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7 Life Sciences BACKGROUND The study of life on Earth ranges from elucidating the evo- {ution of the earliest self-replicat~ng nucleic acids to describing a global ecology comprising over three million species, including hu- mans. Though life has shown enormous diversity and complexity over the last 3.5 billion years, its unifying principles are becoming ever clearer. Chemical and fossil evidence show that earth life as we know it today evolved by natural selection from a few simple cells called prokaryotes because they lacked nuclei. The earliest prokaryotes probably already had mechanisms that allowed them to replicate their genetic information, encoded in nucleic acids, and to express this information by translation into various proteins. These first cells were somehow formed during the Hadean eon that spanned the epoch from about 4.5 to 3.5 billion years ago. Analyses of the chemical compositions and reactions occurring on other planets, on comets and asteroids, and in interstellar space help us reconstruct the steps leading to the formation of the organic building blocks of biopolymers. Understanding this prebiotic evolution is one of 60
61 the major goals of the exobiology program biology of the early Earth and elsewhere In the universe. A second goad of exobiology is to understand the evolution of the first cells with true nuclei. These cells, called eukaryotes, were the precursors of "higher organisms: the unicellular pro- tists, fungi, plants, and animals we know today. The important organeDes of energy metabolis~plastids and m~tochondria- originated 2.0 to 1.5 billion years ago by the symbiosis of prokary- otes. In this process bacteria having one set of specialized functions were engulfed by host cells with complementary requirements and functions. By the early Archean, more than 2.2 billion years ago, the biota had used the process of photosynthesis to create an oxi- dizing atmosphere from one previously poor in oxygen. Carbon dioxide was also removed from the atmosphere in the form of car- bonate precipitates. Myriad bacteria, molluscs, corals, and other organisms contributed to vast limestone deposits and continue to do so today. With these ~d other processes Earth's biota have transformed a sterile planet, intermediate in character between Venus ~d Mars, into the living planet we now enjoy. Global biology concerns itself with the cumulative changes wrought by the biosphere on the atmosphere, hydrosphere, and geosphere. But, conversely, the physical and chemical constraints of Earth have acted on the biota as wed, ~d this too falls in the province of global biology. It is hardly a coincidence that IJyell's Principles of Geology was so influential in the development of Darw~n's early interest in the relationship of life add Earth. As the impact of human activities, such as burning fossil fuels and deforestation, increases, the predictive power of global biology will become as important as its ability to interpret the history of Earth. Global biology and exobiology address questions about the nature of Earth and the origin of life that have concerned us since even before the writing of Genesis. Yet, as these questions are now formulated, both global biology and exobiology are young sciences. As they have grown, they have profited from space missions and from collaborations with earth scientists and planetary scientists. As a result, the goals of these fields are now well defined; we can proceed with specific missions and programs confident of valuable results. In contrast to global biology, exobiology, and the other space sciences, the fields of space biology and space medicine are still
62 formulating their basic theories and research goals. A significant proportion of the entire scientific research effort of the United States addresses questions closely relevant to space biology and space medicine. Yet there have been so few space flights committed to biological observations that the major challenge facing space biology today is to determine how valuable a low gravitational field (m~cr~g) laboratory might prove in addressing fundamental research problems In biology. Some single cells must be able to detect small changes in the magnitude and direction of gravitational force. At a fundamental level we need to understand the molecular mechan~srns whereby a cell detects gravity and converts this signal to a neuronal, ionic, or hormonal response. Plants and animate that have evolved on Earth have done so at one g; they respond to gravity. For example, plant roots grow down and shoots up gravitroprsm. Fertilized eggs orient their cleavage planes relative to the gravity vector. In larger animals ~d plants many of the responses to gravity are additive. Hydrostatic pressure and muscle tension are good exam- pies: the unp act of gravity is probably greater on a giraffe than on a bacterium. Studying systemic effects produced by variations in gravitational force will not only contribute to our theories of physiology but test their predictive value as well. The steering group anticipates that manned space flights ex- tending over years will pose severe psychological and physiological problems. The