A STUDY OF THE EFFECTIVENESS AND GLOBAL PUBLIC HEALTH IMPACT OF GOLDEN RICE Christopher John Jericho A. Balicanta
Micronutrients are crucial for all life, as they help maintain normal bodily structure and functions. The human body, however, has lost the ability to synthesize sufficient quantities of certain micronutrients, called vitamins, on its own and must therefore obtain nutrients from diet (Fitzpatrick et al., 2012). One important micronutrient is Vitamin A an essential substance for promoting the maintenance and proper functioning of various body systems, such as vision, immunity, tissue structure, red blood cell production, and reproduction (Evert, 2013). Vitamin A is a collective name for fat-soluble substances that exist in two major forms: retinal, the active form of Vitamin A, and carotenoids, such as beta-carotene, which are found in plants and converted into vitamin A inside the body (World Health Organization, 2009). Insufficient intake of these vital substances may result to adverse and potentially fatal health conditions. Vitamin A Deficiency, or VAD, is a condition in which a person receives chronically substandard amounts of vitamin A. Individuals who are undernourished with vitamin A may develop certain complications, such as dry eyes (xerophthalmia), inhibited growth, and anemia. Vitamin A deficiency is also the leading cause for blindness in children, and increases the risk of mortality due to severe infections. About half of the children affected by VAD die within 12 months of going blind. VAD also affects pregnant women by causing night blindness, and, in some cases, increases the risk of maternal mortality (WHO, 2013). VAD affects around 250 million children under the age of five, and is classified by WHO as a moderate to severe public health problem in 122 countries, especially in the Southeast Asian 2
and African regions, making it a global health concern (WHO, 2009). Over 90 million children are affected by VAD in the Southeast Asian region alone. Nutritional research in the Philippines has shown a national VAD prevalence of 5.9%, with children six months to five years of age having the highest VAD incidence, with 15.9%, or 1.9 million (Food and Nutrition Research Institute, 2008). Studies have estimated that the improvement of Vitamin A nutrition in children could prevent 1.9 2.7 million deaths worldwide (Tang et al., 2012). Community interventions have been conducted by health organizations in order to alleviate this global problem. Educational programs on nutrition have been organized and vitamin A-rich food have been made available for at-risk communities. Domestic cultivation of vitamin A-rich food were also encouraged of those who do not have direct access to these crops. High-potency vitamin A capsules and supplements have also been administered in communities classified as having a high risk of acquiring VAD. Another approach is the fortification of staple food and condiments. This strategy, however, has not seen popularity in lower-income countries (World Health Organization, 2009). Moreover, the efficacy of Vitamin A capsules and carotenoid-rich plants and crops in delivering vitamin A failed to meet expected supplementation levels (Tang et al., 2012). In this regard, it was theorized that the fortification of staple food crops should be a more effective and accessible approach for vitamin A supplementation in lower-income areas. Rice is the major staple food of nearly half of the worlds population and is produced primarily in Southeast Asia and Africa regions with the highest proportions of Vitamin A deficiency in children under 5 and pregnant women (Mayo-Wilson, Imbad, Herzer, Yakoob, & Bhutta, 2011). The rice plant, while contains carotenoids in the leaves, is unable to synthesize pro-vitamin A in the endosperm, the edible part of the crop. The lack of vitamin A in the staple 3
crop, coupled with the inability to afford a more diversified diet, remain to be major factors in the high prevalence of VAD in lower-income countries (Potrykus, 2010). In an effort to address this problem, plant biologists Ingo Potrykus and Peter Beyer have developed Golden Rice a rice variety with yellow-colored endosperm that is genetically modified in order to biosynthesize beta-carotene, a vitamin A precursor. Golden Rice was produced by introducing two genes (phytoene synthase (psy) and phytoene desaturase (crtl)) into the rice endosperm in order to establish a beta-carotene biosynthetic pathway and activate the production of pro-vitamin A in the rice grain (Tang et al, 2009). The golden color of the rice, hence the label, is a side-effect caused by the significant presence of beta-carotene in