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Home , Animals in space, Plants in space

The Space The brought a new dimension to the study of biology in space. Prior to the shuttle, scientists relied primarily on uncrewed robotic Shuttle: to investigate the risks associated with venturing into the . A Platform Various biological species were flown because they were accepted as models with which to study human disease and evaluate human hazards. The results That Expanded from the pioneering biological experiments aboard uncrewed the Frontiers not only provided confidence that humans could indeed endure the rigors of , they also formed the foundation on which to develop risk mitigation of Biology procedures; i.e., countermeasures to the maladaptive physiological changes the human body makes to reduced gravity levels. For example, the musculoskeletal Kenneth Souza system reacts by losing mass. This may pose no hazard in space; however, on returning to Earth after long , such a reaction could result in an increased risk of bone fractures and serious muscle atrophy.

Unfortunately, most biological research in uncrewed spacecrafts was limited to data that could only be acquired before and/or after spaceflight. With crew support of the experiments aboard the Space Shuttle and Spacelab, and with adequate animal housing and lab support equipment, scientists could train the crew to obtain multiple biospecimens during a flight, thus providing windows into the adaptation to microgravity and, for comparison, to samples obtained during readaptation to normal terrestrial conditions postflight.

With the Space Shuttle and its crews, earthbound scientists had surrogates in orbit —surrogates who could be their eyes and hands within a unique laboratory. The addition of Spacelab and Spacehab, pressurized laboratory modules located in the shuttle payload bay, brought crews and specialized laboratory equipment together, thus enabling complex interactive biological research during spaceflight. Crew members conducted state-of-the-art experiments with a variety of species and, in the case of human research, served as test subjects to provide in-flight measurements and physiological samples.

In addition to the use of biological species to evaluate risks, research aboard the shuttle afforded biologists an opportunity to examine the fundamental role and influence of gravity on living systems. The results of such research added new chapters to biology textbooks. Life on Earth originated and evolved in the presence of a virtually constant gravitational field, but leaving our planet of origin creates new challenges that living systems must cope with to maintain the appropriate internal environment necessary for health, performance, and survival.

408 Major Scientific Discoveries How Does Gravity

Affect Baruch Blumberg, MD and Animals? Nobel Prize winner in medicine, 1976. Professor of Medicine Fox Chase Cancer Center. Throughout the course of evolution, Former director of gravity has greatly influenced the Ames Research Center, California. morphology, physiology, and behavior of life. For example, a support structure—i.e., the musculoskeletal “The United States and other system—evolved to support body countries are committed to space mass as aquatic creatures transitioned travel and to furthering the human to land. To orient and ambulate, need to explore and discover. organisms developed ways to sense the gravity vector and translate this Since April 12, 1981, the information into a controlled response; shuttle has been the major portal to space for humans; its crews have built the hence, the sensory-motor system International Space Station (ISS), a major element in the continuum that will allow evolved. To maintain an appropriate humans to live and work indefinitely beyond their planet of origin. The shuttle blood supply and pressure in the has provided the high platform that allows observations in regions that were various organs of the mammalian body, a robust cardiovascular system previously very difficult to access. This facilitates unique discoveries and reveals developed. Understanding how new mysteries that drive human curiosity. physiological systems sense, adapt, and respond to very low gravity cannot “In the final paragraph of Origin of Species Darwin wrote: be fully achieved on the ground; it There is grandeur in this view of life, with its several powers, having been requires the use of spaceflight as a tool. Just as we need to examine the originally breathed by the Creator into a few forms or into one; and that, entire light spectrum to determine whilst this planet has gone circling on according to the fixed law of gravity, how the visual organs of living from so simple a beginning endless forms most beautiful and most systems work, so too we must use wonderful have been, and are being evolved. the complete gravity spectrum, from hypogravity to hypergravity, to “The shuttle and the ISS now provide a means to study life and its changes understand how gravity influences without the constraints of gravity. What will be the effect of this stress never life both on and off the Earth. before experienced by our genome and its predecessors (unless earlier forms Space biologists have identified and of our genes came to Earth through space from elsewhere) on physiology, the cell, clarified the effects of spaceflight and molecular biology? Expression of many genes is altered in the near-zero on a few representative living systems, gravity; how does this conform to the understanding of the physics of gravity at from the cellular, tissue, and system level to the whole organism. NASA molecular and atomic dimensions? achieved many “firsts” as well as “In time, gravity at different levels, at near-zero on the ISS, at intermediate other major results that advanced our understanding of life in space and on levels on the and , and at one on Earth, can provide the venues to Earth. The agency also achieved many study biology at different scales and enlarge our understanding of the nature technological advances that provided of life itself.” life support for the study of the various species flown.

