The concept of human space exploration has experienced something of a recent revival in the public consciousness. The private SpaceX and Virgin Galactic companies (and their eccentric front men) often make front-page news for their achievements and goals, which ultimately involve traveling to and colonizing distant planets. Though some decry these ambitions as extravagant fantasies, news pertaining to novel developments in extraterrestrial exploration often goes viral over digital media, reflecting genuine public interest in the topic.

Though we are technologically closer to realizing long-distance space travel than we were 50 years ago, significant engineering, financial and logistical obstacles remain. The health and well-being of participants on future exploratory or colonization missions encompasses all of the aforementioned. The medical needs of future explorers and colonists must be adequately met in the face of arguably the most adverse and unpredictable conditions humans will ever venture into.

Furthermore, human participants will also serve as test subjects for extraterrestrial exposure, for durations exceeding existing previous records. The extraterrestrial environment subjects human physiology to a range of physical forces, including microgravity, extreme temperatures, ionospheric plasma and galactic radiation. Each of these causes unique alterations to the physiology of individual body systems. Not only must the biological effects of individual forces on isolated body systems be ascertained, models should also be developed for predicting the whole-body effects produced by simultaneous multi-organ exposure to multiple extraterrestrial forces.

The effect produced by microgravity exemplifies the potential for a single (albeit significant) environmental change to induce profound multi-systemic consequences to human physiology. On Earth, gravity pulls fluids to the lower extremities. In space, absence of gravity causes fluids to redistribute evenly throughout the body. The heart receives an increased volume of fluid returning to it, and compensates by increasing stroke volume. Under terrestrial conditions, increases in stroke volume are usually accompanied by increases in heart rate to boost total cardiac output. In space, distension of the upper-body vasculature induces carotid baroreflexes, which in fact cause a reduction of heart rate via parasympathetic effect.

Despite no alteration to total body fluid volume, the distension of large central vessels produces another paradoxical change: suppression of the so-called renin-angiotensin-aldosterone axis, resulting in net salt and water excretion and increasing hematocrit due to hemoconcentration. Long-term exposure to these conditions produces chronic decreases in heart rate, and cardiac muscular remodelling is also observed. Upon return to Earth (and its gravitational field), this prolonged cardiac deconditioning may cause severe orthostatic intolerance, necessitating a significant readjustment period. The common science fiction portrayal of astronauts running on treadmills while aboard spacecraft has a basis in fact; countermeasures to offset the aforementioned cardiac changes involve regular high-intensity cardiovascular exercise.

The human skeleton and its supportive musculature have evolved in the constant presence of background gravity. In space, absence of the gravitational force’s stimulus causes atrophy of the supportive bones and muscles. As a result, weight-bearing bones undergo significant demineralization, detected by increased levels of excreted phosphate and calcium in bodily waste, and other markers of increased bone resorption. Osteoporosis-like conditions may be induced with prolonged exposure (such as the proposed 2.5-year-long round trip to Mars), and participants may be at risk of fractures produced by even minimal trauma. Increased levels of carbon dioxide and lack of natural sunlight (and Vitamin D) in the confined spacecraft may compound the demineralization process. In conjunction with bony demineralization, the slow-twitch (type 1) muscles surrounding and supporting the postural skeleton also begin to atrophy in the absence of gravity.

An example of how microgravity-induced bone and muscular atrophy may act synergistically to produce pathology is demonstrated by an increased incidence of lumbar and cervical vertebral disc herniation in astronauts following spaceflight. Again, regular high-intensity exercises such as running or resistance-training may serve to offset these degenerative changes.

Radiation exposure is another concern for mission planners. Future explorers may be subjected to high levels of radiation from galactic cosmic rays and solar particle events. These differ from terrestrial radiation sources in that they are high-energy particles rather than electromagnetic waves, e.g., x-rays. High-energy particles are thought to have a strong capacity to damage biological tissues by producing free radicals, which oxidatively damage deoxyribonucleic acid (DNA) within cellular nuclei, among other effects.

Accumulation of DNA damage may induce cellular death (pre-programmed or unprogrammed) or lead to mutations in genes responsible for regulating the cellular life cycle, i.e., causing cancer. The risk of cancer is a significant worry for all participants traveling for long durations. Aside from cancer risk, space radiation is thought to induce other systemic pathologies such as damage to small-caliber blood vessels, induction of neurodegenerative processes similar to Alzheimer’s and premature aging. Adequate shielding of the spacecraft and spacesuits may serve to negate these adverse radiation effects.

