Dan Burbank and Anton Shkaplerov participate in a medical contingency drill in the Destiny laboratory of the International Space Station. This drill gives crew members the opportunity to work as a team in resolving a simulated medical emergency on board the space station.[1]

Space medicine is an area in aerospace medicine that focuses on the medical care of astronauts and spaceflight participants. The spaceflight environment poses many unique stressors to the human body, including G forces, microgravity, unusual atmospheres such as low pressure or high carbon dioxide, and space radiation. Space medicine applies space physiology, preventive medicine, primary care, emergency medicine, acute care medicine, austere medicine, public health, and toxicology to prevent and treat medical problems in space. This expertise is additionally used to inform vehicle systems design to minimize the risk to human health and performance while meeting mission objectives.

Astronautical hygiene is the application of science and technology to the prevention or control of exposure to the hazards that may cause astronaut ill health. Both these sciences work together to ensure that astronauts work in a safe environment. Medical consequences such as possible visual impairment and bone loss have been associated with human spaceflight.[2][3]

In October 2015, the NASA Office of Inspector General issued a health hazards report related to space exploration, including a human mission to Mars.[4][5]

History

Hubertus Strughold (1898–1987), a former Nazi physician and physiologist, was brought to the United States after World War II as part of Operation Paperclip.[6] He first coined the term "space medicine" in 1948 and was the first and only Professor of Space Medicine at the School of Aviation Medicine (SAM) at Randolph Air Force Base, Texas. In 1949, Strughold was made director of the Department of Space Medicine at the SAM (which is now the US Air Force School of Aerospace Medicine (USAFSAM) at Wright-Patterson Air Force Base, Ohio. He played an important role in developing the pressure suit worn by early American astronauts. He was a co-founder of the Space Medicine Branch of the Aerospace Medical Association in 1950. The aeromedical library at Brooks AFB was named after him in 1977, but later renamed because documents from the Nuremberg War Crimes Tribunal linked Strughold to medical experiments in which inmates of the Dachau concentration camp were tortured and killed.[7]

Soviet research into Space Medicine was centered at the Scientific Research Testing Institute of Aviation Medicine (NIIAM). In 1949, A.M. Vasilevsky, the Minister of Defense of the USSR, gave instructions via the initiative of Sergei Korolev to NIIAM to conduct biological and medical research. In 1951, NIIAM began to work on the first research work entitled "Physiological and hygienic substantiation of flight capabilities in special conditions", which formulated the main research tasks, the necessary requirements for pressurized cabins, life support systems, rescue and control and recording equipment. At the Korolev design bureau, they created rockets for lifting animals within 200–250 km and 500–600 km, and then began to talk about developing artificial satellites and launching a man into space.[8] Then in 1963 the Institute for Biomedical Problems (IMBP) was founded to undertake the study of space medicine.[9]

Animal testing

Main article: Animals in space

Before sending humans, space agencies used animals to study the effects of space travel on the body.[10] After several years of failed animal recoveries, an Aerobee rocket launch in September 1951 was the first safe return of a monkey and a group of mice from near space altitudes.[11] On 3 November 1957, Sputnik 2 became the first mission to carry a living animal to space, a dog named Laika. This flight and others suggested the possibility of safely flying in space within a controlled environment, and provided data on how living beings react to space flight.[10] Later flights with cameras to observe the animal subjects would show in flight conditions such as high-G and zero-G.[11] Russian tests yielded more valuable physiological data from the animal tests.[11]

On January 31, 1961, a chimpanzee named Ham was launched into a sub-orbital flight aboard a Mercury-Redstone Launch Vehicle. The flight was meant to model the planned mission of astronaut Alan Shepard. The mission planned to reach an altitude of 115 miles, and speeds up to 4400 miles per hour.[12] However, the actual flight reached 157 miles and a maximum speed of 5857 miles per hour.[12] During flight, Ham experienced 6.6 minutes of weightlessness. After splashing down in the Atlantic Ocean, Ham was recovered by the USS Donner.[13] He suffered only limited injuries during flight, only receiving a bruised nose.[14] Ham's vital signs were monitored and collected throughout the 16 minute flight, and used to develop life support systems for later human astronauts.[14]

