The Apollo 11 mission was the watershed of the manned space program. For the American public Apollo 11 was a symbol of the restoration of the nation's honor and technological preeminence. Within NASA, while Apollo 11 was a political triumph and a source of immense relief, it was not the ultimate event in the space program. It was merely a prelude to even more interesting and significant space activities that lay in the future.
A SPACE PROGRAM FOR THE 1970'S
NASA planners had never viewed the Apollo program as simply a series of missions leading toward a manned lunar landing. They had conceived of it as a program that would achieve both the short-range political objective set by President Kennedy and long-range operational objectives. As George Low, then head of planning for manned spaceflight, informed Congress in 1962, "Apollo is the name of a spacecraft that will have a dual mission capability." It would carry men to the Moon, but would also be used in Earth orbit as an "orbiting laboratory." In the latter capacity, Apollo would be the first step toward "a manned permanent space station."1
NASA planners began to give serious attention to post-Apollo manned programs in mid-1962, when the agency asked the Space Science Board of the National Academy of Sciences to review NASA's present spaceflight capabilities and recommend space program priorities for the post-Apollo period. The board urged NASA to increase emphasis on scientific investigations in space and, "utilizing the unique capabilities of man as an  observer and decision-maker," integrate the scientific and exploratory aspects of the manned program. The board also suggested that a manned Mars landing would satisfy both those interested in science and those favoring space exploration. Accordingly, it recommended that NASA make a manned Mars landing the primary space program priority of the 1970s. 2
NASA's advanced mission planners were interested in a manned Mars mission, but they favored a manned orbiting laboratory or space station as an intermediate step, compatible with the phased development and gradual qualification of man for extended spaceflight preferred by NASA's top administrators. For this reason, they proposed to design a long-range program that involved a gradual extension of flight capabilities and gradual phasing of manned space objectives. This was also an economical approach, since Apollo systems could be used in the initial phase and could be coordinated with the Air Force's manned orbiting laboratory program.3
By late 1966 NASA planners had agreed that the initial phase of the post-Apollo program should be designed to use Apollo systems Designated the Apollo Applications Program, the first phase would center on Earth-orbital flights of 28 to 100 days but would also include extended flights for lunar exploration. Objectives of the orbital flights would include advanced scientific investigations (e.g., a telescope mount for astronomical observations and laboratories for biological and medical studies), evaluation of life systems for long-duration flight, and qualification of man for spaceflights in excess of 14 days. This phase would be followed by an orbiting space station, which would serve as a staging area for advanced lunar operations (including construction of a permanent lunar base) and manned interplanetary flights.4
In spite of reductions in congressional appropriations, delays in the Apollo missions caused by the Apollo 204 fire, and growing public disinterest in the space program, NASA planners continued to refine this basic post-Apollo space program. Between 1967 and 1969, planners at NASA Headquarters and at the centers examined NASA's present and future requirements and capabilities and proposed mission and program options.5 These studies culminated in a long-range program for an Integrated Manned Space Flight Program for the 1970s, which had an overall objective "to build towards a manned planetary capability" by integrating "lunar mission capability" with the capability for a "long-duration manned space station." The mode of integration would be "low cost transportation" via a "reusable cislunar spacecraft system."6
This integrated program was divided into three subprograms: lunar, Earth-orbital, and planetary. The first would be a direct extension of the Apollo program and would include lunar flights through 1974 to permit  surface exploration, deployment of scientific instruments, and surface mapping. The lunar program would lead after 1975 to construction of a permanent manned lunar base, which would be linked to an orbiting space station. The Earth-orbital program would begin with the Apollo Applications Program manned laboratory and would lead to a permanent manned space station. This orbiting station would provide opportunities for scientific investigations in the physical and life sciences relevant to lunar and planetary operations, while serving as a transfer point for flights between the Earth and the Moon. Finally, planetary missions would begin with unmanned explorations of the planets, asteroids, and comets during the 1970s and culminate in a manned interplanetary flight in the 1980s.7
This long-range plan gave continuing impetus to the life sciences. Interest in the planetary missions justified support for exobiology (search for extraterrestrial life, investigations into the origin and evolution of life in the universe), while the need to prepare for extended manned flights warranted efforts to develop a program of fundamental biomedical research and to define a coordinated series of inflight biomedical experiments. The need to qualify man for advanced programs and define his requirements in extended missions allowed NASA's space doctors to add basic and clinical biomedical research to their operational responsibilities.
BIOMEDICAL ASPECTS OF APOLLO
In 1969 NASA decided to increase the number of Apollo flights to provide for lunar surface exploration. This decision increased opportunities to gather data on human physiological and behavioral responses to the conditions of spaceflight, including extravehicular activity, because the first three Apollo missions revealed unanticipated clinical anomalies. It also allowed NASA to restore some of the biomedical experiments that were abandoned after the Apollo 204 fire.
