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Humans in space

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Humans in space
Ronald J. White* & Maurice Averner†
*National Space Biomedical Research Institute and Baylor College of Medicine, One Baylor Plaza, NA-425, Houston, Texas 77030, USA
†NASA Ames Research Center, Moffett Field, California 94035-1000, USA
Many successful space missions over the past 40 years have highlighted the advantages and necessity of
humans in the exploration of space. But as space travel becomes ever more feasible in the twenty-first
century, the health and safety of future space explorers will be paramount. In particular, understanding the
risks posed by exposure to radiation and extended weightlessness will be crucial if humans are to travel far
from Earth.
A
ccomplishments in engineering over the past
100 years have provided unprecedented
opportunities for people to become mobile
and travel rapidly on or near the surface of the
Earth. Taking advantage of these
opportunities, we have become citizens of the world,
taking to the skies so often that the twentieth century will
surely be known as the Century of Air Travel. However,
even now the tools are in our hands to enable us to travel
away from our home planet and become citizens of the
Solar System. There are many reasons why human voyages
of space exploration are worthy of serious discussion at the
dawn of the new millennium. In fact, humans are
beginning to develop the robust infrastructure that will
make the twenty-first century the Century of Space Travel.
But this bold step must be taken with due concern for the
health and safety of future space explorers. This, in turn,
means that we must develop both a new understanding of
the risks posed by the potentially dangerous levels of
radiation and extended weightlessness associated with
future missions of exploration and a more effective means
of coping with these risks. This article describes some of
the benefits and risks of human missions of space
exploration and summarizes the critical questions and
issues that must be dealt with now, before fundamental
decisions are reached concerning the appropriate time for
humans to move away from Earth on voyages of
exploration.
Benefits of human space exploration
Human explorers sent to live in space and to travel to other
planetary bodies projects a captivating and alluring image.
The glamour and excitement of human voyages, as opposed
to automated, robotic missions, does much for public
morale and for our need as humans to go where we have not
yet ventured. But the reason for human exploration goes far
beyond these emotional aspects and is in fact a necessary
component of exploring the Universe1–3.
The experiences of astronauts and cosmonauts over the
past four decades have proven the merits and necessity of
humans as space explorers. Complex tasks, scientific experi-
mentation, and repair and troubleshooting of equipment
and hardware, for example, all require human capabilities
and judgement. There are myriad examples of humans
being required for the success of mission discoveries. The
initially flawed Hubble Space Telescope is a case in point.
Astronauts repaired the faulty scope and have been required
for continued servicing of this multimillion-dollar project.
Without human intervention the project would have a
fraction of the value NASA has been able to glean. The
NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com
© 2001 Macmillan Magazines Ltd
insight progress
Apollo lunar missions provide another example. Astronauts
were imperative on the lunar surface for remedying
unforeseen problems, such as repairing the rover vehicle and
using their training and communication with ground-
based scientists to select representative samples from a given
lunar location and recognize and evaluate interesting
findings. Humans will be imperative for similar goals on the
surface of Mars.
A principal goal of space travel is planetary exploration
and the search for life3. In-depth understanding of planetary
histories and processes will require field investigation.
Although automated robotic missions are often touted as
the most efficient and cost-effective way to perform such
investigation, current robots are inadequate for
accomplishing the complex iterative processes required for
successful scientific field studies. As outlined in a recent
report2, a human mission has much greater promise for
answering principal strategic questions than does a larger
number of robotic missions; it also creates many more
options for modes of exploration that cannot be achieved
robotically. This in itself makes human missions more cost
effective on scientific grounds.
Human presence will be required for the reasoning and
responses necessary to accommodate unexpected discover-
ies and to perform real-time testing of hypotheses. Evidence
of life, for example, is likely to be hidden and microscopic,
requiring long-distance travel over rugged terrain, digging
to great depths, surveying numerous sites, and finely
dissecting rock and soil layers. These are all intricate tasks
that far exceed the current capabilities of robots and are
likely to for a long time. The recent Mars Pathfinder mission
highlights this point. Although this was a successful
mission for achieving its goals, the limitations of the
Pathfinder’s mobile Sojourner rover for scientific investiga-
tion were vast. The rover was able to travel just over 100
metres around the landing site before communication was
terminated, which limited scientific return severely.
