Planning for the Implementation of Golden Rice as an Intervention for Vitamin A Deficiency: Recommendations for India
By
Leah Hosein Stansberry
A Masters Paper submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for The degree of
Master of Public Health in The Public Health Leadership Program
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Abstract
Vitamin A deficiency is a consequence of malnutrition in many developing nations. According to the World Health Organization (WHO), the majority of the global burden of vitamin A
deficiency occurs in South Asia and sub-Saharan Africa. Vitamin A deficiency leads to adverse health outcomes such as night blindness, keratomalacia, and blindness as well as susceptibility to other infections, including HIV-AIDS, measles, respiratory infections, and diarrheal diseases which contribute to under-five mortality. The government of India reports that vitamin A deficiency is still a public health issue affecting 62% of India’s population despite the administration of The National Prophylaxis Programme against Nutritional Blindness
implemented in 1970 which provides mega doses of vitamin A supplementation to infants and children throughout the country. Advances in science and inadequate vitamin A supplementation coverage have led to the development of a creative solution for vitamin A deficiency through plant biotechnology in the creation of Golden Rice for consumption in regions of the world where rice is a staple food. Using genetic engineering, Golden Rice produces beta-carotene, a precursor to vitamin A that is converted to vitamin A in the body. However, minimal scientific data are publicly available in peer-reviewed journals assessing the health and environmental safety and efficacy of the Golden Rice crop. Additionally, external factors surrounding Golden Rice such as agricultural, regulatory, public opinion, and banking sector issues warrant
Introduction
Globally, the majority of children affected with vitamin A deficiency (VAD) lives in Africa and South Asia. The World Health Organization (WHO) estimates that 250 million children under 5 are deficient in vitamin A (WHO, 2016). Of that number, blindness ensues in 250,000-500,000 (WHO, 2016). The government of India reports that VAD affects 62% of India’s population (Government of India, 2014). Fifty-two thousand children become blind and 330,000 children die each year in India as a result of VAD (Semba, et al., 2009). Besides blindness, other adverse health outcomes in India attributed to VAD include night blindness (xerophthalmia), keratomalacia, corneal scarring, under five mortality, and measles (Semba et al., 2009; Stein, Sachdev, and Qaim, 2008).
Malnutrition is documented as the primary reason for VAD in India (Worley, 2014). Malnutrition can be defined in terms of an inadequate daily caloric intake and/or insufficient dietary intake and absorption of essential micronutrients such as iodine, zinc, folic acid, vitamin A, iron, and magnesium (Menon, Thompson, & Sonntag, 2014). Because malnutrition
encompasses micronutrient deficiencies, it is possible for adults and children to have an adequate daily caloric intake, but still be considered malnourished because they do not consume nutritious food that enables good health, physical and cognitive development, and mental function (Menon, Thompson, & Sonntag, 2014).
population that is malnourished (Menon, Thompson, & Sonntag, 2014). A low GHI indicates better nutritional status.According to the India’s 2014 Planning Commission report, India ranks 55 on the Global Hunger Index out of 76 developing nations with a GHI score of 17.8. which classifies its hunger severity as “serious” (Government of India, 2014).Still this represents significant improvement in nutritional status from the first GHI score of 31.2 calculated for India in 1990 which ranked India 96th out of 119 developing nations (Government of India, 2014). By comparison, Mexico, Turkey, and Brazil have GHI scores under 5 (Government of India, 2014). Despite substantial improvement in malnutrition since 1990, India still has the largest percentage of chronically undernourished and stunted children under the age of five in the developing world (Government of India, 2014).
Consequences of malnutrition and micronutrient deficiency such as physical and cognitive impairments are irreversible even with proper nutrition later in life. This adversely affects the economy of a nation (Copenhagen Consensus, 2012). In 2008, the Copenhagen Consensus, a conference of top economists from around the globe, identified micronutrient deficiencies as the primary cause of poor economic development (Copenhagen Consensus, n.d.). The Indian National Science Academy estimates that malnutrition in India results in a loss of productivity equivalent to greater than 10% of lifetime earnings among individuals and 2-3% of India’s gross domestic product (Indian National Science Academy, 2011). In 2012, the
Efforts made by India to reduce VAD and existing gaps
WHO guidelines recommend high doses of Vitamin A to reduce child mortality and morbidity if 20% or higher of children ages 6-59 months of age within a population exhibit VAD. This is defined as: (i). a serum retinol concentration of 0.7 micromoles per liter (µmol/l) or lower or (ii). a prevalence of night blindness of 1% or higher among children ages 24-59 months (WHO, 2011).To combat VAD, India implemented a universal vitamin A supplementation program in 1970 to children ages 6 -59 months in all states in India (Kapil and Sachdev, 2013). Vitamin A supplementation in India is administered through the National Prophylaxis
Programme against Nutritional Blindness (Kapil and Sachdev, 2013). The government of India subsidizes vitamin A supplementation through multiple international organizations such as UNICEF, Sight and Life (a Swiss nutrition think tank), and the Micronutrient Initiative (a Canadian funded non-governmental organization) to provide nine mega doses of vitamin A to children ages 9 months to 5 years of age. First and second doses are administered during routine immunizations and doses 3-9 are administered during set delivery times twice per year either as a syrup or as an oil solution within a red or blue gelatin capsule: blue capsules contain 100,000 IU for children ages 6-11 months of age while the red capsules contain 200,000 IU for children ages 12-59 months (Micronutrient Initiative, 2015). The colored capsules standardize the
immunization and de-worming schedules which are offered on designated Child Health days and other primary health care days (Micronutrient Initiative, 2015). Despite these efforts, India’s vitamin A supplementation program is ineffective with a coverage rate of 53% (World Bank, 2016). UNICEF and the WHO state that achieving a reduction in child mortality requires two conditions: children ages 6-59 months must receive high doses of vitamin A supplements every 4-6 months or approximately twice a year, and vitamin A supplementation must reach at least 70% of children in a country (UNICEF, 2007; WHO, 2011). Some reasons for the gap in vitamin A supplementation coverage described in literature are (Bhutia, de Pee, and Zwanikken, 2013):
Only 44% of villages have access to a village or primary care health center.