initial concern of space medicine is primarily to identify and characterize those physiological systems that do not adapt well to space Bight or that do not subsequently readapt to one g. The vestibular and the cardiovascular systems, for example, may adapt and readapt without further intervention. In contrast, extrapolation from very Acted observations indicates that the effects of bone remodeling win grow more severe with passing months. Similarly, shielding cannot easily control cosmuc radia- tion consisting of the nuclei of heavy atoms (so-called heavy ion radiation). The unp act of one such particle can cause the death of nondividing celIs' such as brain cells. It would be unconscienable to launch long-term manned space flights without-a much better understanding of these phenomena and, where indicated, devel- opment of appropriate prophylaxis and treatment. Until these measures have been taken, it is questionable whether such flights should be planned or contemplated. With the number of Shuttle flights now projected to study these phenomena, we would still
63 have only a meager base of data by 1995. Hence, of necessity, our projections for the period from 1995 to 2015 are tentative. While priorities may change with tune, present observations and extrapolations indicate clear research goals of both basic and cImical significance. Realization of these goals demands the d~ ployment of a dedicated life sciences laboratory equipped with a vivarium and a centrifuge of at least an Afoot radius on a space sta- tion. Nothing less can allow us to determine whether m~crogravity provides an important too] for the study of biology; nothing less will give us our best chance to assure the health, performance, and welfare of astronauts on long-term missions. [IF E SCIENCE GOALS AND MAJOR QUESTIONS Exobiology Goals The goal of exobiology is to understand the origin and early evolution of life and its cosmic distribution. Complex anaerobic ecosystems fueled by photosynthesis ex- isted at least 3.5 billion years ago and possibly earlier. They had produced an oxidizing atmosphere by 2.0 billion years ago. The oldest fossils of eukaryotic organisms are found in rocks about 1.4 billion years old. Exobiologists believe that the basic chemical components of the first cells had to accomplish two fundamental tasks: reproduction and energy storage. Both of these probably in- volved the replication of polymers of KNA. These first RNAs may have been catalytic, somehow directing polymerization of amino acids into proteins. Selective advantage would have accrued to those organisms that let them extract usable energy from organic molecules, sunlight, or minerals not in their final oxidation state. However, relatively complex, prebiotic organic reactions occurred not only on Earth. They also occurred on other planets and in interstellar space. The surfaces of clays or of interstellar grains may have catalyzed these early reactions, even though these same pathways are no longer used by existing cells. A study of this extraterrestrial organic chemistry should provide precedents for early reactions on Earth. It might also indicate whether condi- tions conducive to life have ever existed on other planets in our solar system or beyond.
64 Major Questiom for Exobiology: 1995 to 2015 From 1995 to 2015 the steering group recommends addressing five major questions: 1. Are there organic molecules beneath the polar caps and in the sediments of Mars, in the atmospheres of Jupiter and Titan, in comets and meteorites, and in interstellar space? If so, what are they, and what ~ their distribution? More than 50 organic compounds containing up to 11 atoms have been identified in interstellar space; their relative concentrations differ enormously from that predicted by equilibrium thermodynamics. 2. How can we interpret the early fossils and deposition ot material of biological origin on Earth and relate them to materials from other planets? Are there fossils or definitive evidence of liquid water or former life on Mars, and, if so, what role have they played in early biological evolution? 3. What models of prebiotic chern~cal reactions can be demon- strated experimentally? The correspondence with reactions that do occur or have occurred in nature should be established. 4. What models can be developed for the first replicating system and the first true cells? A critical evaluation of such models might outline the environmental characteristics required for the origin and evolution of life. 5. What is the phylogeny of the archaebacteria, eubacteria, and early eukaryote~, add what were the major events in the evolution of the eukaryotes? Global Biology Goals The goal of global biology ~ to understand the evolution of the liota and its interactions Pith Earth. For nearly 4 billion years the biosphere has influenced, and been influenced by, the atmosphere, the hydrosphere, and the geosphere. The composition of our atmosphere, the abundance of water, the temperature, and the vast carbonate and ferric iron deposits are radically different from conditions on Mars and on Venus. Life has evolved under the constraints of available elements and energy fluxes of our planet. This is a dynamic system; the Bow of sold energy to a rotating Earth, coupled with its own internal radioactive heat source, generates numerous cycles and changes, which act on widely varying time scales. Photosynthetic cycles, for