Major Scientific Discoveries 409 Gravity-sensing Systems— How Do Plants and Animals Know Which Way Is Down or Up?

As living systems evolved from simple unicellular microbes to complex multicellular plants and animals, they developed a variety of sensory organs that enabled them to use gravity for orientation. For example, plants developed a system of intracellular particles called statoliths that, upon seed germination, enabled them to sense the gravity vector and orient their roots down into the soil and their shoots up toward the sun. Similarly, animals developed a variety of sensory systems STS-40 (1991) payload (e.g., the vestibular system of the specialist Millie mammalian inner ear) that enabled Hughes-Fulford working with the Research them to orient with respect to gravity, Animal Holding Facility. sense the body’s movements, and transduce and transmit the signal to the brain where it could be used together the two monkeys flown in a crewed between these hair cells and the with visual and proprioceptive inputs spacecraft, the Space Transportation vestibular nerve that occurred as the to inform the animal how to negotiate System (STS)- 51B (1985) Spacelab-3 gravity signal decreased. In effect, its environment. mission, displayed symptoms the body tried to turn up the gain to resembling space motion sickness receive the weaker gravitational signal Why Do Get Motion during the first few days of spaceflight. in space. This knowledge enabled medical doctors and crew members Sickness in Spaceflight? The basic process of space motion to have a better understanding of why sickness became one of the main One consequence of having space motion sickness occurs. gravity-sensing systems is that while themes of the first two dedicated space living in microgravity, the normal life sciences missions: STS-40 (1 991 ) output from the vestibular system is and STS-58 (1 993). Scientists gained Is Gravity Needed for altered, leading to a confusing set of insights into space motion sickness Successful Reproduction? signals of the organism’s position by probing the structural changes that and movement. Such confusion is occur in the vestibular system of the Amphibian Development mammalian balance organs. Using believed to result in symptoms not too Studies of the entire life span of living , space biologists learned for different from the typical motion systems can provide insights into the the first time that the neural hair cells sickness experienced by seafarers on processes involved in early development of the vestibular organ could change Earth. This affliction, commonly and aging. The Embryology relatively rapidly to altered gravity. termed “space motion sickness,” Experiment flown on STS-47 (1 992) Such neuroplasticity was evident in affects more than 80% of astronauts demonstrated for the first time that the increased number of synapses and cosmonauts during their first few gravity is not required for a vertebrate (specialized junctions through days in orbit. Interestingly, one of species, an amphibian, to ovulate, which neurons signal to each other)

410 Major Scientific Discoveries fertilize, achieve a normal body egg rotation and thereby tried to pattern, and mature to a free-swimming determine whether the response to tadpole stage. This experiment put to gravity was required for normal rest the “gravity requirement” question development. Unfortunately, research that had been debated by embryologists on the ground yielded ambiguous since the late 19th century. results due primarily to the trauma imparted to the eggs by the scientists’ In Earth gravity, frog eggs, when shed, attempts to interfere with rotation. have a bipolar appearance; i.e., the spherical egg has a darkly pigmented During the STS-47 flight, adult female hemisphere containing the nucleus ( Xenopus laevis ) were injected Fertilized frog eggs (above) and free-swimming and much of the cell machinery needed with hormone to induce the shedding tadpoles (below). for development while the opposite, of eggs, followed by the addition of lightly pigmented hemisphere is rich a sperm suspension. Half of a group of in yolk that provides the energy to fertilized eggs were placed in special drive the cell machinery during early water-filled chambers and on a rotating development. Shortly after being shed, centrifuge to provide an acceleration the eggs can be fertilized by sperm environment equivalent to terrestrial released by an adjoining male frog. gravity. The other half were placed in Once fertilized, a membrane lifts off the same type of water-filled chambers, the egg surface and the egg responds but in a temperature-controlled to gravity by orienting the dense incubator and were kept in a yolk-rich hemisphere down and the microgravity environment. Samples darkly pigmented hemisphere up with of developing embryos were taken respect to the gravity vector. This during the flight to capture important geotropic response was what spurred developmental stages for examination early embryologists to interfere with postflight. Some were returned to

Earth as free-swimming tadpoles. The results of the experiment ended the centuries-old debate as to whether gravity is needed for successful reproduction, and demonstrated for the first time that a vertebrate species could be fertilized and develop normally to a free-swimming stage in the virtual absence of gravity. It remains to be seen, however, whether metamorphosis, maturation, and a complete life cycle of an amphibian or other complex organisms can occur in the absence of gravity. In summary, for the first time, a vertebrate species was fertilized and developed through to a free-swimming stage in the virtual absence of gravity.