Animal testing in space continues currently, with mice, ants, and other animals regularly being sent to the International Space Station.[15] In 2014, eight ant colonies were sent to the ISS to investigate the group behavior of ants in microgravity. The ISS allows for the investigation of animal behavior without sending them in specifically designed capsules.[15]

North American X-15

Main article: North American X-15

Rocket-powered aircraft North American X-15 provided an early opportunity to study the effects of a near-space environment on human physiology.[16] At its highest operational speed and altitude, the X-15 provided approximately five minutes of weightlessness. This opportunity allowed for the development of devices to facilitate working in low pressure, high acceleration environments such as pressure suits, and telemetering systems to collect physiological data.[17] This data and technologies allowed for better mission planning for future space missions.[17]

Project Mercury

Main article: Project Mercury

Space medicine was a critical factor in the United States human space program, starting with Project Mercury.[18] The main precaution taken by Mercury astronauts to defend against high G environments like launch and reentry was a couch with seat belts to make sure astronauts were not forcibly moved from their position. Additionally, experienced pilots proved to be better able to cope with high G scenarios.[11] One of the pressing concerns with Project Mercury's mission environment was the isolated nature of the cabin. There were deeper concerns about psychological issues than there were about physiological health effects. Substantial animal testing proved beyond a reasonable doubt to NASA engineers that spaceflight could be done safely provided a climate controlled environment.[11]

Project Gemini

The Gemini program primarily addressed the psychological issues from isolation in space with two crewmembers. Upon returning from space, it was recorded that crewmembers experienced a loss of balance and a decrease in anaerobic ability.[19]

Project Apollo

The Apollo program began with a substantial basis of medical knowledge and precautions from both Mercury and Gemini. The understanding of high and low G environments was well documented and the effects of isolation had been addressed with Gemini and Apollo having multiple occupants in one capsule. The primary research of the Apollo Program focused on pre-flight and post-flight monitoring.[19] Some Apollo mission plans were postponed or altered due to some or all crewmembers contracting a communicable disease. Apollo 14 instituted a form of quarantine for crewmembers so as to curb the passing of typical illnesses.[19] While the efficacy of the Flight Crew Health Stabilization Program was questionable as some crewmembers still contracted diseases,[19] the program showed enough results to maintain implementation with current space programs.[20]

Effects of space-travel

The effects of microgravity on fluid distribution around the body (greatly exaggerated) (NASA)

Main article: Effect of spaceflight on the human body

In October 2018, NASA-funded researchers found that lengthy journeys into outer space, including travel to the planet Mars, may substantially damage the gastrointestinal tissues of astronauts. The studies support earlier work that found such journeys could significantly damage the brains of astronauts, and age them prematurely.[21]

In November 2019, researchers reported that astronauts experienced serious blood flow and clot problems while on board the International Space Station, based on a six-month study of 11 healthy astronauts. The results may influence long-term spaceflight, including a mission to the planet Mars, according to the researchers.[22][23]

Blood clots

Deep vein thrombosis of the internal jugular vein of the neck was first discovered in 2020 in an astronaut on a long duration stay on the ISS, requiring treatment with blood thinners.[24] A subsequent study of eleven astronauts found slowed blood flow in the neck veins and even reversal of blood flow in two of the astronauts.[25] NASA is currently conducting more research to study whether these abnormalities could predispose astronauts to blood clots.

Cardiac rhythms

Main article: Cardiac rhythm problems during space flight

Heart rhythm disturbances have been seen among astronauts.[26] Most of these have been related to cardiovascular disease, but it is not clear whether this was due to pre-existing conditions or effects of space flight. It is hoped that advanced screening for coronary disease has greatly mitigated this risk. Other heart rhythm problems, such as atrial fibrillation, can develop over time, necessitating periodic screening of crewmembers’ heart rhythms. Beyond these terrestrial heart risks, some concern exists that prolonged exposure to microgravity may lead to heart rhythm disturbances. Although this has not been observed to date, further surveillance is warranted.

Decompression illness in spaceflight

In space, astronauts use a space suit, essentially a self-contained individual spacecraft, to do spacewalks, or extra-vehicular activities (EVAs). Spacesuits are generally inflated with 100% oxygen at a total pressure that is less than a third of normal atmospheric pressure. Eliminating inert atmospheric components such as nitrogen allows the astronaut to breathe comfortably, but also have the mobility to use their hands, arms, and legs to complete required work, which would be more difficult in a higher pressure suit.

