3
Societal Challenges

Earth has been called an engineered planet. It is not a stretch to say that the long-term well-being of nearly 7 billion people is unimaginable without engineering and modern technology. Humans are dependent on a complex mix of natural resources and manufacturing processes combined with technological infrastructure for food, water, shelter, and other needs. But this infrastructure and those processes are strained by global development, population growth, climate change, and competition for limited resources. Sustaining the integrity and functionality of Earth’s natural systems while maintaining and even enhancing the well-being of humans will require both new technologies and a much deeper understanding of the Earth’s natural processes. The scientific and technological understandings that come from research at the intersection of the physical and life sciences have the potential of helping to meet those needs.

This chapter discusses a few such applications in agriculture, energy, climate, biomedicine, and novel materials. While these examples may not be comprehensive, they illustrate some of the many ways in which research at the intersection of the physical and life sciences has addressed and will continue to address some of our most difficult societal challenges.1 The committee is mindful of the fact that societal benefits will emerge not only from advances in scientific research at this life sciences/physical sciences intersection but also from increased interactions between the life sciences and various engineering disciplines. However, as important as the

1

Many of the applications discussed in this chapter are also highlighted in the recent NRC report A New Biology for the 21st Century (National Research Council, 2009).



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3 Societal Challenges Earth has been called an engineered planet. It is not a stretch to say that the long-term well-being of nearly 7 billion people is unimaginable without engineer- ing and modern technology. Humans are dependent on a complex mix of natural resources and manufacturing processes combined with technological infrastructure for food, water, shelter, and other needs. But this infrastructure and those processes are strained by global development, population growth, climate change, and com- petition for limited resources. Sustaining the integrity and functionality of Earth’s natural systems while maintaining and even enhancing the well-being of humans will require both new technologies and a much deeper understanding of the Earth’s natural processes. The scientific and technological understandings that come from research at the intersection of the physical and life sciences have the potential of helping to meet those needs. This chapter discusses a few such applications in agriculture, energy, climate, biomedicine, and novel materials. While these examples may not be comprehensive, they illustrate some of the many ways in which research at the intersection of the physical and life sciences has addressed and will continue to address some of our most difficult societal challenges.1 The committee is mindful of the fact that soci- etal benefits will emerge not only from advances in scientific research at this life sciences/physical sciences intersection but also from increased interactions between the life sciences and various engineering disciplines. However, as important as the 1 Many of the applications discussed in this chapter are also highlighted in the recent NRC report A New Biology for the st Century (National Research Council, 2009). 0

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so cietAl chAllenges  latter set of interactions might be for society, they are beyond the scope of this report.2 IDENTIFYING AND COMBATING BIOLOGICAL THREATS In the past few years many people have come to think of biological threats only in the context of war or terrorism. However, natural biological threats have existed throughout history and still exist today. We need to look no further than recent outbreaks of sudden acute respiratory syndrome (SARS), swine influenza, and avian influenza to see that disease organisms can evolve, adapt, and cause epidemics. Early Detection and Intervention The appropriate defense always involves a medicinal attack on such organisms; however, early response to a disease depends on early recognition. In some cases, this means recognition of a weak disease “signal” in the noise of everyday life. To that end, information scientists have begun to collect data about symptoms posted on public health and popular medicine Web sites and have used that information to look for increased incidences and the appearance of clustered events. In addition to its use in detecting chemical threats from a distance, spec- troscopy can be used for remote sensing of pollutant molecules from individual automobiles under normal driving conditions to find and eliminate the worst polluters. Similarly, the remote, noninvasive identification of diseased individuals, by detecting thermal or chemical signals, is used to find and give early treatment to people who are not otherwise recognizably sick. Today there are devices that can “smell” cancer by detecting the metabolites of specific cancer cells (Rovner, 2008). Such identification and treatment could reduce the severity of disease in an individual or mitigate the spread of infectious disease in the larger population. This becomes increasingly important as people fly around the globe within a day and geographical barriers to the spread of disease fall. In addition to the direct effects of disease in individuals, humans’ experience with “mad cow” disease and the swine and avian influenza viruses points to the importance of animal health and welfare and highlights the threat that zoonotic diseases such as the West Nile virus pose to the larger human population. This threat can be to health itself or to the economy. In 2001, Great Britain fought a battle against foot and mouth disease (FMD), a highly contagious virus, slaughter- 2 Some of these areas were explored in the recently released NRC report Inspired by Biology—From Molecules to Materials to Machines (National Research Council, 2008).

