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Advantages of international cooperation in space life sciences research
Acta Astronautica 63 (2008) 776 – 782 www.elsevier.com/locate/actaastro
Advantages of international cooperation in space life sciences research Jancy C. McPhee∗ , Ronald J. White Universities Space Research Association (USRA), 3600 Bay Area Blvd., Houston TX 77058, USA Received 29 June 2007; received in revised form 5 March 2008; accepted 31 March 2008 Available online 19 May 2008
Abstract Today, a worldwide community of life scientists interested in space research is attempting to improve the understanding of general biological processes, aid the development of procedures to reduce the biomedically related risks of space flight, and/or directly support the health care of people who fly in space. Unfortunately, limited resources and subject availability and the technical challenges of performing space experiments have all hampered the full growth and development of space life sciences research. For many years, international cooperation in this field has been considered an attractive approach towards overcoming some of these difficulties, since pooling resources and sharing results would enhance the knowledge of all cooperating partners. International cooperative activities, however, require an investment by each partner and, just as in many other endeavors, the research gain can be directly related to the investment made. In this paper, the authors will discuss four possible types of cooperation: formal data exchange agreements; formal data exchange coupled with standardized data collection; joint strategic and tactical planning and full exchange of standardized data; and joint international team research with full data sharing and standardization. The advantages of these types of cooperation will be described. © 2008 Elsevier Ltd. All rights reserved. Keywords: Research cooperation; International; Integration; Standardization; IMAG Project
1. Introduction Space agencies around the world that support human space flight share similar operational and research goals related to medical care, biomedical risk reduction and mission performance maintenance. These goals translate to the development and implementation of a ground- and space-based human-focused research program. This similarity leads naturally to the question of what form of agency coordination and cooperation can best assist partners in achieving mutual goals and ∗ Corresponding author. Tel.: +1 281 244 6434; fax: +1 281 483 2888. E-mail address: [email protected] (J.C. McPhee).
0094-5765/$ - see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.actaastro.2008.03.014
objectives in a cost-effective way. This paper presents a qualitative discussion of the advantages of some of the basic types of international cooperation. 1.1. Human space flight health and performance issues Data from more than four decades of human spaceflight experience demonstrate that space travel affects every system in the body. In certain situations, health and performance may even be compromised. For example, appropriate adaptation of the body to a weightless or reduced gravity state can cause “deconditioning” problems during the transition into and the time spent in reduced gravity, as well as, during and just after re-entry into a higher gravitational environment. These adaptive
J.C. McPhee, R.J. White / Acta Astronautica 63 (2008) 776 – 782
777
Fig. 1. Complex factors affect human health and performance during spaceflight via multifaceted and integrated physiological changes.
changes are often compounded by the other environmental factors involved in spaceflight (Fig. 1), and taken together, can affect both the health of crewmembers and their ability to perform required mission tasks. Several review articles and textbooks provide background information concerning these changes and some of their effects on health and performance [1–6]. Understanding the integrated effects of spaceflight on humans and developing ways to reduce risks to human health and performance during and after space missions, particularly for some of the long-term exploration missions now being planned, is thus extremely important. 1.2. Difficulties of performing space life sciences research Data about the detailed effects of the space environment on human physiology are both limited and difficult to generate. Flying humans in space is very expensive,
and most space agencies currently have severely limited budgets to fund space life sciences activities. In addition, space experiments are often technically difficult to devise and perform, as the original researcher is remote from the test subject and the absence of gravity can make the experimental design quite challenging. Furthermore, access to space platforms, such as the International Space Station, is limited and often hard to obtain, and the number of crewmembers flying in space each year is small. This small number of test subjects implies that conclusions must often be drawn from a small number of data points. Performing a ground-based flight analog experiment with human test subjects, such as head-down tilt bed rest, is also expensive and time consuming, although much less expensive than a space experiment. Even in these analog studies, obtaining a sufficiently large number of test subjects is still difficult and being able to share resources and knowledge from studies that are carried out by the international space
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community would be very helpful to everyone involved in such human research. In addition to allowing for a greater quantity of data, such cooperation would also allow all of the partners to gain a deeper understanding of the complex effects of spaceflight on the whole body. 1.3. International research cooperation in the space life sciences There are many ways for agencies to cooperate in space life sciences research, but this paper will examine cooperation using only a few types of idealized active cooperation, each defined in a straightforward way. These cooperative activities generally involve both different levels of investment by each partner and different levels of return (generally data) to each partner. We will not consider the question of monetary cost or other investment in what follows, but in any real situation, each agency must weigh that cost against the benefits realized by the cooperative activity. The types of idealized cooperation discussed in this paper are: • Type 0: No formal cooperation. • Type I: Formal data exchange agreements. • Type II: Formal data exchange coupled with standardized data collection. • Type III: Joint strategic and tactical planning and full exchange of standardized data. • Type IV: Joint international team research with full data sharing and standardization. Type IV-A: Harmonious integration of pre-designed international experiments. Type IV-B: De novo international investigator team. There are other varieties of cooperation possible, but these four types illustrate many of the general principles involved in developing plans for international cooperation in space life sciences research. 2. Type 0: no formal cooperation This level is termed “no formal cooperation” because it involves individually performed studies that have not been synergistically combined. Historically, this has been one of the most typical (though not the only) method through which ground-based biomedical research is selected and funded. Individual investigator proposals are submitted to an agency, either in response to a formal announcement or because of the investigator’s own initiative. These proposals are reviewed and selected for individual funding. Data and conclusions from the selected independent studies are published
