Golden rice

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Golden rice
Golden Rice.jpg
Golden rice (back) compared to white rice (front), demonstrating the distinctive golden-yellow colour of the variety
Species Oryza sativa
Cultivar Golden rice
Origin Rockefeller Foundation

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 the rice. [1] [2] It is intended to produce a fortified food to be grown and consumed in areas with a shortage of dietary vitamin A. Vitamin A deficiency causes xerophthalmia, a range of eye conditions from night blindness to more severe clinical outcomes such as keratomalacia and corneal scars, and permanent blindness. Additionally, vitamin A deficiency also increases risk of mortality from measles and diarrhea in children. In 2013, the prevalence of deficiency was the highest in sub-Saharan Africa (48%; 25–75), and South Asia (44%; 13–79). [3]

Contents

Although golden rice has met significant opposition from environmental and anti-globalisation activists, more than 100 Nobel laureates in 2016 encouraged use of genetically modified golden rice which can produce up to 23 times as much beta-carotene as the original golden rice. [4] [5] [6]

History

A simplified overview of the carotenoid biosynthesis pathway in golden rice. The enzymes expressed in the endosperm of golden rice, shown in red, catalyse the biosyntheis of beta-carotene from geranylgeranyl diphosphate. Beta-carotene is assumed to be converted to retinal and subsequently retinol (vitamin A) in the animal gut Carotenoidsynthesis.svg
A simplified overview of the carotenoid biosynthesis pathway in golden rice. The enzymes expressed in the endosperm of golden rice, shown in red, catalyse the biosyntheis of beta-carotene from geranylgeranyl diphosphate. Beta-carotene is assumed to be converted to retinal and subsequently retinol (vitamin A) in the animal gut

Research for development of golden rice began as a Rockefeller Foundation initiative in 1982. [7]

In the 1990s, Peter Bramley discovered that a single phytoene desaturase gene (bacterial CrtI) can be used to produce lycopene from phytoene in GM tomato, rather than having to introduce multiple carotene desaturases that are normally used by higher plants. [8] Lycopene is then cyclized to beta-carotene by the endogenous cyclase in golden rice. [9] The scientific details of the rice were first published 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. [2]

The first field trials of golden rice cultivars were conducted by Louisiana State University Agricultural Center in 2004. [10] Additional trials were conducted in the Philippines, Taiwan, and in Bangladesh (2015). [11] Field testing provided an accurate measurement of nutritional value and enabled feeding tests to be performed. Preliminary results from field tests showed field-grown golden rice produces 4 to 5 times more beta-carotene than golden rice grown under greenhouse conditions. [12]

Crossbreeding

As of 2018, breeders at the Philippine Rice Research Institute, the Bangladesh Rice Research Institute, and the Indonesian Centre for Rice Research were developing golden rice versions of existing rice varieties used with their local farmers, retaining the same yield, pest resistance, and grain qualities. Golden rice seeds may cost farmers the same as other rice varieties. [13]

Approvals

In 2018, Canada and the United States approved golden rice, with Health Canada and the US Food and Drug Administration (FDA) declaring it safe for consumption. [14] This followed a 2016 decision where the FDA had ruled that the beta-carotene content in golden rice did not provide sufficient amounts of vitamin A for US markets. [15] Health Canada declared that golden rice would not affect allergies, and that the nutrient contents were the same as in common rice varieties, except for the intended high levels of provitamin A. [16]

In 2019, golden rice was approved for use as human food and animal feed or for processing in the Philippines. [17] On 21 July 2021, the Philippines became the first country to officially issue the biosafety permit for commercially propagating vitamin A-infused golden rice. [18] The approval came as the first commercial propagation authorisation of genetically engineered rice in South and Southeast Asia. As a result of the permission, golden rice can be grown on a commercial scale in accordance with the terms and conditions specified by the Philippines government. [19] In April 2023, however, the country's Supreme Court ordered the agriculture department to stop commercial propagation of golden rice in relation to a petition filed by MASIPAG (a group of farmers and scientists), who claimed that golden rice poses risk to the health of consumers and to the environment. [20]

Genetics

Golden rice was created by transforming rice with two beta-carotene biosynthesis genes:

  1. psy (phytoene synthase) from daffodil ( Narcissus pseudonarcissus )
  2. crtI (phytoene 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 produced in wild-type rice endosperm.)

