1. Biomedical Risks and Challenges associated with the Mars Space Voyage

The resilience of humans in exploring extreme space environments has been demonstrated during missions to and around the moon. A mission to Mars however, requires humans to adapt to systemic and complex environments beyond the human body’s capacity. Astronauts will encounter both physiological and psychological extremes during the journey, while on the Mars terrain, and the return to Earth. The knowledge and experience gained from biomedical research and its advancements can be used as a reliable medical approach to help mitigate these risks. However, it will be the steadfast preparations and responses that will minimise risks and potential harm, and allow us to more confidentially embark on these missions (Crawford 2010).

The risks associated with a Mars mission may be defined as the provisional probability of an adverse event occurring from exposure to the space environment (Pestov 2006). Specifically, they are the elements that will affect human productivity and well being during a mission. These include the physical environments in which the crew is required to perform operations, and as described later it is known that the human physiological status will change in response to microgravity in particular (Riviere 2009). Additionally, the psychological and social conditions the crew must live and work under will have an impact on astronaut mental health and each of these individual components require support (Grigoriev 2007). A range of physiological and psychological events endured by astronauts is listed with relevance to operational characteristics in Table 1. Some of the physiological risks faced due to microgravity and exposure to excess radiation include cardiovascular complications (Convertino and Cooke, 2005), probable disease or injury (Groopman 2000), bone demineralisation (Genc et al., 2009; Nelson et al., 2009), cataract formation (Lett et al., 1994), and autonomic neural control (Cooke 2007). As a consequence of the intensity of these complications, astronauts will require appropriate medical attention and training. Although some of the risks can be minimised via the availability of general diagnostic and therapeutic equipment, it will be the development of countermeasures to respond to medical issues during the journey that will ensure the crew's health and safe return to Earth.

The risks connected with human health are an invaluable component that requires consideration for successful mission accomplishments. Mars entails a duration travel time of approximately 8 months (each way) with ground settlement of approximately 30-60 days. Hence, an 18 month trip outside the Earth’s environment will enforce risks on the crew’s mental and physical health and medical approaches to mitigate the extreme risks are required (Pestov 2006). For example, although the choice of crew size and heterogeneity may alleviate boredom (Winisdoerffer and Soulez-Lariviere, 1992), the isolation and confinement that astronauts will encounter during the Mars mission will have a negative influence on their psychological health and performance (Mallis and DeRoshia, 2005; Manzey 2004). One of these is the influence of the space environment on astronaut sleeping patterns and sleep disorders, which has been encountered by astronauts aboard the ISS (Atamer et al., 2002). The design of spacecraft capsules has been considered and is certain to alleviate some of these elements (Salisbury, 1992; Winisdoerffer and Soulez-Lariviere, 1992). However, there are some main behavioural factors affecting astronauts during the mission such as social withdrawal, boredom, depression or frustration. Although these are subjective and can be linked to a crew’s personality, there are mental risks that must be managed. Additionally, there are two main areas that convey vast risks and challenges. These are the absence of gravity and the long-term exposure to different forms of radiation, and the effects they will have on astronaut mental and physiological health are described in more detail in the following sections.

2. Microgravity and the Challenges to Astronaut Health

Space exploration has advanced through technological developments, life sciences research, and the expanding knowledge of space environments. However, the mission to Mars will have vast effects on astronaut physiology due to the periods they must endure in the absence of gravity, which is termed ‘microgravity’. Gravity has considerable influences on biophysical and physiological processes of living organisms. Hence, a Mars expedition will challenge the human body through the exposure of long-term microgravity environments and may have an impact on astronaut overall health (Blaber et al., 2010). Life settings in a spacecraft will differ greatly and astronauts will adapt physiologically at the systemic and cellular level to microgravity. This is mainly due to the accelerated deterioration and degeneration of human systems and functions in microgravity conditions. Utilisation of current biomedical technologies will offer support into how medical responses are conducted. However of greater significance is that the basis for the observed effects of microgravity on astronaut health remains largely unknown and further investigation is warranted (Crawford 2010).

Low orbit studies, using piloted space flights, has demonstrated that microgravity does have a negative affect on the human physical condition (Kotovskaia et al., 2003). The adaptation that the human body is faced with during the commencement, proceeding and return of the mission will also differ to some extent. At the beginning of the journey, the different body systems adapt to the micro-gravitational forces through their de-conditioning of functions. For example, lowering of functional capabilities and performances will be experienced as energy utilization by the human body is diminished in microgravity. During the mission an astronaut’s body will be faced with different physiological challenges to each individual body system, and some form of countermeasures are required.

Some of the effects that microgravity has on particular physiological human systems are: (1) Accelerated bone loss, (2) cardiac and vascular alterations, (3), diminished neural control, (4) dysfunctional immune responses, (5) renal stone formation, (6) impaired human performance, and (7) muscle tissue degeneration.

