Microgravity The Space Shuttle cargo capability in the early 1980s stimulated a wave of imaginative research. Space-based microgravity research gave Research new insights into technologies critical to the space program, medical in the , and industry. Shuttle Era NASA dedicated over 20 shuttle missions to microgravity research as a primary payload, and many more missions carried microgravity Bradley Carpenter research experiments as secondary payloads. The space agency’s Cells in Space microgravity research strived to increase understanding of the effects Neal Pellis of on biological, chemical, and physical systems. Living Physical Sciences systems benefited as well. Cells, as they adapted to microgravity, in Microgravity revealed new applications in biotechnology. Bradley Carpenter Iwan Alexander Shuttle-era microgravity research was international in scope, with Commerical Ventures Take Flight contributions from European, Japanese, and Russian investigators Charles Walker as well as commercial ventures. Several missions in which the Spacelab module was the primary payload were either officially sponsored by a partner agency, such as the Japanese or German space agency, or they carried a large number of research experiments developed by, or shared with, international partners. NASA and its partners established close working relationships through their experience of working together on these missions . These collaborations have carried over to operation of the International Space Station (ISS) and will provide the foundation for international cooperation in future missions to explore space.

Much of the Space Shuttle’s legacy continues in research currently under way on the ISS—research that is building a foundation of engineering knowledge now being applied in the design of vehicle systems for NASA’s next generation of exploration missions.

420 Major Scientific Discoveries Cells in Space experiments in cell biology, controlled culture environment. The microbiology, and plant biology. design of equipment for propagation of cells in microgravity involved special The rationale for studying cells in Question: Why fly cells in space? considerations that the Earth-based cell space is the same as it is on Earth. Answer: It helps in space biologist seldom accommodates. Cells can be a model for investigating exploration and provides novel various tissues, tumors, and diseases. approaches to human health NASA’s work with cells can reveal Unique Conditions Created research on Earth. characteristics of how terrestrial life by Microgravity The NASA Biotechnology Program adapts to the In microgravity, gravity-driven sponsored human and animal cell as well as give rise to technologies and convection is practically nonexistent. research, and many of the agency’s treatments that mitigate some of the Gravity-driven convection is familiar to laboratory modules problems humans experience in space us in a different context. For example, supported the cell research and exploration scenarios. Embarking on air conditioners deliver cool air development necessary for space cell biology experiments in space through the vents above. Cooler air is exploration and Earth applications. spawned an almost revolutionary more dense than warm air and gravity The shuttle, in particular, hosted approach to accommodate cells in a settles the more dense cool air closer to the floor, thereby displacing the warm air up to be reprocessed. These Cell Growth in Microgravity: Going same convective flows feed cells on Earth-based cultures where the cooler Without the Flow fluid streams toward the bottom of the vessel, displacing warmer medium to In the early stages of planning for cell the upper regions of the container. culture in space, scientists theorized that This process provides sufficient nutrient transport for the cells to thrive. cells may not survive for long because of a potential inability to assimilate nutrients from the culture fluid. Although What Happens in Microgravity? undisturbed fluid appears not to be Scientists theorized that, in moving, gravity-driven convection mixes microgravity, cells would rapidly the fluid. Gravity continually moves colder, assimilate nutrients from the medium more dense fluid to the bottom of the and, in the absence of gravity-driven Zone of Depletion: convection, the cells would consume vessel, displacing the warmer fluid to the oxygen is depleted rst; top. As the fluid on the bottom is heated, glucose is second; all the nutrients around them. Nutrient other nutrients follow. transport and the mechanical sensing the process is repeated. In space, there mechanism operate differently in the is no gravity-driven convection to mix the medium and keep nutrients well distributed absence of gravity. NASA conducted and available to cells. Therefore, theoretically, cells should experience a decrease research on the Space Shuttle over in the availability of nutrients, thus slowing assimilation down to their intrinsic rate of the last 2 decades of the program to diffusion—a rate potentially insufficient to support life. Oxygen should be the first elucidate the nature of cell response essential to be depleted within a matter of minutes, followed by glucose. In reality, the to microgravity and showed that, while cells do not die. Instead, they adapt to the lower rate of nutrient delivery and proceed most cell cultures can survive in microgravity, substantial adaptation is to survive. Apparently, other more subtle convections (e.g., surface tension driven) may required. The outcome of this cellular supply sufficient transport of nutrients. Understanding these concepts was essential to research is the emergence of space cell the design of cell culture systems for humans in space. biology as a new scientific discipline.

Major Scientific Discoveries 421 Suite of Equipment To meet the various requirements Transition of Cells for a full complement of cell biology experiments, NASA developed a suite of equipment that spans from relatively simple passive cell cultures to complicated space bioreactors with automated support systems. The experiments that were supported included space cellular and molecular biology, tissue engineering, disease modeling, and biotechnology. Launch Return Space cell biology includes understanding the adaptive response Microgravity to microgravity in the context of Changes: metabolism, morphology, and gene r4IBQF expression, and how cells relate to r(FOF&YQSFTTJPO r4JHOBM5SBOTEVDUJPO each other and to their environment. r-PDPNPUJPO r%JGGFSFOUJBUJPO Analog and Flight Research The cell culture in space, and to a certain extent in microgravity analogs, is an environment where mammalian cells will associate with each other spontaneously, in contrast to Earth culture where cells sediment to the Earth Gravity Earth Gravity lower surface of the container and grows as a sheet that is one cell layer thick. In space and in an analog As cells transition to space, changes occur that provide new insights into life systems culture, the association results in the and offer the prospect of understanding the role of gravity in life as it developed on assembly of small tissue constructs. this planet. A stylized cell with its nucleus (red) containing genetic material (blocks), A construct may be made up of a an example of a cell surface receptor and its communication linkage to the nucleus, single type of cell, or it may be and the external simulating factor (yellow ball) are displayed above in three phases: designed to contain several types of cells. As the assembly proceeds, cells 1) on Earth at unit gravity; 2) following launch into microgravity; and 3) return to Earth. divide and undergo a process of Within a few seconds after arriving in microgravity, the cell becomes round and, differentiation where they specialize thereafter, a cascade of changes follows over the next few days and weeks. As the into functions characteristic of their cell adapts to the new environment, it turns on some genes and turns off others. tissue of origin. For example, as liver The ability to respond to certain external stimuli is diminished. This is due to a cells go through this process, they disruption (indicated by the “ ”) of some cell surface receptor signal transduction produce constructs that look and function akin to a native liver pathways. In addition, cells locomote (move) very poorly in microgravity. The ability to specimen. In other instances, colon mature and develop into functional tissues and systems seems to be favored. These cancer cells mixed with normal cells observations provide a basis for robust investigation of microgravity cell biology as will produce assemblies that look and a means to understand terrestrial life in space and to use the space environment to act like a fresh tumor biopsy. foster goals in biomedical research on Earth.

