4
Impact of ISS Changes on Fundamental Biology

INTRODUCTION

NASA research in fundamental biology seeks to understand the changes that occur in the physiology and function of living organisms in a spaceflight environment. Research sponsored by the NASA Office of Biological and Physical Research (OBPR) includes such areas as cell and molecular biology, developmental biology, and gravitational ecology. More recently NASA has begun to bring evolutionary biology into the program. Discussed in this chapter are areas of fundamental biological research in which NASA has developed a substantial program and that are likely to have a significant presence on the ISS, and task questions 3 and 4, which relate to its implementation on the ISS, are considered. It is shown that the downgrading of the ISS from Rev. F to Core Complete and the limitation of crew size to three seriously jeopardize the ability to carry out meaningful science in these fields. The loss or lengthy delay of critical facilities such as the centrifuge and the animal habitats makes some experiments in fundamental biology impossible, while other experiments will be seriously compromised by the lack of crew time.

CELL AND DEVELOPMENTAL BIOLOGY

Program Description

Cell biology studies biological processes at the level of the basic unit of biology, the cell. As such, cell biology underpins the other biomedical disciplines relevant to space biology. Developmental biology focuses on the processes and mechanisms responsible for the development of the zygote into a primordial set of cell types and on subsequent developmental events that produce the mature organism.

The past decade has seen major technical developments in the study of eukaryotic cells, including the application of molecular genetics and molecular biology, advanced imaging technology, cell culture methodologies, protein chemistry, and macromolecular structural determination. These developments have led to dramatic progress in our understanding of fundamental biological processes at the cellular and developmental levels. Fundamental questions that are now within the reach of experimental investigation include those surrounding the mechanisms by which cells replicate and maintain their genomes, regulate survival, generate and maintain a complicated internal cytoarchitecture and organellar substructure, respond to changes in the extracellular environment, and differentiate into specialized tissues and multicellular organisms.

The Space Studies Board report A Strategy for Research in Space Biology and Medicine in the New Century (NRC, 1998) pointed out that, with only a few exceptions, cells are considered incapable of perceiving gravity directly. However, cells in tissues respond indirectly to gravity as a result of changes occurring in the cellular environment, and the report recommended investigating several specific areas of fundamental cell biology in space. Among these areas were the mechanisms of cellular mechanoreception and cellular responses to environmental stresses encountered in spaceflight (e.g., anoxia, temperature shock, vibration). It was also recommended that NASA, in cooperation with the scientific community and industry, should work to develop advanced instrumentation and methodologies for space-based studies at the cellular level. A further recommendation was to evaluate carefully experiments with cells in culture prior to flight, looking at their theoretical and practical justification, the availability of fully tested hardware, the capacity to carry out appropriate controls, adequacy of sample sizes, and the potential for repeating the experiments. In addition, the problems associated with alterations of sedimentation and fluid and gas convection in weightlessness should be considered.



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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences 4 Impact of ISS Changes on Fundamental Biology INTRODUCTION NASA research in fundamental biology seeks to understand the changes that occur in the physiology and function of living organisms in a spaceflight environment. Research sponsored by the NASA Office of Biological and Physical Research (OBPR) includes such areas as cell and molecular biology, developmental biology, and gravitational ecology. More recently NASA has begun to bring evolutionary biology into the program. Discussed in this chapter are areas of fundamental biological research in which NASA has developed a substantial program and that are likely to have a significant presence on the ISS, and task questions 3 and 4, which relate to its implementation on the ISS, are considered. It is shown that the downgrading of the ISS from Rev. F to Core Complete and the limitation of crew size to three seriously jeopardize the ability to carry out meaningful science in these fields. The loss or lengthy delay of critical facilities such as the centrifuge and the animal habitats makes some experiments in fundamental biology impossible, while other experiments will be seriously compromised by the lack of crew time. CELL AND DEVELOPMENTAL BIOLOGY Program Description Cell biology studies biological processes at the level of the basic unit of biology, the cell. As such, cell biology underpins the other biomedical disciplines relevant to space biology. Developmental biology focuses on the processes and mechanisms responsible for the development of the zygote into a primordial set of cell types and on subsequent developmental events that produce the mature organism. The past decade has seen major technical developments in the study of eukaryotic cells, including the application of molecular genetics and molecular biology, advanced imaging technology, cell culture