Role of socio-economic research in developing, delivering and scaling new crop varieties: the case of staple crop biofortification.

The CGIAR biofortification program, HarvestPlus, was founded with the aim of improving the quality of diets through micronutrient-dense varieties of staple food crops. Implemented in four phases - discovery, development, delivery and scaling - the program was designed to be interdisciplinary, with plant breeding R&D supported by nutrition and socio-economic research. This paper explains the need, use and usefulness of socio-economic research in each phase of the program. Ex ante and ex post benefit-cost analyses facilitated fundraising for initial biofortification R&D and implementation in each subsequent phase, as well as encouraged other public, private, and civil society and non-governmental organizations to take on and mainstream biofortification in their crop R&D, policies, and programs. Socio-economics research helped guide plant breeding by identifying priority micronutrient- crop- geography combinations for maximum impact. Health impacts of biofortification could be projected both by using empirical results obtained through randomized controlled bioefficacy trials conducted by nutritionists, and through farmer-adoption models estimating impact at scale. Farmer and consumer surveys and monitoring systems provided the underlying information for estimating farmer adoption models and helped understand input/output markets, farmer and consumer preferences, and additional opportunities and challenges -all of which informed crop breeding and delivery activities, while building the knowledge base for catalyzing the scaling of biofortification.

Proof of concept and early development stage of market-oriented high iron and zinc rice expressing dicot ferritin and rice nicotianamine synthase genes.

Micronutrient deficiencies such as iron (Fe), zinc (Zn), and vitamin A, constitute a severe global public health phenomenon. Over half of preschool children and two-thirds of nonpregnant women of reproductive age worldwide have micronutrient deficiencies. Biofortification is a cost-effective strategy that comprises a meaningful and sustainable means of addressing this issue by delivering micronutrients through staple foods to populations with limited access to diverse diets and other nutritional interventions. Here, we report on the proof-of-concept and early development stage of a collection of biofortified rice events with a high density of Fe and Zn in polished grains that have been pursued further to advance development for product release. In total, eight constructs were developed specifically expressing dicot ferritins and the rice nicotianamine synthase 2 (OsNAS2) gene under different combinations of promoters. A large-scale transformation of these constructs to Bangladesh and Philippines commercial indica cultivars and subsequent molecular screening and confined field evaluations resulted in the identification of a pool of ten events with Fe and Zn concentrations in polished grains of up to 11 µg g-1 and up to 37 µg g-1, respectively. The latter has the potential to reduce the prevalence of inadequate Zn intake for women of childbearing age in Bangladesh and in the Philippines by 30% and 50%, respectively, compared to the current prevalence. To our knowledge, this is the first potential biotechnology public-sector product that adopts the product cycle phase-gated approach, routinely applied in the private sector.

Multiplying the efficiency and impact of biofortification through metabolic engineering.

Ending all forms of hunger by 2030, as set forward in the UN-Sustainable Development Goal 2 (UN-SDG2), is a daunting but essential task, given the limited timeline ahead and the negative global health and socio-economic impact of hunger. Malnutrition or hidden hunger due to micronutrient deficiencies affects about one third of the world population and severely jeopardizes economic development. Staple crop biofortification through gene stacking, using a rational combination of conventional breeding and metabolic engineering strategies, should enable a leap forward within the coming decade. A number of specific actions and policy interventions are proposed to reach this goal.

Reducing Mineral and Vitamin Deficiencies through Biofortification: Progress Under HarvestPlus.

Fundamentally, the prevalence of mineral and vitamin deficiencies is high in developing countries due to the fact that agricultural systems do not produce sufficient foods rich in minerals and vitamins. Biofortification involves breeding staple food crops to increase their micronutrient content, targeting staple foods widely consumed by low-income families globally. In so doing, biofortification contributes to solving the underlying problem of mineral and vitamin deficiencies by increasing the amount of iron, zinc, and provitamin A produced by food systems. When HarvestPlus first started in 2003, there was much doubt among a range of stakeholders, that biofortification would work. First, we had to prove to the plant science community that higher target levels iron, zinc, and provitamin A could be bred into high-yielding, profitable varieties. Presently, over 150 varieties of 12 biofortified crops have passed the agronomic tests of varietal release committees in 30 developing countries. In 3-5 years, biofortified varieties will be available to farmers and consumers in an additional 25 countries. The nutrition community initially questioned the efficacy of biofortified crops - would the levels of retained nutrients and absorption be high enough? HarvestPlus has commissioned 15 efficacy trials, all undertaken in developing countries. While 5 of these studies are still in process, there is already sufficient positive published evidence for iron and provitamin A. Can adoption of biofortified crops by farmers be scaled up, and a public health impact demonstrated? HarvestPlus estimates that 20 million farmers and consumers presently grow and consume biofortified crops in 8 target countries. The final and major challenge is to mainstream biofortification into the fabric of "business-as-usual" of a range of organizations - public and private agricultural research, institutions that focus on bringing improved agricultural technologies to farmers including multi-lateral lending institutions, private companies, non-governmental organizations, and the policies and programs of national governments, regional organizations, and UN agencies.

