all the cells of the body as single particles," says Curtis. "What we need is a gauge of risk that accounts for this and that gives us a handle on the catalytic biological events that, years later, can result in effects such as cancer."

The abnormal transformation of a cell that results from radiation begins with molecular events in the DNA, such as deletions of genes, translocations, and other genetic rearrangements. These events, which can be a precursor to cancer, are probably initiated by single traversals of cell nuclei by charged particles. For that reason, says Curtis, counting the incoming particles that traverse a given point should offer a more scientific basis to assess risk. Curtis' approach introduces a fluence-related risk coefficient. Fluence refers to the number of incoming particles per unit of area. The system is a departure from the standard measure of dose equivalent, which is a calculation of average energy deposition weighted to yield the equivalent dose of gamma rays that would produce the same biological effect. Instead, Curtis accounts directly for heavy-ion exposures, the critical component of the radiation field outside the Earth's magnetosphere.

"We have a lot to learn," says Curtis. "What is the probability per unit fluence of triggering various biological responses--say, for instance, a cellular event that initiates or promotes the formation of a tumor, or cataracts, or neural damage? Different types of particles have different probabilities for inducing tumors. "These are unknowns, and they imply an ambitious future research agenda. The understanding of how cancer is induced by this type of ionizing radiation will come from a study of the biological effects that occur along the tracks of single particles. This coupled with a better understanding by biologists of the succession of important molecular events in the carcinogenic process will allow us to estimate more confidently the risk of radiation exposure on long-term planetary missions."

Curtis is part of a collaboration of physicists, biologists, and educators that is about to undertake these studies at a NASA-funded Specialized Center of Research and Training for Radiation Health. Led by Aloke Chatterjee of LBL's Cell and Molecular Biology Division, the center is teaming researchers at LBL and at Colorado State University's Department of Radiological Health Sciences. Work will focus on developing a better understanding of the health risks of heavy-ion exposures and on training a new generation of research scientists to serve the nation during the approaching era of long-term human space missions.

Heavy ions differ from other types of radiation in terms of the potential severity of their effects on human DNA. "We may have never been subject to heavy ions during evolution," says Chatterjee. "Had the Earth's magnetic field and atmosphere not protected us from heavy ions, I don't believe we would have evolved the same way." To understand this, it helps to picture the architecture of DNA, the macromolecule which regulates the chemical activities of each cell as well as its ability to accurately duplicate itself. DNA consists of two strands that, like a spiraling staircase, wind around one another and are bound by stairstep-like connections. Each stairstep consists of a bound pair of two compounds called nucleotides. Altogether, there are four types of nucleotides, but the same two always pair off together. Thus, if one of the pair is damaged or broken away, the other can serve as a template, facilitating repair by an appropriate replacement nucleotide.

Heavy ions differ from other types of radiation in their ability to cripple this repair mechanism. Other forms of radiation may result in breakages of a single strand of DNA, damaging one-half of a pair of nucleotides, but heavy ions have a greater likelihood of causing double-strand breaks, disrupting ready repair.

Double-strand breaks have been linked to cell death, cell mutation, cell transformation, and carcinogenesis. These double breaks apparently can be repaired by cellular enzymes but to what extent remains unknown. Priscilla Cooper of LBL's Cell and Molecular Biology Division and John Lett of Colorado State University are planning to investigate these enzymatic repair processes.

At the Bevalac, Cooper and Lett will conduct experiments to see how repair varies following irradiation by different heavy ions. Cellular damage near a double-strand break can be quite extensive, and in those cases, the enzymatic repair mechanism may not operate. Chatterjee says researchers also will explore the mechanisms for mutations. Heavy ions can cause biological damage either indirectly or directly.

Stripped of electrons as they travel across the galaxy, heavy ions carry a large positive charge. As they shoot through a human, they primarily interact electromagnetically, mainly with the water that comprises much of a human being. These indirect interactions with the electron clouds within volumes of water--electrons are ripped free, triggering a chaotic cascade of chemical changes--are the most common interaction for a heavy ion.

