The n e w e ng l a n d j o u r na l of m e dic i n e

Review Article

Dan L. Longo, M.D., Editor

Space Medicine in the Era

of Civilian Spaceflight
Jan Stepanek, M.D., M.P.H., Rebecca S. Blue, M.D., M.P.H.,
and Scott Parazynski, M.D.​​

S
ince the first human spaceflight by Yuri Alekseyevich Gagarin From the Aerospace Medicine and Ves-
in 1961, more than 560 persons have flown in space. The vast majority were tibular Research Laboratory, Mayo Clinic,
Scottsdale, AZ (J.S., R.S.B.); and Fluidity
highly trained and rigorously selected astronauts in excellent physical condi- Technologies, Houston (S.P.). Address
tion and health. Currently, astronauts and other participants in spaceflights to the reprint requests to Dr. Stepanek at Mayo
International Space Station must adhere to medical certification standards set by Na- Clinic, Aerospace Medicine Program,
13400 E. Shea Blvd., Scottsdale, AZ
tional Aeronautics and Space Administration (NASA) and its international partners.1-3 85259, or at ­stepanek​.­jan@​­mayo​.­edu.
The emergence of privatized commercial spaceflight is expected to afford paying
N Engl J Med 2019;380:1053-60.
customers, including those with preexisting health conditions, the opportunity to DOI: 10.1056/NEJMra1609012
fly in space. Prospective spaceflight companies and their medical departments will Copyright © 2019 Massachusetts Medical Society.

provide guidance for their suborbital participants and will also increasingly de-
pend on health documentation from clinicians who may not be familiar with the
specific challenges of various activities and mission profiles related to spaceflight.
Current U.S. law, enforced by the Department of Transportation’s Federal Aviation
Administration (FAA), Office of Commercial Space Transportation, mandates that
prospective spaceflight participants provide written informed consent after having
a clear understanding of the inherent risks of the flight.4-7 Although pilots flying
various privatized commercial space vehicles are required to hold a second-class FAA
medical certificate with its attendant medical requirements,8,9 there are currently no
medically binding criteria for determining a participant’s suitability for prospective
commercial spaceflight, beyond guidelines from several aerospace specialty organi-
zations.6,7,10,11
Space medicine is a broad clinical discipline that encompasses the many chal-
lenges facing humans engaged in spaceflight and other aerospace activities. Threats
in the space environment vary according to the duration of the flight and range from
physiological and adaptive alterations of the human body to the psychological chal-
lenges of isolation and distance from Earth. The responsibility for understanding
the ramifications of participants’ preexisting medical conditions and for ensuring the
safety of participants in the expanding spaceflight industry will fall to many clinicians
in collaboration with dedicated space medicine specialists and the aerospace commu-
nity in general. Data and experience gleaned from training and flights will, over time,
help determine the need for additional medical recommendations for persons with
certain medical conditions.
There are numerous emergency or off-nominal situations in spaceflight. An ex-
ample is the loss of integrity of a pressurization system (vehicle or space suits),
which can result in severe hypoxia or decompression illnesses. This review, however,
focuses on the nominal and expected challenges of spaceflight and aims to provide
the practicing clinician with an appreciation of the unique medical and environmental
challenges in light of the expected increase in civilian spaceflight.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Medic a l Ch a l l enge s Each of the various phases of spaceflight pres-

of Spacefl igh t ents unique challenges to the human body. During
launch activities and rocket-powered ascent to
The specific medical challenges and risks in- space, passengers experience increased noise,
herent in any space mission are defined by the vibration, and acceleration forces. The direction,
duration and trajectory of the flight (Table 1). duration, and intensity of these inertial accelera-
A suborbital spaceflight by definition reaches tion forces depend on vehicle design and the
an altitude of more than 100 km above mean sea positioning of the on-board participant (Fig. 1).
level; suborbital space flights are typically of short Most designs provide for increased inertial forc-
duration (a matter of minutes), whereas orbital es that entail primarily back-to-chest acceleration
spaceflights, such as flights to the International (+Gx), which is physiologically a more tolerable
Space Station, can last from days to many months. condition than toe-to-head acceleration (+Gz) or
Missions to the moon will typically be of extended side-to-side acceleration (±Gy). However, even back-
duration, and missions to Mars are likely to re- to-chest acceleration can cause discomfort and
quire several years. The importance of these induce anxiety in some persons.12,13
differences in duration lies in their very different Although suborbital microgravity exposures of
medical-risk profiles. For example, with flights a few minutes are unlikely to cause many adaptive
that are suborbital or in low Earth orbit, the symptoms, participants remaining in orbit for
Earth’s magnetic field and atmosphere provide longer periods may be susceptible to the develop-
shielding from space radiation. Missions beyond ment of space motion sickness, manifested as
low Earth orbit (e.g., flights to the moon or Mars) nausea, headache, and emesis, especially during
present notable challenges because of factors such the first few days.14 Spatial orientation in a three-
as substantial radiation exposure to the human dimensional microgravity environment changes
body from the ubiquitous galactic cosmic radiation from gravity-dependent neurovestibular inputs on
and possible coronal mass ejections from our sun, Earth to reliance on primarily visual reference
and the risks increase with prolonged exposure. points in spaceflight. This transition occurs dur-