Improving nutrition through biofortification: A review of evidence from HarvestPlus, 2003 through 2016.

Biofortification is a feasible and cost-effective means of delivering micronutrients to populations that may have limited access to diverse diets and other micronutrient interventions. Since 2003, HarvestPlus and its partners have demonstrated that this agriculture-based method of addressing micronutrient deficiency through plant breeding works. More than 20 million people in farm households in developing countries are now growing and consuming biofortified crops. This review summarizes key evidence and discusses delivery experiences, as well as farmer and consumer adoption. Given the strength of the evidence, attention should now shift to an action-oriented agenda for scaling biofortification to improve nutrition globally. To reach one billion people by 2030, there are three key challenges: 1) mainstreaming biofortified traits into public plant breeding programs; 2) building consumer demand; and 3) integrating biofortification into public and private policies, programs, and investments. While many building blocks are in place, institutional leadership is needed to continue to drive towards this ambitious goal.

Probability of success of breeding strategies for improving pro-vitamin A content in maize.

Biofortification for pro-vitamin A content (pVAC) of modern maize inbreds and hybrids is a feasible way to deal with vitamin A deficiency in rural areas in developing countries. The objective of this study was to evaluate the probability of success of breeding strategies when transferring the high pVAC present in donors to elite modern-adapted lines. For this purpose, a genetic model was built based on previous genetic studies, and different selection schemes including phenotypic selection (PS) and marker-assisted selection (MAS) were simulated and compared. MAS for simultaneously selecting all pVAC genes and a combined scheme for selecting two major pVAC genes by MAS followed by ultra performance liquid chromatography screening for the remaining genetic variation on pVAC were identified as being most effective and cost-efficient. The two schemes have 83.7 and 84.8% probabilities of achieving a predefined breeding target on pVAC and adaptation in one breeding cycle under the current breeding scale. When the breeding scale is increased by making 50% more crosses, the probability values could reach 94.8 and 95.1% for the two schemes. Under fixed resources, larger early generation populations with fewer crosses had similar breeding efficiency to smaller early generation populations with more crosses. Breeding on a larger scale was more efficient both genetically and economically. The approach presented in this study could be used as a general way in quantifying probability of success and comparing different breeding schemes in other breeding programs.

Food prices, household income, and resource allocation: socioeconomic perspectives on their effects on dietary quality and nutritional status.

BACKGROUND: The recent rise in agricultural commodity prices has been dramatic, and food prices are likely to follow an upward trend, at least in the medium-term. Moreover, the recent financial crisis has also lowered incomes and increased food prices. Not only does this reduce dietary quality, but expenditures for health, sanitation, and education will decline, all of which will have a detrimental effect on health and nutrition outcomes. OBJECTIVE: To provide some perspectives on the role of major socioeconomic factors in driving health and nutrition outcomes. METHODS: We use demand elasticity parameters estimated from household-level survey data to simulate an increase in food prices, which is then mapped into energy and nutrient intakes. Furthermore, we also use household-level data to analyze the implications of unequal intrahousehold distribution of food for the nutritional status of adult women and female children. RESULTS: A 50% increase in food prices results in a decrease in energy intake of 5% to 15% and in a decrease in iron intake of 10% to 30%, depending on the strength of the induced income effect. In a country like the Philippines, this would be equivalent to an increase of 25 percentage points in the proportion of women not meeting their requirements for iron intake. CONCLUSIONS: Increasing food prices will make fighting micronutrient malnutrition in developing countries more difficult. In societies where preference is given to males in the intrahousehold distribution of nonstaple foods, this objective will be even more challenging.

Biofortification: a new tool to reduce micronutrient malnutrition.