Chemical analysis of some of the rock samples by the
onboard spectrometer revealed an unexpected composi-
tion. However, without more sophisticated intervention it
was impossible to perform further evaluation, and without
such information the scientific value was extremely limited.
An astronaut scientist would have been able to make a field
identification of this rock, collect samples and perform field
tests, which would have untold scientific value. There is
great value in in situ analysis of samples on planetary
surfaces. Such sophisticated analysis would be very difficult
if not impossible to automate in the foreseeable future and
furthermore would not lend to iterative experimentation
arising from the results found.
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Altered forces on the human body
Changed physical factors: decreased weight;
fluid pressure; convection; sedimentation
Body Weight-bearing
fluids structures
Gravity receptors
Dynamic interactions
Adaptation
Altered physiological state of the body
Figure 1 The general effects of space flight or reduced gravity (for example, on the
surface of Mars) on the physical and biological elements of the human body.
Answering the principal scientific questions outlined for explo-
ration of Mars will require investigation in geology, palaeontology,
biology, chemistry, geophysics, atmospheric science and climatol-
ogy3. Initial investigations and assessments in these areas can be
achieved by the use of robots, but follow-up detailed investigation
and discovery will have to be done on the surface of the planet by
human crews. On balance, human abilities and capabilities are criti-
cal for deriving the maximum benefits of missions of exploration.
Risks and challenges of human space exploration
Voyages of exploration will subject space travellers to three serious and
related challenges: (1) changes in the physical forces on and within the
body brought about by a reduction in weight of the body’s
components; (2) psychosocial changes induced by the long-term
confinement of such a voyage without the possibility of escape; and
(3) changes in the levels and types of radiation in the environment.
These changes, which act simultaneously, precipitate a cascade of time-
related events in the human body about which we have been learning
slowly for the past 40 years4. The integrated and unmitigated responses
of the body to these challenges present real risks to the health of the
humans undertaking such missions and to the satisfactory completion
of the missions themselves. Some of the risks pose a greater threat than
others do, and the level of understanding of the physiological responses
to space flight varies depending on the body system in question.
Fortunately, it seems that most of these risks may be reduced to an
acceptable level through a vigorous research programme.
Changes in physical forces
Figure 1 illustrates the general biological consequences of the prima-
ry physical events occurring during space flight. Because weight is
decreased to very nearly zero for much of a mission, the weight-
bearing structures of the body are subject to a different set of stresses.
Changed hydrostatic pressure gradients along the body axes cause a
fluid shift within the body, and the input to the body’s many gravity
receptors is altered significantly. Almost all of the body’s components
and systems participate in the response to these events. Ultimately,
many of these systems seem to adapt, but questions still remain
concerning the extent of that adaptation and the stability of the
resultant state of the body. Because of the brevity of this review, only
one example of the effect of weightlessness will be given. For a more
complete list of the risks and the physiological systems implicated by
these risks, see http://criticalpath.jsc.nasa.gov/.
Prolonged exposure to weightlessness during extended space
flight (for example, voyages lasting a year or more) will significantly
1116 © 2001 Macmillan Magazines Ltd
increase the risk of fracture5. Measurements of bone mineral density
during the Mir space flights of 4.5–14.5 months indicate an average
loss of 5.650.8% from the lumbar spine, 1151.4% from the pelvis
and 8.151.2% from the proximal femur6. The extent of bone loss for
individual astronauts or cosmonauts is considerable, varying from
0% to up to 20% (ref. 7). This stands in sharp contrast to a decrease in
bone mass of 2–3% per decade in postmenopausal women. Although
the mechanisms promoting this variation in individual rates of bone
loss are undetermined, it is possible that once weightlessness occurs,
the astronauts’ genetic background and the actions of locally acting
cytokines shift bone remodelling to favour an increase in bone
resorption. Most observers agree that bone loss is likely to be progres-
sive, at least to the point that fracture poses an immediate risk during
an extended space flight, such as a proposed 3.5-year exploration
mission to Mars.
In terms of countermeasures to bone loss, various exercise regi-
mens have not proven effective in space nor has exercise significantly
aided the rapid re-establishment of bone mass after return to Earth.
Dietary calcium and vitamin D supplements have also not prevented
bone loss8. However, we know that bisphosphonates limit bone loss
effectively where bone resorption is increased, and bed-rest studies
examining this approach are underway. Newer agents, perhaps
derived from other current studies on regulatory factors, may prove
more effective ultimately. One hypothesis is that both resistive
exercise and a pharmacological agent will be required to prevent bone
loss during extended space flight.