Astronaut Mark Lee working on the Frog Embryology Experiment in the General Purpose Work Station during the STS-47 (1992) mission.

Major Scientific Discoveries 411 William Thornton, MD Principal investigator for the first in-flight studies of space motion sickness on shuttle. on STS-8 (1983) and STS-51B (1985).

Bring ’em Back Alive The First Human Flight in Space with an Animal

“My training for the Spacelab 3 animal payload began as a toddler in North Carolina, surrounded by and growing up with a great variety of domestic and wild animals. Their humane treatment was my first lesson.

“After additional years of formal and informal education in Dr. Thornton is taking care of one of the two squirrel monkeys on STS-51B. medicine and biophysics, I used my training for research on space motion sickness. For some 18 months during the first “Finally flying on Challenger, we were to open the cage shuttle flights, we completed human studies, which produced inspection ports. All was well except for the who an array of first-time procedures in the US space program, had been a laboratory favorite (this is the animal in the photo) including evoked potentials, coordination, complex reaction but who was now in deep withdrawal. He didn’t eat or time, gastrointestinal activity and pressure, ambulatory blood drink for 2 days and by the third day, dehydration was real. pressure, and electrocardiograms, etc. These experiments I used some tricks learned while feeding wild pets and he answered some urgent operational questions and provided took a banana pellet and another—and more and more, points of departure for the more formal studies that followed. then cage food.

“Like so much of medical science, elemental knowledge “We returned with all animals alive and well and a great deal of our nervous system comes from animal studies on Earth. of experience subsequently incorporated into the shuttle On my first flight (STS-8 in 1983), 24 were flown in a legacy of astronauts and . Now, those of us research animal holding facility. But, to fly animals for study who work with humans and space motion sickness have in the small, enclosed environment of the shuttle is a such remarkable aid as the molecular and ultra-microscopic complex challenge that required years of preparation. studies from animals in Neurolab, another shuttle legacy.”

Animal Development also provided insights into what changes in the structure of the fetal might happen if humans experience balance organ—the vestibular system. Studies with rodents aboard the Space abnormal gravity levels during early On STS-90 (1 998), pups were Shuttle identified stages of early development. Pregnant rats on STS-66 launched at 8 or 14 days postpartum . mammalian development that are (1 994) and STS-70 (1 995) showed After 16 days in microgravity, their sensitive to altered gravity. They that spaceflight resulted in striking sensorimotor functions were tested

412 Major Scientific Discoveries within several hours of landing; e.g., walking, and righting (rolling over). Postflight, the righting response of postnatal pups was profoundly deficient compared to ground control animals, suggesting that removal of gravitational cues during early postnatal development can significantly alter inherent patterns of behavior. In addition, neonatal animals exposed to microgravity during this Neurolab mission failed to undergo normal skeletal muscle growth and differentiation, suggesting that gravity stimuli are essential for generating the structure needed to perform basic ambulatory and righting movements when subjected, postflight, to terrestrial gravity. The Biomass Production System installed on STS-111 (2002) carrying plants grown in the International Biology Space Station (ISS) for return to Earth. ISS Flight Engineer Dan Bursch (pictured) conducted all of the plant experiments. Germination launch. Although the mung bean and The importance of gravity in the oat seeds germinated in orbit, root germination and development of plants growth was somewhat disoriented has been observed and studied for and oats grew more slowly during centuries; however, it wasn't possible spaceflight. In addition, the amount to unravel how a plant detects and of lignin, a biochemical component responds to gravity until access to space of a plant’s “skeletal” system, was was achieved. NASA had to develop significantly reduced in all three specialized equipment to grow plants species, indicating that gravity is and study their response to gravity. an important factor in lignification The agency developed a plant growth necessary for plant structure. unit to fit within a shuttle middeck locker. This unit provided light, water, Plant Growth and an appropriate substrate to support plant growth. On the STS- 51F (1 985) Another pioneering experiment in the mission, seedlings were grown in study of plant responses to gravity was enclosed chambers within the plant the Gravitational Threshold Experiment growth unit; i.e., mung beans ( Vigna flown on the STS-42 (1 992) mission. radiata ), oats ( Avena sativa ), and It tested plant sensitivity to altered pine ( Pinus elliotti ). Mung beans gravitational fields during spaceflight. and oat seeds were planted 16 hours The Gravitational Plant Physiology before launch and germination Facility was built to support plant occurred in space. Pine seedlings were growth and stimulate plants with Multiple generations of plants grew in spaceflight 4 or 10 days post-germination at different levels of gravity using four for the first time. Examples include Apogee (top) and Brassica rapa (bottom).

