Would you sign up for a one-way trip to colonize Mars? For infamy and certain damnation? Or perhaps you are driven by an altruistic desire to colonize the desolate Red Planet? To pave the way for the eventual colonization of extrasolar planets? Or would you do it for the unique scientific insights and gains that could be made from studying humans on other planets?

Whatever your reasons, the visionaries behind the Mars One project are willing to gamble billions of dollars on our collective curiosity and sense of adventure. The non-profit endeavour, which is currently in the astronaut recruitment phase, promises to broadcast every waking moment of this human challenge. The mission’s simple goal is to establish a human colony on Mars by 2021. But can it be achieved? Far from the realm of science fiction, the project has already garnered financial support from Nobel laureates and companies alike. With an estimated cost of only $6 billion, the grandness of the concept is staggering and at times unbelievable. Compare this price tag to the Apollo program which cost an estimated $150 billion (adjusted) in its lifetime and landed 12 men on the Moon. As an advocate for science and space and science in space, the project simultaneously frightens and intrigues me.

I must admit that I have considered applying for the position of space immunologist aboard Mars One. I did not grow up in the era of manned spaceflight. I have never witnessed a live rocket or shuttle launch and yet, I am a staunch supporter of space travel and exploration. Images taken by the Mars rover Curiosity are sprinkled in the files and folders of my computer. Perhaps I’ve read too many science-fiction novels, but in my mind, space travel holds a certain charm; it represents a frontier of possibility.

But before I can climb aboard an 8 month journey into the abyss, to the dismay of my family and friends, I had to investigate the possible harmful effects of spaceflight on immunology.

The Dangers
After mere hours of study, the truth of spaceflight became crystal clear. In its current form, spaceflight is psychological and physiological torture.

Safely harnessed in methodically cramped shuttles equipped with 2 million pounds of solid propellant and 1.8 million litres of supercooled liquid fuel, astronauts must travel a minimum of 6 hours to reach the International Space Station (ISS). Enduring 3 G’s of force and reaching speeds of up to 27,000 km/h, astronauts reach a maximum altitude of 500 km. And this is the absolute shortest and safest trip a space traveller can take. Travelling to other planets presents additional problems. The last time a foot was placed outside the Earth’s protective magnetic field and on the crust of the Moon was in 1972. The entire trip took Apollo 17 a total of 12 days and 13 hours. Time spent in low-gravity and exposure to radiation varies greatly depending on the extent of the missions, but whether you’re weightless and adrift for 400 days on the ISS or on a twelve day journey to the Moon and back, the emotional and physical stress is enormous.

In space, astronauts must endure cramped conditions, high stress, low gravity, and exposure to the sun’s ionizing radiation. In the foreign environment of a shuttle or space station, the human body must adjust to: recycled air, changes in microfluidics resulting in low-blood pressure and blood volumes, abrupt alterations in circadian rhythms from lack of proper day/night light cues, copious release of stress hormones such as glucocorticoids, loss of proper nutrient uptake due to altered GI function, muscle and calcium bone loss, and many other stressors. Space is a dangerous place and interplanetary trips can be quite hazardous to the human body.

The Studies
Direct in situ studies on immune cell function in space are limited. However, if you consider that it costs approximately $60,000 (USD) to take 1 kilogram of weight to the ISS, the few and far between studies that have been conducted gain significant merit. Put another way, it would cost $900 just to bring a single 15 gram mouse aboard the ISS.

To curb costs, immunological studies on the effects of spaceflight are conducted primarily on Earth, either in simulated environments or from collected blood samples pre- and post-flight. Of the few studies performed and analysed on the ISS, the majority use immune cell lines and bacteria.

The environmental hazards of space can begin to be modelled on Earth through the use of clever design and engineering. For example, the effects of solar particle events (radiation) can be monitored by exposing cells and animals to artificial proton and gamma bursts. Weightlessness can begin to be mimicked by hindlimb unloading, a process in which mice are literally elevated by their tails for extended periods of study. Microgravity and low shear forces can be partly replicated by using a Rotating Vessel Wall bioreactor. In these machines, cell cultures are placed in a horizontally spinning field and rotation synchronized with the culture walls. Obviously, these models are far from perfect, and the majority of studies on human immunology in space are from blood samples taken pre-flight and immediately upon return.