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ReseARch inteRsection PhysicAl life sciences  At the of the And ing over 4 million animals to control the disease.3 Prevention and suppression of FMD and other, similarly infectious pathogens depends on early detection, quar- antine, and/or destruction of disease carriers. The rapid remote sensing of such animals could help prevent or reduce the negative impact of these diseases. Using techniques related to speech recognition, mathematicians have worked to map the genetic similarity of influenza viruses. Using color and spatial distribution, subtle evolved differences in virus strains can be identified, and decisions about the potential effectiveness of vaccines become easier (Enserink, 2008). Obviously both symptom recognition and pathogen strain identification are also very useful in the defense against any man-made biological. Prediction of Susceptibility to Disease and Its Prevention Historically, vaccination, simple sanitation and the availability of clean drink- ing water were perhaps the most important developments in disease prevention. However, these methods are useful only for preventing infectious disease, and we are discovering their limitations and drawbacks. Prevention of disease, especially noninfectious disease, remains a critical issue. The impact of fetal nutrition on adult susceptibility to obesity points to the potential benefit of better understanding the sources and causes of noninfectious disease. As these causes are found, we can more easily identify and treat individuals most likely to develop a disease. Doing so entails both a deeper understanding of the biology of disease inception and the physical science of detecting susceptibility. Beyond detection of susceptibility, however, is the need to understand how conclusions drawn from populations translate to therapy for individuals. Here is the greatest need for personalized medicine—that is, diagnosis and treatment tailored to a person’s genetic makeup and potentially to environmental differences as well. Personalized medicine in simple forms is already used—if a breast cancer patient’s tumor is estrogen-receptor positive, then the patient may benefit from treatment with tamoxifen, which prevents estrogen from binding to the receptor and stimulating growth. In the future, analysis of an individual’s gene expression patterns using micro- arrays or even sequencing of his or her entire genome, which will require enormous advances in chemistry and engineering, should allow physicians to diagnose and treat disease with greater accuracy. A greater understanding of the DNA sequence changes that impact protein-coding or RNA-coding should also allow these pro- cesses to be mathematically modeled. 3 Information from “Farm incomes in the United Kingdom 2001/2002.” Available at https:// statistics.defra.gov.uk/esg/publications/fiuk/2002/FIUK_complete.pdf. Accessed January 28, 2009.

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so cietAl chAllenges  CLIMATE AND ITS INTERFACE WITH BIOLOGY Energy generation, energy use, the environment, and Earth’s climate are inextricably bound, and the consequences of these interactions are broad, rang- ing from human comfort and disease to wildlife and agriculture (IPCC, 2007a). While climate science has reached a level of sophistication sufficient to document components of these interactions, such as how humans impact climate (IPCC, 2007b) and how projects impact ecosystems, it is not yet capable of understanding the full consequences of the actions we might take to mitigate those impacts while simultaneously maintaining our energy supply. The technical challenges associated with energy and climate policy require a deeper understanding of the intersection between physical and biological systems and, therefore, the physical and biological sciences. This would be particularly true for global engineering such as modifying the atmosphere to be more reflective or seeding the oceans with iron to induce algae growth and carbon dioxide uptake. Any such efforts must take into account both direct and indirect aspects of the complex interactions that link the climate, ecosystems, and the oceans (Field et al., 2007). Complex Feedback Loops in Climate Science Some of the most pressing scientific questions about climate change concern the risk that warming may lead to large releases of carbon as CO2 or methane from land and ocean stocks, reinforcing the warming trend (Gruber et al., 2004). Such releases and the consequent, possible shift in the relative mix of carbon dioxide and other greenhouse gases increase the possibility of further feedback. Finally, changes in vegetation cover caused by warming will affect absorption rates of solar radiation at the Earth’s surface thereby creating another class of feedbacks that may play a large role in amplifying or perhaps suppressing climate change (Gibbard et al., 2005). The scientific and societal challenge of understanding the role of physical/ biological interactions in climate change is at least as profound in the area of solutions as it is in impacts. Essentially all of the possible approaches for offsetting emissions of greenhouse gases, including biological sequestration, decreased deforestation, and geological and deep ocean sequestration, involve changes to biological systems, with the possibility of indirect impacts that either feed back to climate change or alter the delivery of ecosystem goods and services. Implications of Renewable Energy Even energy technologies that are not explicitly based on combustion or biology will likely have important impacts at the intersection of physical and

