Global harmonization in the care and use of laboratory animals for the space life science research]

Space researches are supported with the international space agencies, NASA and NASDA. Animal experiments on the space life science must conform to the NIH policies and the NASA guide for the care and use of laboratory animals. The goal of the NIH policies is to promote the humane care of animals used biomedical and behavioral research, teaching, and testing. In each institute, the Institutional Animal Care and Use Committee (IACUC) plays an important role in conformity with NIH policies. The IACUC is charged with developing, recommending and monitoring NIH/NASA (ARC and KSC) policies, guides and rules relating to animal acquisition, care and use. In ARC and KSC, investigators will be responsible only for activities directly related to the conduct of their animal experiments. Even if researchers have protocols of the space science in Japan, the animal experiment should be carried out under the global harmonized conditions in accordance with NIH policies and NASA guides.     

Animal habitats for space experiments.

There has been little opportunity for flight experiments using small animals, due to delay of construction of the International Space Station. Therefore, proposals using small animals have been unfortunately excepted from International Space Life Sciences Experiment application opportunity since 2001. Moreover, NASA has changed their development plan of animal habitats for space experiments according to changes of the U.S. space policy and the outlook is not so bright. However, international researchers have been strongly requesting the opportunity for space experiments using small animals. It will be also important for Japanese researchers to make a request for the opportunity. At the same time, researchers have to make an advance in ground based studies toward space experiments and to respond future application opportunities immediately. In this symposium, we explain the AEM (Animal Enclosure Module), the RAHF (Research Animal Holding Facility), and the AAH (Advanced Animal Habitat). It will be helpful for investigators to have wide knowledge of what space experiment is technically possible. In addition, the sample share program will be introduced into our communities. The program will provide many researchers with the organs and tissues from space-flown animals. We will explain the technical aspect of sample share program.     

The ethical acceptability of animal experiments: a proposal for a system to support decision-making

We describe a system to support decision-making on the ethical acceptability of animal experiments for scientific researchers and others responsible for ethical decision-making in animal experiments. The system consists of eight steps. Each step contains a number of substantive questions or a computational rule, leading to a well-articulated moral judgment on specific animal experiments. The system comprises a number of moral assumptions and pre-emptive norms, but leaves enough room for moral discretion and personal responsibility. The general ethical ideas behind the moral choices and assumptions are sketched and potential objections to the overall approach are discussed.     

Cell science and protein crystal growth research for the International Space Station

The recent National Research Council report, Future Biotechnology Research on the International Space Station, evaluates NASA's plans for research in cell science and protein crystal growth to be conducted on the International Space Station. This report concludes that the NASA biotechnology programs have the potential to significantly impact relevant scientific fields and to increase understanding and insight into fundamental biological issues. In order to realize the potential impacts, NASA must focus its research programs by selecting specific questions related to gravitational forces' role in cell behavior and by using the microgravity environment as a tool to determine the structure of macromolecules with important biological implications. Given the time and volume constraints associated with space-based experiments, instrumentation to be used on the space station must be designed to maximize the productivity of researchers, and NASA's recruitment of investigators and support for space station experiments should aim to encourage and facilitate cutting-edge research.     

Future opportunities for life science programs in space

Most space-related life science programs are expensive and time-consuming, requiring international cooperation and resources with trans-disciplinary expertise. A comprehensive future program in "life sciences in space" needs, therefore, well-defined research goals and strategies as well as a sound ground-based program. The first half of this review will describe four key aspects such as the environment in space, previous accomplishments in space (primarily focusing on amphibian embryogenesis), available resources, and recent advances in bioinformatics and biotechnology, whose clear understanding is imperative for defining future directions. The second half of this review will focus on a broad range of interdisciplinary research opportunities currently supported by the National Aeronautics and Space Administration (NASA), National Institute of Health (NIH), and National Science Foundation (NSF). By listing numerous research topics such as alterations in a diffusion-limited metabolic process, bone loss and skeletal muscle weakness of astronauts, behavioral and cognitive ability in space, life in extreme environment, etc., we will attempt to suggest future opportunities.     

