Beyond Earth (ATWG) - Chapter 14 - Biotech: A Near Future Revolution from Space by Lynn Harper
From The Space Library
Chapter 14
Biotech: A Near Future Revolution from Space
By Lynn Harper
"The aggregate of all our joys and sufferings, thousands of confident religions, ideologies and economic doctrines, every hunter and forager, every hero and coward, every creator and destroyer of civilizations, every king and peasant, every young couple in love, every hopeful child, every mother and father, every inventor and explorer, every teacher of morals, every corrupt politician, every superstar, every supreme leader, every saint and sinner in the history of our species, lived there on a mote of dust, suspended in a sunbeam."
Carl Sagan, Pale Blue Dot
But is that the only option for the future?
Despite light years of searching, the only life in the universe we know comes from Earth. In this profound and vibrant isolation, exaltations are whispered - and often unheard - that life is a treasure, rare and miraculous. In the comet-battered landscape of alien worlds, warnings are shouted - and often unheeded — that living worlds are fragile and few and vulnerable. Still, all of our eggs - literally - lay uneasily in this one beautiful precarious basket called Earth. Because, after all, what alternatives do we have?
Four billion years of evolution in the gravity field of Earth has shaped us, inside and out, from each tiny cell to all the organs that enable us to live and think. The space environment is profoundly different from any encountered during the evolution of life on Earth. It is characterized by significant variations in gravitational force, magnetic fields, and radiation. But of all the environmental variables that changed on Earth to shape life over the past 4 billion years, gravity alone did not change. Even in the close orbital environment of Earth's low-Earth-orbit front yard, life experiences a thousand-fold to million-fold reduction in gravity, itself one of the most fundamental organizing forces of nature. The last time an environmental change of this scope was encountered by Earth life was when the first organisms emerged from the sea to the land.
So April 12, 1961 was truly an extraordinary day. On this day, Cosmonaut Yuri Gagarin was the first human being to leave Earth - and — he did not die. Since his historic flight, a wide range of bacteria, plants, animals, fish, insects, primates and, of course, humans have journeyed in space; none of them have died as a result of the biological changes induced by leaving Earth. Only mechanical failures and design flaws have been responsible for the deaths of space travelers. This is important, because life succeeds in ecologies not as individual species, so in order for us to thrive in space over long periods of time a wide range of organisms in addition to humans must be able to live for generations beyond Earth. So far, there have been no biological causes of death in space, and with that fact, alternatives emerge.
However, there is a need for extreme caution as we plan long forays beyond Earth. Life exists in space by changing its biology in response to the truly strange environmental cues elicited from the unusual gravity environments, and some of these changes are worrisome. As of this writing, only microbes, a couple of plant species, and insects have lived for more than one generation beyond Earth. When pregnant animals have flown in space, their developing offspring exhibited unusual responses. In fact, from microbe to human, whether living in space for short times or long times, for parts of a lifetime or over generations, all life that has flown in space has experienced minor to profound biological changes. But in this fact, opportunities arise.
From a biological perspective, space can also be thought of as a new "extreme" environment - extremely low gravity. Because of this, space biosciences research is likely to reveal aspects of terran life that literally cannot be seen on Earth, because they simply cannot emerge while living within the constraints of Earth's gravity. Biotech industry practitioners seek out some of Earth's least habitable environments to harvest the buff life forms that reside there because such extremophiles (creatures who thrive in extreme environments) exhibit biological solutions that can be and have been exploited for medical and commercial benefit in non-extreme environments. The extreme hypogravity of space offers at least the same - and possibly even superior - discovery and wealth-generating potential.
It's not a bug, it's a feature!
From the dawn of manned space flight, space medical experts have treated the biological changes in astronauts and cosmonauts as pathologies to overcome rather than as phenomena to explore.
Developing solutions to space medical problems was significantly hampered because scientists lacked the tools necessary to determine the causes of the problems they saw, and to rapidly evaluate potential solutions. Life is complex, space is one of the most unusual environments life has encountered, and for the past forty years the tools available were inadequate for the job. Then, in the last decade of the last millennium all that changed.