Only 48% of the health centers are adequately staffed with personnel to administer supplementation.
Poor program coordination due to weak partnerships with village health committees results in a lack of outreach to parents regarding the importance of vitamin A
supplementation and education about vitamin A deficiency; no tracking of children who drop out of the supplementation program.
Lack of transportation hinders the ability of parents to take children to health centers as the average distance to a health center is 5 kilometers.
A syrup that has to be measured. Reports exist of personnel using spoons instead of measuring cups thereby administering incorrect doses.
Despite improvements in VAD as a result of vitamin A supplementation programs, shortcomings pose a challenge in low resource settings to the achievement of high population coverage and have stimulated the development of alternative strategies to address VAD. One solution implemented in several developing nations is the biofortification of staple foods in which vitamin A is intentionally added to regularly consumed foods as a means of delivering essential nutrients to a target population. For example, sugar is fortified with vitamin A in Honduras, Guatemala, and El Salvador (Saeterdal, Mora, and De-Regil, 2012). Fortifying staple foods like rice through genetic modification is another creative solution to VAD. This genetically modified rice, called Golden Rice, is the primary focus of this paper.
The Case for Golden Rice
Golden Rice has the potential to address some of the gaps in current supplementation programs in low income settings. First, as a staple food, Golden Rice is a way to mitigate vitamin A deficiency in adults as well as children. The Food and Agriculture Organization of the United Nations defines staple food as “one that is eaten regularly and in such quantities as to constitute the dominant part of the diet and supply a major proportion of energy and nutrient needs” (Food and Agriculture Organization, 1995). Rice consumption in India has hovered around an average of 80 kilograms per capita annually since the 1990s (USDA, 2007). Households spend more money on rice than on any other item - 22% in rural areas and 13% in urban areas of India (USDA, 2007). When Golden Rice is consumed, beta-carotene is absorbed in the small intestine, stored in the liver, and converted into vitamin A (retinol) at the body’s discretion. Therefore, toxicity from vitamin A overdose is not possible from the consumption of beta-carotene (Lobo et al., 2013). In addition, the need for staff availability to administer vitamin A, track children who drop out of the supplementation program, and the need to train human resources to administer correct dosing of vitamin A is eliminated. The current Vitamin A supplementation program depends on health infrastructure, mainly the primary health care system, for delivery. An advantage of Golden Rice as a vitamin A intervention is that it is not dependent on the
availability or accessibility of adequately staffed health centers thereby offering the possibility for scarce human resources to focus on other primary health care needs.
Another advantage of Golden Rice as an intervention is that its distribution may only require modifications to processes that already exist rather than having to create new systems. Achieving a high coverage of Golden Rice will depend on local markets for farmers to obtain seeds for cultivation. The National Seeds Corporation operates under the Department of
certified seeds to farmers, a system which can be used to distribute Golden Rice seeds (Government of India, n.d.).
Food distribution systems already in place can be utilized to distribute Golden Rice (Stein, Sachdev, and Qaim, 2008). At school, free lunches are provided to millions of children in public primary and upper primary schools (Government of India, n.d.). Funds from the national government of India are allotted to state governments who then distribute the funds to schools along with a quota of rice and wheat (100 grams per child per school day) delivered by trucks in the respective districts (Balani, 2013). Schools are responsible for implementing the lunch program by buying food, providing a kitchen, hiring cooks, and preparing and serving food to children (Balani, 2013).Providing Golden Rice in school lunches has the potential to reach 120 million children each school day.
For citizens in rural and residential areas, the Department of Food and Public Distribution implements grain distribution under the National Food Security Act, 2013. The national
ration shops are accessible throughout India even in rural areas, which eliminates the
transportation barrier that prevents parents from driving several kilometers to the nearest village health center for vitamin A supplements.
Cost-effectiveness is another advantage of Golden Rice that cannot be overlooked. Measurement of disease burden in terms of Disability Adjusted Life Year (DALY) considers the loss of health each year from adverse health outcomes (corneal scarring, night blindness, measles, blindness, and under 5 mortality) due to vitamin A deficiency (Stein, Sachdev, and Qaim, 2008). The WHO currently defines cost-effectiveness of interventions in terms of per DALY averted or per Quality Adjusted Life Year (QALY) gained (WHO, 2014). The estimated cost per DALY averted through vitamin A supplementation is $200-250 (WHO, 2011). In contrast, the cost per DALY averted through Golden Rice is estimated to be within the range of $3- $20 USD (Stein, Sachdev, and Qaim, 2006). After the initial financial investment to develop and implement, Golden Rice is an inexpensive Vitamin A intervention to maintain.
