Space
Biology
Fundamentals of Space Medicine — Chapter 2
Space Biology
Gilles Clément, Ph.D
CNRS
"Cerveau et Cognition" Laboratory
Toulouse, France
Kluwer Academic Publishers • Copyright © 2003 • All rights reserved
1
Space
Biology
Key Concepts
• What is Life? Evolution of Life. Life on Mars
• The effects of gravity on cell shape and function.
Gravitational Biology
• The effects of spaceflight on development of animals.
Development Biology
• The effects of spaceflight on development of plants.
Plant Biology
• How space radiation affects cells.
Radiation Biology
• The biological research facilities on board the
International Space Station
2
Space
Biology
The Evolution of Cell
3
• Living cells arose on Earth by the spontaneous aggregation of
molecules about 3.5 billion years ago
– These early (prokaryotic) cells (e.g., bacteria) are small,
with relatively simple internal structures containing DNA,
proteins and small molecules
– They replicate quickly by simply
dividing in two (a single cell can divide
every 20 min and thereby give rise
to 5 billion cells in < 11 hrs). Their
ability to divide quickly (growth rate)
enables these cells to adapt rapidly
to changes in their environment
– Bacteria can utilize virtually any type of organic molecule
as food (including sugars, amino acids, fats,
hydrocarbons,...) and get their energy (ATP) from chemical
processes in absence or presence of Oxygen
Space
Biology
Talking about Contamination
4
• The Apollo-12 Lunar
Module landed on the
Moon 156 meters away
from Surveyor-3, which
landed there 2.5 years
earlier
• The astronauts recovered
a camera of the Surveyor
spacecraft for analysis
back on Earth
• Specimen of a bacteria
(Streptococcus mitis)
were still alive on the
camera
Photo NASA
Space
Biology
The World’s Oldest Living Thing
• Spores of the Bacillus bacteria were
found during the summer of 2000 in salt
crystals buried 600 meters below
ground at a cavern in New Mexico, US
• When they were extracted from the
crystals in a laboratory and placed in a
nutrient solution, the micro-organisms
revived and began to grow
• These bacteria have survived in a
state of suspended animation for
250 million years
• Until then, the world’s oldest living
survivors were thought to be 25-40
million-year-old bacteria spores
discovered in a bee preserved in
amber
5
Space
Biology
The Evolution of Cell
• About 1.5 billion years ago appeared larger and more
complex cells such as those found in higher animals and
plants
– These eukaryotic cells (or protozoa) have a nucleus chich
contains the cell’s DNA, and a cytoplasm where most of
the cell’s metabolic reactions occur
– They get their ATP from aerobic oxidation of food
molecules (respiration) or from sunlight (photosynthesis)
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Space
Biology
Evolution of Organisms
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(deduced from their genes sequences)
rat
toad
shrimp
maize
mushroom (multi-celled)
yeast (one-celled)
Histoplasma capsulatum (causes
lung infection)
Penicillium notatum (produces
the drug penicillin)
vertebrates
invertebrates
plants
fungi
protozoa (multi-celled)
Giardia intestinalis
(causes diarrhea)
protista
Trypanosoma brucei
(causes sleeping
sickness)
Plasmodium gametocyte
(causes malaria)
extremophiles
Sulfolobus
E. coli (causes food poisoning)
Strepococcus pyrogenes
(causes strep throat)
Mycobacterium tuberculosis
(causes tuberculosis)
archaebacteria
eubacteria
Space
Biology
Life on Mars
• This 4.5 billion-year-old rock is a
•
portion of a meteorite (ALH84001)
that was dislodged from Mars and
that fell to Earth in Antarctica about
16 million years ago
It is believed to contain fossil
evidence that primitive life may have
existed on Mars more than 3.6
billion years ago (Science, 1996)
Possible microscopic
fossils of bacteria-like
organisms
High-resolution scanning electron
microscope images of AHL84001
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Space
Biology
Gravitational Biology
• Question:
How cells, as single unicellular organisms
or as the basic unit of multicellular
organisms, are sensitive to gravity?