CLINICAL ASPECTS OF APOLLO
Although a few clinical anomalies were revealed, the Apollo missions collectively demonstrated NASA's ability to predict and prepare for the physiological and behavioral reactions of astronauts to spaceflight. With two exceptions, as Dr. Charles Berry observed, "almost every observation in the physiological realm" was identified during the Gemini program.8
The Apollo missions reaffirmed the belief of NASA's physicians that man was fully qualified for short-duration spaceflights and would not suffer irreversible physiological effects. Lunar surface operations showed that "man can perform very nicely in the one-sixth gravity environment" ....
....and that the metabolic costs of working in that environment were within acceptable limits. Finally, the Apollo experience affirmed the particular value and effectiveness of the general clinical program in quickly identifying inflight clinical problems and in coping with problems not identified before flight. The biomedical results from Apollo showed that man could endure the conditions of lunar flight and short-term lunar operations.9
The Apollo missions also contributed to the identification of clinical problems relevant to advanced manned missions. The physiological decrements that occurred in the final two Mercury flights and in the 8- and 14-day Gemini missions were also observed in the Apollo flights. As in the earlier missions, some of these anomalies-decreased red cell mass, orthostatic disturbance, and vestibular dysfunction-were found to be self-limiting and appeared to be adaptive responses to weightlessness. Data on other potentially adverse changes-dehydration, electrolyte imbalance,  weight loss, bone demineralization-suggested problems that could be serious in long-duration flights.10
The need for preflight clinical monitoring and screening in order to minimize the risk of inflight infectious illness was also evident during Apollo. The crews of Apollo 7 and Apollo 9 developed upper respiratory infections, while one of the members of the Apollo 13 prime crew was exposed to rubella (German measles). The Apollo 7 crew members developed their infections in flight, while the Apollo 9 crew was infected before flight and the launch date had to be delayed for several days. In the case of Apollo 13, a backup crew member had to be substituted for a prime crew member at the last minute.11
These illnesses would have caused serious problems in long-duration flights by placing an additional strain on physiological systems already struggling to adapt to spaceflight. In addition, weightlessness complicated inflight treatment of illness by impairing mucus drainage As decongestants seemed to be ineffective, astronauts would run the risk of ruptured eardrums.12
These experiences underscored the need for a more strict preflight health maintenance program, one that included the families of crews in the screening process and provided for complete isolation of prime and backup crews for specified preflight periods. For this reason, NASA established a Flight Crew Health Stabilization Program before the Apollo 14 flight. An extension of the traditional medical maintenance program, it included routine screening and monitoring, rapid diagnosis and treatment of illness affecting any astronaut or members of any astronaut's family, and serological tests and immunizations for all astronauts and members of their families. The new program also included epidemiological surveillance" of the astronauts and their families, which entailed assessment of the health of those likely to have contact with prime and backup crews during the 90 days preceding a particular flight, and medical histories and medical examinations for those who would have contact with the astronauts during the 21 days before launch. During these 21 days, daily reports were taken on the health of all "primary contacts" and were correlated with information on general disease patterns from public health officials. The combined data were analyzed by computer. This surveillance effort was linked to isolation procedures. During the critical 21-day period, prime and backup crews were confined to strictly limited areas, and their primary contacts were limited to essential personnel and family members. Crew members were strictly isolated from potential disease carriers, such as transient populations, children, and launch site personnel whose medical histories were not known.