Major Scientific Discoveries 413 centrifuge rotors contained within flown on and the International hardware, particularly about plant the facility. Two centrifuge rotors Space Station (ISS), respectively; metabolism in the absence of normal (culture rotors) were used to grow NASA’s Biomass Production System; terrestrial gravity. Biomass Production small seedlings in a 1 gravitational and the European Modular Cultivation System investigators concluded that force (1g) environment (normal System flown on the ISS. This latter plant and transpiration terrestrial level). The other two device enabled more in-depth studies processes did not differ dramatically rotors provided gravity stimulations of plant geotropisms than had been from those on the ground. of varying strength and duration possible in any of the previous flight (test rotors). After stimulation on the experiments with plants. Multiple Generations of Growth— test rotors, images of the seedling Fresh Foods responses were captured on video The early shuttle experiments with recorders. This research identified for plant. plants focused on basic questions the first time the threshold stimulus This small plant is related to cabbge about gravity-plant interactions. for a biological response to gravity. Oat and mustard and The scientific results as well as the seedlings were used in the experiment is widely used as a knowledge gained in the design and and, when the seedlings reached the model for plant fabrication of plant growth habitats proper stage of growth on the 1g biology research. greatly contributed to the development centrifuge rotor, an astronaut transferred of the next generation of growth them to the test centrifuge to chambers. Russian investigators them to a g-stimulus for different from the Institute of Biomedical durations and intensities. The threshold Problems, Moscow, with support of was found to be very low—about 15 US scientists and engineers, provided or 20 g-seconds; i.e., it took a force the equipment necessary to achieve of 1 g applied for 15 to 20 seconds to Arabidopsis seedlings were subjected multiple generations of . generate a plant response. to 1 g in space on a Biorack centrifuge Multiple generations of wheat and Following the pioneering plant while a separate group was held under mustard species were obtained experiments, NASA and others microgravity conditions. The during spaceflight on Mir and the developed equipment with a greater experiments provided evidence that ISS. In addition, a variety of edible range of capabilities, thus enabling intracellular starch grains (statoliths) vegetables were grown during more complex and sophisticated sediment in the presence of a gravity spaceflight, demonstrating that plants scientific experiments. This equipment stimulus and influence how plants are can be used to provide fresh food included the European Space oriented with respect to the gravity supplements for future long-duration Agency’s Biorack flown on Spacelabs; vector. Experiments within the Biomass missions. the Russian Svet and Lada systems Production System revealed much about growing plants within spaceflight

Space Biology Payloads

Pine, Fir Avian Frog, Seedlings

Bacteria Fungi Primate

Cells Insect

Fern Jelly sh Sea Urchin

Fish Snail 3 8 9 4 2 1 0 8 2 6 7 F A B B - Flowering - 3 3 4 4 4 4 4 4 2 1

Yeast 1 1 1 ------S S 5 6 Plant 4 5 - S S S S S S S S S - T T - - T T T T T T T T T S S S S S S T S S S S S S S S S T T T S S S S

414 Major Scientific Discoveries More Dangerous in Space Environment

As reported by Cheryl Nickerson, the interplay between the human immune system and the invading microorganism determines whether infection and disease occur. Factors that diminish immune capability or increase the virulence of the microorganism will greatly increase the likelihood of disease.

