the case study of golden rice

Excerpt: The True Story of the Genetically Modified Superfood That Almost Saved Millions

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The True Story of the Genetically Modified Superfood That Almost Saved Millions

The imperiled birth—and slow decline—of golden rice..

• Science and Technology

The cover of the July 31, 2000, edition of Time magazine pictured a serious-looking bearded man surrounded by a wall of greenery: the stems, leaves, and stalks of rice plants. The caption, in large block lettering, read, “This rice could save a million kids a year.”

The man in question was Ingo Potrykus, a professor of plant sciences at the Swiss Federal Institute of Technology, in Zurich, where Albert Einstein had studied and taught. The rice plants around him, although the joint products of many minds and hands, had been largely inspired by him. Their kernels were not the usual plain white grains of rice. Instead, they had a distinct golden hue, the color of daffodils. When spread out on a black surface, they looked like nothing so much as tiny yellow gemstones.

This was Golden Rice, the fruit of nine years of research, experimentation, and development. The “gold” was in fact beta carotene, a substance that is converted into vitamin A in the human body. Conventional rice plants already contained beta carotene, but only in their leaves and stems, not in the kernels. Golden Rice also carries the substance in the part of the plant that people eat. This small change made Golden Rice into a miracle of nutrition: The rice could combat vitamin A deficiency in areas of the world where the condition is endemic and could, thereby, “save a million kids a year.”

Golden Rice: The Imperiled Birth of a GMO Superfood , Ed Regis, Johns Hopkins University Press, 256 pp., $29.95, October 2019

Vitamin A deficiency is practically unknown in the Western world, where people take multivitamins or get sufficient micronutrients from ordinary foods, fortified cereals, and the like. But it is a life-and-death matter for people in developing countries. Lack of vitamin A is responsible for a million deaths annually, most of them children, plus an additional 500,000 cases of blindness. In Bangladesh, China, India, and elsewhere in Asia, many children subsist on a few bowls of rice a day and almost nothing else. For them, a daily supply of Golden Rice could bring the gift of life and sight.

The superfood thus seemed to have everything going for it: It would be the basis for a sea change in public health among the world’s poorest people. It would be cheap to grow and indefinitely sustainable, because low-income farmers could save the seeds from any given harvest and plant them the following season, without purchasing them anew.

But in the 20 years since it was created, Golden Rice has not been made available to those for whom it was intended. So what happened?

For one, Golden Rice is a genetically modified organism, and as such is weighed down with all the political, ideological, and emotional baggage that has come to be associated with GMOs—stultifying government overregulation, fear and hostility, and criticism (much of it unfounded) from environmentalist and other activist organizations and individuals. Greenpeace, for one, was especially vocal in its condemnation of genetically engineered foods, Golden Rice in particular.

To many, this protracted delay has been unconscionable, and it brought forth reactions as extreme as the hyperbolic claims made by GMO opponents. In 2016, for example, George Church, a professor of genetics at Harvard Medical School, said in an interview with the science publication Edge :

Golden Rice was a tough call strategically for Greenpeace and some of their associates. … A million lives are at stake every year due to vitamin A deficiency, and Golden Rice was basically ready for use in 2002, so it’s been thirteen years that it’s been ready. Every year that you delay it, that’s another million people dead. That’s mass murder on a high scale. In fact, as I understand it there is an effort to bring them to trial at The Hague for crimes against humanity. Maybe that’s justified, maybe it isn’t.

Much of the pro-Golden Rice backlash was overstatement, too. For one thing, it is doubtful that Golden Rice was “ready,” in any but the most technical sense, in 2002. Indeed, some critics would argue that as a proven, viable, agricultural commodity, it is not yet ready even today. Still, the fact is that the crop has been grown, and grown successfully, first in laboratories, then in greenhouses, and finally in open fields since it was invented. The rice has also been subjected to safety studies—toxicity and allergenicity studies—and studies on human consumption, including among American adults and Chinese children. These have found it to be more effective in providing vitamin A than spinach and almost as effective as pure beta carotene oil itself.

So what really happened? Extremist opposition, protests, rhetoric, and even vandalism did not, by themselves, have the power to stop Golden Rice in its tracks or even to substantially hamper the pace of its development. Indeed, the delay may come down to a variety of other, less obvious, factors.

The first source of delay was simply the scientific and technological difficulty of inventing a new crop type, one that was nutritionally enhanced by molecular methods to express beta carotene in a part of the rice plant that did not normally do so. The tasks of genetically engineering a new metabolic pathway in the plant, getting the plant to express the desired trait at the most beneficial levels of concentration, and then transferring that newly engineered trait into several different varieties of rice successfully—all of these things were, at the time, new, untried, and unproven technologies.

The second cause was the fact that plants themselves are recalcitrant experimental subjects: They grow only so fast and no faster, and the cycle of germination, maturation, and seed production is a process that can’t really be sped up. However, this same process can easily be slowed down, or even terminated, by a variety of causes such as disease; insect attack; natural disasters and weather events including floods, frosts, heat waves, and droughts; vandalism; or simple human misjudgment or mishandling.

But it was something else altogether that had the greatest power to impede the development of Golden Rice, and that was government regulation. That power resided in a complex set of operational guidelines, restrictions, and requirements that created enormous obstacles for the Golden Rice scientists to overcome. Governments imposed these constraints in the name of safety; chiefly responsible for these restrictions is an international treaty known as the Cartagena Protocol on Biosafety and its highly controversial Principle 15, otherwise known as the “precautionary principle.”

