This book closes yet another chapter in the continuing effort of biomedical scientists to characterize the responses of man to perhaps his last frontier-space. The results of Project Mercury (1961-1963) have been well documented (NASA, 1965) and need not be reiterated here. Chapter 2 in the continuing manned space flight epic was the Gemini Program (1965-1966). The principal objectives of the ten Gemini Missions were to perfect the techniques of rendezvous, station keeping, docking, and extravehicular activity-all critical to the Apollo lunar landing goal. Three flights of the Gemini series were of biomedical interest: Gemini 4, 5, and 7, lasting four, eight, and fourteen days, respectively. Several inflight measurements or experiments were accomplished on these missions, as well as preflight and postflight studies.
The significant results of the Gemini investigations are listed in table 1. In general, the presence of postflight orthostatic intolerance observed following Mercury flights was confirmed. Other biomedical findings included: moderately decreased postflight exercise capacity and red cell mass; minimal loss of bone mineral and muscle nitrogen; and the relatively high metabolic cost of extravehicular activity. These findings have been reported in detail elsewhere (NASA, 1967; 1968).
The Apollo (1963-1973) results presented in this volume constitute the third chapter of the biomedical manned space flight story. Eleven manned missions were completed in the five-year span of the Apollo Program, from prelunar flights (missions 7 through 10); the first lunar landing (mission 11), and five subsequent lunar exploratory flights (missions 12 through 17). Apollo 13 did not complete its intended lunar landing mission because of the pressure vessel explosion in the Service Module. Instead, it returned to Earth following a partial lunar orbit.
As stated elsewhere in this report, biomedical studies in Apollo were limited essentially to the preflight and postflight mission phases, along with inflight crew monitoring and observation. Inflight biomedical experiments were originally planned for Apollo. These, however, were subsequently cancelled by senior program management on  the basis of the operational complexity of the Apollo flights. Despite this setback, considerable biomedical information was gathered and served as a basis of the ambitious Skylab Program, then in its formative stages.
The purpose of this section is to summarize the significant Apollo biomedical findings and the tentative conclusions that may be drawn.
Apollo crew health problems in the preflight period were generally minor in nature and, for the most part, involved the skin. Viral upper respiratory and gastroenteric illnesses were next in frequency. The Apollo 9 launch had to be postponed for three days because the three crewmen developed viral upper respiratory symptoms. The only other instance in which preflight mission plans had to be altered for medical reasons was the Apollo 13 mission. The exposure of one of the crew to rubella (German measles) and his lack of demonstrable immunity to this viral disease resulted in a management decision to substitute a backup crewman on this mission. Beginning with the Apollo 14 mission, a Flight Crew Health Stabilization Program was instituted for the purpose of limiting, insofar as was practicable, the exposure of the prime and backup crews to communicable, infectious diseases. This program was described in Section II. Although it is difficult to assess the effectiveness of such a program, it doubtless served to focus attention on the problem, and in all probability reduced the number of direct crew contacts with persons who could possibly transmit infectious agents, particularly upper respiratory viruses, to the members of the crew.
Apart from cases of minor superficial dermatitis and skin or mucous membrane irritation secondary to trauma, abrasion or exposure to spacecraft environment, several more potentially serious inflight medical events deserve mention. The Apollo 7 crew developed viral upper respiratory infections during their mission which were uncomfortable nuisances and responded fairly well to decongestants. No secondary bacterial infections developed, and antibiotic therapy was not required. Apollo 7 was NASA's first experience with inflight illness.
 In the ill-fated Apollo 13 mission, prostatic congestion, dehydration secondary to emergency water intake restriction, and prolonged wearing of a urine collection device together induced a urinary tract infection in one crewman. The infectious agent in this case was Pseudomonas aeruginosa. The astronaut responded well to postflight antibiotic routine supportive therapy.
One of the Apollo 15 crewmen experienced a single run of bigeminal cardiac rhythm (22 coupled beats) as he lay in his couch observing Lunar Module tunnel leak rates. This was the fir-t significant arrhythmia observed during any American space flight. Another Apollo 15 crewman exhibited a few supraventricular premature contractions resulting in coupled beats but not a sustained bigeminal rhythm. It was at first conjectured that a dietary deficiency of potassium might have been a contributory factor. Subsequent careful analysis of the dietary intake and mission simulation studies with potassium restriction failed to substantiate this hypothesis. The etiology remains obscure. Fatigue following strenuous lunar surface activity most certainly was a factor. Other contributory factors are speculative and are likely to remain so. It should be noted that the crewman with the sustained bigeminal episode subsequently sustained a myocardial infarction in April 1973, some 21 months after his flight of July 1971. Thus, coronary atherosclerosis was very likely a factor in this case.
Perhaps the most significant inflight illness from an operational viewpoint, and from its probable impact on future missions, was "space motion sickness." Thus, Apollo witnessed the addition of vestibular disturbances to the list of significant biomedical findings incident to space flight.