422 Major Scientific Discoveries These microgravity-inspired technologies are now used in cell culture and some tissue engineering studies. Scientists and physicians can produce tissues to be used as research Mary Ellen Weber, PhD models (e.g., cardiac tissues; cancers on STS-70 (1995) of the kidney, liver, colon, prostate, and STS-101 (2000). breast, and brain). Microgravity cultures are used in biotechnology Colon Cancer Cells’ to produce cell by-products that can unique response be used to treat diseases and produce in microgravity: vaccines to prevent diseases. reassembly and reconstruction of Astronaut Mary Ellen Weber with the space NASA Develops Special their tissue origin. bioreactor on STS-70. Equipment to Grow Cells— Space Bioreactor “One of my fondest memories of my shuttle missions was working preflight with the bioreactor team on its first experiment in space. I can still vividly The use of microgravity cell culture to remember my awe in watching colon cancer cells growing into cancer tissue, engineer tissues from individual cells and the satisfaction in seeing it all come together. The experiment held so began in systems where cells were grown in a tubular vessel containing much promise early on that it was manifested on the mission well before all its a bundle of hollow fibers that carried details were worked out, and this gave me, its assigned crew member, the nutrients to the cells in the tube. opportunity to work far more closely with these dedicated scientists than usual As concepts for space bioreactors in getting it ready to go as well as the opportunity to learn far more about the matured, the cylindrical rotating science. Most researchers get to see their hard work come to fruition first hand, systems emerged because of several and as I watched the bioreactor successfully working in space, I was really advantages: greater volume; a format that supported both analog culture struck—unexpectedly so—by the fact that they could not be there to witness on Earth and space cell culture; and it with me. It gave me a great sense of responsibility to do right by them, and it a natural association of cells with made me all the more proud to be a part of it.” each other rather than with the plastic or glass vessel. The system could be rendered compatible with Earth or space by setting the rotation regime characteristics consistent with heart), and gas exchange module to the gravitational conditions. NASA maintaining live cells and set the that delivered oxygen and removed performed a validation of the first stage for the first rotating bioreactor carbon dioxide (essentially acting as rotating bioreactor system on Space experiments in space. a lung). The results showed that Transportation System (STS)-44 microgravity afforded continuous The first investigation on the shuttle (1 991 ). No cells were used for the suspension of the cells, spontaneous (STS-70 [1 995]) used colon cancer validation test. Instead, scientists used association, cell propagation, and cells as the test population to determine small beads made of inert polymer formation of a tissue construct. whether the new bioreactor system as surrogate cells. This enabled was compatible with cell assembly, The space bioreactor facilitated rapid observation of the media delivery growth, and maturation. The bioreactor assembly, substantially larger system and movement of “cells” was composed of a cylindrical culture constructs, and metabolically active along flow streams in the culture fluid. vessel, culture medium reservoir, cells. The experiment confirmed the Results of the experiment showed waste reservoir, pump (functions as a hypothesis that microgravity facilitates

Major Scientific Discoveries 423 tissue morphogenesis (formation) and Interest in space cell culture opened Microgravity-induced set the stage for use of the space the new vista of space cell biology. Changes at the Cell Level environment to identify the essential Mammalian cells are enclosed by stages in tissue engineering that are a pliable lipid membrane. On Earth, Cells Adapt to Microgravity novel to microgravity. The ability to those cells have a characteristic On STS-62 (1994 ), NASA demonstrated engineer tissue from individual cells shape; however, when in microgravity, that cells could grow in microgravity provided tissue for research, drug most mammalian cells become more culture without succumbing to the lack testing, disease modeling and, spherical. Following this shape change, of convective mixing of the medium. eventually, transplantation into a cascade of adaptive changes occurs. This demonstration occurred in a static afflicted individuals. Subsequent colon Some genes are turned on while culture system wherein rapidly dividing cancer experiments on STS-85 (1 997) others are turned off, some receptors colon cancer cells and slowly dividing identified some of the novel metabolic on the surfaces of cells cease to cartilage cells were placed in small properties and demonstrated the transduce signals to the inside, many culture vessels held at 4°C (39°F) mechanism used by the cancer to cells cease locomotion (movement), (refrigeration temperature) until spread to other organs. and other cells will mature and change arriving in microgravity and reaching function spontaneously.

ColCon Ca ncer C ell Culture s

SStandardtandard GGround-basedround-based Space Monolayer BBioreactorioreactor Cell BioreactorBioreactor CulturCultureree CulturCultureree CellCell CultureCulture

No Three-dimensional Tissue 2 mm (0.8 in.) >10 mm (0.4 in.)

>10 mm (0.4 in.)

The first experiment using living tissue in the space bioreactor developed at Johnson Space Center used human colon cancer cells to determine whether there are specific advantages to propagation of cells in space. NASA conducted this experiment on STS-70 (1995) and again on STS-85 (1997). The right panel shows the large tissue assemblies that readily formed within a few days in microgravity when compared with the ground-based bioreactor analog, where the assemblies were much smaller and less well developed. For reference, the left panel shows the same cells in standard culture on Earth, where the cells grew and attached to the petri dish in a single layer with little evidence of tissue formation. This experiment set the stage for using space cell culture to produce tissues with a greater parity to the actual tumor in situ in the patient. Furthermore, unlike the standard culture, it demonstrated the signature biochemicals associated with the disease.

424 Major Scientific Discoveries orbit where the temperature was raised conditions. Thus, bioreactors to Immune Cells Have Diminished to 37°C (98.6°F) (body temperature) support these cells for long-term Locomotion in Microgravity to initiate growth. Results showed that experiments needed to accommodate colon cancer cells rapidly assimilated re-feeding and waste disposal to ensure The immune cells known as nutrients from the medium while health of the tissue. The results of this lymphocytes locomote and traverse cartilage took more than twice as long experiment set the requirements for many environments within the body to deplete nutrients. Neither cell final design of the space bioreactors to to engage invading microbes and population succumbed to the depletion grow bulk culture in microgravity. effect their destruction or inactivation. but, rather, changed their metabolic Experiments conducted on STS-54 profile to adapt to more stringent (1 993) and STS-56 (1 993) were the first

Cell Locomotion

Pre-experiment Setup A Non-locomoting Lymphocyte

Matrix

Cells

Earth Gravity Microgravity Experimental Experimental

B Locomoting Lymphocyte

Locomotory Distance

Leading Edge

Human immune cells (lymphocytes) locomote through tissue matrix (intercellular cement) as part of their normal function in mediating immunity. Experiments performed in the analog culture system indicated a profound loss of the ability to locomote through matrix. This experiment described above was performed on STS-54 (1993) and STS-56 (1993). The matrix material is gelled collagen cast in two separate upper and lower phases, and the interface is loaded with human lymphocytes. Some were incubated as ground controls and others were transported to the shuttle. Locomotion remained arrested throughout the preparation and transport to space by maintaining them at 4°C (39°F). Upon arrival in microgravity, the temperature was raised to 37°C (99°F) in the experimental and control specimens. The lower left control shows how the lymphocytes locomote symmetrically up and down. Distance of locomotion to the leading edge can be measured using a microscope. In space, the experimental specimens evidenced very little locomotion. Non-locomoting lymphocytes are round and incapable of deforming (photo A), whereas locomoting lymphocytes deform and extend the process toward the direction of movement (photo B). The loss of locomotion in space indicates a potential defect in immunity in space. Loss of locomotion for extended periods of time can profoundly impact immunity. Locomotion is essential to this trafficking of lymphocytes through lymphoid organs and to sites of infection or invasion by cancer cells.

