1 INTRODUCTION

Despite the tremendous possibility to obtain valuable scientific data and results by robotic planetary exploration it is an evident next step that sooner or later a human mission to Mars should become an irresistible attraction for mankind once different successful robot missions are realised. With the finalization of the International Space Station (ISS) in sight, a permanent lunar base and a manned mission to Mars are the next big step in human space exploration. Robotic exploration has proven the performance of state of the art technology extra terra and as it successfully proceeds, broadens the necessary political and financial support for the realisation of a human mission to Mars. However, human participation will be essential to perform repair or replacement operations of defective equipment. The Hubble Space Telescope servicing missions carried out by the Space Shuttle (STS 61 (1993), STS 82 (1997), STS103 (1999), STS109 (2002) and STS125(2009)), show that a human flight program can upgrade robotic explorations. Through servicing and improving performance of earlier instruments not planned before the lifetime of the Hubble telescope is extended at least for another decade. Moreover, without the participation of man, the public support for space faring programs will probably be smaller, thereby making it more difficult to allocate the required budgets.

After more than 50 years of space exploration it has become obvious that human missions cannot be successful without the combination of advanced robotic instruments and human flexibility. Robust and multifunctional instruments are necessary not only to reach specified goals, but also to set up life support systems (LSS) that enable long-term space residence.

2 LIFE SUPPORT SYSTEM (LSS) AND RECYCLING OF MATERIAL

Human space explorations are limited by safety considerations, the necessity for spacesuits (environmental factors) and the mass of human life support systems. Life support and safety precautions take a large part of the budget in human space exploration; however this is balanced by the fact that humans are ideally suited for intensive field study and other tasks requiring complex physical articulation, expert knowledge and, especially, flexibility. Up till now, human residence in space has been limited to low earth orbit (LEO) or to short walks on the moon surface making a life support system rather simple and not very demanding. The necessary food and water is provided to the crew by transport vehicles whereas waste is discarded in simple containers. The set-up of human space travel to Mars necessitates more complex life support systems that should recycle waste and produce valuable products such as food and vitamins.

Depending on the mission scenario, a journey to Mars will take about 500 to 1000 days and, without any life supporting system, require between 100 and 200 metric tons of material as calculated in the HUMEX-study presented to ESA (Horneck et al. 2006) or the Bioregenerative Life Support System (BLSS) (Hu, Bartsev and Liu 2010). This current theoretical estimate is optimistic, and when translated into engineering systems will require increased margins, spares and fail-safe performance and as such it is likely to increase significantly. Hence, such a mission is not feasible if the astronaut is not spending part of his time recycling waste and producing basic amounts of food. Therefore a successful Mars explorer not only needs to be a skilled pilot but he also needs to be a farmer and a cook preparing his food before being a scientist.

The LSS can take many different shapes, depending on the length of the mission and the place of implementation (on board or on planet). At one end, there are the established systems that provide sufficient supply of food, water, oxygen and only recycle part of the air and water by physical and chemical technology. This technology has performed well in different space missions and on board the ISS, but has major mass restrictions for a mission covering periods of 500 days and more. An alternative approach is to develop a life support system that mirrors the set-up of a municipal purification plant containing biological organisms that transforms human waste to minerals, gasses or liquids that can be used to culture plants or feed animals and in this way provide in all necessary food requirements. This is the rationale of the MELliSSA (Micro-Ecological Life Support System Alternative) as studied by ESA (Hendrickx et al. 2006). But Russian as well as NASA programs also have running studies on this concept (Tikhomirov et al. 2003, Wheeler et al. 2008, Meleshko et al. 1994). A basic setup for a LSS for long-term interplanetary missions is represent in Figure 1. Given the relation between system mass and mission duration a breakeven point for a bioregenerative life support systems is estimated to be at 2.5–3 years (Ferl et al. 2002). However, we have to admit that we still are far from an optimal biological life supporting system and more test plants are necessary to study the dynamics of such a system especially under spaceflight conditions.

