the golden ration: a study of the effectiveness and global public health impact of golden rice

24
1 THE GOLDEN RATION: 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.

Upload: cj-balicanta

Post on 21-Jul-2016

18 views

Category:

Documents


2 download

DESCRIPTION

A literature review on the safety and effectiveness of Golden Rice (Oryza sativa) and its potential local and global public health impact.

TRANSCRIPT

Page 1: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

1

THE GOLDEN RATION:

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

Page 2: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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 world’s 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

Page 3: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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

Page 4: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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 µg/g of carotenoids, 31 µg/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 ¼ 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

Page 5: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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 µg/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 µg vitamin A from 100 g (½ 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,

Page 6: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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).

Page 7: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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

Page 8: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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 Asia’s 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

Page 9: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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

Page 10: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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

Page 11: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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 country’s 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).

Page 12: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

12

Aside from the attainment of the crop’s 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 program’s 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

Page 13: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

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.

REFERENCES

Al-Babili, S. & Beyer, P. (2005). Golden Rice – five years on the road – five years to go? TRENDS in Plant Science, 10(12), 565-573. doi:10.1016/j.tplants.2005.10.006

Amin, L., Azlan, N. A. A., Ahmad, J., Ibrahim, R. (2011). Public Perception of the Ethical Aspects of Golden Rice in Malaysia. The International Journal of Science in Society, 2(3), 15-34.

Breithaupt, H. (2008). Up to the challenge? EMBO Reports, 9(9), 832-834. doi:10.1038/embor.2008.157

Evert, A. (Ed.). (2013). Vitamin A. Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/002400.htm

Fitzpatrick. T, Basset, G., Borel, P., Carrari, F., DellaPenna, D., Fraser, P., … Hellmann, H. (2012). Vitamin Deficiencies in Humans: Can Plant Science Help? The Plant Cell, 24, 394-414.

Food and Nutrition Research Institute. (2008). 7th national nutrition survey: 2008 biochemical survey component. Vitamin A nutriture. [PDF Presentation]. Retrieved from http://www.fnri.dost.gov.ph/images/stories/7thNNS/biochemical/biochemical_vad.pdf

Golden Rice Humanitarian Board. (n.d.). Golden Rice and Intellectual Property. The Golden Rice Project. Retrieved August 31, 2013, from http://goldenrice.org/Content1-Who/who4_IP.php

Golden Rice Humanitarian Board. (n.d.). Golden Rice Risk Assessment (2). The Golden Rice Project. Retrieved August 31, 2013, from http://goldenrice.org/Content2-How/how3a_biosafety.php

Page 14: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

14

Goodman, R.E., Wise, J. (2006). Bioinformatic Analysis of Proteins in Golden Rice 2 to Assess Potential Allergenic Cross-Reactivity. (Study No. BIO-02-2006). Retrieved from http://www.allergenonline.org/Golden%20Rice%202%20Bioinformatics%20FARRP%202006.pdf

Greenpeace. (2012). Golden illusion: The broken promises of “golden” rice. Retrieved from http://www.greenpeace.org/seasia/ph/PageFiles/462570/Golden%20Illusion.pdf

Grune, T., Lietz, G., Palou, A., Ross, C., Stahl, W., Tang, G., … Biesalski, H.K. (2010). β-Carotene Is an Important Vitamin A Source for Humans. The Journal of Nutrition, 140(12), 2268S-2284S. doi:10.3945/jn.109.119024

International Rice Research Institute. (n.d.). FAQ, Sources and Links. IRRI. Retrieved October 10, 2013, from http://irri.org/index.php?option=com_k2&view=item&id=10245&lang=en

Mayo-Wilson, E., Imbad, A., Herzer, K., Yakoob, M.Y., Bhutta Z.A. (2011). Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. British Medical Journal, 343, 1-19. doi: 10.1136/bmj.d5094

Paine, J., Shipton, C. A., Chaggar, S., Howells, R., Kennedy, M. J., Vernon, G., … Drake, R. (2005). Improving the nutritional value of Golden Rice through increased pro-vitamin A content. Nature Biotechnology, 23, 482-487.

Potrykus, I. (2010). Lessons from the ‘Humanitarian Golden Rice’ project: regulation prevents development of public good genetically engineered crop products. New Biotechnology, 27(5), 466-472. doi:10.1016/j.nbt.2010.07.012

Qaim. (2009). The economics of genetically modified crops. Annual Review on Resource Economics, 1, 665-693. doi:10.1146/annurev.resource.050708.144203

Secretariat on the Convention on Biological Safety. (2000). Cartagena Protocol on Biosafety to the Convention on Biological Diversity: text and annexes. Montreal: Secretariat of the Convention on Biological Diversity.

Page 15: The Golden Ration:  A Study Of The Effectiveness And Global Public Health Impact Of Golden Rice

15

Stein, A., Sachdev, H.P.S., Qaim, M. (2006). Potential Impacts of Golden Rice on Public Health in India. Nature Biotechnology, 24, 1200-1201.

Tang, G., Hu, Y., Yin, S., Dallal, G. E., Grusak, M. A., & Russel, R. M. (2012). β-Carotene in Golden Rice is as good as β-carotene in oil at providing vitamin A to children. The American Journal of Clinical Nutrition, 96, 658-664. doi:10.3945/ajcn.111.030775

Tang, G., Qin, J., Dolkinowski, G. G., Russel, R., & Grusak, M. A. (2009). Golden Rice is an effective source of vitamin A. The American Journal of Clinical Nutrition, 89, 1776-1783. doi:10.3945/ajcn.2008.27119

Verma, C., Nanda, S., Singh, R.K., Singh, R.B., Mishra, S. (2011). A Review on Impacts of Genetically Modified Food on Human Health. The Open Nutraceuticals Journal, 4, 3-11. doi:10.1167/iovs.10-6973

World Health Organization. (2009). Global prevalence of vitamin A deficiency in populations at risk 1995–2005: WHO Global Database on Vitamin A deficiency. Geneva: World Health Organization.

World Health Organization. (2013). Micronutrient Deficiencies. WHO | World Health Organization. Retrieved September 29, 2013, from www.who.int/nutrition/topics/vad/en/