Micro-gravity research has been conducted primarily in orbit. Ground-based studies, involving extended periods of bed rest, water immersion, or head-down tilt, have addressed certain questions related to fluid redistribution and lack of exercise. Parabolic flights in the KC-135 "vomit comet" and other jet aircraft provide brief sub-orbital exposure to micro gravity (on the order of 30 seconds) interspersed with hyper gravity (acceleration greater than 1 g) - these have been used primarily for studies in motion sickness, coordination, and ergonomics. The subjects of micro-gravity research have been plants and animals, as well as humans.
The basic survivability of weightlessness for periods of at least a few days was established by the dog Laika, aboard the Soviet Sputnik II, launched on November 3, 1957 (only one month after the first Sputnik). Both the Soviet Union and the United States tested their launch, life-support, and reentry systems on numerous animals before risking manned flight. The United States' Skylab missions of 28, 59, and 84 days in 1973-1974 surpassed all previous endurance records for space flight, and continue to serve as important benchmarks in US space medicine: they remain the longest missions ever flown by the US. The Soviet Union has since completed a number of long-duration missions that far surpass Skylab: Vladimir Titov and Moussa Manarov returned from the Mir space station on December 21, 1988, after 366 days in orbit. These long-duration space flights, as well as the ground tests and aerial flights alluded to earlier, have revealed many problems with prolonged exposure to weightlessness.
The following summary is derived primarily from Living Aloft: Human Requirements for Extended Spaceflight [2], Pioneering Space: Living on the Next Frontier [3], and a series of articles [4, 5, 6, 7, 8, 9, 10] that appeared in the Journal of the American Medical Association. Articles from Science News and Aviation Week and Space Technology are also cited.
Fluid Redistribution: Under normal gravity conditions, body fluids tend to pool in the lower extremities. In micro gravity, fluid pressure equalizes, and fluids shift toward the head. This precipitates many of the problems described below. Medical complications might be avoided if Earth-normal fluid pressure could be maintained. American and Soviet crews have experimented with periodic use of lower-body negative-pressure suits designed to pull fluids into the lower extremities [11, 12].
Fluid Loss: The brain interprets the increase of fluid in the cephalic area as an increase in total fluid volume. In response, it activates excretory mechanisms [13]. This compounds calcium loss and bone demineralization. Blood volume may decrease by 10 percent, which contributes to cardiovascular deconditioning [14]. Fluid volume may stabilize at some reduced level, but crew members must consume a good deal of water to prevent dehydration.
Electrolyte Imbalances: Changes in fluid distribution lead to imbalances in potassium and sodium, and disturb the autonomic regulatory system [15]. One countermeasure has been to swallow 3 grams of sodium chloride in 400 milliliters of water three times on the final day of orbit, in preparation for returning to normal gravity [16].
Cardiovascular Changes: Lower diastolic blood pressure and a tendency to spontaneous syncope (fainting) have been noted consistently among space crews; these are attributed to fluid loss. On Salyut and Skylab, the heart's stroke volume and cardiac output were generally elevated during flight but fell to subnormal levels upon return to Earth. Radiographic measurements indicated a progressive decrease in cardiac size.
A more elaborate study was conducted during a flight of the shuttle Discovery in 1985 (mission 51-D, April 12-19, 1985), with data collected from four crew members. Discovery was better equipped for cardiovascular research, but its 7-day flight was significantly shorter than any of the Skylab missions. In this study, both systolic and diastolic pressures rose, with a mean increase of 20 percent - contrary to earlier findings. In comparing Discovery and Skylab, one expert speculated that the reason for the discrepancy might be that the Discovery blood pressure readings were taken earlier in the flight.
Other Discovery measurements confirmed previous findings. Echocardiography revealed that the volume of the right ventricle decreased by 35 percent during the first day of flight; the left ventricle increased by 20 percent during the first day, then decreased to 85 percent of its preflight volume during the second day. Stroke volume varied with the left ventricular volume, while heart rate increased by 20 percent. As a result, cardiac output (heart rate times stroke volume) increased substantially during the first day, then decreased to preflight level. Increased blood pressure and near-normal cardiac output indicated an increase in peripheral vascular resistance (pressure divided by output) [17, 18, 19, 20].