As no spare parts from Earth can be sent, it is essential that this LSS is totally reliable, controlled and self-sustainable (Rapp 2006). If a CELLS (controlled ecological life supporting system) is set-up to provide life support on Mars, it should be considered how this system will be transported to Mars and if this system should be active during transport to Mars. A robotic mission could be set-up to transport a lyophilized system to Mars and try to use Martian water to activate it. Usage of indigenous water on Mars would lead to a significant mass saving as well as a risk reduction. Furthermore, a lyophilized system could prove advantageous as bacteria and spores are less prone to radiation-induced damage, when transported under a dry inert atmosphere. Although this is an option, this approach reduces the choice of useful microorganisms and should be included in the development and set-up of a CELLS. Taking into account the needs to prevent contamination of the Martian surface with terrestrial organisms extensive precautions will be required, making the robotic mission nearly as complex as a manned mission.

On the other hand a fully closed system carrying its own water mass will be to large to be enclosed in a single cargo and needs multiple cargo flights and a complex robotic handling to connect different modules (Rapp 2006). The MELiSSA system for example, studied by ESA is composed of 4 compartments (Hendrickx et al. 2006). The BLSS system designed by Hu, contains 7 compartments. The CELLS system could be assembled inside a module created by docking different cargo’s in a Martian orbit and finally execute a soft landing of the whole system. After a successful landing, the CELLS system could be activated just in time before the arrival of the astronauts. In order to exclude the risk on contamination a self destructing system should be included that is activated if any abnormal evolution is detected in the CELLS modules in order to fully prevent the risk of interplanetary contamination (Horneck 2008). The latter scenario supposes that during transport all life supporting systems on board the spacecraft don’t make use of a biological regeneration system, with the result that the astronaut will arrive at Mars with a quit large load of waste, which has to be recycled, before the crew can return. Moreover it also supposes that the system is safely shutdown after the crew leaves the Martian planet. In addition to mass and volume at least two other important factors have to be considered in a LSS and can be critical in relation to a long-term voyage to and a residence on Mars, namely the relatively uncharacterized conditions with cosmic radiation and altered gravity as major contributing factors, and the processing of micropollutants.

2.1 The extraterrestrial environment The earth’s atmosphere and magnetic field provides relatively effective shielding for different types of radiation present in space. During prolonged space travel crew members as well as biological components will be exposed to two main radiation sources, namely solar energetic particles (SEPs) from the Sun and galactic cosmic rays (GCRs) from outside the heliosphere. The lower energies of SEPs make shielding possible, the higher-energy GCRs are more of a concern as they require more dense materials to provide efficient shielding, but of which the use is limited due to mass restrictions (McNutt, Horsewood and Fiehler 2010).

The difference between LEO and long duration interplanetary missions is that they leave the protection of the Earth’s magnetosphere, which effectively shields of cosmic radiation. Designing spacecraft radiation shielding also requires minimizing exposure to secondary ionizations induced by high mass (Z) high energy or HZE particles during their passage through various materials. It has been shown, based on straightforward physics considerations, that the aluminium currently used in spacecraft hulls is a poor shield (due to the energy of the secondary ionizations) and that pure hydrogen is the most efficient material for fragmenting heavy charged particles (Wilson et al. 2001). As such, research is focussing on various hydrogen-rich materials such as polyethylene (PE) for use in spacecraft construction and passive shielding. PE shielding produces a mixture of fragmentation products of low and intermediate LETs (linear energy transfer) that inflict DNA damage that the cells are able to repair more efficiently, i.e. more single stranded breaks and less clustered double stranded breaks (Mukherjee et al. 2008). These passive shielding materials will increase the total amount of radioprotection, but they are unlikely to completely block GCR and SEP. Therefore the option for an active shielding for long duration interplanetary manned missions was studied (Spillantini 2010, Tripathi, Wilson and Youngquist 2008). Amongst the four categories of active shielding are: electrostatic fields, plasmas, confined and unconfined magnetic fields. However to date these electrostatic shields are unsuitable for GCR shielding since their required electrostatic potentials exceeds our current capabilities.