This principle states that if a product of modern biotechnology poses a possible risk to human health or the environment, then it is prudent to restrict or prevent the introduction or use of that product or technology, even if the magnitude or nature of the risk is uncertain, speculative, scientifically unproven, or even unknown. Although it may have been benign in its intent, the effect of the principle has been to slow the pace of biotechnology research and development—and in some cases even to halt it, at least temporarily, at multiple times during the research and development process.

In the case of Golden Rice, the combined result of these three factors—the scientific difficulty of the project, the slow and stately rate of plant growth and reproduction, and a body of stifling government regulations governing biotechnology research and development—was to prolong the incubation time of a food that, absent externally imposed government restrictions, could otherwise be saving the sight and lives of millions of people.

The story of Golden Rice thus makes for a sad and maddening tale of scientists being repeatedly thwarted in their attempts to invent, improve, breed, field-test, and disseminate a potentially lifesaving food.

Yet despite all these roadblocks, Golden Rice has still emerged as the world’s first purposefully created biofortified crop. The project began in 1990, when Potrykus and his colleague Peter Beyer, of the University of Freiburg, started working to genetically engineer a metabolic pathway into a variety of Oryza sativa , the world’s most commonly consumed rice species, so that the plant’s edible kernels would contain beta carotene. It is an understatement to say that their task was daunting. There was no assurance when they started out that what they contemplated was even technologically possible, since it had never been done before. But the two men were highly motivated by the horrors of persistent vitamin A deficiency in developing countries, and they viewed their work as a calling—one from which they would not be deterred.

It took almost a decade of laboratory experimentation to invent Golden Rice, but by 1999, Potrykus, Beyer, and a group of colleagues finally succeeded. They inserted a set of genes into the rice genome so that the plant’s beta carotene accumulated not only in the plant’s leaves and stems, as it normally did, but also in the rice kernels themselves, just as if nature had intended things to work that way from the very beginning.

Once they accomplished that small but powerful technological trick, the inventors naively imagined that the hard part was now behind them. Little did they know that the most difficult tasks still lay ahead. Looking back on it all afterward, Potrykus reflected, “Had I known what this pursuit would entail, perhaps I would not have started.”

Once they had their initial proof-of-concept rice in hand, the inventors moved swiftly to develop Golden Rice further, first to improve the product and then to make it available, for free, to poor farmers in developing countries. In April 2000, they licensed their rice technology to the British agrochemical company Zeneca on a quid pro quo basis: The company retained the right to sell Golden Rice seeds commercially, perhaps as a health food, on the condition that the company financially supported the inventors’ future work on the rice and let them distribute the seeds at no cost to small-scale farmers. Zeneca later merged with the Swiss-based company Syngenta, but the terms of the original arrangement remained unchanged.

On Feb. 9, 2001, Greenpeace, which had a long record of opposition to all GMO foods and crops, issued a statement that an adult would have to eat 9 kilograms (about 20 pounds) of cooked Golden Rice daily to prevent persistent vitamin A deficiency, and that “a breast-feeding woman would have to eat at least 6.3 kilos in dry weight, which converts to nearly 18 kilos [40 pounds] of cooked rice per day.” Since the bioavailability of beta carotene in the rice was not then known, there was no factual basis for these claims, which in any case were later proved false. At about the same time, the Indian anti-GMO crusader Vandana Shiva called Golden Rice a “hoax.” It was the beginning of a propaganda war against the rice that has only intensified.

Around the same time, the Cartagena Protocol on Biosafety was making waves. The protocol had been adopted in the year 2000 by more than 100 nations, including members of the European Union (but neither the United States nor Canada). The written document, which came into force in 2003, governed the handling, packaging, identification, transfer, and use of “living modified organisms” among the parties to the agreement.

The agreement contained one version of the precautionary principle. Exactly what that principle, which focused on avoiding unknown risks, meant in practice was not immediately clear. It is more of an ideal, a standard of perfection to be aimed at, than a real-world guide to action or public policy. On the one hand, it sounds like a dressed-up variant of a number of innocuous platitudes such as “look before you leap” or “better safe than sorry.” On the other, it can equally well be interpreted as a doctrine of “guilty until proven innocent.”

In light of the Cartagena Protocol, every aspect of Golden Rice development—from lab work to field trials to screening for “regulatory clean events”—was entangled in a Byzantine web of rules, guidelines, requirements, restrictions, and prohibitions. The simple transfer of seeds from one country to another became a major logistical problem. It could take “more than two years to transfer, for example, breeding seed from the Philippines to Vietnam, and one year from USA to India, during which time 30 politically loaded questions were asked in the Indian parliament,” Potrykus said. “These Cartagena conditions are enforced, despite common sense suggesting that it is extremely difficult to construct a hypothetical risk from seed transfer between two breeding stations in different countries, especially for Golden Rice.”

Golden Rice was unique among genetically engineered foods, and the properties that made it different also made it immune to many of the conventional criticisms of GMOs. Golden Rice was not invented for profit, and after 2004, when Syngenta renounced all commercial interest in the rice, it would no longer be developed for profit. The rice would benefit the poor and disadvantaged, not modern, multinational corporations. It would be given free of charge to subsistence farmers who can save seeds and plant them from one harvest to the next, without restriction or payment of fees or royalties. The rice was not developed primarily for the benefit of farmers, as were most other GMOs that had been designed to be resistant to herbicides or pesticides. Instead, it was developed for the sole purpose of helping users: the malnourished poor suffering from vitamin A deficiency. And Golden Rice is not a crop upon which a major genetic engineering effort conferred a relatively minor advantage such as a longer shelf life or slightly improved taste, as was true, for example, of the long-since-abandoned Flavr Savr tomato. That’s why, for all the vitriol, the real villain of the story is regulation, rather than activism run amok.