(hopefully in the accessible, peer-reviewed literature), thus making the results of the investigations known to all. The data and results then find their way into the base of scientific knowledge through these original publications and through review articles and textbooks. These later reports and compilations of the results of multiple studies provide some summary and low-level integration that is not available by looking at only the isolated, independent investigation results. The advantages of this approach are: the research is strongly related to investigators’ research strategy and goals and thus captures the investigators’ spirit; the latest research tools and techniques are generally applied to the problems at hand; and the creative and innovative ideas of the research community are captured in the research program. There is no question that this is an effective approach to generate knowledge, but it is most effective when the research budget, available experimental facilities and other resources are sufficient to support a large active research community (in the US National Institutes of Health program, this approach is informally termed the “field of a thousand flowers”). Despite the resource limitations constraining life sciences programs within space agencies, individual ground- and space-based investigations selected and funded in this way have long played a major role in the space research world. Of course, there are a number of drawbacks to not formally cooperating. There are delays in transferring data from one investigator to another in the meaningful way that allows sequential investigations to build on one another rapidly. In the space life sciences, such delays are magnified because of the multi-year processing time frequently required for an experimenter to collect enough subjects, analyze and publish the data. In addition, important space biomedical data may not be published at all or not be published in a widely accessible journal. This may be partially due to the fact that available data sets often have a very small number of test subjects and are difficult to defend as a definitive study, as required by many journals. Another important drawback of independent investigations is the difficulty of pooling data from different studies and of comparing results obtained by different investigators who may each use non-standardized approaches to data collection and analysis. 3. Type I: formal data exchange agreements One of the simplest ways for space agencies to cooperate is to formally exchange data and information related to research of common interest. Usually, the
J.C. McPhee, R.J. White / Acta Astronautica 63 (2008) 776 – 782
agreement to exchange such ground-based and spaceflight data and information occurs after the research has been completed, although data exchange agreements can be developed in advance of actual data collection. In addition to the exchange of the previously published results of the studies involved, this exchange may involve unpublished results and expert interpretations of the results. Formal data exchange agreements could also involve the development and publication of joint review articles. The advantages of this mode of cooperation include: access to both published and unpublished data generated by both parties; provision of additional information (metadata) concerning the way that the data were collected; discussions between individual experts who actually collected the data; and often unpublished interpretations of the meaning of the data. However, it should be noted that the data from the two (or more) parties involved may not agree with one another because of the lack of standardized experimental methods, instrumentation, protocols and data analysis techniques. This situation sometimes raises controversy that requires additional studies. A good example of this type of cooperation involves the long-standing cooperation between the United States (National Aeronautics and Space Administration—NASA) and the Soviet Union/Russia. Beginning in 1962 with an agreement between NASA and the Soviet Academy of Sciences (amended in 1965 to include Bioastronautics), the two parties met, discussed their common interests, and eventually exchanged research and medical data from various space missions and ground-based analogs. A formal working group in Space Biology and Medicine was established following a second agreement put in place in May 1972. That working group held annual meetings through 1981 and discussed and exchanged data related to the Soyuz and Apollo programs, as well as the Skylab and Salyut programs. Further agreements (in 1987, 1992, etc.) have continued the joint activity and included discussions and data exchanges related to Shuttle, Spacelab, the Russian Mir space station and the International Space Station. This cooperative activity included two significant publications involving joint reviews of data and knowledge in space biology and medicine [7,8]. 4. Type II: formal data exchange coupled with standardized data collection One way to improve the return from a data exchange agreement is to superimpose an agreement to carry
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out the data collection in a pre-arranged standard way. Of course, this approach only works when the agreement is made prior to data collection by at least one of the parties. This kind of agreement can include standardization of the choice of experimental methods and instrumentation used to collect the data, or it may extend to the standardization of the actual protocols and data analysis techniques used in conjunction with the data collection. In this case, the parties would generally be comparing similar data from each side that could be viewed directly without additional analysis or filtering. Although this idea sounds like a simple thing to do, with the obvious benefit of allowing the parties to discuss the data using the same “language”, in practice it is not necessarily easy. In many cases, investigators have a long history of using certain individual techniques to collect and analyze data, and getting them to agree to use a different “standard” method of collection and analysis may not be easy. Because an agreement to use standardized methods of data collection must precede the actual collection of the data (at least by one party), this technique has been applied from time-to-time when joint large-scale groundbased or space-flight research has been undertaken by an international team of investigators; this case will be described in Section 6. The authors know of no clear examples of the use of standardized research methods with completely independent space life sciences investigations. 5. Type III: joint strategic and tactical planning and full exchange of standardized data This type of cooperative activity, like Type II, is simple to explain but rarely used in practice in the space life sciences. In fact, it involves a level of joint strategic and tactical planning that is rare in the management of life sciences in general. In effect, each agency must decide to rely on the other to carry out a major component of the joint research agenda of the two agencies. Thus, the joint research agenda is divided in two and each agency assumes control of one part of the program. This approach could be very beneficial from a resource perspective if it reduces the scope of a single agency’s program but still has the capability of satisfying the research needs of both agencies by an exchange of data. Although this approach could be used with or without standardization, it makes the most sense from a research management perspective only with standardization if the results are truly important to both parties.