Therefore the presented concept was developed partly as a shelter module with eventual expansion to a habitat module. The question how this set-up is compatible with a photosynthetic module, necessary for biodegradation is not answered. A temporary protection of a small volume shelter as proposed by Spillantini (2010) is no option because of the need of a large habitat where the astronauts can live and work. The development of such a habitat should also meet with the restrictions for photosynthesis and allow the growth of microorganisms, algae or edible plants. Because these organisms are as sensitive to ionizing radiation as man, the shielding needs to include the life supporting system. There is always a risk that radiation-induced mutations alter the performance or functions of microorganisms that, due to their short doubling time, may quickly protrude throughout the culture. Studies on radiation sensitivity of ecosystems show that large differences in radiation sensitivity of an ecosystem results in the loss of the whole system when the sensitive organism is a prey for the more resistant predator (Doi et al. 2005). As such the presence of various types of radiation during the trip to Mars and on the surface of Mars is not solely a problem for the crewmembers but also needs consideration with respect to the LSS as it based on the recycling of waste by bio-degradation through living micro-organisms.

If photosynthesis is essential for an efficient LSS or to produce supplementary nourishment, additional problems arise. Photosynthesis during a space voyage requires that sufficient light, ranging from wavelengths between 400 en 800nm, reaches the plant surface to sustain plant development. On the other hand shielding of ultraviolet and ionizing radiation is necessary to prohibit genetic damage to the different organisms in the life support system. To have effective photosynthesis however, we need light in sufficient amounts in order to be productive. This can be made possible by application of stable fluorescent or phosphorescent coatings on the UV-shielding material as is applied in fluorescent lighting systems (Wheeler et al. 2008). Careful construction of such systems is necessary. In addition, if the LLS is expanded for use on Mars, it has to take in to account the changing spectral quality of the light in different positions on the Martian soil, combined with heavy dust storms and a lower gravity (0.377 x g), which causes dust to descent far less effectively from covers. Another remaining risk is that plant yield will be influenced by stress inflicted by radiation and reduced gravity conditions in space and on Mars (Lehto, Lehto and Kanervo 2006).

2.2 Micropollutants Micropollutants consist of thousands of synthetic and natural trace contaminants that may be present in water and air at low to very low concentration. Many of these micropollutants raise considerable toxicological concerns, particularly when present as components of complex mixtures. Elimination of these contaminants can be problematic especially in an integrated LSS as they require specific microbiotic composition. We know that many sanitary products like soap, toothpaste etc… contain antimicrobial components as triclosan that are difficult to eliminate by fermentation. Reports indicate rather an adsorption of these pollutants from sewage water but not degradation (Schwarzenbach et al. 2006). A similar product is diclofenac. This frequently used anti-inflammatory drug degrades very slowly (Strenn et al. 2004). Physical or chemical methods (burning) will need to be included in order to safely eliminate these components. For a lot of other products, such as pharmaceuticals, effective degradation methods in a biological recycling system are not yet known and therefore should be tested. This is of particular interest since astronauts on extended space missions will need a basic set of pharmaceuticals to counteract the adverse effects of space travel (Horneck et al. 2006). Extra medication may be necessary to provide (at least partial) protection against the negative effects of microgravity or radiation (cfr. next paragraph). It is essential that these medicines are well dosed and fully eliminated from all the waste after recycling. This should necessitate new pharmakinetic studies or even the development of new drugs with high turnover that will remediate this problem. The scope of these studies should even be extended, as some of these micropolluents mimic quorum-sensing mechanisms, which is an essential step in the set-up of an ecological microbial waste treatment fermentation (Egli 2004). The set-up of a life support system including algae or higher plants in combination with animals (fish, birds, rodents) will require specific medicines and disinfectant with similar specification in relation to its chemical stability or breakdown.