Some of the other effects of weightless space flight include: cardio-
vascular and fluid-related problems of orthostatic hypotension
immediately following space flight9–11, the possibility of altered car-
diac susceptibility to ventricular arrhythmias12, and reduced cardiac
muscle mass and diminished cardiac function13; neurovestibular-
related problems at the beginning of a flight involving space motion
sickness14, and during and just after landing involving disorientation,
gait changes, and impaired balance and neuromuscular coordina-
tion15–18; muscle-related problems of atrophy involving loss of muscle
mass, strength and endurance19–22; circadian rhythm-related
problems involving sleep and performance23,24; and immune-related
problems involving infections and immunodeficiency25,26.
Psychosocial and neurobehavioural changes
Based on documented evidence from both US and Russian space
missions in which astronauts and cosmonauts experienced personal
and interpersonal problems27,28, adverse psychosocial reactions
Table 1 Psychosocial and neurobehavioural issues under investigation for
improving crew health and safety during prolonged space flight
Biological mechanisms of What cellular, molecular and organismic changes in
dysfunction the function of the nervous system occur during
conditions present in prolonged space flight?
Motivation, cognition and How can neurobehavioural and cognitive functions,
performance physical and emotional distress, motivation and
operational performance be assessed and enhanced
during a mission?
Pharmacology in space What does microgravity do to the pharmacokinetics,
bioavailability, side effects and efficacy of medications
for stress reactions?
Individual factors What characteristics of astronauts are predictive of
neurobehavioural resiliency and stable interpersonal
performance during a mission?
Team and interpersonal What aspects of leadership, crew selection and
optimization composition, training, communication, social
interaction, decision-making and error management
facilitate functioning within a multicultural crew and
between the crew and ground personnel?
Organizational, cultural and What organizational, professional and management
management factors goals, policies and priorities most affect crew
communication, performance, problem solving and,
ultimately, health and safety?
The six interrelated themes and example questions define the range of factors that are critical for
improving crew health and safety during prolonged space flight and for optimizing individual and
crew performance.
NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com

Table 2 A comparison of some space-related health concerns with medical issues on Earth
Research area Space
Bone Bone loss and increased fracture risk
Increased kidney-stone formation
Injury to soft connective tissue
Cardiovascular Postflight orthostatic intolerance
Cardiac atrophy
Heart rhythm disturbances
Performance/Sleep Errors due to sleep loss and disruption of the biological clock
Immunology/Infection Activation of dormant viruses in the body
Increased infection risk
Space flight-related anaemia
Interference with wound healing
Muscle Muscle loss and atrophy
Neurovestibular Space motion sickness and body orientation problems
Re-entry vertigo
Postflight dizziness, balance, posture and gaze stability
Radiation effects Cancer
Damage to central nervous system
Cataracts and other diseases
among astronauts during prolonged flights are now recognized as a
serious risk to mission success. Astronauts aboard exploration-class
space missions will endure behavioural challenges for a much longer
period of time and in different circumstances. Exploration mission
stressors include confinement for up to three years with the same
small group of people; isolation from family and friends; limited
communication with Earth, including a delay of up to 24 minutes in
bi-directional communications; and loss of privacy due to habitabili-
ty constraints. Additional neurobehavioural risks are posed by
prolonged exposure to microgravity, radiation and equipment
failure in space. Judging from current evidence, language, culture,
gender and differences in work role will also pose challenges to crew
communication and effectiveness.
Without mitigation, these stressors can impose a burden on
astronaut behavioural capability and health, both individually and
collectively. They have the potential to erode cognitive performance;
change neuroendocrine, cardiovascular and immune responses;
disrupt appetite, sleep and other basic regulatory physiology; lead to
neuropsychiatric impairment through anxiety and depression; and
potentiate serious interpersonal problems among crewmembers.
Thus, research is focusing on finding ways to ensure that astronaut
neurobehavioural health is maintained, that performance capability
is facilitated by appropriate habitat and human-systems interfaces,
and that crew psychosocial functioning is optimized effectively.