These values were higher by a few percentage points for poorer families (because pre-Golden Rice Vitamin A intakes were much lower) and lower for richer families (because they were not as vitamin A deficient as poorer families) (Stein, Sachdev, and Qaim, 2008).
Finally, India’s current vitamin A supplementation program depends heavily on funding from the Canadian government (Micronutrient Initiative, 2015). Reliance on outside funding is not sustainable because international donors may not always contribute the necessary funding to continue the program (Micronutrient Initiative, 2015). In contrast, Golden Rice would be grown by India’s farmers for India which removes the reliance on external funding and makes it a more sustainable vitamin A intervention.
Despite these benefits, numerous challenges exist in bringing Golden Rice and other GM crops to the market. Countries interested in GM crop development must first have
comprehensive regulatory guidelines to ensure that the process of development and testing GM crops is consistent with international regulations. Then several years of research and
development starting from transforming local crop varieties with the desired genetic trait through environmental and animal testing of the new GM crop are needed to comply with the regulatory frameworks by demonstrating that the GM food is safe for the environment and human
consumption. In addition, interaction with the public during the development process is necessary for fostering consumer acceptance. A GM food crop that has been successfully
implemented in a low resource setting is eggplant known as Bt brinjal. Approved by Bangladesh in 2013, Bt brinjal can serve as a model for India’s commercialization of Golden Rice.
Bringing a GM crop to market: Bt brinjal in Bangladesh
The Bangladesh Agricultural Research Institute (BARI) and the Bangladesh Rice
crops as a means to achieve food security (BDRC, 2009). As a staple food in Bangladesh,
eggplant is grown year round. The Bangladesh Agriculture Research Institute estimates that up to 70% of eggplant crops are lost to fruit and shoot borer infestation which impacts farmers’
incomes from a loss of eggplant crop and the expense of purchasing insecticides to treat the infestation every 2-3 days. Pesticides are used an average of 140 times during a growing season of 180-200 days. In addition, farmers in Bangladesh experience adverse health effects from the use of pesticides as they often spray with no physical protection such as masks or shoes (BDRC, 2009; ISAAA, 2014). The creation of Bt brinjal, a genetically modified eggplant, was approved by the Ministry of Environment and Forests of Bangladesh in order to increase crop yields thereby increasing food security to support population growth, improve farmers’ health, and the health of consumers by providing a staple food free of pesticide residue (ISAAA, 2014).
Overall, the process of testing Bt brinjal began in 2005 with nine local varieties being tested. In accordance with the Biosafety guidelines from the Ministry of Environment and Forest, the selected local varieties were grown for two seasons in the greenhouse followed by two seasons in open fields. All nine varieties were grown from 2005-2006 and 2007-2008 in confined areas of greenhouses. Seven varieties were then grown in limited open field trials for two
capita income is $700 USD (ISAAA, 2014). The process leading to the approval and commercialization of Bt brinjal in Bangladesh is summarized in Table 2.
Table 2
Chronology Study Activity Result
Step 1 Obtain approval from Bangladesh
government to import Bt brinjal Seeds were donated to BARI by theMaharashtra Hybrid Seeds Company (Mahyco) in India
Step 2 2005 Conventional and Bt seeds were grown for a side by side
comparison in greenhouses at the Bangladesh Agriculture Research Institute and seven regional agricultural research institutions in designated plots of wire mesh netting in greenhouses
Average shoot damage in Bt brinjal crops ranged from 0.06%-0.4%; conventional brinjal shoot damage averaged 0.18%-1.7%. Damaged eggplant fruit from Bt brinjal plants ranged from 2.5-20% and 24-60% in conventional brinjal
Step 3 Open field trials and Environmental
studies on pollen transfer Cross-pollination had no adverse effects on non-Bt brinjal plants; no change in plant behavior; Bt brinjal reduced the need for insecticide which has a positive effect on the environment in terms of lower levels of insecticide in the soil and groundwater
Step 4 2007 BARI met with focus groups, agricultural and regulatory professionals to discuss consumer acceptance
Obtained information on how to market Bt brinjal and gain consumer acceptance
Step 5 Safety/Toxicity studies conducted at BARI in rats, chickens, cows, fish
Bt protein secreted by brinjal plants did not affect non-target insects, birds, wild animals; no toxicity detected or allergenic metabolites by blood analysis, weight gain, feed conversion & protein efficiency ratios; Bt protein not detected in cow milk or in cooked eggplant
Step 6 2013 Submission of results by BARI to the National Technical Committee for Crop Biotechnology of the Ministry of Agriculture for approval (NTCCB)
NTCCB submitted a report of the findings to the Ministry of
Agriculture in September 2013 who recommended to the Ministry of Environment and Forests that Bt brinjal be approved
As a result of safety assessments and economic evaluation, the Ministry of Environment and Forests approved four genetically engineered local varieties of Bt brinjal for cultivation in Bangladesh on Oct 30, 2013 to be planted in four different regions of Bangladesh over two hectares of land monitored by a Biosafety Committee. The Minister of Agriculture distributed the Bt brinjal seedlings developed by BARI to twenty small scale farmers in January 2014 at a ceremony in the presence of hundreds of people including policy makers, scientists, farmers, and the media (ISAAA, 2014).