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ReseARch inteRsection PhysicAl life sciences  At the of the And biological sciences. For example, large-scale harvesting of wind energy may alter atmospheric transport and turbulence. Large-scale solar collection will alter energy absorption at Earth’s surface, the partitioning of energy into evaporation and sensible heat, and, at least in some cases, the light available for photosyn - thesis. Large-scale hydro, wave, or tide power will likely have widespread effects on hydrology and on the organisms and people that use the water resources. Thoroughly assessing the impacts of these technologies to ensure that they create the smallest possible set of environmental problems is a key challenge for the future, one that is potentially as important as understanding the mechanisms and impacts of climate change. MEDICINE The importance of physics and chemistry to medicine is well known. The dis- covery of X rays and nuclear magnetic resonance by physicists in the first half of the twentieth century led the way to the diagnostic X rays, CAT scans, and MRIs of today. The ability of chemists to isolate, analyze, and synthesize complex organic molecules led to the modern pharmaceutical industry. Not only have these histori- cal trends continued, they have accelerated, and many new medicines have come from advances in our understanding of molecular interactions, chemical reactivity, and synthesis. The future will require further development of physics techniques and new understandings in chemistry and chemical methods to enhance the effi- ciency of industrial syntheses and reduce the generation of by-products that harm the environment. Imaging Physicists and applied physicists are working out the theory and design for improved imaging of biologically important entities, from the human body as a whole to individual cells and molecules. Applications range from diagnostics to minimally invasive surgery or radiation treatment. Advances in high-resolution light microscopy allow researchers to image the position and movement of molecules at the nanometer scale in real time (Pinaud and Dehan, 2008). Biological processes involve the binding of molecules, large or small, and sometimes a number of them simultaneously, to large, protein-based receptors. Using novel imaging techniques, molecules may be found to exist in close proximity with one another in a cell. This could mean that the molecules act together or on similar structures in that cell and could aid in understanding the binding mechanisms. When the equations for x-ray diffraction were first elucidated, the work seemed like pure, esoteric physics. Now biophysicists at the national laboratories