the endosperm, as opposed to regular, carotenoid-free, white rice (Schaub, Al-Babili, Drake, & Beyer, 2005). Since its inception in 2000, Golden Rice has been continually developed in order to increase the pro-vitamin A content in its rice grain. Further improvements in genetic engineering resulted to an enhanced version of Golden Rice that contains about 23 times more beta-carotene in the endosperm (Paine et al, 2005). Recent studies have shown that Golden Rice provides adequate amounts of vitamin A to humans and is expected to provide substantial nutrition to populations with rice as a regular component of their diet (Tang et al, 2010, 2012). Despite these proposed benefits and the acclaim of the scientific community and the public sector, being a genetically modified (GM) crop, Golden Rice has met numerous opposition, especially from various anti-GM organizations, such as Greenpeace and Friends of the Earth, as well as militant groups. These groups claim that Golden Rice, as a GM food, may cause unpredictable and possibly harmful effects on humans and the environment, as well as food security. Greenpeace also promotes traditional supplements as the more stable and effective 4
solution for VAD (Greenpeace, 2012). This conflict may have been contributory to the lengthy process of regulation and testing which delays the distribution of this vital crop to undernourished populations. This paper aims to dispel those claims and prove that Golden Rice is a safe and effective approach for the alleviation of vitamin A deficiency, as well as a sustainable intervention in lower-income populations affected by this potentially fatal, yet preventable condition. Golden Rice has been proven by numerous scientific research to provide significant dietary amounts of Vitamin A in humans. While the prototype in 2000 has been criticized by both the scientific community and anti-GM groups for having substandard vitamin A content as compared to the average Vitamin A requirements in humans, researchers have continuously conducted research in order to increase the amounts of carotenoids in the rice endosperm. In 2005, researchers Paine et al. have produced a Golden Rice variant, named Golden Rice 2, which contains as much as 37 g/g of carotenoids, 31 g/g of which is beta-carotene, marking a 23-fold increase in provitamin-A content (Paine et al., 2005). The impact of Golden Rice 2 in supplying vitamin A requirements in children was then analyzed for a theoretical estimate based on the Vitamin A content of the grains and the following assumptions: (1) The Recommended Daily Allowance (RDA) for children aged 1 to 3 is 300 mg vitamin A. (2) The retinol equivalency ratio is 12:1, which represents an ideal vitamin A conversion in humans. A single serving was also defined to contain 60 g (about cup) of dry, cooked Golden Rice, which was estimated to be lower than the typical serving in countries with rice as their staple crop. It has been shown from the results of the analyses that 72 g of cooked Golden Rice supplies about 50% of the RDA in children. The data, however, may have been underestimated 5
as beta-carotene bioavailability, or the rate in which beta-carotene is absorbed in the body, may be higher as compared to fruits and vegetables in which the retinol equivalency ratio is defined (Paine et al., 2005). This implies the viability of Golden Rice 2 in supplying Vitamin A requirements in a three-meal daily diet in children. Clinical research in succeeding years have reinforced this theoretical claim by Paine, et al. In 2009, a pioneering study involving human volunteers showed a very efficient bioconversion of beta-carotene to vitamin A in humans (Tang et al., 2009). In the study, the participants were asked to consume Golden Rice grown and prepared in a controlled setup, which was tested to contain 20-30 g/g beta-carotene. The participants had their blood samples taken regularly, which were then analyzed for carotenoid and pro-vitamin A levels. The results from the clinical analyses have shown that the conversion factor, or the amount of vitamin A converted in the body from beta-carotene in the rice, is 4:1, which translates into a conversion of 500-800 g vitamin A from 100 g ( cup) rice. This, in turn, indicates an 80-100% attainment of the estimated average requirement and supplies 55-70% of the recommended daily allowance (RDA) for both adult men and women (Tang et al., 2009). Results from a separate study have also shown that a 100-150 gram Golden Rice serving in children provides about 60% of the Chinese Recommended Nutrient Intake for 6-8 year old children (Tang et al, 2012). The potential nutritive benefits of Golden Rice on women and children, two of the most VAD-vulnerable subgroups, were also presented in a study by Potrykus (2010). The study, conducted in Bangladesh, a sample low-income country, shows that the incorporation of Golden Rice into the standard diet could provide 60-120% of the WHO recommended daily intake for Vitamin A. This figure places well-above the 50% daily requirement for the prevention of VAD, 6