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This approach is sometimes used elsewhere in the space program when each agency develops different major hardware components to fly on a given space mission or satellite. In this case, the agencies involved agree to partner closely and exchange research data rather than each carrying out expensive and duplicative hardware developments. Although this approach has been rare in the life sciences, a similar cooperative activity has sometimes developed that involves one agency developing a major space research facility and inviting one or more other agencies to make use of that facility for some predetermined quid pro quo. For example, the European Space Agency developed a biological research facility called BIORACK and flew it on six Spacelab missions in partnership with the US and other agencies [9]. The quid pro quo in this case involved various reduced mission costs on one side and utilization of part of the facility on the other. Unfortunately, full exchange of real scientific data was not part of the agreements. 6. Type IV: joint international team research with full data sharing and standardization 6.1. Type IV-A: harmonious integration of pre-designed international experiments This level of cooperation involves the development of a large, integrated set of synergistic investigations starting from a well-defined set of independent, but overlapping, proposals. The basic idea behind this level of cooperation is the same whether starting proposals come from different space agencies, independently carrying out proposal solicitation, review and tentative selection, or come from only one space agency moving from independent to integrated investigations. One of the best examples of this type of cooperation is the last of the Spacelab missions, Neurolab. Neurolab (STS-90, April 1998) was originally proposed as NASA’s contribution to the US program of activities making up the 1990s “Decade of the Brain”. A large interagency and international partnership developed between NASA and the US National Institutes of Health (NIH), US National Science Foundation, US Office of Naval Research, French Space Agency, Canadian Space Agency, Japanese Space Agency, German Space Agency and European Space Agency. In 1993, NASA released an Announcement of Opportunity for this mission that resulted in receipt of 172 scientific proposals from the worldwide scientific community. Peer review carried out by a special study section of the US NIH assessed the scientific quality of each sin-
gle proposed investigation. Then, each proposal was separately reviewed for engineering feasibility and appropriateness for the Shuttle environment. This competitive front-end review served to filter the pool of investigators who would participate in the final Neurolab study and resulted in tentative selection of 31 primary studies. Following this tentative selection, special research teams were formed to develop team proposals that synergistically combined sets of investigations. Research teams included [10]: Developmental and Cellular Neurobiology, Vestibular Function, Spatial Orientation and Visuo-motor Performance, Autonomic Nervous System Regulation, Sleep and Circadian Rhythms, and Learning and Behavior. Each of the team proposals were reviewed for soundness and scientific merit by a special non-advocate peer panel. Following this review and additional feasibility studies, 26 investigations were selected for flight. Although the results from these investigations were published in a variety of scientific journals, the major results are summarized in a special publication [11]. Although this is an excellent example of broad international cooperation, it is not a perfect example of this type, because there was only full data sharing and standardization within each of the research teams and not between teams. Cooperation of this type is usually most suitable whenever a suite of investigations will be carried out efficiently within a facility with constrained and limited resources. In this case, the integration plan enhances synergy by use of the same equipment, same analysis, animal sharing plans, and sample sharing plans. The investigators benefit by access to data related to, but not absolutely required by, their experiment. Scientific integration (intradisciplinary, interdisciplinary, and interspecies) capitalizes on the fact that scientific results from integrated experiments are often greater than the sum of individual investigations, since the processes which permit a complex organism to adapt to a gravity-free environment are complex and involve many organ systems and many interrelated pathways. In addition to focusing on scientific integration, considerable attention is given to operational integration. This facet of integration involves identifying ways to promote hardware sharing and developing and using standardized research techniques. Also, using identical human subjects for multiple experiments helps to allow conclusions to be drawn about the relationships among different physiological changes observed in space. Although an integrated protocol is always difficult to develop, the final protocol, when executed, should result in a greater return on the investment of each investigator
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than would have been gained from merely summing the original, independent investigations.
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Oversight Committee
Project Review Committee
6.2. Type IV-B: de novo international investigator team There are very few examples of this type of close cooperation, but one example focusing on ground-based research is the International Multidisciplinary Artificial Gravity (IMAG) Project. Although the Project has never been fully implemented as designed, significant components have been carried out, and these experiences are sufficient to use this example in a qualitative way. The IMAG project was a partnership developed among three space agencies to carry out a series of ground-based campaigns focused on the development of an integrated countermeasure to spaceflight deconditioning using artificial gravity (small radius centrifugation), exercise, and nutritional regulation. American, German and Russian space agency and institutional partners developed a highly invested collaboration to perform coordinated, standardized bed-rest studies at three different sites (one for each partner) with multiple campaigns of centrifuge research. The first phase of the collaboration involved a multidisciplinary Pilot Study at the US site only to test that the selected multidisciplinary measurements, procedures, and subject selection criteria were useful and to obtain some preliminary information on the effects of rotational centrifugation on the measured physiological parameters. Later phases were planned to perform standardized research at all three partner sites simultaneously, with rapid data exchange, thus increasing the potential total amount of test subject data available and the number of variables that could be tested for each partner. Accordingly, prior to the Pilot Study, an overarching Standardization Plan was developed by the partners that would eventually be used at all three partner sites in the future, multi-site phases of the project. Details on the contents of this Standardization Plan, how the partners developed it, and lessons learned from the collaboration are available [12]. The infrastructure and techniques developed to standardize and coordinate the IMAG Project work, maximize efficiency of the multi-campaign phases, and share the data are briefly described here. In order to avoid much of the difficulty creating multidisciplinary, integrated proposals from independent investigation proposals, a basic principle for the IMAG Project was that proposals would be developed by a standing Joint Investigator Team, and the investigators would be chosen prior to the formation of any detailed proposals, independent or integrated. Members of the team were to be chosen via whatever manner was appropriate for each
Project Implementation and Standardization Team NASA
DLR
RSA
Project Site
Project Site
Project Site
Joint Investigator Team
Project Study Campaign
Fig. 2. Infrastructure of the IMAG Project, a Type IV cooperation.
