Private Spaceflight: A New Landscape for Dealing with Medical Risk.

As NASA and other space agencies make plans to proceed with human exploration missions beyond low earth orbit (LEO), the private sector, including Space X, Virgin Galactic, Blue Origin, Space Adventures and others, echo these plans with initiatives of their own to send humans further into space. Development of more sub-orbital flight opportunities, orbital flight opportunities to LEO and even higher risk endeavors will certainly result in exposure to medical risks for an expanding and heterogeneous population of civilians. To date, a handful of "space tourists" have flown to the International Space Station (ISS), at their own expense, ushering in a new era in which anyone with reasonably good health and even those with physical disability may consider becoming space travelers. Indeed, medical and behavioral issues of healthy, professional astronauts, have not been problematic on short orbital flights. However, recent attempts to test the potential limitations in astronauts on extended duration orbital flights in preparation for future missions beyond LEO raise concern about individual differences in ability to tolerate the hazardous spaceflight environment. Given the rapid development of opportunities for non-professionals and the employees of private companies to travel into space, this is an appropriate time to consider the development of selection strategies for non-government space travelers, including the development of genomic and other modern tools to assess susceptibility to spaceflight risk.

Shallow metabolic depression and human spaceflight: a feasible first step.

Synthetic torpor is an induced state of deep metabolic depression (MD) in an organism that does not naturally employ regulated and reversible MD. If applied to spaceflight crewmembers, this metabolic state may theoretically mitigate numerous biological and logistical challenges of human spaceflight. These benefits have been the focus of numerous recent articles where, invariably, they are discussed in the context of hypothetical deep MD states in which the metabolism of crewmembers is profoundly depressed relative to basal rates. However, inducing these deep MD states in humans, particularly humans aboard spacecraft, is currently impossible. Here, we discuss shallow MD as a feasible first step toward synthetic torpor during spaceflight and summarize perspectives following a recent NASA-hosted workshop. We discuss methods to safely induce shallow MD (e.g., sleep and slow wave enhancement via acoustic and photoperiod stimulation; moderate sedation via dexmedetomidine), which we define as an ~20% depression of metabolic rate relative to basal levels. We also discuss different modes of shallow MD application (e.g., habitual versus targeted, whereby shallow MD is induced routinely throughout a mission or only under certain circumstances, respectively) and different spaceflight scenarios that would benefit from its use. Finally, we propose a multistep development plan toward the application of synthetic torpor to human spaceflight, highlighting shallow MD's role. As space agencies develop missions to send humans further into space than ever before, shallow MD has the potential to confer health benefits for crewmembers, reduce demands on spacecraft capacities, and serve as a testbed for deeper MD technologies.

Effect of gamma irradiation on the structural stability and functional activity of plasma-derived IgG.

Plasma-originated commercial intravenous immunoglobulin, which is used for a variety of clinical purposes, has been studied to determine the effect of virus-inactivating doses of gamma irradiation on the structural-functional characteristics of the protein. A detailed analysis has been performed in response to a concern that the use of conventional gamma irradiation may damage biologically active proteins. The results demonstrate that although gamma irradiation of the IgG may have some impact on protein structure, the damage can be reduced or even prevented by appropriate irradiation conditions. At the virucidal dose of gamma irradiation (50 kGy) and a temperature of -80 °C, the integrity of the polypeptide chain of immunoglobulin and the secondary structure of IgG can be completely protected, while conformational changes in tertiary structure are significantly minimized to a level that preserves functional activity. The irradiated IgG retains specific antigen-binding properties and F(c)-binding activity, indicating that the conformational integrity of the most important structural regions is not affected by γ-irradiation. These results present strong evidence that gamma irradiation treatment can be effectively implemented for inactivation of pathogens in IgG solutions that are used for intravenous injection.

Hypothermia postpones DNA damage repair in irradiated cells and protects against cell killing.

Hibernation is an established strategy used by some homeothermic organisms to survive cold environments. In true hibernation, the core body temperature of an animal may drop to below 0°C and metabolic activity almost cease. The phenomenon of hibernation in humans is receiving renewed interest since several cases of victims exhibiting core body temperatures as low as 13.7°C have been revived with minimal lasting deficits. In addition, local cooling during radiotherapy has resulted in normal tissue protection. The experiments described in this paper were prompted by the results of a very limited pilot study, which showed a suppressed DNA repair response of mouse lymphocytes collected from animals subjected to 7-Gy total body irradiation under hypothermic (13°C) conditions, compared to normothermic controls. Here we report that human BJ-hTERT cells exhibited a pronounced radioprotective effect on clonogenic survival when cooled to 13°C during and 12h after irradiation. Mild hypothermia at 20 and 30°C also resulted in some radioprotection. The neutral comet assay revealed an apparent lack on double strand break (DSB) rejoining at 13°C. Extension of the mouse lymphocyte study to ex vivo-irradiated human lymphocytes confirmed lower levels of induced phosphorylated H2AX (γ-H2AX) and persistence of the lesions at hypothermia compared to the normal temperature. Parallel studies of radiation-induced oxidatively clustered DNA lesions (OCDLs) revealed partial repair at 13°C compared to the rapid repair at 37°C. For both γ-H2AX foci and OCDLs, the return of lymphocytes to 37°C resulted in the resumption of normal repair kinetics. These results, as well as observations made by others and reviewed in this study, have implications for understanding the radiobiology and protective mechanisms underlying hypothermia and potential opportunities for exploitation in terms of protecting normal tissues against radiation.