The toolkits available to biologists can be divided into two great epochs - before the Human Genome Project, and after the Human Genome Project. Before the Human Genome Project hit its stride in 1995, scientists had developed a number of hypotheses about why life responded so oddly in space. They were often right, especially about gross effects, but equally often they were spectacularly wrong, especially about subtle effects. Space biologists just scratched their heads about some responses, unable to formulate a sensible explanation of the biological responses they were observing.
Before the Human Genome Project, trying to understand what was happening to life in space was like trying to figure out what was wrong with your car by staring at the hood. At some point, you have to get inside and look at the machinery, but the tools that could delve into cells and tissues and illuminate what's happening there simply did not exist before 1995.
But amazing new tool kits have been developed over the past ten years - and the biotech revolution is still accelerating with new devices offered daily. Three technical revolutions—the biotech revolution, the infotech revolution, and the revolution in superminiaturized machines—each of extraordinary significance, and each offering exceptional capabilities, converged to form the most powerful investigative toolkits in the history of biology.
For decades, the U.S. government has invested billions of dollars to reduce the cost of a pound of payload to space by a factor of ten. It has never succeeded. However, the purpose of a space mission is not to launch the rocket; the purpose is to deliver people and equipment to extraterrestrial locations for the purposes of discovery and development. And this is where the biotech/infotech/miniaturization revolution changes all the value equations for space. Use of these new tools amplifies the value of a space biosciences payload pound a million times or more over what was possible before 1995.
Discoveries and Dollars — A Life Saving, Wealth Generating Story
This convergence provides new meaning—and a wealth of new possibilities—to the already compelling story of life. Using the tools spawned by the Human Genome Project and its prolific offspring, we can tell a new traveler's tale: the biological story of the only life in the universe we know in its first generations beyond the planet of origin.
This story is told not only in words and pictures, but also in the dialect of life itself - the language of genes and proteins. This space saga can generate wealth. It's biological message can save lives. And it will tell us whether life from Earth is planetbound, or what biological costs and opportunities will be available to us if we live for generations beyond our planet of origin.
For just as scientists seek extreme environments on Earth in their search for novel biological solutions that can be applied to terrestrial problems, the space environment is an unexplored extreme environment, the extreme of very low gravity, which offers exceptional potential for life saving and wealth generating advances.
The opportunity to bring the biotech revolution to space is an historic first, and is likely to reveal features of terrestrial life that literally cannot be seen on Earth. It also allows us to determine whether life from Earth is biologically bound to this world, and to explore the biological costs and opportunities inherent in living beyond Earth. And that's just the beginning.
Recent results show that the space environment yields unique knowledge that is medically important and commercially interesting. In the near future, commercial space biolabs can be used to develop and test new intellectual property products for high yield markets, especially in infectivity research, tissue/organ cultures and products, and insights into combating some of the debilitating effects of aging. Together, these three areas tap into a market valued at more than $100 billion annually. This is serious money to be made from "doing well by doing good". Small space "cottage" industries have produced space habitats for the model organisms that pioneered the Human Genome Project as well as the analytical laboratories for studying them.
Amazingly, the biotech revolution has not yet been used in space - except for a few cases. But these very cases caused jaws to drop and history to be made, as we will see below.
The New Case for Space Biotech.
Early concepts for commercial involvement in orbiting laboratories such as the International Space Station envisioned that companies would pay to use manufacturing facilities in space to exploit the unusual features of the microgravity environment to create new products in situ. This vision has never been realized for a variety of reasons and it is not proposed here—at least not for the near future.
In the last five years new technologies have emerged from the biotech revolution that could be applied to research in space. A new entrepreneurial paradigm is emerging and will provide a valuable new product in the biotech portfolio - patentable intellectual property based on space research using commercially available biotechnologies adapted to space. Four case studies are described here to profile the major opportunities foreseen: Cell and tissue cultures, infectivity, aging, and agriculture.
