Golden rice is a variety of rice (Oryza sativa) produced through genetic engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of rice. The research was conducted with the goal of producing a fortified food to be grown and consumed in areas with a shortage of dietary vitamin A, a deficiency which is estimated to kill 670,000 children under the age of 5 each year.
Golden rice differs from its parental strain by the addition of three beta-carotene biosynthesis genes. The scientific details of the rice were first published in Science in 2000, the product of an eight-year project by Ingo Potrykus of the Swiss Federal Institute of Technology and Peter Beyer of the University of Freiburg. At the time of publication, golden rice was considered a significant breakthrough in biotechnology, as the researchers had engineered an entire biosynthetic pathway.
In 2005, a new variety called Golden Rice 2, which produces up to 23 times more beta-carotene than the original golden rice, was announced. Although golden rice was developed as a humanitarian tool, it has met with significant opposition from environmental and anti-globalization activists. Studies have found that golden rice poses "no risk to human health", and multiple field tests have taken place with no adverse side-effects to participants.
Golden rice was designed to produce beta-carotene, a precursor of vitamin A, in the edible part of rice, the endosperm. The rice plant can naturally produce beta-carotene in its leaves, where it is involved in photosynthesis. However, the plant does not normally produce the pigment in the endosperm, where photosynthesis does not occur. A key breakthrough was the discovery that a single phytoene desaturase gene (bacterial CrtI) can be used to produce lycopene from phytoene in GM tomato, rather than having to introduce the multiple carotene desaturases that are normally used by higher plants. Lycopene is then cyclized to beta-carotene by the endogenous cyclase in Golden Rice.
Golden rice was created by transforming rice with only two beta-carotene biosynthesis genes:
- psy (phytoene synthase) from daffodil (Narcissus pseudonarcissus)
- crtI (carotene desaturase) from the soil bacterium Erwinia uredovora
(The insertion of a lcy (lycopene cyclase) gene was thought to be needed, but further research showed it is already being produced in wild-type rice endosperm.)
The psy and crtI genes were transformed into the rice nuclear genome and placed under the control of an endosperm-specific promoter, so they are only expressed in the endosperm. The exogenous lcy gene has a transit peptide sequence attached so it is targeted to the plastid, where geranylgeranyl diphosphate formation occurs. The bacterial crtI gene was an important inclusion to complete the pathway, since it can catalyze multiple steps in the synthesis of carotenoids up to lycopene, while these steps require more than one enzyme in plants. The end product of the engineered pathway is lycopene, but if the plant accumulated lycopene, the rice would be red. Recent analysis has shown the plant's endogenous enzymes process the lycopene to beta-carotene in the endosperm, giving the rice the distinctive yellow color for which it is named. The original golden rice was called SGR1, and under greenhouse conditions it produced 1.6 µg/g of carotenoids.
Golden rice has been bred with local rice cultivars in the Philippines and Taiwan and with the American rice cultivar 'Cocodrie'. The first field trials of these golden rice cultivars were conducted by Louisiana State University Agricultural Center in 2004. Field testing provides a more accurate measurement of nutritional value and enables feeding tests to be performed. Preliminary results from the field tests have shown field-grown golden rice produces 4 to 5 times more beta-carotene than golden rice grown under greenhouse conditions.
In 2005, a team of researchers at biotechnology company, Syngenta, produced a variety of golden rice called "Golden Rice 2". They combined the phytoene synthase gene from maize with crt1 from the original golden rice. Golden rice 2 produces 23 times more carotenoids than golden rice (up to 37 µg/g), and preferentially accumulates beta-carotene (up to 31 µg/g of the 37 µg/g of carotenoids). To receive the Recommended Dietary Allowance (RDA), it is estimated that 144 g of the most high-yielding strain would have to be eaten. Bioavailability of the carotene from golden rice has been confirmed and found to be an effective source of Vitamin A for humans.
In June 2005, researcher Peter Beyer received funding from the Bill and Melinda Gates Foundation to further improve golden rice by increasing the levels of or the bioavailability of pro-vitamin A, vitamin E, iron, and zinc, and to improve protein quality through genetic modification.
Potential use to combat vitamin A deficiency
The research that led to golden rice was conducted with the goal of helping children who suffer from vitamin A deficiency (VAD). In 2005, 190 million children and 19 million pregnant women, in 122 countries, were estimated to be affected by VAD. VAD is responsible for 1–2 million deaths, 500,000 cases of irreversible blindness and millions of cases of xerophthalmia annually. Children and pregnant women are at highest risk. Vitamin A is supplemented orally and by injection in areas where the diet is deficient in vitamin A. As of 1999[update], there were 43 countries that had vitamin A supplementation programs for children under 5; in 10 of these countries, two high dose supplements are available per year, which, according to UNICEF, could effectively eliminate VAD. However, UNICEF and a number of NGOs involved in supplementation note more frequent low-dose supplementation should be a goal where feasible.
Because many children in countries where there is a dietary deficiency in vitamin A rely on rice as a staple food, the genetic modification to make rice produce the vitamin A precursor beta-carotene is seen as a simple and less expensive alternative to vitamin supplements or an increase in the consumption of green vegetables or animal products.
Initial analyses of the potential nutritional benefits of golden rice suggested consumption of golden rice would not eliminate the problems of vitamin A deficiency, but should be seen as a complement to other methods of vitamin A supplementation. Since then, improved strains of golden rice have been developed containing sufficient provitamin A to provide the entire dietary requirement of this nutrient to people who eat about 75g of golden rice per day.