Major Scientific Discoveries 425 to show that these important immune microgravity will give new insights to STS -1 05 (20 01 ) hosted an experiment cells have diminished locomotion in the changes necessary for adaptation. on human ovarian carcinoma, asking microgravity. Lymphocytes from a total whether space cell culture gave a gene New technology allows for the of six donors were introduced into expression profile more like the actual investigation of changes in more than natural matrix (collagen) and kept at tumor in the patient or like that observed 10,000 genes in a single experiment. 4°C (39°F) until achieving orbit, in standard cell culture on Earth. The first genetic signatures for cells where the temperature was raised to Results showed tissue-like assemblies in microgravity were conducted on 37°C (98.6°F). Results showed that that expressed genes much in the STS -1 06 (2000) using human kidney locomotion was inhibited by more than same profile as in the tumor. This is cells as a test model. The results 80% in all specimens. Locomotion is a significant because these results give provided a provocative revelation. critical function in the immune system. scientists a more robust tool to identify Out of 10,000 genes tested, more Cessation does not have immediate specific targets for chemotherapy as than 1,600 were significantly changed effects; however, if sustained, it can well as other treatments. in expression. Normally, a suite of contribute to a decline in immune genes refined through evolution is on Space cell culture offers a unique function in space. Preparation for the order of 20 to 40 genes. The opportunity to observe life processes long-duration (in excess of 1 year) enormous response to microgravity that otherwise may not be apparent. excursions in space will require suggests there is not a refined suite, Forcing terrestrial life to muster its extensive research and preparation to and the response is made up of genes adaptive mechanisms to survive the ensure the immune system functions that are essential to adaption—some new environment makes evident some normally throughout the entire are incidental and unrelated to new characteristic and capabilities mission. From strictly a cell biology adaptation, and some are consequential of cells and other terrestrial life. perspective, the experiment was to the incidental activation of One of the observations is the induction a milestone demonstration that unnecessary genes. Analysis of gene of differentiation (the process by which locomotion can be modulated by a expression showed that hypergravity cells mature and specialize). The physical factor (gravity) rather than (centrifugations at 3 gravitational shuttle hosted numerous experiments a biochemical factor. force [ g]) has a more refined set of that confirmed unique differentiation about 70 genes. This is likely due to patterns in cancer cells from colon, Gene Expression Changes terrestrial life experiencing hypergravity ovary, and adrenals as well as human during accelerations (running, starting, kidney cells and mouse cells that Gene expression—defined as which or stopping). On the other hand, analog differentiate into red blood cells. genes are turn on and/or off in response microgravity culture on Earth also had All but the mouse cells were on to changing conditions—changes a large response suite of 800 genes. STS -1 05. The mouse cell experiment with almost every stimulus, stress, or Of those genes, only about 200 were was performed on STS -1 08 (20 01 ). alteration offered by our environment shared with the microgravity suite. and activities. Most of these responses In summary, these experiments at the gene level occur in suites of The significance of these results is opened a new understanding of the genes that have been refined through multifold. For short-duration missions, differentiation process and products evolution. This is why life systems we will want to manage any untoward of cells. The processes revealed can adapt to various environmental effects brought about by the response. aspects useful in proposing new stimuli to survive and even thrive. For long-duration missions in space approaches to treatment of disease Since all Earth organisms evolved and permanent habitation on planetary and tissue engineering and to in Earth gravity, the effect of surfaces, we will want to know understanding complex developmental microgravity on these genetic whether there is a refinement in the pathways. On the product side, suites was unknown. Understanding gene suite and whether, in conjunction materials were produced that may lead the response at the genetic level to with the new environment, it poses to new biopharmaceuticals, dietary the possibility for permanent changes. supplements, and research tools.

426 Major Scientific Discoveries Gene Expression Differs at Three Gravity Levels

Microgravity 3g Analog Culture y t i s ) l n a e t t n n I e

n m i o r i e s p s x e r e ( p x E

Expression Intensity (control)

NASA performed experiments using human kidney cell 10,000 genes are up-regulated or down-regulated compared cultures on STS-105 (2001) and STS-106 (2000) to investigate with the control, meaning that it is unlikely that terrestrial life the gene expression response to microgravity and compare has a preformed, inherited set of genes used to adapt to it to hypergravity and to an analog culture system on Earth. microgravity. The cells were then subjected to 3 gravitational In a sample set (10,000 genes), the genes turned on and off force ( g) using a centrifuge. The array is more compacted. compared with the control in normal culture on Earth. If the Fewer than 70 genes are affected, suggesting that terrestrial life expression is identical in control and experimental conditions, has a history of responding to hypergravity. The last panel the dots line up on the diagonal line passing through the shows the same cells in response to microgravity analog cell origin. Genes that are turned on are above and beyond the culture. More than 700 genes modified in response to the first parallel diagonal line. Genes below and beyond the first analog system that rotates the cell culture, such that the cells parallel diagonal are decreased in expression compared are falling continuously. Analysis indicated that it shared about with the control. In microgravity, more than 1,600 of the 200 genes with that observed in microgravity.

Observations from early experiments system, durability, and conveniently pliable product when contrasted to strongly suggested that the space observed characteristics of maturity native cartilage; and 3) showed that environment may promote conditions and functionality. STS-79 (1 996) flew on transplantation the less mature, that favor engineering of normal a bioreactor containing beef cartilage more pliable space cartilage remodels tissues for research and t ransplantation. cells to the Russian space station into the recipient site much better Experiments in ground-based analog . The culture set a landmark for than mature cartilage. The study culture suggested that microgravity 137 consecutive days of culture suggests that microgravity and space can facilitate engineering of functional in microgravity. Results from this technology are useful in developing cartilage starting from individual cells. experiment and subsequent ground- strategies for engineering tissues from (Cartilage is the tissue that forms the based research: 1) confirmed the utility a small number of cells. joints between bones.) Cartilage of microgravity in tissue engineering; tissue was chosen because of its low 2) showed that generation of cartilage metabolic demand on the culture in microgravity produces a very

Major Scientific Discoveries 427 Human Prostate Cancer Cells

On STS-107 (2003), NASA performed an experiment to investigate a model of metastatic prostate cancer. Prostate cancer is more manageable as a local disease, Flight which is why there is such emphasis on preventive measures. Management of the disease becomes difficult when the tumor metastasizes to bone. Therein, the tumor establishes a relationship to that which contributes to its intractable state. Space cell culture offers an environment consistent with culturing two different kinds of cells harmoniously and also favors reassembly of cells into ordered tissue arrays. The upper cylinder shows the rapid assembly of the cells into tissue constructs that Ground are much larger than those in the lower cylinder (controlled on Earth). The assemblies propagated in space achieved diameters approaching 2 cm (0.79 in.), while those on the ground were about 3 mm (0.19 in.). The result demonstrated the value of space cell culture in providing robust models for investigating human Coculture of Bone Marrow Stromal Cells and disease. These specimens were not analyzed, since they were not recovered from Prostate Cancer Cell Line the ill-fated Columbia mission.

Human Prostate provide a platform for demonstrating The Future of Space Cancer Cells Grew Well the contribution of the normal cell Cell Biology in Microgravity environment to the establishment and maintenance of the tumor at a new site. Research in cell science plays a In pursuit of using space to understand With such a model, we may identify significant role in . disease processes, NASA conducted new targets for therapy that help Cells, from bacteria to humans, are experiments on STS-107 (2003) prevent establishment of metastases. the basic unit of all life. As is true to understand the special relationship for Earth-based biomedical research between prostate cancer and bone in cells, the observations must be marrow cells. Prostate cancer, like breast cancer, is a glandular tumor that is a manageable disease when treated at its origin. In contrast, Important Questions: when tumors spread to other areas of the body, the disease becomes Does the cell respond directly to the change in gravitation force, or is it responding to intractable. The experiment on conditions created by microgravity? STS-107 modeled the metastatic What does terrestrial life do to adapt and thrive in space? site in the bone for prostate cancer. Results showed the largest tissue Does microgravity influence how life might evolve after many generations in space? constructs grown in space and What is the effect of microgravity on cells from major organs and the immune and demonstrated the outcome of the digestive systems? cohabitation of these two cell types. It also showed that we could produce How much gravity is necessary to have normal function? these models for research and

428 Major Scientific Discoveries

What Is the Relationship Between Gravity and Biological Responses?