methodologies, protein chemistry, and macromolecular structural determination. These developments have led to dramatic progress in our understanding of fundamental biological processes at the cellular and developmental levels. Fundamental questions that are now within the reach of experimental investigation include those surrounding the mechanisms by which cells replicate and maintain their genomes, regulate survival, generate and maintain a complicated internal cytoarchitecture and organellar substructure, respond to changes in the extracellular environment, and differentiate into specialized tissues and multicellular organisms. The Space Studies Board report A Strategy for Research in Space Biology and Medicine in the New Century (NRC, 1998) pointed out that, with only a few exceptions, cells are considered incapable of perceiving gravity directly. However, cells in tissues respond indirectly to gravity as a result of changes occurring in the cellular environment, and the report recommended investigating several specific areas of fundamental cell biology in space. Among these areas were the mechanisms of cellular mechanoreception and cellular responses to environmental stresses encountered in spaceflight (e.g., anoxia, temperature shock, vibration). It was also recommended that NASA, in cooperation with the scientific community and industry, should work to develop advanced instrumentation and methodologies for space-based studies at the cellular level. A further recommendation was to evaluate carefully experiments with cells in culture prior to flight, looking at their theoretical and practical justification, the availability of fully tested hardware, the capacity to carry out appropriate controls, adequacy of sample sizes, and the potential for repeating the experiments. In addition, the problems associated with alterations of sedimentation and fluid and gas convection in weightlessness should be considered.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Finally, the report concluded that investigations involving single cells and cell culture models should be analyzed in ground-based studies. The Strategy report (NRC, 1998) also reviewed the current state of the field of developmental biology and the potential for meaningful investigations of development processes in microgravity. It stressed two main questions relevant to future investigations conducted in space: Can organisms undergo normal development in microgravity? Are there developmental phenomena that can be studied better in microgravity than on Earth? It was concluded that the space environment may indeed be useful for understanding certain biological phenomena in developing systems. Specific systems in which gravity was considered likely to play a critical role in development and/or maintenance include the vestibular system and the multiple sensory systems that interact with the vestibular system. The answers to these questions could have profound effects on the performance of astronauts in space and their postflight recovery on Earth. Gravity was also expected to influence topographical neural space maps that exist throughout the brain, with attendant effects on neuroplasticity, i.e., long-term changes in neuron structure and function in response to changes in their activity. Finally, the report concluded that analyses of complete life cycles in space could determine if some developmental events are affected by reduced gravity, and that high priority should be given to testing vertebrate models, including avian systems. If developmental effects are detected, control experiments must be performed on the ground and in space with the latter, including the use of a space-based 1-g centrifuge. Important issues related to these goals should be investigated in ground-based studies as preludes for investigation in space. Controls for the effect of non-gravitational stresses likely to be encountered in space, such as loud noise and vibration, must also be performed on the ground so that space experiments can be designed to isolate the effects of microgravity from the effects of other stresses. A number of experiments under way within current NASA fundamental biology and biotechnology programs in cell and developmental biology are asking questions pertinent to the recommendations made in the Strategy report (NRC, 1998). An examination of the NASA task book relevant to fundamental biology (NASA, 2001c) found 102 entries, nearly all of them ground-based studies. Emphasis is being placed on the development and function of the vestibular system, otoliths and hair cells, bone, smooth and skeletal muscle, adrenal cells, endothelial cells, and lymphocytes. Studies are under way in the areas of proprioreception, hormone response, signal transduction, immune response, neuronal development and plasticity, early embryonic development and stem cell migration, aging, neurosecretion, cytoskeleton and motility, cell survival, circadian rhythms, and homeostasis and energy metabolism. Some use is being made of “simpler” eukaryotic, multicellular organisms such as fruit flies and zebra fish, as well as unicellular prokaryotes. Overall, these studies stress the potential importance of cell and developmental biology for both basic research and countermeasure research in bioastronautics. Note that the assessment in the next subsection largely ignores the cell and developmental biology of plant systems, which are discussed in a separate section. Impact of ISS Changes In terms of cell and developmental biology research, the critical resources of the Rev. F configuration included a crew of six or seven members, habitat holding racks for mice and rats (including special inserts for animal biotelemetry