U.S. manned space flight: the first twenty years, a biomedical status report.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently our most serious problem. Its etiology remains obscure, but the "sensory conflict" theory appears most plausible. No valid predictive tests of susceptibility exist and presently we must rely on medication for prevention or mitigation of symptoms. Adaptation/biofeedback techniques may prove useful. Cardiovascular "deconditioning" may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.     

Vestibular factors influencing the biomedical support of humans in space

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.     

Motion sickness susceptibility during rotation at 30 rpm in free-fall parabolic flight

Free fall per se whether in parabolic or orbital flight may be regarded as a "partial" motion environment with respect to eliciting motion sickness, requiring an additional component to render this environment "complete" or stressful. Parabolic flight in toto falls in the category of a "complete" motion environment in that some persons became motion sick with head fixed and eyes closed. In the present experiment we selected subjects who were symptom free or nearly symptom free in the KC-135 with head fixed. All tests were conducted with the subject rotating at 30 rpm in a rotating litter chair, and comparisons were made between head-fixed and head-moving conditions (right-left) in the free-fall phase of parabolic flight and under simulated free-fall phases in the laboratory. With head fixed most subjects were insusceptible; with head moving left-right susceptibility was slightly higher in the laboratory than aloft. An additional comparison was made correlating susceptibility in the free-fall phases of parabolic flight with susceptibility to experimental motion sickness in Skylab. In both situations cross-coupled angular accelerations were generated by executing head and body movements out of the plane of rotation. In parabolic flight 9 of 15 subjects reached an endpoint just short of frank motion sickness. In the Skylab workshop all eight of the astronauts tested were symptom free at the end of the test. The explanation for the difference in susceptibility rests in two factors: (1) Basic susceptibility in free fall is lower than on the ground, and (2) in Skylab the astronauts who needed to adapt had achieved this goal prior to the first test on Mission-Day 8.     

ELITE-S2: the multifactorial movement analysis facility for the International Space Station

Experimental observations of adaptation processes of the motor control system to altered gravity conditions can provide useful elements to the investigations on the mechanisms underlying motor control of human subject. The microgravity environment obtained on orbital flights represents a unique experimental condition for the monitoring of motor adaptation. The research in motor control exploits the changes caused by microgravity on the overall sensorimotor process, due to the impairment of the sensory systems whose function depends upon the presence of the gravity vector. Motor control in microgravity has been investigated during parabolic flights and short-term space missions, in particular for analysis of movement-posture co-ordination when equilibrium is no longer a constraint. Analysis of long-term adaptation would also be very interesting, calling for long-term body motion observations during the process of complete motor adaptation to the weightlessness environment. ELITE-S2 is an innovative facility for quantitative human movement analysis in weightless conditions onboard the International Space Station (ISS). ELITE-S2 is being developed by the Italian Space Agency, ASI is to be delivering the flight models to NASA to be included in an expressed rack in US Lab Module in February 2004. First mission is currently planned for summer 2004 (increment 10 ULF 2 ISS).     

Individual differences in susceptibility to motion sickness among six Skylab astronauts