To gain insight to this issue, investigators compared responses of the food-borne bacterial pathogen Salmonella typhimurium , grown in the microgravity of spaceflight, to otherwise identical ground-based control cultures. Interestingly, they found that the spaceflight environment profoundly changed the gene expression and virulence characteristics (disease-causing potential) of the pathogen in novel ways that are not observed when growing the cells with traditional culture methods. This work also identified a “master molecular switch” that appears to regulate many of the central responses of Salmonella to the spaceflight environment.

On both the STS-115 (2006) and the STS-123 (2008) shuttle missions, scientists investigated the spaceflight response of Salmonella grown in various growth media containing different concentrations of five critical ions. The effects of media ion composition on the disease-causing potential of Salmonella were dramatic. Flight cultures grown in media containing lower levels of the ions displayed a significant Astronaut Heidemarie Stefanyshyn-Piper, in increase in virulence as compared to ground control cultures, whereas flight the middeck of the Space Shuttle Atlantis, activates the MICROBE experiment, which cultures grown in higher ion levels did not show an increase in virulence. The wealth investigated changes to Salmonella virulence of knowledge gained from these Salmonella gene expression and virulence studies after growth in space. provides unique insight into both the prevention of infectious disease during a spaceflight mission and the development of vaccines and therapeutics against

infectious agents on Earth.

2 4 6 5 7 1 8 0 2 9 5 4 8 6 3 1 0 9 2 6 7 8 9 0 7 7 7 7 8 5 5 5 5 5 5 6 6 5 6 6 6 6 6 7 7 6 7 5 ------S S S S S S S S S S S S S S S S S S S S S S S S T T T T T T T T T T T T T T T T T T T T T T T T S S S S S S S S S S S S S S S S S S S S S S S S

Major Scientific Discoveries 415 Why Do Astronauts taken from rats during and following Bones the STS-58 flight enabled us to Get Weak Muscles determine that the atrophy was clearly Skeletal bone, much like skeletal and Bones? a response to microgravity while the muscle, atrophies when unloaded. Bone muscle lesions were a result of re-entry mass loss as a consequence of skeletal and readaptation stresses,” Riley said. unloading during spaceflight is a well- Muscles established risk for long-term human The Space Transportation System For the STS-58 mission, muscle space exploration. A great deal of the (STS)-58 (1 993) mission opened a physiologists examined the contractile insight into “why” and “how” bone new window on how properties of rat muscles and mass loss occurs in flight resulted from affects muscle structure and function. demonstrated large changes that research with rodents both on board the Previously, scientists knew that correlated well with the biochemical US Space Shuttle and the Russian skeletal unloading (lack of gravity) and morphological changes they had . Such research revealed previously observed. As Ken Baldwin that bone formation becomes uncoupled resulted in the atrop hy of muscle fibers. Until this flight, all of the of the University of California at Irvine from resorption (process of minerals skeletal muscles studied were obtained stated, “The uniqueness of performing leaving the bone) and normal bone from humans or rats postflight, several spaceflight studies aboard STS-58 mineral homeostasis is compromised. using the rodent model was that we hours after readapting to terrestria l Consistent with several previous gravity. Consequently, distinguishing discovered marked remodeling of studies, results from the Physiological the structural and biochemical changes both structure and function of skeletal Systems Experiments series of payloads muscle occurring after such a short made in response to microgravity from (STS- 41 [1 990], STS-52 [1 992], changes readapting to Earth postflight duration in space. The results enabled STS-57 [1 993], and STS-62 [1 994]) was very difficult. During the STS-58 scientists to better predict what could showed that bone formation in the mission, crew members obtained tissue happen to humans if countermeasures weight-bearing bones of male rats was samples from animals and processed (i.e., exercise) were not instituted early inhibited by short-term spaceflight. these samples for detailed structural on in long-duration space missions.” Radial bone growth in the humerus and biochemical analyses postflight, The fundamental research with (long bone in the arm or forelimb that thus avoiding the effects of re-entry animals aboard the shuttle Spacelabs runs from the shoulder to the elbow) and readapting to Earth’s gravity. contributed markedly to the current was also decreased, though no changes Danny Riley of Wisconsin Medical understanding of the effects of in longitudinal bone growth in the College summed up how sampling spaceflight on skeletal muscle. The tibia (shin bone in leg) were detected. in flight changed his understanding. results laid the foundation for defining These effects were associated with a “When we looked at muscle samples optimal countermeasures that minimize decrease in the number and activity of that we obtained from previous the atrophy that occurs in the human bone-forming cells (osteoblasts). missions, we saw muscle atrophy and response to microgravity. Results of experiments on board STS-58 muscle lesions, small tears. Samples and STS-78 (1 996) provided further 6 8 0 7 1 5 8 3 6 7 9 0 1 2 3 4 5 1 5 7 9 0 5 3 0 0 1 0 2 1 1 2 2 2 2 3 3 3 3 3 3 8 8 8 8 9 9 9 ------1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ------S S S S S S S S S S S S S S S S S S S S S S S S T T T T T T T T T T T T T T T T T T T T T T T T S S S S S S S S S S S S S S S S S S S S S S S S