3 MONITORING THE SAFETY AND PERFORMANCE OF THE LSS AND THE HEALTH OF THE ASTRONAUTS

Exposure of humans to the harsh environment of space is not without risks. During the flight to Mars, the crew and all their belongings are exposed to microgravity and different types of radiation. The effect of microgravity on bone metabolism in vivo and in vitro was studied in different flights (Carmeliet, Coenegrachts and Bouillon 2007, Bacabac, Van Loon and Klein-Nulend 2007) and presented in different reviews (Loomer 2001, Turner 2000). Due to lack of gravity astronauts show extreme weakness and have problems to walk. This can compromise safe landing on Mars and should be taken into consideration if planning Mars walks. It was suggested to take medication e.g. Zoledronate, in order to reduce bone breakdown. However these products could have strong side effects on vascular conditions. Zoledronate exerts anticancer effects by inhibiting tumor-induced angiogenesis and malignant osteolysis and hence the possibility that it will interact with revascularisation after prolonged microgravity exposure should be considered (Wu et al. 2009).

Recent results, measuring the protein carbonylation in relation to UV or gamma-irradiation, showed that the high resistance of Deinococcus radiodurans to ionizing radiation is directly linked to proteome protection (but not DNA protection) (Krisko and Radman 2010). This means that antioxidants are valuable radiation protection products. L-selenomethionine was tested as a food additive in rats radiated with a wide spectrum of electromagnetic radiation (Guan et al. 2004) but also nanoparticles of cerium oxide show antioxidant activity and are promising candidate drugs (Rzigalinski et al. 2006).

These countermeasures make it necessary for the astronauts to take extensive medication. In order to precisely control possible side effects of this medication and space travel the need for advanced personal medicine follow up is necessary. For this objective simple but adequate biomarkers should be developed. We have validated a proof-of-concept biodosimeter for diagnosing cellular stress response during the Foton M3 and previous space missions (Dieriks et al. 2009, Van Oostveldt et al. 2007). In addition, we have recently analyzed the secretome of normal human fibroblasts and fibroblasts isolated from patients with Progeria syndrome to identify potential biomarkers. Out of the 88 molecules that we screened, 20 showed a significant level increase or decrease, with a differential response to space conditions between the two cell types (Dieriks et al., accepted in Molecular Medicine Reports). Although potentially useful, these biomarkers need to be analysed in follow up experiments involving astronauts. The astronauts presently occupying ISS would be a perfect test case.

As astronauts have only limited medical training and expertise, these analyses should be simple to execute on easy to access material (blood, tears, urine, sputum…). Ultimately, (bio)-markers should be sought for evaluating not only the human body but also the whole environment; including air, water and food and preferably their fluctuations should be monitored in real-time, just like simple physical (temperature, humidity) or chemical sensors (Figure 1). On the other hand, image analysis of cell cultures or human physiology may prove sensitive indicators but are difficult to implement in practice and may have different, subjective interpretations. A multiparametric approach, relying on multiple biomarkers that can be easily monitored (e.g. from bodily fluids) and/or objectively analyzed may resolve this issue. This technology can be further integrated into different LIC’s (Labs on a chip) and used to monitor the status of the life support systems or microbiological safety of food, as well as diagnose of different human samples (Whitesides 2006).

4 EARTH BENEFITS FROM THE PREPARATION OF A MARS, SPACE VOYAGE

The development of a compact CELLS system necessary for Mars exploration providing safe conversion of waste and sewage to minerals or clean water will also be extremely useful for specific life support systems on earth. For example, in the organisation of emergency aid during different disasters like floods or earthquakes a compact, easy to transport life support system can be life saving for hundreds of people. Miniaturization will become increasingly more important on Earth as well. Some of the limitations present in space, such as mass and space for the MELiSSA, are not limiting the applicability on Earth.

Continuous monitoring human health status at reasonable price has to be realised for a crew on the way to Mars but is nearly a must in our future society. We therefore believe that if different research teams can work together to reach a final goal: Mars, we will create a new worldwide drive for mankind, which will create benefits for all Earth inhabitants.

There is still a long way to go, not only for the technology but also, and probably more important for political decision makers to expand their thinking beyond the present 2-4 years (political) time frames. They need to convince the general public that interplanetary travel is only possible if all inhabitants of the planet are convinced to work together for a safe travel to Mars. If this initiative is successful, it will not only explain many questions about the origin and evolution of our solar system, but will also prove that mankind has evolved to a society where (international) collaboration prevails from competition. Then, we will be at the dawn of a new society.