After the astronaut dons the spacesuit, air is replaced by 100% oxygen in a process called a "nitrogen purge". In order to reduce the risk of decompression sickness, the astronaut must spend several hours "pre-breathing" at an intermediate nitrogen partial pressure, in order to let their body tissues outgas nitrogen slowly enough that bubbles are not formed. When the astronaut returns to the "shirt sleeve" environment of the spacecraft after an EVA, pressure is restored to whatever the operating pressure of that spacecraft may be, generally normal atmospheric pressure. Decompression illness in spaceflight consists of decompression sickness (DCS) and other injuries due to uncompensated changes in pressure, or barotrauma.

Decompression sickness

Decompression sickness is the injury to the tissues of the body resulting from the presence of nitrogen bubbles in the tissues and blood. This occurs due to a rapid reduction in ambient pressure causing the dissolved nitrogen to come out of solution as gas bubbles within the body.[27] In space the risk of DCS is significantly reduced by using a technique to wash out the nitrogen in the body's tissues. This is achieved by breathing 100% oxygen for a specified period of time before donning the spacesuit, and is continued after a nitrogen purge.[28][29] DCS may result from inadequate or interrupted pre-oxygenation time, or other factors including the astronaut's level of hydration, physical conditioning, prior injuries and age. Other risks of DCS include inadequate nitrogen purge in the EMU, a strenuous or excessively prolonged EVA, or a loss of suit pressure. Non-EVA crewmembers may also be at risk for DCS if there is a loss of spacecraft cabin pressure.

Symptoms of DCS in space may include chest pain, shortness of breath, cough or pain with a deep breath, unusual fatigue, lightheadedness, dizziness, headache, unexplained musculoskeletal pain, tingling or numbness, extremities weakness, or visual abnormalities.[30]

Primary treatment principles consist of in-suit repressurization to re-dissolve nitrogen bubbles,[31] 100% oxygen to re-oxygenate tissues,[32] and hydration to improve the circulation to injured tissues.[33]

Barotrauma

Barotrauma is the injury to the tissues of air filled spaces in the body as a result of differences in pressure between the body spaces and the ambient atmospheric pressure. Air filled spaces include the middle ears, paranasal sinuses, lungs and gastrointestinal tract.[34][35] One would be predisposed by a pre-existing upper respiratory infection, nasal allergies, recurrent changing pressures, dehydration, or a poor equalizing technique.

Positive pressure in the air filled spaces results from reduced barometric pressure during the depressurization phase of an EVA.[36][37] It can cause abdominal distension, ear or sinus pain, decreased hearing, and dental or jaw pain.[35][38] Abdominal distension can be treated with extending the abdomen, gentle massage and encourage passing flatus. Ear and sinus pressure can be relieved with passive release of positive pressure.[39] Pretreatment for susceptible individuals can include oral and nasal decongestants, or oral and nasal steroids.[40]

Negative pressure in air fill spaces results from increased barometric pressure during repressurization after an EVA or following a planned restoration of a reduced cabin pressure. Common symptoms include ear or sinus pain, decreased hearing, and tooth or jaw pain.[41]

Treatment may include active positive pressure equalization of ears and sinuses,[42][39] oral and nasal decongestants, or oral and nasal steroids, and appropriate pain medication if needed.[40]

Decreased immune system functioning

Astronauts in space have weakened immune systems, which means that in addition to increased vulnerability to new exposures, viruses already present in the body—which would normally be suppressed—become active.[43] In space, T-cells do not reproduce properly, and the cells that do exist are less able to fight off infection.[44] NASA research is measuring the change in the immune systems of its astronauts as well as performing experiments with T-cells in space.