A lost generation

The funding policies of the NIH have made it increasingly difficult for young researchers to procure research funds. This threatens to drive a whole generation of young people away from careers in basic biomedical research.     

Establishing a knowledge trail from molecular experiments to clinical trials

During the development cycle of a new antibody therapy, the therapeutic agent will be tested on subsequently more biologically complex models. New experiments' designs are based upon data gathered from prior models. New researchers who inherit the data and researchers from groups with different cultures or expertise are often called upon to interpret these data. Experiments which are not recorded consistently or employ ambiguous terminology can make interpreting these results difficult. The researcher who had originally collected the data may not be at hand to correct any misunderstanding or offer clarification and data can be unknowingly misused. This introduces an element of risk into the therapy development process. We have developed a reporting guideline for recording therapy experiments. This guideline consists of a checklist of data to be recorded from antibody therapy experiments performed in molecular, cellular, animal and clinical model.     

Use and misuse of an imprecise concept: alternative methods in animal experiments

The concept of inhumanity of Russell & Burch in 1959 with proposals for human procedures in experiments on animals by way of replacement, reduction and refinement (the 3 R's) and the revival of these by Smyth (1978) as alternatives to animal experiments are presented. Since then under the name 'alternative methods', replacement of in vivo by in vitro methods has found great public attention and promotion. It is argued that alternative methods are a fallacy, because in the progress of research a continual control and reinvestigation of findings on each system level is required until knowledge is complete, which makes in vivo experiments irreplaceable. True alternatives exist only for refinement within a system level. On the level of the organism, refinement would be in the care of animals and experimental procedure through alleviation of stress. The possibilities which refinement offers for animal welfare have been nearly forgotten and need promotion among researchers, animal technicians and attendants.     

比较医学动物实验计算机辅助设计系统的研发

目的开发一款辅助研究者设计比较医学动物实验方案和学习实验设计的应用软件。方法根据实验动物应用的"科学、伦理、经济"原则筛选比较医学动物实验技术资料,运用关系数据库架构原理分析和组织入选数据,通过解析比较医学动物实验规律和特点设计程序框架和模块,采用C++语言、MFC库进行面向用户的程序设计。结果建立了程序相关资源库和模型选择、实验动物、环境条件、实验步骤、方案输出5个功能模块,并完成整个软件测试。结论研发成功比较医学动物实验计算机辅助设计系统,该系统能够基于微型计算机为用户提供有效、易用的动物实验辅助设计和自助学习功能。     

Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 μl. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 μl h⁻¹). The reservoir volume of culture medium is 230 μl. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.     

Experiment facilities for life science experiments in space.

To perform experiments in microgravity environment, there should be many difficulties compared with the experiments on ground. JAXA (Japan Aerospace Exploration Agency) has developed various experiment facilities to perform life science experiments in space, such as Cell Culture Kit, Thermo Electric Incubator, Free Flow Electrophoresis Unit, Aquatic Animal Experiment Unit, and so on. The first experiment facilities were flown on Spacelab-J mission in 1992, and they were improved and modified for the 2nd International Microgravity Laboratory (IML-2) mission in 1994. Based on these experiences, some of them were further improved and flown on another missions. These facilities are continuously being improved for the International Space Station use, where high level functions and automatic operations will be required.     