• Method:
To study of the effects of gravity on:
– Cell morphology:
• shape
• cytostructure (skeleton)
• polarization (up-down orientation)
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Space
Biology
Cell Shape depends on Gravity
Load and strains exerted by internal masses on cell structures
and membranes in 1-G are absent in 0-G.
Due to the absence of sedimentation in 0-G the particles and
components are almost evenly distributed in the cell volume.
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Space
Biology
Gravitational Biology
• Question:
How cells, as single unicellular organisms
or as the basic unit of multicellular
organisms, are sensitive to gravity?
• Method:
To study of the effects of gravity on:
– Cell morphology:
• shape
• cytostructure (skeleton)
• polarization (up-down orientation)
– Cell function:
• secretion
• transportation of substances in and out the cell
• immune response
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Space
Biology
Cell Function
Nutrients (glucose)
12
Nutrients (food)
Information
Information
G
O2
O2
CO 2
G
Response
(e.g. multiplication
for lymphocyte)
?
CO 2
Response
(e.g. walking)
Space
Biology
Gravitational Biology
• Question:
How cells, as single unicellular organisms
or as the basic unit of multicellular
organisms, are sensitive to gravity?
• Method:
To study of the effects of gravity on:
– Cell morphology:
• shape
• cytostructure (skeleton)
• polarization (up-down orientation)
– Cell function:
• secretion
• transportation of substances in and out the cell
• immune response
– Cell-Cell interaction:
• communication
• differentiation
13
Space
Biology
Results of Space Experiments
14
• Bacteria
– increase in growth rate (proliferation)
– increased resistance to antibiotics
Bacteria grown
under the same
ambient
conditions as
Skylab, but on
Earth
0-g
1-g
Colonies of
bacteria (Bacillus
subtillus) cultured
on board Skylab
Space
Biology
Results of Space Experiments
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• Mammalian Cells
– Rats
• decrease in growth rate
of blood cells
• increase in growth
hormone secretion
(less release into the
blood)
• changes in
cystoskeleton synthesis
• increase in number of
synapses (connections)
between the sensory
cells of the balance
system
Photo NASA
Space
Biology
Human Cells in Space
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• Reduction in the number of red blood
cells (space anemia)
– red blood cells carry the oxygen to
the muscles
– reduction in plasma volume (due to
fluid loss) causes an over-abondance
of oxygen-carrying capability
– muscles lose mass and require less
oxygen
Plasma (55%)
– this over-abondance of oxygen is
detected by the kidney
White blood cells
Red blood cells
– the kidney reduces the production of
an hormone (erythropoietin, EPO)
which, in turn, decreases red blood
cell formation
Adapted from Lujan and White (1994)
Space
Biology
Human Cells in Space (cont’d)
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• Resistance to bacteria or virus is altered
(immune reaction)
– lymphocytes produce antibodies
which counteract the invading body
– activation of lymphocytes in-vivo is
depressed after space flight
– lymphocytes can be purified from
blood and activated by exposure to
various substances in culture (in vitro)
viruses
microbes
– lymphocytes activation in-vitro is reduced by 90% inflight
(probably due to changes in membrane structure)
– however,T-lymphocytes activation in-vitro in space is
accompanied by an increase in secretion of interferon
(a molecule which interferes with virus growth)
– use of space for synthesis of bio-molecule (biotechnology)
Space
Biology
Bio-Processing in Space
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• The absence of convection
and sedimentation can help
the separation and isolation
of biological specimens
• The increase in surface tension
will improve transport processes,
and consequently secretion and
growth
• Objective: to cultivate proteins (hormones, enzymes,
Photo NASA
antibodies) and cells that secrete a medically-valuable
substance
• The purified product would be returned to Earth for medical
use, product characterization, or improvement of groundbased separation techniques
• Challenged by ground-based computer graphics models, and
by genetic-engineering techniques (cloning process)
Space
Biology
•
•
•
•
•
•
•
•
•
•
•
•
Some Biological Materials
Candidate for Space Processing
Alpha-1-antitrypsin
Antihemophilic factor
Beta cells pancreas
Epidermal growth factor
Erythropoietin
Granulocyte stimulating factor
Growth hormone
Immunoglobulins
Interferon
Transfer factor
Urokinase
Protein crystals of
larger size and quality
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emphysema
hemophilia
diabetes
burns
anemia
wound healing
growth problems
immune deficiency
viral infections
multiple sclerosis
thrombosis
for X-ray or diffraction analysis
of their 3-D-molecular structure
Photo NASA
Space
Biology
Amphibian Development
• After fertilization of the amphibian eggs, two rotations occur :
– The whole egg detaches from its jelly capsule and rotates on
itself so that the heavier vegetative pole moves downwards
– An hour or so later,
just the egg cortex
rotates by 30 deg relative
to the cytoplasm.
