by Mary E. Gearing
figures by Kristen Seim

Summary: In addition to providing energy in the form of calories, our food also supplies us with essential vitamins and other nutrients to keep us healthy. Vitamin, or “micronutrient”, malnutrition is a substantial contributor to disease. To increase micronutrient consumption, many countries fortify their food with these vitamins. Another strategy to improve vitamin intake and prevent disease, especially in developing nations, is the development of genetically modified organisms (GMOs). How do traditional fortification and GMOs compare, and are they equally effective and safe? Golden Rice, engineered to contain high levels of the vitamin A precursor beta-carotene, is a good case study to discuss these points and examine the science behind efforts to improve nutrition through genetic modification.

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Despite public health and humanitarian efforts, malnutrition continues to be a scourge on the developing world. It is estimated that at least 3.1 million children die each year and 161 million have stunted growth due to malnutrition [1]. The problem is not only that food is scarce, such that children aren’t getting enough calories, but also that the food they consume does not have the vitamins and minerals they need. Deficiencies in iron, iodine, zinc, folic acid, and vitamin A are among the most common, with almost half the world’s population suffering from one or more deficiencies [1,2].

Wealthy nations have well-defined fortification programs that add these nutrients to commonly consumed foods, and supplements are also readily available [3]. Due to their cost, these efforts may be less successful in poorer countries, and genetic modification is being explored as an alternative strategy to add these micronutrients to food. The textbook example of biofortification is Golden Rice, genetically engineered to contain high levels of the vitamin A precursor beta-carotene [4]. Opponents of this strategy, including Greenpeace, argue that Golden Rice and other genetically modified (GM) crops do not eliminate the true problem of poverty in the developing world [5]. Golden Rice was first field tested over 10 years ago, but GM controversy has prevented its widespread adoption.

What’s the fuss about micronutrients?

Micronutrients are a group of compounds that are needed by our bodies in small amounts. They perform a wide range of functions in the body, and chronic micronutrient deficiencies are thus a major cause of disease [6]. Examples you may have heard of include anemia and goiter, caused by iron and iodine deficiencies, respectively.

If one eats a varied diet, including lots of fruits, vegetables, and other unprocessed foods, obtaining the necessary micronutrients isn’t a problem. Staple food fortification is another way to ensure that a population consumes adequate levels of micronutrients. Looking at a cereal box, you’ll see that the phrase “fortified with multiple vitamins and minerals,” meaning that those micronutrients have been added in during production. Iodized salt and Vitamin D-containing milk are other classic examples of staple food fortification. In the United States, the FDA mandates and regulates fortification in order to prevent diseases caused by nutrient deficiencies and to restore nutrients that may be lost during food processing [3]. Other developed countries have similar programs, which have been deemed a public health success.

Many developing nations are not so lucky. These populations often rely on cheap staple crops like rice and corn to survive – they do not have access to a wide variety of nutrient-rich foods, chiefly due to the high costs of growing or purchasing them. Rice-based diets in particular are a major cause of micronutrient deficiency. Although rice is a staple food for nearly half of the world’s population, including 90% of Asia, it has a very low nutrient content. The few micronutrients rice does contain are located in the outer layer of the grain, which is removed during the refining process [4].

Micronutrients play a large role in growth and development, so these deficiencies are especially detrimental to children. Vitamin A deficiency (VAD), affecting one-third of children in the world under age 5, is the leading cause of childhood blindness. Vitamin A is key to immune system function, and children with VAD are more likely to contract common illnesses like measles than children without a deficiency. They are also more likely to die from respiratory and diarrheal diseases [7]. VAD hasn’t gone unnoticed – the administration of Vitamin A supplements has saved about 600,000 lives per year in low- and middle-income countries [8]. However, as with other deficiencies, these efforts haven’t been enough to eliminate VAD. Traditional fortification and supplementation programs are costly and logistically complicated, and the question now is whether we should try additional tactics to increase micronutrient consumption.

How does biofortification work?

Another strategy to eliminate micronutrient deficiencies is biofortification. Biofortification increases the nutritional value of crops through either selective breeding or genetic modification (Figure 1). Instead of adding nutrients to the food after harvesting, as in staple food fortification, the plants themselves are altered so that they produce these nutrients [9]. Selective breeding begins with a plant variety that already contains some amount of the vitamin or mineral of interest. These plants are then bred to generate plants that have higher levels of the compound, and the process is repeated over many generations to develop a plant variety with desirable levels of the compound. Selective breeding has produced multiple plant strains with improved nutritional value, but it’s not always an option. For crops that are difficult to breed, genetic modification may be a better option than selective breeding [10]. Since it’s such a popular staple crop, rice is a good target for biofortification; however, rice plants do not contain any vitamin A or vitamin A precursors, so selective breeding of rice cannot be used to prevent VAD [4].

Figure 1. There are multiple ways to obtain necessary micronutrients. Micronutrients can be obtained through a varied diet rich in fruits and vegetables or through supplements. Staple food fortification adds micronutrients to commonly eaten foods. Biofortified crops are bred or engineered to produce micronutrients.

Scientists instead turned to genetic modification to reduce VAD. Foods like carrots and sweet potatoes have high levels of the vitamin A precursor beta-carotene; when humans eat these foods (or beta-carotene capsules,) a percentage of the ingested beta-carotene is converted to vitamin A. Using our knowledge of biochemistry, would it be possible to create rice that has high beta-carotene levels? After seven years of work, and the insertion of three genes (two from daffodil, one from bacteria), a multidisciplinary team of scientists succeeded in making GR1. Although these genes are not identical to those found in carrots or sweet potatoes, they alter the rice plants’ metabolism so that the plants produce the same compound, beta-carotene, confirmed by chemical analysis. The improved strain GR2, which replaced a daffodil gene with a corn gene, produces up to 23 times more beta-carotene.