partner. For those partners requiring competitive selection, they could be chosen competitively on the basis of their past scientific merit, their demonstrated ability to work well in an international team atmosphere, and the merit and feasibility of very early conceptual ideas. Working also with the Project Implementation and Standardization Team, these selected investigators could then efficiently design de novo the single or multiple project research campaign proposals to be implemented at the three experimental sites, taking care that the needs of each physiological discipline are satisfied, without interference, and that experimental standardization is maintained. The integrated proposals would then be evaluated efficiently for scientific merit by a standing, multi-agency peer review committee with full knowledge of the goals, standardization plans and past experiments of the project. An Oversight Committee would then ensure that the goals of all partners were being met by the research campaigns (See Fig. 2). As a proof of concept for the cooperative approach and for the utility of the centrifuge in the development of a multi-system countermeasure, the Pilot Study was carried out in the US. The IMAG Project Pilot Study proposal was developed by a specially chosen multidisciplinary team of 27 investigators from seven different physiological disciplines, without prior development of independent investigator proposals. This integrated proposal was reviewed for soundness and merit by an independent panel of experts (named the Project Review Committee in Fig. 2). The integrated proposal included research activities in seven physiological disciplines (bone, muscle, cardiovascular, nutrition, sensory–motor, immunology and psychology). The Pilot Study was completed early in 2007 [13]. A variant of this type of cooperation would involve groups of international investigators forming the research team and approaching the space agencies for funding. Although this approach has the advantage of
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having a compatible team of researchers already formed to carry out the research program, there are almost no examples using this method, probably because the various space agencies have never formally requested proposals that utilize it. 7. Summary and conclusions All of our experience in carrying out cooperative activity over the last 25 years argues that there is a clear benefit to cooperating to do space life sciences research, despite the fact that expressing that benefit is difficult and imprecise. Through cooperation, especially if begun early in the formation of a study, each partner can gain the greatest quantity of high-quality data and an increased opportunity for developing an integrated physiological view of the effects of spaceflight on the human body. Standardization, via cooperation, ensures the comparability of data, and using standardization in multiple sites and campaigns could promote a larger yield of data for all partners with the highest efficiency. No matter how partners cooperate, gaining additional benefits requires some cost in the form of an investment of time, money and/or infrastructure, but hopefully, partners will find those benefits well worth the cost. Acknowledgment Preparation of this paper was supported through Cooperative Agreement NNJ06HG25A between the Universities Space Research Association Division of Space Life Sciences and the National Aeronautics and Space Administration. References [1] M.J. Fregly, C.M. Blatteis (Eds.), Handbook of Physiology, Section 4: Environmental Physiology, vols. I and II, Oxford University Press, Oxford, 1996.
[2] A.I. Grigoriev, A.D. Egorov, Physiological aspects of adaptation of main human body systems during and after spaceflights, Advances in Space Biology and Medicine 2 (1992) 43–82. [3] A.E. Nicogossian, C.L. Huntoon, S.L. Pool, Space Physiology and Medicine, Lea & Febiger, Philadelphia, 1994. [4] G. Clement, Fundamentals of Space Medicine, Springer, New York, 2004. [5] J.C. Buckey, Space Physiology, Oxford University Press, New York, 2006. [6] H. Hinghofer-Szalkay, R.J. White, Physiological considerations of human performance in space, in: N.A.S. Taylor, H. Groeller (Eds.), Physiological Bases of Human Performance During Work and Exercise, Churchill Livingstone Edinburgh, 2008. [7] M. Calvin, O.G. Gazenko (Eds.), Foundations of Space Biology and Medicine, Joint USA/USSR Publication in Three Volumes (vol. I—Space as a Habitat; vol. II—Ecological and Physiological Bases of Space Biology and Medicine; vol. III—Space Medicine and Biotechnology), NASA, Washington, 1975. [8] A.E. Nicogossian, S.R. Mohler, O.G. Gazenko, A.I. Grigoriev, Space Biology and Medicine, Joint US/Russian Publication in Five Volumes (vol. I—Space and Its Exploration, 1993; vol. II—Life Support and Habitability, 1994; vol. III—Humans in Spaceflight, 1996; vol. IV—Health, Performance, and Safety of Space Crews, 2004; vol. V—Reference Material, TBD), American Institute of Aeronautics and Astronautics, Reston, 1975. [9] B. Fitton, B. Battrick (Eds.), A World without Gravity by G. Seibert et al. ESA SP-1251, June 2001, p. 447. [10] D.R. Liskowsky, M.A.B. Frey, F.M. Sulzman, R.J. White, The neurolab mission and biomedical engineering: a partnership for the future, Biomedical Engineering (Japan) 10 (1) (1996) 11–25. [11] J.C. Buckey, J.L. Homick (Eds.), The Neurolab Spacelab Mission: Neuroscience Research in Space, NASA SP-2003-535 (2003), NASA Lyndon B. Johnson Space Center, Houston. [12] J. McPhee, I. Larina, M. Heer, Life Sciences Research Standardization, Journal of Gravitational Physiology 13 (2) (2006) 59–72. [13] E. Warren, R. Reinertson, M.E. Camacho, W.H. Paloski, Implementation of the NASA artificial gravity bed rest pilot study, Journal of Gravitational Physiology 14 (1) (2007) 1–4.