This rotation establishes
the dorso-anterior axis
and depends on a
transient array of
parallel microtubules
at the vegetal cortex
• Very roughly, the animal pole corresponds to the head,
and the vegetal pole corresponds to the dorsal side
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Space
Biology
Amphibian Development (cont’d)
Movie:
21_crescent
When the cortex does not
rotate normally, the embryo
fails to develop
Cortex rotation:
The cytoplasm rotates
with respect to the
overlying cortex by
about 30 degrees.
The gray crescent is
only visible in certain
amphibian eggs
Movie:
21_frogeggs
Document NASA
21
Space
Biology
Embryonic Development
22
The early stages
are closely similar
among species
(drawn to scale)
The later stages
are more divergent
(not drawn to scale)
Fish
Salamender
Chick
Human
Space
Biology
Development in Space
23
• Invertebrates
– Aquatic species less susceptible to
microgravity than terrestrial species
• fertilization and larval development
normal in sea urchin eggs
• formation of skeletal hard parts
(shells, spicules) which involve
calcium carbonate is altered
during development in microgravity
– Insects:
• development abnormalities in
drosophilas bred in space
• stick insect: reduced hatching rate
of eggs, but embryonic
development before hatching
showed no major morphological
anomalies
Movie:
23_sts107bio
Document NASA
Photo NASA
Space
Biology
Invertebrates in Space
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Spiders use both the wind and
gravity to determine the
required thickness of web
material
Documents NASA
First web built in space
Space
Biology
Early Development in Space
25
• Vertebrates
– no vertebrates have been raised from conception to sexual
maturity in space
– no birds or reptiles have bred in orbit
– fertilized chicken and quail eggs have flown: few young
chick embryos have survived; normal development of eggs
launched at later developmental stages.
– frog eggs fertilized in-flight:
• differences in early
embryogenesis
• but tadpoles at feeding
stage are not different
Ground
from controls
– Therefore, gravity-driven rotation of
Flight
egg is not essential for development.
The major embryonic axis forms independently of gravity
Space
Biology
Later Development in Space
26
• Vertebrates
– tadpoles born in space have difficulties to inflate their lungs
in microgravity
– tadpoles born in space exhibit larger
visual-oriented responses during 9 days postflight
– fish (medaka) larvae raised in space swim normally when
tested on Earth (Ijiri,1997)
Movie:
26_fishsts89
Courtesy K. Klenska, OHB
Development in Space (cont’d)
Space
Biology
• Mammals
Photo NASA
– flown pregnant rats gave birth to normal neonates after
flight
– during postflight delivery, flight dams have twice as
many abdominal contractions as the ground controls
– flown neonate rats show persistent slower weightbearing behavior (walking, surface righting) postflight.
Therefore, gravity is required for this critical
developmental period
The Neurolab mission
was 16-day long
27
Space Research in Plant Biology
• Mechanism of gravity perception
(gravitropism)
• Development of closed ecological
life support systems
• Plants respond to environmental
stimuli such as light (phototropism),
water (hydrotropism), and magnetic
or electric fields. These responses
are masked on Earth by the
overriding response of plants to
gravity
• Role of the absence of 24 hr cycles in light
and temperature on circadian rhythms in plants.