The psy and crtI genes were transferred into the rice nuclear genome and placed under the control of an endosperm-specific promoter, so that 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 is formed. The bacterial crtI gene was an important inclusion to complete the pathway, since it can catalyse multiple steps in the synthesis of carotenoids up to lycopene, while these steps require more than one enzyme in plants. [21] 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 colour for which it is named. [22] The original golden rice was called SGR1, and under greenhouse conditions it produced 1.6 µg/g of carotenoids.

Golden Rice 2

In 2005, a team of researchers at Syngenta produced Golden Rice 2. They combined the phytoene synthase (psy) gene from maize with crtl gene from the original golden rice. Golden Rice 2 produces 23 times more carotenoids than golden rice (up to 37 µg/g) because psy gene of maize is the most effective gene for carotenoid synthesis, and preferentially accumulates beta-carotene (up to 31 µg/g of the 37 µg/g of carotenoids). [23]

Vitamin A deficiency

Prevalence of vitamin A deficiency. Red is most severe (clinical), green least severe. Countries not reporting data are coded blue. Data collected for a 1995 report. Vitamin A deficiency.PNG
Prevalence of vitamin A deficiency. Red is most severe (clinical), green least severe. Countries not reporting data are coded blue. Data collected for a 1995 report.

The research that led to golden rice was conducted with the goal of helping children who suffer from vitamin A deficiency (VAD). Estimates show that around 1.02 billion people are severely affected by micronutrient deficiencies globally, with vitamin A to be the most deficient nutrient in the body. [24] In 2012, the World Health Organization reported that about 250 million preschool children are affected by VAD, and that providing those children with vitamin A could prevent about a third of all under-five deaths, which amounts to up to 2.7 million children that could be saved from dying unnecessarily. [25] The World Health Organization has classified vitamin A deficiency as a public health problem affecting about one third of children aged 6 to 59 months in 2013, with the highest rates in sub-Saharan Africa (48 per cent) and South Asia (44 per cent). [26]

VAS programs began in the 1990s in response to evidence demonstrating the association between VAD and increased childhood mortality. Between 1990 and 2013, more than 40 efficacy studies of VAS in children 6–59 months of age were conducted, and two systematic reviews and meta-analyses have concluded that VA supplements can considerably reduce mortality and morbidity during childhood. [24] As of 2017, more than 80 countries worldwide are implementing universal VA supplementation (VAS) programs targeted to children 6–59 months of age through semi-annual national campaigns. [24] Periodic, high-dose vitamin A supplementation is a proven, low-cost intervention which has been shown to reduce all-cause mortality by 12 to 24 per cent, and is therefore an important program in support of efforts to reduce child mortality. [26] However, UNICEF and a number of NGOs involved in supplementation note more frequent low-dose supplementation is preferable.

As many children in VAD-affected countries rely on rice as a staple food, genetic modification to make rice produce the vitamin A precursor beta-carotene was seen as a simple and less expensive alternative to ongoing 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 could complement other supplementation. [27] [28] Golden Rice 2 contains sufficient provitamin A to provide the entire dietary requirement via daily consumption of some 75 grams (3 oz) per day. [4]

Vitamin A deficiency is usually coupled to an unbalanced diet. Since carotenes are hydrophobic, sufficient fat must be present in the diet for golden rice (or most other vitamin A supplements) to alleviate vitamin A deficiency. Moreover, this claim referred to an early cultivar of golden rice; one bowl of the latest version provides 60% of RDA for healthy children. [29] The RDA levels advocated in developed countries are far in excess of the amounts needed to prevent blindness. [30]