Recommendations for how to use Bt brinjal as a model for Golden Rice adoption in India
Table 2 delineates the major steps in the development of Bt brinjal for cultivation and consumption in Bangladesh. With the exception of Step 4, the steps were guided by the regulatory frameworks for Bangladesh, which are consistent with international laws for GM crops. Planning for the implementation of Golden Rice as a vitamin A intervention for India should entail a process similar to that of Bangladesh which would be in compliance with India’s national regulatory guidelines and consistent with global standards for GM crops. Furthermore, animal studies conducted for Golden Rice approval as required by the international OECD Guideline should be followed by human clinical trials/ bioavailability studies to demonstrate the efficacy of Golden Rice in vitamin A-deficient populations. In addition, Golden Rice acceptance should be promoted during the planning phase of implementation. India’s regulatory frameworks and the corresponding international laws should guide the Golden Rice development process. They are briefly described below.
India’s Regulatory System
Cooperation (OECD) Guideline 408 Toxicity studies in rodents, WHO guidelines, and the joint Food and Agriculture Organization of the United Nations/ World Health Organization Codex Alimentarius. Like Bangladesh, India is party to all of the global frameworks and as a signatory nation, is obligated to incorporate the global regulations into its national guidelines for GM crop approval. India has a regulatory system for GM crops similar to that of Bangladesh composed of four ministries, five committees, and several pieces of legislation. Highlights of the international frameworks are shown in Table 4 along with the corresponding Indian legislation and various aspects of GM crop testing covered in the regulatory frameworks.
Table 3
Agency Roles/Responsibilities
Ministry of Environment
and Forests (MOEF)
Oversees the GEAC
Responsible for implementing the Biotechnology Rules of 1989 under the EPA Act which is based on the Cartagena Protocol
Ministry of Science and
Technology (MOST)
Department of Biotechnology is under MOST and provides guidelines to GEAC
Oversees RDAC and RCGM regulatory committees
RCGM interacts with IBSCs from institutions engaged in GM research Department of Biotechnology evaluates the biosafety and risk assessment
of GM products based on the EPA Act and OECD Guidelines contained in India’s regulatory frameworks
Ministry of Agriculture
(MOA) and State
Governments
MOA and States approve commercial release of GM crops after field trials States approve field trials for GM crops through 'No Objection' Certificates MOA responsible for sale, production, and quality of GM seeds
State agriculture departments coordinate with MOA to monitor GM crops for 3-5 years after commercialization
MOA implements Protection of Plant Varieties & Farmers’ Rights Act 2001, the Plant Quarantine Order 2003, Seed Policy 2004
Ministry of Health and
Family Welfare
(MOH&FW)
Implements the The Food Safety and Standard Act of 2006 based on WHO recommendations and Codex Alimentarius to regulate the manufacture, labeling, distribution, sale, and import of GM foods
Note: GEAC- Genetic Appraisal Committee; RDAC- Recombinant DNA Advisory Committee; RCGM- Review Committee on Genetic Manipulation; IBSC- Institutional Biosafety Committee; MEC- Monitoring and Evaluation Committee. Information derived from Ahuja and Jotwani, (2007) and Department of Biotechnology, India (n.d.).
Table 4
Global Regulatory Framework
Aspects for Evaluation defined by Framework India’s Equivalent National Legislation
Cartagena Protocol Risk Assessment:
Identification of novel genetic and physical characteristics in the GM crop
Genetic technique used in creating GM crop
Probability and risk of adverse effects in the environment
Consequences of adverse effects Recommendations of whether risks are
manageable or acceptable Risk management strategy
Monitoring of GM crop in its environment after commercialization
Suggestions for handling, storage, transport, packaging, labelling, disposal, intended use
EPA Biotechnology Rules 1989
Guidelines and Standard Operating Procedures of Confined Field Trials for Regulated, Genetically Engineered Plants, 2008
Revised Guidelines for Research in Transgenic Plants, 1998
Codex Alimentarius Biosafety assessment:
the molecular structure of the modified genome
comparison of the conventional crop genome data to the GM crop data evidence that the crop poses no risk to
humans or the environment when grown and consumed on a large scale
potential for the inserted gene(s) to produce toxins or cause an allergic reaction
nutritional analysis of the GM crop compared to its conventional counterpart
Guidelines and Safety Assessment of Foods Derived from GE Plants, 2008
Recombinant DNA Safety Guidelines and Regulations, 1990
Revised Guidelines for Safety in Biotechnology, 1994
Food and Safety Standard Act 2006
OECD Guideline 408 Toxicology assessment in rodents: blood analysis
examination of organ tissues body weight
food/water consumption
examination of animal’s external body
WHO Determine unintended effects:
Allergenicity per the Codex Alimentarius Gene transfer per the Codex Alimentarius Outcrossing per the Cartagena Protocol
Note: Information contained in this table was derived from the Codex Alimentarius (2016), Ahuja and Jotwani, (2007), OECD (1998), Convention on Biological Diversity (2012), and WHO (2016).
Overview of the Development Process
The International Rice Research Institute (IRRI) should spearhead the development of Golden Rice from local varieties of Indian rice in partnership with the Golden Rice Network in India that was established by the inventors of Golden Rice (Golden Rice Humanitarian Board, n.d.). The IRRI is a non-profit agricultural organization committed to improving food security in nations that utilize rice as a staple food (IRRI, n.d.). Using Table 2 as a model for India, Step 1 has already been completed in India as Golden Rice seeds have been donated to India’s
The inventors of Golden Rice estimate that the entire process from developing Golden Rice through approval for commercialization will take at least 10 years (Potrykus 2010). This timeframe can vary depending on how quickly Golden Rice progresses through the mandated stages of approval from lab to greenhouse to confined field trials, to multi-location trials, to large
Animal Studies then Small Scale Human Clinical Trial
scale field trials, to approval for seed production, and finally to commercialization. Because animal studies for allergenicity and toxicity will be conducted concurrently with Golden Rice seed development, a thorough review of data showing that the transferred beta-carotene gene is safe for animals, beneficial insects, and the environment will determine whether permission is granted to proceed to subsequent stages. The proposed steps for implementing Golden Rice derived from India’s regulations for GM crop testing are presented in Table 5. Differences between the implementation for Golden Rice in India and Bt brinjal for Bangladesh are discussed in the following section.