Had Golden Rice not faced overly restrictive regulatory conditions, it could have been cultivated by rice farmers and distributed throughout some of the poorest regions of South and Southeast Asia. It would have already saved millions of lives and prevented millions of children from going blind.

Excerpted from  Golden Rice . Used with permission of the publisher, Johns Hopkins University Press. Copyright © 2019.

Ed Regis is the author of Golden Rice: The Imperiled Birth of a GMO Superfood .

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Golden Rice

• Nutrition & Food Security

The International Rice Research Institute (IRRI) and its national research partners have developed Golden Rice to complement existing interventions to address vitamin A deficiency (VAD). VAD is a serious public health problem affecting millions of children and pregnant women globally.

In South and Southeast Asian countries, where at least half of daily caloric intake is obtained from rice, Golden Rice can help in the fight against VAD, particularly among the people who depend mostly on rice for nourishment.

Golden Rice is intended to be used in combination with existing approaches to overcome VAD, including eating foods that are naturally high in vitamin A or beta-carotene, eating foods fortified with vitamin A, taking vitamin A supplements, and optimal breastfeeding practices.

Golden Rice has been assessed to be as safe as ordinary rice with the added benefit of beta-carotene in the grains by  Food Standards Australia New Zealand (22 February 2018) , Health Canada (16 March 2018) , the  United States Food and Drug Administration (24 May 2018)  and Department of Agriculture-Bureau of Plant Industry (19 December 2019) .

In July 2021, the Philippines became the first country in the world to approve Golden Rice for commercial propagation .

Updates on the Golden Rice Project

As of 2022, Golden Rice has begun pilot-scale deployment in the Philippines. It is still under regulatory review in Bangladesh.

Biosafety approval is a prerequisite for inclusion in the rice variety listing of the National Seed Board (NSB) of Bangladesh.  To complete the biosafety review process, the Bangladesh Rice Research Institute (BRRI) lodged an application to the National Technical Committee on Crop Biotechnology (NTCCB) at the Ministry of Agriculture on November 26, 2017, who forwarded the application to the National Committee on Biosafety (NCB) at the Ministry of Environment on December 4, 2017.

PHILIPPINES

DA-PhilRice is leading pilot deployment in the Philippines , with the first batch of Golden Rice seeds distributed for planting in selected provinces during the 2022 wet season planting. Golden Rice is registered with the National Seed Industry Council as NSIC 2022 Rc682GR2E, or Malusog 1, hence the naming shift from Golden Rice to Malusog Rice in the country.

Golden Rice was assessed through the Joint Department Circular (JDC) No. 1 series of 2016 , which comprises three regulatory review processes: for direct use as food and feed, or for processing (FFP); for field trial; and for commercial propagation. Regulatory applications assessed through this process underwent approval through five different government agencies – the Department of Agriculture (DA), Department of Science and Technology (DOST), Department of Environment and Natural Resources (DENR), Department of Health (DOH), and Department of Interior and Local Government (DILG)-- as well as by a panel of independent scientific, socio-cultural, and economic experts.

The biosafety permit for the commercial propagation of GR2E Golden Rice was issued by the DA-BPI on 21 July 2021.

On 18 December 2019, the FFP permit was issued by the DA-BPI, approving GR2E Golden Rice for direct use as food and feed, or for processing in the Philippines.

The biosafety permit for field trial was released by DA-BPI on 20 May 2019. The field trial--conducted in DA-PhilRice stations in Munoz, Nueva Ecija, and San Mateo,Isabela--was completed in October 2019.

IRRI’s work with Golden Rice

IRRI works with its national research partners to develop Golden Rice as a complementary food-based approach to improve vitamin A status, using popular local inbred varieties from each country. IRRI’s work will support and strengthen the:

Development of Golden Rice varieties suitable for smallholder farmers in partner countries Breeders at the Philippine Department of Agriculture - Philippine Rice Research Institute ( DA-PhilRice ), the Bangladesh Rice Research Institute ( BRRI ), and the Indonesian Center for Rice Research ( ICRR ) are developing Golden Rice versions of existing rice varieties that are popular with their local farmers, retaining the same yield, pest resistance, and grain qualities. Golden Rice seeds are expected to cost farmers the same as other rice varieties. Once PhilRice, BRRI, and ICRR are able to secure an approval from their respective regulatory agencies, cooking and taste tests will be done to make sure that Golden Rice meets consumers' needs.

Safety assessment of Golden Rice The environmental safety of Golden Rice is assessed through field tests and other evaluations in each partner country. Golden Rice is analyzed according to internationally accepted guidelines for food safety.

Research and development of Golden Rice adhere to scientific principles developed over the last 20 years by international organizations such as the World Health Organization (WHO) , the Food and Agriculture Organization of the United Nations (FAO) , the Organization for Economic Co-operation and Development (OECD) and the Codex Alimentarius Commission . These are the same principles that inform the safety assessments of national regulatory agencies, such as FSANZ, Health Canada, and the US FDA, which have already assessed Golden Rice as safe to plant and safe to eat.