Cell and tissue cultures in space. Good cell and tissue cultures can accelerate by years the discovery of the causes of and cures for diseases. This can potentially save millions, if not billions, of dollars that would otherwise be spent on unproductive research. It can also generate millions or billions of dollars of revenue. Most importantly to most of us, it accelerates the development of life saving pharmaceuticals. But the value of a cell/tissue culture depends on how well that culture mimics what really happens in the body. For many diseases on Earth, there are no good cell/tissue culture models - yet. Surprisingly, space appears to hold one of the keys to this problem.
More than a decade ago, transplant surgeon Timothy Hammond, M.D. of Tulane University was looking for a tissue culture model for kidney disease. Kidney disease is one of the most expensive diseases to treat because there are only two treatment options for the advanced stages of the disease—dialysis or transplant. Kidney disease incidence increases with age, and so is rising as a national health cost as baby boomers age. 100,000 people per year in the US are diagnosed with kidney failure, and this country spends $20 billion/year treating this disease. There was no good cell/tissue culture for kidney disease until Hammond connected with what is currently known as the Biological Systems Office (BSO) at NASA Johnson Space Center. Hammond collaborated with Dr. Neil Pellis, subsequently the Co-Director of the Cell Biology program, and was introduced to the technology called the Rotating Wall Vessel (RWV).
The RWV, invented by David Wolf, Ray Schwarz, and Tinh Trinh, of the NASA Johnson Space Center, mimics the effects of microgravity on cells. When Hammond grew kidney cells in the Rotating Wall Vessel, the results were dramatically better than any others that had been grown. Tissues grown in the RWV began to re-acquire their three dimensional structure and biochemistry, which had been missing in standard terrestrial cultures, and electron microscopy of the cells showed that the microvilli, an important characteristic of kidney cells in the body but absent in standard cultures, had returned in abundance. The team reasoned that if the RWV was good, then space was the gold standard, and three additional pioneering investigations in space confirmed and extended their early findings in the RWV and showed even greater promise. Their results were published in prestigious peer reviewed journals (REF) and Stelsys, the entrepreneurial arm of Johnson and Johnson, became the first paying customer on the ISS as a result of both RWV and space flight data.
The reason that the space environment and RWV yield such improvements in cell cultures is because they more closely approximate the "cues" actually given cells as they grow in the body, which cells grown in Petri dishes on Earth cannot. To grow a tissue culture on Earth, cells are removed from the body and placed in a Petri dish where they grow flat. Cells are not smart, but they are very adaptable, and they obtain their information from the top, the sides and the bottom. In flat Petri dishes, the bottom information is missing and consequently the cells grow very differently than they do in the body. Scientists know this, and so in an attempt to overcome that problem, they suspended the cells in fluid. To prevent them from settling in suspension, they placed the cells in a mechanical mixer.
Unfortunately, the mechanical force needed to maintain the cells in suspension was so great that cell aggregates fragmented, and again, the cells did not grow the way they do in the body.
Space—and to a lesser extent the RWV—allow the three-dimensional structure of the tissues to emerge in cell cultures. In space, this occurs because nutrients and wastes do not separate on the basis of density differences, the cells do not settle to the bottom of the culture system, and nutrients and waste removal can be circulated with very gentle mixing that allows much larger cell aggregates—tissues—to form as a result. The RWV tumbles gently around a cylinder packed with nutrients, so it also reduces shear and turbulence in the mixing process, thus providing a gentler growth environment, also in three dimensions. (However, gravity does limit the size of the 3-dimensional tissues formed in the RWV when it's used on Earth.)
The biotech revolution allows researchers to read genomic instructions encoded in cells grown in the space environment, and to correlate these instructions with their physiological meaning, which is to say, to understand cause and effect to a much greater degree of precision that has been previously been possible.
This depth of understanding is important because most diseases—and treatments—are not single-element events. Rather, they are a symphony of multiple signals, transduction of environmental data, genomic instructions, protein responses, and feedback. Fortunately, the biotech revolution has produced superminiaturized analytical laboratories that can be fielded on spacecraft for on-orbit analysis, following which samples can then be fixed or flash-frozen and returned to Earth for more comprehensive examination. Companies can then take this information and, using contemporary biotech tools, engineer the organisms and systems needed to replicate the results on Earth.