Research

In 2009, results of a clinical trial of golden rice with adult volunteers concluded that "beta-carotene derived from golden rice is effectively converted to vitamin A in humans". [31] A summary for the American Society for Nutrition suggested 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." [32] 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. [33]

A 2012 study showed that the beta-carotene produced by golden rice is as effective as beta-carotene in oil at providing vitamin A to children. [34] The study stated that "recruitment processes and protocol were approved". [34] However, in 2015, the journal retracted the study, claiming that the researchers had acted unethically when providing Chinese children golden rice without their parents' consent. [35] [36]

Golden rice improves vitamin A intake and may reduce vitamin A deficiency among women and children. [37] Food derived from golden rice varieties is as safe as food derived from conventional rice varieties. [38]

Controversy

Critics of genetically engineered crops have raised various concerns. An early issue was that golden rice originally did not have sufficient beta-carotene content. This problem was solved by the advancing of GR2E event. [30] The speed at which beta-carotene degrades once the rice is harvested, and how much remains after cooking are contested. [39] However, a 2009 study concluded that beta-carotene from golden rice is effectively converted into vitamin A in humans. [40]

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. [41] [42] The International Rice Research Institute (IRRI) has emphasised the non-commercial nature of their project, stating 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." [43]

Vandana Shiva, an Indian anti-GMO activist, argued the problem was not the plant per se, but potential issues with loss of biodiversity. Shiva argued that golden rice proponents were obscuring the limited availability of diverse and nutritionally adequate food. [44] 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. [45] However, Keith West of Johns Hopkins Bloomberg School of Public Health has said that foodstuffs containing vitamin A are often unavailable, only available in certain seasons, or are too expensive for poor families to obtain. [46]

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". [47] Author Michael Pollan, who had criticized the product in 2001, being unimpressed by the benefits, expressed support for the continuation of the research in 2013. [48]

In 2012, controversy surrounded a study published in The American Journal of Clinical Nutrition . [49] The study, involving feeding GM rice to children from 6 to 8 years old in China, was later found to have violated human research rules of both Tufts University and the federal government. Subsequent reviews found no evidence of safety problems with the study, but found issues with insufficient consent forms, unapproved changes to study protocol, and lack of approval from a China-based ethics review board. Additionally, the GM rice used was brought into China illegally. [50] [51]

Support

The Bill and Melinda Gates Foundation supports the use of genetically modified organisms in agricultural development and supports the International Rice Research Institute in developing golden rice. [52] In June 2016, 107 Nobel laureates signed a letter urging Greenpeace and its supporters to abandon their campaign against GMOs, and against golden rice in particular. [53] [54]

In May 2018, the U.S. Food and Drug Administration approved the use of golden rice for human consumption, stating: "Based on the information IRRI has presented to FDA, we have no further questions concerning human or animal food derived from GR2E rice at this time." [55] This marks the fourth national health organisation to approve the use of golden rice in 2018, joining Australia, Canada and New Zealand who issued their assessments earlier in the year. [56]

In December 2021, an opinion piece in Proceedings of the National Academy of Sciences of the United States of America called on regulators to "allow Golden Rice to save lives", which the authors say has been delayed due to "fear and false accusations", leading to estimated 266,000 lives lost per year due to vitamin A deficiency. [57]

Protests

On August 8, 2013, an experimental plot of golden rice being developed by IRRI and DA-PhilRice in Camarines Sur province of the Philippines was uprooted by protesters. [29] [48] [58] British author Mark Lynas reported in Slate that the vandalism was carried out by a group of activists led by Kilusang Magbubukid ng Pilipinas (KMP) (literally 'Farmers' Movement of the Philippines'). [48] [59]

Distribution

A recommendation was made that golden rice be distributed free to subsistence farmers. [60] Free licenses for developing countries were granted quickly due to the positive publicity that golden rice received, particularly in Time magazine in July 2000. [61] Monsanto Company was one of the companies to grant free licences for related patents owned by the company. [62] 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 would not make more than $10,000 per year, no royalties would need to be paid. In addition, farmers would be permitted to keep and replant seed. [63]

See also

Related Research Articles

<span class="mw-page-title-main">Lycopene</span> Carotenoid pigment

Lycopene is an organic compound classified as a tetraterpene and a carotene. Lycopene is a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and vegetables.