Using bioavailability studies, scientists determined that just 72 grams (about 1/3 cup) of dry GR2 rice per day would provide enough beta-carotene to prevent VAD in a child [11]. Children were given a specified amount of Golden Rice to eat, and the amount of vitamin A they produced was measured with a small blood sample. This conversion rate of beta-carotene to vitamin A (vitamin A equivalency) was used to calculate the amount of Golden Rice needed to prevent vitamin A deficiency based on intake guidelines. This type of experiment can be conducted for any food or supplement, and studies have also shown that Golden Rice and beta-carotene supplements have similar vitamin A equivalencies [12].

How does biofortification compare to traditional methods?

With VAD as a case study, we can compare traditional fortification/supplementation methods to biofortification. The most convincing arguments in favor of biofortification are cost and feasibility. UNICEF and other relief organizations have relied heavily on donations from governments and private foundations to fund fortification and supplementation programs in impoverished areas. Funding is not guaranteed, especially in instances of economic crisis and political turmoil. Poorer countries also lack the necessary infrastructure and logistics needed to distribute supplements and fortified foods. In UNICEF’s 104 priority countries for vitamin A supplementation, the coverage rate of target populations is only 58%, and this number fluctuates greatly from year to year [7].

Traditional supplementation programs require consistent monetary investment; USAID estimates costs for Ghana or a country of similar size to be 2-3 million dollars annually [13]. In contrast, biofortification is markedly less expensive. In the case of Golden Rice, the GM company Syngenta has agreed to provide free GR2 seeds to farmers making less than $10,000 per year (about 99% of the target population.) Once the farmers have these seeds, no further investment would be necessary, as they can continue planting the seeds year after year, and beta-carotene production is stable over multiple generations of Golden Rice plants. Biofortification’s costs come from crop development and represent only a fraction of sustained supplementation’s costs [4].

Some groups, notably Greenpeace, argue that biofortification, especially through genetic modification, is not appropriate – instead of introducing GM crops into poor countries, we should be helping farmers learn to grow a variety of crops to improve their overall diet composition [5]. One example is the cultivation of beta-carotene rich sweet potatoes as a secondary crop in Africa; again, the disadvantages of these types of programs are high cost and logistical burdens. Although Golden Rice and other GM crops don’t fix the problem of poverty, they could have a major positive impact on disease rates. GM advocates are careful to make the point that biofortification should be just one component of public health efforts in the developing world, and it will be most effective when used in conjunction with poverty-reduction programs [4].

Another major hurdle GM crops face is safety, as many consumers believe that inserting foreign DNA into a plant may make the plant unfit to consume. Golden Rice and other GM crops undergo very rigorous safety screening in order to be approved by regulators such as the FDA or the European Food Safety Authority (EFSA) (see this article). Many people don’t realize that crop breeding strategies can also drastically change the composition of plants. One important example is mutation breeding: seeds are exposed to chemicals and radiation that generate a pool of seeds with different mutations, some of which may be beneficial. As of 2010, 2543 crop varieties had been derived using mutation breeding, but safety testing is not mandated for these crops as it is for GMOs like Golden Rice, and breeding efforts are much more loosely regulated [14-16].

GM opponents worry that the new genes in GMOs may be toxic. In the case of Golden Rice, the only protein new to the human diet is the bacterial gene mentioned above; the other new proteins are commonly consumed by humans and thus unlikely to cause harm. [14,15]. In fact, studies have shown that the proteins in Golden Rice (including the bacterial protein) are both nontoxic and nonallergenic [15]. Since rice is thoroughly cooked at high temperatures, its proteins are inactivated by heat, further reducing the risk of toxicity [14].

Will farmers actually use GM crops like Golden Rice? One key issue is how well Golden Rice will grow; for it to be accepted and used widely, the crop yields must be similar to rice strains currently in use [11]. GR genes have been introduced into multiple rice strains to create Golden Rice varieties optimized for growth in different environments [4]. Educational programs will also be necessary so that farmers are informed and can feel comfortable planting Golden Rice and other biofortified crops [15]. Golden Rice has the same mouthfeel and taste as traditional rice, attributes that should increase its acceptance. Saffron and turmeric are commonly used to produce yellow rice dishes, so the yellow color of Golden Rice should not prevent its adoption.

Table 1. A selection of staple crops in development for improved nutrient composition.[17]

Looking beyond Golden Rice, there are a large number of biofortified staple crops in development (Table 1). Many of these crops are designed to supply other micronutrients, notably vitamin E in corn, canola, and soybeans, as well as increased iron availability in rice and corn. Protein content is also a key focus; protein-energy malnutrition affects 25% of children because many staple crops have low levels of essential amino acids. Essential amino acids are building blocks of proteins and must be taken in through the diet or supplements. So far, corn, canola, and soybeans have been engineered to contain higher amounts of the essential amino acid lysine. Crops like corn, potatoes and sugar beets have also been modified to contain more dietary fiber, a component with multiple positive health benefits [17].

Malnutrition represents a silent epidemic in the developing world, with millions of children dying each year. Biofortification may not be a perfect solution to the problem of poverty in these countries, but it has the potential to greatly reduce the burden of disease. Much work remains to be done, but biofortified crops like Golden Rice may indeed be worth their weight in gold when it comes to preventing disease.

The original version of this article stated that cassava could not be selectively bred. Although cassava has historically been difficult to breed, HarvestPlus has developed vitamin A cassava through selective breeding.

Mary E. Gearing is a Ph.D. candidate in the Biological and Biomedical Sciences Program at Harvard University.

This article is part of the August 2015 Special Edition, Genetically Modified Organisms and Our Food.

References

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