and marks a 60-80% increase in vitamin A nutrition, as compared to the standard diet of fruits, vegetables, poultry and fish. Apart from the effectiveness, determining whether Golden Rice is safe to consume for humans is also a main priority for Golden Rice researchers. Concerns of potential toxicity and allergenicity (property to cause allergic reactions) have been raised due to possible mutations that may arise from genetic modification (Greenpeace, 2012). However, studies on the molecular structure and beta-carotene content of Golden Rice, as well as clinical testing, have shown that the consumption of Golden Rice is expected to cause very minimal toxic or allergenic effects. Since the main additional feature in Golden Rice is its beta-carotene content, studies have been conducted in order to ensure its safety in humans. A study by experts in the field of carotenoids have examined the properties of beta-carotene and its effects in humans. Results from the consensus conference conducted through examination of published data on carotenoids have resulted to a scientific agreement that beta-carotene in Golden Rice is a safe and effective source of vitamin A in humans (Grune et al., 2010). A comprehensive bioinformatics study by Goodman & Wise (2006) inspected the potential allergenic properties of Golden Rice. The proteins in the rice grain have been subjected to a comparative assessment with 1,537 potential allergens from the Allergen Online database and 2,529 allergenic protein sequences. Results have shown no structural or genetic similarity between any of the Golden Rice proteins and all suspected allergens from the entire database. These findings imply that the consumption of Golden Rice causes no allergic reactions in humans and no possible scenario of heightened risks may be produced for any individual Golden Rice consumer (Goodman & Wise, 2006). 7
The safety of Golden Rice has also been corroborated by clinical trials on children and adults. In two separate Golden Rice consumption trials on children and adults, participants were monitored for possible side effects or anomalous reactions to the genetically modified rice grain. Thorough post-intake evaluations have reported no manifestations of abnormal effects. Furthermore, after a one-year follow-up assessment, no complaints or adverse effects have been recorded from the participants (Tang et. al., 2009, 2012). As discussed, research has well substantiated the safety and effectiveness of Golden Rice in providing Vitamin A supplementation to humans. A broader perspective, however, will be required in the examination of the economic advantage and sustainability of this program, more specifically in low-income, rice-dependent countries, where vitamin A deficiency is most prevalent. A study by Stein, Sachdev & Qaim (2006) presents scenarios on the projected annual impact of Golden Rice in India based on varying levels of beta-carotene in the grain. The high- impact scenario, deemed realistic, predicts a reduced mortality of up to 40,000 out of the annual burden of 71,600 a 55% reduction. This figure translates to 1.3 million disability-adjusted life years (DALYs) saved (DALYs refer to the sum of all individual healthy life-years lost through disease and is used as an economic quantifier for the impact of a health intervention). Even in a pessimistic, low-impact scenario, an overall mortality reduction of at least 8.8% is expected (Stein, et al., 2006). In comparison, traditional intervention programs, such as subsidized Vitamin A supplements and food fortificants, cost about $134 and $84 to save one DALY, respectively (Fitzpatrick et al., 2012). Golden Rice, on the other hand, will provide the same amount of nutrition for about $3 per DALY inclusive of all intermediate costs, such as government 8