To illustrate a few examples, the elevation of blood flow and tissue fluid pressures has already been noted and examinations on astronauts have suggested that microgravity may have an impact on head bone density (Hargens 1994). Additionally, animal studies have demonstrated a relationship between decreased cerebrovascular resistances during microgravity (Gotoh et al., 2003). Alterations in pulmonary blood circulation, fluid content, and uneven distribution among various zones of the lungs have also been observed by researchers from the Chinese Space Program, yet the basis for these systemic changes remain unclear (Sun et al., 2000).

The absence of gravitational forces on the human body is also certain to have an influence of bone mineralisation, resorption and matrix formation. The question is will it limit long-term human space exploration (Holick 2000)? The exposure to microgravity is known to cause a decrease in bone mass and alter bone geometry due to the lack of weight-bearing forces on the skeleton (Vico and Alexandre, 1992). Shifts in bone fluid have been previously acknowledged and reviewed (McCarthy 2005). Osteopenia, which is the result of lowered bone mineral density, and can lead to osteoporosis, are the main challenges that microgravity will have on the human skeletal system. Specifically, bone mass reduction has been noted in trabecular structures of bone in the lower limbs due to fluid regulation, endocrine control and calcium homeostasis (Oganov et al., 2006). The changes in bone mass, mineral density, mineral and fluid flow and content in different skeletal segments suggest that bone metabolism may be dependent on gravity magnitude and direction.

Studies on animals have shown that either aerobic or resistance exercise can be used as a countermeasure and maintain bone formation and prevent bone resorption (Smith et al., 2008). Long-term space flights have also shown accelerated skeletal muscle wasting in astronauts, which subsequently reduces their performance capabilities (Vandenburgh et al., 1999). However, these may be attenuated by physical exercise.

The use of a weight-bearing musculoskeletal apparatus may minimise musculoskeletal degeneration, however reducing further degeneration may also require the aid of pharmaceuticals. The use of pharmaceuticals such as gallium nitrate, which is used to inhibit bone resorption in patients with Pagets bone disease, has been investigated, although it did not prevent bone loss in rats during microgravity (Apseloff et al., 1992). The different effect drugs may have on bone during microgravity has been reviewed previously (Shapiro 2006), and challenges associated with impaired circulatory responses in the human vascular system have also been shown (Hughson 2009). Furthermore, impairment of the immune system and its response have also been investigated (Borchers et al., 2002; Paulsen et al., 2010). The innovative and multidisciplinary area of tissue engineering may have advantages to help the human body systems combat the space environment (Conza et al., 2001). Collectively, it will be essential to have innovative physical equipment and medical countermeasures ready for use to help combat the degeneration of astronaut human body systems.

3. Space Radiation and Astronaut Health

A long duration space journey will also expose astronauts to immense dosages and different kinds of radiation. For example, cosmic radiation originates from astronomical events outside our galaxy, such as supernovas (de Gouveia Dal Pino et al., 2010; Potgieter, 2010). Conversely, solar radiation contains particle events that are intermittently released in bursts from solar flares or coronal mass ejections (Potgieter 2010). Astronauts will be subjected to both of these intensities which are almost 100 times higher than Earth’s terrestrial radiation (Clément and Slenzka 2006).

The evaluation of present-day knowledge of cosmic radiation at extreme altitudes and durations illustrates radiation is a significant hazard to astronaut health (Bagshaw 2010). Studies have shown that an increase in cataract formation occurs in astronauts who have been exposed to higher doses of radiation during spaceflight (Cucinotta et al., 2001). Furthermore, exposure to heavy ions during the Mars mission might damage the human brain and compromise an astronaut’s overall health and mission success (Rice et al., 2009). Additionally, the primary concern is the increased risk of astronauts developing cancer. This is largely due to the exposure to protons and particles of high atomic number and high energy (HZE particles) during the journey and while on the Mars terrain (Kennedy and Todd, 2003). It is known that ionising radiation creates free-radicals in human cells and tissues (Biaglow 1981) which produce active molecules that can damage proteins, lipids and nucleic acids, the building blocks of DNA (Ward 1988).