Direct nuclear interactions involve energy deposition directly in a DNA molecule. This phenomenon can cause various types of DNA damage, including double-strand breaks.

"We don't know whether both direct and indirect mechanisms are responsible for mutations," says Chatterjee. "When we understand that, we will be in a position to resolve other questions: Can we mitigate DNA damage? Can we protect cells?"

Spacecraft shielding will provide a fortress of protection for the astronauts. But no conceivable spacecraft wall can completely shield out ionizing radiation.

What configuration of materials would most effectively shield astronauts? Jack Miller, a nuclear physicist in LBL's Research Medicine and Radiation Biophysics Division, is conducting studies and experiments that can help answer this question. Miller currently heads a program initiated by LBL's Walter Schimmerling, who is now on leave to NASA to head its radiation health program.

Miller says that a critical test for shielding on an interplanetary spacecraft will be how well it mitigates the biological effects resulting from iron nuclei. Among the heavier ions, iron is relatively abundant. When galactic cosmic-ray heavy ions are weighted both by their numbers and by their potential biological effects, iron is the most significant.

"We have a very complex problem," says Miller. "For every different material and thickness of shielding, you get a different radiation environment inside the spacecraft.

"For instance, if you tell me that you have an iron nucleus coming in at a certain energy, I can compute how thick a piece of aluminum you would need to stop it. But a problem remains. Though you might be able to stop the iron particles, some of them are going to be involved with head-on collisions with the nuclei of aluminum atoms. When that happens, they will fragment into lighter nuclei that will continue to traverse the spacecraft. It is very difficult to predict what the products of those collisions will be. And it is impractical to have a spacecraft shield that can stop all these secondary particles."

Studies conducted by the Schimmerling-Miller group aim to measure this secondary radiation field, with the ultimate goal of minimizing its effect on astronauts.

In a typical experiment, a beam of heavy ions from the Bevalac is directed at a piece of shielding material, behind which detectors are placed to measure the complex radiation field produced by interactions between the beam and shield. In related work, similar detectors have been used to study the role of nuclear fragmentation in LBL's experimental cancer radiotherapy program, in which beams from the Bevalac are used to bombard tumors.

"Neon is one of the ions commonly used in the Bevalac radiotherapy program," explains Miller, "but what happens as these ions traverse the body? A neon nucleus has 10 protons and 10 neutrons, and we know that some of the neon ions will fragment as they pass through bone and tissue. Neon can fragment in a number of ways -- for example, into a carbon and two helium nuclei -- with varying consequences for the surrounding healthy tissue. These studies have allowed us to begin to characterize and quantify this complex radiation field." This knowledge currently is being used to help NASA design spacecraft shielding.

Rather than test every conceivable material and thickness of shielding, NASA is relying on computer models. One such model has been developed by Stan Curtis and another by Lawrence Townsend and John Wilson of NASA's Langley Research Center. The models predict the radiation environment, given a specific particle energy and thickness of shielding material. The LBL group provides input to the model in terms of nuclear fragmentation cross sections, a mathematical expression of the probability of particular fragments resulting from nuclear collisions with the shielding.

The Bevalac makes it possible to verify and to refine the predictions about which shielding materials are most effective. Different materials can be irradiated and tested at LBL's cosmic ray factory. Ultimately, through feedback from this research, efficient, protective shielding material will be fabricated.

Miller says this work represents the fruits of decades of theoretical work and scientific experimentation. "In many respects," he says, "we have developed a very sophisticated understanding of the effects of radiation. But in some areas, our understanding is still quite limited. We know a great deal about the effects of high doses and high dose rates, but much less about the lower dose rates typical from exposure to cosmic rays in space. "By taking advantage of the synergy among scientists in many different disciplines, we can develop a more precise understanding of the space radiation environment. Our ultimate goal is to make extended human habitation in space a practical reality."

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