On April 29, 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight on the International Space Station, microbes seem to adapt to the space environment in ways "not observed on Earth" and in ways that "can lead to increases in growth and virulence".[45]

In March 2019, NASA reported that latent viruses in humans may be activated during space missions, adding possibly more risk to astronauts in future deep-space missions.[46]

Increased infection risk

A 2006 Space Shuttle experiment found that Salmonella typhimurium, a bacterium that can cause food poisoning, became more virulent when cultivated in space.[47] On April 29, 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight on the International Space Station, microbes seem to adapt to the space environment in ways "not observed on Earth" and in ways that "can lead to increases in growth and virulence".[45] More recently, in 2017, bacteria were found to be more resistant to antibiotics and to thrive in the near-weightlessness of space.[48] Microorganisms have been observed to survive the vacuum of outer space.[49][50] Researchers in 2018 reported, after detecting the presence on the International Space Station (ISS) of five Enterobacter bugandensis bacterial strains, none pathogenic to humans, that microorganisms on ISS should be carefully monitored to continue assuring a medically healthy environment for astronauts.[51][52]

Effects of fatigue

Further information: Fatigue and sleep loss during spaceflight

Human spaceflight often requires astronaut crews to endure long periods without rest. Studies have shown that lack of sleep can cause fatigue that leads to errors while performing critical tasks.[53][54][55] Also, individuals who are fatigued often cannot determine the degree of their impairment.[56] Astronauts and ground crews frequently suffer from the effects of sleep deprivation and circadian rhythm disruption. Fatigue due to sleep loss, sleep shifting and work overload could cause performance errors that put space flight participants at risk of compromising mission objectives as well as the health and safety of those on board.

Loss of balance

Leaving and returning to Earth's gravity causes “space sickness,” dizziness, and loss of balance in astronauts. By studying how changes can affect balance in the human body—involving the senses, the brain, the inner ear, and blood pressure—NASA hopes to develop treatments that can be used on Earth and in space to correct balance disorders. Until then, NASA's astronauts must rely on a medication called Midodrine (an “anti-dizzy” pill that temporarily increases blood pressure), and/or promethazine to help carry out the tasks they need to do to return home safely.[57]

Loss of bone density

Spaceflight osteopenia is the bone loss associated with human spaceflight.[3] The metabolism of calcium is limited in microgravity and will cause calcium to leak out of bones.[10] After a 3–4 month trip into space, it takes about 2–3 years to regain lost bone density.[58][59] New techniques are being developed to help astronauts recover faster. Research in the following areas holds the potential to aid the process of growing new bone:

Loss of muscle mass

Main article: Reduced muscle mass, strength and performance in space

In space, muscles in the legs, back, spine, and heart weaken and waste away because they no longer are needed to overcome gravity, just as people lose muscle when they age due to reduced physical activity.[3] Astronauts rely on research in the following areas to build muscle and maintain body mass:

Impairment of eyesight

Main article: Visual impairment due to intracranial pressure

During long space flight missions, astronauts may develop ocular changes and visual impairment collectively known as the Space Associated Neuro-ocular Syndrome (SANS).[2][3][61][62][63][64][65][66] Such vision problems may be a major concern for future deep space flight missions, including a human mission to Mars.[61][62][63][64][67]

Loss of mental abilities and risk of Alzheimer's disease

See also: Alzheimer's disease, Effect of spaceflight on the human body, and Health threat from cosmic rays

On December 31, 2012, a NASA-supported study reported that human spaceflight may harm the brain of astronauts and accelerate the onset of Alzheimer's disease.[68][69][70]

On 2 November 2017, scientists reported that significant changes in the position and structure of the brain have been found in astronauts who have taken trips in space, based on MRI studies. Astronauts who took longer space trips were associated with greater brain changes.[71][72]

Orthostatic intolerance

The Beckman cardiovascular reflex conditioning system inflated and deflated cuffs in Gemini and Apollo flight suits to stimulate blood flow to lower limbs.[73]

"Under the effects of the earth's gravity, blood and other body fluids are pulled towards the lower body. When gravity is taken away or reduced during space exploration, the blood tends to collect in the upper body instead, resulting in facial edema and other unwelcome side effects. Upon return to earth, the blood begins to pool in the lower extremities again, resulting in orthostatic hypotension."[74]

In space, astronauts lose fluid volume—including up to 22% of their blood volume. Because it has less blood to pump, the heart will atrophy. A weakened heart results in low blood pressure and can produce a problem with “orthostatic tolerance,” or the body's ability to send enough oxygen to the brain without fainting or becoming dizzy.[74]

Radiation effects

Comparison of Radiation Doses – includes the amount detected on the trip from Earth to Mars by the RAD on the MSL (2011–2013).[75][76][77][78]