416 Major Scientific Discoveries evidence of changes at both the structural and the gene expression levels New Technology for associated with spaceflight-induced bone loss. Alterations also occurred in Three-dimensional Imaging bone mineral distribution, ultrastructure and geometry, and mechanical Rodent inner-ear hair cells are almost properties as well as in site and gene- identical to human inner-ear hair specific decreases in expression of cells. These cells are important for the bone matrix proteins (structural proteins with minerals attached). Taken together, vestibular system. Space biological these results suggest that significant research contributed novel tissue-specific alterations at the technologies for diagnostic medicine structural and molecular levels on Earth. NASA developed accompany bone loss in microgravity. three-dimensional (3-D) imaging At the cellular level, spaceflight software to facilitate and expedite Surgical planning using 3-D virtual was also shown to affect bone, imaging software. Dr. Stephen Schendel, cartilage, and tendons, resulting in the microscopic analysis of thin Stanford University. sections of the body’s balance organ— reduced matrix production or altered matrix composition. the vestibular system of the inner ear. The software enabled reconstruction of the innervation pattern of the rodent’s inner ear much faster than traditional manual How do bone cells sense and respond to changes in gravity? Some scientists methods. Not only did the technology greatly accelerate the analyses of electron suggest that certain cell types, when microscopic images, it also was adapted to construct 3-D images from computerized exposed to microgravity, reduce their axial tomography (CAT) and magnetic resonance imaging (MRI) scans of humans, activity or metabolism as well as the providing surgeons with 3-D dynamic simulations for reconstructive breast cancer amount of new protein normally surgery, dental reconstruction, plastic surgery, brain surgery, and other delicate produced and enter a “resting” phase. This microgravity effect could be due surgeries. Such simulations enable doctors to visualize and practice procedures prior to a direct effect on the mature to surgery, resulting in a much shorter time for the patient to be under anesthesia differentiated cell (final cell type for and a lower risk surgery. a specific organ like bone; e.g., osteoblast) so that the cell generates some “signal” during spaceflight, thus driving the cell to enter a resting phase. Another possibility is that the cell division cycle is delayed so that cells simply develop into their differentiated state more slowly than normal. A series of experiments was flown on STS -11 8 (2007) and STS -1 26 (2008) that studied bone marrow cell (the progenitors of bone cells) 3-D reconstructions of rodent inner-ear hair cells using Ross software. population changes in microgravity