65 example, have dally periods; while tune scales for plate tectonics are In the millions of years. Major Questions for Global Biology: 1995 to 2015 From 1995 to 2015 the steering group recommends addressing · six questions: 1. What are the major features of the water cycle? Not only is water essential to life, it drives or influences nearly aD the other biogeochem~cal cycles as a solvent, as a source of aerosols, or as a carrier of particulates. On a longer time scale it is the major agent of erosion and subsequent sedimentation. 2. What are the reactions and the fluxes of the other biogenic elementscarbon, nitrogen, sulfur, and phosphorus? During the past century the atmospheric concentration of carbon dioxide has increased from 200 to 300 ppm; methane, a trace gas, may provide a significant component of the flux of carbon. The turnover of atmospheric nitrogen is slow; we do not understand whether the seern~ng balance between nitrogen fixation and denitrification Is affected by the production of nitrogen dioxide by lightning. Prior to industrialization most sulfur was introduced into the atmo- sphere by vuIcanism. There ~ also significant biogenic production of hydrogen sulfide and (CHESS by anaerobic organisms. Photo phases are dissolved or borne as particulates; animal depositions may account for most soil replenishment. It is far more difficult to measure flux than concentration of these compounds; yet values for flux are essential for proper modeling. 3. What are the major sedimentation and erosion processes that the biota influence? About 99 percent of Earth's carbon exists ~ carbonate sediments, most of them derived from biomin- eral~zation. Rates of erosion by wind and water depend on the extent and type of vegetation. 4. How productive are the major ecosystems? The rate of photosynthesis is influenced by the amount of light of appropriate wavelength reaching the Earth's surface, and, hence, is influenced by the Earth's adbedo. Most of the energy converted by plants, algae, and photosynthetic bacteria is expressed in the synthesis of carbohydrates: CO2 + H2O ~ CH2O + O2. The albedo of the Earth depends not only on its atmospheric composition, but also on the life in its oceans and on its land manes.
66 5. What are the impacts of major human activities? Exten- sive use of fossil fuels and other industrial activities are increasing atmospheric concentrations of carbon dioxide, sulfur dioxide, and other gases. Deforestation in the tropics leads to increased ero- sion, reduced synthesis of ozone by photosynthesis, ~d reduced transpiration of water. The release of chIoroiluorocarbons into the atmosphere may be reducing the ozone layer and increasing the greenhouse effect. 6. Can the vast amounts of empirical data that will come from satellite and other global arrays of instruments be incorpo- rated into a predictive mode} for Earth as a whole, leading to the formulation of new principles? To mode] Earth systems on tune scales from days to millennia presents complexity without precedent. Space Biology Goals The goal of space biology 38 to determine whether the unique opportunity of experimentation at microgTav~ty can advance OUT und;erstanding of basic phenomena in biology. Throughout its entire evolution, life on Earth h" experienced only a one-g environment. The influence of this omnipresent force is not weD understood except that there is clearly a biological ret spouse to gravity in the structure and functioning of living organ- isms. Access to a microgravity (micro-g) space station laboratory may facilitate research on the cellular and molecular mechanisms involved in sensing an acceleration as low as lo-6 g and sum sequently transducing this signal to a neural, ionic, or hormonal signal. Propagating selected species of plants ~d animals through several generations at micro In such a space laboratory would advance our understanding of these biological responses. Major Questions for Space Biology: 1995 to 2015 From 1995 to 2015 the steering group recommends addressing four major questions: I. How do plant cells detect the gravity vector and transduce this force to hormonal Ed nonhormonal signals? This gravitropic response utilizes growth-stimulating hormones, such as gibberellin and indoleacetic acid, and the inhibiting hormone abscisic acid. These same hormones, along with electric current, are involved