See also: Spaceflight radiation carcinogenesis

Soviet cosmonaut Valentin Lebedev, who spent 211 days in orbit during 1982 (an absolute record for stay in Earth's orbit), lost his eyesight to progressive cataract. Lebedev stated: “I suffered from a lot of radiation in space. It was all concealed back then, during the Soviet years, but now I can say that I caused damage to my health because of that flight.”[3][79] On 31 May 2013, NASA scientists reported that a possible human mission to Mars may involve a great radiation risk based on the amount of energetic particle radiation detected by the RAD on the Mars Science Laboratory while traveling from the Earth to Mars in 2011–2012.[67][75][76][77][78]

Sleep disorders

Further information: Sleep in space and Performance Errors due to Fatigue and Sleep Loss

Spaceflight has been observed to disrupt physiological processes that influence sleep patterns in human beings.[80] Astronauts exhibit asynchronized cortisol rhythmicity, dampened diurnal fluctuations in body temperature, and diminished sleep quality.[80] Sleep pattern disruption in astronauts is a form of extrinsic (environmentally caused) circadian rhythm sleep disorder.[80]

Spaceflight analogues

Biomedical research in space is expensive and logistically and technically complicated, and thus limited. Conducting medical research in space alone will not provide humans with the depth of knowledge needed to ensure the safety of inter-planetary travelers. Complementary to research in space is the use of spaceflight analogues. Analogues are particularly useful for the study of immunity, sleep, psychological factors, human performance, habitability, and telemedicine. Examples of spaceflight analogues include confinement chambers (Mars-500), sub-aqua habitats (NEEMO), and Antarctic (Concordia Station) and Arctic FMARS and (Haughton–Mars Project) stations.[67]

Space medicine careers

Physicians in space medicine generally work in operations or research at NASA or, more recently, space companies that are flying private or commercial astronauts or spaceflight participants.

Operational space medicine provides direct medical support to astronauts and spaceflight participants, conducting medical screening and overseeing their preflight, inflight, and postflight medical care and preparations. As such, operational space medicine physicians are generally physicians trained in a clinical specialty--such as emergency medicine, family medicine, or internal medicine--who have undergone additional residency or fellowship training in aerospace medicine. Board certification in aerospace medicine is the gold standard for physicians who practice operational space medicine.

Research physicians study specific space medical problems, such as the Space Associated Neuro-ocular Syndrome, or focus on medical capabilities for future deep space exploration missions. Research physicians do not have clinical responsibilities in the care of astronauts and thereby are often not specialty-trained in aerospace medicine.

Related degrees, areas of specialization, and certifications

Space nursing

Space nursing is the nursing specialty that studies how space travel impacts human response patterns. Similar to space medicine, the specialty also contributes to knowledge about nursing care of earthbound patients.[81][82]

Medicine in flight

Further information: Medical treatment during spaceflight and Sleep in space

Sleep medicine

The use of hypnotic sleep aids is widespread among astronauts, with one 10 year long study finding that 75% and 78% of ISS and space shuttle crew members reported taking such medications while in space.[83] Of astronauts who took hypnotic medications, frequency of use was 52% of all nights. NASA allocates 8.5 hours of 'downtime' for sleep per day for astronauts aboard the ISS, but the average duration of sleep is only 6 hours.[84] Poor sleep quality and quantity can compromise the daytime performance and attentiveness of space crew. As such, improving nighttime sleep has been a topic of NASA-funded research for more than half a century.[85] The following pharmacological and environmental strategies have been investigated in the context of sleep in space:

Ultrasound and space

Ultrasound is the main diagnostic imaging tool on ISS and for the foreseeable future missions. X-rays and CT scans involve radiation which is unacceptable in the space environment. Though MRI uses magnetics to create images, it is too large at present to consider as a viable option. Ultrasound, which uses sound waves to create images and comes in laptop size packages, provides imaging of a wide variety of tissues and organs. It is currently being used to look at the eyeball and the optic nerve to help determine the cause(s) of changes that NASA has noted mostly in long duration astronauts. NASA is also pushing the limits of ultrasound use regarding musculoskeletal problems as these are some of the most common and most likely problems to occur. Significant challenges to using ultrasounds on space missions is training the astronaut to use the equipment (ultrasound technicians spend years in training and developing the skills necessary to be "good" at their job) as well as interpreting the images that are captured. Much of ultrasound interpretation is done real-time but it is impractical to train astronauts to actually read/interpret ultrasounds. Thus, the data is currently being sent back to mission control and forwarded to medical personnel to read and interpret. Future exploration class missions will need to be autonomous due to transmission times taking too long for urgent/emergent medical conditions. The ability to be autonomous, or to use other equipment such as MRIs, is currently being researched.