Today, nearly all of this research is done on Earth in laboratory or
special environments (such as Antarctica) and focuses on psycholog-
ical (for example, personality) and behavioural (for example,
leadership) characteristics of individuals and groups in relation to
performance and stress reactions29,30. Objective measures of
neurobehavioural performance are being investigated along with a
number of new unobtrusive technologies for computer recognition
of emotional distress. The neurobiological processes underlying
stress and arousal responses are also being studied in animals and
human models to identify the most appropriate behavioural and
pharmacological countermeasures. The ultimate goal is to reduce
risk by appropriate monitoring of physiological function and
behaviour, and by having an appropriate arsenal of countermeasures
available to enhance performance, motivation and the quality of life
during an exploration voyage. Table 1 provides examples of the scope
of issues under scientific investigation.
Changes in the radiation environment
Human missions of exploration will expose crewmembers to
transient radiation from solar particle events and to continuous
radiation from high-energy galactic cosmic rays31,32. The protons and
high-atomic-number energetic particles (HZE) involved may exert
NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com © 2001 Macmillan Magazines Ltd
insight progress
Earth
Osteoporosis and other bone disorders
Orthostatic intolerance
Heart disorders, such as sudden cardiac death due to heart rhythm
disturbances
Sleep problems due to jet lag, shift work and extended work schedules
Accidents due to sleepiness
Immune system disorders
Viral outbreaks due to stress conditions (shingles, cold sores)
Anaemia and other blood disorders
Muscle wasting diseases
Muscle weakening due to prolonged bed rest, immobilization, nerve crush
injury and ageing
Vertigo and other balance disorders
Risks from exposure to naturally occurring and work-related radiation
sizeable biological effects even at low fluence, and there are consider-
able uncertainties associated with secondary particle effects (for
example, HZE fragments or neutrons). Although the health risks
from exposure to radiation (X-rays, gamma rays or electrons)
encountered on Earth are comparatively well known, the health risks
from space radiation remain far from understood. Several indepen-
dent factors contribute to the overall risk to astronauts exposed to the
complex radiation environment of exploration missions. Of
primary concern is the induction of late-occurring cancers33. But
damage to the central nervous system is also potentially a mission-
compromising event because of the possibility of cell loss from
radiation damage affecting the functional integrity of the central
nervous system34. Recent studies35,36 also point to previously
unknown mechanisms of radiation-induced cellular pathologies
based on the communication between damaged and undamaged
cells and the induction of unstable states that lead to late expression of
genetic damage. Space radiation seems to be uniquely effective
in causing such cellular changes. Current research strategies focus
on shielding, risk estimation and risk mitigation and use both
cellular systems and animal models, together with proton and HZE
particle accelerators.
Future directions — the challenge of integrative physiology
The experiences of the past 40 years of space-related research and
health care have shown that, to manage effectively the health and
related mission risks of future space explorers, it is not enough to
separately address the loss of bone that occurs during a nearly weight-
less state, with its attendant increased risk of fracture, or the problems
of increased cancer risk caused by the natural radiation that
accompanies space flights away from low-Earth orbit. Meeting the
health-related challenges of human space exploration requires that
one abandon any model of the human body that has the muscles,
bones, heart and brain acting independently. Body parts will not
travel on exploration missions. Instead, the individual space
traveller’s body must be viewed realistically, with all parts connected
and fully interacting. Development and use of such an integrative
approach must capitalize on the investments that have been and
continue to be made in molecular biology and on the new and emerg-
ing capabilities in computing, information storage, modelling, and
fast, parallel processing that characterize today’s technology. This
will not be easy; the problems and challenges that must be faced are
many and great and have been discussed for several years37.
In the United States, the National Space Biomedical Research
Institute has already embarked on just such an integrative physiology
programme with NASA support (see www.nsbri.org). The ultimate
result of this long-term programme will be the development of a
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insight progress
quantitative description of a healthy human being that contains
state-of-the-art information on each component of the body and on
how these components relate to each other. This description, termed
a ‘digital human’, will contain virtually everything known about
human physiology, from biochemical to cellular to organ to system
information and then to interactions among the systems. It will serve
as an integrated repository of knowledge on mechanisms and their
coordinated operation in the intact human.
Realizing this goal involves the demonstration of a deep
understanding of functional elements in human performance, from
systems physiology to the individual genotype responsible ultimately
for performance characteristics. It involves the development of
models of component systems assembled in a hierarchical or
relational way, and the development of an understanding of how
environmental stresses impact on the function and adaptation of the
resultant phenotype. In practical terms, realizing this goal also
requires a strategy for integrating components and results from a
number of investigators (and laboratories) into a coherent synthesis
of human function.