In particular, since carotenes are hydrophobic, there needs to be a sufficient amount of fat present in the diet for golden rice (or most other vitamin A supplements) to be able to alleviate vitamin A deficiency. In that respect, it is significant that vitamin A deficiency is rarely an isolated phenomenon, but usually coupled to a general lack of a balanced diet (see also Vandana Shiva's arguments below). The RDA levels accepted in developed countries are far in excess of the amounts needed to prevent blindness. Moreover, this claim referred to an early cultivar of golden rice; one bowl of the latest version provides 60% of RDA for healthy children.
The University of California and Rutgers University have conducted studies showing "...higher crop yields, reduced pesticide use and fewer pesticide-related health problems..." amongst Chinese farmers who used GM rice strains. This was published in the peer reviewed journal Science in 2005.
Dr. José L. Domingo of the Laboratory of Toxicology and Environmental Health, School of Medicine, at Rovira i Virgili University in Spain said, "According to the information reported by the WHO, genetically modified products that are currently on the international market have all passed risk assessments conducted by national authorities." These assessments found no risk to human health. Dr. Domingo advocates continued research in the areas of GM rice and its effects on humans.
Clinical trials / food safety and nutrition research
In 2009, research results of a clinical trial of Golden Rice with adult volunteers from the USA were published in the American Journal of Clinical Nutrition. It concluded that "beta carotene derived from Golden Rice is effectively converted to vitamin A in humans". In a summary about the research the American Society for Nutrition suggests the implications of the research are that "Golden Rice could probably supply 50% of the Recommended Dietary Allowance (RDA) of vitamin A from a very modest amount — perhaps a cup — of rice, if consumed daily. This amount is well within the consumption habits of most young children and their mothers".
In response to the research, a group of 20 scientists suggested in an open letter that there might be deficiencies in clinical trials: "There is now a large body of evidence that shows that GM crop/food production is highly prone to inadvertent and unpredictable pleiotropic effects, which can result in health damaging effects when GM food products are fed to animals. More specifically, our greatest concern is that this rice, which is engineered to overproduce beta carotene, has never been tested in animals, and there is an extensive medical literature showing that retinoids that can be derived from beta carotene are both toxic and cause birth defects."  However, it is well known that beta carotene is found and consumed in many nutritious foods eaten around the world, including fruits and vegetables. Beta carotene in food is a safe source of vitamin A.
The Food Allergy Resource and Research Program of the University of Nebraska undertook research in 2006 that showed the proteins from the new genes in Golden Rice did not show any allergenic properties.
In August 2012, Tufts University and others published new research on Golden Rice in the American Journal of Clinical Nutrition showing that the beta carotene produced by Golden Rice is as good as beta carotene in oil at providing vitamin A to children. The study states that "recruitment processes and protocol were approved", but questions have been raised about the use of Chinese children to test the effects of Golden Rice.
Critics of genetically engineered crops have raised various concerns. An early issue was that golden rice originally did not have sufficient vitamin A. This problem was solved by the development of new strains of rice. The speed at which vitamin A degrades once the rice is harvested, and how much remains after cooking are contested. However, a 2009 study concluded that golden rice is effectively converted into vitamin A in humans and a 2012 study that fed 68 children ages 6 to 8 concluded that golden rice was as good as vitamin A supplements and better than the natural beta-carotene in spinach.
Greenpeace opposes the use of any patented genetically modified organisms in agriculture and opposes the cultivation of golden rice, claiming it will open the door to more widespread use of GMOs. However this is rejected by the International Rice Research Institute (IRRI), claiming that "None of the companies listed ... are involved in carrying out the research and development activities of IRRI or its partners in Golden Rice, and none of them will receive any royalty or payment from the marketing or selling of Golden Rice varieties developed by IRRI."
Vandana Shiva, an Indian anti-GMO activist, argued the problem was not the plant per se, but potential problems with poverty and loss of biodiversity. Shiva claimed these problems could be amplified by the corporate control of agriculture. By focusing on a narrow problem (vitamin A deficiency), Shiva argued, golden rice proponents were obscuring the limited availability of diverse and nutritionally adequate food. Other groups argued that a varied diet containing foods rich in beta carotene such as sweet potato, leaf vegetables and fruit would provide children with sufficient vitamin A. However Keith West of Johns Hopkins Bloomberg School of Public Health countered that foodstuffs containing vitamin A are either unavailable, or only available at certain seasons, or that they are too expensive for poor families in underdeveloped countries.
In 2008 WHO malnutrition expert Francesco Branca cited the lack of real-world studies and uncertainty about how many people will use golden rice, concluding "giving out supplements, fortifying existing foods with vitamin A, and teaching people to grow carrots or certain leafy vegetables are, for now, more promising ways to fight the problem".
On August 8, 2013 an experimental plot of golden rice being grown in the Philippines was uprooted by protesters. Mark Lynas, a famous former anti-GMO activist, reported in Slate that the vandalism was carried out by a group of activists led by the extreme left-inclined Kilusang Magbubukid ng Pilipinas (KMP) (unofficial translation: Farmers' Movement of the Philippines), to the dismay of other protesters. No local farmers participated in the uprooting, only the small number of activists damaged the Golden Rice crops, because the farmers believe in their local customs which imply that killing a living rice plant is unlucky.
Potrykus has enabled golden rice to be distributed free to subsistence farmers. Free licenses for developing countries were granted quickly due to the positive publicity that golden rice received, particularly in Time magazine in July 2000.  Monsanto Company was one of the first companies to grant free licences.
The cutoff between humanitarian and commercial use was set at US$10,000. Therefore, as long as a farmer or subsequent user of golden rice genetics does not make more than $10,000 per year, no royalties need to be paid. In addition, farmers are permitted to keep and replant seed.
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