The generation of the circadian rhythms is likely to
involve the membrane transport systems, and these
systems are affected by microgravity
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Document NASA
Space
Biology
Space
Biology
Gravity Perception in Plants
Plants have gravity-sensing organs in their roots, which
involve the sedimentation of particles (statoliths)
Zea maize root cap
Photos ESA
On Earth, in a
root placed
vertically, the
statoliths
(black particles)
are sedimented
at the bottom
end of the cell
When the root is placed
horizontally for 3 hours, the
statoliths are now sedimented
onto the lateral walls of the cell
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Gravity Perception in Plants
30
Removal of the root abolishes the capacity to detect gravity
Photos ESA
Space
Biology
Zea maize
• Is it the movement of the statoliths
through the cytoplasm, or the
pressure they exert on other (lower)
cellular components, that is involved
in graviception?
• What is the threshold for gravity
perception?
Space
Biology
Roots grow randomly in 0-G,
but can be reoriented uniformly on
exposure to 1-G for as little as 3 hours
Photo ESA. Courtesy of G. Perbal
31
Space
Biology
Plant Development in Microgravity
1-G
0-G
apical stem
leaf
32
0-G Effects
Changes in orientation
of stem and leaves
axillary bud
stem
adventilious roots
More adventilious roots
secondary root
Faster growth of
secondary roots
primary root
Changes in orientation
of secondary roots
Reduction of the primary
root growth
root cap
Photo ESA. Courtesy of G. Perbal
Loss of apical
dominance
Space
Biology
Plant Biology in Space — Results
33
• On-board centrifuge experiments
have demonstrated that the
minimum force that is sensed by
plant organs is in the range of
1/1000 of g
• The root is able to perceive its
orientation with respect to a linear
acceleration vector and to
generate a signal of curvature in
less than 30 seconds
• The reproductive phase is completed in microgravity when
the culture conditions (gas and liquid exchanges) are
adequate
• Whether or not a seedling growing from the beginning in
microgravity can flower and produce normal seeds remains
a matter of debate
Photo NASA
Space
Biology
Seed Viability and Cell Division
34
• LDEF: Long-Duration Exposure Facility
– 12 million tomato seeds in space for 6 years
– Postflight measurement of germination
Germination %
Flight
73.8
Ground Control
70.3
– Conclusion: Seeds remain viable in space
• Cell Division and Chromosomal Damage in
embryos of cultured Hemerocallis (daylily)
Cells in division (%)
Cells in metaphase (%)
Chromosome damage (%)
Double nuclei (%)
Ground
2.6
31.3
0
0
Flight
0.4
11.3
1.7
3.1
– Conclusion: The space (microgravity ?)
environment results in reduced cell
division and increased chromosomal
damage
Documents
NASA
Space
Biology
Ionizing Radiation in Space
• Charged particles trapped
in the ‘Van Allen belts’
– Trapped electrons (7 MeV)
– Trapped protons (600 MeV)
– Trapped heavy ions (50 MeV,
limited penetration capacity)
• Solar Particles
– Solar wind
– Solar-flare protons
and heavy ions
• Galactic Cosmic Radiation
– 87% high-energy protons producing nuclear
disintegration stars and secondary neutrons
– 12% alpha particles (helium nuclei)
– 1% heavy nuclei ions, ranging from lithium to iron,
with high charge and high energy (1020eV, HZE)
35
Space
Biology
“Light Flashes”
Light flashes observed by the crew during two Skylab
orbits passing through the South Atlantic Anomaly
36
Space
Biology
“Light Flashes” (cont’d)
• “We all did see these corona discharges. […] Most of the time (we saw them)
during our sleep periods when we were lying in our bunks. […] They appeared
as either a bright round flash or a particle streaking rapidly across your eyeball
in a long thin illuminated line. I could determine whether it was my left eye or
my right eye that did it at the time” —Pete Conrad, Apollo 12
• “If I was thinking about watching for them, I would see one every minute or
somewhat less. One of them would be a flash, and about one minute later there
would be a line. It did not appear to make any difference whether we were in
lunar orbit, translunar, transearth, or anything else. If you just wanted to look for
them, you could see them going by” —Alan Bean, Apollo 12