The Effects
The stressful, dangerous, and restrained environment experienced during spaceflight can impact the immune system by altering microbial growth and virulence, immune cell distribution and differentiation, and immune cell function and response.

The low gravity and isolated conditions experienced during spaceflight are not only permissive to bacterial growth but seem to support increased pathogenicity. In studies of space-born Salmonella enterica, Escherichia coli, and Bacillus subtilis, bacteria were shown to have greater rates of growth in low gravity. The low gravity reduces shear forces and may allow for more rapid bacterial colony formation. Along these lines, it was also found that increased concentrations of antibiotics were required to inhibit and kill the highly proliferative bacteria. Later studies have even shown that bacteria grown either in space or under simulated microgravity here on Earth had increased virulence and pathogenicity. Samples of bacteria grown in space and returned to Earth were found to be more pathogenic than their Earthly brethren. This increased proliferative and pathogenic capacity coupled with the contained and shared environment found on spaceships raises serious health concerns for the astronauts aboard. In a recent study from astronauts aboard the ISS, it was noted that the microbiome of individuals eventually become both unified and disrupted, likely as a result of the shared environment and drastic changes in diet and digestion. In space, the altered bacterial selection, replication, and virulence poses a potential threat to travellers. In fact, it is common for astronauts to experience a reactivation of latent but dangerous herpes and varriola viruses as a result of general immune suppression, nutritional deficiency and a permissive environment.

The physical stress of takeoff, landing, and the low-gravity conditions all act in combination to lower the immune response. The peripheral blood leukocytes of returning space-farers are generally disrupted in number and composition. Immune cells from animals and humans were found to have lower levels of adhesion molecules and overall hypoplasia of the primary lymphoid organs. There was generally an increase in granulocytes and a decrease in monocytes and natural killer T cells.

Cytoskeletal structure in the absence of gravity is also deregulated and in immune cells this can lead to a breakdown in cell signalling and motility. In a study aboard the ISS, the monocyte cell line J-111 was found to have significantly decreased motility. Interestingly, T cell mobility in the Jurkat cell line was increased in space but immune function and response to ConA mitogenic stimulus was almost completely aborgated. Humoral responses were also shown to be altered. Upon vaccination with foreign antigen, the model organism Pleurodeles waltl was found to have a different VDJ preference in space.

[pullquote align=”right”]The Mars One mission promises to safely position colonizing humans on the surface of the red planet in a staggeringly short 10 years’ time.[/pullquote]

Overall, spaceflight may be conducive to an immunosuppressive response but the effects of landing often convolute the findings. Peripheral blood leukocytes of returning astronauts show decreased activation and pro-inflammatory cytokine secretion with higher levels of circulating IL-10. The physical and emotional stress of space travel along with the utterly foreign environment can have varied effects on the immune system of humans.

The Mars One mission promises to safely position colonizing humans on the surface of the red planet in a staggeringly short 10 years’ time. From an immunological perspective, the feasibility of this project is entirely unknown. Although studies have shown a clear immunosuppressive effect, they rely heavily on ground-based sampling and models. This sampling method confounds the effects of space travel with the high stress of a high-impact landing and in a recent study of blood samplings onboard the ISS, many of the effects were found to be less severe. Ground-based models are never perfect and in situ studies performed on the ISS suffer from complicated culturing and isolation methods.

Mars is a desolate, dangerous, unshielded, and low-gravity (0.3 G) environment. Our fragile human bodies have undergone millions of years of evolution under the polar opposite – warm, protective, and heavy Earth. The dangers of a mission to Mars are undoubtedly high; the risks are still unknown, but the rewards potentially enormous. It’s doubtful that I will ever muster the courage to sign up for this mission, but I will watch and laud over every single moment of this human feat in engineering, dedication, and science.

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Yuriy Baglaenko

Founding Editor
Yuriy is a 4th year PhD student studying the suppression of autoimmunity at the University of Toronto. He is an avid musician with an at-home amateur recording studio and a mediocre intramural volleyball player.
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