Vestibular disturbances with nausea were noted by Soviet Cosmonaut Titov during his one-day, Vostok 2 flight on August 6, 1961, and by the crews of other later Soviet flights. No astronauts had been subject to any motion sickness symptoms until the early Apollo experience. In retrospect, however, the anorexia and reduced caloric intake observed on certain Gemini and later Apollo flights, may have been, in fact, early symptoms of vestibular disturbance.
Apollo 8 and 9 especially were plagued with vestibular problems: five of the six crewmen developed stomach awareness, three of the six, nausea, and two of these six proceeded on to frank vomiting. In Apollo 15 and 17, three of six of the crewmen also experienced stomach awareness. The flight plans of Apollo 8 and 9 required that certain crewmen leave their couches soon after orbital insertion. All three Apollo 8 crewmen noted some motion sickness symptoms (stomach uneasiness or awareness, nausea, or vomiting), confined generally to the first day of flight. There is some confusion concerning the etiology of the Apollo 8 crew's symtomatology, since the Commander felt that a viral gastroenteritis accounted for (or aggravated) his symptoms. In Apollo 9, the vestibular disturbance lasted for a considerably longer time and, in the case of the most severely affected crewman, necessitated a postponement of the flight plan. Thus, an additional problem area was introduced into the American space experience. This disturbance, which had long plagued the Soviets, and which had been predicted in the early 1960's as a probable effect of weightless flight, had made its belated American debut. Its late appearance was probably related to the relative immobility of the crews in their spacecraft during the Mercury and Gemini flights and the absence of any rotation of the vehicle- themselves.
 Postflight Phase
The principal astronaut illnesses during the postflight period were upper respiratory infection- (four instances) and influenza (types B and A2) contracted during numerous debriefing sessions and public relations appearances. The only other unusual finding of this period was probably related to vestibular dysfunction. A single astronaut reported a mild sensation of being tilted slightly "head down," particularly when recumbent. This sensation lasted for about seven days after the flight. It is an interesting observation of presently obscure etiology.
The late appearance of the space motion sickness syndrome in the American manned space flight experience and its sudden elevation to prominence as a problem of compelling concern in future manned space flight activities are sufficient reasons to warrant a few additional comments on the subject. Increased mobility of bead and body permitted by the larger volume of the Apollo spacecraft, as compared with earlier vehicles, apparently results in motion sickness symptoms during the early adaptive period following orbital insertion. Individual susceptibility varies widely and neither previous history of motion sickness at one g nor responses to current vestibular tests at one g have any predictive value for susceptibility aloft.
It should be stressed that most Apollo crewmen experienced only mild motion sickness symptoms, and only three vomited. Most symptoms subsided completely after two to five days in space. Further, symptoms could be controlled or lessened by reducing bead movement during the first few days of flight, although some head and body movement is required for the process of adaptation to proceed. Extravehicular activity at one-sixth g on the lunar surface resulted in no disorientation or vestibular disturbance, nor was there any apparent change in the sensitivity of the vestibular system on suddenly returning to one g. Indeed, there was only one episode of postflight vestibular disturbance.
Clearly, then, we are confronted with a complex problem. An aggressive attack on the problem from several approaches is indicated: to devise reliable predictive tests; to improve medications for symptom control; to investigate training methods and procedures which will increase the threshold to space motion sickness or to mitigate its symptoms during flight. A formidable task awaits us.
Postflight orthostatic intolerance was consistently demonstrated in Apollo. The familiar signs of increased pulse rate, decreased systolic and reduced pulse pressures were universally demonstrated during appropriate stress testing, lower body negative pressure, or passive standing. This intolerance was short-lived and, except in the case of the Apollo 15 crew, was not apparent beyond the second or third postflight day. Other postflight corroborative data such as decreased body weight, diminished resting calf girth, reduced supine leg volume, decreased cardiothoracic ratio, and decreased red cell mass all  argue in favor of reduced effective circulating blood volume as an important principal factor in the orthostatic intolerance phenomenon. The Apollo findings do not indicate whether the intolerance is present during flight, and if so, its onset and time course.
The answers to these questions must await inflight testing. If intolerance does develop during flight, it apparently is of little consequence, since it had no discernible effect on Apollo crew performance. The positive pressure garment tested in Apollo appeared to offer some protective benefit by reducing the pooling of extravascular fluid in the lower extremities.
Reduced work capacity and oxygen consumption of significant degree was noted in 67 percent (18 of 27) of the Apollo crewmen tested on recovery. This decrement was transient, and 85 percent of those tested (23 of 27) returned to preflight baseline values within 24 to 36 hours. A significant decrease in cardiac stroke volume was associated with diminished exercise tolerance. As we noted in the case of the cardiovascular "deconditioning" phenomenon, the Apollo findings do not indicate whether the exercise decrement has its onset during flight. If it does, Apollo could shed no light on its inflight time course. Judging from the astronauts' performance on the lunar surface, we have no reason to believe that any serious exercise tolerance decrement occurs during flight, except that related to lack of regular exercise and muscle disuse atrophy.
