Global Challenges and Directions for Agricultural Biotechnology: Workshop Report (2008)

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2 Opportunities for Applying Biotechnology T he world population has increased from 2.5 billion in 1950 to 6.7 billion today and is estimated to reach almost 9.2 billion by 2050 (United Nations, 2007). With that growth comes the challenge of producing enough food to meet the demands of the world’s people and an even greater challenge of producing it in a way that conserves the biodiversity and other natural resources on which societies depend. One estimate is that agricultural production will need to increase by 50 percent by 2020 to meet the world’s demand for food (Shah and Strong, 1999). Technological innovation has helped to ease some problems posed by population growth; over the last 50 years, agricultural productivity has doubled worldwide and even tripled in developing economies (Doering et al., 2002). During the 20th century, the Green Revolution drew on the research of conventional plant breeders to develop higher-yielding crops that were successful in increasing the global food supply. However, the new crop varieties introduced in the Green Revolution created depen- dence on additional farming inputs and created some new environmental problems. Today, with finite acreage of high-quality agricultural land on which to grow food (Tilman et al., 2001), biotechnology has emerged as a   Since the October 2004 workshop, the agricultural biotechnologies cited in the workshop have progressed rapidly, yet the opportunities for their application are still relevant and have yet to be fulfilled. In a forthcoming National Research Council report, Emerging Tech- nologies to Benefit Farmers in Sub-Saharan Africa and South Asia (2008), several promising appli­ cations of biotechnology are described to address the problems that small-holder ­farmers encounter in developing countries.  

10 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY potential tool for overcoming the current limitations on food production. Many have asked whether biotechnology can live up to its promise and whether it will also generate new dependences and problems. This chapter describes some of the opportunities for using biotechnol- ogy in an agricultural and environmental context as discussed by partici- pants in the workshop, and Box 2-1 provides a summary of opportunities for applying biotechnology. Although increasing crop yields by over- coming agronomic and environmental constraints is the most commonly recognized target of biotechnology, there are many other possibilities for developing useful applications, such as improving the sustainability of farming processes, developing more-nutritious foods, improving water quality, and identifying useful genetic material in nature. The workshop consisted of a series of presentations by lead speakers followed by com- mentary and shorter presentations by panels of experts. The presentations focused on specific ways in which biotechnology could address a problem or constraint, and the discussions examined the needs of the developing world relative to the potential of biotechnology. IMPROVING CROP PRODUCTIVITY Biotechnology is the application of scientific and engineering prin- ciples to the processing or production of materials by biological agents to provide goods and services (NRC, 2002a). Agricultural biotechnology encompasses a growing list of techniques that range from simple probes to determine whether an individual plant or animal is carrying a spe- cific gene to measurement of the activity of all an organism’s genes (its genome) simultaneously. One technique common in agricultural biotech- nology is the integration of a gene from one species into the genome of another. This technique is commonly referred to as genetic engineering, and the resulting product is described as transgenic (having a foreign gene). Genetic engineering allows novel characteristics to be introduced into a plant; this could not generally be accomplished with standard breeding techniques. Although some commercial products of genetic engineering are well known and were the focus of some of the presentations, the power of biotechnology goes far beyond the ability to make transgenic crops. Being able to recognize the characteristics of an individual organism on the basis of its genetic makeup and having the power to mimic the biological   By 2007, a total of 23 countries were growing transgenic crops. In order of acreage, they include the United States, Argentina, Brazil, Canada, India, China, Paraguay, South Africa, Uruguay, Philippines, Australia, Spain, Mexico, Colombia, Chile, France, Honduras, Czech Republic, Portugal, Germany, Slovakia, Romania, and Poland (ISAAA, 2008). 

OPPORTUNITIES FOR APPLYING BIOTECHNOLOGY 11 Box 2-1 Selected Opportunities for Applying Biotechnology Crop Productivity Overcoming biotic stresses Insects Weeds Overcoming abiotic stresses Soil fertility Heat stress Drought stress Inefficiency of resource use Nutritional Value of Crops Enhancing vitamin concentrations Enhancing mineral concentrations Enhancing protein content Plant-Made Pharmaceuticals Vaccines Protein therapeutics Improved Food Security Reducing post-harvest loss Reducing risks to food production Alternative uses Biodiversity Engineering safeguards to protect existing biodiversity Preserving biodiversity Natural Resource Conservation Renewable energy Phytoremediation activity of an organism by using its own cellular and molecular machinery are capabilities that allow us to deepen our understanding of all organ- isms. That knowledge has led to the development of some practical tools, examples of which were identified by workshop participants and are listed in Box 2-2. Ganesh Kishore, of DuPont Agriculture and Nutrition, provided an overview of some available biotechnologies to improve crop productivity, and the presentation provided context for shaping subse- quent discussions. 