Table 5
Chronology Study Activity Purpose
Step 1 Obtain approval from the Indian government to import Golden Rice seeds and obtain a license from the Golden Rice Humanitarian Board that allows India to receive free seeds
Seeds have been donated to India by the Golden Rice Humanitarian Board for conventional breeding into local varieties
Step 2 Eight agricultural institutions comprising the Golden Rice Network will breed local rice varieties with the beta-carotene producing trait from the Golden Rice seeds. Per international and national regulatory frameworks, local non-GM rice will be grown in contained greenhouses along with Golden Rice for a side by side comparison
Data to be obtained regarding: allergenicity of Golden Rice varieties, nutritional analysis of Golden Rice when cooked and of grains in storage, molecular biology of beta-carotene gene expression; Hold hearing to update the public
Step 3 Small scale open air multi-location field trials of both conventional rice and Golden Rice
Agronomic performance; Determine if cross-pollination occurs and whether it has adverse effects on local plants; determine if there are changes in plant behavior from the presence of Golden Rice in the environment; Hold hearing to update public of progress.
Step 4 Safety/Toxicity studies conducted in rats and dogs
Determine if disease is detected in animal tissues or allergenic metabolites by blood analysis; evaluation of weight gain, feed conversion & protein efficiency ratios; Hold hearing to update the public on progress. Step 5 Meet with focus groups, agricultural
and regulatory professionals to discuss consumer acceptance; Conduct National Family Health Survey
Obtain data on how to communicate the Golden Rice message and market Golden Rice
Step 6 Efficacy studies and Taste Tests conducted in Human Clinical Trials
Step 7 Farmer education Teach farmers agricultural practices associated with cultivating Golden Rice
Step 8 Submission of results from Steps 1-7 by the Golden Rice Network to India’s Ministry of Environment and Forests
Ministry of Environment and Forests reviews data, approves Golden Rice and submits recommendation for
commercialization and seed production to Indian states and Ministry of Agriculture; Hold public ceremony for final approval and distribution of Golden Rice to farmers
Step 9 Post-market monitoring of Golden Rice for five years by state agriculture departments according to India’s regulatory guidelines
To send data back to the Ministry of Agriculture regarding beta-carotene gene presence in other native plants, seed quality, farmer satisfaction or issues
Conducting Animal Studies
requires a rodent species and a non-rodent species which they have specified to be rats and dogs (Government of India, n.d.). The 90- day animal feeding studies in at least two animal models would show reproducibility and safety when parameters for toxicity are assessed as denoted in Table 4 (OECD, 1998). Additionally, examination of bodily tissues and organs from two species of animals fed a balanced diet that incorporated Golden Rice would provide a scientific basis for the effects of Golden Rice on health. Because every country has to complete their own biosafety studies and regulatory approval process as required by the international frameworks such as the Cartagena Protocol, OECD Guidelines, and Codex Alimentarius, 90-day animal studies in rats has to be conducted for toxicity assessment each time a country decides to pursue approval of Golden Rice. Using the Bt brinjal model from Bangladesh, animal studies would be conducted following the successful completion of confined greenhouse trials and small scale field trials.
Finally, in Bangladesh, animal studies for Bt brinjal were conducted by BARI, the agricultural research institute of Bangladesh, not a private company like Syngenta (the owner of intellectual and technical property rights to Golden Rice). The capability to conduct animal studies exists at several public research institutions in India (Kumar and Sinha, 2015; Golden Rice Humanitarian Board, 2015). Data from India’s own institutions may be viewed more credibly by the citizens of India than data originating from Syngenta because heightened sensitivity to private foreign companies dominating India’s agriculture is well documented in literature (Herring 2006; Scoones, 2008; Croser, 2015).
Conducting Human Clinical Trials and Bioavailability Studies
that Bt protein, which is toxic to insects, is not detected in cooked Bt brinjal. On the other hand, Golden Rice is a nutritive intervention with no prior precedent of human consumption among a population experiencing malnutrition, and intended to be consumed as part of the daily dietary intake to prevent disease or improve chronic vitamin A deficiency.
Pilot Studies and Acceptability Testing
Assuming that animal feeding studies detect no toxicity and Golden Rice receives GEAC approval for large scale field trials, animal data would be presented to obtain Institutional
Feeding human subjects Golden Rice as a substitute for conventional rice at meals and then measuring serum retinol (vitamin A) levels will provide an indication of bioavailability, the amount of beta carotene that is converted into vitamin A in the target population. Data on
vitamin A deficiency to date has been collected using only serum retinol concentrations. New evidence indicates the presence of elevated C reactive protein in the blood as a result of infection or inflammation which inversely correlates with serum retinol concentrations; thus, if
inflammation or infection is present in the body, high C-reactive protein concentrations are present in conjunction with low serum retinol levels because inflammation and infection
decrease the absorption of vitamin A or provitamin A. (Kapil and Sachdev, 2013; Thurnham and McCabe, 2012). This is a relevant factor that must be considered when conducting human trials for VAD interventions given the potential of the target population in India to have infectious disease or other inflammatory conditions. In this proposed human clinical trial, serum retinol concentrations should be accompanied by C reactive protein levels for accurate interpretation of vitamin A status (Thurnham and McCabe, 2012).