To summarize: in weightlessness, an increase of fluid in the thoracic area leads initially to increases in left ventricular volume and cardiac output; as the body seeks a new equilibrium, fluid is excreted, the left ventricle shrinks, and cardiac output decreases; upon return to gravity, fluid is pulled back into the lower extremities, and cardiac output falls to subnormal levels. It may take several weeks for fluid volume, peripheral resistance, cardiac size, and cardiac output to return to normal.
Red Blood Cell Loss: Blood samples taken before and after American and Soviet flights have indicated a loss of as much as 0.5 liters of red blood cells. Studies conducted in Spacelab I in 1983 showed that hemoglobin and hematocrit increased significantly from preflight levels, due to a decrease in plasma volume. There was no significant decrease in serum erythropoietin (a hormone that stimulates red blood cell production), and no evidence of abnormal cell maturation. Scientists are looking into the possibility that weightlessness may cause a change in splenic function that results in premature destruction of red blood cells [21]. There is also evidence of loss through microhemorrhages in muscle tissue (see below). Cosmonauts have ameliorated the loss by consuming 2 to 3.5 liters of fluid per day. Soviet doctors believe the loss is mostly a normal adaptation to space that does not endanger human health [22].
Muscle Damage: Muscles atrophy from lack of use. Contractile proteins are lost, and tissue shrinks. Serum samples taken before and after space flight have shown an increase in circulating nitrogen and creatinine kinase, both of which are indicators of muscle breakdown. Muscle loss may be accompanied by a conversion of muscle type: rats exposed to weightlessness show an increase in the amount of "fast-twitch" white fiber relative to the bulkier "slow-twitch" red fiber, which is thought to carry the burden in endurance exercise [23].
In 1982, cosmonauts returned from a 211-day mission "in obviously debilitated condition. Although they had exercised daily, their muscles were so flabby that they were barely able to walk for a week, and for several weeks afterwards required intensive rehabilitation" [24].
In 1987, rats exposed to 12.5 days of weightlessness showed a loss of 40 percent of their muscle mass and "serious damage" in 4 to 7 percent of their muscle fibers. "The affected fibers were swollen and had been invaded by white blood cells that 'clean up' infected or inflamed areas. Blood vessels had broken and red blood cells had entered the muscle. Half the muscles had damaged nerve endings" [25]. The damage may have resulted from factors other than simple disuse, in particular: stress, poor nutrition, and reduced circulation - all of which are compounded by weightlessness; and radiation exposure - which is independent of weightlessness. Biopsies of human astronaut muscle are required in order to determine whether they suffer the same pathology as the rats.
There is concern that damaged blood supply to muscle may adversely affect the blood supply to bone as well. Suggested countermeasures include exercise plus anabolic steroids. Cosmonauts have also used a "Tonus-2" device to electrically stimulate their muscles [26].
Bone Damage: Wolff's Law states: "Every change in the form and the function of bones, or in their function alone, is followed by certain definite changes in their internal architecture, and equally definite changes in their external conformation, in accordance with mathematical laws." Bone tissue is deposited where needed and resorbed where not needed. This process is regulated by the piezoelectric behavior of bone tissue under stress [27, 28, 29]. Because the mechanical demands on bone are greatly reduced in a micro-gravity environment, the bones essentially "dissolve". Bone disuse symptoms include: loss of calcium, nitrogen, and phosphorus; decreased bone size and volume; and formation of urinary stones [30].
Skylab astronauts lost 7.9 percent of their bone calcium in 3 months. Soviet cosmonauts have averaged 14 percent loss over 6 months, though one cosmonaut lost 19 percent on a 140-day flight while others lost only 8 percent on a 175-day flight [31]. The margin of error for measurements obtained through photon absorptiometry is 3 to 7 percent, which is large relative to the estimated losses. On Skylab, bone loss was also estimated through calcium-balance studies: "While mean urine calcium content continued to increase rapidly after takeoff, it reached a plateau within 30 days. In contrast, mean fecal calcium continued to increase steadily throughout flight. These measurements were continued upon return, and they indicated that urine calcium content had usually been reduced to preflight levels by the 10th day after landing, but that fecal calcium was not reduced until the 20th postflight day" [32].