12 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY Box 2-2 Some Tools of Biotechnology (Apart from Genetic Engineering) • Marker-assisted breeding uses conventional breeding techniques informed by specific genetic sequences, or “markers,” that segregate according to particular traits. Markers speed up breeding programs by allowing researchers to determine, early in the life of a progeny, whether the traits they hoped to combine from two organisms are present simply by checking for the presence of the markers. • Tissue culture is used in clonal propagation of plants for which sexual breeding has proved inefficient. It has been important for reproduc- ing crops used across the African continent, including oil palm, plantain, banana, date, eggplant, pineapple, rubber tree, cassava, maize, sweet potato, yam, and tomato. • Cloning and in vitro fertilization allow the manipulation of germ cells for animal-breeding programs, genetic-resource conservation, and germplasm enhancement. • Gene profiling or association mapping tracks the patterns of heritability of variations (alleles) of many genes. The quantitative trait loci (QTLs) collectively contribute to complex plant traits, such as drought tol- erance and robust seed production, and understanding of the groupings of QTLs provides insights into how genes work in concert to produce a particular characteristic. • Metabolomics provides a snapshot of all the metabolites being produced in a plant cell at any given time under different environmental conditions. Overcoming Biotic Stresses to Crops Insects and weeds can cause substantial crop losses. Kishore described the first generation of commercial transgenic products, the pest-protected and herbicide-tolerant crops that were first introduced in the United States. In one example, as young plants of herbicide-tolerant soybeans emerge, the field is treated with glyphosate; this kills the weeds, but the crops tolerate the herbicide. The benefits of the method include the 

OPPORTUNITIES FOR APPLYING BIOTECHNOLOGY 13 savings in time, labor, and energy involved in managing weeds and the ability to avoid tillage, which causes soil drying and erosion. In a second example, pest-protected crops have been genetically engineered to pro- duce a bacterial toxin, an insecticide derived from Bacillus thuringiensis (Bt), which kills lepidopteran pests of corn and cotton. According to Kishore, many U.S. farmers did not recognize how much the European corn borer affected both the productivity and the quality of their crop until they cultivated Bt corn, compared the resulting yields, and saw how much they had been losing. Transgenic crops have now been widely planted in the United States, China, Canada, Argentina, Brazil, and South Africa and are at varying stages of evaluation or adaptation in many other countries. Some major crops protected against biotic constraints include transgenic maize, cot- ton, and soybean, but, as noted in the workshop, other transgenic crops are under development. Participants noted in particular the efforts to develop weed-resistant plants and to insert Bt genes into pro-vitamin A white starchy sweet potatoes to make them resistant to weevils. Overcoming Abiotic Stresses to Crops Although herbicide-tolerant and Bt crops are the most common types of transgenic crops, there is great interest in introducing other charac- teristics into plants to make them more productive in poor agronomic conditions. Nutrient-Poor Soil Soil degradation affects one-fourth of agricultural land worldwide (GEF, 2003) and is one of the most important limitations on agricultural production in the developing world. The African landscape is plagued by weathered soils and poor soil fertility (Holden, 2006). Although investment in improving soil fertility is needed, Kishore described how researchers at such companies as DuPont have used plants—for example, corn and a ­ rabidopsis—to produce transgenic plants with improved responsive- ness to nitrogen. Crops that have been genetically engineered to more efficiently fix nitrogen, and thus reduce the need for external inputs of fixed nitrogen, could enable farmers to lower their production-related input costs while improving crop performance. Heat and Drought Stress Water security is projected by the United Nations Population Fund as one of the top global issues in the 21st century (UNFPA, 2002). More than 

