Mars or bust: science helps those with the right stuff keep their stuff right.

The Apollo moon missions were a 21st-century idea that was slipped into the 20th century, said former astronaut Eugene Cernan in his 1999 book The Last Man on the Moon (St. Martin's Press). In the 1970s, soon after Cernan and his Apollo 17 crew completed the last moon mission of the 20th century, NASA developed the ferrylike space shuttle that has since dominated the U.S. space fleet. The shuttle was not intended to fly further than the distance required to orbit Earth, so there was no need to consider the health risks of years-long journeys into outer space.

Recently, however, plans to travel beyond Earth orbit have received new life. In January 2004, President Bush announced an initiative to return people to the moon, build a base there, and eventually travel to worlds beyond, namely Mars. As a first step, NASA's current official goal is to get back to the moon no later than 2020.

Sending people to Mars, however, would produce a unique set of complications for engineers and mission planners, most of which arise because the planet is so far away. William H. Paloski, a scientist at the Johnson Space Center in Houston, explains that the most probable mission would spend 6 months traveling outward; 18 months on the planet building a habitat, researching, and waiting for Mars and Earth to realign; and then 6 months homeward bound.

By comparison, a moon mission would be only 2 weeks long. In terms of duration, the difference between a moon and Mars mission is comparable to that between taking a family vacation in a spaceship and moving into one.

Early this year, in a document called a Bioastronautics Roadmap, NASA described the health risks of long-duration space travel. At the top of the list of risks is cosmic radiation. To protect astronauts from atomic nuclei that zip around the universe with high energy, some engineers propose deploying a giant magnetic field to surround the ship and deflect the radiation.

Biomedical researchers are already making progress on other items on NASA'S risk list. Microgravity atrophies muscles and depletes bone mass. A noisy spaceship and unnatural lighting disrupt sleep-wake cycles. And because there will be only limited medical expertise and equipment on board, an accident or illness, if serious, could abort a mission. Solutions to these problems would help make a Mars mission a go.

TETHERED TO TREADMILLS To the NASA physicians watching videos of astronauts on the moon, it was obvious that the few days of weightlessness on their lunar voyage had diminished the men's strength. By the time they stepped out on the lunar surface, "these individuals looked very spastic moving around on the moon" says Kenneth M. Baldwin, a member of the National Space Biomedical Research Institute (NSBRI), a consortium that coordinates a range of research in areas from psychology to medical technology. He notes that the physicians were surprised that the astronauts didn't injure themselves while performing tasks.

Baldwin, a physiology professor at the University of California, Irvine, studies muscle loss in space. The first muscles to atrophy in microgravity, Baldwin says, are in the calves, thighs, and back. "These are all the muscles that define posture and the ability to oppose gravity," he explains, "They're all compromised" by space conditions.

Currently, astronauts at the International Space Station exercise for at least 2.5 hours per day 6 days a week, either on a rowing machine or a treadmill. Most astronauts prefer the treadmill, Baldwin says. It's equipped with bungee cords to simulate 60 percent of Earth's gravity and to keep the user from floating away.

According to Baldwin, when these astronauts come back to Earth after 60 to 100 days in space, even though they've exercised, they've lost 25 to 30 percent of the muscle mass in their calves, thighs, and backs. "This implies that no matter what they've been doing in space, it hasn't prevented atrophy," Baldwin says.

He says that a better muscle-conditioning regimen could keep astronauts strong. Toward this end, he and his colleagues are exploring the genes and proteins responsible for muscle growth and, conversely, muscle loss in mice.

Rodents serve as good models for muscle loss in people, Baldwin says. When researchers suspend mice in slings that keep their hind legs off the ground, the unused leg muscles atrophy.

Baldwin's team has found that just a few days of muscle idleness reduce the activity of genes that regulate protein synthesis and the amounts of certain proteins in those muscles. Mice with atrophied muscles produce smaller-than-normal amounts of a protein called insulin receptor substrate 1 (IRS 1), which normally turns on several genes responsible for the production of other proteins in muscles.