Advantages of international cooperation in space life sciences research Jancy C. McPhee∗ , Ronald J. White Universities Space Research Association (USRA), 3600 Bay Area Blvd., Houston TX 77058, USA Received 29 June 2007; received in revised form 5 March 2008; accepted 31 March 2008 Available online 19 May 2008
Abstract Today, a worldwide community of life scientists interested in space research is attempting to improve the understanding of general biological processes, aid the development of procedures to reduce the biomedically related risks of space flight, and/or directly support the health care of people who fly in space. Unfortunately, limited resources and subject availability and the technical challenges of performing space experiments have all hampered the full growth and development of space life sciences research. For many years, international cooperation in this field has been considered an attractive approach towards overcoming some of these difficulties, since pooling resources and sharing results would enhance the knowledge of all cooperating partners. International cooperative activities, however, require an investment by each partner and, just as in many other endeavors, the research gain can be directly related to the investment made. In this paper, the authors will discuss four possible types of cooperation: formal data exchange agreements; formal data exchange coupled with standardized data collection; joint strategic and tactical planning and full exchange of standardized data; and joint international team research with full data sharing and standardization. The advantages of these types of cooperation will be described. © 2008 Elsevier Ltd. All rights reserved. Keywords: Research cooperation; International; Integration; Standardization; IMAG Project
1. Introduction Space agencies around the world that support human space flight share similar operational and research goals related to medical care, biomedical risk reduction and mission performance maintenance. These goals translate to the development and implementation of a ground- and space-based human-focused research program. This similarity leads naturally to the question of what form of agency coordination and cooperation can best assist partners in achieving mutual goals and ∗ Corresponding author. Tel.: +1 281 244 6434; fax: +1 281 483 2888. E-mail address: [email protected] (J.C. McPhee).
0094-5765/$ - see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.actaastro.2008.03.014
objectives in a cost-effective way. This paper presents a qualitative discussion of the advantages of some of the basic types of international cooperation. 1.1. Human space flight health and performance issues Data from more than four decades of human spaceflight experience demonstrate that space travel affects every system in the body. In certain situations, health and performance may even be compromised. For example, appropriate adaptation of the body to a weightless or reduced gravity state can cause “deconditioning” problems during the transition into and the time spent in reduced gravity, as well as, during and just after re-entry into a higher gravitational environment. These adaptive
J.C. McPhee, R.J. White / Acta Astronautica 63 (2008) 776 – 782
777
Fig. 1. Complex factors affect human health and performance during spaceflight via multifaceted and integrated physiological changes.
changes are often compounded by the other environmental factors involved in spaceflight (Fig. 1), and taken together, can affect both the health of crewmembers and their ability to perform required mission tasks. Several review articles and textbooks provide background information concerning these changes and some of their effects on health and performance [1–6]. Understanding the integrated effects of spaceflight on humans and developing ways to reduce risks to human health and performance during and after space missions, particularly for some of the long-term exploration missions now being planned, is thus extremely important. 1.2. Difficulties of performing space life sciences research Data about the detailed effects of the space environment on human physiology are both limited and difficult to generate. Flying humans in space is very expensive,
and most space agencies currently have severely limited budgets to fund space life sciences activities. In addition, space experiments are often technically difficult to devise and perform, as the original researcher is remote from the test subject and the absence of gravity can make the experimental design quite challenging. Furthermore, access to space platforms, such as the International Space Station, is limited and often hard to obtain, and the number of crewmembers flying in space each year is small. This small number of test subjects implies that conclusions must often be drawn from a small number of data points. Performing a ground-based flight analog experiment with human test subjects, such as head-down tilt bed rest, is also expensive and time consuming, although much less expensive than a space experiment. Even in these analog studies, obtaining a sufficiently large number of test subjects is still difficult and being able to share resources and knowledge from studies that are carried out by the international space
778
J.C. McPhee, R.J. White / Acta Astronautica 63 (2008) 776 – 782
community would be very helpful to everyone involved in such human research. In addition to allowing for a greater quantity of data, such cooperation would also allow all of the partners to gain a deeper understanding of the complex effects of spaceflight on the whole body. 1.3. International research cooperation in the space life sciences There are many ways for agencies to cooperate in space life sciences research, but this paper will examine cooperation using only a few types of idealized active cooperation, each defined in a straightforward way. These cooperative activities generally involve both different levels of investment by each partner and different levels of return (generally data) to each partner. We will not consider the question of monetary cost or other investment in what follows, but in any real situation, each agency must weigh that cost against the benefits realized by the cooperative activity. The types of idealized cooperation discussed in this paper are: • Type 0: No formal cooperation. • Type I: Formal data exchange agreements. • Type II: Formal data exchange coupled with standardized data collection. • Type III: Joint strategic and tactical planning and full exchange of standardized data. • Type IV: Joint international team research with full data sharing and standardization. Type IV-A: Harmonious integration of pre-designed international experiments. Type IV-B: De novo international investigator team. There are other varieties of cooperation possible, but these four types illustrate many of the general principles involved in developing plans for international cooperation in space life sciences research. 2. Type 0: no formal cooperation This level is termed “no formal cooperation” because it involves individually performed studies that have not been synergistically combined. Historically, this has been one of the most typical (though not the only) method through which ground-based biomedical research is selected and funded. Individual investigator proposals are submitted to an agency, either in response to a formal announcement or because of the investigator’s own initiative. These proposals are reviewed and selected for individual funding. Data and conclusions from the selected independent studies are published