14 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY a half-billion people live in countries defined as water-stressed or water- scarce, and by 2025 that figure is expected to increase to 2.4-3.4 billion (UNFPA, 2002). Drought-resistant transgenic crops could be useful in alle- viating the demand for water in agriculture. Kishore described DuPont’s work on corn varieties that maintain high yields under drought condi- tions and the development of drought-tolerant millet and sorghum, two staple crops; drought tolerance could have a large effect on agricultural productivity in Africa. It is unclear how well the technology will work under a multitude of field conditions—influenced by factors such as regional and geographic differences—and whether two or more types of stress (such as stress caused by heat and stress caused by drought) will have a compound effect on productivity. Salinity Salt tolerance was mentioned by workshop participants as useful in the developing world. Soils are often poor in quality because of salinity, and salt tolerance in crops such as rice and other cereals and vegetables would allow saline soils to be used more productively. Mariam Sticklen, of Michigan State University, described her work on a barley gene that confers salt tolerance in transgenic oats. Efficiency of Resource Use Multiple lines of research are being conducted to find the genetic basis of a plant’s ability to efficiently use resources, such as sunlight and nutri- ents. Kishore described research to improve the plants’ ability to utilize whatever nutrition is available, starting with sunlight, carbon dioxide, and nutrients in soil. Beans and high-yield rice are two crops being exam- ined for efficiency of resource use. IMPROVING THE NUTRITIONAL VALUE OF CROPS Advances in biotechnology have not only shown a potential for improving food production but have broadened the spectrum of available agricultural products (FAO, 2000; Dargie, 2001). Some 2-3 billion people suffer from widespread micronutrient and protein deficiencies, and mal- nutrition accounts for about 50 percent of deaths among children under the age of 5 (WHO, 1998; Micronutrient Initiative, 2008). The challenge will be to provide them with adequate nutrition. Food crops that are either conventionally bred or genetically engi- neered for enhanced nutritional value can be used to alleviate micro- nutrient deficiencies in the developing world (Bouis, 2002; Toenniessen, 

OPPORTUNITIES FOR APPLYING BIOTECHNOLOGY 15 2002). High-carotenoid canola and “golden” rice have been engineered to combat vitamin A deficiency (Guerinot, 2000; Ye et al., 2000) that is the single most important cause of preventable child blindness in developing countries and which affects the health and survival of at least 254 million “at risk” children of preschool age (WHO, 1995). Benjavan Rerkasem, of Chiang Mai University in Thailand, noted that lysine-enriched maize hybrids developed in China are being successfully grown by poor farmers there and in remote border areas in Vietnam and Laos (Prasanna et al., 2001). Crops are also being biofortified with micronutrients such as iron, iodine, vitamin A, and folic acid; and staple crops, such as sweet potatoes, are being enhanced with zinc (Pollack, 2003; HarvestPlus, 2008). Research- ers at DuPont are engineering an increase in the nutrient density of veg- etable proteins by increasing biologically available phosphates in grains, increasing several essential amino acids, and improving the oil and starch components of seeds. Those are just a few examples of work being done around the world. Dietary diversity, biofortification, and supplementation are other ways to deal with nutritional deficiencies. In addition to incorporating novel genes into plants, biotechnology can be used to identify genes in native plant populations that could improve human health and nutrition. Researchers with the Brazilian Agricultural Research Corporation (Embrapa), part of the Ministry of Agriculture, have looked for diversity in the carbohydrate and carot- enoid content of cassava and discovered a sugary cassava with both a higher sugar concentration and a different starch structure. Those researchers also discovered “golden cassava,” which contains high con- centrations of β-carotene, lycopene, and lutein. Carotenoid genes of golden cassava could be bred into other cassava varieties to improve nutritional quality. IMPROVING FOOD SECURITY Food security involves more than adequate production in the field. The timing of the harvest, availability of food throughout the year, flex- ibility in the use of a crop, and ability to store food are important compo- nents of food security. Biotechnology can reduce the risk of variability in food availability in several ways. Post-Harvest Losses Post-harvest losses can be enormous in developing countries. Between field and plate, reports quote losses of 10–100 percent in some fruits and vegetables in Africa. If genetic resistance to post-harvest pests and fungi are built in, this can increase the ability of farmers to store crops and crops 

16 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY stand a better chance of making it to the market. Biotechnology can also facilitate the preservation of nutrients from farm to plate. For example, cassava juice is high in beta-carotene, but it quickly loses potency when stored. Embrapa researchers have worked with Amazon natives to devise a convenient powder of cassava juice that can be reconstituted into vita- min-rich juice. Those technological solutions might not, however, be able to compen- sate for the lack of infrastructure, according to Bongiwe Njobe, director general of South Africa’s Department of Agriculture. She described a situation with maize production in Zambia where the absence of roads inhibited the transportation and distribution of maize before the rainy season. Once the rain set in, transport of the maize crop to markets was lost, and the country found itself vulnerable. Risks to Food Production Biotechnology can address food security issues by reducing risks to food production in two ways: by increasing the reliability of production and by smoothing supply and demand in rural markets. After harvest in rural areas, there can be a large drop in prices; a severe decrease in the market price of maize in Africa can have a devastating effect on farm fam- ilies. Anything that can be done to increase storability or to smooth pro- duction and consumption throughout the year will have highly beneficial effects on family health, well-being, and opportunities. Transgenic crops can potentially have a sizable effect on smoothing production, according to Kishore, who described Monsanto’s work on genes that confer toler- ance to chilling-injuries. Cold-tolerant crops could help to increase the optimal timeframe of a crop’s production and allow farmers to choose crops that sell later in urban markets and to wait until markets are more favorable for their sale. If poor farmers were able to get seeds into a field 3-8 weeks earlier, they would have more flexibility to escape late-season plant diseases, drought, and pest attacks. They would also have oppor- tunities for staggering crops and planting multiple crops to extend the timeframe when farmers can bring crops to market. Alternative Uses Biotechnology can increase the availability of alternative types of crops. Embrapa researchers have developed cassava varieties that meet the specific needs of local communities. For example, cassava has been engineered to produce better glucose syrup and used as beer precur- sors. Another example of an alternative crop use is the production of 