<span class="mw-page-title-main">Vitamin A</span> Essential nutrient

Vitamin A is a fat-soluble vitamin and an essential nutrient for animals. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinal, retinoic acid, and several provitamin (precursor) carotenoids, most notably beta-carotene. Vitamin A has multiple functions: it is essential for embryo development and growth, for maintenance of the immune system, and for vision, where it combines with the protein opsin to form rhodopsin – the light-absorbing molecule necessary for both low-light and color vision.

Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a primary deficiency, whereas when due to an underlying disorder such as malabsorption it is called a secondary deficiency. An underlying disorder can have 2 main causes:

<span class="mw-page-title-main">Carotenoid</span> Class of chemical compounds; yellow, orange or red plant pigments

Carotenoids are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, archaea, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, canaries, flamingos, salmon, lobster, shrimp, and daffodils. Over 1,100 identified carotenoids can be further categorized into two classes – xanthophylls and carotenes.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

<span class="mw-page-title-main">Ingo Potrykus</span>

Ingo Potrykus is Professor Emeritus of Plant Sciences at the Institute of Plant Sciences of the Swiss Federal Institute of Technology (ETH), Zurich from which he retired in 1999. His research group applied gene technology to contribute to food security in developing countries. Together with Peter Beyer, he is one of the co-inventors of golden rice. In 2014 he was chairman of the Golden Rice Humanitarian Board.

<span class="mw-page-title-main">Carotenosis</span> Skin discoloration caused by carotenoids

Carotenosis is a benign and reversible medical condition where an excess of dietary carotenoids results in orange discoloration of the outermost skin layer. The discoloration is most easily observed in light-skinned people and may be mistaken for jaundice. Carotenoids are lipid-soluble compounds that include alpha- and beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin. The primary serum carotenoids are beta-carotene, lycopene, and lutein. Serum levels of carotenoids vary between region, ethnicity, and sex in the healthy population. All are absorbed by passive diffusion from the gastrointestinal tract and are then partially metabolized in the intestinal mucosa and liver to vitamin A. From there they are transported in the plasma into the peripheral tissues. Carotenoids are eliminated via sweat, sebum, urine, and gastrointestinal secretions. Carotenoids contribute to normal-appearing human skin color, and are a significant component of physiologic ultraviolet photoprotection.

<span class="mw-page-title-main">Vitamin A deficiency</span> Disease resulting from low Vitamin A concentrations in the body

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia is one of the first signs of VAD, as the vitamin has a major role in phototransduction; but it is also the first symptom that is reversed when vitamin A is consumed again. Xerophthalmia, keratomalacia, and complete blindness can follow if the deficiency is more severe.

<span class="mw-page-title-main">Genetically modified plant</span> Plants with human-introduced genes from other organisms

Genetically modified plants have been engineered for scientific research, to create new colours in plants, deliver vaccines, and to create enhanced crops. Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. Many plant cells are pluripotent, meaning that a single cell from a mature plant can be harvested and then under the right conditions form a new plant. This ability is most often taken advantage by genetic engineers through selecting cells that can successfully be transformed into an adult plant which can then be grown into multiple new plants containing transgene in every cell through a process known as tissue culture.

<span class="mw-page-title-main">Beta-carotene 15,15'-dioxygenase</span> Mammalian protein found in Homo sapiens

In enzymology, beta-carotene 15,15'-dioxygenase, (EC 1.13.11.63) is an enzyme with systematic name beta-carotene:oxygen 15,15'-dioxygenase (bond-cleaving). In human it is encoded by the BCDO2 gene. This enzyme catalyses the following chemical reaction

Vitamins occur in a variety of related forms known as vitamers. A vitamer of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.