Space Shuttle era

With the additional lifting capability presented by the Space Shuttle program, NASA designers were able to create a more comprehensive medical readiness kit. The SOMS consists of two separate packages: the Medications and Bandage Kit (MBK) and the Emergency Medical Kit (EMK). While the MBK contained capsulate medications (tablets, capsules, and suppositories), bandage materials, and topical medication, the EMK had medications to be administered by injection, items for performing minor surgeries, diagnostic/therapeutic items, and a microbiological test kit.[99]

John Glenn, the first American astronaut to orbit the Earth, returned with much fanfare to space once again on STS-95 at 77 years of age to confront the physiological challenges preventing long-term space travel for astronauts—loss of bone density, loss of muscle mass, balance disorders, sleep disturbances, cardiovascular changes, and immune system depression—all of which are problems confronting aging people as well as astronauts.[100]

Future investigations

Feasibility of Long Duration Space Flights

In the interest of creating the possibility of longer duration space flight, NASA has invested in the research and application of preventative space medicine, not only for medically preventable pathologies but trauma as well. Although trauma constitutes more of a life-threatening situation, medically preventable pathologies pose more of a threat to astronauts. "The involved crewmember is endangered because of mission stress and the lack of complete treatment capabilities on board the spacecraft, which could result in the manifestation of more severe symptoms than those usually associated with the same disease in the terrestrial environment. Also, the situation is potentially hazardous for the other crewmembers because the small, closed, ecological system of the spacecraft is conducive to disease transmission. Even if the disease is not transmitted, the safety of the other crewmembers may be jeopardized by the loss of the capabilities of the crewmember who is ill. Such an occurrence will be more serious and potentially hazardous as the durations of crewed missions increase and as operational procedures become more complex. Not only do the health and safety of the crewmembers become critical, but the probability of mission success is lessened if the illness occurs during flight. Aborting a mission to return an ill crewmember before mission goals are completed is costly and potentially dangerous."[101] Treatment of trauma may involve surgery in zero-gravity,[102] which is a challenging proposition given the need for blood sample containment. Diagnosis and monitoring of crew members is a particularly vital need. NASA tested the rHEALTH ONE[103] to advance this capability for on-orbit, travel to Moon and Mars. This capability is mapped to Risk of Adverse Health Outcomes and Decrements in Performance Due to Medical Conditions that occur in Mission, as well as Long Term Health Outcomes Due to Mission Exposures. Without an approach to perform onboard medical monitoring, loss of crew members may jeopardize long duration missions.

Impact on science and medicine

Astronauts are not the only ones who benefit from space medicine research. Several medical products have been developed that are space spinoffs, which are practical applications for the field of medicine arising out of the space program. Because of joint research efforts between NASA, the National Institutes on Aging (a part of the National Institutes of Health), and other aging-related organizations, space exploration has benefited a particular segment of society, seniors. Evidence of aging related medical research conducted in space was most publicly noticeable during STS-95. These spin-offs are sometimes termed as "exomedicine".

Pre-Mercury through Apollo

Dr. Stephen Hawking used the "talking wheelchair" or the Versatile Portable Speech Prosthesis. To operate the VSP, Dr. Hawking used a thumb switch and a blink-switch that was attached to his glasses to control his computer.[109]

Ultrasound microgravity

The Advanced Diagnostic Ultrasound in Microgravity Study is funded by the National Space Biomedical Research Institute and involves the use of ultrasound among Astronauts including former ISS Commanders Leroy Chiao and Gennady Padalka who are guided by remote experts to diagnose and potentially treat hundreds of medical conditions in space. This study has a widespread impact and has been extended to cover professional and Olympic sports injuries as well as medical students. It is anticipated that remote guided ultrasound will have application on Earth in emergency and rural care situations. Findings from this study were submitted for publication to the journal Radiology aboard the International Space Station; the first article submitted in space.[115][116][117]

See also

References

Notes
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