OPPORTUNITIES FOR APPLYING BIOTECHNOLOGY 17 plant-administered medications. Vaccines that are based on edible plants may offer the developing world a locally grown, more stable, and less expensive production method compared to conventional pharmaceutical production (Arntzen, 1997a,b; Tripurani et al., 2003). Increasing the reliability of production creates the possibility for other mechanisms—such as the development of financial systems (including savings accounts, financing of agriculture, and financing of agricultural inputs) and other infrastructure—to stabilize a rural economy and reduce both the risk of crop failure and the financial risk taken by farmers in producing food. PROTECTING AND PRESERVING BIODIVERSITY Biodiversity is a term used to describe the array of the world’s species, the genetic variability in and among populations of a species, and the distribution of species among local habitats, ecosystems, landscapes, and whole continents or oceans (NRC, 1999). The number of naturally occur- ring species of plants and animals tends to be higher in many developing countries of the tropics than of industrialized countries of temperate cli- mates. Preserving that biodiversity is important for maintaining the func- tioning of natural ecosystems, which provide part of the base of natural resources, such as water and pollinators, that supports such human activi- ties as farming. The biodiversity in natural ecosystems is also a source of genetic variability that is useful in crop development, as mentioned in a presentation by Luiz Carvalho, of Embrapa in Brazil. For example, genes that confer resistance to diseases can often be found in the wild relatives of domesticated crops, and these genes may sometimes be used by con- ventional breeders and molecular breeders to enhance the characteristics of crops. The discovery of diversity in carbohydrate and carotenoid types in cassava is another example of finding valuable properties in plants that can improve human nutrition and health. The role of biodiversity in natural and managed ecosystems has mul- tiple aspects. For example, some participants in the workshop criticized industrialized models of agriculture and cited how genetically narrow monocultures place crops and agricultural systems at risk for devasta- tion by disease. They advocated for more diverse agricultural production farming systems and greater genetic diversity in crops. Some in the workshop suggested that applying new agricultural bio- technologies without disrupting the biodiversity in many developing   There are concerns about quality control, potential drug overdose, and other potential risks associated with the use of food crops to produce drugs (Graham, 2000; Coghlan, 2005). 

18 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY countries presents a serious challenge. The capacity does not exist, they believe, to look critically at what may or may not be beneficial in particu- lar settings. Several workshop participants expressed their concern about how the introduction of transgenic crops would affect gene flow, agricultural productivity, and the natural environment. Rerkasem brought up the example of weedy rice, believed to be a natural hybrid of cultivated and wild rice species or a result of the de-domestication of cultivated rice (IRRI, 2008). The flourishing of weedy rice in Thailand’s central rice bowl reduced yields of cultivated rice, illustrating the risk of genetic exchange between cultivated and wild varieties and how they can have unpredictable outcomes. According to Rerkasem, because gene flow is unpredictable even in wild species, mechanisms of addressing biosafety concerns will need to be considered before transgenic crops are moved from the laboratory to the field to ensure that they do not reduce natural biodiversity. Workshop participants described research that is under way to develop safeguards to block gene flow; according to some, the technology already exists to prevent gene escape. Richard Meagher, of the University of Georgia, described plants that can produce sterile pollen or seeds (for example, sterile because of thiamine deficiency) and plants that can be engineered for male or female sterility. Sticklen mentioned that another method to block gene flow is to transform new genes into chloroplasts rather than into nuclear DNA; chloroplasts are maternally inherited in most flowering plants, and the new genes will not be found in pollen. Biotechnology can be used for more than the creation of genetically engineered crops: it can be used to preserve biodiversity and aid in genetic resource conservation efforts. Carvalho suggested that surveys are needed to determine the status of existing biodiversity, evaluate its value and importance, and identify endangered species and genes. On the basis of the survey results, he argued, measurable targets for the sustainable use and conservation of various species could be set. An overarching challenge is the lack of human capacity on the ground to monitor what happens to biodiversity when new living systems are introduced, what happens in the long term, whether there are benefits, and whether there are serious disruptions of ecological life. Work is under way in several countries to characterize indigenous plant varieties and animal breeds with biotechnologies to document and safeguard biodiversity. For instance, Carvalho described an Embrapa program in native Krahos communities in Brazil that had lost their t ­ raditional plant varieties and faced community collapse due to lack of food. Embrapa, which had been collecting samples of biodiversity in the 