Hypogravity Hypergravity e s n o p s e R

l a c i g o l o i B

0.00001 0.001 0.010.1 10 Mars

Shuttle and Gravity Moon Earth Space Station

The future of space cell biology includes a critical question regarding the relationship of gravity to various biological responses within the systems of the human body as well as in microbes, plants, animals, and bioprocessing systems. The possible relationships are depicted as lines on the graph, where values are known for the shuttle, space station, and Earth. The knowledge of the actual relationship will enable better understanding of human adaptability on the moon (1/6 gravitational force [ g]) and Mars (3/8 g). Furthermore, it will assist in the design of artificial g technologies. Knowledge of biologic responses on Earth reveals that the response relationships to stimuli are sigmoid, as in the yellow and green curve, and that the range of the response is usually within one tenfold increment of the normal physiologic state (Earth). Thus, the green relationship may be the most likely one. With this probability, research on moon and Mars gravity becomes more important in exploration planning. Depending where on the “ g” scale the s-shaped part of the curve flexes, that is the amount of g that will begin to restore normal function.

consistent at the tissue, organ, and on cell-based research to investigate radiation, and environmental factors whole-organism level to be useful in fundamental life process, diseases, and will come from cell studies conducted developing treatments. Because we the effects of drugs and environment in space and in analog culture systems. cannot perform experiments that may on life. Thus, part of our understanding The answer to the last question may be difficult or even unethical in of microgravity, hypogravity (such as have the most impact on risk reduction humans, biomedical researchers rely the level found on Mars or the moon), for humans exploring space. The answer

Major Scientific Discoveries 429 will not only reveal the gravity force Physical Sciences The lift created by air flowing around necessary to have acceptable the wings keeps an airplane and your physiologic function (bone health, in Microgravity seat aloft under you—and that’s a good muscle conditioning, gastrointestinal What is Gravity? thing. Now imagine being in an performance, etc.), it also may set airplane that has somehow turned off requirements for the design of vehicles, Gravity is a difficult thing to escape. its lift. In this scenario, you would habitats, exercise systems, and other It also turns out to be a difficult thing fall as fast as the airplane was falling. countermeasures. The pervasive to explain. We all know enough to say With your seat falling out from under question is: How much gravity do you that things fall because of gravity, you at the same rate, the seat would need? We do not know the mathematical but we don’t have easy answers for no longer feel your weight. No force basis of the relationship of gravity to how gravity works; i.e., how the mass would be holding you in it. In fact, you biologic function. The history of of one object attracts the mass of would be approximately weightless research in space focused on another, or why the property that gives for a short period of time. microgravity (one millionth of Earth matter a gravitational attraction gravity) and, of course, there is a wealth (gravitational mass) is apparently the in Space of data on biologic function on Earth. same property that gives it momentum Given these two sets of data, at least (inertial mass) when in motion. Gravity The essence of conquering gravity four different relationships can be is a fundamental force in physics, but and sustaining weightlessness for envisioned. Of the four, the sigmoid how gravity is bound to matter and longer than a few seconds is velocity. (s-shaped) relationship is the most how gravitational fields propagate in A spacecraft has to be moving very fast likely. The likely level for biological space and time are among the biggest to continually fall toward Earth but still systems will be around 1/ 10 g. Since questions in physics. stay in space. Reaching that speed of a the moon and Mars are 1/6 and 3/8 g, little over 27,500 km (1 7,000 miles) per Regardless of how gravity works, it’s respectively, it will be critically hour provides a lot of the excitement clear that Earth’s gravity field cannot be important that scientists have an of . It takes a great deal of easily escaped—not even from a couple opportunity to determine biological energy to put an object into Earth orbit, hundred miles from our planet’s surface. response levels and begin to conduct the and that energy goes primarily into If you stepped into a hypothetical space mathematical relationship between g attaining orbital velocity. An astronaut elevator and traveled to the 100,000th and biological function. in Earth orbit has kinetic energy floor, you would weigh almost as much equivalent to the explosion of around As NASA proceeds toward a phase as you do on Earth’s surface. That’s 454 kg (1 ,000 pounds) of TNT. Once an of intensified use of the International because the force that the Earth exerts astronaut reaches orbital velocity, he or Space Station (ISS) for research, on your body decreases at a rate she is a long way toward the velocity it is important to have a robust plan inversely proportional to twice your needed to escape Earth’s gravity, which that will continue the foundational distance from the center of the Earth. is 1.4 times orbital velocity. research conducted on the shuttle and In an orbit around the Earth, the force procure the answers that will reduce exerted by our planet’s mass on a When you’re in a vehicle moving fast health risks to future spacefarers. spacecraft and its contents keeps enough to fall continually toward the When the United States enacted the them continually falling toward the Earth, it doesn’t look or feel like you’re national laboratory status of the ISS, Earth with an acceleration inversely falling. At least, not the kind of falling it set the stage for all federal agencies proportional to the square of the that people are accustomed to—the to use the microgravity environment distance from the center of the planet. kind that ends in a painful collision for their research. Increasing the That’s Newton’s law of gravitation. with the ground. You have the feeling science content of orbiting facilities of being light, and the things around Gravity certainly works on and in will bring answers that will enable you are light, too. In fact, everything airplanes. When you are traveling in reduction of risks to explorers and help floats if not fastened to something. an airplane during a steady flight, ensure mission success. Items in the spacecraft are falling with gravity keeps you firmly in your seat.

430 Major Scientific Discoveries director at Marshall Space Flight What is Microgravity? Center from 1960 to 1970) had more practical applications, such as making ball bearings in space. Several simple Astronaut and Shuttle Orbit experiments were flown on Apollo 14 and performed by the crew on the New return from the moon. More Accidental Wrench experiments were conducted on the Wrench Release Orbit three missions—an early space station built in the 1970s—with promising results reported in areas such as semiconductor crystal growth. By the time of Skylab, however, the next era of space exploration was on the horizon with the approval of the in 1972.

Fundamental Physics One of the great questions of physics is the origin of long-range order in systems of many interacting particles. Imagine an astronaut tethered to the outside of the shuttle. The astronaut and the shuttle are in orbit together. If the astronaut releases a tool, the tool generally goes into a slightly different orbit The concept of order among particles is because it has to maintain a different speed to achieve the same orbit as the shuttle. The astronaut, a broad one—from simple measures of shuttle, and tool are in orbit with their outward acceleration from the Earth, balanced by Earth’s order, such as the density of a collection gravity. The slight differences in orbit make it seem, to the astronaut, that a small acceleration is of molecules or the net magnetization of pushing the wrench away. This is microgravity. the atomic nuclei in an iron bar, to complex patterns formed by solidifying you. With everything accelerating falling fast enough for air resistance to alloys, turbulent fluids, or even people toward Earth at precisely the same rate deform it, the absence of gravitationally milling about on an urban sidewalk. within this falling frame of reference, created hydrostatic pressure in the In each of these systems, the “particles” Earth’s gravity is not apparent. To an falling lead drop that allowed it to involved interact nearly exclusively with outside observer, gravity is still assume a spherical shape as the liquid only their near neighbors; however, it’s obvious—it’s the reason you’re in an was driven by thermodynamics into a a common observation in nature that orbit and not flying away from Earth in volume of minimum exposed surface. systems composed of many interacting a line to space. The falling shot quickly hardened as it elements display ordering or coherent cooled, and it collected in a water bath structures over length scales much larger at the bottom of the tower. The than the lengths describing the particles Early Low-gravity Technology shot-manufacturing industry relied on or the forces that act between them. this early low-gravity technology until The consequences of being weightless The term for the distinctive large-scale the first decade of the 20th century. were merely hypothetical until the behavior that results from cooperatively dawn of space travel, with one small interacting constituent particles is exception: One hundred years prior to Physics Environment in Space “emergent phenomena.” Emergent the launch of the first beyond phenomena are of interest to science Earth’s atmosphere, spherical lead shot Spaceflight provides a good place to because they appear to be present at was manufactured by allowing molten conduct experiments in physics— virtually every scale of the natural lead to solidify in free fall inside a experiments that would not be possible world—from the microscopic to the shot tower. As long as the shot wasn’t on Earth. Wernher von Braun (center

Major Scientific Discoveries 431 galactic—and they suggest that common principles underlie many different complex natural phenomena. Critical Point Experiments Test Theories

Phase transitions at a critical point The critical point of xenon is 289 K, 5.8 MPa—or 15.85°C (60.53°F), 57.2 atm. Note provide physicists with a well-controlled that the axis on the left is logarithmic. Research on STS-52 (1992) measured the phase model of an emergent phenomenon.