In space, changes to the central nervous system result from exposure to multiple physical forces. On Earth, intracranial pressure (ICP) is tightly regulated by the cerebral blood vessels. The shift of fluid towards the head produces rises in ICP. Potentially compounding an increase in arterial blood volume is an engorgement of the large vessels draining the head, such as the jugular veins. On Earth and when upright, spontaneous venous return from structures above the heart occurs as a result of gravity. In space, congestion of large-caliber veins occurs because of the lack of gravity.

This effect is thought to contribute to a rise in intracranial pressure and facial swelling, and is known as “space obstructive syndrome.” Further compounding these physical fluid shifts is the presence of increased carbon dioxide levels within the enclosed spacecraft, present as a metabolic waste product by crew. Increases in carbon dioxide are known to produce dilation of the intracranial blood vessels. Consequently, incidence of headache among crew members is proportionally linked to cabin carbon dioxide levels. If head trauma occurs to an astronaut by accident (e.g., during a space walk or impact), it is not known if trauma occurring upon a background of already increased ICP will be more severe compared to head trauma of the same magnitude occurring on Earth.

The human vestibular system is a series of fluid-filled canals within the skull, responsible for sensation of balance and orientation. When head acceleration occurs, shifts of fluid within the vestibular canals move the microscopic hairs at their base, inducing a sensory signal that travels to the brain. These vestibular signals are integrated with visual input to allow physical orientation, enabling balance and hand-eye coordination. In space, fluid shifts can significantly disrupt vestibular physiology, producing “space motion sickness” phenomena. Space motion sickness causes disorientation, nausea and vomiting, and can be severe enough to incapacitate a crew member. It may also alter hand-eye coordination, resulting in decreased ability to conduct fine-motor tasks that may be crucial to mission success. After several hours to days, most acclimatize to the novel physical environment; however in severe cases, acclimation does not occur and medications such as traditional anti-emetics may be required.

An increase in the virulence of microorganisms is also observed in space. Studied species have included the bacteria Salmonella and Pseudomonas and the Candida species of fungus, all of which are common sources of infection on Earth. Experiments conducted in low-Earth orbit have demonstrated increased bacterial production of factors permitting their enhanced growth and invasive ability. Spaceflight experiments using E. coli, another common terrestrial pathogen, demonstrated a shrinkage in organism size, a thickening of their cell membranes and enhanced tendency to grow in clusters, all of which boost their ability to resist antibiotic action.

When enhanced bacterial pathogenicity is combined with a weakening of the host immune system, close-quarters cohabitation and increased stress responses seen during spaceflight, risk of infection may be significant for the crew relative to Earth. Larger doses of standard antibiotics may therefore be required to fight infection. Though increasing dose is simple in theory, in the context of shifted body fluids, drug pharmacodynamic profiles may be significantly altered. For example, many drug by-products are excreted by the kidney through urine. Renal filtration rate may be altered by the shift of fluids into the upper body vasculature, meaning that drug metabolites are not excreted rapidly enough, potentially leading to a buildup of toxins in the bloodstream.

Though humans have been to space since the early 1960s, reported pathology arising during spaceflight has been minimal. Contingency planning is therefore based largely upon speculative scenarios. Pathology may include trauma or intrinsic ailments, both imposed upon altered physiology. Healing of pathology may also be compromised in this adverse environment given the immune dysregulation, increased steroid stress hormones, heightened microbial virulence and altered drug pharmacodynamics in space.

Trauma is of particular concern given that future space participants may conduct space walks or planetary exploration. Even in reduced gravity, objects still retain their mass and can produce severe acceleration-type injuries. Risk of trauma may be minimized by proper space suit and helmet design. Due to bone demineralization, relatively minor forces can cause disproportionately severe fractures, potentially compromising mission success. Another particular concern is that of appendicitis, a common condition. There have been at least two reported incidences of suspected appendicitis arising in Russian cosmonauts, neither of which actually were such upon further (presumably costly) investigation.

As real appendicitis is a medical emergency, requiring immediate surgery, false diagnoses are highly undesirable and may abruptly end the mission. In light of this risk, some have proposed prospective crew undergo preemptive appendicectomy prior to spaceflight, similar to the protocol required of participants on long-term missions to Antarctica, another remote area without easy access to modern health care facilities.