For the space programme, the goal of such work is to provide a
personalized human model for each member of the crew of an explo-
ration voyage. Comprehensive individual models of the anatomy,
physiology, functional status, and medical and environmental
history of each astronaut will then contribute to monitoring,
diagnosis, treatment and outcome prediction, as well as assisting
mission planners and the crew themselves in reducing health and
mission risks. But the payoff from this integrative approach, if suc-
cessful, will extend far beyond the world of space exploration. An
understanding of the functioning of the healthy body will enable
researchers to probe not only the mechanisms responsible for the
many changes that occur during space flight, but also those factors
responsible when some pathway or component within the body
becomes dysfunctional, as it does during injury or disease. In fact, as
Table 2 shows, many of the medical concerns associated with space
flight are related strongly to familiar medical issues on Earth. The
problem of providing appropriate health care for future space
explorers acts only as a focusing lens to enable us to see more clearly
the problems we face in providing quality health care in general. The
great challenge of biology is to develop the tools to implode the
explosive accumulation of knowledge and information about our
biological selves. Perhaps, then, the ultimate reason for human space
exploration is to enable us to discover ourselves. ■
1. Hoffman, S. J. & Kaplan, D. L. (eds) Human Exploration of Mars: The Reference Mission of the NASA
Mars Exploration Study Team <http://www-sn.jsc.nasa.gov/marsref/contents.html> (Lyndon B.
Johnson Space Center, Houston, TX, 1997).
2. Space Studies Board, National Research Council. Scientific Opportunities in the Human Exploration of
Space (National Academy Press, Washington DC, 1994).
3. Special Report: Sending Astronauts to Mars
<http://www.sciam.com/2000/0300issue/0300currentissue.html> Sci. Am. 97 (March 2000).
4. Nicogossian, A., Huntoon, C. & Pool, S. (eds) Space Physiology and Medicine 3rd edn (Lea and
Febiger, Philadelphia, 1994).
5. Morey-Holton, E. R., Whalen, R. T., Arnaud, S. B. & Van Der Meulen, M. C. in Handbook of
Physiology. Section 4: Environmental Physiology (eds Fregly, M. J. & Blatteis, C. M.) 691–719
(American Physiological Society, New York, 1996).
6. Grigoriev, A. I. et al. Clinical and physiological evaluation of bone changes among astronauts after
long-term space flights. Aviakosm Ekolog Med. 32, 21–25 (1998). [In Russian.]
1118 © 2001 Macmillan Magazines Ltd
View publication stats
7. Vico, L. et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing
bones of cosmonauts. Lancet 355, 1607–1611 (2000).
8. Smith, S. M. et al. Calcium metabolism before, during and after a 3-month spaceflight: kinetic and
biochemical changes. Am. J. Physiol. 277, R1–R10 (1999).
9. Buckey, J. C. et al. Orthostatic intolerance following spaceflight. J. Appl. Physiol. 81, 7–18 (1996).
10. Wautenpaugh, D. E. & Hargens, A. R. in Handbook of Physiology. Section 4: Environmental Physiology
(eds Fregly, M. J. & Blatteis, C. M.) 631–674 (American Physiological Society, New York, 1996).
11. Reyes, C., Freeman-Perez, S. & Fritsch-Yelle, J. Orthostatic intolerance following short and long
duration spaceflight. FASEB J. 13, A1048 (1999).
12. Fritsch-Yelle, J. M. et al. An episode of ventricular tachycardia during long-duration spaceflight. Am.
J. Cardiol. 81, 1391–1392 (1998).
13. Levine, B. D., Zuckerman, J. H. & Pawelczyk, J. A. Cardiac atrophy after bed-rest deconditioning: a
non-neural mechanism for orthostatic intolerance. Circulation 96, 517–525 (1997).
14. Oman, C. M., Lichtenberg, B. K., Money, K. E. & McCoy, R. K. MIT/Canadian vestibular experiments
on the Spacelab-1 mission: space motion sickness: symptoms, stimuli, and predictability. Exp. Brain
Res. 64, 316–334 (1986).
15. Lackner, J. R. & DiZio, P. Human orientation and movement control in weightless and artificial
gravity environments. Exp. Brain Res. 130, 2–26 (2000).
16. Reschke, M. F., Bloomberg, J. J., Harm, D. K. & Parker, D. E. in Space Physiology and Medicine 3rd edn
(eds Nicogossian, A. E., Huntoon, C. L. & Pool, S. L.) 261–285 (Lea and Febiger, Philadelphia, 1994).