One of the Skylab experiments dealt with motion sickness, comparing susceptibility in the workshop aloft with susceptibility preflight and postflight. Tests were conducted on and after mission-day 8 (MD 8) by which time the astronauts were adapted to working conditions. Stressful accelerations were generated by requiring the astronauts, with eyes covered, to execute standardized head movements (front, back, left, and right) while in a chair that could be rotated at angular velocities up to 30 rpm. The selected endpoint was either 150 discrete head movements or a very mild level of motion sickness. In all rotation experiments aloft, the five astronauts tested (astronaut 1 did not participate) were virtually symptom free, thus demonstrating lower susceptibility aloft than in preflight and postflight tests on the ground when symptoms were always elicited. Inasmuch as the eyes were covered and the canalicular stimuli were the same aloft as on the ground, it would appear that lifting the stimulus to the otolith organs due to gravity was an important factor in reducing susceptibility to motion sickness even though the transient stimuli generated under the test conditions were substantial and abnormal in pattern. Some of the astronauts experienced motion sickness under operational conditions aloft or after splashdown, but attention is centered chiefly on symptoms manifested in zero gravity. None of the Skylab-II crew (astronauts 1 to 3) was motion sick aloft. Astronaut 6 of the Skylab-III crew (astronauts 4 to 6) experienced motion sickness within an hour after transition into orbit; this constitutes the earliest such diagnosis on record under orbital flight conditions. The eliciting stimuli were associated with head and body movements, and astronaut 6 obtained relief by avoiding such movements and by one dose of the drug combination 1-scopolamine 0.35 mg + d-amphetamine 5.0 mg. All three astronauts of Skylab-III experienced motion sickness in the workshop where astronaut 6 was most susceptible and astronaut 4, least susceptible. The higher susceptibility of SL-III crewmen in the workshop, as compared with SL-II crewmen, may be attributable to the fact that they were based in the command module less than one-third as long as SL-II crewmen. The unnatural movements, often resembling acrobatics, permitted in the open spaces of the workshop revealed the great potentialities in weightlessness for generating complex interactions of abnormal or unusual vestibular and visual stimuli. Symptoms were controlled by body restraint and by drugs, but high susceptibility to motion sickness persisted for 3 days and probably much longer; restoration was complete on MD 7. From the foregoing statements it is clear that on and after MD 8 the susceptibility of SL-II and SL-III crewmen to motion sickness under experimental conditions was indistinguishable. The role played by the acquisition of adaptation effects prior to MD 8 is less clear and is a subject to be discussed.     

Nausogenic properties of various dynamic and static force environments.

Motion sickness can occur when an accelerating force acting on the human body repeatedly changes amplitude and direction or both. It also can occur without any motion after transfer into a constant force field significantly different from Earth-gravity. Dynamic and static causes of motion sickness can be distinguished accordingly. Space sickness, too, has dynamic as well as static aspects. Dynamic space sickness might depend on increased bilateral differential sensitivity of the peripheral and central vestibular apparatus, whereas static space sickness may be caused by erroneous compensation of bilaterial asymmetries of the otolith-system in the microgravity environment. Experiments in airplanes, cars and on a vestibular sled have shown that the susceptibility to motion sickness is highest for changes of acceleration in the negative X-axis (as compared to the other axes) of the body. During reciprocating linear accelerations on the vestibular sled, standstill periods of movement and the direction of movement cannot correctly be indicated, because the peripheral vestibular apparatus lacks true motion detectors.     

Relative efficacy of the proposed Space Shuttle antimotion sickness medications

Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants. NASA has at the moment proposed a combination of promethazine and ephedrine (P/E) and one of scopolamine and dextroamphetamine (S/D), both given orally, as well as a transdermally applied scopolamine (TAS), as preventive and ameliorative measures. The reported double-blind study, tests the early phase actions and efficacy of the transdermal scopolamine (Transderm (TM)-V of ALZA Corporation) and compares these in detail to the oral medications. Motion sickness resistance was tested by standardized head movements while accelerating at 0.2 degree/sec2 to a maximum rotation of 240 degrees/sec, with an intermediate plateau of 10 min at 180 degrees/sec. To permit weighting motion sickness protection against other system influences, cardiovascular, psychological (subjective and objective), and visual parameter changes were documented for the three therapeutic modes. The relative impact of the various modalities on operational and experimental components of space missions is discussed. A comparison to intramuscularly administered promethazine (a backup therapeutic mode suggested for Space Shuttle use) is also included.     

A new goldfish model to evaluate pharmacokinetic and pharmacodynamic effects of drugs used for motion sickness in different gravity loads.

This paper proposes a new goldfish model to predict pharmacodynamic/pharmacokinetic effects of drugs used to treat motion sickness administered in differing gravity loads. The assumption of these experiments is that the vestibular system is dominant in producing motion sickness and that the visual system is secondary or of small import in the production of motion sickness. Studies will evaluate the parameter of gravity and the contribution of vision to the role of the neurovestibular system in the initiation of motion sickness with and without pharmacologic agents. Promethazine will be studied first. A comparison of data obtained in different groups of goldfish will be done (normal vs. acutely and chronically bilaterally blinded vs. sham operated). Some fish will be bilaterally blinded 10 months prior to initiation of the experiment (designated the chronically bilaterally blinded group of goldfish) to evaluate the neuroplasticity of the nervous system and the associated return of neurovestibular function. Data will be obtained under differing gravity loads with and without a pharmacological agent for motion sickness. Experiments will differentiate pharmacological effects on vision vs. neurovestibular input to motion sickness. Comparison of data obtained in the normal fish and in acutely and chronically bilaterally blinded fish with those obtained in fish with intact and denervated otoliths will differentiate if the visual or neurovestibular system is dominant in response to altered gravity and/or drugs. Experiments will contribute to validation of the goldfish as a model for humans since plasticity of the central nervous system allows astronauts to adapt to the altered visual stimulus conditions of 0-g. Space motion sickness may occur until such an adaptation is achieved.     