Evidence suggests that non-weight-bearing bones such as the skull or fingers are not affected. In the legs and spine, however, calcium is lost from both the cortical (outer) and trabecular (inner, spongy) bone tissue. Experts fear that the body's calcium balance might be restored before the bones have replaced the lost minerals, resulting in permanent damage. While cortical bone may regenerate, loss of trabecular bone may be irreversible [33, 34].
As of 1986, diet and exercise had been ineffective in preventing the damage. Davis concludes that the astronauts' treadmill tethers do not provide enough tension to jolt their skeletal systems adequately: "Their heels never come into contact with the treadmill belt" [35]. On the other hand, devices that do strike the heel have also been tried without success, and Woodard cites evidence that "even marathon running does not stimulate significant bone formation." He notes the positive relationship between muscle mass and bone mass, and instead of hours-long endurance exercise on treadmills and similar equipment, he proposes 30 minutes of strength training per day [36, 37]. Keller, Strauss, and Szpalski also propose high-intensity exercise for brief periods [38]. Another attempted countermeasure has been the periodic use of a "penguin suit" designed to place an axial load on the musculoskeletal system [39]. Medical researchers are also studying the metabolism of black bears, which suffer no bone loss during five months of winter inactivity. A substance unique to black bears was isolated in 1988, but its metabolic function had yet to be determined [40, 41].
When Yuri Romanenko completed his 326-day mission in December 1987, there was speculation that Soviet medical researchers had finally identified a leveling-off of the bone loss: not only was this a new endurance record, it also surpassed the old record by 89 days - the largest increment ever [42]. Nevertheless, such long endurance space flights remain controversial.
Hypercalcemia: Fluid loss and bone demineralization conspire to increase the concentration of calcium in the blood, with a consequent increase in the risk of developing urinary stones [43, 44].
Immune System Changes: Weightlessness induces changes in both the distribution and efficacy of immune agents: there is an increase in neutrophil concentration and decreases in eosinophils, monocytes, and B-cells [45]; a rise in steroid hormones and damage to T-cells [46]. In Spacelab I (1983), when human lymphocyte cultures were exposed in vitro to concanavalin A, the T-cells were activated at only 3 percent of the rate of similarly treated cultures on Earth [47]. Similar experiments must be conducted on blood drawn during space flight to determine whether the T-cells react as poorly in vivo. Whether such changes adversely affect the body's immune response is not known, but crew members do seem to be more susceptible to infection after returning to Earth. There is concern that, once introduced, infection could spread quickly in the closed environment of a spacecraft. Loss of T-cell function may also hamper the body's resistance to cancer - a danger exacerbated by the high-radiation environment of space [48].
Interference With Standard Medical Procedures: Fluid redistribution affects the way drugs are taken up by the body, with important consequences for space pharmacology [49]. Bacterial cell membranes become thicker and less permeable, reducing the effectiveness of antibiotics [50]. Space surgery will also be greatly affected: "tissue planes tend to separate, and organs float and bob in the operative field ... surface tension tends to keep venous bleeding oozing along surfaces, while pulsatile arterial bleeding forms droplets, streamers, and clouds" [51].
Vertigo and Spatial Disorientation: Without a stable gravitational reference, crew members experience arbitrary and unexpected changes in their sense of verticality. At various times, an individual may feel that he is upright, lying horizontally, or hanging upside down. Also, rooms that are thoroughly familiar when viewed in one orientation (as during training in Earth-based mock-ups) may become unfamiliar when viewed from a different up-down reference. Skylab astronaut Ed Gibson reported a sharp transition in the familiarity of the wardroom when rotated approximately 45 degrees from the "normal" vertical:
Being upside down in the wardroom made it look like a different room than what we were used to. When I started to rotate back and go approximately 45 degrees or so off the attitude which we normally call "up," the attitude in which we had trained, there was a very sharp transition in my mind from a room that was sort of familiar to one which was intimately familiar.