67 in phototropism; the interactions between the two responses are complex. Investigations of these processes are unport ant for the development of a successful Controlled Ecological Life Support System (CEL.SS). 2. Can higher plants and animals be propagated through sev- eral generations at m~cro-g? Though many embryos orient their cleavage planes relative to the gravity vector, we do not understand whether gravity, per se, is essential to gametogenesis, fertilization, implantation In animals, organogenesis, or development of normal sensorimotor responses. Given the effects of m~cro-g on deminer- alizatioct in bones, muscle wasting, and vestibular function, there is some question whether vertebrates can develop normally at micro-g. 3. What is the relative contribution of gravity to sensorunotor functions? The otolith organs ~ the inner ear allow us to detect linear accelerations In three orthogonal directions and distinguish these from rotation, which is detected by the semicircular canals. These responses, already complex, are further integrated with visual and proprioceptive input. The ability to remove or to vary signals from the otolith should help us understand the interactions of these sensory systems and shed msight on the nature of motion sickness. 4. What are the fundamental biochemistry and physics of biom~neralization? Understanding the physical and chemical pros cesses of biomineralization on Earth is necessary to fully under- stand the potential effects in m~crogravity environments. This process almost always occurs within membrane vesicles or is as sociated with polymers of carbohydrates or of proteins. Scores of biominerals exist, the most common being CaC03, calcite or aragonite, and Ca~O(PO4~6(OH)2 the hydroxyapatite of bones. Macroscopic solubility products do not readily explain the growth of these aggregates of crystallites. Space Medicine Goal The goat of space medicine is to understand the human ~oi- ology underlying the prophylaxis and therapy of maladaptations encountered; in extended space travel and to d;evelop prophylaxis and therapy to treat them if it is feasible. Space flights extending for weeks or months have already
68 caused several physiological problems that could endanger astro- nauts during longer flights or on their return to Earth. At m~cro- g, fluid accumulates ~ the upper body; subsequently, astronauts must remain horizontal for hours to weeks on return to Earth. During flight, extensor muscles atrophy, and, of greater concern, bone calcium and phosphate are lost from weigh~bear~ng bones. We do not know whether these effects reach a plateau. If not, they could irreversibly compromise the health of an astronaut or even lead to death. Numerous other effects of prolonged weightlessness, compounded by the rigors of the confiner] environment of a sta- tion, pose serious threats to health and performance. The heavy ion radiation of outer space is not only mutagenic but also could have disastrous effects on the brain. Each such particle inflicts severe damage or even death to nondividing cells. Major Questions for Space Medicine: 1995 to 2015 From 1995 to 2015 the steering group recommends addressing · · six mayor questions: I. Are there adverse effects of weightlessness that grow pros gressively more debilitating as flights are extended incrementally from months to years? We already anticipate severe problems with bone loss, and probably with muscle atrophy =d cardiovascular decondition~g. Others that cannot be predicted may also occur. These could involve the immune and the endocrine systems. The rigors of confinement will probably compound these physiologi- cal effects and profoundly affect behavior. A series of controlled experunents will help to sort out the effect of inevitable human variability on responses. 2. What are the hormonal, nutritional, and mechanics cor- relates and mechanisms of biom~neralization? Although doctors may develop empirical procedures to alleviate the severity of de- m~neralization, we must understand the underlying molecular and cellular biology of bone remodeling and of calcium and phosphate homeostasis. A similar question concerning biomineralization was posed for space biology, rejecting the frequent and productive interactions between clinicians and biologists. 3. What are the fundamental genetic, hormonal, and mechan- ical factors that determine muscle development and maintenance? Our working hypothesis is that during muscle wasting the rate of breakdown of muscle protein exceeds the rate of synthesis. We
69 must understand the factors coupling weightlessness to the controls of those genes encoding muscle proteins as well as those genes encoding muscle-specific proteases. 4. What are the biological effects of prolonged exposure to heavy ion radiation? It is difficult to reproduce with particle ac- celerators the exact spectrum of radiation encountered In outer space where heavy iron, 56Fe, traveling at 0.9 times the speed of light, Is the predorn~nant particle. Cultures of cells as well as plants, rodents, and higher primates must be exposed and subse- quently analyzed to enlarge the empirical data base. In parallel, we should explore the basic biophysics of the heavy ion damage in hopes of developing prophylaxis and therapies. It would be imprudent even to plan extended missions until these serious medFical issues are resolved. 5. How can we ensure adequate life support systems for long- term space travel? The development of a Controlled Ecological Life Support System (CELSS) is essential to missions of long duration. Although this development is, ~ a sense, a technological issue' it is so complex and requires so many advances in our understanding of biology that we can regard it as a major scientific goal that spans the interests of space medicine, space biology, and global biology. Aside from the challenges of growing plants at m~cr~g, and the utility of CELSS as a life support aid, the concept of constructing, at least partially, an artificial ecosystem is of great interest to the science of ecology. It may offer a research too} of considerable value for study of the principles by which natural ecosystems function. 