An additional aspect of Golden Rice that should be tested during the small scale human trial is taste. Cooking properties and flavor compared to conventionally grown local varieties of rice are equally important factors as safety in consumer acceptance. In the Bangladesh Bt brinjal experience, tests for physical appearance were similar between the Bt brinjal and conventional eggplant. For Golden Rice, physical appearance will not be the same as conventional rice because Golden Rice is yellow in color due to the production of beta-carotene in the rice grains (Paine et al., 2005).Golden Rice will need to taste similar to the local varieties of rice the Indian population is accustomed to eating to gain consumer acceptance.
Following the completion of the small scale pilot study and subsequent IRB/Ethics committee approval for a large scale human trial, a cohort study should be conducted according to the recommendation of the International Conference on the Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in areas in India previously mentioned to have a high prevalence of VAD. The International Conference on the Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), recommends that drugs for chronic use be tested in at least 300-600 patients for six months and in 100 patients for one year for a total of 1,500 patients before receiving approval (Thabane, 2010; ICH, 2001). Ideally, test subjects would represent women of reproductive age and children since evidence suggests these two groups exhibit the highest prevalence of vitamin A deficiency (WHO, 2011). The initial duration of testing of six months is based on the expert opinion of the ICH that adverse events typically occur within the first few months of exposure to a substance (FDA, 2016). The data would be entered into the Clinical Trial Registry of India, which is publicly available and conducive to transparency. Clinical trial data will determine whether Golden Rice improves vitamin A status in vitamin A -deficient populations. In combination with environmental data, clinical trial data will enable policymakers in India to objectively determine whether Golden Rice can be approved for commercialization. In addition, assessing whether beta-carotene levels in Golden Rice are lost during storage and cooking (if any) are needed (Royal Swedish Academy of Agriculture and Forestry, 2008). Literature reports Golden Rice to contain 37 micrograms of beta-carotene per gram of rice grains (dry weight). No information is available on carotene content of cooked Golden Rice or whether
adoption as the rice would be stored in grain storage facilities in the vicinity of ration shops until it is ready for distribution as is the case for conventional rice.
Ensuring Golden Rice Acceptance Marketing
Other aspects of the Bangladesh Bt brinjal model that can be applied to India for Golden Rice acceptance include BARI meeting with focus groups, scientific, agricultural and regulatory professionals in July 2007 to discuss consumer acceptance, more than six years ahead of Bt brinjal approval for commercialization which occurred on October 30, 2013. Factors that
contributed to consumer acceptance of Bt brinjal in Bangladesh are not available in the literature, but the Philippines is currently conducting large scale field trials of Golden Rice (Golden Rice Humanitarian Board, n.d.). Their marketing strategy can be a model for India. The marketing strategy asked the following questions: Who are the people considered to be credible by the Philippine people? Who do they believe- clinics, radio, neighbors, celebrities, etc.? What will
motivate consumers to buy Golden Rice and cook it for their families? Farmers are also integral
to Golden Rice implementation because they will need to be convinced to grow Golden Rice.
consumer acceptance and the success of Golden Rice as a vitamin A intervention. Also, marketing surveys similar to those in the Philippines should be conducted in all twenty-nine states by the Ministry of Health and Family Welfare which conducts the National Family Health Survey in India among all states every few years. The most recent survey conducted in 2015 reached approximately 568,000 households (National Institute for Population Sciences, n.d.). Answers obtained from these surveys can guide the marketing campaign and plan the
communication of the Golden Rice message to influence behavioral modification towards
consumption of Golden Rice.
Public Hearings
Press conferences and public hearings were held throughout the seven years to provide progress updates on Bt brinjal greenhouse and field trials in Bangladesh (BDRC, 2009). Holding press conferences and public hearings throughout the Br brinjal development process was likely a contributing factor to consumer acceptance. Media attention in India during Golden Rice development can help foster community buy-in which is essential for Indian citizens to decide to become consumers of Golden Rice. Also, press conferences and public hearings are a way to inform the public about vitamin A deficiency, how Golden Rice would work as an intervention, and create transparency about agricultural developments.
Teaching
conditions. In the event of any adverse events to the environment, animals, or humans, in Bangladesh, the Bt brinjal plants were to be uprooted and burned. Providing farmers with the necessary knowledge to be successful could influence their decision to grow Golden Rice.
Preparing the Regulatory Framework for Golden Rice in India- Gaps in India’s Regulation
Codex Alimentarius
Despite having a comprehensive regulatory system consistent with international
guidelines, there are some opportunities for enhanced regulatory control or enforcement in preparation for Golden Rice. The Codex Principles for Risk Analysis of Foods Derived from Modern Biotechnology states that scientific data for risk assessment should include data from diverse sources including the developer of the food product, scientific literature, technical information, international bodies, regulatory agencies, and independent scientists (Codex
Alimentarius, 2016). Bangladesh did not have Bt brinjal studied by an independent group or have its Bt brinjal data evaluated by independent agencies. At present, public agricultural research institutions in India who are partners in the Golden Rice Network will conduct field trials and safety assessments on Golden Rice in conjunction with the IRRI, but the results need to also be evaluated by independent scientists who are not associated with India’s Syngenta/IRRI/Golden Rice Network. Perhaps this will be a function of the new independent, non-government owned Biotechnology Authority that will be established. Alternatively, publishing animal studies and human clinical trial data would also enable an independent review.