Table 1. Medical and Environmental Challenges According to the Type of Spaceflight.*

Mission Profile Medical Challenges Environmental Challenges

Short-Term Long-Term
Suborbital spaceflight Anxiety, psychological factors, space Minimal Noise, vibration, acceleration forc-
motion sickness, hypocapnia es, confinement, microgravity
Low Earth orbit
Short sojourn Anxiety, psychological factors, space Minimal Microgravity adaptation: fluid shifts
(<48 hr) motion sickness, hypocapnia resulting in headache, conges-
tion; low back pain from spinal
elongation
Longer sojourn Altered T-cell function, plasma-volume Mild radiation-induced changes, Microgravity
(≥48 hr) shifts, neurovestibular deconditioning, SANS (risk proportional to
cardiovascular deconditioning, SANS flight duration)
Beyond low Earth orbit
Lunar (1–2 wk) Neurovestibular deconditioning, cardiovas- Radiation-induced changes, Microgravity, radiation, isolation
cular deconditioning, plasma-volume SANS
shifts, SANS, radiation-induced changes
Planetary (>12 mo) Radiation-induced changes, altered nutri- Radiation-induced changes, Microgravity, radiation, isolation
tional status, neurovestibular decon- altered musculoskeletal
ditioning, cardiovascular decondition- system, SANS
ing, bone and muscle loss, renal-stone
formation, plasma-volume shifts,
SANS, altered immunity

* SANS denotes spaceflight-associated neuro-ocular syndrome.

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 Space Medicine in the Er a of Civilian Spaceflight

ing the first 48 to 72 hours of exposure, when

persons are particularly sensitive to space motion +Gz
sickness and may have impaired performance of Sensation: pulled
tasks such as visual tracking and hand–eye coor- down in seat
dination. Space motion sickness can detract from
enjoyment of the first few days of spaceflight and
may require the use of antiemetic medications,
which can have unwanted side effects.14
Prolonged stays in microgravity environments +Gy
result in clinically significant physiological adap- Sensation: pushed
tations and alterations of the human body. Because to the left
of the absence of gravity-induced hydrostatic pres-
sure gradients, there is a fluid shift from the pe-
riphery of the body to the central compartment
+Gx
Sensation: pressed
and head, frequently resulting in facial puffiness back in seat
and congestion and occasionally causing head-
ache15 (Fig. 2). Over a period of several days, the
body compensates for this fluid shift through
diuresis, which reduces extracellular fluid and
plasma volume and is associated with a decrease in
body mass during the first 30 days in the micro-
gravity environment (compounded by altered met-
abolic requirements and altered appetite), followed
by stabilization at a new steady-state level.16 Car-
diac function swiftly adapts to the fluid shift–
related alterations with compensatory increases
in cardiac output.17 Fortunately, no serious car-
diac dysrhythmias or alterations are known to Figure 1. Acceleration Vectors and Associated Sensations.
be caused by spaceflight.18,19 The body sensation associated with each acceleration vector is the oppo-
Because of the absence of hydrostatic pres- site of the vector direction. Most vehicle designs provide for increased
sure gradients, baroreceptor responses are grad- inertial forces that entail primarily back-to-chest acceleration (+Gx).
ually attenuated in proportion to the amount of
time spent in microgravity (e.g., measurable
changes can be observed after approximately to a slight lengthening of the vertebral spine and
4 days in microgravity, as described during Space skeletal deconditioning.24 These factors are asso-
Shuttle missions).20,21 On the return to Earth, this ciated with an increased incidence of back pain
baroreceptor attenuation can initially result in and an increased risk of intervertebral disk her-
orthostatic hypotension, until gradual readapta- niation.25 Participants in spaceflight who remain
tion to terrestrial gravity occurs. Pulmonary func- in orbit for days to weeks may have this discom-
tion and gas exchange do not appear to be nega- fort; in particular, persons with preexisting back
tively affected and, hence, should not limit human or neck conditions or chronic pain may be sus-
performance in microgravity.22,23 The absence of ceptible to exacerbation of underlying signs and
natural ambient airflow patterns raises the pos- symptoms. The near absence of gravity also leads
sibility of a relative accumulation of exhaled car- to relative changes in abdominal organ position,
bon dioxide surrounding a person, which can lead with a headward shift of the diaphragm, influenc-
to a gradual increase in carbon dioxide through ing findings on physical examination and im-
rebreathing of the exhaled air. This concern is aging studies such as ultrasonography. This dia-
addressed by adequate air circulation in enclosed phragmatic shift also causes a 15% decrease in
areas of space vehicles, as well as efficient carbon functional residual capacity and a mild decrease
dioxide scrubbing (i.e., absorption and removal of in ventilation, which appear to have a minimal
carbon dioxide) in the space vehicle atmosphere. effect on gas exchange and alveolar ventilation
Prolonged exposure to microgravity can lead because of improved ventilation–perfusion match-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