Although elaborate and confining and not without deficiencies, the health stabilization program was effective in reducing the incidence of  preflight and inflight infections. In the first five Apollo flights (7 to 13), 67 percent (14 of 21) of the prime crew members experienced infectious illness before or during flight, while in the final four Apollo missions (14 to 17), only 6 percent (1 of 16) had problems with infection. The one instance in the latter case involved infection of the skin rather than the respiratory system.13
A third significant biomedical result of the Apollo missions was the identification of two unanticipated anomalies-vestibular dysfunction (motion sickness) and cardiac arrhythmias (irregularities in heartbeat). Motion sickness was a problem that NASA's physicians had expected in the Mercury flights, largely because it was a problem among Russian cosmonauts. However, motion sickness did not emerge as a problem until Apollo 8, when one crewman suffered nausea for two days and another had vomiting and diarrhea. Both ailments apparently stemmed from vestibular disturbance, though both astronauts also suffered from gastroenteritis. In Apollo 9, the lunar module pilot experienced severe motion sickness with recurrent vomiting and dizziness, causing the cancellation of scheduled extravehicular activity involving the lunar module. The lunar module pilot on Apollo 10 and two of the crew members on Apollo 13 suffered "moderately severe" motion sickness, and the Apollo 15 lunar module pilot and the Apollo 17 commander and lunar module pilot experienced minor motion sickness ( stomach awareness"); 33 percent (11 of 33) Apollo crew members experienced mild (stomach awareness) to severe (nausea, vomiting) motion sickness.14
Because it had seemed that motion sickness was an anomaly peculiar to Soviet missions, NASA physicians had made no provision for systematic study and quantitative assessment of vestibular disturbances in the Apollo program.* Consequently, they could not positively identify vestibular dysfunction as the cause of the ailments. Efforts to correlate prior history of motion sickness with observed inflight instances of motion sickness were unsuccessful. Of the 33 Apollo astronauts, 27 had a "positive motion sickness history," but only 9 of these experienced motion sickness in flight. More important, on Apollo 8 and Apollo 9, the nausea and vomiting could have resulted from factors other than vestibular dysfunction.15
Nonetheless, NASA physicians assumed that vestibular dysfunction was the most likely cause of the observed ailments. They speculated that it had developed during the Apollo missions because the Apollo space capsule was large enough to permit increased mobility and head movements and because the missions required considerable movements on the part of  the lunar module pilot (the crewman most often affected by motion sickness). To test this assumption, the crews of the Apollo 10 through Apollo 17 missions were instructed to limit head movements during the first five days of flight, the length of time considered normal for physiological adaptation to weightlessness. This approach appeared to reduce the incidence of motion sickness symptoms.16
In an effort to determine whether any vestibular change occurred in flight, NASA conducted a special study as part of the postflight evaluation of the Apollo 16 astronauts. Physicians tested the astronauts' ability to balance on rails of various widths in both eyes-open and eyes-closed states ("post-dural response") and studied side-to-side eye movement in response to stimuli ("nystagmus"). Both tests were standard medical procedures for evaluating vestibular performance, and they indicated probable vestibular changes resulting from the conditions of spaceflight.17
The Apollo flights and the special studies failed to produce conclusive evidence of vestibular dysfunction at a level of significance that would permit generalizations. However, one NASA physician observed, the discovery of probable vestibular disturbance posed a 'problem of compelling concern in future manned space flight" and warranted "an aggressive attack on the problem." It indicated a need for research to obtain "reliable predictive tests," to identify effective medications for symptoms control," and to devise 'training methods and procedures" to increase the space motion sickness "threshold" and mitigate" the inflight symptoms. 18
The other unanticipated result of the Apollo program was the discovery of arrhythmias in one of the members of the Apollo 15 crew. This being the only such instance uncovered during the manned space program, NASA physicians surmised that it was related to the particular flight. Supporting this view was the discovery during postflight evaluations that all three Apollo 15 crew members experienced prolonged orthostatic hypotension. Although this condition was 'consistently demonstrated" in all Apollo flights and had been identified as early as the Mercury flights, it was short-lived (reversed within 48 to 72 hours) in all but the Apollo 15 mission NASA physicians identified two unique characteristics of this mission: exhaustion of crew members due to an excessive workload and difficulty in sleeping, and evidence of a potassium insufficiency that may have been due to the inflight diet. On Apollo 16 and Apollo 17 the crew members were given a revised work schedule and a diet that included potassium supplements. In addition, they were instructed to take sleeping medications during their flights. Apparently because of these procedures, the Apollo 16 and Apollo 17 crews were 'completely free" of 'cardiac difficulties." However, in the absence of controlled studies, physicians could not be certain that these factors had influenced the situation.19
 The clinical results from Apollo, then, underscored the need for fundamental biomedical investigations to support advanced manned missions. They reaffirmed the findings from the Gemini flights concerning the need for intensive investigation of cardiovascular, musculoskeletal, and endocrine systems and metabolic functions. In addition, they pointed to the need for controlled studies of vestibular and neurological functions and workload tolerances, and for improved procedures for minimizing the incidence of inflight illness and for treating such illness when it occurred.
