On the day this past January that President Bush was scheduled to announce a major new space policy, more than 100 scientists jammed into the Grandstand Sports Bar in Montgomery, Texas, to watch the address. They had been waiting years for this moment, but even when the president mentioned plans for a Moon base by 2020, to be followed by "human missions to Mars and to worlds beyond," the scientists didn't cheer. "The reaction was serious," recalls John Charles, a biophysicist who was in the crowd. "It was more like, 'we've got an awful lot of work to do.'"

This group of physiologists, biochemists, physicists, psychologists and physicians from around the nation (who happened to be at a conference in Montgomery) has been working on a challenge perhaps even more daunting than constructing a spacecraft to carry astronauts up to 498 million miles to Mars and back: getting them home alive and well.

In 1997, experts at NASA and at the National Space Biomedical Research Institute, a Houston-based consortium of university and national labs, set out to identify the health problems engendered by such a journey, which would take about three years, round trip. They've identified 55 threats, from radiation-induced cancers to depression. Some problems, like malnutrition (how to store enough water and grow a three-year supply of food), won't be impossible to solve, the scientists predict. Other challenges, though, are so complex as to provide fodder for critics who insist that prolonged space exploration is better suited to robots than people.

The record for the longest stay in space belongs to Russian medical specialist Valery Polyakov, who spent 438 days aboard the Russian station Mir, which was launched in 1986 and decommissioned in 2001. The International Space Station, run by a partnership of 16 nations including the United States, Canada, Russia and Japan, was first occupied in 2000 and has housed nine expeditions for stays up to 195 days.

One of the biggest problems confronting people who spend more than a month or two in space is the potentially devastating loss of bone tissue, which could result in fractures. On Earth, bone tissue, stimulated by the pulling and pushing of muscles acting against gravity, normally cranks out new bone cells. But in the microgravity of space, beyond the reach of Earth's and Mars's gravitational fields, the breakdown of bone tissue accelerates while new production slows, resulting in dangerously thinned and fragile bones.

For years, scientists have measured astronauts' bone density and also conducted studies in which Earth-bound volunteers spent weeks lying in bed, to simulate how muscles go slack in microgravity. Linda Shackelford, a physician who heads the Johnson Space Center's bone and muscle lab, says the researchers working on the problem have made progress. One way to slow bone loss in space, the evidence suggests, is exercising with a machine that generates some of the resistance that gravity typically provides. NASA put a prototype of the exercise machine on the International Space Station for its first mission. Astronaut Bill Shepherd, who spent nearly five months in the station, until March 2001, worked out with that machine six days a week for up to 45 minutes a day. "He looked pretty good when he came back," Shackelford says, adding that medical tests showed that space station astronauts who used the machine have generally experienced less bone loss in the spine, hip and pelvis than Mir cosmonauts. NASA scientists are also studying whether astronauts might benefit from the drug alendronate, which slows the breakdown of bone tissue and is routinely prescribed to women on Earth with osteoporosis.

Physical problems are not the only kind Mars astronauts face. For most of NASA's 46-year history, the agency has downplayed emotional woes. And the fliers themselves, beginning with the can-do Mercury astronauts, the first Americans to orbit Earth (between 1961 and 1963), tended to be closemouthed about psychological troubles. Though NASA set up a Behavior and Performance Laboratory in 1984, it wasn't until 1995, when U.S. astronaut Norm Thagard spent 115 days on Mir with two Russian cosmonauts, that U.S. space officials publicly acknowledged that astronauts needed additional training for the psychological challenges of long spells in space.

During his stay on Mir, Thagard, a physician and engineer who had flown four shuttle missions, repeatedly told ground controllers that he wanted to speak with his family and colleagues more than once a week, as he'd been doing, and that he felt isolated. Poor planning by NASA and the Russian space agency kept him from conducting most of his experiments, putting him at loose ends. He lost 13 pounds because he didn't much like the Russian food—soups, jellied meats and fish. After returning to Earth, he told reporters that if the mission had been extended another three months, he might not have made it.

Other astronauts also had difficulties on Mir. Some quarreled with cosmonauts. Others couldn't sleep for long periods or sank into depression and refused to speak to mission controllers or fellow fliers. Many cosmonauts complained that mission controllers were too demanding. In 1997, cosmonaut Vasily Tsibliev, exhausted after four months in space, lost control of an approaching unmanned supply ship that rammed into Mir, cracked its hull and sent the station into a slow spin that took days to stop.

Given the occasional need for a reality check in space, where a voice delay of up to nearly half an hour might preclude talk therapy with a psychologist on Earth, researchers at the University of Pennsylvania School of Medicine and Rutgers University are trying to develop an onboard computer that "reads" an astronaut's face for signs of emotional distress. Harvard University researchers have devised a series of mental tests that can be administered by a hand-held computer and that would help evaluate whether an astronaut is perhaps too fatigued to perform a complex task like a spacewalk.

In contrast to a flight on a shuttle or even a stint on the space station, a journey to Mars would most likely preclude sending a sick astronaut home for treatment. And if giving CPR is tricky on Earth, it's downright bizarre if the resuscitator is floating inside a spacecraft. Scientists have programmed a computerized dummy patient on which astronauts practice in-flight emergency care. They have tested—with good results, says Hal Doerr, head of medical operational support at the agency's space biomedical institute—a dummy on the KC-135 airplane that NASA uses to simulate weightlessness. The so-called vomit comet executes dives and climbs to negate gravity's effect for as many as 25 seconds at a time.

Ionizing radiation, emitted by the Sun and other celestial objects, can penetrate a spacecraft and wreak havoc with human cells, potentially increasing the risk of cancer. To be sure, no astronaut has developed cancer attributable to radiation exposure in space, but so far the flights have been limited to low-Earth orbit or a few brief jaunts to the Moon. Preventing damage caused by solar and cosmic radiation is years away, says Frank Sulzman, manager of the space radiation health project at the Johnson Space Center. Adding a radiation shield to a spacecraft could add billions to the cost, according to some estimates. Though scientists have developed guidelines for how much radiation astronauts can be exposed to in low-Earth orbit, where the planet's magnetic field blocks some radiation, they're still in the dark about safe levels of radiation in deeper space, where radiation levels are higher. Last year, NASA opened a new $34 million Space Radiation Laboratory at Brookhaven National Laboratory in Upton, New York, to test the effects of radiation on microorganisms, human cells in lab dishes, and lab rodents. The researchers want to know how cosmic radiation affects the central nervous system and at what levels radiation causes cellular damage that could lead to malignant growth. In a few years, Sulzman says, the agency will set new standards for radiation exposure on short-term missions to the Moon, but it will be a decade or so before they've done enough lab research to establish guidelines for a voyage to Mars.

Some scientists question whether enough can ever be done to make a Mars journey reasonably safe. "I think everybody knows that high-energy radiation is going to be a terribly serious problem," says Robert Park, a University of Maryland physicist and director of public information at the American Physical Society. Park has long argued that only robots are suited to explore space. Also, he believes that even medically trained astronauts will lack the technology as well as the experience with weightlessness to handle serious medical emergencies in space, which are bound to arise. "There's always a problem when dealing with human beings," he says. "If a robot develops a problem, it's a pity, but we send up another one and don't declare a national day of mourning."

Charles, of the biomedical astronautics group, says if the United States decides to send people to Mars and back, the nation may simply have to live with the reality that the voyage—among the most hazardous undertakings in history—could not possibly be fail-safe. "All the problems may never be solved," he says, adding: "At some point a responsible program official will have to sign his or her name on the dotted line and say, 'We acknowledge that there is a level of risk remaining and we accept it.'"