Golden rice is a variety of Oryza sativa rice 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, which is estimated to kill 670,000 children under 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.
Golden Rice is still being developed and evaluated and has not yet been approved for widescale use in any country.
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.
Golden rice was created by transforming rice with two beta-carotene biosynthesis genes:
- psy (phytoene synthase) from daffodil (Narcissus pseudonarcissus)
- crtI from the soil bacterium Erwinia uredovora
(The insertion of a lyc (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 lyc 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.
Subsequent development 
Golden rice has been bred with local rice cultivars in the Philippines, Taiwan and with the American rice cultivar 'Cocodrie'. The first field trials of these golden rice cultivars were conducted by Louisiana State University Agricultural Centre in 2004. Field testing will allow a more accurate measurement of the nutritional value of golden rice, and will enable 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.
A 2012 article forecast that golden rice would clear final regulatory hurdles and be available to farmers in the Phillipines in 2014 or 2015. The International Rice Research Institute (IRRI) is currently coordinating the Golden Rice Network with other partners who have expertise in agriculture and nutrition to research and develop Golden Rice. In 2011, IRRI announced that Helen Keller International, a leading global health organization that reduces blindness and prevents malnutrition worldwide, was joining their Golden Rice project to further develop and evaluate Golden Rice.
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. It can be considered as the genetically engineered equivalent of fluoridated water or iodized salt.
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). Hence, assuming a bioavailability on par with other natural sources of provitamin A, Greenpeace estimated that for the first strain of golden rice, adult humans would need to eat an infeasible amount (9 kg/day) to meet the RDA levels accepted in developed countries.[dead link] (Note, however, that the RDA levels accepted in developed countries are far in excess of the amounts needed to prevent blindness.) Moreover, this claim referred to a prototype cultivar of golden rice; more recent versions have considerably higher quantities of vitamin A in them.
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.
According to Dr. Jose' L. Domingo of the Laboratory of Toxicology and Environmental Health, School of Medicine, at Rovira I Virgili University in Spain, "According to the information reported by the WHO [World Health Organization], genetically modified (GM) products that are currently on the international market have all passed risk assessments conducted by national authorities. These assessments have not indicated any risk to human health. Dr. Domingo also advocates continued research in the areas of (GM) rice and its effect(s) 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, was 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 (for reviews see Pusztai and Bardocz , 2006; Schubert, 2008; Dona and Arvanitoyannis, 2009). 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. One of these is that golden rice originally did not have sufficient vitamin A. This problem was solved by the development of new strains of rice. However, there are still doubts about the speed at which vitamin A degrades once the plant is harvested, and how much would remain after cooking. A 2009 study of boiled golden rice fed to volunteers concluded that golden rice is effectively converted into vitamin A in humans and a 2012 study of golden rice that fed 68 children ages 6 to 8, and concluded that the golden rice was as good as vitamin A supplements and better than the natural beta-carotene in spinach.
Greenpeace opposes the release of any genetically modified organisms into the environment, and is concerned that golden rice is a Pandora's Box that will open the door to more widespread use of GMOs.
Vandana Shiva, an Indian anti-GMO activist, argued the problem was not that the crop had any particular deficiencies, but that there were potential problems with poverty and loss of biodiversity in food crops. These problems are aggravated by the corporate control of agriculture based on genetically modified foods. By focusing on a narrow problem (vitamin A deficiency), Shiva argued, the golden rice proponents were obscuring the larger issue of a lack of broad availability of diverse and nutritionally adequate sources of food. Other groups have argued a varied diet containing foods rich in beta carotene such as sweet potato, leafy green vegetables and fruit would provide children with sufficient vitamin A. However Professor West (Johns Hopkins Bloomberg School of Public Health) has argued that foodstuffs containing Vitamin A are either unavailable, or only available at certain seasons, or that they are too expensive for most poor families in underdeveloped countries.
Because of lacking real-world studies and uncertainty about how many people will use golden rice, WHO malnutrition expert Francesco Branca concludes "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".
Potrykus has spearheaded an effort to have golden rice distributed for free to subsistence farmers. This required several companies which had intellectual property rights to the results of Beyer's research to license it for free. Beyer had received funding from the European Commissions 'Carotene Plus' research program, and by accepting those funds, he was required by law to give the rights to his discovery to the corporate sponsors of that program, Zeneca (now Syngenta). Beyer and Potrykus made use of 70 intellectual property rights belonging to 32 different companies and universities in the making of golden rice. They needed to establish free licences for all of these, so Syngenta and humanitarian partners in the project could use golden rice in breeding programs and to develop new crops.
Free licenses for developing countries were granted quickly due to the positive publicity that golden rice received, particularly in Time magazine in July 2000. Golden rice was said to be the first genetically modified crop that was unarguably beneficial. 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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