(hopefully in the accessible, peer-reviewed literature), thus making the results of the investigations known to all. The data and results then find their way into the base of scientific knowledge through these original publications and through review articles and textbooks. These later reports and compilations of the results of multiple studies provide some summary and low-level integration that is not available by looking at only the isolated, independent investigation results. The advantages of this approach are: the research is strongly related to investigators’ research strategy and goals and thus captures the investigators’ spirit; the latest research tools and techniques are generally applied to the problems at hand; and the creative and innovative ideas of the research community are captured in the research program. There is no question that this is an effective approach to generate knowledge, but it is most effective when the research budget, available experimental facilities and other resources are sufficient to support a large active research community (in the US National Institutes of Health program, this approach is informally termed the “field of a thousand flowers”). Despite the resource limitations constraining life sciences programs within space agencies, individual ground- and space-based investigations selected and funded in this way have long played a major role in the space research world. Of course, there are a number of drawbacks to not formally cooperating. There are delays in transferring data from one investigator to another in the meaningful way that allows sequential investigations to build on one another rapidly. In the space life sciences, such delays are magnified because of the multi-year processing time frequently required for an experimenter to collect enough subjects, analyze and publish the data. In addition, important space biomedical data may not be published at all or not be published in a widely accessible journal. This may be partially due to the fact that available data sets often have a very small number of test subjects and are difficult to defend as a definitive study, as required by many journals. Another important drawback of independent investigations is the difficulty of pooling data from different studies and of comparing results obtained by different investigators who may each use non-standardized approaches to data collection and analysis. 3. Type I: formal data exchange agreements One of the simplest ways for space agencies to cooperate is to formally exchange data and information related to research of common interest. Usually, the
J.C. McPhee, R.J. White / Acta Astronautica 63 (2008) 776 – 782
agreement to exchange such ground-based and spaceflight data and information occurs after the research has been completed, although data exchange agreements can be developed in advance of actual data collection. In addition to the exchange of the previously published results of the studies involved, this exchange may involve unpublished results and expert interpretations of the results. Formal data exchange agreements could also involve the development and publication of joint review articles. The advantages of this mode of cooperation include: access to both published and unpublished data generated by both parties; provision of additional information (metadata) concerning the way that the data were collected; discussions between individual experts who actually collected the data; and often unpublished interpretations of the meaning of the data. However, it should be noted that the data from the two (or more) parties involved may not agree with one another because of the lack of standardized experimental methods, instrumentation, protocols and data analysis techniques. This situation sometimes raises controversy that requires additional studies. A good example of this type of cooperation involves the long-standing cooperation between the United States (National Aeronautics and Space Administration—NASA) and the Soviet Union/Russia. Beginning in 1962 with an agreement between NASA and the Soviet Academy of Sciences (amended in 1965 to include Bioastronautics), the two parties met, discussed their common interests, and eventually exchanged research and medical data from various space missions and ground-based analogs. A formal working group in Space Biology and Medicine was established following a second agreement put in place in May 1972. That working group held annual meetings through 1981 and discussed and exchanged data related to the Soyuz and Apollo programs, as well as the Skylab and Salyut programs. Further agreements (in 1987, 1992, etc.) have continued the joint activity and included discussions and data exchanges related to Shuttle, Spacelab, the Russian Mir space station and the International Space Station. This cooperative activity included two significant publications involving joint reviews of data and knowledge in space biology and medicine [7,8]. 4. Type II: formal data exchange coupled with standardized data collection One way to improve the return from a data exchange agreement is to superimpose an agreement to carry
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out the data collection in a pre-arranged standard way. Of course, this approach only works when the agreement is made prior to data collection by at least one of the parties. This kind of agreement can include standardization of the choice of experimental methods and instrumentation used to collect the data, or it may extend to the standardization of the actual protocols and data analysis techniques used in conjunction with the data collection. In this case, the parties would generally be comparing similar data from each side that could be viewed directly without additional analysis or filtering. Although this idea sounds like a simple thing to do, with the obvious benefit of allowing the parties to discuss the data using the same “language”, in practice it is not necessarily easy. In many cases, investigators have a long history of using certain individual techniques to collect and analyze data, and getting them to agree to use a different “standard” method of collection and analysis may not be easy. Because an agreement to use standardized methods of data collection must precede the actual collection of the data (at least by one party), this technique has been applied from time-to-time when joint large-scale groundbased or space-flight research has been undertaken by an international team of investigators; this case will be described in Section 6. The authors know of no clear examples of the use of standardized research methods with completely independent space life sciences investigations. 5. Type III: joint strategic and tactical planning and full exchange of standardized data This type of cooperative activity, like Type II, is simple to explain but rarely used in practice in the space life sciences. In fact, it involves a level of joint strategic and tactical planning that is rare in the management of life sciences in general. In effect, each agency must decide to rely on the other to carry out a major component of the joint research agenda of the two agencies. Thus, the joint research agenda is divided in two and each agency assumes control of one part of the program. This approach could be very beneficial from a resource perspective if it reduces the scope of a single agency’s program but still has the capability of satisfying the research needs of both agencies by an exchange of data. Although this approach could be used with or without standardization, it makes the most sense from a research management perspective only with standardization if the results are truly important to both parties.