systems), a 2.5-m, 1-g centrifuge, a life sciences glove box, a cryofreezer, an insect habitat, an aquatic habitat, an avian research facility, an avian development facility, and a budget commensurate with the needs of world-class cell and developmental biology research. A number of these critical resources have been considerably delayed or eliminated (Liskowski, 2002a). For example, the advanced animal habitat has been eliminated along with the avian research facility, essentially precluding the ability to characterize the genetic and developmental response of nonhuman vertebrates such as rats and mice to long-term exposure to space. Deployment of the centrifuge accommodation module and the 2.5-m, 1-g centrifuge and associated software (by NASDA), a critical element of control experiment design, has been delayed until at least 2008. Other facilities are

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences currently planned, but the implementation of most has been delayed. These include (see also the section in Chapter 3 on ISS facilities for bone and muscle research) the general-purpose incubator, the ARTIC 80 °C freezer (installed in 2002), the 80 °C freezer (MELFI, in 2003), the cell culture unit (2005/2006), the insect habitat (Canadian Space Agency, in 2006) and its included small internal centrifuge, two core facility habitat holding racks (2004/2005) for the first, followed by the second approximately 2 years later), and the life sciences glovebox (2005/2006). The avian research facility will be only on the shuttle and not available on the ISS. The aquatic habitat is being built by the Japanese Space Agency (NASDA) but apparently will not be available until after 2008. Dramatic cuts have been announced in the budget for fundamental space biology (Liskowski, 2002b), of which developmental biology is a part. The task group noted that ISS restructuring is under way, with consideration of how to reinstate some of these eliminated facilities. It is difficult to predict exactly the time needed to carry out research in cell and developmental biology, but experience shows the importance of significant direct intervention by trained crew members and suggests that requirements for crew time tend to be greater than initially anticipated. The reduction from a six- or seven-member to a three-member crew suggests that sufficient time will simply not be available, since the skeleton crew will have to focus on space station operation rather than research activities. In addition, there appear to be few opportunities for adequate preflight crew training in the requisite research techniques. Thus, most experiments will need to be largely self-contained and highly automated. Planned Experiments That Have Been Eliminated From the information provided by NASA (e.g., Ostrach, 2002), it is noted that two scheduled ISS experiments in developmental biology had been deselected as of December 2001. These are experiments 96-01-207, “Relationship of morphogenesis and mineralization to gravitaxis,” by P.J. Duke, University of Texas, and 99-02/03-026, “Effect of microgravity during the critical period of Zebrafish vestibular development,” by S. Moorman, Case Western Reserve University. Effect on Cell and Developmental Biology The projected reductions and delays in the deployment of research facilities on the ISS pose major challenges to the vitality of research in cell and developmental biology. For example, the elimination of the advanced animal habitat and plant research unit will make it difficult to carry out a comprehensive program in developmental biology aimed at understanding the manner in which complex organisms, especially eukaryotes, respond to long periods in space. Included in this impact will be difficulties in fully applying a number of elegant genetic systems pertinent to the study of cell and developmental biology. While this loss could potentially be offset in part by using insect and avian systems, it would still severely limit, and probably eliminate, some of the most important vertebrate models. The loss of crew time poses further problems. The impact is not only on the performance of experimental procedures during a flight interval but also on the preparation of material for further analysis upon reentry. Further, a shuttle flight rate of only four per year will severely limit the ability to transport research material to and from the ISS. Finally, the delay of deployment of the 2.5-m, 1-g centrifuge critically limits the design of necessary control experiments. An important capability of the ISS was expected to be its provision of an environment in which studies could be carried out in space, eliminating the confounding variables associated with launch and reentry. Without the centrifuge, critical control experiments in which organisms are maintained at 1 g at the same time and place as they are maintained in microgravity are not possible, critically compromising the interpretation of results.