Baldwin says that he intends to measure amounts of IRS 1 by monitoring blood chemistry in astronauts during tests of various exercise regimens. The results could tell researchers whether a specific workout is beneficial even before muscle atrophy becomes physiologically evident.

But a good exercise program doesn't benefit just muscles. Bone profits from a routine in which it must bear weight or, at least, the simulation of weight. Peter R. Cavanagh of the Cleveland Clinic Foundation agrees with Baldwin that space exercise has not worked well so far. "My feeling is, exercise hasn't been tailored correctly" to keep bones healthy, he says. An astronaut on the space station loses 1.5 percent of his or her hip-bone mass each month. In comparison, the typical postmenopausal woman loses 1 percent of her hip-bone mass each year.

It's normal for bone to leach minerals such as calcium, magnesium, and phosphorous, but on Earth, the body simultaneously replenishes those materials to rebuild bone. In microgravity, the usual cues for bone production, such as weight bearing, are missing. As a consequence, abnormally large amounts of calcium leave bones and enter the bloodstream. Losing bone density can lead to osteoporosis and a higher risk of fracture. Moreover, calcium in the blood collects in the kidney, where it can aggregate as a kidney stone--a painful and potentially debilitating condition.

Cavanagh concedes that researchers don't know whether Mars' gravity--which is 38 percent of Earth's--would be enough to protect astronauts from bone loss. Therefore, scientists are working to artificially manufacture gravity that is at least as strong as that of Earth. This force would be useful on Mars, on the moon, and on spacecraft making long trips.

In September, researchers from the University of California, Irvine displayed the prototype for a contraption that produces a gravitylike force that's five times as strong as Earth's gravity. It's dubbed the Space Cycle, or the "artificial-gravity gym." One astronaut rides a bicycle that travels around a pole producing centrifugal force. Opposite the bike is a moving cage that also circles the pole. A second astronaut can exercise in that cage under the influence of the faux gravity that the rider is creating (see video at www.nsbri.org/NewsPublicOut/Squat_Movie_05_17_05.mov).

SOMNONAVIGATION It's difficult for astronauts to find quality sleep for several reasons. The space shuttle is notoriously noisy, sleeping in mierogravity is awkward, and the shuttle's dim lighting can confuse the circadian system. Although astronauts routinely take medications to treat ailments from colds to motion sickness during their missions, a 1999 study found that 4:5 percent of all medication taken in space is sleeping pills.

"NASA allots 8 hours a day for astronauts to sleep ... however, a number of studies show that they sleep an average of 4 to 6 hours," says neurologist George C. Brainard of Thomas Jefferson University in Philadelphia. "If you continue to lose sleep day after day, there's a noted decrease in alertness and performance.... If you have chronic, partial sleep loss for 3 years, that's a [Mars-mission] deal breaker."

Sleep and wakefulness are two aspects of the circadian system, an internal timekeeper that regulates various fife rhythms in all vertebrates. At the heart of this system is the suprachiasmatic nucleus, a bundle of neurons in the brain's hypothalamus.

For the bundle to do its job, Brainard explains, it needs to synchronize with aspects of the body's external environment, such as daylight and darkness. The eyes provide the windows through which this brain area gathers information.

Scientists have determined that blue light at wavelengths between 460 and 480 nanometers, when absorbed by cells in the eye's retina, is the strongest stimulus for a healthy circadian rhythm. They've also found that signals are transmitted directly from the retina to the suprachiasmatic nucleus and that they bypass the visual-cortex region of the brain.

The discovery, about 5 years ago, that blue light is important to wakefulness and sleep has major implications for designing lighting schemes. The healthiest lighting must inform the circadian system as well as the visual system, says Brainard.

In the August Journal of Biological Rhythms, he reviews how light regulates consciousness. He suggests that further research can offer guidelines for lighting in spaceships that reduces astronauts' sleep problems. Rather than sleeping pills, the proper regimen of ambient light could give astronauts sought-after hours of shut-eye.

Through NSBRI, Brainard and Charles A. Czeisler of Harvard Medical School in Boston are working with companies such as Philips to develop fluorescent lights that are enriched in the blue part of the light spectrum. The researchers are also exploring light-emitting diodes, or LEDs, as an alternative to conventional lightbulbs (SN: 7/16/05, p. 43).