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This approach is sometimes used elsewhere in the space program when each agency develops different major hardware components to fly on a given space mission or satellite. In this case, the agencies involved agree to partner closely and exchange research data rather than each carrying out expensive and duplicative hardware developments. Although this approach has been rare in the life sciences, a similar cooperative activity has sometimes developed that involves one agency developing a major space research facility and inviting one or more other agencies to make use of that facility for some predetermined quid pro quo. For example, the European Space Agency developed a biological research facility called BIORACK and flew it on six Spacelab missions in partnership with the US and other agencies [9]. The quid pro quo in this case involved various reduced mission costs on one side and utilization of part of the facility on the other. Unfortunately, full exchange of real scientific data was not part of the agreements. 6. Type IV: joint international team research with full data sharing and standardization 6.1. Type IV-A: harmonious integration of pre-designed international experiments This level of cooperation involves the development of a large, integrated set of synergistic investigations starting from a well-defined set of independent, but overlapping, proposals. The basic idea behind this level of cooperation is the same whether starting proposals come from different space agencies, independently carrying out proposal solicitation, review and tentative selection, or come from only one space agency moving from independent to integrated investigations. One of the best examples of this type of cooperation is the last of the Spacelab missions, Neurolab. Neurolab (STS-90, April 1998) was originally proposed as NASA’s contribution to the US program of activities making up the 1990s “Decade of the Brain”. A large interagency and international partnership developed between NASA and the US National Institutes of Health (NIH), US National Science Foundation, US Office of Naval Research, French Space Agency, Canadian Space Agency, Japanese Space Agency, German Space Agency and European Space Agency. In 1993, NASA released an Announcement of Opportunity for this mission that resulted in receipt of 172 scientific proposals from the worldwide scientific community. Peer review carried out by a special study section of the US NIH assessed the scientific quality of each sin-
gle proposed investigation. Then, each proposal was separately reviewed for engineering feasibility and appropriateness for the Shuttle environment. This competitive front-end review served to filter the pool of investigators who would participate in the final Neurolab study and resulted in tentative selection of 31 primary studies. Following this tentative selection, special research teams were formed to develop team proposals that synergistically combined sets of investigations. Research teams included [10]: Developmental and Cellular Neurobiology, Vestibular Function, Spatial Orientation and Visuo-motor Performance, Autonomic Nervous System Regulation, Sleep and Circadian Rhythms, and Learning and Behavior. Each of the team proposals were reviewed for soundness and scientific merit by a special non-advocate peer panel. Following this review and additional feasibility studies, 26 investigations were selected for flight. Although the results from these investigations were published in a variety of scientific journals, the major results are summarized in a special publication [11]. Although this is an excellent example of broad international cooperation, it is not a perfect example of this type, because there was only full data sharing and standardization within each of the research teams and not between teams. Cooperation of this type is usually most suitable whenever a suite of investigations will be carried out efficiently within a facility with constrained and limited resources. In this case, the integration plan enhances synergy by use of the same equipment, same analysis, animal sharing plans, and sample sharing plans. The investigators benefit by access to data related to, but not absolutely required by, their experiment. Scientific integration (intradisciplinary, interdisciplinary, and interspecies) capitalizes on the fact that scientific results from integrated experiments are often greater than the sum of individual investigations, since the processes which permit a complex organism to adapt to a gravity-free environment are complex and involve many organ systems and many interrelated pathways. In addition to focusing on scientific integration, considerable attention is given to operational integration. This facet of integration involves identifying ways to promote hardware sharing and developing and using standardized research techniques. Also, using identical human subjects for multiple experiments helps to allow conclusions to be drawn about the relationships among different physiological changes observed in space. Although an integrated protocol is always difficult to develop, the final protocol, when executed, should result in a greater return on the investment of each investigator
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than would have been gained from merely summing the original, independent investigations.
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Oversight Committee
Project Review Committee
6.2. Type IV-B: de novo international investigator team There are very few examples of this type of close cooperation, but one example focusing on ground-based research is the International Multidisciplinary Artificial Gravity (IMAG) Project. Although the Project has never been fully implemented as designed, significant components have been carried out, and these experiences are sufficient to use this example in a qualitative way. The IMAG project was a partnership developed among three space agencies to carry out a series of ground-based campaigns focused on the development of an integrated countermeasure to spaceflight deconditioning using artificial gravity (small radius centrifugation), exercise, and nutritional regulation. American, German and Russian space agency and institutional partners developed a highly invested collaboration to perform coordinated, standardized bed-rest studies at three different sites (one for each partner) with multiple campaigns of centrifuge research. The first phase of the collaboration involved a multidisciplinary Pilot Study at the US site only to test that the selected multidisciplinary measurements, procedures, and subject selection criteria were useful and to obtain some preliminary information on the effects of rotational centrifugation on the measured physiological parameters. Later phases were planned to perform standardized research at all three partner sites simultaneously, with rapid data exchange, thus increasing the potential total amount of test subject data available and the number of variables that could be tested for each partner. Accordingly, prior to the Pilot Study, an overarching Standardization Plan was developed by the partners that would eventually be used at all three partner sites in the future, multi-site phases of the project. Details on the contents of this Standardization Plan, how the partners developed it, and lessons learned from the collaboration are available [12]. The infrastructure and techniques developed to standardize and coordinate the IMAG Project work, maximize efficiency of the multi-campaign phases, and share the data are briefly described here. In order to avoid much of the difficulty creating multidisciplinary, integrated proposals from independent investigation proposals, a basic principle for the IMAG Project was that proposals would be developed by a standing Joint Investigator Team, and the investigators would be chosen prior to the formation of any detailed proposals, independent or integrated. Members of the team were to be chosen via whatever manner was appropriate for each
Project Implementation and Standardization Team NASA
DLR
RSA
Project Site
Project Site
Project Site
Joint Investigator Team
Project Study Campaign
Fig. 2. Infrastructure of the IMAG Project, a Type IV cooperation.