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Impact on Readiness of Principal Investigators The important studies in cell and developmental biology in space involve long-term commitments on the part of investigators. With continued losses of funding and the associated uncertainties in the availability of facilities, crew time, and the 2.5-m, 1-g centrifuge, the developmental biology community may become unwilling to be involved in the microgravity research program. Even when funds and technical capacity are available, there are often long delays from selection to flight, and the possibility of having an experiment removed from the queue downstream remains an important consideration. These are serious problems that not only stifle enthusiasm within groups of colleagues, but also become an important factor in academic career decisions, especially for young investigators and students. Without confidence that high-quality science can be accomplished, these investigators will have no practical choice but to seek other opportunities to which to apply their talents. Research That Can Still Be Done on the ISS Five experiments in cell and developmental biology have been identified that were flown in 2001 under the cellular biotechnology program on UF-1 and ISS 7A.1 (Trinh, 2002b). They involved the production of growth factor and antigen synthesis by cells in culture; tumor cell gene expression; and renal differentiation and hormone production. An encouraging number of additional ground-based studies are identified in the NASA task book that included analyses of stress, neuronal plasticity, vestibular function, bone and muscle physiology signal transduction, and immune response(NASA, 2001c). On the other hand, only five experiments in cell and molecular biology and one in developmental biology are currently on the list of those selected for definition in 20011 (Appendix I), perhaps accurately reflecting the extent of the remaining research capacity on the ISS. As discussed above, the absence of the 2.5-m, 1-g centrifuge and the limited crew time negatively impact cell and developmental research in a general and pervasive manner. The avian development and insect units can provide some relief when they become available, but even there, uncertainties surrounding crew time for research and hardware lead to a less-than-positive sense of potential. The expanded use of lower organisms such as the fruit fly and C. elegans may be worth considering in the present climate in view of their small size and the potential for genetic analysis. The Strategy report (NRC, 1998) noted that engineering demands and expense, and the difficulty of repeating experiments in space in sufficient number for analysis, place substantial burdens on the testing of hypotheses about the role of gravity in normal developmental events. These issues are highly relevant to cell and developmental biology and are exacerbated in the current climate of ISS cutbacks, as is reflected in the minimal level of research in cell and developmental biology that is currently being carried out on or planned for the ISS. The question for the present evaluation, then, is whether the ISS can, in its expected Core Complete configuration, carry out high-quality research aimed at answering basic questions in cell and developmental biology. Without proper resolution of the issues raised above, it may be necessary to further delay studies of this nature in cell and developmental biology on the ISS, emphasizing in the interim basic ground-based research. In fact, as stated in the guidelines in the Strategy report (NRC, 1998), there are substantial issues that can, and must, be settled first by ground-based research, including most prominently the testing of protocols and equipment. However, for this approach to be effective, it will be essential to provide sufficient funds to perform the recommended research. 1   Experiment list was provided by NASA and contains experiments already selected, as of February 2002, for future flight on the ISS.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Factors Limiting Utilization of the ISS As outlined throughout the previous sections, many factors limit utilization of the ISS for fundamental biological research in cell and developmental biology. They include the elimination of key facilities and equipment or uncertain delays in their installation, inadequate crew time for research, and the absence of a concrete set of research priorities within which to plan. Limitations on funding for developing experiments are an additional concern; for example, funding for fundamental biology in OBPR has remained at a plateau level for several years. Overlying these important specific issues, however, is a pervasive uncertainty as to if and when relief from these problems can reasonably be expected. At the level of prudent experimental planning, there is a discomfortingly long time line from initial conceptualization to actualization of a study, bringing further uncertainties about whether a study will still be state of the art in concept and approach by the time it can be flown. These uncertainties negatively impact not only the ability to develop scientific strategies but also investigator morale and commitment. Maximizing ISS Research Potential It is clear that many opportunities originally envisioned for research in cell and developmental biology have been dramatically curtailed. There is concern as to whether the current Core Complete stage of the ISS can truly support the highest-quality cutting-edge research in cell and developmental biology. Nevertheless, it appears that some possibilities may exist. A workshop titled “Space Biology in the Early International Space Station,” held at NASA Ames Research Center on March 14-15, 2002, and chaired by B.S. Blumberg and K.M. Baldwin, was convened to explore the type, scope, and value of biological research that could be best accomplished on the ISS, given the constraints of the present realities. To carry out high-quality science is difficult under the best of conditions. The challenge for ISS research is to identify, within current vehicle constraints, high-priority, high-quality, hypothesis-driven experiments that can be sufficiently replicated and validated with adequate controls, including in-flight gravitational controls. Careful ground-based evaluation of facilities and experiments in advance flight, always important, becomes even more critical now in order to ensure