APOLLO BIOMEDICAL EXPERIMENTS
Biomedical experiments were flown during the last two Apollo missions, 16 and 17. BIOSTACK and BIOCORE were experiments designed to measure the biological effects of various types of radiation that are screened out by the Earth's atmosphere. BIOSTACK was an experiment to assess effects of high-energy particles on the germination and growth of selected plant spores and on the embryological development of eggs of selected arthropods. BIOCORE measured the effects of high-intensity radiation on the organs and tissues of a pocket mouse. Both were primarily scientific investigations, but had the secondary objective of evaluating the biological effects of an environmental factor that could prove significant in long-duration manned spaceflight. Neither experiment produced results significant to planning for advanced manned missions.20
A third biomedical experiment, flown on Apollo 16, investigated the effects of radiation on the cellular physiology and genetic components of several types of microorganisms. The objective was to determine whether the levels of ambient high-intensity radiation in the space capsule had any significant effect on the viability of microorganisms. Since terrestrial microorganisms would be carried into space by men, it was important to know whether the radiation level in the space capsule would be sufficient to destroy them and, if not, whether they would undergo genetic changes that could cause them to become dangerous to man. This experiment revealed no significant differences in survival rates and rates of genetic change between the microbes flown aboard the spacecraft and those used as ground-based controls.21
The final experiment was designed to investigate a phenomenon reported by the crews of the Apollo 11, 12, and 13 flights. In each of these flights, crew members reported seeing light spots and light flashes  whenever the capsule was dark and the crew members' eyes were closed NASA scientists hypothesized that the cause of the f lashes was high energy cosmic rays penetrating the space capsule and striking the crew members' retinas. To test this hypothesis, investigators had the crew members of Apollo 14 and 15 count light flashes for specified periods while blindfolded. At the same time, test subjects on the Earth were doing the same. In the Apollo 16 and 17 missions, the crew members wore a head device that contained special photographic plates which recorded cosmic-ray strikes while the crew members counted light flashes. The data from this experiment supported the original hypothesis.22
Although these experiments yielded no information of immediate concern in relation to manned spaceflight, they proved that cosmic radiation penetrates the space capsule. While the levels of ambient radiation in the space capsule were well below the acceptable tolerance level for short-term exposure, prolonged exposure could have unanticipated and unpredictable effects on physiology. Thus, low-level radiation, while insignificant in the Mercury, Gemini, and Apollo flights, might be a significant factor in long-duration flights.
BIOMEDICAL OBJECTIVES OF THE POST-APOLLO SPACE PROGRAM
Planning for the post-Apollo biomedical program reflected two significant changes in the role and responsibilities of biomedicine in the space program. First, the biomedical program was no longer constrained by the requirements of specific manned missions or a single manned spaceflight objective. Although the scheduling and packaging of biomedical experiments and the operational support duties of space physicians would be influenced by the systems and flight profiles of the specific manned missions, the scope and direction of the biomedical program would no longer be determined solely by engineering and operational considerations. Second, the biomedical program for the 1970s reflected the increasing importance of basic research and clinical medicine in the space program. By 1970, space physicians had shed their flight surgeon image and were gaining recognition as medical scientists and clinicians. NASA's biomedical plans for the 1970s reflected the emerging need for comprehensive and fundamental research in biomedicine and for integration of the biological, biomedical, and bioengineering efforts.23
Various advisory groups examined and made recommendations concerning NASA's biomedical requirements in the post-Apollo space  program. Those which had the greatest influence on NASA's biomedical planning for the 1970s were prepared by the Space Medicine Advisory Group in 1964 and by the Space Science Board of the National Academy of Sciences in 1965. The Space Medicine Advisory Group report focused entirely on the medical requirements and medical experiments for a manned orbiting laboratory The authors determined weight experiments for a manned orbiting laboratory. Weightlessness was identified as the critical variable in long-duration spaceflight, and the authors proposed a series of experiments to test the effects of weightlessness on human physiology and performance, acting singly or in combination with other factors.24
The Space Science Board study was not limited to a particular type of mission and assessed NASA's broad requirements for a long-range integrated program of research in biology, medicine, and physiology. It concluded that biomedical preparations for long-duration spaceflight should center on fundamental investigations into the interactions between internal and external environments. "Physiology and behavioral processes" (internal environment), the authors stated, 'respond to stresses slowly over time," so that the significance of these processes is directly proportional to mission duration. Of primary concern were cardiovascular response, bone and muscle metabolism, red blood cell concentration, blood clotting mechanisms, and long-term decrements in performance. The factors in the external environment that would influence these processes included physical factors (weightlessness, alterations in circadian rhythm, radiation, thermal stresses), behavioral factors (isolation, confinement, monotony, close quarters), and engineering factors (artificial atmosphere, toxic contaminants, noise, vibrations). Research on these interactions, according to the authors, should be conducted in an orbiting laboratory in which space crews and space capsule systems could be evaluated in missions of 28 to 1,000 days.25
In May 1969 the medical staff of the Manned Spacecraft Center prepared a detailed plan for a biomedical research and operations program for the 1970s. Strongly influenced by the studies noted above, the primary author, Dr. Charles A. Berry, noted that the flight certification" approach to the qualification of man for spaceflight, which was required in the manned program of the 1960s, would not suffice for the 1970s and 1980s "Major modifications" would be necessary in this approach and in "the level of investigative efforts" to make possible "unconditional qualification of man for "extended space missions." Reiterating word-for-word the recommendations in the 1965 Space Science Board report, Berry said:
Special emphasis must be placed on the physiological and behavioral processes that respond to stress slowly with time and are likely to become important during  prolonged space flight Of particular interest are weightlessness, cardiovasculcar function, bone and muscle metabolism, hematological changes, vestibular function, and long-term decrements in physiological and behavioral performance. 26
This level of effort, Berry said, is required to enable exploitation of man's 'unique capabilities" as both decision maker and observer. Since man will be an essential component of advanced flight programs and must be accommodated" to any number of possible program alternatives," the investigative requirements" of the biomedical program of the 19705 must include efforts to obtain greater knowledge of man's psychophysiological response to space flight"; expand present understanding of design requirements for man/machine systems"; and develop "long duration flight systems and operation capabilities."27 Berry stated that the biomedical program must concentrate on assessing the interactions between man's "internal environment" and the stresses" imposed by the physical environment of space and the artificial environment of the space capsule.