Space motion sickness medications: interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.     

Neurobiological responses of fish to altered gravity conditions: a review

In vertebrates (including man), altered gravitational environments such as weightlessness can induce malfunctions of the inner ears, based on an irregular dislocation of the inner ear otoliths from the corresponding sensory epithelia. This dislocation leads to an illusionary tilt, since the otolithic inputs are not confirmed by the other sensory organs, which results in an intersensory conflict. Vertebrates in the orbit therefore face severe orientation problems. In humans, the intersensory conflict may additionally lead to a malaise, commonly referred to as space motion sickness (SMS). During the first days at weightlessness, the orientation problems (and SMS) disappear, since the brain develops a new compensatory interpretation of the available sensory data. The present review reports on the neurobiological responses--particularly of fish--observed at altered gravitational states, concerning behaviour and neuroplastic reactivities.     

Psychological adaptation and salutogenesis in space: Lessons from a series of studies

Individuals who adapt positively to an inhospitable or extreme environment can derive benefit from their experiences. This positive effect may include an initial improvement in mental health as someone adjusts to the environment (adaptation) as well as more sustained personal growth during the mission (salutogenesis). We review relevant findings from our prior work, including two post-mission surveys of astronauts and cosmonauts, and three studies of crewmembers during missions in a space station simulator, the Mir space station, and the International Space Station (ISS). We also present new analyses showing evidence for adaptation to ISS missions. This finding replicates our previous results from the simulation study, but this effect was not found on the Mir. A better understanding of psychological adaptation and salutogenesis during space flight should help us develop strategies to enhance crewmembers’ in-flight stress tolerance and post-flight adjustment.     

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights.

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods--shielding and anti-carcinogens.     

Free fall: a partial unique motion environment

Conditions leading to the elicitation of motion sickness have been divided into two main categories: partial motion environments, in which head movements are required to elicit motion sickness, and complete motion environments, in which independent movements of the head are not required for the production of symptoms. It is postulated that, according to this categorization, free fall constitutes a partial motion environment. In support of this hypothesis evidence is reviewed from Skylab missions, experiments in parabolic flight, and ground-based studies.     

Excretion of amino acids by humans during space flight

We measured the urine amino acid distribution patterns before, during and after space flight on the Space Shuttle. The urine samples were collected on two separate flights of the space shuttle. The first flight lasted 9.5 days and the second flight 15 days. Urine was collected continuously on 8 subjects for the period beginning 10 d before launch to 6 d after landing. Results: In contrast to the earlier Skylab missions where a pronounced amino aciduria was found, on shuttle the urinary amino acids showed little change with spaceflight except for a marked decrease in all of the amino acids on FD (flight day) 1 (p<0.05) and a reduction in isoleucine and valine on FD3 and FD4 (p<0.05). Conclusions: (i) Amino aciduria is not an inevitable consequence of space flight. (ii) The occurrence of amino aciduria, like muscle protein breakdown is a mission specific effect rather than part of the general human response to microgravity.     

Human missions to Mars: new psychological challenges and research issues

Human exploratory missions to Mars represent the most exciting future vision of human space flight. With respect to the distance to travel and mission duration, these missions will provide unique psychological challenges that do not compare to any other endeavor humans ever have attempted. The present paper presents outcomes of two recent projects sponsored by the European Space Agency--Humex and Reglisse--where these challenges and risks have been analyzed in some detail, and where concepts for future research have been developed. This presentation involves three steps. At first, it will be shown that our current psychological knowledge derived from orbital spaceflight and analogue environments is not sufficient to assess the specific risks of mission into outer space. Secondly, new psychological challenges of missions to Mars will be identified with respect to three different areas: (1) individual adaptation and performance, (2) crew interactions, and (3) concept and methods of psychological countermeasures. Finally, different options and issues of preparatory psychological research will be discussed.     