• Three explanations have been proposed :
– Emission of photons by particles
slowed by fluid in the eye
(Cerenkov radiation)
– Light generated by particles
ionizing fluid in the eye
– Artificial light stimulus caused by particles
impacting retinal sensors in the eye
37
Space
Biology
Biological Effects of Radiation
38
• Through bombardment of spacecraft material, protons produce
neutrons. These neutrons, upon colliding with a hydrogen
nucleus, liberate their energy
• Living organisms contain many hydrogen-rich compounds,
such as proteins, fat, and water (70%)
• Acute effects:
– Skin effect, graying and loss of hair
– Eye lens opacification (cataract)
– Decrease in blood cells counts (weakness, anemia, infection)
– Loss of non-dividing cells
• Late effects:
– Sterility
– Cancer in blood-forming organs (bone marrow, thymus,
spleen), stomach, colon, bladder
– Genetic effects which arise from cell chromosome
aberrations and translocations (DNA strand break)
Space
Biology
Issues in Radiation Biology
39
• Most results obtained during short-term
space missions in low Earth orbit
• In lower organisms (plants and insects),
disturbances in genetic (inheritable)
material and in development were observed
in otherwise normal-appearing individuals
• Remains to determine if these effects
Photo NASA
will lead to tumor induction and life
shortening in organisms with longer life spans
• Microlesions induced by single heavy ions first discovered
via spaceflight experiments. These findings initiated biological
investigations using particles accelerators on Earth
• It is possible that the effects of radiation are more important in
microgravity. Some biological effects, and their protection,
can be studied only in space
What are the effects of space
radiation at tissue level?
40
“Phantom Torsos” are mounted
inside and outside the ISS to
study radiation dosages on
crewmembers
Photos NASA
Photo ESA
Space
Biology
X-ray picture of
Phantom Front
Section.
Lines represent
Phantom sections.
Dark area shows the
location of the active
dosimeters (heart,
liver, kidneys).
Passive dosimeters
are mounted at
roughly 1,600
locations
Space
Biology
ESA Biolab onboard ISS
Movie:
41_columbus
Courtesy of ESA
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Space
Biology
ISS Centrifuge Accommodation Module
Documents NASA/NASDA
42
Space
Biology
Biology Research onboard ISS
• Cell Culture Unit*
• Aquatic Habitat*
• Advanced
Animal Habitat*
• Plant Research
Unit*
• Insect Habitat**
• Egg Incubator**
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Research in cell and tissue biology
Capability to maintain and monitor animal and
plant cell and tissue culture for up to 30 days
Egg to egg generation studies for examination
of life stages. Can accommodate small fresh
water organisms for up to 90 days
Housing for up to 6 rats or 12 pregnant mice
for studies of mammals development
Studies of all stages of growth and development
for plant specimens up to 30 cm (root+shoot)
Multigenerational and radiation biology
Incubation and development of small reptilian
and avian eggs prior to hatching
* can be used on the 2.5-m diameter centrifuge (0.01-2.0 g)
** equipped with internal 0.01-1.5 g centrifuges
Movie:
43_neurobio
Document NASA
Space
Biology
Additional Reading
• Clément G (2003) Fundamentals of Space Medicine. Dordrecht:
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Kluwer Academic Publishers
Dutemple L (2000) The Complete Idiot’s Guide to Life Sciences.
Indianapolis, IN: Alpha Books
Evans M L, Moore R, Hasenstein KH (1986) How roots respond to
gravity. Scientific American 255 : 112-119
Ingber DE (1998) The architecture of life. Scientific American 278:
48-57
Oser H, Battrick B (eds) (1989) Life Sciences Research in Space.
Nordwijk, NL: ESA Publication Division, ESA SP-1105
Perbal G (2001) The role of gravity in plant development.
In: A World Without Gravity. Fitton B, Battrick B (eds) Noordwijk, NL:
ESA Publications Division, ESA SP-1251, pp 121-136
Cell & Molecular Biology Research in Space. The FASEB Journal,
Volume 13 (Supplement) 1999
Plant Biology in Space: Proceedings of the International Workshop.
Planta, Volume 203 (Supplement) 1997
http://www.nas.edu/ssb/csbm1.html
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