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so cietAl chAllenges 5 (Brookhaven, Argonne, and Lawrence Berkeley) and elsewhere routinely use high- powered synchrotron beamlines to see individual atoms of drug molecules binding to their protein targets. This allows chemists to modify the structures of the drugs based on images and not on live patient response, speeding up the process of mak- ing drugs more specific and more powerful, and giving hope for a new constellation of antibiotics aimed at drug-resistant pathogens. In some cases, common and necessary imaging techniques are not without the potential to do harm. For well over 100 years, X rays have been used for diag- nostic and therapeutic processes, sometimes damaging vital organs. The mecha- nisms of radiation-induced damage involve cells committing suicide via a process called apoptosis. Recently, drugs have been developed that can trigger natural cellular mechanisms that resist this process and thereby mitigate such damage (Bhattacharjee, 2008). Treatment and Devices Research at the intersection of the physical and life sciences has made significant contributions to the development of new treatments and devices, a few examples of which are briefly discussed here. For diabetics, advances in nanotechnology have resulted in nano-scaled dispensers of insulin that, when combined with continuous monitoring of blood sugar levels, allow for the administering of the right amount of insulin in a continuous manner. Further, joint efforts by chemists and micro- biologists are seeking to understand the processes by which insulin is generated and other hormonal activity is regulated by the pancreas, with the ultimate goal of creating artificial pancreas. Such efforts offer hope to diabetics whose disease has caused the destruction of that organ (Halford, 2008). Intersectional research also has shed light on the interaction between mind and machine. As an example, the implantation of a small electrical interface into a monkey’s brain allows the monkey to control a prosthetic arm by its thoughts. A computer analyzes the response of the monkey’s brain to a stimulus and transmits an electrical impulse to the prosthesis. With practice, a monkey learns what kind of response is needed to operate the arm (Cary, 2008). AGRICuLTuRE AS A RESOuRCE FOR FOOD AND ENERGY Since the first use of fire, fuel has consisted of biological products derived from plants, which are in turn created via photosynthesis. Fuels such as wood, crude oil, or coal are not primary fuels; rather they are batteries, storing energy from the Sun. Historically, it has always been sufficient for humans to harvest these biobased materials, whether they are found above or beneath Earth’s crust, and simply burn

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ReseARch inteRsection PhysicAl life sciences  At the of the And them. In the twenty-first century, however, demand for energy will likely outstrip the availability of these sources, and their unfettered use will be complicated by concerns about products of combustion (see discussion of climate, below). Researchers and technologists have developed non-bio-based sources of energy and means to store it. However in many cases these technologies utilize toxic or less abundant substances—for example platinum or palladium catalysts, gallium arsenide solar collectors, and nickel, cadmium, lithium, or even tried-and-true lead batteries—whose supply or disposal is problematic. Increasingly, the fuels needed to meet energy demand are being farmed— whether plant oils for biodiesel or plant sugars for fermentation into ethanol. But dependence on agriculture for fuel carries hidden financial, environmental, and security costs. For one thing, a large percentage of the arable land in the world is already in farm production. Additionally, fresh water needed for irrigation is unevenly distributed and in many places in short supply. And, as agriculture becomes the source of fuel as well as food, the supply of both becomes more vulner- able to common weather, biological, and environmental risks. In short, agriculture as it is currently practiced can reliably offset only a small fraction of the global growing demand for energy (Field et al., 2008). Current research is focused on understanding the biological mechanisms that generate usable fuel so that more fuel material can be produced from incident sunlight. This would mean growing better plants, especially those that will not be used for food, or by adapting their photosynthetic infrastructure to the manufac- ture of fuel. Building Better Plants and Getting More Out of Them Currently agriculture-based liquid fuels are created by fermenting plant sugars—usually corn or sugarcane—into ethanol or reforming plant oils into biodiesel. But, short of burning plant waste for process energy, as is done with sugarcane bagasse, both processes utilize fruit or seeds that constitute less than half the mass of the plant while ignoring the greater mass of stalks and leaves. Other research has led to biobased production of more energy-dense fuels than ethanol (BP, 2008). Enzymatic depolymerization of the cellulose and hemicellulose of those stalks and leaves, yielding fermentable sugars, is becoming more cost effective, as is thermal decomposition of the same materials to yield raw materials for indus- trial fuel synthesis. These near-term opportunities can be paired with longer-term strategies for harnessing the potential of plants. Identification, isolation, and manufacture of the key enzymes that catalyze depolymerization of cellulose lie at the intersection of the biological, physical, and engineering sciences, as do efforts to better understand natural systems and how to modify them to yield materials of greater catalytic activity. Low-resource peren-