Nutrition evaluation by an independent organization After obtaining the necessary permits and approvals, an independent community nutrition study will be conducted to evaluate the contribution of Golden Rice to Vitamin A status of target communities.

Deployment of Golden Rice in priority areas IRRI supports its national partners in developing pilot-scale deployment strategies to ensure that Golden Rice reaches the farmers and consumers that need it the most. A sustainable delivery program co-designed by IRRI and its national counterparts will also be implemented to ensure that Golden Rice is affordable, acceptable, and accessible in vitamin A deficient communities.

For more information on Golden Rice, visit the Golden Rice FAQs .

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A plant that produces tomatoes in its leafy parts and potatoes in its roots? Well, this actually exists. It is called a pomato, marketed as TomTato , and is a chimera obtained by the classic technique of grafting. At the end of the 20th century, human beings learned to create molecular grafts, using the smallest pieces of a plant: its genes. But since then, genetically modified organisms (GMOs) have met with fierce opposition from a segment of society. The best example of this is Golden Rice; created in the 1990s, it has been lost in limbo for two decades and has not yet emerged, even though it could solve a vitamin A deficiency that affects a third of children under the age of five and causes more than 100,000 deaths a year . The story of Golden Rice illustrates the tensions surrounding GMOs, an innovation that was created for the benefit of humanity, but which has never quite taken off.

The Golden Rice tale begins in 1984, when the development of the first GM plant spurred interest in producing nutritionally fortified varieties. During a meeting organised at the International Rice Research Institute (IRRI) in the Philippines by the Rockefeller Foundation, the foundation’s head of biotechnology, Gary Toenniessen, asked the participants which gene they would like to see introduced into rice. Peter Jennings, an IRRI expert who had developed the successful IR8 variety in the 1960s, suggested creating a yellow grain. For years Jennings had been looking unsuccessfully for a variety of this colour, a sign of the presence of beta carotene, the precursor of vitamin A. Deficiency of this essential micronutrient in the diets of 250 million children is the leading cause of preventable childhood blindness and increases mortality from a weakened immune system.

A single cup to cover 60% of children’s daily vitamin A requirements

In the year 2000, with the encouragement of the Rockefeller Foundation, Golden Rice finally saw the light of day at the hands of Peter Beyer from the University of Fribourg and Ingo Potrykus from  the Swiss Federal Institute of Technology in Zurich. The two scientists used the Agrobacterium bacteria to insert the genes for the enzymes phytoene synthase ( psy ) from the daffodil and phytoene desaturase ( crtI ) from the soil bacterium Erwinia uredovora into the rice grain; both provided the grain with the necessary building blocks for completing the biosynthesis of provitamin A or beta carotene. In 2005, researchers at Syngenta Biotechnology replaced the psy gene from the daffodil with the psy gene from maize, creating a new improved version that produced 23 times more beta carotene.

The first transgenic crop designed to improve human nutrition was hailed as a breakthrough that promised to solve a serious problem. In subsequent years, studies confirmed that it was effective as a source of vitamin A , that a single cup would be sufficient to cover 60% of children’s daily vitamin requirements , that the introduced proteins were not allergenic and that it could be crossed with the most widely used local varieties . In 2018 it was approved in the USA, Canada, Australia and New Zealand. And yet, twenty years after its creation, it is still not grown for consumption anywhere in the world, nor has it been approved in the countries of the world that would benefit most from it.

“ I strongly believe that the benefits and safety of Golden Rice have been sufficiently supported by scientific evidence, ” Tuskegee University plant biotechnologist Channapatna Prakash, editor of the journal GM Crops & Food , tells OpenMind . And yet, the path towards the acceptance of this crop has been strewn with obstacles. In 2015, a study in China on its nutritional benefits in children was retracted when it was found that the trial had not passed the relevant ethical approvals, and families were not informed about the GM nature of the rice. Doubts also remain about the deterioration of beta carotene in stored or cooked grain and about the assimilation of this fat-soluble compound when fats are scarce in the diet, as is the case in many of the children targeted. But for the plant biotechnologist José Miguel Mulet, from the Polytechnic University of Valencia, “ as problems have appeared they have been solved. That’s how science works, ” he tells OpenMind .

Opposition to GMOs, a big stumbling block

A major stumbling block for Golden Rice has been opposition from a segment of society. “ The fears and cautions remain because anti-GMO activists who are opposed to Golden Rice simply keep saying so despite all the evidence to the contrary, and the complicit media provide airtime to them ,” Prakash says. Queensland University of Technology plant biotechnologist Jean-Yves Paul tells OpenMind about the opposition in the Philippines, a country that approved Golden Rice as safe to eat in December 2019, but where many steps have yet to be taken before it can be commercialised: “ The Philippines is a main driver of the criticisms and roadblocks. Activist and anti-GM groups are really active and well supported there and have severely damaged the image of Golden Rice over the years in a country where unfortunately this technology is much needed .”

The mistrust finds support in the UN’s Cartagena Protocol , which is guided by the precautionary principle to block GMOs even without testing, something that is not required of new varieties developed by other techniques, such as mutations produced by bombardments of radiation . “For more than 20 years, Golden Rice has undergone overwhelming studies on its biosafety, bioavailability, environmental impact, biodiversity, etc., and every conceivable question has been asked. It is probably the most intensively tested crop and food ever!” Prakash says. But for Ingo Potrykus, co-creator of Golden Rice, the rejection is complex: “Opposition to GMOs is in part a matter of scientific literacy but more so an emotional matter,” he tells OpenMind .

