We Choose to Go the Moon … Again … and Here's What It Means for Physiology

Fifty years ago, humans landed on a planetary body for the first time. Three years later, the Apollo programme ended. The longest time on the lunar surface? Three days. Relegated to low Earth orbit by mission and hardware, subsequent programmes – the US Space Shuttle and the International Space Station (ISS) – enabled impressive scientific strides (National Academies of Sciences, Engineering, and Medicine, 2018). We now understand much more about the conditions necessary for humans to thrive as planetary explorers. Thanks to the ISS, humans have been living continuously off of our planet for 19 years, the longest stay being 340 days. For this and future generations, a continuous human presence in space has become the norm. As a base for accumulating long duration exposure to the microgravity (free-fall) environment, the ISS program has helped physiologists define previously unrecognized risks. Spaceflight-associated neuro-ocular syndrome is characterized by papilloedema and macular swelling that appears to be associated with persistent elevations in cephalad (and therefore capillary) hydrostatic pressure (Zhang & Hargens, 2018). Perhaps sharing a similar aetiology, thrombi have recently been documented in the jugular veins of some long-duration astronauts (Marshall-Goebel et al., 2019). Such findings suggest that restoration of venous pressure dynamics may need to become part of occupational health routines for future space workers. With low earth orbit emerging as an innovation hub for the research and manufacturing sectors, we're poised to leave low earth orbit with a renewed focus on exploration. The Artemis programme, announced by NASA last year, will place the first woman and the next man on the lunar surface in 2024 (National Aeronautics and Space Administration, 2019). In Greek mythology, Artemis is the twin sister of Apollo. The name of the programme – like the composition of its crews – signifies a promise that space exploration will remain gender-inclusive. But the Artemis programme bears little resemblance to its Apollo predecessor. Enabled by the Space Launch System – the most powerful rocket ever created – and the Orion spacecraft – a joint American and European venture – Artemis will deliver tons of equipment to the vicinity of the Moon and eventually Mars. The first launch is less than a year away. In less than 10 years, women and men will live on the Moon for months at a time. Artemis will place a transfer station, or Gateway, in a near rectilinear halo orbit which is extremely stable in the vicinity of the Moon. With purpose-built spacecraft shuttling from Earth to the Gateway, and from the Gateway to the lunar surface, the Moon will be the testing ground to perfect the technology, skills and techniques for future exploration of Mars and other planets. Commercial partners are essential to develop the next generation of lunar landers, focusing on a sustained human presence at the lunar south pole within a decade. This unprecedented government–commercial partnership will involve a third partner: scientists with a thirst to study and utilize the lunar environment for research. An early focus on research emulates expeditions to Earth's polar regions a century ago. Polar research stations remain a hotbed of activity today. If lunar research outposts seem more fantasy than fact, consider that the rocket for the first Artemis mission is now being assembled in Louisiana. The first contracts for the Gateway have already been released, and companies such as Boeing, Blue Origin and SpaceX are completing their designs for human lunar landing systems. Late 2018, a team of university and NASA researchers published direct evidence that frozen water is mixed in the lunar regolith in the cold (approximately −240°C), permanent shadows of craters at the poles (Li et al., 2018). These areas hold special intrigue for lunar geologists and biologists alike. Eventually, this ice might be used to sustain residents of the Moon. On the contrary, the rims of these craters are illuminated by the sun nearly continuously because the Moon's rotational axis is nearly vertical: ideal for solar power generation. Although the composition, pressure and temperature of the Orion capsule's atmosphere will be comparable to Earth's, extravehicular and lunar activity requires a hypobaric, hyperoxic environment. Ambient pressure within suits is reduced to approximately 240 mmHg to aid mobility and maintain at terrestrial levels. Oxygen delivery, CO2 removal and thermal management can support conditions of moderate, but not maximal, physical activity. In these micro-environments, the suit, not the human, often defines the limiting factors to human performance. These unusual aspects of physiology are shared by other occupational athletes who work in sealed, suited environments (e.g. divers). However, planetary exploration poses two unique physiological challenges and research prospects not encountered in terrestrial suited environments. First, outside the Earth's van Allen belts, ionizing radiation from galactic cosmic radiation and solar particle events exposes tissues to high linear energy transfer events (mostly high energy protons and high-atomic-number ions) that can exceed 1 GeV. Both primary and secondary events (ionizing radiation resulting from collisions with metallic spacecraft hulls and the lunar surface) contribute to the physiological stress. The resulting damage can overwhelm DNA repair mechanisms and increase long-term risks of cancer and cataracts (Barcellos-Hoff et al., 2015). The second area has more profound implications. All life that we know evolved with Earth gravity. Does biology require Earth's gravitational field? Or, can organisms as large and complex as humans adapt successfully to gravitational forces different from Earth's? Comprehensive answers to these questions continue to elude gravitational biologists, impeding our progress to colonize other planets. The flexibility of the Artemis architecture can be used to address both topics. With its relative proximity to Earth and a gravitational field only one-sixth that of Earth's, the lunar surface is the perfect location for fractional gravity laboratories. Because Artermis creates a permanent presence on the moon, landers and habitats can be customized for scientific disciplines, like lunar vivariums to house cell cultures and model organisms, including rodents. To date, the longest a mammalian model (Mus musculus) has been placed in a microgravity environment is 91 days (Cancedda et al., 2012). Mortality was 50%. A ‘life cycle’ experiment was first completed on the space station Mir with plants more than 20 years ago, yielding results consistent with the notion that plant development is largely independent of gravity (Musgrave et al., 2000). However, a comparable experiment has never been attempted with mammals. Is gravity an obligatory requirement for reproductive and developmental success? Is the biological impact of the gravity continuum linear at less than 1 G? For example, would halving the gravitational stress load halve a physiological response? To what extent does gravity drive evolution? How would gene expression and phenotype change with successive generations of animals reared in microgravity or fractional gravity? Could selective breeding be used to amplify or suppress traits associated with gravity adaptation, affording new insights into the role of gravitational loading in health and disease? Similar approaches have provided considerable insight into the role of exercise training (Garton et al., 2016). A successful (and therefore reproducing) lunar colony of animal models could inform virtually any aspect of physiology. Studies of this nature have high translational impact for space exploration, and potentially for terrestrial conditions associated with reduced physical activity and gravitational loading (e.g. prolonged bed rest). We are returning to the Moon as a stepping stone to the future exploration of Mars. Determining whether mammals can reproduce successfully on the Moon will set the stage for sustainable colonization of the planets, another step for humankind that will inspire our and future generations.