6. Under the conditions of space, what are the optimal inter- actions between humans, machines, and computers? May con- struction and observation tasks will be done under extremes of pressure, temperature, and radiation hostile to the human organ- ism. Human judgment and ingenuity are valuable or indispensable to some of these jobs. This should not be seen as a choice between man and robot, but ~ a challenge to integrate their respective capabilities. This wall require fundamental research not only in machine design but also in human neurophysiology. ~:COMMENDE:D PROGRAM: POST-1995 Two basic requirements dominate most of these recommen- dations. Global biology and exobiology require ground-based observations and experiments to calibrate and verify satellite
70 observations. Space biology and medicine require one-g controls for experiments and observations at m~cro-g. Recommendations for Exobiology The steering group envisions a series of observation and sam- ple return rrlissions complemented by ground-based analyses and experiments. 1. Determine the properties of the atmospheres of Mars, Ti- tan, and Jupiter with greater precision. The reactions leading to any organic compounds found there should be compared with models for chemical synthesis on the primitive Earth. 2. Return sedimentary rock and soil samples from Mars after a careful analysis and selection of sites. The initial compositional analyses can be done at the sites. Complete analyses will require a full range of laboratory procedures including electron microscopy and microprobe analyses. This study should include searches for organic molecules and for fossil evidence of primitive life forms, and deterrrunation of important isotopic abundances, such as carbon, nitrogen, oxygen, and hydrogen. 3. Return samples from asteroids and comets to Earth and analyze them with the methods now used to analyze meteorites and captured interplanetary dust particles. The design and execu- tion of these missions should be closely coordinated with planetary . sciences. 4. Continue to explore fossils, isotope enrichment, and other evidence of prebiotic and early life on Earth. 5. Refine laboratory experiments simulating likely prebiotic reactions as more results from missions accumulate and as molec- ular biology lends more insights into the fundamental structures and reactions of cells. Recommendations for Global Biology The steering group projects a series of satellite flights to de- fine the major ecosystems over the entire Earth ~d to measure remotely their contributions to the major biogeochern~cal cycles. Data obtained from these flights should Al be calibrates! against measurements at selected sites to assure detection of long-term trends.
71 1. Determine the predominant plants for the major ecosys- tems, and measure their chlorophyll content and rate of biomass formation. 2. Measure the seasonal variations in carbon dioxide fixation for these ecosystems. 3. Measure the production rates, reactions, and fluxes of sev- eral trace gases for the major ecosystems. These measurements will require the refinement of gas chromatography, mass spectrometers, color imagers, laser fluoroscopes, and synthetic aperture radar. 4. Compare the unpacts of human activities, such as deforesta- tion and industrialization, with well-established baselines. These goals are included in the Mission to Planet Earth (described in Chapter 2~. The two programs should proceed in close colIabora- tion. 5. Develop correlative models to accommodate vast amounts of diverse data. The will require that special attention be paid to data reduction and archiving and to computational facilities. These correlations shouic! lead to interpretative and predictive models. B-ecommendations for Space Biology and Space Medicine The steering group believes that these disciplines require a series of missions, each addressing one of the mad car research prom lems previously discussed. 1. Construct a dedicated life sciences laboratory with a large variable-speed centrifuge to hold plants and animals and to prm vice one-g controls. Without adequate controls, most of the exper- iments at micro will be of limited value. This centrifuge will also facilitate experunents addressing the effects of reduced gravity as found on the Moon. (As will be required for m~cr~g experiments in the physics of solution, some experiments treating the set- tling of amyloplasts or growth of crystab will require a frequency analysis and isolation from accelerations exceeding loss g.) 2. Consistently employ four to eight critically selected plant and animal species, such as the nematode Caenorhabditis elegans and the cress Arabidopsis thaliana for as many gravity-related experiments as possible. This focus wait extend and refine descries tions of the physiolog~es and genetics of these species, including techniques to clone them and extensive analyses of their genomes.