Economic feasibility

There are also criticisms from the academic community. Developing country agriculture experts Glenn Davis Stone of Washington University in St. Louis and Dominic Glover of the Institute of Development Studies question whether Golden Rice is capable of delivering on its promises , and not because of the opposition from activists. Glover tells OpenMind that the proclamation that rice will be offered free to farmers with incomes under $10,000 a year as a “humanitarian project” is a “misrepresentation.” “As far as we know, nobody has proposed that the seed will be provided for nothing, as a routine,” he notes. “It would be expensive to do so.”

Not only does Glover question whether farmers will, without subsidies, choose to grow Golden Rice over other varieties that offer different advantages such as “yield, disease resistance, tolerance to abiotic stresses, cooking qualities, consumer prices…,” but ultimately he doubts that it will really be the solution to vitamin A deficiency over more traditional alternatives such as nutritional programmes or encouraging more variety in crops. “What have been the opportunity costs of investing in Golden Rice rather than other strategies,” he asks.

For the moment, the roll-out of Golden Rice continues to stagnate. “Bangladesh was claimed to be on the brink of giving approval, but the decision was deferred indefinitely, for unstated reasons,” says Glover. Meanwhile, advocates of the crop condemn the obstruction. “It’s pure politics. There is no scientific reason,” Prakash laments. “All this delay while half million children may die or go blind this year because of vitamin A deficiency. It is beyond pathetic, it is criminal!” For his part, Potrykus is confident that his life’s work will eventually see the light of day: “The opposition will delay, but cannot prevent the use of Golden Rice.”

Javier Yanes

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Golden Rice is an effective source of vitamin A 1, 2, 3, 4

Background: Genetically engineered “Golden Rice” contains up to 35 μ g β -carotene per gram of rice. It is important to determine the vitamin A equivalency of Golden Rice β -carotene to project the potential effect of this biofortified grain in rice-consuming populations that commonly exhibit low vitamin A status.

Objective: The objective was to determine the vitamin A value of intrinsically labeled dietary Golden Rice in humans.

Design: Golden Rice plants were grown hydroponically with heavy water (deuterium oxide) to generate deuterium-labeled [ 2 H] β -carotene in the rice grains. Golden Rice servings of 65–98 g (130–200 g cooked rice) containing 0.99–1.53 mg β -carotene were fed to 5 healthy adult volunteers (3 women and 2 men) with 10 g butter. A reference dose of [ 13 C 10 ]retinyl acetate (0.4–1.0 mg) in oil was given to each volunteer 1 wk before ingestion of the Golden Rice dose. Blood samples were collected over 36 d.

Results: Our results showed that the mean (±SD) area under the curve for the total serum response to [ 2 H]retinol was 39.9 ± 20.7 μ g·d after the Golden Rice dose. Compared with that of the [ 13 C 10 ]retinyl acetate reference dose (84.7 ± 34.6 μ g·d), Golden Rice β -carotene provided 0.24–0.94 mg retinol. Thus, the conversion factor of Golden Rice β -carotene to retinol is 3.8 ± 1.7 to 1 with a range of 1.9–6.4 to 1 by weight, or 2.0 ± 0.9 to 1 with a range of 1.0–3.4 to 1 by moles.

Conclusion: β -Carotene derived from Golden Rice is effectively converted to vitamin A in humans. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00680355","term_id":"NCT00680355"}} NCT00680355 .

INTRODUCTION

The intake of vitamin A provides humans with an important nutrient for vision, growth, reproduction, cellular differentiation and proliferation, and integrity of the immune system. Vitamin A deficiency can result in visual or ocular malfunctions such as night blindness and xerophthalmia ( 1 ) and can reduce immune responsiveness ( 2 ), which can result in an increased incidence or severity of respiratory infections, gastrointestinal infections ( 3 ), and measles ( 4 ). Vitamin A can be obtained from food, either as preformed vitamin A in animal products (eg, eggs and dairy products) or as provitamin A carotenoids, mainly β -carotene in plant products (eg, dark-green leafy vegetables and fruit).

Clinical and subclinical vitamin A deficiency is still a problem, affecting 250 million schoolchildren worldwide ( 5 , 6 ). To prevent clinical vitamin A deficiency in developing countries, chemically synthesized vitamin A supplements have been distributed periodically to deficient populations ( 7 – 9 ). This has been shown to be an efficient and generally safe strategy. However, supplementation programs with a periodic mass distribution have been difficult to sustain because of high distribution costs. Recently, food-based interventions to increase the availability of provitamin A–rich foods and their consumption have been suggested as a realistic and sustainable alternative to overcome vitamin A deficiency globally ( 10 ). However, the efficacy of carotenoid-rich foods in the prevention of vitamin A deficiency has been questioned in several recent studies, which reported little or no nutritional benefit of vitamin A from the increased consumption of dark-green or yellow vegetables ( 11 , 12 ). Recently, studies have shown that the equivalency of vegetable provitamin A carotenoids to vitamin A is in the range of 10–27 μ g all-trans β -carotene to 1 μ g retinol activity ( 13 – 16 ). These studies showed that food matrices greatly affect the bioavailability of vitamin A and carotenoids.