deregulation, marketing, research and development (Potrykus, 2010). This then implies savings of $81-$131 per DALY. Furthermore, the World Bank standard defines an effective intervention to cost less than $150 per DALY, thus making Golden Rice an exceptionally cost-effective intervention on Vitamin A deficiency (Breithaupt, 2008). Further economic benefits may arise from an increased adoption of other biofortified GM crops, which may follow from the widespread implementation of Golden Rice. Consumption of these nutritionally-enhanced crops is expected to lead to a four-fold increase in unskilled labor productivity, which may then lead to an increase in real incomes of farm by 0.9% and 0.4% per cent in China and in Asias other developing countries, respectively (Amin, Azlan, Ahmad, & Ibrahim, 2011). An expected increase in worldwide welfare income from a model health benefit analysis amounted up to $15 billion, with majority of these gains manifested in Asia (Qaim, 2009). While the production and testing of Golden Rice may require high initial investments bio-safety regulations could reach up to $100,000 in the Philippines long-term costs are expected to be low once the crop is fully integrated into the agro-economic landscape (Beyer, 2008). Also, major financial support, amounting to nearly $20 million, by philanthropic organizations such as the Bill and Melinda Gates Foundation and the Rockefeller Foundation, should greatly help ease the economic burden of research funding on developing countries (International Rice Research Institute, n.d.; Nayar, 2011). Moreover, Golden Rice, as any other local rice variety, can be distributed through local trade channels. In contrast to vitamin A capsules and fortified food, Golden Rice should, in principle, require minimal monitoring, maintenance and logistic costs; only a marginal increase in the existing rice production 9
investment should be able to sustain its continual deployment (Al-Babili & Beyer, 2005; Potrykus, 2010). Integration into the diets of rural populations is also expected to be much faster and more sustainable than other vitamin A-rich crops, as local rice farmers may be able to produce the Golden Rice themselves through conventional rice production methods without having to allocate separate land for production of less marketable and non-dietary crops. Yield factors and risks in Golden Rice are about the same as traditional rice crops, no additional fertilizers or other crop yield enhancers are needed. The proprietary technology used for Golden Rice has also been donated by its inventors for humanitarian use, which means farmers earning less than $10,000 a year may freely produce, consume and distribute Golden Rice seeds and harvest within the framework allotted by the proprietors. The economic factor of Golden Rice should only be limited by costly deregulation procedures and development, but overall, the potential effects of the biofortified crop is expected to outweigh its sustainable long-term costs (Fitzpatrick et al., 2012). Despite the discussed health benefits and cost-effectiveness, Golden Rice has faced numerous opposition, which might primarily be due to the generally negative public opinion on genetically modified organisms. Environmental and human health issues remain to be the primary deterrents for the propagation of Golden Rice seeds, as well as other GM crops. Greenpeace (2012) cites that Golden Rice could impose adverse effects due to the changes in the genetic makeup of the plant, as compared to conventional breeding methods. A primary concern expressed by Greenpeace (2012) is the possibility of a contamination of traditional rice fields. Greenpeace believes that Golden Rice could inadvertently fertilize non-GM rice varieties, irreversibly affecting their genetic information and 10
then degrading their quality, potentially rendering both wild and domestic rice crops inedible for future generations. However, it has long been known that rice, including GM varieties, is ordinarily a self-pollinator, and thus the probability of cross-pollination is low, especially when rice fields are separated by as little as a few meters. Wild rice varieties are also found to seldom grow near domestic fields. Lastly, should cross-pollination occur between Golden Rice and non- GM varieties, research has determined that Golden Rice genes do not strengthen or weaken non- GM rice qualities, thus negating its potential of producing unwanted weed and affecting biodiversity (IRRI, n.d.). Scientific communities have also shown a consensus which affirms that GM crops pose no novel risk as compared to conventionally produced crops (Potrykus, 2010). Moreover, before Golden Rice seeds are approved for propagation, they undergo extensive testing and approval in accordance to numerous international safety regulations, including the Cartagena Safety Protocol, a global set of guidelines on handling, transfer and use of living modified organisms in order to ensure adequate protection from potential risks to human health and biodiversity (Secretariat of the Convention on Biological Diversity, 2000). In the Philippine setting, GM crops such as Golden Rice are also subject to thorough regulatory research in accordance to international standards. Risk-benefit assessments are conducted by the Institutional Bio-safety Committee (IBC) on the proposed crop. The National Committee on Bio-safety in the Philippines (NCBP) then studies the crop for potential harmful effects. Upon the approval by the IBC and NCBP, an application for field testing is submitted to the Bureau of Plant Industry, which then conducts additional risk assessments for gene contamination, toxicity and other environmental effects. Lastly, an application for the permit for propagation and commercialization should be secured and will only be approved once field 11