"Degradation" in man's ability to perform mental and physiological tasks," Berry said, results from "fluctuations in the physical properties and chemical composition of the internal environment." The human body seeks to counteract" or minimize" these fluctuations through "highly complex compensatory mechanisms." Short-duration exposure to stress produces "accommodative" changes which are "self-adjusting" and shortlived reactions that "possess defensive value to the organism" and' assure viability of the organism." However, when accommodative measures are prolonged, " acclimative processes" occur that allow an organism to adapt to extended exposure to stress factors.
Neither of these processes, as the Mercury and Gemini flights revealed, causes serious or irreversible changes in physiological and behavioral performance in the short run. However, without more intensive investigations it is impossible to determine their long-range effects. Acclimative processes, Berry said, worked to the advantage of the Gemini astronauts by allowing them to adapt to the weightless state. However, these processes are "operative at a level where detection is difficult." The threshold of acclimatization is unknown, and it is possible that the imposition of stresses over a long period may cause"these mechanisms to be overpowered." In such a case, the result would be "degradation of performance in vital functions."28
Given these uncertainties, Berry continued, the primary objective of the biomedical program must be to obtain fundamental data necessary "to permit confident extrapolation to major extensions in mission duration." This fundamental understanding must involve determination of "the precise nature, the ultimate severity, and the fundamental etiology of all changes in man's functional capabilities during and following prolonged  space flight." To achieve this, the biomedical program must take account of "circumstances" that are peculiar to biomedical research. First, it is difficult to identify "normative functional capabilities" because individuals with similar physical and mental characteristics show "different physiological responses to some stresses," while a single individual may respond differently to an identical stress imposed at different times." second, stresses are "difficult to evaluate singly" since they tend to act in combination Finally, it is often difficult to identify potentially serious physiological changes because "powerful compensatory mechanisms can mask" physiological decrements "until the conditions become critical."29
Given the requirements for advanced manned flights and these peculiarities of biomedical research, Berry contended, the biomedical program of the 1970s must seek answers to three critical questions: (1) whether physiological changes observed in spaceflight reflect gradual adaptation" or progressive deterioration of bodily functions," (2) whether the changes are "self-limiting" (i.e., do not lead to progressive deterioration) as mission duration increases, and (3) whether methods for evaluating changes "are sufficiently sensitive to detect all occurring accommodative and acclimative processes." The "primary goal" of the biomedical program then must be to qualify man by demonstrating that he can "acclimatize to the space flight environment" without serious and irreversible "physiological and performance decrements," can "withstand re-entry stresses" following these acclimatizations, and can reacclimatize successfully to normal earth conditions."30
Man's qualifications for extended space missions, according to Berry, would be established when "at least one crew" of ' no fewer than three astronauts" successfully flew a "six-month mission" without any crewman having' medical problems referable to his flight experience." In this flight and in all preliminary flights. detailed investigations would have to be made of neurophysiology, pulmonary function and energy metabolism, cardiovascular function, endocrinology, hematology, microbiology, and behavior. If no serious decrements were observed in these areas during the six-month exposure, it could be assumed that "man can tolerate this environment for any length of time."31
Berry argued for an integrated approach to the study of human responses in each of these areas. Changes in physiological and behavioral systems and functions would have to be correlated with operative stress factors acting singly and in combination. Berry grouped these stress factors in four categories: "natural environmental factors"-weightlessness (affecting bone and muscle, cardiovascular function, psychomotor performance, and vestibular function), radiation, meteorites, altered periodicities, magnetic fields, extraterrestrial life; "spacecraft environment factors"-mechanical forces, linear acceleration, vibration, impact,  noise and blast, microbiology, toxicology, enriched oxygen atmosphere energy metabolism; habitability factors"-cabin atmosphere, nutrition thermoregulation, water management, waste management personal hygiene and clothing, spacecraft architecture, crew selection, size and composition, work, rest, sleep, and recreation; and "operational factors"-oculovisual effects, extravehicular activity, artificial gravity clinical medical care, data management, simulation.32
There were practical limitations to the implementation of this research program: the traditional problem of integrating bioinstrumentation and biomedical experiment packages into predetermined engineering and operational modes, and the new problem of developing medical and behavioral experiments that could be adapted to any of several types of spacecraft systems and flight configurations. The need to qualify man for extended duration flights aboard spacecraft that were yet to be defined led to the conception of the Integrated Medical and Behavioral Laboratory Measurement System. In the words of its chief architect Sherman P. Vinograd, the system was designed as a rack and module system" that could be "assembled into working consoles according to the requirements of the spacecraft and the experiments program for any particular mission." It would enable biomedical scientists to gain "sound scientific knowledge of human responses" while having "minimal or no impact'' on the design or operation of the basic flight system.33