Pure materials, as determined by boundary between normal liquid helium and superfluid helium. (Superfluids, such as thermodynamics, exist in a particular supercooled helium-4, exhibit many unusual properties. The superfluid component state (a “phase”) that is a function only has zero viscosity, zero entropy, of temperature and pressure. At a point and infinite thermal conductivity.) 100 1,000

called a “critical point,” simple ) This shuttle research confirmed s Solid e r 10 single-phase behavior breaks down and e

the renormalization group theory h 100 Liquid

p Critical

collective fluctuations sweep through s better than any Earth research. o Point

m 1.0 the system at all length scales—at least t

a 10

These types of research questions ,

in theory. The leading theory that has a Vapor are now being studied on the P M 0.1 ( been developed to describe emergent 1.0

e Triple International Space Station. r phenomena, such as critical point u point s s

e 0.01 fluctuations, is called “renormalization r 0.1 NASA tested the theory for P -200 -100 0 100 group theory.” It provides a model gas-liquid critical phenomena on -368 -148 32 212 that explains how the behavior of a STS-97 (1997). Temperature ºC, ºF system near a critical point is similar over a large range of scales because the physical details of many interacting molecules appear to average out over those scales as a result of

Small particles in a colloidal solution assemble to form an ordered crystalline structure, such as the opalescent crystalline particles shown in this image taken on STS-73 (1995). Building an understanding of emergent phenomena remains one of the great challenges of physics. Explaining the origins of long-range order and structures in complex systems is key to advancing potential breakthroughs, and the The Lambda Point Experiment cryostat experiments in fundamental physics aboard the assembly (identified by the JPL insignia) in shuttle played a significant role. the STS-52 (1992) payload bay.

432 Major Scientific Discoveries cooperative behavior. Renormalization impacting the crystal are diffracted by The first step in growing protein group theory is one of the great the electron densities of each atom of crystals is preparation of as pure a developments of physics during the each molecule arranged in a highly protein sample as can be obtained in 20th century. The most precise tests ordered crystal array. Because nearly quantity. This step was made easier for of this theory’s predictions for critical each atom of each molecule is in a many molecules in recent years with point phenomena relied on experiments highly ordered and symmetrical the ability to increase the products of carried aboard the shuttle. crystal, the x-ray diffraction pattern individual genes through gene with a good crystal is also highly amplification techniques; however, Careful critical point experiments ordered and contains information every purification step is still a tradeoff required the ultimate in precise control that can be used to determine the with loss of starting material and the of pressure and temperature to the structure of the molecule. Obtaining likelihood that some of the molecules in extent that the difference in pressure, high-quality protein crystals has solution will denature or permanently caused by gravity, between the top been a critical step in determining a change their shape, effectively and the bottom of a small fluid sample protein’s three-dimensional structure becoming contaminants to the native in a laboratory on Earth by the mid since the time when Max Perutz first molecules. After biochemists have a 1970s became the limiting factor in used x-ray crystallography to reasonably pure sample in hand, they experimental tests of renormalization determine the structure of hemoglobin turn to crystal-growing recipes that group theory. in 1959. A few proteins are easily vary many parameters and hunt for a Research on Space Transportation crystallized. Most require laborious combination that will produce suitable System (STS)-52 (1 992) measured trial-and-error experimentation. crystals. Although usable crystals can the phase boundary between normal liquid helium and superfluid helium. Superfluids, such as supercooled helium-4, exhibit many unusual properties. The superfluid component has zero viscosity, zero entropy, and infinite thermal conductivity. This shuttle research confirmed the renormalization group theory better than any Earth research.

Protein Crystal Growth A foundation for the explosion of knowledge in biological science over . the past 50 years has been the d e v r e understanding of the structure of s e r

s t molecules involved in biological h g i r

l l A

functions. The most powerful tool for . l a n determining the structure of large r u o J

l biomolecules, such as proteins and a c i s y

DNA, is x-ray crystallography. In h p o i B

traditional x-ray crystallography, an , 8 9 9 x-ray beam is aimed at a crystal made 1 of the molecule of interest. X-rays © This molecular structure of the Tobacco Mosaic Virus was captured at 1.8-angstrom (0.18-nanometer) resolution from analysis of crystals obtained on experiments performed on the International Microgravity Laboratory-2 mission (STS-65) in 1994. The best of these crystals was 30 times larger and produced 237% more data than any previous Earth-grown crystals and yielded what was, at that time, the highest-resolution structure of a virus ever obtained.

Major Scientific Discoveries 433 be as small as 0 .1 mm (0.004 in.) on a side, the crystals often take weeks or even months to grow, so biochemists will normally try many combinations Eugene Trinh, PhD simultaneously and in specially Payload Specialist and NASA expert in designed trays. It is not unusual to microgravity sciences on STS-50 (1992) spend several years finding good US Microgravity Laboratory-1 growth conditions for a protein. Spacelab mission.

Effects of Gravity on Protein “The Space Shuttle gave scientists, for Crystal Growth the first time, an opportunity to use the Eugene Trinh, PhD, a payload specialist Gravity has two principal effects in space environment as an experimental for this mission, is working at the protein crystal growth. The first is to tool to rigorously probe the details of Drop Physics Module using the glove cause crystals to sink to the bottom of physical processes influenced by gravity box inside the first US Microgravity Laboratory science module on STS-50. the solution in which they are growing. to gather better theoretical insight As a result, the growing crystals can and more accurate experimental data. This precious new information could not pile up on each other and fuse, thus becoming a single mass that can’t be have been otherwise obtained. It furthered our fundamental understanding of used for data collection. The second nature and refined our practical earthbound industrial processes.” effect of gravity is to produce weak but detectible liquid flow near the surface of the growing crystals. Having contributed some of its dissolved protein Littke’s experiment aboard STS-61A, Modeling Protein Crystal Growth the D-1 Spacelab mission (1 985), to the growing crystal, liquid near the Physicists and biochemists constructed where he reported achieving crystal crystal surface is lighter than liquid models of protein crystal growth volumes as much as 1,000 times larger farther away. Due to gravity, the lighter processes to understand why some than comparable Earth-based controls, liquid will rise. The consequences of proteins produced better crystals in opened a huge level of interest this flow for crystal quality are complex microgravity while others did not, including many international and and even now not fully understood. and why crystals sometimes started commercial investigators. Professor At the beginning of the shuttle era, growing well but later stopped. Charlie Bugg of the University of German chemist Walter Littke thought Investigators applied techniques like Alabama, Birmingham, working with that liquid flow near the growth surface atomic force microscopy to examine Professor Larry DeLucas, who went would interfere with the molecules the events involved in the formation on to fly on the US Microgravity on the surface finding their places in of crystalline arrays by large and Laboratory- 1 mission (1 992) as a a crystal. Before the first launch of the rather floppy protein molecules. payload specialist, eventually developed shuttle, he conducted several promising The role of impurities in crystal a community of nearly 100 investigators short rocket-launched experiments in growth and crystal quality was first interested in flying proteins. which several minutes of low gravity documented through the work of were achieved in a suborbital flight. Some investigators obtained crystals Professor Alexander McPherson that gave spectacular results, including (University of California, Irvine), Protein Crystallization the highest resolutions ever attained at Professor Peter Vekilov (University on the Shuttle the time for the structure of a virus and, of Houston, Texas), and Professor The first protein crystallization in several instances, the first crystals Robert Thorne (Cornell University, experiments on the shuttle were suitable for structural analysis. Other Ithaca, New York), along with many conducted in a simple handheld device proteins, however, seemed to show no others. A simplified picture of a carried aboard in an astronaut’s kit. benefit from space crystallization. A popular model is that proteins that Encouraging results from Professor major focus of NASA’s research was to grow better crystals in microgravity explain this wide range of results. have small levels of contaminants in