The Food Safety and Standard Act
Golden Rice seeds, but not the end product of Golden Rice grains that will be consumed. The FSSA contains no specific criteria that GM foods should meet in order to receive India’s approval for human consumption.
The Seed Act Policy
The Seed Act Policy 2004 requires certification that seeds be registered and be laboratory tested for purity before being sold on the market. Indications are that a lack of enforcement of the Seed Act Policy 2004 and Protection of Plant Varieties & Farmers’ Rights Act 2001 is a gap that needs to be filled in planning for Golden Rice because low quality and fake Bt cotton seeds are a current problem in India (Ramaswami, Murugkar, and Shelar, 2009). Golden Rice is a food product that will be eaten. Low quality or fake Golden Rice seeds will not yield rice with an adequate content of beta-carotene and will therefore, not improve vitamin A status, which is the purpose of this intervention.
Price Control
Legislative measures may also be needed to control the price of seeds on the markets so that Golden Rice seeds are affordable for farmers. If Golden Rice Intellectual and Technology Property Rights permit, allowing public agricultural institutions to produce Golden Rice seeds could create competition which could act as price control. Another option is government-imposed price-control. This approach has been used for the only other GM crop available in India, Bt cotton. State governments mandated that all seed companies reduce the price of Bt cotton seeds from 1600 rupees per packet to 750 rupees per packet ($18 USD). This price control was implemented in 2006 and has been credited for high Bt cotton adoption among India’s farmers (Ahuja and Jotwani, 2007).
Even if India improves its regulatory landscape and follows the systematic introduction process outlined in this paper, other factors in India’s environment may be barriers to Golden Rice adoption.
Public opposition
Historically, anti-GM activity has taken root in India since the first GM crop, Bt cotton, was approved. Opposition groups argued in 1998 that Bt cotton and GM crops in general would create a dependence on seed corporations and a monopoly on seeds that would lead to expensive seed prices, little or no profit and debt accrual for farmers (Croeser, 2015). The current anti-GM movement in India encompasses two dimensions: activism to influence public opinion towards opposing GM crops and activism to promote organic agricultural practices as an alternative to transgenic crops.
heritage based on the premise that organic farming has been an agricultural practice for thousands of years (Croeser, 2015). Organic farming has experienced substantial growth from 2.5 million hectares in 2005 to encompass 4.4 million hectares in 2013 (IFAD, n.d.). A 2014 agriculture economics paper indicates that in India, the equivalent of $200 million USD per year for the last 10 years has been spent on opposing GM crops. (Wesseler and Ziberman, 2014). Farming Factors
Issues affecting farmers deserve some consideration during the planning process as they are potential obstacles to Golden Rice cultivation. In order for the poorest to afford Golden Rice, it would need to be priced lower than conventional rice. While doing so may entice consumers buy it, lower market prices for Golden Rice could have the unintended effect of farmers electing not to grow Golden Rice because they may not net a profit while products of organic farming are profitable by selling for 20-30% above the price of conventional products (Stein, Sachdev, and Qaim, 2008; Te Pas and Rees, 2014; IFAD, n.d.).
There is also a need to drive policy that would change banking operations to allow farmers to be eligible for bank credit. Lending policies at banks favor credit approval for the minority of farmers (less than a 25% of India’s farmers) who have irrigated fields compared to farmers who depend on rainfall (USDA, 2007). Therefore, the majority of farmers are not eligible to obtain credit from banking institutions. The United Nations notes that because small farmers in India do not qualify for bank loans, they use private lenders who charge up to 20%
interest on a four-month loan. Farmers sign over their land as collateral (United Nations, 2016).
Loss of crops due to water shortage is another issue affecting overall farming in India that
lack of irrigation both of which have led to reduced rice yields in India in recent years according to the USDA. Because this is a problem for conventional rice now, it would likely also affect Golden Rice (USDA, 2007; PRS Legislative Research, 2016). Investments are needed in agricultural research and innovation to reduce soil erosion, increase the absorption of rainfall, and manage groundwater more efficiently because these are obstacles to not only Golden Rice cultivation, but also India’s overall food security (World Bank, 2012; PRS Legislative
Research, 2016).
Table 5 highlights some issues and concerns specific to India that may be potential barriers to the adoption of Golden Rice as a vitamin A intervention.
Table 5
Topic Questions and Issues relevant to Golden Rice
___________________________________________________________________________
Farmer income security Will Golden Rice be profitable for farmers?
Contamination of conventional rice Loss of biodiversity from cotton Bt gene being detected in traditional non-Bt cotton varieties has raised alarm about GM crops
Agricultural issues Groundwater depletion, soil erosion,
Ban on GM crop trials India’s decision to halt the release of Bt brinjal in 2010 has also stopped field trials on all GM crops; India’s Supreme Court ordered the establishment of an independent non-government owned Biotechnology Regulatory Authority which has not yet happened
Intellectual and Technical Property IRRI stipulations state Golden Rice is to be developed by public- private Rights partnerships which raises concerns about who owns Golden Rice
varieties and could affect cost of Golden Rice seeds
State permission for crop trials GM crop developers must obtain a “No Objection” certificate from State governments to conduct crop trials. States can approve or deny
Golden Rice cultivation according to current laws in India.