OPPORTUNITIES FOR APPLYING BIOTECHNOLOGY 19 region, had the traditional landraces in its gene bank and was able to return the original landraces to the Krahos. Embrapa researchers then teamed up with the Krahos to rescue traditional knowledge associated with the Krahos agricultural system, to educate and train the residents in other agricultural methods, and to collaborate with them to organize and maintain a germplasm collection. The use of field-plot germplasm collections and in vitro tissue-culture methods gave residents a powerful tool to preserve regional biodiversity. This example illustrates how the techniques of biotechnology have been used to conserve biodiversity and the cultural heritage of native people. ENHANCING NATURAL RESOURCE CONSERVATION Agricultural biotechnology can have secondary effects that enhance natural resource conservation and protect the environment. By devel- oping drought-tolerant crops, researchers can help farmers to conserve water resources. Crops that are genetically engineered to produce Bt toxin require less spraying of pesticides, and reduction in spraying reduces the potential environmental harm caused by pesticides. Agriculture accounts for more than 30 percent of global greenhouse gas emissions (FAO, 2006a); however, herbicide-resistant crops promote no-till cultivation practices which help to reduce soil erosion, emissions of greenhouse gases, and carbon loss (Robertson et al., 2000; Lal et al., 2004; Zheng et al., 2004). Renewable Energy Workshop participants noted that biotechnology could play a major role in addressing the world’s energy and resource needs in the future. Trees that are genetically engineered to grow faster could help to meet the world’s demand for industrial wood and potentially reduce the need to harvest trees from natural forests. New plastics made from biodegradable plant polymers may one day provide an environmentally safer alterna- tive to traditional plastics made from fossil fuel. Global energy demands are forecasted to increase by 40 percent in the next 20 years (EIA, 2003). If energy demand is met by fossil fuel use, much more carbon dioxide will be produced. Agricultural products can be engineered to provide fuel alternatives in the form of biodiesel and biofuel: Sticklen described research to engineer rice straw, a major environmental contaminant in developing nations, so that it is biologically broken down into useful alcohol-based fuels. 

20 GLOBAL CHALLENGES FOR AGRICULTURAL BIOTECHNOLOGY Phytoremediation Many populations are regularly exposed to toxic substances, such as arsenic and mercury, and thus live in environments that are deleterious to their health. In Bangladesh alone, an estimated 57 million people—44 percent of the population—are at risk of exposure to toxic concentrations of arsenic in drinking water (UNESCO, 2008). About 6 million people in the Amazon are at risk of methylmercury poisoning from the nearly 5,000 tons of mercury deposited in tributaries as a result of gold mining (Veiga, 1997; Harada et al., 2001). Many land and water resources are contami- nated on a global scale and cannot be remediated by physical methods, but biotechnology-based alternatives could provide solutions to problems of environmental contamination. For phytoremediation, Meagher described one system for cleaning up the environment that uses native plants to degrade organic pollut- ants, such as trichloroethylene and polycyclic aromatic hydrocarbons, and process them into less harmful molecules. Elemental pollutants—such as arsenic, mercury, and radionuclides—cannot be readily metabolized or broken down; however, plants can extract, concentrate, and accumulate those pollutants from the soil for aboveground harvest and disposal. Determining which plants to exploit for that purpose and finding safe dis- posal sites is part of the research. The plants used to accumulate the pol- lutants would ideally be nonfood plants—something inedible—to prevent accidental poisoning and would grow between productive food crops so that farmers could maintain land productivity. Genetically engineered phytoremediants have already shown promis- ing results in initial field tests. The first field trials of a native hybrid accu- mulator of nickel have successfully extracted nickel. Researchers have also successfully used RNA interference to inhibit plants from converting a form of arsenate into another form that collects in roots; such inhibition allows plants to transport arsenic to their shoots and leaves, which can then be harvested. Cottonwood trees are among the several species that have been engineered to grow in mercury-contaminated soil and remove high concentrations of mercury.