434 Major Scientific Discoveries solution that preferentially adhere with an applied electric field, including the Continuous Flow Electrophoresis to the growing surface and slow the zone electrophoresis and isoelectric System. Several flights included a growth of the molecule-high step focusing, use the charge on a molecule McDonnell Douglas Astronautics layers that form the crystal. that is dependent on the solution Company technical expert who traveled properties (pH, ionic strength, etc.) on board as a payload specialist. Accelerated transport of contaminant around the molecule to separate species due to buoyant flow on Using this facility on the shuttle mixtures of molecules. The throughput Earth will increase the population middeck, Robert Snyder of the Marshall and resolution of these techniques of contaminant species on the surface, Space Flight Center, along with his are limited by the flow induced in the eventually inducing the formation of colleagues, discovered a new mode of solution containing the molecules, defects. Such proteins will produce fluid behavior—electrohydrodynamic heat generated by the electric current better crystals in microgravity because instability—that would limit the passing through the liquid, and strongly adhering contaminants are performance of electrophoresis sedimentation of the large molecules transported by slower molecular devices even after the distortion of during the necessary long separations. diffusion rather than convection, and gravity was eliminated. The discovery It was recognized that electrophoresis, their surface concentration on the of this instability in space experiments one of the earliest candidates for crystal remains lower. and subsequent confirmation by space experiments, would solve the mathematical analysis allowed This research has given a detailed problem of the disruptive heat-driven electrophoresis practitioners on Earth scientific foundation to the art and flows by minimizing the effect of to refine their formulations of technology of protein crystallization, gravity. Warmer, lighter liquid electrophoresis liquids to minimize the thus providing structural biologists wouldn’t rise in the electrophoresis consequences of electrohydrodynamic with a mechanistic understanding of cell, and device performance might be effects on their separations. This led to one of their principal tools. dramatically improved. experiments, conducted in a French-built Professor Milan Bier (University facility by French pharmaceutical Biotechnology and of Arizona, Tucson)—a pioneer in company Roussel-Uclaf SA, Paris. biological separations whose Electrophoresis The opportunity to conduct sequential discoveries did much to establish experiments of increasing complexity In the 1970s and early 1980s, the electrophoresis as a laboratory was one of the benefits of these shuttle biotechnology industry identified a large tool—conducted several important microgravity missions. Interest shown number of biological molecules with flight experiments with NASA. by these commercial and international potential medical and research value. As Professor Bier’s work on the organizations initiated in early shuttle The industry discovered, however, that Isoelectric Focusing Experiment missions continues today on the the difficulty of separating molecules of proceeded and flew on several early International Space Station (ISS). interest from the thousands of other shuttle missions, he came to molecules inside cells was a barrier to understand the impact of gravitational the production of therapeutic materials. effects on Earth-based electrophoresis. Materials Processing and Separation techniques for biological He developed designs for Materials Science molecules rely on using small electrophoresis equipment that The semiconductor industry grew up differences between molecules to minimized the impact of gravity. with the space program. The spatially separate the components of a Within a few years, these designs progression from commercial mixture. The mobility differences that became the industry standard and transistors appearing in the 1950s to separation methods use can result from a basic tool of the biotechnology the first integrated circuits in the 1960s the size of the molecule, substrates industry. Commercial organizations and the first microprocessors in the to which the molecule binds, or charge became interested in the potential 1970s was paralleled, enabled, and on the molecule in solution. of space-based bioseparations. McDonnell Douglas Astronautics driven by the demanding requirements Separation methods relying on the Company sponsored seven flights of space vehicles for lightweight, interaction of biological molecules of a large electrophoresis device— robust, efficient electronics.

Major Scientific Discoveries 435 Since the beginning of semiconductor technology, a critical issue has been the production of semiconductor crystals from which devices can be fabricated. As device technology advanced, more stringent device performance and manufacturing requirements on crystal size, homogeneity, and defect density demanded advances in crystal growth technology. In the production of semiconductor crystals, when molten semiconductor freezes to form a crystalline solid, variations in the temperature and composition of the liquid produce density variations that cause flows as less-dense fluid rises. These flows can cause poor distribution of the components of the molten material, leading to nonuniformities and crystal defects. Studying semiconductor crystal growth in low gravity, where buoyancy-driven Solidification of a liquid is an unstable process under many conditions. An initially flat boundary will flows would be extremely weak, evolve into an elaborate web of branched dendrites. In metals, the properties of the resulting solid are would give insight into other factors highly dependent on the structure formed during solidification, making the understanding of interface at work in crystal growth. There was evolution an important goal of materials science. also hope that in microgravity, quiescent conditions could be attained of Soviet microgravity research. Crystal The results of materials processing in which crystallization would be growth in space was a challenge and materials science experiments “diffusion controlled” (i.e., controlled because of the power needed by the strongly influenced scientific by stable, predictable mechanisms furnaces and the containment required understanding in several proportional to simple gradients of to meet NASA safety standards. technologically important areas: temperature and composition) and that, Eventually, however, furnaces were n Control of homogeneity and structural under these conditions, material of built and flown on the shuttle not only defects in semiconductor crystals higher quality than was attainable on by NASA but also by the European n Control of conditions for production Earth would be produced. Space Agency and the space agencies of industrial alloys in processes like of Japan, Germany, and France. Large sintering and precipitation hardening In the early 1970s, semiconductor furnaces flew on pallets in the cargo crystal growth was one of the first bay and in Spacelab while small n Measurement of accurate concepts identified by the National furnaces flew on the shuttle middeck. thermophysical properties, such as Research Council for materials To quantify the role of gravity in surface tension, viscosities, and processing in space. Promising early semiconductor crystal growth, NASA diffusivities, required for accurate results, especially on Skylab, spurred supported a comprehensive program of process modeling plans for semiconductor research on the experiments and mathematical Liquid phase sintering experiments shuttle. Materials processing and modeling to build an understanding of semiconductor crystal growth performed in low gravity yielded the the physical processes involved in unexpected results that the shape experiments were also a prominent part semiconductor crystal growth.

436 Major Scientific Discoveries distortion of samples processed in the solid during freezing, and thermal essential to obtain benchmark data on microgravity is considerably greater conditions applied to the metal. the growth rates, shapes, and branching than that of terrestrially processed The formation of structures during the behavior. In the 1990s, a series of samples. Sintering is a method for solidification of practical systems is experiments designed by Professor making objects from powder by heating further complicated by the multiplicity Martin Glicksman, then at the the material in a sintering furnace below of liquid and solid phases that are Rensselaer Polytechnic Institute, Troy, the material’s melting point (solid state possible in alloys of multiple elements. New York, was conducted on shuttle sintering) until its particles adhere to missions using an instrument named the Understanding the processes that control each other. Sintering is traditionally Isothermal Dendritic Growth the growth of dendrites on a growing used to manufacture ceramic objects and Experiment. The experiments carefully solid is a foundation for how processing has also found uses in fields such as measured the characteristics of single conditions determine the internal powder metallurgy. This result led to growing dendrites in an optically structure of a metal. Gravity can have a improved understanding of the transparent liquid; accurately visible influence on the growth of underlying causes of the shape changes determined the relationship among dendrites because of the disruptive of powder compacts during liquid-phase temperature, growth rate, and tip shape; effects of flow caused by temperature sintering with significant impact on a and established the importance of gradients near the dendrite. Therefore, $1.8 billion/year industry. long-range interactions between removing the effects of gravity was dendrites. Data from those experiments Space experiments on the prediction are widely used by scientists who work and control of microstructure in to improve the physical understanding solidifying alloys advanced theories and mathematical models of pattern of dendritic (from dendron , the Greek formation in solidification. word for tree) growth and yielded important contributions to the We learned the underlying physics of understanding of the evolution of freckle formation (a defect in the solid-liquid interface morphologies and formation alloy that changes its the consequences for internal structure physical characteristics) from early of the solid material. Introductions to results of materials research. It was metallurgy traditionally begin with a shown that convection was directly triangle made of three interconnected responsible for the formation of concepts: process, structure, and freckles, and that rotating the sample properties. According to this triangle, can suppress freckle formation. the study of metallurgy concerns The contributions of the materials how processing determines structure effort led to many innovations in crystal for various metals and alloys and also growth and solidification technology, determines properties. A solidifying including the use of magnetic fields, metal develops a characteristic rotating crucibles, and temperature- structure on several distinct interacting control techniques. In addition, the length scales. The microstructure analytical tools developed to (usually on the scale of tens of microns) understand the results of space is formed by the typically dendritic experiments were a major contribution pattern of growth of the solid interface. to the use of computational modeling The macroscale pattern of a whole These two samples show fracture patterns in as a tool for growth process control casting is determined by, among other sand at two different low confining pressures. in manufacturing. things, the distribution of solutes The confining pressure is an equal, all-sided rejected from the solid, shrinkage of pressure that is experienced, for example, by rock at some depth in the Earth. Very low confining pressures are not obtainable on Earth due to gravity.