<span class="mw-page-title-main">Damascenone</span> Chemical compound

Damascenones are a series of closely related chemical compounds that are components of a variety of essential oils. The damascenones belong to a family of chemicals known as rose ketones, which also includes damascones and ionones. beta-Damascenone is a major contributor to the aroma of roses, despite its very low concentration, and is an important fragrance chemical used in perfumery.

<span class="mw-page-title-main">Biofortification</span> Breeding crops for higher nutritional value

Biofortification is the idea of breeding crops to increase their nutritional value. This can be done either through conventional selective breeding, or through genetic engineering. Biofortification differs from ordinary fortification because it focuses on making plant foods more nutritious as the plants are growing, rather than having nutrients added to the foods when they are being processed. This is an important improvement on ordinary fortification when it comes to providing nutrients for the rural poor, who rarely have access to commercially fortified foods. As such, biofortification is seen as an upcoming strategy for dealing with deficiencies of micronutrients in low and middle-income countries. In the case of iron, the WHO estimated that biofortification could help cure the 2 billion people suffering from iron deficiency-induced anemia.

<span class="mw-page-title-main">Genetically modified rice</span>

Genetically modified rice are rice strains that have been genetically modified. Rice plants have been modified to increase micronutrients such as vitamin A, accelerate photosynthesis, tolerate herbicides, resist pests, increase grain size, generate nutrients, flavors or produce human proteins.

Peter Beyer is a German Professor for Cell Biology at the Faculty of Biology of the University of Freiburg. He is known as co-inventor of Golden Rice, together with Ingo Potrykus from the ETH Zurich.

Yellow cassava is a new, yellow-fleshed breed of one of the most popular root crops in the tropics. Regular cassava is a staple crop in tropical countries which 300 million people rely upon for at least 10% of their daily caloric intake, in 15 African countries "In the Democratic Republic of the Congo, cassava is estimated to provide more than 1000 kcal/day to over 40 million people". Three yellow root cassava varieties, UMUCASS 36, UMUCASS 37, and UMUCASS 38, are being grown in Nigeria for their high concentrations of β-carotene. β-carotene is a precursor to Vitamin A. Vitamin A deficiency is a major issue, especially in Africa. Nigeria in particular sees a prevalence of Vitamin A deficiency in nearly one third of children under five years old. Since cassava is a major food staple, yellow cassava shows great potential to alleviate Vitamin A deficiency in Africa.

<span class="mw-page-title-main">15-Cis-phytoene desaturase</span> Class of enzymes

15-cis-phytoene desaturases, are enzymes involved in the carotenoid biosynthesis in plants and cyanobacteria. Phytoene desaturases are membrane-bound enzymes localized in plastids and introduce two double bonds into their colorless substrate phytoene by dehydrogenation and isomerize two additional double bonds. This reaction starts a biochemical pathway involving three further enzymes called the poly-cis pathway and leads to the red colored lycopene. The homologous phytoene desaturase found in bacteria and fungi (CrtI) converts phytoene directly to lycopene by an all-trans pathway.

<span class="mw-page-title-main">Phytoene desaturase (lycopene-forming)</span>

Phytoene desaturase (lycopene-forming) are enzymes found in archaea, bacteria and fungi that are involved in carotenoid biosynthesis. They catalyze the conversion of colorless 15-cis-phytoene into a bright red lycopene in a biochemical pathway called the poly-trans pathway. The same process in plants and cyanobacteria utilizes four separate enzymes in a poly-cis pathway.

Peter M. Bramley is a British biochemist and emeritus professor of biochemistry at Royal Holloway, University of London, where he was the Head of the School of Biological Sciences from 2006 to 2011. His research focuses on the biosynthesis of carotenoids in plants and microorganisms

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