BACKGROUND: The density of minerals and vitamins in food staples eaten widely by the poor may be increased either through conventional plant breeding or through the use of transgenic techniques, a process known as biofortification. OBJECTIVE: HarvestPlus seeks to develop and distribute varieties of food staples (rice, wheat, maize, cassava, pearl millet, beans, and sweet potato) that are high in iron, zinc, and provitamin A through an interdisciplinary, global alliance of scientific institutions and implementing agencies in developing and developed countries. METHODS: In broad terms, three things must happen for biofortification to be successful. First, the breeding must be successful--high nutrient density must be combined with high yields and high profitability. Second, efficacy must be demonstrated--the micronutrient status of human subjects must be shown to improve when they are consuming the biofortified varieties as normally eaten. Thus, sufficient nutrients must be retained in processing and cooking and these nutrients must be sufficiently bioavailable. Third, the biofortified crops must be adopted by farmers and consumed by those suffering from micronutrient malnutrition in significant numbers. RESULTS: Biofortified crops offer a rural-based intervention that, by design, initially reaches these more remote populations, which comprise a majority of the undernourished in many countries, and then penetrates to urban populations as production surpluses are marketed. In this way, biofortification complements fortification and supplementation programs, which work best in centralized urban areas and then reach into rural areas with good infrastructure. CONCLUSIONS: Initial investments in agricultural research at a central location can generate high recurrent benefits at low cost as adapted, biofortified varieties become available in country after country across time at low recurrent costs.

Estimating the global costs of vitamin A capsule supplementation: a review of the literature.

BACKGROUND: Vitamin A supplementation reduces child mortality. It is estimated that 500 million vitamin A capsules are distributed annually. Policy recommendations have assumed that the supplementation programs offer a proven technology at a relatively low cost of around US$0.10 per capsule. OBJECTIVES: To review data on costs of vitamin A supplementation to analyze the key factors that determine program costs, and to attempt to model these costs as a function of per capita income figures. METHODS: Using data from detailed cost studies in seven countries, this study generated comparable cost categories for analysis, and then used the correlation between national incomes and wage rates to postulate a simple model where costs of vitamin A supplementation are regressed on per capita incomes. RESULTS: Costs vary substantially by country and depend principally on the cost of labor, which is highly correlated with per capita income. Two other factors driving costs are whether the program is implemented in conjunction with other health programs, such as National Immunization Days (which lowers costs), and coverage in rural areas (which increases costs). Labor accounts for 70% of total costs, both for paid staff and for volunteers, while the capsules account for less than 5%. Marketing, training, and administration account for the remaining 25%. CONCLUSIONS: Total costs are lowest (roughly US$0.50 per capsule) in Africa, where wages and incomes are lowest, US$1 in developing countries in Asia, and US$1.50 in Latin America. Overall, this study derives a much higher global estimate of costs of around US$1 per capsule.

Rural drinking water at supply and household levels: quality and management.

Access to safe drinking water has been an important national goal in Bangladesh and other developing countries. While Bangladesh has almost achieved accepted bacteriological drinking water standards for water supply, high rates of diarrheal disease morbidity indicate that pathogen transmission continues through water supply chain (and other modes). This paper investigates the association between water quality and selected management practices by users at both the supply and household levels in rural Bangladesh. Two hundred and seventy tube-well water samples and 300 water samples from household storage containers were tested for fecal coliform (FC) concentrations over three surveys (during different seasons). The tube-well water samples were tested for arsenic concentration during the first survey. Overall, the FC was low (the median value ranged from 0 to 4 cfu/100ml) in water at the supply point (tube-well water samples) but significantly higher in water samples stored in households. At the supply point, 61% of tube-well water samples met the Bangladesh and WHO standards of FC; however, only 37% of stored water samples met the standards during the first survey. When arsenic contamination was also taken into account, only 52% of the samples met both the minimum microbiological and arsenic content standards of safety. The contamination rate for water samples from covered household storage containers was significantly lower than that of uncovered containers. The rate of water contamination in storage containers was highest during the February-May period. It is shown that safe drinking water was achieved by a combination of a protected and high quality source at the initial point and maintaining quality from the initial supply (source) point through to final consumption. It is recommended that the government and other relevant actors in Bangladesh establish a comprehensive drinking water system that integrates water supply, quality, handling and related educational programs in order to ensure the safety of drinking water supplies.

Biofortification of staple food crops.

Deficiencies of vitamin A, iron, and zinc affect over one-half of the world's population. Progress has been made to control micronutrient deficiencies through supplementation and food fortification, but new approaches are needed, especially to reach the rural poor. Biofortification (enriching the nutrition contribution of staple crops through plant breeding) is one option. Scientific evidence shows this is technically feasible without compromising agronomic productivity. Predictive cost-benefit analyses also support biofortification as being important in the armamentarium for controlling micronutrient deficiencies. The challenge is to get producers and consumers to accept biofortified crops and increase their intake of the target nutrients. With the advent of good seed systems, the development of markets and products, and demand creation, this can be achieved.