72 3. Precede m~cro-g experiments, which will be infrequent and expensive, with thorough simulations at one-g (e.g., extended bed-rest for cardiovascular Reconditioning or demineralization and clinostat experiments for gravitropism). In-flight controls at one- g are mandatory to account for potential artifacts, such as the acceleration of launch, vibrations, and astronaut activities. 4. Evaluate the biological effects of heavy ion radiation thor- oughly using accelerator sources. If possible, these experiments should employ the selected organisms already mentioned. 5. Require a prototype of CELSS to function satisfactorily on Earth for several years before attempting to launch such a system into space. Evaluate in highs those components whose functions might be altered at m~cro-g. 6. Establish empirically a data base of the ranges of human physiological and behavioral responses to m~cro-g under prolonged isolation. All astronauts should participate in nor~invasive or mini- mally invasive tests as well as monitors of behavioractivity levels and general speech patterns, for example. All such tests must be consistent with weD-established standards of personal privacy and medical ethics and must not interfere with astronaut safety or job performance. Many of these basic data such as pulse, blood pressure, basic metabolic rate can be obtained from rniniatur~zed devices worn on the skin, or from simple automated analyses of urine and drops of blood. (Although this study does not address the delivery of health care, it is obvious that many of the measure- ments required for research are required for diagnosis. Economy can be realized without compromising either function.) 7. NASA should make a major investment in robotics, both developing new instruments and computers and optimizing the interactions between humans and robots. Significance of Recommendations By 2015 we hope to have an inventory of organic compounds found on other bodies in the solar system. By 2015 we expect more definitive information on the past and present liquid water on Mars, as well as the results of the preliminary search for fossils and other evidence of past life. The greatly enlarged data base of global biology and earth science should permit refined predictions of atmospheric patterns over decades. We should have much more insight into the Sequence
73 of life on the general evolution of Earth. In particular, we should understand whether major perturbations, such as glaciation or mass extinction, reflect events originating outside the Earth or if they are predictable transitions in the evolution of a closed system with constant energy flux. The knowledge gained from these measurements wiD focus our searches for minerals and fuels. Also, with an appreciation of the ecological impacts of human activities, rational and balanced conservation programs can be implemented. It is quite possible that an increased respect for our planet waif accompany an increased understanding of it. The steering group has proposed investigations at micro-g of several biological phenomena, such as gravitropism development, sensorimotor integration, and bone remodeling. It has also called for ~ Controlled Ecological Life Support System. These initial experunents should determine whether m~cro-g offers an effective experimental approach to some basic problems in biology. If such experiments are performed with flexible formats and appropriate controls, they may well reveal unanticipated phenomena of even greater interest. Although serendipity is hardly the basis of a ret search strategy, the steering group believes it a wise investment to apply some of the resources of the dedicated life sciences bay oratory to define the full range of questions best addressed at micro-g. By 2015, and even by 2005 if there is a dedicated life sciences laboratory, we should have fully described the physiological and behavioral responses of human beings subjected to m~cro-g and to heavy ion radiation for periods of over a year. Anticipating significant adverse effects, we should at least have defined which of these effects might be alleviated and be wed on the way to realizing treatments. We should have acquired a greatly refined insight into the unique limitations and capabilities of humans and Of robots in space flight. Most unportantly, understanding the optimum interactions of humans and robots should permit us to evaluate rationally their appropriate roles in commercialization, exploration, and research in space. This program in life sciences should be adequately funded and properly integrated with the other space sciences and with ground-based investigations. It will make a significant contribu- tion to understanding the evolution of our planet and ourselves. If pursued with reason and caution, it will help define our proper relationship to Earth.