Attempted countermeasures include "Cuban Boots" (named for Cuban cosmonaut Arnaldo Mendez) that apply pressure to the bottoms of the feet to simulate standing on solid ground, and architectural design features that visually distinguish "floor" and "ceiling" surfaces. There is evidence that, in adapting to the new environment, the brain comes to rely more on visual cues and less on other senses of motion or position. Upon return to gravity, the old sense of balance and posture must be reacquired. In orbit, Skylab astronauts lost the sense of where objects were located relative to their bodies when they could not actually see the objects. After returning home, one crew member fell down in his house when the lights went out unexpectedly [52, 53].
Space Adaptation Syndrome: This is the preferred term for a form of motion sickness that occurs in space flight. It did not occur in the Mercury and Gemini programs, probably because the astronauts were firmly strapped into small capsules. American astronauts first experienced it in the larger Apollo; Soviet cosmonauts discovered it somewhat earlier. Now that astronauts and cosmonauts routinely float around in relatively roomy orbital laboratories, about half of them are afflicted. Symptoms include nausea, vomiting, anorexia, headache, malaise, drowsiness, lethargy, pallor, and sweating. The sickness is believed to be caused by sensory conflicts within and between the vestibular and visual systems, leading to a neural mismatch that affects the autonomic nervous system. However, susceptibility to Earth-bound motion sickness does not correlate with susceptibility to space sickness. The sickness is usually self-limiting, lasting from one to three days. Attempted countermeasures include: medications; head movement schedules - analogous in principle to vaccination - to accelerate the process of adaptation; head restraints; and autonomic response control through biofeedback training [54, 55].
Loss of Exercise Capacity: This may be due to decreased motivation as well as to the physiological changes described above. Cosmonaut Valeriy Ryumin wrote in his memoirs: "On the ground, [exercise] was a pleasure, but here we had to force ourselves to do it. Besides being simple hard work, it was also boring and monotonous." Weightless exercise can also be clumsy: equipment such as treadmills, bicycles, and rowing machines must be festooned with restraints to prevent the user from simply shoving off. Perspiration doesn't drip off, but accumulates on the surface of the skin. Skylab astronauts described disgusting pools of sweat half an inch deep sloshing around on their breastbones. Clothing becomes saturated, and several towels may be needed to wash off afterwards [56, 57].
Degraded Sense of Smell and Taste: The increase of fluids in the head causes stuffiness similar to a head cold. Foods take on an aura of sameness, and there is a craving for spices and strong flavorings such as horseradish, mustard, and taco sauce [58, 59].
Weight Loss: Fluid loss, lack of exercise, and diminished appetite result in weight loss. Space travelers tend not to eat enough, and meals and exercise must be planned to prevent excessive loss [60, 61].
Flatulence: Digestive gas cannot "rise" toward the mouth, and is more likely to pass through the other end of the digestive tract - in the words of Skylab crewman-doctor Joe Kerwin: "very effectively with great volume and frequency" [62]. Without gravity there is no convection; contaminants neither rise nor settle, but remain suspended in the air.
Facial Distortion: The face becomes puffy, and facial expressions become difficult to read - especially when viewed sideways or upside down. Voice pitch and tone are also affected, and speech becomes more nasal. These distortions interfere with communication and can lead to misunderstandings between crew members and between the crew and ground controllers [63].
Changes in Posture and Stature: In weightlessness, the neutral body posture approaches the fetal position. The change in posture, as well as the need for restraints, affects the man-machine interface and calls for modifications of work stations from typical terrestrial designs [64]. Also, in the absence of loading, the human spine tends to straighten and lengthen. Each of the Skylab astronauts gained an inch or more of height, which adversely affected the fit of their space suits [65].
Changes in Coordination: Earth-normal coordination unconsciously compensates for self weight. In weightlessness, the muscular effort required to reach for and grab a tool or control is reduced, and there is a tendency to reach too "high" [66].