loss of bone mineralization due to the unloading

Short-term physiological alterations Long-term physiological alterations
of the skeleton. Loss of bone mineral density has
been shown in the lumbar spine, pelvis, trochan-
Central fluid shift (nasal ter, femoral neck, and calcaneus.30 Certain areas of
SANS
and sinus congestion, the skeleton have no detrimental change (e.g., the
headache) Transient orthostatic symptoms ulna and radius) and some may have an increase
on reexposure to gravity
Neurovestibular changes in bone density (the skull). Bone density loss is
associated with motion
Bone density loss a serious concern for long missions (e.g., a flight
sickness
to Mars); however, countermeasures such as con-
sistent resistance and aerobic exercise, nutritional
Back pain support, and use of antiresorptive medications
Nephrolithiasis have been shown to help preserve bone density.31,32
In line with the potential loss of bone mineral
Anxiety
density, loss of skeletal-muscle strength is a seri-
Radiation-induced changes
ous concern during long spaceflights.33 Skeletal-
muscle loss can contribute to postflight ortho-
static symptoms on reexposure to gravity and
may hamper the ability to safely carry out tasks
Muscle deconditioning required on the return to Earth or arrival at a
more distant destination, such as the surface of
Mars. The detrimental effects of prolonged mi-
crogravity on bone and muscular architecture
are more likely to affect career astronauts, until
participants in commercial spaceflights have op-
portunities to take part in long missions.
In 2011, a sentinel case of unusual neuro-
Figure 2. Short-Term and Long-Term Physiological Alterations Associated
with Spaceflight.
ocular symptoms associated with long-duration
SANS denotes spaceflight-associated neuro-ocular syndrome.
spaceflight was reported.34 This led to the recog-
nition of a constellation of symptoms that define
spaceflight-associated neuro-ocular syndrome, or
SANS. Findings include variable optic disk edema,
ing in the absence of gravity. Sleep aboard space refractive changes (distance vision more affected
vehicles is often suboptimal because of multiple than near vision) that are often unilateral (right
factors, including ambient noise, a tight opera- eye affected more often than left eye), and infarcts
tional schedule, circadian dysregulation, conges- in the nerve-fiber layer with associated cotton wool
tion due to fluid shifts, back discomfort, and an spots.35-38 Flattening of the optic globe can be iden-
unfamiliar sleeping environment with a lack of tified on magnetic resonance imaging, and ocu-
gravity-related proprioceptive input.26,27 lar coherence tomography can show venous en-
Additional system-specific concerns have been gorgement and choroidal thickening or folding.
reported even for short spaceflights. For example, It has been postulated that this syndrome may
there have been several case reports of urinary be related to intracranial hypertension associated
retention in the first days after entering micro- with microgravity-induced fluid shifts, though this
gravity.28,29 Typically, this condition is self-resolv- hypothesis continues to undergo review and con-
ing and rarely requires a temporary period of self- sideration of alternative explanations.37 Recent
catheterization. However, for the lay participant, findings suggest that the syndrome may be as-
such experiences may greatly reduce enjoyment of sociated with body mass and potential alterations
the flight. Furthermore, self-catheterization adds in one-carbon metabolism pathways.39 The syn-
additional risks such as microtrauma and the in- drome is currently the focus of intensive study;
troduction of infection, altering the mission risk at this point, it remains unclear whether SANS
profile and introducing a potential need for more could pose a serious risk to participants in fu-
comprehensive medical evaluation or care. ture spaceflights of long duration or whether
Prolonged sojourns in microgravity result in any preexisting morphologic, genetic, or physio-

