IIN NTTR RO OD DU UC CTTIIO ON N TTO O SSPPA AC CEE D DEEVVEELLO OPPM MEEN NTTA ALL B BIIO OLLO OG GYY Eran Schenker, MD* and David M. Warmflash, M.D.# *Israel Aerospace Medicine Institute and, Department of Obstetric & Gynecology, Hadassah University Hospitals Mt. Scopus Jerusalem Israel; #NASA Johnson Space Center, Houston, TX, 77058. If humanity is to transform itself into a multi-planet species it is imperative that the life cycle, from egg to grave, can proceed in the new environments in which the life is transplanted. In order to assure this, a great deal of research is necessary and several questions and issues must be addressed. The two areas of investigation that are most important to the development of terrestrial life forms off the Earth are gravity and space radiation. Therefore, research focuses on the influences of variations in gravity level as well as on the effects of radiation on biological development. Altered Gravity Environments The possibility of bringing human and other terrestrial life forms to off-Earth environments raises the potential for a variety of situations vis-à-vis the gravity environment and its effects on development. In the near future, exploration class pre-colonial human missions to destinations such as Mars, the asteroid belt and Jupiter’s moon Europa may expose astronauts and other terrestrial animals to periods of several months to a few years of weightlessness aboard the interplanetary spacecraft, interspersed with bouts of exposure to fractional g levels (perceived gravity levels between 0 and 1 g) while on the surface of the destination planets or within rotating intermittent artificial gravity rooms aboard the spacecraft. Because the disadvantages of rotational artificial gravity increase with the selected gravity level, if full time artificial gravity is employed by way of a rotating spacecraft, it may be decided that full Earth gravity is not desirable and some fraction of terrestrial gravity may be employed aboard the spacecraft in lieu of a full g. Additionally, if humans colonize Mars, they and the other species that they bring with them will be full-time inhabitants of an environment in which the ambient g level is approximately 0.38 that of the terrestrial level in which they evolved. While a centrifuge large enough to accommodate small mammals will soon fly aboard the international space station (ISS), allowing for studies of the effects of fractional g levels on development, studies have thus far addressed the effects of full weightlessness as well as hypergravity (levels higher than 1 g) in order to gain insight into the role of gravity and the effects of altering the level of gravity that the organism perceives. To date, a variety of studies aimed at providing insight into developmental gravitational biology have been carried out on a variety of organisms. To address the issue of human pregnancy in space the influence of the gravity vector on fetal lay was investigated (Schenker, 1995) and these preliminary studies suggest that, even in a relatively late stage of human pregnancy, gravity plays a major role and that some gravitation level will likely be necessary for humans to successfully populate off-Earth environments. This preliminary indication is supported by studies involving earlier stages of human reproduction and well as animal studies focussing on various stages. To begin, it is plausible that weightlessness could affect the human hypothalmo-pituitary axis enough to effectively render humans infertile so that pregnancy would not occur in weightlessness. While it should be noted that these human studies are preliminary and need to be controlled for factors such as stress and radiation, the general implication is that a great deal of research is required before serious plans can be made for space or interplanetary colonization. Non-human studies can potentially offer a great deal of insight not only into human development in future colonies but for the requirements connected with raising multiple generations of animals as part of a closed life-support system during pre-colonial exploration-class missions. Various animal models are thus useful for study and are summed up here and each is described in more detail in subsequent readings. Drosophila: Drosophila development has been extensively studied in terrestrial environments and this species offers the advantage of having a genome that has been completely sequenced. Therefore, a great deal of information about its genetics, including developmental mutations is available. Additionally, its genetic homology to vertebrates, short life cycle, external development, small size, large number of offspring, large number of indicator lines and mutants, and ability to be transported in cold storage to the desired environment (ie. altered gravity environment) offer important advantages to space developmental biology . C. elegans: C. elegans development has been extensively studied in terrestrial environments and this species offers the advantage of having a genome that has been completely sequenced. A complete map of its development is available with tracking of each cell division from egg to adult. Like drosophila, it shares extensive homology with vertebrates at the molecular level, has a short life cycle, is small, develops externally, can be placed into cold storage and a large data base of mutants is available. Also, the developmental patterns of several genes are known and GFP-marker lines are available. Amphibia: Like drosophila and C. elegans, amphibia have short developmental periods, using only a few days to proceed from fertilization to larva and this is an advantage when studying this period in altered gravitational environments. The life cycle through adulthood, however, is relatively long in Xenopus laevis, but comparable to mouse in Xenopus. tropicalis. Amphibia also share homology to mammals at the molecular level and for the mechanisms of tissue induction, developmental patterns of several genes are known and some GFP-marker lines are available. Amphibia produce durable eggs and embryos in large numbers, fertilization and development are external (so as in the the case of C. elegans and drosophila, development can be videotaped), a genome mapping project has begun and some mutations are available. While embryos are opaque, tadpoles of some species are semitransparent. Preliminary flight data have been collected from several amphibian species showing that eggs are stratified based on the gravity vector and that cytoplasmic localization of maternal factors (necessary for formation of the germ line and initial axes) are potentially affected by gravity. Additionally, it has been shown that Xenopus laevis larvae fail to inflate their lungs in a weightless environment suggesting that a complete life cycle in weightlessness would not be possible for such an air breathing amphibian. Fish: Most data regarding fish come from zebrafish, but some are from studies involving other species. As in the case of amphibia, a genome project is proceeding for zebrafish, genetic information related to developmental mutations is available, there is a great deal of homology to mammals at the molecular level, developmental patterns of several genes are known, indicator lines are being developed, they have a short life cycle, fertilization and development are external and eggs and embryos are hardy and produced in large numbers. As opposed to amphibia however, zebrafish embryos are transparent. Additionally, significant flight data are available for vestibular system development. Mouse: As in the case of amphibia and zebrafish, a genome project is proceeding for mice, genetic information related to developmental mutations is available, there is a great deal of homology developmental patterns of several genes are known, indicator lines are available and they mice a short developmental cycle (21 days gestation) and short life cycle (4 months). Additionally, since adults are small, habitats take less space than those of other mammals. Rat Rats have a developmental cycle similar to mice and, as in the case of mice, some flight data are available and a genome project has begun. Additionally, some well-developed rat models for human disease and pathophysiology are available as is a significant rat database of maternal fetal behavior. Avians: Avians share Extensive homology with mammals at the cell, tissue and molecular level, developmental patterns of many genes are known, a genome project is proceeding, some mutants are available, they have short developmental cycles (21 days for chick, 16 days for quail), though with relatively long life cycles, they can be studied in large numbers and early embryos cane be stored at cool temperatures and subsequently re-warmed to in order to restart development at desired times. Flight data exist as well, indicating that there are some sensitive periods during which these embryos do not do well in the flight environment. Space Radiation Least understood among the sources of radiation in space flight is the galactic cosmic radiation (GCR) and this, along with other forms of radiation presents a problem for space biology. For an overall discussion on space radiation biology, see the module on radiation biology. In terms of biological development, space radiation is a major factor that must be understood in order for humanity to move deeper into space. Studies involving various animal models have been conducted and it has been found that during space flight (in which there is exposure to radiation) mutations occur in drosophila (Ikenaga et. Al. 1997, also see “Genetic effects of HZE and cosmic radiation” http://idb.exst.nasda.go.jp/ideadata/04012/199906E04012000/199906E04012000.ht ml) and that the mutation rate in space for C. elegans is twice or three times as great as what we would have anticipated on the ground (Hartman). A great deal of research remains to be carried out in the area of the effects of space radiation on development.