that meager opportunities are not wasted. Care must be taken not to succumb to the temptation to carry out a particular experiment simply because it is possible, especially if the research will be weak, uncontrolled, and of low priority. One way to maximize the potential for research in cell and developmental biology would, of course, be to resurrect the missing funding and facilities, including a proposed buyback of rodent and plant research capability. In the absence of such facilities, meaningful studies of vertebrates will be difficult, but a carefully chosen small set of insects and simpler multicellular eukaryotic organisms, such as drosophila and C. elegans, could be selected for initial investigations, in the hope that more complex vertebrate organisms can be worked with in the future. Organisms for which the entire genome has been sequenced should be given priority. The European Biolab offers an excellent model that should be investigated in this regard (ESA, 2002); this unit, which will include two 60-cm centrifuges, is designed for experiments involving cell culture, microorganisms, and small invertebrates. NASA should encourage the development and deployment of this unit and work to ensure that it will be available for use by U.S. investigators. The admonition of the Strategy report (NRC, 1998)—to carefully evaluate experiments with cells in culture prior to flight with regard to their theoretical and practical justification—remains a timely recommendation and should be included in the planning of all future experiments. Vigilance will have to be continued to discriminate between effects directly related to microgravity from those arising secondarily from environmental variables such as perturbations in diffusion, turbulence, and radiation, for example. Adequate funding should be provided to encourage this ground-based preparation and to help maintain the scientific community for the future.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Even when specific questions and appropriate systems can be identified, experiments will have to be planned that require a minimum of crew time. Advances in biotechnology, in-flight automation, telecommunication, miniaturization of systems, and bioinformatics for online data offer some hope. The concept of sending up material at low temperature for study at physiological temperatures on the ISS also offers potential. At the other end of the experimental time line, facilities for cryo-storage of selected biological material prior to return must be developed and placed on the ISS in order to optimize options for postflight sample analysis on Earth. PLANT BIOLOGY Program Description The study of plants in space is driven by two objectives (NRC, 1998). The first is to determine how best to grow plants in a spacecraft environment. A goal of NASA is to mount missions, sometime in the future, to remote areas of our solar system and to set up and maintain a human presence on the Moon and/or on Mars. These long-duration stays by humans in space, cut off from constant resupply from Earth, will require that the astronauts be able to produce at least some of their own food. Therefore the farming of plants in space, as part of an advanced life support (ALS) system, will be a necessity. Growing plants efficiently and successfully in space has proven to be difficult. There are practical problems to overcome, such as how best to get water to the roots without subjecting them to anaerobic conditions, or how best to handle the elevated levels of carbon dioxide and ethylene that are commonly found in human-occupied spacecraft. For each potential crop, the optimal light intensity and quality and the maximal crop density must be known. Most of the important problems have been identified, and solutions have been proposed. Tests of these solutions have thus far produced promising results (WCSAR, 2001), but there are still significant technical barriers to overcome. The second objective of space research on plants is to obtain fundamental knowledge about the extent to which gravity is required for and/or influences plant development and physiology. A few responses to gravity, such as gravitropism and circumnutation, are already well known and have been studied extensively on Earth. The pivotal question requiring experiments with plants in space, as explained in the Strategy report (NRC, 1998), had been whether a plant can successfully go through its complete life cycle in microgravity. The repeated failure of the Russians to grow any plant through a full generation in space had increased the importance of performing a definitive experiment to answer this question. In fact, it has been recognized by the plant gravitational biology community that a plant should be grown through at least two successive generations in space, in order to answer this question (NRC, 1998). Ideally the experiment should have an on-board 1-g centrifuge control, but despite the lack of a centrifuge control and less than optimal conditions, this question has now been answered. An experiment on Mir, using Brassica rapa, succeeded in growing the plants through more than two complete generations, despite many technical difficulties (Musgrave et al., 2000). More recently, Arabidopsis plants have been grown through a single generation on the ISS (University of Wisconsin-Madison, 2001). These experiments effectively eliminate the possibility that gravity is a requirement at some stage for the survival of plants, but there is still a real possibility that a lack of gravity might alter some aspect of plant development or physiology. Spaceflight experiments to date have shown some minor effects of the microgravity environment on plant development. However, the lack of a 1-g on-board control has made it impossible to separate responses caused by a lack of gravity from responses to other parameters of spaceflight, such as vibration, enhanced carbon dioxide, or lack of air circulation. Moreover, many plant processes, such as photosynthesis, have never been studied in a microgravity environment.