To tackle potential medical issues arising in space, not only must planners tackle the uncertainties pertaining to mechanisms, presentation and severity of pathology, but also the extreme limitations in diagnostic and treatment capabilities available on board a spacecraft. As previously discussed, all body systems are potentially affected by the extraterrestrial environment, and pathology may involve single or multiple systems simultaneously. On Earth, certain protocols such as Advanced Trauma and Life Support exist for treatment of trauma—devised to provide a universal approach to the critically injured patient and to rapidly diagnose potentially life-threatening physiological decompensations. Mission participants, whether physicians or non-physicians, should be adequately trained in these principles, with necessary modifications and contingencies to account for physiological changes produced in space.

In cases of severe compromise, for example those requiring assisted breathing, facial swelling may complicate the intubation process. In cases of severe hypotension, it is not known how administration of large volumes of fluid such as saline will affect somebody with existing physiological and pathological decompensation. Furthermore, supplies of life-saving equipment and medication, for example infusible fluids may be limited. A proposed way to tackle this issue is to allow for on board self-sustainability—for example a device that can turn the drinking water supply into fluid suitable for intravenous infusion.

Similarly, a three-dimensional (3D) printer may be included on board, with ability to rapidly fabricate equipment such as scalpels, bandages, casts or even pharmaceuticals for as-needed use. A single 3D printer may therefore save critical space by allowing for as-needed fabrication rather than carrying a space-occupying yet finite supply of medical equipment.

In situations of internal bleeding when simple tourniquets are inappropriate, more drastic surgery may be warranted. Relative to Earth, surgery in space may carry greater risks. For example, the intestines are essentially free floating within the abdomen, tethered only to the posterior abdominal wall by the mesentery. Consequent to microgravity, bowel may therefore freely float out of an abdominal incision, creating a risk of contamination or damage. In cases of bleeding in space, blood does not collect or pool in the same way it does on Earth, but instead forms domes or miniature droplets on surfaces.

If these domes are disrupted by instruments, blood may float off the surface, potentially creating a biohazard. As surgery is a fine-motor task, vestibular disruption (previously discussed) may make performing even simple surgical tasks incredibly difficult and time-consuming. Inclusion of a surgical robot may address onboard surgical needs. Surgical robots have become widely used in certain surgical subspecialties, particularly urology. They utilize arm-like actuators that actually have a greater range of motion and are not susceptible to fatigue compared to the human hand. Commonly they are situated a short distance from the patient, with the operating surgeon controlling it in real time using “video game–like” controllers. The distance between the surgeon and robot can potentially be expanded, and robotic surgery has been conducted underwater and even across the Atlantic Ocean. Though this would effectively permit a surgeon on Earth to perform surgery in space, as distance between the surgeon and robot increases, the time taken for radio signals to travel in between operator and robot also increase.

For example, Mars is several million miles from earth. Radio signals can take more than 20 minutes to travel from Earth to Mars. Obviously, if a patient were critically ill or actively bleeding, this time delay renders the technology impractical. As of present, it seems like a medically trained crew member is essential personnel. Recently, fully autonomous robotic surgery in an animal was demonstrated for the first time. If this technology is developed into a feasible solution for human surgery, an autonomous surgical robot could address the issue of needing an onboard surgeon and also allow independence from Earth-based surgical solutions.

The extraterrestrial environment subjects humans to numerous adverse physical forces, each of which can produce multiple effects throughout the body. The body of evidence available in the literature largely pertains to individual forces (e.g., microgravity) acting upon individual systems (e.g., the cardiovascular system). The cumulative effects on the whole body are harder to predict. For example, when considering the danger of space radiation, predictive models of mortality risk secondary to cancer have been devised. NASA places the overall cumulative risk of cancer mortality for Mars mission participants at less than 10 percent; however others have predicted it to be as high as 50 percent. Due to the large number of variables incorporated into modelling space radiation risk, calculations may become large and unwieldy.

Machine learning (ML), a branch of artificial intelligence, has been proposed to tackle these problems. ML is ideally suited to very large, complex data sets that are difficult or even impossible for humans to interpret using traditional statistical methods. ML techniques are already being applied to large health care databases to delineate novel relationships between variables or for clinical prediction. ML may present a viable approach to link the systemically disparate arms of research into spaceflight physiology and pathology, and to predict how superimposed pathology may affect an already altered body.

It is obvious that long-term exposure to extraterrestrial conditions, even without any “pathology,” can significantly alter body physiology. It is unknown how pathology may occur or present in space, though we can make predictions based upon our existing knowledge and the known body changes occurring in space. Planners must consider these issues if long-distance space travel or colonization is to be realized. Though the concept of “space medicine” or “space surgery” may seem esoteric to the average person, this article has attempted to “demystify” fundamental concepts and research into theories that most with basic scientific knowledge should understand.