"The thing that's promising about [LEDs] is that they're smaller, use less energy, produce less heat, and there's no glass so they're resistant to strong vibrations and high gravitational forces" that can buffet a spaceship, Brainard notes.

His team is testing various combinations of light wavelengths and intensities for their effects on people's mood, behavior, and performance on cognitive tests. The winning formula will illuminate future spaceships and moon and Mars habitats, as well as buildings here on Earth, Brainard predicts.

DANGER, WILL ROBINSON Even assuming that astronauts can keep their wits about them by getting enough sleep and keep their muscles and bones healthy by exercising in artificial gravity, the possibility of a freak accident remains. "In space, you might not have weight, but you have inertia," explains Lawrence A. Crum of the University of Washington in Seattle. "[Astronauts] move 1,000-pound devices and push them around.... There was one case where a person almost got crushed."

The longer that astronauts are in space, the higher the risk of serious injury. The question, then, is how to treat trauma when the nearest hospital is millions of miles away.

Trauma response is always of interest to the military. So, the Defense Advanced Research Projects Agency is cofunding, with NSBRI, Crum's efforts to create an ultrasound device that could stop internal bleeding, such as that caused by collision with a heavy object. He aims to make the ultrasound device small and fighter than 50 pounds, so it can easily travel on the battlefield or in space. It should also be foolproof enough so that a soldier or astronaut who isn't a physician could save a companion's life in an emergency.

Crum's solution is known as high intensity focused ultrasound (HIFU). It's a more powerful and more intensely focused version of the ultrasonic waves used to image babies in a womb. Such waves reflect at boundaries between fluid and soft tissue or soft tissue and bone. A specialized probe placed against the skin detects the reflections, and a computer analyzes them. But, at high intensities, targeted waves can destroy a specific bit of tissue, for instance, cauterizing a blood vessel to stop internal bleeding.

The ancient Egyptians used scalpels to cut out bad portions of our body," Crum remarks. "There's been a lot of progress in medicine, but people still use scalpels to cut out bad portions of the body."

Crum notes that in Europe, China, Japan, Mexico, and several other countries, an HIFU device too large for space is already being used to destroy tumors. It's "becoming the treatment of choice for many forms of cancer," says Crum. In the United States, trials are about to begin for treatment of pancreatic cancer.

On a space mission, Crum envisions the ultrasound device's first order of business being to image a person's internal organs to locate sites of bleeding. Then, an HIFU operator would focus the sound waves on the ruptured blood vessel and increase their intensity to 1 million times that used for imaging. Crum says that HIFU could heat tissue to 80[degrees]C--high enough to cauterize a blood vessel and stop the bleeding.

For hospitals on Earth, a Seattle-based company called Therus Corp. is developing a device based on this principle. It would seal the wound that's produced when a catheter is removed from an artery.

HIFU could do much more than cauterize a blood vessel, says Crum. He envisions it finding and destroying tumors, blood clots, and kidney stones in astronauts visiting Mars. With HIFU, surgical procedures could be completed without exposing a person's internal organs to the environment, thus avoiding infections or the microgravity debacle of body liquids dispersing into the surroundings.

LIVE LONG AND PROSPER Whether people venture beyond the moon in the next 30 years or the next 300, the ongoing research to address health issues could still be benefcial. Bone- and muscle-loss studies could reveal new ways to keep elderly people strong and aid recovery of patients who are bedridden or have spinal cord injuries.

Light and sleep research could improve treatments for chronic insomnia and the depression that strikes some people when they lack sun exposure. Discoveries in this area could also reset the body clocks of shift workers. On Earth, HIFU may benefit emergency trauma care and provide noninvasive treatments for blood clots and cancers.

Regardless of the space missions to come, Earth-based spin-offs of space-targeted research are inevitable--if cordless power tools, superalloy golf clubs, and high-tech foam mattresses are any indication. The answers to the current lineup of biomedical space challenges just might slip elements of 22nd-century medicine into the 21st century.