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Impact of ISS Changes Since the early days of ISS planning it has been envisioned that the ISS would contain two facilities essential for plant science experiments. The first is a plant research unit (PRU) in which to grow plants and conduct long-term experiments on plants under conditions of controlled light intensity, temperature, carbon dioxide, and humidity. This unit would not contain a centrifuge, but it would be capable of being attached to a large-diameter centrifuge (see below). The PRU, in the absence of a centrifuge, would be suitable for the range of ALS experiments whose goal is to learn how to grow plants in space but not for the experiments in fundamental biology, whose goal is to understand the mechanisms by which plants respond to gravity. The second facility is a 2.5-m centrifuge, to which the PRU (and comparable animal modules) could be attached. It would provide the 1-g conditions needed as controls for microgravity experiments on the ISS. The combination of the PRU and the centrifuge would provide a suitable facility for experiments in fundamental plant biology. Two PRUs have already been built in the United States, and both have been or are being flight tested. The units differ with respect to the size of the plants that can be accommodated and the parameters that are controlled; each unit would be of particular value for a specific set of plant experiments. The first to fly on the ISS is the advanced astroculture (ADVASC) unit, produced by the Wisconsin Center for Space Automation and Robotics (WCSAR), which has been flown on two missions (6A to 7A.1 and UF-1 to 8A). Its development was funded by the Space Product Development (SPD) Program in Code UM. This unit is a two-middeck-locker-equivalent unit and will not fit on the large centrifuge in its present state but could be modified to fit the centrifuge. It will accommodate plants up to 12 inches high. WCSAR is also developing a commercial plant biotechnology facility (CPBF) with a chamber that will permit the use of larger plants (up to 19 inches). It uses half an EXPRESS rack and will not be suitable for use on the centrifuge. It is anticipated that the CPBF will be completed by FY 03. It will be available for both commercial and fundamental plant research aboard the ISS. The second unit was produced by ORBITEC (NASA, 2001b) (funded by Code UF) as a prototype for the plant research unit (PRU). This biomass production system (BPS) will not fit on the centrifuge in its current configuration. It was expected that the BPS would be developed into a PRU that could be attached to the centrifuge. However, funds to continue this work have been eliminated, and the current BPS unit is probably not suitable for future use on the ISS. The status of the 2.5-m centrifuge is not certain, but it will not be part of the ISS at Core Complete. The current plans are for deployment of the centrifuge in 2008 at the earliest. The lack of a suitable PRU and of an on-board centrifuge in going from Rev. F to the Core Complete design will have a severe negative impact on what can be accomplished on the ISS in fundamental plant science. On the other hand, the Europeans are planning to deploy two facilities that will significantly improve the situation. The first is their European Modular Cultivation System (EMCS), which will fit in an Express Rack on the U.S. Destiny lab (ESA, 2001) and is scheduled to be deployed on the ISS in July 2004. The EMCS will contain two 60-cm-diameter centrifuges, capable of g forces between 0.001 and 2 g and holding four experimental containers (ECs). Each EC will be illuminated and will have controlled humidity, temperature, and gases. Since an EC is only 60 x 60 x 120 mm, only small plants such as Arabidopsis can be grown in it. Nevertheless, almost all of the fundamental plant biology research questions likely to be proposed for study in space (as outlined in the NRC’s 1998 Strategy report) could be addressed with this facility, since it will provide both controlled conditions at microgravity and the necessary on-board 1-g controls. In addition to the EMCS, the European Columbus module will contain the Biolab (ESA, 2002). It, too, will have two 60-cm-diameter centrifuges and will have illuminated ECs that will accommodate small plants. While the Biolab is planned primarily for experiments involving cell cultures, microorganisms, and small invertebrates, it can be used for plant experiments as well. At present, no plant experiments have been deselected. Seven plant experiments, supported by Code UF, are currently under definition and/or development. These are listed in Appendix J. Four of these experiments fall into the area of advanced life support, while three are directed toward fundamental