partner. For those partners requiring competitive selection, they could be chosen competitively on the basis of their past scientific merit, their demonstrated ability to work well in an international team atmosphere, and the merit and feasibility of very early conceptual ideas. Working also with the Project Implementation and Standardization Team, these selected investigators could then efficiently design de novo the single or multiple project research campaign proposals to be implemented at the three experimental sites, taking care that the needs of each physiological discipline are satisfied, without interference, and that experimental standardization is maintained. The integrated proposals would then be evaluated efficiently for scientific merit by a standing, multi-agency peer review committee with full knowledge of the goals, standardization plans and past experiments of the project. An Oversight Committee would then ensure that the goals of all partners were being met by the research campaigns (See Fig. 2). As a proof of concept for the cooperative approach and for the utility of the centrifuge in the development of a multi-system countermeasure, the Pilot Study was carried out in the US. The IMAG Project Pilot Study proposal was developed by a specially chosen multidisciplinary team of 27 investigators from seven different physiological disciplines, without prior development of independent investigator proposals. This integrated proposal was reviewed for soundness and merit by an independent panel of experts (named the Project Review Committee in Fig. 2). The integrated proposal included research activities in seven physiological disciplines (bone, muscle, cardiovascular, nutrition, sensory–motor, immunology and psychology). The Pilot Study was completed early in 2007 [13]. A variant of this type of cooperation would involve groups of international investigators forming the research team and approaching the space agencies for funding. Although this approach has the advantage of
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having a compatible team of researchers already formed to carry out the research program, there are almost no examples using this method, probably because the various space agencies have never formally requested proposals that utilize it. 7. Summary and conclusions All of our experience in carrying out cooperative activity over the last 25 years argues that there is a clear benefit to cooperating to do space life sciences research, despite the fact that expressing that benefit is difficult and imprecise. Through cooperation, especially if begun early in the formation of a study, each partner can gain the greatest quantity of high-quality data and an increased opportunity for developing an integrated physiological view of the effects of spaceflight on the human body. Standardization, via cooperation, ensures the comparability of data, and using standardization in multiple sites and campaigns could promote a larger yield of data for all partners with the highest efficiency. No matter how partners cooperate, gaining additional benefits requires some cost in the form of an investment of time, money and/or infrastructure, but hopefully, partners will find those benefits well worth the cost. Acknowledgment Preparation of this paper was supported through Cooperative Agreement NNJ06HG25A between the Universities Space Research Association Division of Space Life Sciences and the National Aeronautics and Space Administration. References [1] M.J. Fregly, C.M. Blatteis (Eds.), Handbook of Physiology, Section 4: Environmental Physiology, vols. I and II, Oxford University Press, Oxford, 1996.
[2] A.I. Grigoriev, A.D. Egorov, Physiological aspects of adaptation of main human body systems during and after spaceflights, Advances in Space Biology and Medicine 2 (1992) 43–82. [3] A.E. Nicogossian, C.L. Huntoon, S.L. Pool, Space Physiology and Medicine, Lea & Febiger, Philadelphia, 1994. [4] G. Clement, Fundamentals of Space Medicine, Springer, New York, 2004. [5] J.C. Buckey, Space Physiology, Oxford University Press, New York, 2006. [6] H. Hinghofer-Szalkay, R.J. White, Physiological considerations of human performance in space, in: N.A.S. Taylor, H. Groeller (Eds.), Physiological Bases of Human Performance During Work and Exercise, Churchill Livingstone Edinburgh, 2008. [7] M. Calvin, O.G. Gazenko (Eds.), Foundations of Space Biology and Medicine, Joint USA/USSR Publication in Three Volumes (vol. I—Space as a Habitat; vol. II—Ecological and Physiological Bases of Space Biology and Medicine; vol. III—Space Medicine and Biotechnology), NASA, Washington, 1975. [8] A.E. Nicogossian, S.R. Mohler, O.G. Gazenko, A.I. Grigoriev, Space Biology and Medicine, Joint US/Russian Publication in Five Volumes (vol. I—Space and Its Exploration, 1993; vol. II—Life Support and Habitability, 1994; vol. III—Humans in Spaceflight, 1996; vol. IV—Health, Performance, and Safety of Space Crews, 2004; vol. V—Reference Material, TBD), American Institute of Aeronautics and Astronautics, Reston, 1975. [9] B. Fitton, B. Battrick (Eds.), A World without Gravity by G. Seibert et al. ESA SP-1251, June 2001, p. 447. [10] D.R. Liskowsky, M.A.B. Frey, F.M. Sulzman, R.J. White, The neurolab mission and biomedical engineering: a partnership for the future, Biomedical Engineering (Japan) 10 (1) (1996) 11–25. [11] J.C. Buckey, J.L. Homick (Eds.), The Neurolab Spacelab Mission: Neuroscience Research in Space, NASA SP-2003-535 (2003), NASA Lyndon B. Johnson Space Center, Houston. [12] J. McPhee, I. Larina, M. Heer, Life Sciences Research Standardization, Journal of Gravitational Physiology 13 (2) (2006) 59–72. [13] E. Warren, R. Reinertson, M.E. Camacho, W.H. Paloski, Implementation of the NASA artificial gravity bed rest pilot study, Journal of Gravitational Physiology 14 (1) (2007) 1–4.