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 Space Medicine in the Er a of Civilian Spaceflight

logical factors might alter or help predict and be mitigated by just-in-time refresher training.
mitigate this risk. Increasing distance from Earth introduces a com-
munications delay — up to 40 minutes for Mars
missions — that poses a challenge to emergency
Ps ychol o gic a l Ch a l l enge s
of Spacefl igh t real-time assistance (e.g., telemedicine guidance
from ground-based medical support); furthermore,
Isolation from friends and family can be a chal- evacuating and returning to Earth is no longer
lenge on long missions, as can conflict among possible.42,43 Therefore, on-board medical expertise
flight participants. The selection of compatible will be of even greater value.
teammates for long-duration flights is particu-
larly important for the success of the mission. A r e a s of Uncer ta in t y
Even during commercial flights of shorter dura-
tion, the choice of crewmates may greatly affect The available medical literature on human re-
a participant’s experience. In addition, the unusual sponses to spaceflight is based predominantly on
environment and spaceflight-associated stressors a male population of fit professional astronauts,
may induce anxiety in a participant, with unpre- many of whom have military experience. Although
dictable manifestations that may affect that per- several self-funded civilians, some with known
son’s experience or the experience of fellow par- preexisting health problems, have flown suc-
ticipants. Careful observation by medical support cessfully to the International Space Station,44-46
staff during high-fidelity training may reveal ab- the number (seven participants in total) is too
normal or disruptive reactions of potential par- small to aid in providing broad recommendations
ticipants to flight-related stressors.13 for large numbers of prospective spaceflight par-
ticipants.
The FAA is responsible for the regulation of
L imi tat ions of Medic a l Supp or t
commercial space transportation in the United
Medical support capabilities are inherently lim- States and has commissioned studies of human
ited during spaceflights,40 reinforcing the need health and performance in commercial space-
for careful mission planning and assessment of flight. Three studies have been performed to date
medical risk for each participant. The safety of a that have specifically investigated the ability of
short suborbital flight rests in the ability to laypersons to tolerate the stresses of simulated
swiftly return to medical support infrastructure suborbital spaceflights.12,13,47 The participants in
on the ground. It is unlikely that commercial these studies were subjected to centrifuge tests
spaceflight vehicles will carry medical resources or simulating the acceleration profiles (+Gx and +Gz)
attendants with medical skills; therefore, man- that are expected to occur on suborbital space-
agement of any medical event occurring during flights. The study participants ranged from 19 to
flight will probably take place only after landing. 89 years of age and had a large variety of stable
In the event of a serious injury during a long flight, medical conditions that are prevalent in the gen-
the probability of a successful medical evacuation eral population, including hypertension, pulmo-
or complex longer-term care while on board the nary disease, stable coronary artery disease, and
space vehicle is low. Medical support during lon- diabetes; some of the participants were taking
ger-duration missions in low Earth orbit, such as medications to treat their disorders. Participants
aboard the International Space Station, is provided with well-controlled medical conditions were able
by communication with medical teams on the to physiologically tolerate the acceleration profiles
ground and resources that are available aboard in the centrifuge without difficulty. However,
the orbiting station, including medical supplies 6% of the study participants chose to stop the
(e.g., medications and blood products) — which centrifuge exposure, most often because of anxi-
are limited in variety, amount, and shelf life — ety or motion sickness, and 14% of participants
and a limited supply of medical equipment, such had unsafe or potentially problematic behaviors.13
as ultrasound machines.41 Medical support is also The importance of gathering and publishing
provided by medical officers who are part of the data from the training of prospective spaceflight
crew. Erosion of critical emergency skills on the participants in order to inform and enhance safety
part of these medical officers can occur and can and mitigate risks cannot be overstated. Fortu-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