Major Scientific Discoveries 437 Fluid Behavior Changes designers had to create fuel systems that which causes bubbles to rise in in Space would perform even if the plane were liquids or hot air to rise around a flame, upside down or in free fall. Rocket is the result of gravity producing a Many people connect the concept of and satellite designers, however, had to force proportional to density within liquids in space with the familiar image create systems that would operate a fluid. Many aspects of a vehicle of an astronaut playing with a wiggly without the friendly hand of gravity design, such as its mechanical structure, sphere of orange juice. And, yes, to put liquids at the bottom of a tank, are driven primarily by the large forces liquids in space are fun and surprising. let bubbles rise to the top of a liquid, experienced during launch. For fluid But, because many space systems that and cool hot electronic equipment with and thermal systems, low gravity use liquids—from propulsion and the natural flow of rising hot air. becomes a design driver. thermal management to life support— involve aspects of spaceflight where Without gravity, liquid fuel distributes A great deal of low gravity research surprises are not a very good idea, itself in a way that minimizes its total performed in the 1960s focused on understanding the behavior of liquids in free energy. For most fuels, liquid at the making liquid systems in space space became a well-established branch surface of the tank has a lower energy reliable. Low gravity experiments were of fluid engineering. than the liquid itself, which means the performed by dropping the experiment fuel spreads out to wet the solid from a tower or down a deep shaft or The design of space vehicles—fluid surfaces inside the tank. When bubbles flying it in an aircraft on a parabolic and thermal management systems, in are created in a fluid in space, in the trajectory that allowed the experiment particular—made low gravity a practical absence of other factors the bubbles to fall freely for about 20 seconds. concern for engineers. Decades before will sit where they are. Buoyancy, The experiments possible in drop the space program began, airplane shafts and aircraft didn’t allow enough time to test many technologies. As a result, engineers weren’t sure how some familiar technologies would work in the space environment. Low-gravity fluid engineering began with Apollo-era research focused on controlling liquid fuels; i.e., making sure liquid fuels didn’t float around inside their tanks like an astronaut’s orange juice. NASA performed most of this research in drop facilities, where experiments conducted in up to 5 seconds of free fall allowed basic ideas about fluid management to be investigated. The arrival of the Space Shuttle opened the window for experiment duration from seconds to days and inspired the imaginations of scientists and engineers to explore new areas.

Astronauts Kathryn Thornton and Kenneth Bowersox observe a liquid drop’s activity at the Drop Physics Module in the science module aboard the Earth-orbiting Space Shuttle Columbia (STS-73 [1995]). The two were joined by three other NASA and two guest researchers for almost 16 days of in-orbit research in support of the US Microgravity Laboratory mission.

438 Major Scientific Discoveries Drop physics experiments using advanced noncontact manipulating techniques on US Microgravity Laboratory (USML)-1 and USML-2 (STS-50 [1992] and STS-65 [1994], respectively) helped scientists understand the complex physical mechanisms underlying the seemingly simple processes of droplet shaping, splitting, and fusion.

The source of engineering problems The shuttle enabled researchers to Boulder, examined the fluid-like with liquids in space is the partially explore many new kinds of fluid behavior of loosely compressed soils filled container, or the gas-liquid behavior. Two examples out of many and helped in understanding when interface. Without gravity, surface include: the Mechanics of Granular and how, in situations like earthquakes, tension—the force that pulls a liquid Materials experiment, and the soils abruptly lose their load-bearing drop into a sphere—together with the Geophysical Fluid Flow Cell capability. Data from the experiment attraction of the liquid to the solid experiment. The Mechanics of will also help engineers predict the surfaces of the container determine Granular Materials experiment, performance of soils in future habitat the shape that a liquid will assume in developed by Professor Stein Sture foundations and roads on the moon, a partially filled container. at the University of Colorado, Mars, and other extraterrestrial To understand the unique behavior of liquids in space, researchers needed to look at the critical pieces of information Fluid Behavior in a Propellant Tank in the liquid boundaries. Fluid physics experiments in the Spacelab Program, such as the Surface Tension-Driven Convection Experiment developed for Professor Simon Ostrach of Case Western Reserve University, Cleveland, Ohio, and the Drop Physics Module developed for Professors Robert Apfel of Yale University, New Haven, Connecticut, and Taylor Wang of Vanderbilt University, Nashville, Tennessee, led a wave of research into the properties of liquid interfaces and their roles in fluid motions. This research contributed to advances in other areas, such as microfluidics, in which the properties of liquid Earth Environment Microgravity interfaces are important.

One of the earliest concerns about fluid behavior in microgravity was the management of propellants in spacecraft tanks as they orbited the Earth. On the ground, gravity pulls a fluid to a bottom of a tank (Earth environment, left). In orbit, fluid behavior depends on surface tension, viscosity, wetting effects with the container wall, and other factors. In some cases, a propellant can wet a tank and leave large gas bubbles in the center (microgravity, right). Similar problems can affect much smaller experiments using fluids in small spaces.

Major Scientific Discoveries 439 applications where the weight of the soil is much lower than on Earth. The Geophysical Fluid Flow Cell experiment, developed by Professor John Hart at the University of Colorado, Boulder, used the microgravity environment to create a unique model of the internal motion in stars and gaseous planets, with a device that used an electric field to simulate gravity in a spherical geometry. The Geophysical Fluid Flow Cell flew on Spacelab 3 (1 985), and again on US Microgravity Laboratory-2 (1 995). Results from the experiment, which first appeared on the cover of Science magazine in 1986, provided many basic insights into the characteristics of gas flows in stars and gaseous planets. Hart and his colleagues were able to reproduce many of the flow patterns observed in This demonstrates the difference between flames on Earth (left) and in microgravity (right). The flame gaseous planets under controlled and in microgravity is different because there is no upward buoyant force causing air to rise, so flames in quantified conditions inside the space produce no buoyant convective flow that carry them upward. Geophysical Fluid Flow Cell, thus providing a basis for analysis and In the near-absence of gravity, fires will cause a vigorous motion of the physical interpretation of some of the ignite and spread differently than they neighboring atmosphere as warm gas, distinctive dynamic features stars and do on Earth. Fires produce different less dense than the gas around it, rises gaseous planets. combustion products, so experiments due to its buoyancy under gravity. in space are essential to creating a The upward buoyant flow draws science-based fire safety program. surrounding air into the fire, increasing Combustion in Microgravity Research aboard the shuttle gave reaction rates and usually increasing the What Is Fire Like in Microgravity? scientists an understanding of ignition, intensity of the fire. In space, buoyancy propagation, and suppression of fires in is negligible. Fire safety specialists The crew of a spacecraft has few space. NASA is using the pioneering must take into account the effects of options in the event of a major fire. results of shuttle-era research to design cooling and ventilating airflows, which Fortunately, fires in spacecraft are rare; a new generation of experiments for can significantly accelerate fires. however, because both rescue and the ISS to help engineers design safer Under “typical” conditions, however, escape are uncertain possibilities at vehicles and better fire-suppression combustion in space is slower than on best, fire prevention, detection, and systems in the future. Earth and is less complete. Soot suppression continue to be an ongoing particles are larger in space because The biggest difference between space- focus of NASA research even after particles spend more time growing in and Earth-based fires is that on Earth, more than 30 years of study. the fuel-rich reaction zone. As a result, the heat released by combustion