Infectivity. Because of similar features in the cell-culture environment, bacterial cultures grown in the RWV exhibited over a 20-fold increase in infectivity compared with Petri-dish grown cultures. The surprised research team, led by Dr. Cheryl Nickerson, hunted for the biological explanation for this greater infectivity, and genomic and proteomic analysis revealed that it was caused by mechanisms that had not been predicted by current infectivity theory. Prior theory, in other words, was incomplete, a discovery made possible by the RWV.
The data were immediately published, of course, because the results revealed that research in this deadly and expensive medical area was not correctly informed. The terrestrial paradigm for infectivity was at best incomplete and at worst wrong—all because of limitations in standard culture conditions. The next step in this investigation is in queue, now waiting for a flight opportunity. (REF) Similarly, cancer, liver, brain, colon, bone, muscle, and other tissues have shown superior results when grown in the RWV, and are awaiting further investigation in space.
Aging. One of the most intriguing research areas is the role Earth-orbiting laboratories can play in providing insights to help combat aging. From mouse to man, when mammals live in space for a long period of time they lose bone and muscle mass, experience cardiovascular deconditioning, vestibular disturbances, hormonal imbalances, immune suppression, brain repatterning, and balance problems. The only other instance when all of these factors change simultaneously is during the aging process.
However, mice, men and women get better after they return to normal gravity. It is now possible to compare the processes of aging with the processes of space deconditioning by examining the molecules that begin the process, the cells changed by it, and the resulting impact on tissues, organs, systems, and whole organism. This particular class of work is important to every person on the planet.
Agriculture. Millions of dollars are spent each year to rid paper mills of lignin, a key structural component that occurs naturally in plants that interferes with paper making. The ecological cost to remove lignin is so significant on the paper-making process that paper companies developed expensive "knock-out" versions of the major plants used in paper production in an attempt to eliminate lignin.
A knock-out is a strain of the plant in which a single gene has been eliminated, knocked out. Doing so enables scientists to determine, in theory and sometimes in practice, the role of that particular gene.
However, life is not that simple; lignin, they found, is produced by a complex ensemble of genes that the knockouts didn't solve. In space, however, lignin production is significantly reduced, and by learning the genomic choreography by which this occurs new strains could be engineered on Earth, saving millions in environmental remediation costs.
Realizing the Potential
Given those interesting findings, why aren't the biotech companies and biosciences communities clamoring for more time on the ISS or other orbiting laboratories? There are several reasons.
One of the key factors that enabled the biotech industry on Earth to progress so quickly over the last decade is that the new tools provided the ability to perform very quick learning. Learn fast, learn often is their paradigm. Thus, in order for biotech to realize the potential that zero gravity—and for that matter lunar or Mars gravities offers—they need more frequent flights to do iterative studies. In biotech, a learning cycle is defined as the time it takes to define an experiment, develop the necessary hardware and protocols, perform the experiment, analyze the resulting data, and prepare for the next cycle. Typical learning cycles in biotech are measured in days and weeks.
Unfortunately, the learning cycles for space experiments are usually measured in years, a barrier that has slowed biotech utilization of the ISS to a trickle.
On the other hand, it's an opportunity, too, because meeting the emerging customer need for rapid learning cycles is what could make the emerging commercial space industries a success.
Make Space Research More Like Terrestrial Research
No one does biological research on Earth the way it must be done in space. For example, experiments in terrestrial labs are not begun by shaking them violently for several minutes, as occurs during lift-off and ascent to orbit. In fact, all parts of the space experience are significantly different from any type of terrestrial biological research. Expert guides are needed to translate commercial investigation procedures that work successfully on the ground to investigations that work successfully in the unusual environment, and under the unusual accommodations and constraints, of space.