The first phase in development of the integrated measurement system began in June 1967, and it was hoped that the system would be ready for evaluation during the Apollo Applications Program. By 1969 Vinograd doubted that the system would be ready before 1973 though the fundamental principle of modularity would be incorporated into the Apollo Applications flights. The system would be adaptable to programs following Apollo Applications and would ensure an ongoing capability for measuring physiological, behavioral, biochemical, and microbiological functions during spaceflight and for effective "data management" of measurements recorded in flight. (The experimental objectives and measurement capabilities of this system are described in Appendix D.)
The integrated measurement system was only one mode for gathering data on medical and behavioral responses to spaceflight. Until its development was completed, medical and behavioral experiments would be conducted with experiment packages adapted to specific flight programs. Moreover, inflight research, regardless of the mode, could not be divorced from ground-based research. First, the instruments and techniques to be used in flight required prior evaluation and calibration; for  example, a measurement of the effect of weightlessness on a function would be meaningless unless the instrument had been validated through measurements in normal gravity Second, inflight measurements had to have some basis for comparison, so that all the functions to be measured in flight also had to be measured in controlled ground-based studies. Finally, an effort had to be made to determine whether inflight measurements could best be obtained through automated instruments controlled from the ground or through instruments managed by flight crews. Full implementation of the expanded biomedical research program and the qualification of man for extended duration missions required a thorough study of the efficacy of each of these modes.34
AN INTEGRATED LIFE SCIENCES PROGRAM
The biomedical program described by Berry in May 1969 became the heart of an integrated life sciences research and development program for the 1970s. Since the space program of the 1970s would have no single major manned objective, all manned programs would be, in effect, advanced manned programs. Consequently, there was no longer a need to make distinction between advanced R&D and manned spaceflight programs. Likewise, the distinction between space biology and space biomedicine was losing significance. The successful planning of future manned programs depended as much on fundamental research in the biological sciences as it did on mission-oriented medical research and bioengineering. Moreover, in advanced manned programs the astronauts would be expected to function as scientific observers and experiment controllers as well as pilots and explorers.
Thus, NASA was moving away from compartmentalization of its life sciences activities into space biology, human research and biotechnology, and space medicine. For the 1970s, life sciences activities would have to accord with the uncertainties of the new space program. All research and development in biology, medicine, and biotechnology would bear directly or indirectly on the long-range goal of the agency: qualification of man as an operator, passenger, and scientific investigator in long-duration space missions. In short, the requirements for an indeterminate manned space program would force an integrated approach to biology and medicine.
The overall objective of the integrated life sciences research and development program was to obtain the fundamental knowledge necessary to make man 'an effective and fully-protected operating element of the systems required for the approved Skylab, tentatively approved Space Shuttle, and planned but unapproved space station programs. This would require understanding of the biological processes affecting human adaptation and tolerance to the conditions of  spaceflight, the physiological and behavioral processes specific to man and having paramount importance" in future manned missions, and the human factors involved in integrating man and machine in advanced flight systems.35 The program required integration, rather than separation of biology, medicine, and human factors engineering. This approach did not, however, take into account extraterrestrial life and its formation.
The principal aim of biological research in this integrated life sciences program was investigation of the basic biological processes related to "adaptiveness and tolerance" to spaceflight conditions for the purpose of identifying, measuring, and understanding "the mechanisms underlying functional adaptation of organisms in space." This program of bioresearch" gave priority to research related to spaceflight factors that stimulate adaptive responses and the mechanisms of these responses at the cellular and clinical levels; genetic effects, if any, of space environmental factors, particularly long-duration exposure to low-level radiation; and biological effects of weightlessness, acting singly or in combination with other factors.36 The bioresearch program was a modification of the old biosciences program, the major change being that biological investigations would be conducted to support the long-range manned program rather than for strictly scientific purposes.