Radiobiological problems in space

Summary An overview is presented on radiation problems in space, with emphasis on aspects of major interest for manned space exploration. A classification of the radiation hazards is presented and strategies for their evaluation are discussed. Space radiation problems are compared with characteristic aspects of radiation research in other disciplines, in order to provide further insight into those aspects that are unique to space.The research described in this paper was carried out while the author was a NASA VisitingThe research described in this paper was carried out while the author was a NASA VisitingThe research described in this paper was carried out while the author was a NASA VisitingThe research described in this paper was carried out while the author was a NASA Visiting     

Automated workflow for large-scale selected reaction monitoring experiments

Targeted proteomics allows researchers to study proteins of interest without being drowned in data from other, less interesting proteins or from redundant or uninformative peptides. While the technique is mostly used for smaller, focused studies, there are several reasons to conduct larger targeted experiments. Automated, highly robust software becomes more important in such experiments. In addition, larger experiments are carried out over longer periods of time, requiring strategies to handle the sometimes large shift in retention time often observed. We present a complete proof-of-principle software stack that automates most aspects of selected reaction monitoring workflows, a targeted proteomics technology. The software allows experiments to be easily designed and carried out. The steps automated are the generation of assays, generation of mass spectrometry driver files and methods files, and the import and analysis of the data. All data are normalized to a common retention time scale, the data are then scored using a novel score model, and the error is subsequently estimated. We also show that selected reaction monitoring can be used for label-free quantification. All data generated are stored in a relational database, and the growing resource further facilitates the design of new experiments. We apply the technology to a large-scale experiment studying how Streptococcus pyogenes remodels its proteome under stimulation of human plasma.     

Preparing normal tissue cells for space flight experiments

Deterioration of health is a problem in modern space flight business. In order to develop countermeasures, research has been done on human bodies and also on single cells. Relevant experiments on human cells in vitro are feasible when microgravity is simulated by devices such as the Random Positioning Machine or generated for a short time during parabolic flights. However, they become difficult in regard to performance and interpretation when long-term experiments are designed that need a prolonged stay on the International Space Station (ISS). One huge problem is the transport of living cells from a laboratory on Earth to the ISS. For this reason, mainly rapidly growing, rather robust human cells such as cancer cells, embryonic cells, or progenitor cells have been investigated on the ISS up to now. Moreover, better knowledge on the behavior of normal mature cells, which mimic the in vivo situation, is strongly desirable. One solution to the problem could be the use of redifferentiable cells, which grow rapidly and behave like cancer cells in plain medium, but are reprogrammed to normal cells when substances like retinoic acid are added. A list of cells capable of redifferentiation is provided, together with names of suitable drugs, in this review.     

NASDA aquatic animal experiment facilities for Space Shuttle.

National Space Development Agency of Japan (NASDA) has been developed aquatic animal experiment facilities for space experiments using NASA Space Shuttle. Vestibular Function Experiment Unit (VFEU) has been firstly designed and developed for Spacelab-J mission (STS-47), and 8 days space experiment with carp has been performed. Following, the VFEU, Aquatic Animal Experiment Unit (AAEU) has been developed to accommodate small aquatic animals second International Microgravity Laboratory mission (IML-2, STS-65). Four kinds of space experiments with goldfish, medaka, newt, and newt eggs have been performed for 15 days mission duration. Then, VFEU has been improved to accommodate marine fish under low temperature condition for Neurolab (STS-90) and STS-95 missions. 17 days (STS-90) and 9 days (STS-95) experiments with oyster toadfish have been performed by using the VFEU. This report summarizes the outline of these aquatic animal experiment facilities.     

The National Institutes of Health system for enhancing the science,safety, and ethics of recombinant DNA research

Oversight of recombinant DNA research by the National Institutes of Health (NIH) is predicated on ethical and scientific responsibilities that are akin, in many ways, to those that pertain to the oversight of animal research. The NIH system of oversight, which originated more than 25 years ago, is managed by the NIH Office of Biotechnology Activities (OBA), which uses various tools to fulfill its oversight responsibilities. These tools include the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) and the Recombinant DNA Advisory Committee. The OBA also undertakes special initiatives to promote the analysis and dissemination of information key to our understanding of recombinant DNA, and in particular, human gene transfer research. These initiatives include a new query-capable database, an analytical board of scientific and medical experts, and conferences and symposia on timely scientific, safety, and policy issues. Veterinary scientists can play an important role in the oversight of recombinant DNA research and in enhancing our understanding of the many safety and scientific dimensions of the field. These roles include developing appropriate animal models, reporting key safety data, enhancing institutional biosafety review, and promoting compliance with the NIH Guidelines.     