Although free-radicals are generally generated during cellular metabolism (and cells have evolved mechanisms to reduce adverse effects), the severity of radiation that astronauts are exposed to during a Mars mission are certain to damage human tissues, and possibly result in the development of malignant and cancerous tumours. Studies have revealed that long-term radiation exposure on living organisms result in mutations to DNA (Clément and Slenzka 2006; Ikenaga et al., 1997; Hartman et al., 2001). Furthermore, a study involving the irradiation of female Rhesus monkeys demonstrated a significant harm to endometrial cells in the womb (Clément and Slenzka 2006; Wood, 1991). Some studies using mice have however suggested countermeasures to help prevent these effects (Kennedy et al., 2006; Kennedy et al., 2007). Although short-term studies of astronauts post-flight have indicated there is no observed correlation with cancers, they did indicate an increase in chromosome damage and abnormalities (Clément and Slenzka 2006; Obe et al., 1997; George et al., 2000; Durantea et al., 2003). Biomedical countermeasures can be used to help reduce the levels of detrimental physiological consequences. However, it may be the development of novel material for astronaut suits (Vana et al., 2006) and advancements in spacecraft design (Wilson et al., 2001), that will ultimately reduce challenges and risks involving astronaut exposure to radiation.

4. Bioastronautics Countermeasures

The safeguard of astronaut health may take decades in preparation before long-term missions can be safely embarked upon. The medical challenges associated with maintenance of crew safety, health and optimum performance during Mars missions must be evaluated and overcome (Crawford 2010). Although some significant research has been undertaken, our knowledge is still limited regarding the physiological and psychological changes that humans will encounter during long-term exposure and adaptation to a space environment. This is particularly the case for understanding changes that are occurring at the cellular level. Specifically, by having in place appropriate countermeasures and medical support consequences that arise throughout the mission can be addressed. NASA has facilitated the development of such countermeasures through a biomedical challenges research program, to ensure safe and healthy human space travels. Originally termed the bioastronautics initiative, it was a biomedical research program put in place to evaluate the physiology of humans exploring space in preparation for landing humans on the moon (Harmon, 1965; Kaufman, 1964). Recently, it has been transformed to the Human Research Program (HRP) (humanresearchroadmap.nasa.gov).

The HRP is a strategic platform for the identification, assessment and implementation of countermeasures against the risks and challenges associated with human exposure to the environment of space (Blaber et al., 2010). The primary objectives of the program are to identify and assess risks by prioritising and allocating resources to reduce these risks, and produce outcomes that result in countermeasures (Charles 2005). The HRP contains 45 recognized risks associated with space travel. These are categorised into sixteen disciplines with five main classifications: Autonomous Medical Care (AMC), Behavioural Health and Performance (BHP), Human Health and Countermeasures (HHC), Advanced Human Support Technologies (AHST) and Radiation Health (RH) (Convertino and Cooke, 2005; Blaber et al., 2010).

Three different missions, primarily the ISS, Lunar and Mars have been categorized and assigned risks with an assigned priority scale from 1 (high risk) to 5 (lower risk). Although the HRP is an initiative developed by the United States, it is strengthened by international collaboration of diverse research fields (McPhee and White 2008). These collaborations leverage new and unique capabilities and integrated countermeasures. The deliverable accomplishments are further complemented through several different international programs that are in place for medical support. The international space station (ISS) program uses the Multinational Medical Operations Panel (MMOP) to review ISS medical and habitability issues, and delivers the best medical operations (Duncan et al., 2008).

The Multinational Space Medicine Board (MSMB) uses the Astronaut Medical Evaluation Requirements Document as the governing document for standardized selection of international crewmembers for the ISS. The Multinational Medical Policy Board (MMPB) is an international group that develops medical policies for the ISS program. The Human Research Multilateral Review Board (HRMRB) is the international administration that reviews all experiments (in-flight and terrestrial) to ascertain the safety and health involving all human research.

5. Conclusions

Collectively, the success of the first human mission to Mars will be achieved through the accessible deliverables that these different programs described offer, and how their countermeasures are implemented through medical selection processes and the international mission medical support offered. Operative analog prototypes for Lunar and Mars explorations have been explored on Earth (Stuster 2005). However, the cumulative, long-duration burdens associated with an astronaut’s health-capacity and their ability to adjust to all mission conditions imposes considerable concerns that have to be further investigated before human Mars exploration advances.

An evidence-based approach to space medicine is also critical, incorporating past studies of microgravity-related conditions and their terrestrial counterparts (Williams 2003). The data being generated from current research provides the basis for such an approach, and will ultimately help solve the medical challenges of human space flight. In addition, although not the focus of this review, development of sound realtime communications systems will be necessary, to ensure both the smooth running of all operations and the rapid response to situations that arise on missions. Finally, as many spaceflight-induced medical complications have parallels to medical problems here on Earth, any medical advances made in space or "space-like" conditions can have valuable applications on Earth. Thus the potential benefits of these research programs are far-reaching, both in terms of advancing human knowledge and contributing to addressing medical issues faced in a space environment and back on Earth.

Acknowledgements: The authors declare that no competing financial interests exist. The authors also wish to thank the anonymous reviewers for their comments and suggestions to improve manuscript quality.