440 Major Scientific Discoveries NASA fire safety experiments examined the effects of weak cabin airflows on fires. Here, a piece of paper burns in a flow like those used to cool avionics systems in space. NASA research showed that weak flows can have a strong influence on material flammability. fire detectors in space need to be more produced in microgravity were often burning of fuel drops has been used by sensitive to larger smoke particles than not detected by the sensor technology both General Electric (Fairfield, do fire detectors on Earth. employed in detectors deployed on Connecticut) and Pratt & Whitney the shuttle, even though the detectors (East Hartford, Connecticut) to improve The experiments of David Urban of worked reliably on Earth. An alternate the jet engines they manufacture. the NASA Glenn Research Center technology more sensitive to large Droplet combustion experiments in and his colleagues, included on the particulates provided superior space produced well-controlled data US Microgravity Payload-3 mission detection. This technology, which uses that allowed Williams and Dryer to (1 996), examined particulate-forming scattering of a laser beam by particles validate a comprehensive model for combustion in microgravity and in the airstream, is now deployed liquid fuel combustion. This model observed that the larger particulates aboard the ISS. was integrated into the simulations that engine manufacturers use to optimize Combustion of Fuels for Power designs. Another experiment, led by Paul Ronney of the University of Beyond its initial motivation, Southern California, Los Angeles, combustion research on the shuttle also used microgravity to study the weakest helped scientists better understand the flames ever created —1 00 times basic processes of burning hydrocarbon weaker than a birthday candle. Data fuels that according to the US on how combustion reactions behave Department of Energy provide the near the limits of flammability were US economy with 85% of its energy. used to help design efficient Research by Forman Williams of the hydrogen-burning engines that may University of California, San Diego, eventually meet the need for clean and Fred Dryer of Princeton University, transportation technologies. New Jersey, and their students on the In nearly perfect weightlessness, an ethanol droplet on the Microgravity Science Laboratory-1 mission in 1997 burns with a spherical flame.

Major Scientific Discoveries 441 Commercial Ventures Take Flight Industry Access to Space Charles Walker Payload specialist on STS-41D (1984), Shuttle-inspired Innovation STS-51D (1985), and STS-61B (1985). NASA’s charter included “seek and encourage … the fullest commercial “As a corporate research engineer use of space.” Acting in that I had dreamed of building an direction, NASA promoted the industry in space. Business Space Shuttle during the 1970s as conducted in orbit for earthly benefit a platform for industry. would be important. The Space Private industry is in business to Shuttle could begin that revolution. provide goods and services for a financial return. Innovation is “The first industry-government joint important. Microgravity—a physical endeavor agreement, negotiated in Charles Walker, payload specialist, works at the environment that was new to industry 1979 between NASA and the commercial Continuous Flow Electrophoresis at the time—proved to be intriguing. McDonnell Douglas Astronautics System on STS-61B. High-efficiency processing and Company, my employer, would facilitate space-enabled product research and free-floating containerless manipulation development among different industrial sectors. It also presented an opportunity and shaping of materials could become for me to realize that personal dream. reality with an absence of convection, buoyancy, sedimentation, and “NASA’s astronauts had already successfully conducted limited company density differentiation. Highly proprietary and public NASA research protocols during four flights with McDonnell purified biological separations, new Douglas’ electrophoresis bioseparation equipment. Then NASA allowed one of combinations and structures of our researchers to continue the work in person—exceedingly rare among materials with valuable properties, researchers, and the first for industry. and contamination-free solidifications prepared in orbit and returned to “As the company’s noncareer, non-NASA astronaut candidate, I had to the Earth became industry objectives for same medical and psychological screening as NASA’s own. Training mixed in prospective space processing research. with my continuing laboratory work meant a frenzied year. Preparations for flight In 1985, NASA and the National were exhilarating but they weren’t free. McDonnell Douglas paid NASA for my Bureau of Standards were responsible flights as a payload specialist astronaut. for the first sale of a product created in space. Designated “Standard “Working with NASA and its contractor personnel was extraordinarily rewarding. Research Material 1960,” this product I conducted successively more advanced applied commercial research and was highly uniform polystyrene latex development as a crew member on board three shuttle missions over a 16-month microspheres (specifically, sizes of period. It seemed the revolution had begun. 10 and 30 micrometers mean diameter) used in the calibration of scientific “I’m sorry to see these first-hand opportunities for applied research recede into and medical instruments. Dozens of history. Spaceflight is a unique, almost magical, laboratory environment. companies purchased “space beads” Disciplined research in microgravity can change human science and industry for $350 per batch. This milestone as surely as humanity’s ancient experiences in the control of heat, pressure, came from an in-space investigation and material composition.” that produced both immediate science and an application.

442 Major Scientific Discoveries For-profit businesses vary in their commercialize biotechnology products need for scientific research. Companies processed in microgravity. The often prioritize the application company developed a proprietary (product) as more important than its means of assaying disease-related scientific basis. For them, reliable, biomarkers through microgravity practical, and cost-effective process processing. This research objective knowledge is sufficient to create was aimed at shortening and guiding marketable products. But, if convinced drug development on Earth. From that research can add value, companies five rapid, shuttle-based flight will seek it. Various industries looked opportunities (over a 15-month period), at the shuttle as an applied science the company discovered a candidate and technology laboratory and, perhaps, for a salmonella vaccine. Even as even a platform for space-based Astrogenetix prepared to file an product production. Industry found investigational new drug application that production was not especially with the US Food and Drug feasible in small spacecraft such as the Administration, it was researching shuttle, but they were successful with candidates for a methicillin-resistant scientific-technology advancements. Staphylococcus aureus vaccine. The company conducted this later work McDonnell Douglas’ space-based in microgravity on board the shuttle’s research and development section was final flights. Looking to the future, the first to fly on seven missions, and Astrogenetix is among the first these missions took place from 1982 to commercial firms with an agreement 1985. The electrophoresis applications from NASA for use of the International work was technically a success. It Space Station (ISS) national laboratory. improved bio-separations over Earth gravitational force processing. For In the materials area, Paragon Vision example, when a cell-cultured human Sciences (Mesa, Arizona) developed hormone erythropoietin (an anemia new contact lens polymers. During therapy) was to be purified 100 times three flight experiments, the company better than ground-based separations, looked into the effects of gravity- a 223 times improvement was driven convection on long molecular obtained. Protein product throughput chain formation, resulting in an per unit of time also improved 700 improved ground-based process and times. After the Challenger accident Paragon’s proprietary HDS ® (Space Transportation System Technology materials product line. [STS]- 51L) in 1986, access to space Shuttle-based investigations amount to for commercial efforts was severely fewer than 6 months of laboratory restricted, thus ending the business time. Yet there have been significant venture. The demonstration of outcomes across multiple disciplines. possibilities, together with McDonnell The national laboratory capability at the Douglas’ investments in ground- ISS seemingly offers a tremendous based cell culturing and assaying, made future of returns. for the effort’s enduring advances. In 2009, Astrogenetix (Austin, Texas)— a subsidiary of Spacehab/Astrotech (Austin, Texas)—was organized to

Major Scientific Discoveries 443