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so cietAl chAllenges  nial plants such as grasses or algae that grow quickly can be harvested to produce relatively large amounts of plant mass to feed these cellulose depolymerization processes. Better understanding of microorganism culture, the productive potential of soils, and the locations where they provide the greatest net benefit are keys to better utilization of these nontraditional crops. Researchers are also beginning to isolate “biofuel” genes—that is, genes respon- sible for increasing plant production of sugars, cellulose, and oil—as well as more efficient enzymes to process cellulose, and to grow more drought- and salt-resistant plants and to increase planting density (Kintisch, 2008). Understanding how these genes work has the potential to increase our understanding of how physical scien- tists and engineers might utilize similar processes for artificial systems. Moreover, because of the resilience of agricultural pests and their evolutionary potential, it will be necessary to understand more completely the ways plants protect themselves and how we can help protect them in the face of a fragile and hostile environment. Hydrogenases and Synthetic Photosynthesis Enzymes and organisms that could produce hydrogen in biological systems have been known for 75 years. These enzymes, which allow the splitting of water into hydrogen and oxygen, are complex and only now becoming better understood. In their ability to use the energy from light to power this reaction, these enzymes are analogous to the complex plant structures responsible for photosynthesis. Of the opportunities at the intersection of the physical and biological sci- ences, perhaps none has such intriguing potential as understanding, controlling, and improving photosynthesis, with the goal of decoupling it from plants. While photosynthesis is so common as to be all around us, understanding it and adapting it remains a huge challenge. Effectively, plants use catalysts derived from common metals to harvest sun- light, to split water into oxygen and hydrogen, and to generate plant material from carbon dioxide. And while the photochemical yield in photosynthesis is high, the steps that actually fix CO2 and lead to the production of plant material—the biomass that will become fuel—are much less efficient. One research goal is to isolate the active species responsible for the various reactions of photosynthesis, conveniently split water, separate the resulting oxygen and hydrogen or other reduced species, then use those reduced species as a fuel in themselves or as the raw material in a fuel-making process. Other goals include enhancement of the local flora to increase the CO2-fixing efficiency. Industrially usable catalysts inspired by this chemistry with significantly greater yield than natural systems could produce fuel from waste carbon dioxide as plants do. Such technology would simultaneously address a portion of the world’s growing demand for energy and rid the planet of atmospheric carbon dioxide.

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ReseARch inteRsection PhysicAl life sciences  At the of the And Beyond Combustion Much of the fuel we burn is used to generate electricity, typically at about 30 percent efficiency. However, combustion has environmental drawbacks beyond the emission of carbon dioxide. Depending on conditions, carcinogenic and pol- luting products of incomplete combustion, such as particulates, nitrogen oxides, and polycyclic aromatic hydrocarbons, can also be produced. Biological systems generate their energy directly in mitochondria at efficiencies of near 90 percent. The energy chemistry in mitochondria is analogous to that in fuel cells, wherein hydrogen and oxygen in the presence of catalysts are converted to water while generating electricity. Understanding the common-metal catalysts in mitochondria and their adapta- tion to fuel cells, especially for mobile applications, could simultaneously reduce energy use by improving efficiency and reduce their unwanted by-products of combustion. There are encouraging results in this field as well (Winther-Jensen et al., 2008). MATERIALS SCIENCE The commercial development and production of materials mimicking biological systems has been the focus of much industrial research effort. However, many bio- logical materials remain outside commercial reproduction capability. For instance, long spider silk proteins, as fabricated into strands, have the tensile strength of steel, yet the structure of spider silk. As desirable as these characteristics are, the commer- cial manufacture of spider silk as an advanced material continues to elude engineers. Composite materials—steel-reinforced concrete or glass-fiber-reinforced plastic— have been staples of construction and engineering for years; yet they do not achieve the strength and toughness of biocomposites such as bone or tooth enamel. Progress is being made in understanding the structure, physical properties, and means by which these materials are fabricated. Synthetic biology has been used to increase production under controlled conditions (UCSF, 2008). Further efforts in replication, manufacture, or modification could lead to lighter, stronger, more resilient, and, moreover, biodegradable engineered materials. This intriguing area is the subject of a recent NRC report on biomimetic materials (NRC, 2008). OPPORTuNITIES As modern science dawned hundreds of years ago, its practitioners hoped to understand the large questions of life, including its origin and the maintenance of youth and health. Over time, scientists found those questions too complex to