Neurohumoral mechanism of space motion sickness.

This paper reviews existing hypotheses concerning the mechanisms of adaptation of the vestibular apparatus and related somatosensory systems to microgravity with reference to the flight data. Having in view theoretical concepts and experimental data accumulated in space flights, a conceptual model of the development of a funtional system responsible for the termination of vestibular dysfuntion and space motion sickness manifestations is presented. It is also shown that changes in the hormonal status during motion sickness induced by vestibular stimulation give evidence that endocrine regulation of certain functions can be involved in adaptive responses.     

The evolution of a serviceable EURECA

Within the European space platform program the EURECA is being established as a ground-based platform for short microgravity missions. The development towards a serviceable platform for longer, scientific missions is described. The plan of an advanced space-based platform for increasing payload demands is outlined. The platform design and the adaptation to scientific missions and servicing operations are investigated. The cost-effective utilization of the different platform types using new operational concepts is analyzed in parametric life cycle cost calculations for different payloads and mission scenarios.     

Concept study on Deep Space Orbit Transfer Vehicle

In this paper, the concept of Orbit Transfer Vehicle for Deep Space Exploration (Deep Space OTV) is proposed, and its effectiveness and feasibility are discussed. Basic concept is the separation of two functions required for the deep space exploration, the transportation to the destination, and the exploration at the destination. Deep Space OTV is a spacecraft specialized for the transportation to the deep space destination. It is an expendable spacecraft propelled by solar electric propulsion. The payload of Deep Space OTV is Explorer, which is a spacecraft specialized for the exploration at the deep space destination. The effectiveness of the concept is discussed qualitatively, focused on the merits of the separations of two functions. The feasibility of Deep Space OTV is discussed based on the conceptual design of the spacecraft and its applicability to deep space missions. Several deep space missions are modeled and the payload capacity of Deep Space OTV is estimated. The missions include Asteroid rendezvous, Mars orbiter, Lunar lander, and so on.     

Concept study on Deep Space Orbit Transfer Vehicle

In this paper, the concept of Orbit Transfer Vehicle for Deep Space Exploration (Deep Space OTV) is proposed, and its effectiveness and feasibility are discussed. Basic concept is the separation of two functions required for the deep space exploration, the transportation to the destination, and the exploration at the destination. Deep Space OTV is a spacecraft specialized for the transportation to the deep space destination. It is an expendable spacecraft propelled by solar electric propulsion. The payload of Deep Space OTV is Explorer, which is a spacecraft specialized for the exploration at the deep space destination. The effectiveness of the concept is discussed qualitatively, focused on the merits of the separations of two functions. The feasibility of Deep Space OTV is discussed based on the conceptual design of the spacecraft and its applicability to deep space missions. Several deep space missions are modeled and the payload capacity of Deep Space OTV is estimated. The missions include Asteroid rendezvous, Mars orbiter, Lunar lander, and so on.     

Using Spacelab as a precursor of science operations for the Space Station

For more than 15 years, Spacelab, has provided a laboratory in space for an international array of experiments, facilities, and experimenters. In addition to continuing this important work, Spacelab is now serving as a crucial stepping-stone to the improved science, improved operations, and rapid access to space that will characterize International Space Station. In the Space Station era, science operations will depend primarily on distributed/remote operations that will allow investigators to direct science activities from their universities, facilities, or home bases. Spacelab missions are a crucial part of preparing for these activities, having been used to test, prove, and refine remote operations over several missions. The knowledge gained from preparing these Missions is also playing a crucial role in reducing the time required to put an experiment into orbit, from revolutionizing the processes involved to testing the hardware needed for these more advanced operations. This paper discusses the role of the Spacelab program and the NASA Marshall Space Flight Center- (MSFC-) managed missions in developing and refining remote operations, new hardware and facilities for use on Space Station, and procedures that dramatically reduce preparation time for flight.