There can be no doubt of the decrement in exercise tolerance in the immediate postflight period. It would seem that multiple factors are probably responsible for the observed decrement. Lack of exercise and muscle disuse atrophy have already been mentioned. Catabolic tissue processes may be accentuated by increased cortisol secretion as a consequence of mission stress and individual astronaut reaction to such stress. Additional factors associated with the return to Earth's gravity may also be implicated. Thus, the observed diminished stroke volume (cardiac output) is certainly contributory and, in turn, is doubtless a reflection of dimished venous return and contracted effective circulating blood volume induced by space flight factors. Other probable contributory factor are unstable fluid and electrolyte flux states and fatigue, both of which defy accurate objective assessment.
Nutrition and Mineral Balance
Apollo crewmen were provided with adequate dietary nutrients and exhibited clinically normal gastrointestinal function, although their appetites were generally somewhat diminished. Since no strict metabolic balance study was performed during Apollo, only relatively crude estimates of the various balance parameters can be made.
The diminished appetites aloft may have been due primarily to early space motion sickness symptoms such as stomach awareness or mild nausea. There is no evidence that any inflight metabolic anomaly, including hypokalemia, was secondary to marginal or deficient nutrient or mineral intakes.
All Apollo crewmen lost weight ranging from one to twelve pounds with a mean loss of approximately six pounds on a balanced diet providing 2500 calories (10,475 Joules) per man per day. Again, not all the food provided was consumed. Most of  the weight loss (roughly 60 percent) was attributable to water and electrolyte loss; the remainder of the loss was attributed to lipid (30 percent) and muscle (10 percent) catabolism.
The partially controlled metabolic study conducted in conjunction with the Apollo 17 mission provided our only insight into inflight mineral balance during the Apollo Program. These data must be regarded as only grossly indicative of actual balance trends. The results argue in favor of a mild to moderate negative balance of sodium, potassium, nitrogen, phosphorus and calcium. Exchangeable potassium values were decreased in Apollo 15 and 17 but not in 16. The increased inflight cortisol secretion would argue in favor of increased tissue catabolism and potassium loss. The negative calcium balance observed in Apollo 17 and the slight losses in bone density in about half of the Apollo astronauts are consistent with the losses observed in subjects at bed rest for a comparable time period.
Postflight decreases in total body water and intracellular fluid volume are consistent with body weight loss and contracted effective circulating blood volume. Decreased potassium 40 and exchangeable potassium with increased urinary nitrogen argue in favor of muscle catabolism and potassium loss.
Postflight increases in renin, aldosterone, and antidiuretic hormone are consistent with the body s attempt to expand various body compartment volumes, conserve water and electrolytes, and restore venous return, cardiac output, and orthostatic tolerance to preflight levels. The finding of increased inflight aldosterone secretion is somewhat unexpected.
Investigations in Gemini revealed that effective circulating blood volume was reduced following flight. This reduction was effected by a decrease in red cell mass, averaging about 17 percent and by a decrease in plasma volume in most instances. The mean red cell mass loss m Apollo 7 and 8 was two percent with a ten percent loss registered for Apollo 14 through 17. Plasma volume was also consistently decreased following these Apollo flights.
The loss of red cell mass in Gemini was thought to be due to hemolytic destruction of the cells secondary to oxidative changes in the corpuscular membrane. The Apollo data, however, revealed no change in red cell survival times, indicating that the red cell mass decrement is relative to inhibition of erythropoiesis rather than to intravascular hemolysis.
Thus, red cell mass loss was demonstrated in Apollo, but to a lesser extent than in Gemini. Determination of the precise stimulus responsible for red cell loss (marrow depression), the time course of the red cell mass reduction and its subsequent recovery must await further study. It is generally held, however, that this phenomenon is another in a series of adaptive changes to the space environment, that it is self-limiting in character and that it poses no threat to extended manned space missions.
Table 2 lists the significant biomedical findings of the Apollo experience. In substance, the findings indicate that man generally adapts well to and functions  effectively in the space environment (and on the lunar surface) for time periods up to two weeks in duration. Inflight medical problems such as space motion sickness and the cardiac arrhythmias episode were observed for the first time in the American manned space flight experience. Although these problems are potentially serious, they are not insurmountable. Once their etiology is understood, they can be dealt with effectively.
A number of decremental biomedical changes have been observed following the Apollo missions-which are thought to be accommodative changes of the various body systems to the new space environment-and to weightlessness in particular. It is felt that many of these accommodative changes are self-limiting in nature such as decreased red cell mass, orthostatic intolerance and vestibular disturbances; others, such as reduced exercise tolerance, muscle mass loss, and bone demineralization may require preventive or remedial measures, particularly on long-duration space flights.
Understanding the mechanisms of action responsible for the Apollo biomedical findings and devising suitable countermeasures where appropriate will challenge the ingenuity of biomedical scientists for years to come. We feel that we can meet that challenge.