In recent years, scientists have introduced the biosynthetic pathway for provitamin A carotenoids into staple foods, including genetically engineered Golden Rice, which contains 1.6–35 μ g β -carotene per gram of dry rice. Golden Rice–1, which was transformed with a construct containing a phytoene synthase gene from daffodil, contains 1.6 μ g carotenoids (0.8 μ g β -carotene) per gram of dry rice ( 17 ). Golden Rice–2 was transformed with a construct containing a phytoene synthase gene from maize and contains up to 35 μ g β -carotene per gram of dry rice ( 18 ). Because the vitamin A equivalency of various foods and supplements varies from 2 μ g β -carotene to 1 μ g retinol (when provided as a β -carotene supplement in oil) to 27 μ g β -carotene to 1 μ g retinol (when provided as vegetable β -carotene) ( 11 , 13 ), and this equivalency is matrix dependent, it is important to determine the vitamin A equivalency of β -carotene from Golden Rice. This information is critical for the purpose of designing informed, food-based nutritional strategies for rice-eating regions throughout the world where vitamin A deficiency is common. Because vitamin A is homeostatically regulated in the circulation of healthy subjects and it is impossible to distinguish the newly formed vitamin A from endogenous vitamin A ( 19 ), we chose intrinsic labeling of the provitamin A carotene as the optimal approach to determine its vitamin A equivalence. We produced intrinsically labeled Golden Rice, fed the rice to healthy volunteers, and used an isotope reference method to determine the conversion factor of Golden Rice β -carotene to vitamin A.

MATERIALS AND METHODS

Production of intrinsically labeled golden rice.

Rice seeds were imbibed and germinated on cheesecloth suspended over distilled water. After 4 d, seedlings were planted in trays suspended over 20-L tubs of nutrient solution containing the following macronutrients: KNO 3 , 1 mmol/L; KH 2 PO 4 , 1 mmol/L; Ca(NO 3 ) 2 , 1 mmol/L; MgSO 4 , 1 mmol/L; K 2 SiO 4 , 0.1 mmol/L; CaCl 2 , 25 μ mol/L; H 3 BO 3 , 25 μ mol/L; MnSO 4 , 2 μ mol/L; ZnSO 4 , 2 μ mol/L; CuSO 4 , 0.5 μ mol/L; H 2 MoO 4 , 0.5 μ mol/L; and NiSO 4 , 0.1 μ mol/L. No deuterium oxide was added. Iron was added in chelated form as Fe(III)HEDTA ( N -hydroxyethyl-ethylenediamine-triacetic acid) at 20 μ mol/L. MES buffer (adjusted with potassium hydroxide) was added at 2 mmol/L to maintain the nutrient solution pH between 5.4 and 5.8. Plants were maintained on this solution until flowering (≈3.5 mo after planting) in a greenhouse in Houston, TX; the nutrient solution was topped off, as needed, with a refill solution containing the same nutrients as above, but without additional MES buffer or K 2 SiO 4 . A complete change-out of the solution (using starting solution) was performed at 6-wk intervals. Approximately 7 d after flowering, the plants were transferred to a new nutrient solution containing 23 atom% 2 H 2 O, 20 μ mol/L Fe(III)HEDTA, 2 mmol/L MES buffer, and the following macronutrients: KNO 3 , 5 mmol/L; KH 2 PO 4 , 2 mmol/L; Ca(NO 3 ) 2 , 2 mmol/L; MgSO 4 , 1 mmol/L; K 2 SiO 4 , 0.1 mmol/L; CaCl 2 , 25 μ mol/L; H 3 BO 3 , 25 μ mol/L; MnSO 4 , 2 μ mol/L; ZnSO 4 , 2 μ mol/L; CuSO 4 , 0.5 μ mol/L; H 2 MoO 4 , 0.5 μ mol/L; and NiSO 4 , 0.1 μ mol/L. The 23 atom% 2 H 2 O allowed us to achieve a target peak enrichment of M + 9 [original mass of β -carotene ( M ) plus 9 atoms of 2 H] for the Golden Rice β -carotene (determined empirically in pilot studies). At this time, plants were also placed in a clear plastic-walled labeling system ( Figure 1 ), which maintained an elevated 2 H 2 O concentration in the gas atmosphere surrounding the plants and panicles. Plants were maintained on this media, with the solution topped off as needed (using the same 2 H 2 O solution) until the panicles had matured (≈3 wk later). During this labeling period, the temperature within the labeling system was maintained between 26 and 31°C, and the relative humidity was maintained between 45% and 55%. At maturity, whole panicles were collected and stored at −20°C until further processing. For processing, seeds were de-hulled with an Impeller Husker (model FC2K; Yamamoto Co, Ltd, Yamagata-ken, Japan); seeds were subsequently polished in small batches for 30 s with an electric grain polisher (model “Pearlest;” Kett Electric Laboratory, Tokyo, Japan). Polished seeds were stored at −80°C until shipped to Boston, where they were cooked and analyzed before the clinical studies.

Photograph of the labeling chamber (A) and system components used to produce polished Golden Rice-2 (B). Components of the labeling system: 1, Golden Rice-2 in deuterated nutrient solution at seed fill stage; 2, carbon dioxide sensor; 3, tower fan for air mixing; 4, air conditioning unit; 5, dehumidifier; 6, collection tub for transpired heavy water from plants (collected from dehumidifier); 7, carbon dioxide supply; 8, water-free air.

