Today, the exploration of space remains one of the most stimulating and exciting areas
of scientific research and technological development. One of the objectives for the
next 10 years is to create, and then implement, a long-term plan for the robotic and
human exploration of the solar system, with Mars and the Moon as first targets. To
undertake such a future mission requires major efforts of global and interdisciplinary
cooperation between scientific, industrial, and legislative parties. This was recently
highlighted in the report by the Committee on Human Spaceflight of the National Academy
of Sciences of the United States of America.
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Past space missions in Earth orbit have demonstrated that humans can survive and work
in space for durations of up to several months and return to Earth with relatively
limited health consequences. However, there are pending technological, medical, and
psychological issues to be solved before adventuring in longer and more distant space
missions, such as those envisioned in a space exploration program. For example, protection
against ionizing radiation, problems with lunar and Martian dust, a reliable closed
life-support system in transit and on the surface, psychological issues such as those
affecting cognition, behavior, and performance during and after long-duration space
travel, general metabolic disturbances such as prevention of bone loss and muscle
atrophy, and the potential irreversibility of these changes, as well as balance and
coordination as the main limiting factors for a manned mission to Mars. Similarly,
the known enhanced infectious disease risks as humans travel and live within these
stressful, confined environments, require special attention. Furthermore, technological
breakthroughs, primarily in life-support systems and recycling technologies are required
to reduce the costs of these expeditions to more acceptable levels. Solving such issues
will need creative scientific and technological approaches relevant to clinical and
industrial applications here on Earth.
In the United States, NASA Human Research Program implements a constantly evolving
Human Research Roadmap that represents a “risk reduction strategy for human space
exploration.”
2,3
In Europe, European Space Agency (ESA) supported several preliminary studies enabling
the definition of priorities to prepare for interplanetary-manned exploration missions,
such as the HUMEX (study on the Survivability and Adaptation of Humans to long-duration
Exploratory Missions)
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or FIPES (Facility for Integrated Planetary Exploration Simulation).
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ESA has also developed a comprehensive and targeted ground program to validate effective
countermeasures through the bed rest studies, including the testing of the use of
artificial gravity applied through a short-arm centrifuge. However, Europe had not
developed its own human exploration roadmap. On the basis of the current knowledge,
an action plan approved by the European scientific and industrial communities, and
relying on ESA programs, integrating the expertise of non-ESA member states as well
as of the European Eastern countries is needed.
In 2012, the European Union funded the project THESEUS (Towards Human Exploration
of Space: A European Perspective, supported by the EU Seventh Framework Program for
Research and Technology Development). The goals of THESEUS were to develop an integrated
life sciences research roadmap enabling European human space exploration, in synergy
with the ESA strategy, taking advantage of the expertise available in Europe, and
identifying the potential of non-space applications and development. As any human
exploration initiative can only be conceived of as a well-coordinated series of programs
at the international level, the issue of international cooperation and coordination
with other nations, agencies, and programs has been central to the establishment of
such a roadmap. Space agencies are currently jointly discussing their plans for exploring
the Moon and Mars.
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Any research roadmap enabling human exploration of these targets should, both, incorporate
these plans in its making, and influence such plans to ensure that basic and applied
research priorities as defined and expressed by the relevant communities are addressed
in a consistent manner by these agencies. To enable this, the concerned space agencies
were represented as observers in THESEUS and international experts were invited to
participate in the expert groups.
THESEUS had three objectives: (i) identify disciplinary research priorities, (ii)
focus on fields with high-terrestrial application potential, and (iii) build a European
network as the core of this strategy. These three objectives were tackled through
five tightly interrelated clusters involving 137 international scientists:
Integrated Systems Physiology
Psychology and Human-Machine Systems
Radiation
Habitat Management
Health Care
The conclusions of those expert groups can be found online on the THESEUS website.
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A series of publications is forthcoming in NPG Microgravity dedicated to the reports
condensed as reviews of the cluster on Integrated Systems Physiology.
Why did we decide to publish this topic as a series of reviews? The actual human research
program is the culmination of the 40-year space flight experience, including both
short- and medium-term duration missions. The scientific results from these missions
have demonstrated that space flights have an impact on almost all physiological systems
including muscle atrophy, bone demineralization, cardiovascular and metabolic dysfunctions,
impaired cognitive processes, and reduced immunological competence, on which undernutrition
is superimposed. All these physiological responses lead to a physiological deconditioning
in space that may affect crew health and performance, and thus the success of the
mission, but also that may interfere with a healthy return to Earth. Countermeasures
were investigated to mitigate some of the maladaptive changes associated with space
flight. These included drugs, nutrition, and physical exercise on various workout
devices and others. None of them were proven to be fully effective, but given the
relative short duration of the missions, most astronauts returning to Earth did not
encounter difficulties in recovering. Significant knowledge has undoubtedly been accumulated
on the physiological changes associated with the adaptation of humans to short-term
space flights.
Nowadays, human space flight programs have entered the next phase of space exploration
toward the Moon and Mars, and there are clearly inherent medical challenges with such
a goal. We have clearly much less information regarding the physiological changes
associated with the long-duration missions extending from 30 days to months in orbit
than we have for short-term missions. Preliminary observations from limited number
of astronauts exposed to 6 months in space now suggest that our previous hypotheses
that systems would have adapted to the space environment within this period, are not
proving to be correct.