But if we use the current NASA system, the time and effort that any company must invest to get an investigation to space is great, the paperwork burden crippling, and the space environment itself fraught with opportunities for experimental error that can invalidate any investigation's potential. Unless there are guides make this process much easier, companies will pursue other terrestrial avenues, even if they are not as effective, and all of us will suffer as a result. And while there are expert guides at the NASA centers and at NASA Centers of Excellence throughout the country, the entire NASA system is not organized to support the types of research—or the high-frequency learning cycles—that the new biotech revolutions call for.
From Earth Orbit to Mars, A Journey of Generations and Discoveries
When we go to another world, one of two equally profound events will occur. Either we will encounter alien life and know, finally, that we are not alone. Or, we ourselves will be the origin of life on that world.
This makes the study of Earth life in its first generations on other planetary bodies uniquely important for determining a fundamental aspect of life in the universe: can life evolve—not just live—beyond its planet of origin? Is life from Earth biologically bound to this one world? What are the implications for expanding life beyond Earth?
Soon we will have the opportunity to study Earth life in its first generations on other worlds, on the Moon and Mars. Each of these environments is unique, with features found nowhere else in the solar system. They differ significantly from our home planet in gravitational force, magnetic fields, day/night cycles, and radiation stresses.
Other than research conducted on the astronauts themselves, initial research in Earth orbit, on the Moon, and on Mars will start with the smallest simplest organisms, the best understood organisms on Earth, both because they are easiest to handle and because we need to build our knowledge from simplest to most complex. This research will identify specific biochemical mechanisms by which a wide range of organisms adapt to each new environment, from conception through maturity, reproduction, and death over multiple generations.
All life, from microbe to human, has shown fascinating and unpredicted changes as a result of spaceflight. Space biologists concur that the effect of different gravity levels, especially those below 1 G, are unknown and unpredictable from current paradigms, and that their study will reveal new knowledge about life on Earth, and empirically, about life in the universe.
Past Successes Herald Future Progress. Many people are alive today because we studied life in space, but few people know that procedures used in all intensive care wards worldwide are based on the technologies pioneered by Apollo. This is because intensive care wards rely on telemetry - the transmission of medical data from the patient to nurses and doctors in a way that alerts caregivers to life-threatening changes in patient condition. Perfection of these technologies was achieved because NASA doctors needed to monitor astronaut health remotely.
Even fewer know that the Micro-Electro-Mechanical Systems industry (MEMS) owes a significant fraction of its wealth and its products, currently yielding more than $5 billion per year in revenue, to breakthroughs achieved by Dr. Lynn Roylance's in developing a device to measure blood flow in the hearts of rats in space. Pacemakers, airbag crash sensors, and fetal surgery monitors are among the fruits of this research.
Implantable insulin pumps, shock trousers, telemedicine, remote surgery, 3-D observations for diagnostic and reconstructive medicine, implantable medical devices, and many, many more advances have resulted from the study of life in space.
Some argue that all of these advances would have occurred without the space program, and perhaps this is so, but theirs is a hypothesis without data because that's not how these advances were achieved. All who are alive today because space biosciences made these technologies available sooner rather later may feel that their penny-per-year investment in space biosciences was money well spent.
Based on actual history, then, we can expect that the knowledge and technology products developed as a result of our future efforts in space will offer important insights to help prevent death, enable life, ensure that a significant number of people attain a substantially higher quality life for much longer periods of time, and in the process, generate exceptional wealth and numerous jobs. Clearly, then, it's time to bring the biotech revolution to space.
Oases Beyond other worlds, and the vast spaces between, them are biological laboratories on many levels. They hold unique clues about the events that enable life, change evolutionary trajectories, and ultimately create the two most mysterious forces of nature, life and intelligence. Space laboratories in orbit, on the Moon, on Mars, and beyond, will enable the first empirical tests of whether it is possible for life from one world to thrive on others, and will reveal features about life on Earth that cannot be seen from any other vantage point.
And while arguments may rage on many subjects about space exploration and life in the universe, this we know: Very different futures are available to a species that can thrive beyond their planet of origin as compared with those whose destinies are constrained to a single world. Which future will you choose?
Extracted from the book Beyond Earth - The Future of Humans in Space edited by Bob Krone ©2006 Apogee Books ISBN 978-1-894959-41-4
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