Rice preparation

The rice was cooked by using a rice cooker (SR-G18FG; Panasonic, Chachoengsao, Thailand) by adding water in a quantity of 150% weight of the rice. The rice was cooked for 30 min. Our analysis showed that the total amount of Golden Rice β -carotene in the dose was the same before and after it was cooked (0.99 or 1.53 mg β -carotene in a dose). The cooked rice was divided into portions (130 g cooked rice containing 0.99 mg β -carotene or 200 g cooked rice containing 1.53 mg β -carotene) and kept at −15°C until served within 1–3 mo. On the day of feeding, the rice was brought to room temperature and then heated with a microwave oven [60 s by using a Panasonic NN-Sensor 953 (Genius) 1350-W microwave oven, 2.2 cubic feet capacity].

Volunteers and study design

The study protocol was approved by the Tufts Medical Center Institutional Review Board. Persons who had not taken vitamin A or β -carotene supplements within the past month and who were not disqualified based on several exclusion criteria were eligible to become study volunteers. Potential subjects were accepted into the study if they had none of the following conditions: severe or symptomatic cardiac disease or hypertension; history of bleeding disorders; chronic history of gastric, intestinal, liver, pancreatic, or renal disease; any portion of the stomach or the intestine removed (other than an appendectomy); history of intestinal obstruction, malabsorption, or use of antacid drugs; cancer (active or use of medications for a history of cancer treatment within the past 5 y); history of chronic alcoholism; a convulsive disorder; or abnormal results in screening blood or urine samples. Five volunteers (2 men and 3 women) from the Boston area were admitted to participate in the study after they were interviewed and signed the Informed Consent Form for the study.

The full study for each volunteer lasted 36 d to draw several blood samples and to study blood response curves. On day 1 of the study, the volunteers consumed [ 13 C 10 ]retinyl acetate ( M retinol + 10) in an oil capsule as a reference dose. We first tested the use of 0.43 mg [ 13 C 10 ]retinyl acetate as a reference dose in one of the subjects. Subsequently, we used 0.99 mg [ 13 C 10 ]retinyl acetate as the reference dose for the other 4 volunteers to ensure successful detection of labeled retinol in each volunteer, even those with a higher body mass. The [ 13 C 10 ]retinyl retinyl acetate in an oil capsule was given together with 200 g cooked white rice, 10 g butter, 50 g peeled cucumbers, 0.2 g salt, 5 g vinegar, and a 500-mL bottle of water at breakfast (time 0). The total calorie content of the meal was ≈450 kcal (23% from fat). A second standardized meal (lunch) was eaten by all volunteers 4 h after the breakfast meal; this second meal contained 60 g turkey meat, 50 g white bread, 20 g roasted cashew, and 100 g cucumber (peeled) salad with 15 g corn oil and 5 g vinegar (total energy: 600 kcal, 40% from fat). On day 8 of the study, the volunteers consumed the same breakfast meal as on day 1, but 200 g white rice was replaced with labeled Golden Rice (either 130 g cooked Golden Rice together with 70 g cooked white rice containing 0.99 mg β -carotene or 200 g cooked Golden Rice containing 1.53 mg β -carotene). Also on day 8, the standardized lunch (as above) was eaten by all of the volunteers 4 h after the breakfast meal. The amount of Golden Rice in the breakfast meal varied because we were trying to study as many subjects as possible with a limited amount of intrinsically labeled rice. Our results showed that our method can effectively assess the vitamin A equivalency of β -carotene doses as low as 1 mg in rice.

A total of 30 serum samples (10 mL each) were obtained from each subject at the following time points: day 1 at 0 (just before the breakfast dose), 5, 8, 11, and 13 h (after the dose); day 2 at 0 (24 h after the dose taken before the day 2 breakfast), 5, and 11 h (after the day 2 breakfast); day 3 at 0 (48 h after the dose taken and before the day 3 breakfast) and 11 h (after the day 3 breakfast); days 4, 6, and 7 at 0 h (before each day's breakfast); day 8 at 0 (before the Golden Rice breakfast dose), 5, 8, 11, and 13 h (after the Golden Rice dose taken); day 9 at 0 (24 h after the dose taken and before the day 9 breakfast), 5, and 11 h (after the breakfast); day 10 at 0 (48 h after the dose taken and before the day 10 breakfast) and 11 h (after the day's breakfast); days 11, 13, 15, 19, 22, 29, and 36 at 0 h (before each day's breakfast) ( Figure 2 ). Fasting serum samples were collected at the 0-h time points. The serum samples were kept at −70°C until analyzed. The retinol ( M retinol + 10) derived from the [ 13 C 10 ]retinyl acetate dose, the retinol ( M retinol + 5) formed from the labeled Golden Rice β -carotene, and the intact Golden Rice β -carotene ( M + 9) were followed in all samples up until the end of the study.

Experimental design for the Golden Rice human study. Three sets of dashed lines are used to amplify the overall time period to progressively larger scales. The first order (upper scale) includes the entire 36-d study and sampling period. The second order (middle scale) represents days 1–15 of more frequent blood sampling. Each cell on the horizontal time axis represents a 24-h period, with the division line representing the fasting blood collection time (0 h). The cells in black represent days 1 and 8, the days on which the tracers were ingested. The third order (lower scale) is common for these 2 dosing and high-multiple blood-sampling days (days 1 and 8), with each cell on the time axis representing 1 h. The 0 time represents the first blood sampling of the day, and all other numbers represent the times of subsequent sampling (in h) relative to the time of first sampling. The anchor symbols represent the oral dosing of the tracer. The arrows indicate the times at which blood samples were collected. d, day in the study; h, hour after study dose or after fasting blood sample, RAc, retinyl acetate.