nately, it appears that most participants in space- landing as a result of the stresses of reentry and
flight are very willing to take part in biomedical readaptation). Deliberate attention to these aspects
studies and even to voluntarily provide their data in preparation for the spaceflight, medical assess-
for review and publication.44,45,47 Even so, it is likely ment, and preventive strategies may be warranted.
that many advances in our understanding of how The diagnosis of any clinically significant allergies
the average person performs during spaceflight (e.g., food allergies) before prolonged spaceflights
will be achieved only after commercial spaceflight may be of particular importance as well.
becomes more commonplace and aggregate data
are gathered and reported in the medical literature. Medic ol eg a l C onsider at ions
The challenge for space medicine profession-
als rests in the limited amount of time they will As the space-faring population shifts from highly
be able to spend with commercial spaceflight par- screened career astronauts to lay participants who
ticipants, whereas members of the medical sup- may have preexisting medical conditions, there
port staff work closely with professional astronauts will be a shift in the medicolegal considerations
and spend many months training as a team. The and liability for the space industry as a whole.
Code of Federal Regulations stipulates that the Although the goal of the commercial spaceflight
training of prospective spaceflight participants industry has been to expand access to space and
is to be focused on their ability “to be able to aim for inclusiveness in participation, there is
respond in case of an emergency.”48 There are no some concern that persons with a clinically sig-
specified training requirements beyond that ge- nificant medical history may not be able to toler-
neric statement. A strong collaboration among fu- ate the stressors of flight. There is a need to bal-
ture spaceflight participants, the clinicians who ance the desire to protect laypersons who have
care for them, and the industry operators is neces- medical conditions by restricting their access to
sary to understand the risks for individual partici- spaceflight with respect for their autonomy in
pants, their capacity for informed consent, and making decisions regarding risk, informed con-
their training needs in order to ensure an appro- sent, and participation despite potential adverse
priate response in the case of an emergency. outcomes.
The preparation and training will certainly be The FAA has indicated a preference for partici-
less rigorous for a short suborbital flight than pant autonomy, specifically stating that those de-
for an extended stay in low Earth orbit or a lunar siring to participate in spaceflight have the right
mission. Participants in suborbital spaceflight will and responsibility to make their own decisions
need some degree of team training and practice of regarding risk and informed consent.53 The ad-
emergency procedures; they also will possibly ministration has placed the burden of education
need training in an analogue environment, such on the spaceflight industry itself, requiring that
as centrifuge exposures, parabolic flights, and commercial operators inform all potential space-
altitude-chamber training, to become familiar flight participants of all spaceflight-related risks
with environmental stressors and life-support sys- and ensure that participants understand these
tems. Participants in longer-duration missions, risks before consenting to participate.1,2 However,
especially persons with preexisting health condi- it is difficult to legally show that participants fully
tions who are critically reliant on a healthy im- understand their risks and the legality of their own
mune system, may also be subject to the known consent, raising concern about potential liability
effects of the spaceflight environment (thought despite the consent process. It is unlikely that even
to be mediated by radiation and stress responses) the mandated informed-consent process will pre-
on immune function. Alterations in T-cell func- vent the potential for legal claims between par-
tion, the skin microbiome, and bacterial viru- ticipants and industry providers in the case of
lence, as well as asymptomatic viral reactivation, mishap or injury.54,55
have been described.49-52 On the basis of current
data, it is difficult to definitively discern which C onclusions
factors in humans appear to be the root cause for
some of the alterations that have been reported The field of space medicine is poised for a sub-
(e.g., an increase in the neutrophil count after stantial transition from primarily government-

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 Space Medicine in the Er a of Civilian Spaceflight

focused spaceflights carrying a few career astro- guidance for persons with certain medical con-
nauts to a large and diverse group of participants, ditions. A strong collaboration among practicing
mainly private citizens, who will be traveling to clinicians, space medicine specialists, and the
space, in most cases for short suborbital missions aerospace community will ensure the safety of
but in some cases to locations in low Earth orbit the participants in the expanding spaceflight
or farther. Data and experience accumulated from industry.
mission training and actual spaceflights will Disclosure forms provided by the authors are available with
help determine the need for additional medical the full text of this article at NEJM.org.

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