Besides these physiological changes, weightlessness also introduces myriad practical problems. The malfunctioning zero-gravity toilet was a continuing nuisance on early Shuttle flights. The zero-gravity showers on Salyut and Skylab had to be watertight from floor to ceiling and drained by vacuum; users had to plug their noses and breathe through an air hose to keep from inhaling water droplets. (The Shuttle has no shower; astronauts use wet-wipes.) Over-stuffed or poorly-packed containers have a jack-in-the-box effect when opened; to astronaut Ed Gibson, the Skylab film vault was a "snake pit". Splashed or spilled water, food crumbs, dropped pencils, and other litter hangs suspended in the air until it settles into a corner someplace (not necessarily on the "floor") or migrates to an air vent. Actions that rely on weight for force, or friction for stability, are nearly impossible to accomplish, and work stations must provide alternative means of restraint. But these are all merely engineering problems; there is little doubt that they can be overcome through refinements in design and training. They pale in comparison to the biological problems.
Many of the physiological changes do not pose problems as long as the crew remains in a weightless environment. Trouble ensues upon the return to life with gravity. The reentry process itself is especially dangerous: after the crew has become semi-adapted to weightlessness, it is suddenly subjected to acceleration greater than 1 g. After a 237-day mission in 1984, Soviet cosmonauts felt that if they had stayed in space much longer, they might not have survived reentry [67].
In 1987, in the later stages of his 326-day mission, Yuri Romanenko was highly fatigued - both physically and mentally. His work day was reduced to 4.5 hours, while his sleep period was extended to 9 hours, and daily exercise on a bicycle and treadmill consumed 2.5 hours. Romanenko was accompanied by Alexander Alexandrov for the final 23 weeks in orbit. At the end of the mission, the Soviets implemented the unusual procedure of sending up, along with the replacement crew, a "safety pilot" to escort Romanenko and Alexandrov back to Earth. Despite his rigorous daily exercise, Romanenko had lost about 15 percent of the muscle volume in his legs. A NASA medical expert predicted: "The muscular weakness and neurological changes in Romanenko caused by his long exposure to zero-g will require that he literally relearn how to walk during his re-adaptation to gravity" [68]. Nevertheless, an enthusiastic American reporter observed: "He apparently is in excellent shape, and is even able to stand up briefly" [69]. It was expected that for several days he would suffer significant orthostatic intolerance, and would be unable to stand erect without fainting or feeling faint.
Apparently, Soviet space medical experts saw reason for optimism in the general health and readaptation of Romanenko and Alexandrov. Their successors - Vladimir Titov and Moussa Manarov - went on to complete a 366-day mission, from December 21, 1987, to December 21, 1988. Titov and Manarov looked "drawn and pale" when they emerged from their reentry capsule after a year in space, but experts were impressed by how quickly they were able to readapt. When they were first raised to an upright position, they had difficulty maintaining their equilibrium. Within 3 hours, they were walking with assistance. Within 48 hours, they were "walking freely and were making normal gestures and movements" [70]. Within 2 months, they had completely readapted to normal gravity, and "experienced no aftereffects." Subsequent studies indicated that changes to their musculoskeletal, cardiovascular, and immunological systems were close to those observed on missions lasting only 5 or 6 months. Soviet medical experts credited their "rapid readaptation" to their elaborate regimen of exercise and other countermeasures such as the lower-body negative-pressure device [71].
Be that as it may, a 2-month convalescence can be considered "rapid" only with respect to the more pessimistic predictions extrapolated from earlier experience. Such a long recuperation time is unacceptable for interplanetary missions: after months of space flight, the crew must arrive healthy, self-sufficient, and ready to work. The entire surface time envisaged by many Mars proposals does not exceed 1 to 3 months, and there will be no ground crew waiting to greet the Earthlings and nurse them back to health. (Or so it is generally assumed.)
The goal of space medicine is to prevent the body's complete adaptation to weightlessness. Pharmacology may play an important role, but the pervasiveness of the adaptations, the side effects and interactions of drugs, and the body's altered response to drugs in weightlessness make this strategy highly problematic. Special garments and devices such as the lower-body negative-pressure suit, the penguin suit, and Cuban boots appear to be effective countermeasures against certain specific effects, but they may also interfere with mobility and work. Regular periods of rigorous exercise require a high degree of discipline and motivation that may diminish over the course of a multi-month mission.
A possible alternative - or perhaps, a supplement - to all of this is artificial gravity.