17. Young, L. R., Oman, C. M., Watt, D. G. D., Money, K. E. & Lichtenberg, B. K. Spatial orientation in
weightlessness and readaptation to Earth’s gravity. Science 225, 205–208 (1984).
18. Daunton, N. G. in Handbook of Physiology. Section 4: Environmental Physiology (eds Fregly, M. J. &
Blatteis, C. M.) 765–783 (American Physiological Society, New York, 1996).
19. Baldwin, K. M. Effect of spaceflight on the functional, biochemical, and metabolic properties of
skeletal muscle. Med. Sci. Sports Exerc. 28, 983–987 (1996).
20. Edgerton, V. R. et al. Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. J.
Appl. Physiol. 78, 1733–1739 (1995).
21. Fitts, R. H., Riley, D. R. & Widrick, J. J. Physiology of a microgravity environment. Invited review:
Microgravity and skeletal muscle. J. Appl. Physiol. 89, 823–839 (2000).
22. Edgerton, V. R. & Roy, R. R. in Handbook of Physiology. Section 4: Environmental Physiology (eds
Fregly, M. J. & Blatteis, C. M.) 721–763 (American Physiological Society, New York, 1996).
23. Czeisler, C. A. & Khalsa, S. B. in Principles and Practice of Sleep Medicine 3rd edn (eds Kryger, M. H.,
Roth, T. & Dement, W. C.) 353–375 (Saunders, Philadelphia, 2000).
24. Gündel, A., Polyakov, V. V. & Zulley, J. The alteration of human sleep and circadian rhythms during
spaceflight. J. Sleep Res. 6, 1–8 (1997).
25. Taylor, G. R. Overview of spaceflight immunology studies. J. Leukoc. Biol. 54, 179–188 (1993).
26. Gmünder, F. K. & Cogoli, A. in Handbook of Physiology. Section 4: Environmental Physiology (eds
Fregly, M. J. & Blatteis, C. M.) 799–814 (American Physiological Society, New York, 1996).
27. Kanas, N. Psychiatric issues affecting long duration space missions. Aviat. Space Environ. Med. 69,
1211–1216 (1998).
28. Ellis, S. R. Collision in space. Ergon. Design 8, 4–9 (2000).
29. Connors, M. M., Harrison, A. A. & Akins, F. R. Living Aloft (NASA, Washington, 1985).
30. Palinkas, L., Gunderson, E. K. E., Holland, A. W., Miller, C. & Johnson, J. C. Predictors of behavior
and performance in extreme environments: the Antarctic space analogue program. Aviat. Space
Environ. Med. 71, 619–625 (2000).
31. Schimmerling, W. Radiobiological problems in space: an overview. Radiat. Environ. Biophys. 31,
197–203 (1992).
32. Nelson, G. A. in Handbook of Physiology. Section 4: Environmental Physiology (eds Fregly, M. J. &
Blatteis, C. M.) 785–798 (American Physiological Society, New York, 1996).
33. Space Studies Board, National Research Council. Radiation Hazards to Crews of Interplanetary
Missions (National Academy Press, Washington DC, 1996).
34. Vazquez, M. E. Neurobiological problems in long-term deep space flights. Adv. Space Res. 22,
171–183 (1998).
35. Azzam, E. I., de Toledo, S. M. & Little, J. B. Direct evidence for the participation of gap junction-
mediated intercellular communication in the transmission of damage signals from a-particle
irradiated to nonirradiated cells. Proc. Natl Acad. Sci. USA 98, 473–478 (2001).
36. Kadhim, M. A. et al. Transmission of chromosomal instability after plutonium alpha-particle
irradiation. Nature 355, 738–740 (1992).
37. Boyd, C. A. R. & Noble, D. (eds) The Logic of Life: The Challenge of Integrative Physiology (Oxford
Univ. Press, Oxford, 1993).
Acknowledgements
The authors acknowledge many helpful discussions with R. J. Cohen, J. F. Dicello, D. F.
Dinges, C. Golden, A. R. Kennedy, J. I. Leonard, C. M. Oman, R. J. Schwartz and J. R.
Shapiro. Support for the preparation of this paper was provided by NASA, both directly
and through Cooperative Agreement NCC 9-58 with the National Space Biomedical
Research Institute.
NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com