Team:Calgary Ethics/Collaboration

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Collaborating with the Guelph iGEM team 2008

Part I

Introduction

Micronutrient deficiency is a major cause of life threatening diseases and mortality through-out the world (1; 2). The UN World Summit on Children Micronutrient goal was:"Achieve sustainable elimination of iodine deficiency disorders by 2005 and vitamin A deficiency by 2010 (3). In poor, developing countries, micronutrient deficiency has been the major cause of impaired mental and physical functioning, mainly among children (1; 2). The four major micronutrients of concern in the developing world are iron, vitamin A, zinc and iodine(2). Our focus will be on Vitamin A deficiency. Roughly 400 million people worldwide are at risk of vitamin A deficiency. Of those 400 million affected, 100-200 million are children (1; 4). It can lead to progressive damage to the eye and eventually causes blindness. The WHO reports that 2/3 of deficient children die within two months of becoming blind(4).

Vitamin A deficiency is most prevalent among children located in Southeast Asia and Africa(5; 6), where staple foods are low in vitamin A (i.e. wheat, rice, maize…etc) and the poor cannot afford foods that would fulfill their Vitamin A requirements . Mammals must ingest provitamin-A Carotenoids from dark green vegetables, or yellow or orange fruits(7) and vegetables or fat soluble Vitamin A from animal products like eggs, butter and fish liver oils in order to synthesize Vitamin A in the body. Vitamin A is essential for protein metabolism, maintenance of epithelial cells, proper functioning of the immune system and retina, and for growth and reproduction (8). In order to reduce Vitamin A deficiency in developing countries, Beta-Carotene, the pro-vitamin A precursor, or Retinol, the animal version of Vitamin A, must be provided by some means to those who are deficient. There are currently 3 delivery systems for combating micronutrient deficiency; supplementation, increasing or diversifying dietary in-take and food fortification, which includes commercial or industrial fortification, as well as biofortification, microbial biofortification and home fortification(1; 9; 10). There is also a fourth and more recent delivery system, which can be labeled the synthetic biology approach (the approach the Guelph iGEM team takes). This paper will explore and highlight the major E3LS implications of the current and possible future delivery systems, for Beta-Carotene, a Provitamin A carotenoid. The goal of addressing the E3LS implications is to help advance towards realistic applications. These implications must be considered and weighed in an effort to make the best choices for fighting deficiencies all over the world.

Part II

Overview of the different approaches

Food fortification (11) is a food based strategy and includes commerical and industrial fortification, home fortification, biofortification and if implemented crops or animals; microbial biofortification and synthetic biology. In this context, fortification in general means to improve or strengthen the levels of nutrients in a target product. The several types of food fortification are distinct because different techniques and procedures are used to fortify the target foods.

Biofortification involves creating micronutrient-dense staple crops using traditional breeding techniques(7) and/or biotechnology. Cross breeding has been around for decades and has been used to fortify numerous crops. Using biotechnology to biofortify staple crops is more modern. The most popular example of this approach is the transgenic 'Golden Rice'(12; 13), which has been fortified with Beta-Carotene with the purpose to try to improve Vitamin A levels in people with deficiencies.

Microbial Biofortification involves using probiotic bacteria, which ferment to produce Beta-carotene, in the foods we eat or directly in the human intestine. The probiotic bacteria that are often selected for addition to food are lactic acid bacteria (LAB) because they are presumed to have beneficial effects on the host(14). An example of this would be mixing lactic acid bacteria (LAB) with animal feed so that animal meats and bi-products such as milk are enriched in Vitamin A.

Commercial and Industrial fortification This approach involves fortifying commercially available products such as flour, cooking oils and butter with Beta-carotene or Retinol. This fortification process occurs during manufacturing.

Home Fortification This approach consists of supplying deficient populations with home mixed vitamins and minerals in packages or tablets that can be added when cooking meals. This approach is basically a merger of supplements and fortification.

Supplementation This has been the most widely used approach so far in fighting Vitamin A deficiency. There have been many successful campaigns using supplementation. Vitamin A supplements come in the form of tablets, syrup and capsules and can be provided in biannual large doses (micronutriets: dietary intake V supplement use). In most campaigns, the supplements have been handed out during national immunization days, like those dedicated to polio. However, National Micronutrient Days (NMDs), like those started in Africa in 1999, are becoming a more popular way to ensure supplements are received biannually(15).

Increasing and diversifying dietary intake This approach involves creating larger and more diverse diets for the target population. This may require the population to increase their production of food which may be paired with educational campaigns to provide the information about which foods promote higher levels of vitamin A in the body. Another possibility is increasing the distribution of food to the region from another area.

Synthetic Biology Approach

Although techniques of synthetic biology are used in aspects of biofortification and microbial fortification, it is also an individual approach. This approach involves engineering a synthetic operon of beta-carotene metabolic genes in a plasmid, which may then be transferred to a diverse set of bacterial hosts. The biofortified probiotic hosts may be implemented in many ways to produce Beta-Carotene for humans. The probiotics may be place directly in the human intestine or they may be associated with our foods. One possibility may be mixing the probiotics with animal feed so that animal meats and animal bi-products are enriched with vitamin A. (Guelph iGEM team)

Part III

The E3LS Implications of the Various Approaches (Pro V Con)

	Pros	Cons
Economic argument Biofortification	once introduced, biofortified crop systems are highly sustainable and require minimal intervention (16)
Environmental argument	Trace minerals can help plants resist disease and withstand other environmental stressors (16)	Currently there is a lack of adequate knowledge on the impact that GM crops have on local ecosystems (16) Monocultures reduce biodiversity
Ethics argument		Many people believe genetically modifying crops is wrong because nature shouldn't be altered
Legal argument		Who is responsible for regulation and quality control?
Social argument		farmers and consumers may not accept sensory changes of biofortified crops (16)
Other	biofortification is a well suited approach for developing countries since it utilizes the fact that the daily diet of low income micronutrient deficient populations, is large quantities of staple foods(16)

	Pros	Cons
Economic argument Microbial biofortificaitoan	Additional benefits offered by LAB may lower subsequent health care service costs	Costs for delivering live bacteria and overseeing administering could be high
Environmental argument	Vehicle for delivery exists in nature (Lactobacilli)
Ethics argument		difficult to establish clinical trials and to prove efficacy - may be seen as inappropriate for direct human application
Legal argument		Who would be in charge of regulation and quality control? -no regulatory definitions for functional foods or prebiotics (17) - health claims can be difficult to obtain for probiotic products (14)
Social argument	if Lactic acid bacteria used, there may be beneficial effects in addition to reducing VAD deficiency (14)	People may feel uncomfortable ingesting live bacteria -intestinal health is not-well understood by consumers (17)
Other	Lactic acid bacteria are generally recognized as safe ((18) -LAB have beneficial effects on the host in addition to reducing deficiency (14)	difficult to demonstrate the efficiacy of prebiotics in humans (17)

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2) Collaboration with the Calgary Wetlab iGEM team 2008 We provide also E3LS feedback to the wetlab team from Calgary.

3) Collaboration with a presenter at Synbio 4.0 where we provide feedback on synbio regulation ideas.

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