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences biology problems. In addition, the ADVASC experiments, already flown in Increment 2 and 4, are manifested for Increments 5, 6, and 7 as well. These experiments are a combination of apparatus testing and experiments supported by commercial partners. As discussed, the change in the ISS from Rev. F to Core Complete is expected to result in a reduction in crew size from six or seven to three. The effect of this change on the plant science experiments is difficult to assess. Most of the currently planned experiments will require some involvement by the crew, and experience from Mir indicates that the crew time requirements could be considerable. In some experiments, for example, crew must be involved almost every day to plant seeds, make the physiological measurements, and harvest the material at specific times. In addition, before flight the crew will have to be trained extensively in many of the procedures that must be carried out. As one of a crew with only three members, it is difficult to see how a crew member would have the time to undergo the necessary training. Further time-line planning for the ISS could therefore lead to the deselection of some of these plant experiments. To sum up, the impact on the plant science program of the changes in facilities on the ISS could be limited, or it could be severe. Until the EMCS and Biolab arrive at the ISS, the only plant growth units would be the two commercial WCSAR units-the ADVASC and the CPBF. They should be suitable for the ALS experiments. As soon as the EMCS or Biolab is on the ISS and available for general use, meaningful fundamental plant biology experiments can be undertaken. However, if the crew size remains at three, it may severly limit the types of experiments that can be carried out. Factors Limiting Utilization of the ISS Three factors limit utilization of the ISS by the plant science community. The first is the availability of the needed facilities. Although two plant growth units are currently under development in the United States, only the WCSAR units are likely to be available on the ISS at Core Complete. These units are suitable only for ALS experiments. There will be no U.S.-produced facilities suitable for fundamental plant biology studies. In the absence of a PRU and the 2.5-m centrifuge, the EMCS and Biolab facilities that are being developed in Europe are essential for plant experiments, especially in fundamental plant sciences. The second limiting factor is funds for the development of plant experiments. It is essential that the ground-based background experiments be completed and the equipment and protocols for flight experiments be thoroughly tested on Earth before any experiment is carried out on the ISS. There has, unfortunately, been a lack of sufficient funds for this precursor ground-based research—indeed, the funds available for fundamental biology in OBPR have remained flat for several years. If funds for this type of work are diverted to cover other areas of need, there will not be opportunities for PIs to develop new experiments. The shortness of the list of currently funded plant experiments for the ISS means that the community of plant researchers willing and able to utilize the ISS at some future date is in danger of dropping below a critical mass. Finally, the lack of crew time, both for training for the experiments on the ground and then, when onboard, for running the experiments, may limit the ALS experiments, even if the facilities for this type of experiment are aboard the ISS. Maximizing ISS Research Potential There are four prerequisites for maximizing the research potential of the ISS in the plant science area: Continued development of suitable experimental facilities. First, funds should be restored to permit the BPS to be developed into a PRU that can be utilized on the large-diameter centrifuge.

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Factors Affecting the Utilization of the International Space Station for Research in the Biological and Physical Sciences Although the Europeans are developing two facilities that should be ideal for experiments involving small plants such as Arabidopsis a PRU, is needed that can handle larger plants, such as would be grown in a spacecraft on a long-duration mission. The date on which the centrifuge will be deployed on the ISS needs to be firmed up and made available to researchers, so that they do not have unrealistic expectations about when they will be able to do valid fundamental plant biology experiments on the ISS. The development of the WCSAR units needs to continue so that ALS experiments can take place on the ISS in the period before the PRU/centrifuge facility is available. Agreements need to be reached between SPD and Code UF to make these units available to all researchers. Availability and accessibility of the EMCS and Biolab. NASA needs to encourage the Europeans to continue with the development of the EMCS and Biolab modules and to ensure that they are deployed on the ISS. Agreements need to be reached with ESA about the availability of the EMCS and Biolab for use by U.S. investigators. Adequate funding for the preparation of plant experiments for future increments. Because of the many delays and uncertainties surrounding flight experiments, the community of plant scientists interested in making use of the ISS is small. This community must be nurtured by providing enough funding to complete all the preliminary, ground-based experiments. Certainty about funding for preliminary studies, coupled with firm plans for flight opportunities, will significantly expand plant scientists’ interest in conducting experiments on the ISS. Sufficient crew time. There is a sense of discouragement about the possibility that there will be only three crew members on the ISS at Core Complete. Those scientists who have already completed flight experiments know that the requirements for crew time are always more, rather than less, than the amount initially anticipated. There is no point in proposing experiments that involve a significant amount of crew time, even if the facilities for the experiments are available. If the ISS is to be a major research facility, it is essential that the number of crew be increased beyond three.