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so cietAl chAllenges  answer with the information that was available, and broke the sciences into smaller disciplines in the physical and biological realms. Today, after 200 years of studying those more specific disciplines, many of the most fascinating and important problems lie at the intersection and reintegration of these two realms. And, for the first time, twenty-first-century scientists have the tools and knowledge base to address the large issues that impact the maintenance and quality of life. While this will not be easy, the significant advances in agricul- ture, energy, medicine, and understanding of climate that appear to be increasingly likely by such intersectional work are required to sustain not only our way of life but also its very existence. REFERENCES Bhattacharjee, Y., 2008. Drug bestows radiation resistance on mice and monkeys, Science 320: 163. BP, 2008. http://www.bp.com/liveassets/bp_internet/globalbp/STAGING/global_assets/downloads/B/Bio_biobutanol_ fact_sheet_jun06.pdf. Accessed August 21, 2008. Cary, B., 2008. Monkeys control robot arm with their thoughts, New York Times, May 29, 2008. Enserink, M., 2008. Mapmaker for the world of influenza. Science 320: 310. Field, C.B., J.E. Campbell, and D.B. Lobell, 2008. Biomass energy: the scale of the potential resource. Trends in Ecology & Evolution 23: 65-72. Field, C.B., D.B. Lobell, H.A. Peters, and N.R. Chiariello, 2007. Feedbacks of terrestrial ecosystems to climate change. Annual Review of Environment and Resources 32: 1-29. Gibbard, S., K. Caldeira, G. Bala, T.J. Phillips, and M. Wickett, 2005. Climate effects of global land cover change, Geophysical Research Letters 32: L23705. Gruber, N., P. Friedlingstein, C.B. Field, R. Valentini, M. Heimann, J.E. Richey, P. Romero-Lankao, E.D. Schulze, and C.T.A. Chen, 2004. The vulnerability of the carbon cycle in the 21st century: An assessment of carbon- climate-human interactions. The Global Carbon Cycle: Integrating Humans, Climate, and the Natural World: 46-76. Washington, D.C.: Island Press. Halford, B., 2008. Perfecting an artificial pancreas, Chemical Engineering News 86: 46-47. IPCC, 2007a. Climate Change 00: The Physical Science Basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, S. Solomon, D. Qin, M. Manning, Z. Chen, M. Marquis, K. B. Avery, M. Tignor, and H. L. Miller, editors. Cambridge, United Kingdom and New York, NY, USA: Cambridge University Press. IPCC, 2007b. Summary for Policymakers in Climate Change 00: Impacts, Adaptation and Vulnerability. Contri- bution of Working Group II to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, M. L. Parry, O.F. Canziani, J. P. Palutikof, P. J. van der Linden, and C. E. Hanson, editors. Cambridge, UK: Cambridge University Press. Kintisch, E., 2008. Sowing the seeds for high-energy plants, Science 320: 478. National Research Council, 2009. A New Biology for the st Century. Washington, D.C.: The National Academies Press. National Research Council, 2008. Inspired by Biology: From Molecules to Materials to Machines. Washington, D.C.: National Academies Press. Pinaud, F., and M. Dehan, 2008. Zooming into live cells, Science 320: 187-188. Rovner, S.L., 2008. Sniffing out cancer, Chemical Engineering News 22: 81-83. UCSF, 2008. http://www.ucsf.edu/science-cafe/conversations/voigt/ Accessed August 21, 2008. Winther-Jensen, B., O. Winther-Jensen, M. Forsyth, and D.R. MacFarlane, 2008. High rates of oxygen reduction over a vapor phase–polymerized PEDOT electrode, Science 321: 671-674.