evaluation is successful. This process ensures the safety and efficacy of all GM crops implemented in the Philippines (Beyer, 2008). Another point of opposition presented is the declining trend of global vitamin A deficiency attributed to existing programs and supplements. It has been argued that governments should focus their funding instead on well-proven traditional methods to combat VAD, such as food supplements and dietary diversification. However, research has presented economic disadvantages of this claim, especially in developing countries. Traditional food supplements are projected to be less sustainable and affordable than Golden Rice, as previously presented, costing about $130 more per healthy life-year saved than the biofortified staple crop (Breithaupt, 2008). Also, in terms of delivery and logistics, Golden Rice provides better self-sufficiency as the crop may be propagated in local farms and distributed through local formal and informal trade channels without risk of endangering local crop competition (Qaim, 2009). The establishment of Golden Rice as an effective and affordable intervention for VAD could have immense impacts on developing countries affected with vitamin A deficiency, especially the Philippines. One such envisaged implication is the significant improvement of the countrys public health sector. Rice is one of the central crops of Philippine agriculture, and constitutes a large part of the average Filipino diet. The implementation of the program, submitted for approval in 2013, could greatly aid in the cost-effective delivery and accessibility of vitamin A supplementation, especially in remote rural areas. Projections expect a 6-47% reduction of DALYs lost per year in the Philippines due to the incorporation of Golden Rice into the average diet (Amin, et al., 2011). 12
Aside from the attainment of the crops proposed benefits, the substantiation of the safety and effectiveness of Golden Rice could be an avenue for an improved agricultural research landscape and a better understanding on how biotechnology may be utilized to improve public health. The exploration of other crops like corn and wheat for biofortification may be involved in future studies. The incorporation of other micronutrients such as iron and folate into crops may also be possible areas of research and implementation (Qaim, 2009). More sound education on GM organisms delivered by this project may then improve the reception of the government, as well as the masses, on these products. Results of this research may also be referenced to improve on the current government regulatory policies on genetically modified crops. As exposed by several studies summarized by Potrykus (2010), excessive and often unscientific regulatory practices such as the system currently employed result in grave social repercussions. The annual cost of delays in implementation amounts to around $15 billion of GDP in Asia alone and millions of healthy life- years lost. A possible restructuring of the national assessment program on GM crops may aid in the maximization of the benefits generated by GM products. It should be acknowledged, even with the programs overwhelming health and economic benefits, that Golden Rice is proposed to be neither the sole, nor the best, solution for the alleviation of VAD. It is also campaigned neither to completely cure, nor fully prevent Vitamin A deficiency, as the case in any other vitamin A supplement. The Golden Rice project, however, seeks to effectively bridge the accessibility gap between proper micronutrient supplementation and VAD-affected populations through staple crop biofortification. This paper, through a review of research literature, determines that Golden Rice is a safe, effective and affordable supplement 13
to existing interventions for the sustainable alleviation of Vitamin A deficiency. Golden Rice is therefore highly recommended for propagation and consumption in the Philippines.
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