Clearly, the primary thrust of the next bioastronautics research will be to further
explore the rate and magnitude of the effects of long-duration space flight on crew
health and performance, to develop more effective and efficient countermeasures based
on specific understanding of the mechanisms of sensing and responding to microgravity,
and to facilitate post-flight readaptation to the terrestrial environment. Such basic
and upstream research is a clear prerequisite activity aimed at improving, in the
long term, the capability for interplanetary travel and life on planetary surfaces.
This objective is far from being trivial. Although space medicine has been practiced
for more than half a century, it is quite nascent, relative to the physiological and
clinical capability, and knowledge required for long-term space flight. For example,
a significant challenge in the evolution of space medicine will be to determine how
the physiological adaptation to space may alter the physiopathology of disease, or
the manifestation of illness and injury in space. An answer to that can obviously
be found by reviewing the clinical experience of flight physicians who treated diseases
in space. But the strongest approach is to create an integrated model of the physiopathological
adaptation of multiple organ systems to microgravity. The exploration of space requires
a systematic understanding of human body, from the molecular to integrated system
levels, as it responds to the unfamiliar environment of space travel.
This integrated physiological approach is definitely a new but necessary method in
bioastronautics. Also, it has been recognized for a long time, though not executed
as a required scientific line of attack. Research has for decades been conducted along
body functions, i.e., muscle, bone, cardiovascular system, or nutrition taken independently.
The best examples to demonstrate the limits of such an approach lie in the incomplete
success of the current countermeasure programs, in which scientists focused on some
organ systems and symptoms in a piecemeal manner rather than targeting at once in
an integrated manner all of the body physiological systems affected by gravity. The
association between the negative energy balance and both the decreased protein synthesis
rate and the cardiovascular deconditioning, or the dual effect of amino acid supplementation
that appears helpful on muscle mass but not on bone, demonstrate this point. A holistic
approach to space-condition adaptation should now be developed.
The transition of space research from independent physiological functions to a more
rigorous integrated approach requires a focused, competitive research strategy for
solving targeted risk areas of human health and performance. Reaching these goals
will not only provide the basis for critical, high-quality health care for crews on
orbit, as well as a smooth recovery on return, but also result in a wealth of physiological
data. Evaluation of these data will undoubtedly help addressing medical challenges
of long-term space flight. The data will provide the basis for well-conceived and
evidence-based decisions to such physiological concerns as radiation exposure, vestibular
dysfunction, immunology, mineral metabolism, protein synthesis, chronobiology, and
sleep, cardiology as well as food and nutrition in space, taken as a whole. Another
essential consideration for planetary exploration is reduced gravity as opposed to
weightlessness. The effects of a long-duration exposure to the reduced gravity levels
that will be experienced during stays on the Moon (0.16 g) and Mars (0.38 g) are completely
unknown. It seems unlikely that the countermeasures developed on board the International
Space Station, will adequately protect crews journeying to Mars and back over a 30-month
period, or prevent the effects of a long-duration exposure to reduced gravity on the
Moon or Mars. There is therefore a need to get basic knowledge on the physiological
adaptation to reduced gravity levels, which will, again, be used to design an “integrated
countermeasure” for preventing the detrimental effects of weightlessness or reduced
gravity on the physiological systems of the body. The advantage presented for the
first time by the systematic study of microgravity in space, Moon, Mars, and Earth
gravity as a continuum will for the first time enable better understanding of how
the human body as well as other organisms sense and process gravity.
Finally, the full use of ground-based applications of bioastronautics promise to yield
a wealth of knowledge. For decades, clinicians and physiologists working in space
research have worked separately without awareness or taking advantage of potential
strong mutual questioning. Good examples for that is research on aging and chronic
diseases. In our search of the environmental factors that fueled the pandemic of chronic
diseases, we face a paradox. Although sedentary lifestyle has been highlighted for
decades as one of the main factors triggering the development of current chronic diseases
such as obesity, insulin resistance, hypertension, muscle disuse, and bone demineralization,
the physiology of physical inactivity has received little attention. Clearly, the
causal relationships between sedentary behaviors and those disorders are essentially
based on epidemiological studies or on the indirect beneficial effects of exercise
training. None of these studies provide evidence to support a cause-and-effect relationship,
but they indirectly suggest that sedentary behaviors and poor nutrition are the second
leading cause of death in the United States, right after tobacco, and major contributors
to the diseases associated with aging.
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Along with microgravity, the physiological adaptations to space flight require an
adaptation to physical inactivity and lack of postural change that is exceedingly
well simulated in the ground-based bed rest analog of microgravity.
In addition to space medicine-related questions, bed rest represents a unique model
to investigate the mechanisms by which physical inactivity and lack of postural change
leads to the development of current societal chronic disorders, but also to test the
efficacy of the countermeasure programs in preventing or reducing the development
of these disorders. More importantly, because bed rest studies are conducted in healthy
subjects who are expected to recover, new therapeutic avenues can be studied.
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In the context of integrated systems physiology, THESEUS considered the following
objectives:
To delineate what are the next priorities of high-quality research in physiology needed
to support the next phase of space exploration;
To define these priorities in a new integrated approach of the deconditioning syndrome
based on which a new generation of countermeasures may be tested in the context of
Mars exploration;
To better use the results of space physiology and their analogs to strengthen our
knowledge of the role of sedentary behaviors on Earth in the development of current
societal chronic diseases.
Five reviews are included. They are dedicated to the fields of nutrition and metabolism,
immunology, muscle and bone, neurophysiology, and cardiovascular function. All of
them made a significant effort to address each topic from an integrated physiology
perspective. Finally, a concluding review summarizes the roadmap and compares it with
the existing US-NASA roadmap.