The termination of the Biosatellite Project and cutbacks in space program funds precluded an independent biological program; however, integration into the manned flight program afforded new opportunities for biological investigations. Several biological experiments were scheduled for the Apollo Applications-Skylab missions, and one major unmanned biological flight was flown in late 1970. The latter, carrying the "orbiting frog otolith experiment," was designed to obtain information on biological response to weightlessness in a critical area, neurophysiology, that was difficult to study directly with humans. The experiment was selected because the otolith is the critical component of the vestibular apparatus-that part of the inner ear that influences balance and spatial orientation-and dysfunctions of the otolith can cause motion sickness and serious degradations in performance. The data from the otolith experiment revealed that the "basic neural control process" underlying vestibular function undergoes an accommodative response to weightlessness that is complete by the fifth day of exposure. Thus, this experiment supported the empirical conclusion based on manned flights, that man makes a positive adaptation to the weightless environment.37
The otolith experiment also yielded information on vestibular responses  to noise and vibrations Biomedical scientists had long assumed that noise and vibration were potential stress factors in manned f light. However, NASA physicians, having found no evidence of decrements attributable to these factors in the manned flights of the 1960s, considered them of secondary importance in the overall biomedical program. In the otolith experiment' the hair cells of the frog's otolith showed a significant response to noise and vibration. These results encouraged NASA's biomedical planners to investigate these factors in Skylab.38
The otolith experiment epitomized the emerging integrative approach to biomedical and life sciences research. It was intended to meet the needs of both pure science and applied (mission-oriented) research. It was carefully designed as an investigation of a phenomenon that was of interest to both biologists and space physicians, to both scientists and mission planners. 39 NASA life scientists hoped that this type of approach would be continued in the 1970s.
Toward this end, efforts were initiated to plan a series of similar flights for "definitive investigations of the effects of weightlessness." In coordination with the Naval Aerospace Medical Institute, NASA envisioned a series of missions that would culminate in a year-long study in an orbiting space station. In this final phase, several primates, attended by a veterinarian, would be experimental subjects in a special laboratory on the anticipated, but unapproved, manned space station. NASA planners saw this as a means to obtain the level of understanding of biological processes in flight that biomedical scientists had long demanded, while not interfering with the pace of the manned effort.40 Budgetary cutbacks and the abandonment of plans for a space station stifled the further development of this project and of the integrative approach to biological investigations in space.
BIOENVIRONMENTAL SYSTEMS RESEARCH (HUMAN FACTORS)
The requirements for advanced manned programs included the qualification of spacecraft systems, as well as man, for long-duration spaceflight, primary concerns being life support and protective systems. In long-duration flights, life systems would have to do more than sustain crews and provide minimal comfort for brief periods. They would have to "effectively and reliably" regenerate or recycle oxygen and water, provide for the "degradation" of solid and liquid waste materials, and ensure the cleansing and reconditioning of the space capsule atmosphere. Equally important, they would have to be engineered to provide for human comfort-personal hygiene, management of bodily wastes, thermal and humidity idity control, elimination of odors, and so on.41
 In an effort to develop a life support system acceptable for long-duration manned flights, NASA sponsored the Advanced Integrated Life Support System. Basically, this was a closed environmental system simulator which would be used to establish a technological base'' for the support, well-being, and efficiency of the crew" in advanced manned flights Through ground-based integrated operational manned tests simulating orbiting conditions," the AILSS would provide opportunities for testing the overall system and the integrity of the coordinated subsystems and for evaluating the reliability and maintainability of life support technology. The overall plan called for an extended series of tests increasing in duration from 90 to 180 days in which the focus would be on advanced oxygen and water regeneration technology."42
The prototype simulator was available in early 1970 and the first test began on June 13, 1970 and extended to September 11, 1970 - 90 days. Four men were the test subjects for the entire 90-day run, and the test was conducted as if the simulator were an orbiting space station The primary objective was to "demonstrate the capability to operate a multi-man life support system in a continuous regenerative mode for a 90-day period without resupply" The 90-day test demonstrated this capability, but revealed that maintenance would be a critical factor in advanced manned programs In this test, 237 items had to be repaired and 242 man-hours were required for repairs. It was concluded that in advanced manned flights NASA would have to give major consideration to the maintainability and ease of repair of life support systems and subsystems and would have to include scheduled and unscheduled maintenance" in the engineering and operational constraints The test results also indicated that in the design of future life systems NASA would have to give maintainability priority over redundancy.43