Micronutrient fortification of plants through plant breeding: can it improve nutrition in man at low cost?

Can commonly-eaten food staple crops be developed that fortify their seeds with essential minerals and vitamins? Can farmers be induced to grow such varieties? If so, would this result in a marked improvement in human nutrition at a lower cost than existing nutrition interventions? An interdisciplinary international effort is underway to breed for mineral- and vitamin-dense varieties of rice, wheat, maize, beans and cassava for release to farmers in developing countries. The biofortification strategy seeks to take advantage of the consistent daily consumption of large amounts of food staples by all family members, including women and children as they are most at risk for micronutrient malnutrition. As a consequence of the predominance of food staples in the diets of the poor, this strategy implicitly targets low-income households. After the one-time investment is made to develop seeds that fortify themselves, recurrent costs are low and germplasm may be shared internationally. It is this multiplier aspect of plant breeding across time and distance that makes it so cost-effective. Once in place, the biofortified crop system is highly sustainable. Nutritionally-improved varieties will continue to be grown and consumed year after year, even if government attention and international funding for micronutrient issues fades. Biofortification provides a truly feasible means of reaching malnourished populations in relatively remote rural areas, delivering naturally-fortified foods to population groups with limited access to commercially-marketed fortified foods that are more readily available in urban areas. Biofortification and commercial fortification are, therefore, highly complementary. Breeding for higher trace mineral density in seeds will not incur a yield penalty. Mineral-packed seeds sell themselves to farmers because, as recent research has shown, these trace minerals are essential in helping plants resist disease and other environmental stresses. More seedlings survive and initial growth is more rapid. Ultimately, yields are higher, particularly in trace mineral-'deficient' soils in arid regions.

Coliforms in the water and hemoglobin concentration are predictors of gastrointestinal morbidity of Bangladeshi children ages 1-10 years.

The presence of pathogens in the water and children's poor nutritional status are likely to increase morbidity in developing countries. Understanding the interactions between the environmental and nutritional factors is important from the standpoint of improving child health. In this study, we analyzed the effects of fecal and total coliforms in the water available at the source and that stored in the household on the spells of gastrointestinal morbidity of 99 Bangladeshi children at three time points in an 8-month period. Fecal and total coliforms in the stored water were significant predictors (P < 0.05) of morbidity that was modeled using dynamic random effects models. Moreover, children with better hemoglobin status experienced lower morbidity. An empirical model for the proximate determinants of hemoglobin concentration showed significant negative associations between children's hookworm loads and hemoglobin. While the children's intakes of bioavailable iron, iron from meat, fish, and poultry, and iron from animal sources were not significant predictors of hemoglobin status in this population, the need for broader interventions for improving child health was apparent.

Plant breeding: a new tool for fighting micronutrient malnutrition.

The final permanent solution to micronutrient malnutrition in developing countries is a substantial improvement in dietary quality--higher consumption of pulses, fruits, vegetables, fish and animal products that the poor already desire but cannot presently afford. Meanwhile breeding staple foods that are dense in minerals and vitamins provides a low-cost, sustainable strategy for reducing levels of micronutrient malnutrition. Getting plants to do the work of fortification, referred to as "biofortification," can reach relatively remote rural populations that conventional interventions are not now reaching and can even have benefits for increased agricultural productivity. Biofortification, thus, complements conventional interventions. The symposium articles discuss several examples of ongoing research projects to develop and disseminate nutrient-dense staple food crops and issues that remain to be resolved before successful implementation can be attained.

Three criteria for establishing the usefulness of biotechnology for reducing micronutrient malnutrition.

The fundamental reason that plant breeding using either conventional breeding or biotechnology is so cost-effective is that the benefits of a one-time investment at a central research location can be multiplied over time across nations all over the world. Supplementation and fortification incur the same recurrent costs year after year in country after country. However, each intervention has its own comparative advantages, such that a combination of several interventions is required to substantially reduce micronutrient malnutrition. Improving the density of trace minerals in plants also reduces input requirements and raises crop yields. A simulation model for India and Bangladesh demonstrated that $42 million invested in conventional breeding in developing and planting iron- and zinc-dense varieties of rice and wheat on only 10% of the acreage used for these crops would return $4.9 billion in improved nutrition (including a total of 44 million prevented cases of anemia over 10 years) and higher agricultural productivity.