Major Scientific Discoveries 417 using primary white blood cell Do Cells Grow (macrophage) cultures, respectively. The mouse study identified phenotypic Differently in (any observable characteristic or trait Spaceflight and of an organism, such as its structure or function) shifts in the bone marrow Affect Crew Health? cell subpopulations, including a subpopulation of macrophages. Cell and Molecular Biology On STS-95 (1 998) scientists placed A large number of experiments bone cartilage cells into cartridges with microorganisms were flown. carried in a special cell culture device Nearly all revealed that higher Human renal cortical cell culture grown built by the Walter Reed Army Institute populations of cells are obtained from on STS-90 (1998). for Research, Washington, D.C. cultures grown under microgravity Samples of these cells were collected conditions than are obtained in Summary on Flight Days 2, 4, 7, and 9. The media cultures grown statically on the ground, in which the cells grew were also possibly due to a more homogeneous The Space Shuttle’s unique capabilities, collected on the same days, and the distribution of cells. Recent studies coupled with the unbounded curiosity, conversion of glucose to lactate in the of microbial cultures grown in space energy, and creativity of scientists and media—a sign of metabolic activity— resulted in a substantial increase in engineers, enabled huge leaps in our was determined postflight. Following virulence in the space-grown cultures knowledge of how biological species, flight, these cells were analyzed for their when used postflight to infect mice. including humans, react and adapt to the state of differentiation and parameters The response of terrestrial life to near weightlessness of orbital showing the cell cycle activity. The microgravity at the molecular level is spaceflight. Over the past 3 decades, results strongly indicated that these cells reflected in the response of many of space biologists demonstrated that were affected by flight. Flight cells were an organism’s genes when gravity is gravity, and the lack thereof, affects life metabolically less active and produced significantly reduced in the at cellular and molecular levels. They fewer matrix components (necessary environment. Human renal (kidney) determined how amazingly durable for structure) than the cells grown on cell cultures flown on the Space and plastic biological systems can be the ground. In contrast to this, the Transportation System (STS)-90 (1 998) when confronted with a strange new flight cells showed a greater content mission exhibited a genetic response environment like space. Even in the of cyclins (proteins related to different to microgravity that exceeded all Columbia Space Transportation System stages of the cell cycle), suggesting expectations. More than 1,600 of the (STS) -1 07 (2003) tragedy, the survival that these cells were undergoing more 10,000 genes examined in the renal of the small soil nematode worms and proliferation (producing more cells) cells showed a change in expression the on board was an extremely than their ground control counterparts. (i.e., increased or decreased production stunning example of plant and microbial Exposure to spaceflight also resulted of the protein products of the genes) responses and resiliency to severe stress. in cartilage cells undergoing more cell as a result of spaceflight. Armed with division, less cell differentiation these results, investigators are now Over the past 4 decades of space (maturation), and less metabolic activity focusing on specific groups of genes biology research, our textbooks were compared to ground controls. This is the and their functions to try and unravel rewritten, whole new areas of study first time that cell cultures flown in why certain genes and metabolic were created, new technologies were space were shown to exhibit alterations pathways may be amplified or reduced developed for the benefit of science in their normal cell cycles. due to a change in gravity. and society, and thousands of new

418 Major Scientific Discoveries Microgravity —A Tool to Provide New Targets for Vaccine Design

The use of spaceflight as a tool for new discoveries has piqued the interest of scientists and engineers for decades. Relatively recently, spaceflight also gained the attention of commercial entities that seek to use the unique environment of space to provide opportunities for new product design and development.

For example, Astrogenetix, Inc. was formed by Astrotech Corporation, Austin, Texas, to commercialize biotechnology Astronaut John Phillips activating a Fluid Processing Apparatus containing tubes of microorganisms on STS-119 (2009). products processed in the unique environment of microgravity. Astrogenetix developed capabilities to offer a turnkey platform Specifically, Astrogenetix used assays of bacterial virulence in the for preflight sample preparation, flight hardware, mission microscopic worm . Bacteria, worms, and planning and operations, crew training, and certification processes growth media were launched separated in different chambers of needed within the highly regulated and complex environment of the Fluid Processing Apparatus, which was developed by Bioserve human spaceflight. Space Technologies, Boulder, Colorado. Astronauts hand-cranked Astrogenetix’s primary research mission is to discover the hardware twice, first to initiate the experiment by mixing therapeutically relevant and commercially viable biomarkers— bacteria, worms, and growth media and at a later scheduled time substances used as indicators of biologic states—in the to add fixative to halt the process. This was the first direct assay microgravity environment of space. By applying a biotechnology of bacterial virulence in space without the effects of re-entry into model to this unique discovery process, the company finds Earth’s atmosphere and delays due to offloading the experiment novel biomarkers that may not be identifiable via terrestrial from the Space Shuttle. This experimental model identified single experimentation. Through this method, Astrogenetix expects to gene deletions of both Salmonella sp and Methicillin-resistant shorten the drug development time frame and guide relevant Staphylococcus aureus for potential acceleration of vaccine-based therapeutics agents (or diagnostics) into the clinical trial process applications. The investigative team included Timothy Hammond, more quickly and cost-effectively. Patricia Allen, Jeanne Becker, and Louis Stodiek.

scientists and engineers were educated discovery, and the historic lunar and trained. In the words of Nobel missions by the Apollo astronauts, Prize-winner Baruch Blumberg, the Space Shuttle expanded the “Like the pioneering voyages of the boundaries of biology, providing early European explorers to the New insights into the role and influence World, Darwin’s voyages of scientific of gravity on living systems.”

Major Scientific Discoveries 419