The 90-day test of the simulator epitomized the integrated approach to life sciences research and development Although the life support systems were the prime focus of the test, their evaluation was integrated with evaluations of capabilities for human performance, biomedical monitoring, and man-systems integration The biomedical component included "constant medical attendance by licensed physicians, daily status checks, constant radiation exposure monitoring, biweekly clinical blood chemistries, and weekly electrocardiography and pulmonary spirometry " Emphasis was placed on "special studies" of constant exposure to "low-level stresses" which could be simulated, in this case, confinement and carbon dioxide levels. The overall results of the biomedical evaluation "revealed that the 90-day manned test was medically benign " No changes attributable to prolonged confinement were identified, though the carbon dioxide study "produced preliminary results suggestive of biochemical trends developing from exposure to carbon dioxide."44
 The long-range plan for the Advanced Integrated Life Support System called for extension of simulations to 120 and 180 days and 'final validation" in a 180-day "space flight experiment" aboard an orbiting space station However, budget cutbacks and the curtailment of plans for a space station precluded implementation of this long-range plan.45
The basic objectives of the biomedical effort within the integrated life sciences program were the same as those described by Berry in his program report of May 1969; identification of clinically significant physiological and behavioral reactions to the conditions of extended spaceflight and gradual qualification of man for spaceflight lasting 180 days. The inflight investigative effort was to begin with the Apollo Applications Program (redesignated Skylab in 1971) and conclude with a six-month evaluation aboard the projected space station As the 1970s unfolded, however, Apollo Applications-Skylab became the final stage of the old manned program rather than the initial phase of a new manned program Consequently, the program of inflight biomedical research had to be collapsed to accommodate the package of medical and behavioral experiments to three missions lasting 28, 59, and 84 days.
This reduction precluded the "level of investigative effort" that Berry had hoped for, forced elimination of some investigative categories, and caused a reduction in the number of experiments Nonetheless, NASA life scientists viewed this as their first real opportunity to conduct controlled studies in space and proceeded with the development and packaging of experiments related to "areas which are judged to be most critical and most feasible at this time."46
The Apollo Applications-Skylab experiments were grouped in six categories Category 1 (experiment M070), study of nutritional and musculoskeletal function, consisted of four integrated experiments with the collective objective of assessing inflight alterations in musculoskeletal status and evaluating biochemical changes and nutritive requirements as they differ from those in the Earth environment. The four correlated experiments were intended to provide "precise measurements" of the input and output of calcium, nitrogen, and other biochemicals, bone demineralization, and hormonal and electrolyte changes detected in studies of blood and bodily waste products.
The three experiments in category 2 concerned cardiovascular function and would measure the cardiovascular reflexes that normally regulate blood pressure and the distribution of blood in the body: the "onset, rate of progression, and the severity" of changes in cardiovascular function;  and changes in cardiovascular function during given workloads on a bicycle ergometer."
Category 3, hematology and immunology, consisted of four experiments to determine physiological effects of spaceflight as indicated by changes in the volume, mass, and composition of the blood and blood elements and in the immune responses of the blood Changes in immune responses would be indicated by alterations in the bacterial populations of the blood and the genetic makeup of the leukocytes.
Category 4 was related to neurophysiology and consisted of two experiments to 'evaluate central nervous system responses as a function of space flight." One experiment would investigate changes in vestibular function, while the other would utilize electroencephalograms to assess effects of prolonged spaceflight on patterns of "sleep and wakefulness."
The fifth category involved one experiment, a 'time and motion study" to assess "behavioral effects." Its objective was "to evaluate the relative consistency between ground-based and inflight task performance" by observing films of the astronauts performing selected tasks in flight. The study was expected to yield information that would be useful in improving the design of space capsule subsystems and the training of astronauts for performance of inflight tasks.
The final category involved two experiments that were intended to measure pulmonary function and energy expenditure. Measurements obtained during rest, during "calibrated exercise" on the bicycle ergometer, and during selected ' operational type tasks" would be used to determine whether a correlation existed between the "energy costs" of mission-oriented physical activity'' and alterations in "respiratory gas metabolism."47
The diversity of NASA's biomedical programs would have been inconceivable in the 1960s, for the manned program of that decade required space physicians and life scientists to focus their efforts on mission-oriented research and mission operations and precluded the implementation of broad, research-oriented, and integrated biomedical programs. Yet, that same manned program provided a strong justification for specialization in space medicine and biology and medicine, the impetus for the emergence of space medicine as a distinctive field of medical specialization, and the opportunity for observation of the biological and physiological effects of a unique environment.
* A vestibular experiment had been planned for Apollo but was scrapped after the Apollo 204 fire.