_____________________________________________________________________________________ Note: Information contained in this table was derived from IRRI (n.d.); USDA (May 2007); PRS Legislative Research (2016); Government of India (n.d.).
http://www.moef.nic.in/downloads/public-information/minister_REPORT.pdf
Evaluation of Golden Rice
If India chooses the path to Golden Rice, the following questions adapted from the UNICEF Guidelines for Innovation are relevant for the process of evaluating progress following implementation (UNICEF, 2015):
Short-term Evaluation
1. Is Golden Rice financially and environmentally sustainable? Feedback from farmers regarding cultivation and net profit for their efforts will be important determinants along with assessing any beta-carotene gene transfer to local rice varieties.
2. Will the target population for Golden Rice be able to provide feedback? They can attest to the taste, affordability, and accessibility of Golden Rice and whether they are using it. 3. Are the risks involved in the implementation of Golden Rice acceptable? One risk of
allotted for marketing to win consumer acceptance when there are other needs that could potentially be addressed with those funds.
Long-term Evaluation
4. Has vitamin A status improved from the dietary intake of Golden Rice among the target population? Evaluations of serum retinol levels, night blindness, and other physical consequences of VAD at designated time points following implementation will attest to the effectiveness of Golden Rice as an intervention for VAD.
Conclusion
Is Golden Rice worth pursuing? What is the relation in terms of time, cost, and benefit relative to the effectiveness of Golden Rice in solving the problem of vitamin A deficiency? In light of the huge financial investment needed for social marketing to gain consumer acceptance for Golden Rice (which is not guaranteed to happen), a timeline of at least ten years from development through approval, the enactment of “No Objection Certificates” by Indian states granting permission for GM crop field trials, public opposition to GM crops, and a delay in the establishment of a Biotechnology Regulatory Authority, perhaps India is not ready for Golden Rice yet. India is a developing nation with limited resources. The calculations from Stein (2006) project a cost of roughly $40 million USD for Golden Rice development with a whopping $15-30 million USD of that amount allocated for marketing to convince India to use Golden Rice. It
also delineate other high priority needs in India such as unequal distribution of food and an alarming statistic that 30% of crop harvests are ruined because of inadequate storage facilities.
A recent WHO bulletin states that the current thinking on the cost-effectiveness of an intervention is undergoing a reformation. The new thinking is that when trying to assess the cost-effectiveness of a given intervention, consideration needs to be given as to whether the
intervention costs less than other viable interventions and whether there are other high priority needs existing in a population (WHO, 2014). While vitamin A deficiency is a significant public health issue in India, it is a symptom of a root cause, malnutrition. Populations suffering from malnutrition often exhibit multiple nutrient deficiencies (WHO, 2011). The WHO reports that 50% of malnutrition globally is due to diarrhea and intestinal worms caused by poor sanitation. Diarrhea, one of the consequences of chronic malnutrition, ranks third as a cause of childhood mortality in India accounting for 300,000 deaths annually (Lakshminarayanan and Jayalakshmy, 2015). UNICEF states that diarrhea prevalence can only be halted if open defecation is
eradicated, and fifty percent of India, representing approximately 620 million people, practice open defecation (UNICEF, 2014; Worley, 2014). The Population Reference Bureau asserts that the underlying cause of malnutrition in India is a lack of sanitation, notably clean water and toilets (Worley, 2014). Diarrhea is attributed to a lack of clean water for hand washing; a lack of toilets perpetuates the problem by contaminating ground water and water resources (Worley, 2014). Diarrhea prevention through improved sanitation would then also ameliorate malnutrition and the manifestations of malnutrition such as vitamin A and other micronutrient deficiencies.
Survey conducted by The Bangladesh Bureau of Statistics indicated that 99% of households in Bangladesh purchase and use fortified oil. Fortified oil consumption was shown to decrease vitamin A deficiency from 83% to 64% (Fiedler 2015). For a price tag of $ 1.27 million USD annually, fortified oil is financially sustainable; 406, 877 DALYs can be averted at $3.25 USD per DALY (Fiedler, 2015).
Home gardens have been described in literature as a sustainable and cost-effective
approach to combating VAD because green leafy vegetables also contain other micronutrients for optimum health such as folate, vitamin C, and iron; vitamin A-rich vegetables such as butternut squash, carrots contain other nutrients such as riboflavin and magnesium (Kapil and Sachdev, 2013). Home gardens are considered to be a better approach for states that suffer from inadequate food intake which include Uttar Pradesh, Madhya Pradesh, and Bihar (Keatinge et al., 2013; Kapil and Sachdev, 2013). Gardening is also the WHO recommended strategy to combat micronutrient deficiency (WHO, 2011). Keasinge et al. (2011) show that teaching households in Northern India to plant 6-meter by 6-meter home gardens sustained a family of four and provided more than the required daily intake of folate and vitamins A and C from growing twenty-four vegetables which yielded 250-300 kilograms of produce in a year. In contrast, Golden Rice only provides one necessary micronutrient.
Addressing the underlying causes of malnutrition that have been identified will yield more benefits than just improving vitamin A status and are less time-consuming than a GM food intervention. Although I think Golden Rice exemplifies a brilliant and noble application of molecular biology, the best approach is to invest resources in a multi-pronged strategy. A
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