Results of space experiments

Life science research in space was started in Europe with the first Biostack experiment flown onboard Apollo 16 in 1972. Biostack was designed to investigate the biological effects of single heavy ions of cosmic radiation. Among several undertakings towards this goal, the Biostack achieved the highest precision in the determination of the spatial correlation of the observed biological response of single test organisms to the passage of single heavy ions, which is the mandatory requirement. It also provided information on the influence of additional spaceflight factors, such as microgravity, on radiation effects and measurements of the spectrum of charge and energy of the cosmic radiation. The experiment was performed as an international cooperation effort. This report gives a summary of the biological data accumulated in this and the follow-on experiments of the Biostack program.Invited paper presented at the International Symposium on Heavy Ion Research: Space, Radiation Protection and Therapy, Sophia-Antipolis, France, 21–24 March 1994     

Codifying Collegiality: Recent Developments in Data Sharing Policy in the Life Sciences

Over the last decade, there have been significant changes in data sharing policies and in the data sharing environment faced by life science researchers. Using data from a 2013 survey of over 1600 life science researchers, we analyze the effects of sharing policies of funding agencies and journals. We also examine the effects of new sharing infrastructure and tools (i.e., third party repositories and online supplements). We find that recently enacted data sharing policies and new sharing infrastructure and tools have had a sizable effect on encouraging data sharing. In particular, third party repositories and online supplements as well as data sharing requirements of funding agencies, particularly the NIH and the National Human Genome Research Institute, were perceived by scientists to have had a large effect on facilitating data sharing. In addition, we found a high degree of compliance with these new policies, although noncompliance resulted in few formal or informal sanctions. Despite the overall effectiveness of data sharing policies, some significant gaps remain: about one third of grant reviewers placed no weight on data sharing plans in their reviews, and a similar percentage ignored the requirements of material transfer agreements. These patterns suggest that although most of these new policies have been effective, there is still room for policy improvement.     

The scope for improving the design of laboratory animal experiments.

The factors which need to be taken into account in designing a 'good' experiment are reviewed. Such an experiment should be unbiased, have high precision, a wide range of applicability, it should be simple, and there should be a means of quantifying uncertainty (Cox 1958). The relative precision due to the use of randomized block designs was found to range from 96% to 543% in 5 experiments involving 30 variables. However, a survey of 78 papers published in two toxicology journals showed that such designs were hardly used. Similarly, designs in which more than one factor was varied simultaneously ('factorial designs') were only used in 9% of studies, though interactions between variables such as dose and strain of animal may be common, so that single factor experiments could be misleading. The consequences of increased within-group variability due to infection and genetic segregation were quantified using data published by G?rtner (1990). Both substantially reduced precision, but toxicologists continue to use non-isogenic laboratory animals, leading to experiments with a lower level of precision than is necessary. It is concluded that there is scope for improving the design of animal experiments, which could lead to a reduction in animal use. People using animals should be required to take formal training courses which include sessions on experimental design in order to minimize animal use and to increase experimental efficiency.     

Animal experiments using mammals are essential to the study on the mechanisms of phenomena produced in the human body in the space environment.

The animal experiments have contributed to the physiology and medicine concerned with the care and cure of patients as well as with an understanding of mechanisms of various diseases and human health. In particular, the numerous mammals have been used for the medical researches. Similarly, to investigate the phenomena in the human body that occur in the space environment, the various mammals have been used for the medical researches in space. Since the human with frontier spirits will never stop continuing the space development and utilization, the space medical and physiological researches using mammals as well as subjects are more important and necessary for the future space activities. The mammal modules in spacecrafts and space station are produced for the rodents at this time. Therefore, from various viewpoints, the rats and mice are the first choice for space mammal experiments of medical or life science researches and space modules for the mammal should be carefully and extensively designed.