[ 13 C 10 ]Vitamin A as an isotope reference

To quantify the amount of vitamin A formed from the Golden Rice β -carotene, a known amount of vitamin A that is differently labeled can be used as a reference dose. We used 1 mg [ 13 C 10 ]vitamin A [in the present study: M retinol = retinol – H 2 O = m / z (mass/charge, a unit for mass spectrometry) 268, M [ 13 C 10 ]retinol = m / z 268 + 10 = m / z 278] in an oil capsule as a reference dose given 1 wk before the Golden Rice meal. Our initial test showed that our method can trace the vitamin A body response after ingestion of 0.43 mg [ 13 C 10 ]vitamin A—a physiologic dose.

Blood sample analysis

An HPLC instrument equipped with a C 18 column was used to separate the serum retinol ( 20 ). The fractions containing retinol in the HPLC eluent were collected individually and derivatized for gas chromatography/electron capture negative chemical ionization–mass spectrometry (GC/ECNCI-MS) ( 21 ) to measure retinol enrichment from the reference vitamin A dose ( M retinol + 10 = m / z 278) or Golden Rice β -carotene ( M retinol + 5 = m / z 273) dose. The total enrichment of labeled retinol was determined by the evaluation of negative ions at M retinol [ m / z 268–270 ( 13 C 0 − 13 C 2 )], M retinol + 5 [ m / z 273–277 ( 2 H 5 – 2 H 9 )], and M retinol + 10 [ m / z 278–280 ( 13 C 10 – 13 C 12 )]. The whole enrichment of the retinol from the Golden Rice β -carotene was calculated as 2 times the sum of the enrichment of M retinol + 5, M retinol + 6, M retinol + 7, M retinol + 8, and M retinol + 9 based on the assumption of the symmetric distribution of the labeled Golden Rice β -carotene.

Concentrations of serum carotenoids and retinoids were determined using HPLC equipped with a C30 column ( 22 ). For enrichment of intact β -carotene, liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry ( 23 ) was used to determine the absorption of intact β -carotene after consumption of the cooked Golden Rice.

Areas under the curve of labeled retinol or β -carotene in the serum

Total serum responses (nmol) to the [ 2 H] β -carotene dose and the [ 13 C 10 ]retinyl acetate dose were determined by multiplying the total serum volume (0.0435 L/kg body wt) by the concentration of [ 2 H] β -carotene and [ 2 H]retinol and [ 13 C 10 ]retinol in the circulation (nmol/L, determined for each time point of serum sampling by adding all of the enrichment masses). Areas under the curve (AUCs) for serum labeled retinol or β -carotene responses (in nmol·d) after the [ 2 H] β -carotene dose and the [ 13 C 10 ]retinyl acetate dose were calculated by using the curves of total serum responses (in nmol; y axis) compared with time (in d; x axis) via Integral-Curve of Kaleidagraph (Synergy Software, Reading, PA). The conversion of the AUC unit from nmol·d to μ g·d was done by using M retinol = 291 for [ 2 H 5 ]retinol and M = 296 for [ 2 H 10 ]retinol. Because of the 7-d delay in the administration of the Golden Rice dose, the AUCs were calculated for 21 d after each labeled tracer.

Retinol equivalence calculations

The AUC of serum [ 2 H]retinol response (from the labeled Golden Rice) was compared with the AUC of the vitamin A reference dose (0.4–1.0 mg [ 13 C 10 ]retinyl acetate; molecular mass = 336). The amount of 2 H retinol was calculated as follows:

Conversion factor calculations

The amount of a given oral dose of Golden Rice β -carotene (0.99–1.53 mg) compared with the amount of vitamin A derived from the β -carotene dose was defined as the β -carotene to vitamin A conversion factor. Thus, the conversion factor of Golden Rice β -carotene (calculated β -carotene from all -trans β - carotene plus one-half of all other provitamin A carotenoids) to vitamin A was determined as follows:

where 536 is the molecular mass of β -carotene, and 286 is the molecular mass of retinol.

Statistical analyses

Statistical analyses was performed to assess the significance of differences between vitamin A conversion factors by sex and to determine correlations between conversion factors and the BMI of each subject. Systat version 10.2 (Systat Software Inc) was used for data analysis.

Confirmation of intrinsically labeled Golden Rice with enriched β -carotene

We grew Golden Rice hydroponically with mineral nutrients and introduced 23 atom% heavy water ( 2 H 2 O) to the hydroponic medium after flowering ( Figure 1 ) to intrinsically label the Golden Rice β -carotene with deuterium ( 2 H). Our HPLC analysis showed that, in the grains, all-trans β -carotene was the dominant carotenoid (≈20 μ g β -carotene in a gram of dry rice) together with small amounts of lutein, anhydrolutein, zeaxanthin, cryptoxanthin, 13- cis β -carotene, and 9- cis β -carotene ( Figure 3 ). With this labeling method, the intrinsically labeled Golden Rice β -carotene showed a protonated molecule of m / z of M β c + H + = 536 + 1 (representing unlabeled β -carotene) and a range of isotopomers with the most abundant showing an enrichment of 9 deuterium at M enrich- β c = M β c + H + + 9 mass units ( Figure 4 ) as analyzed by using the liquid chromatography/mass spectrometry with a positive atmospheric pressure chemical ionization interface (the total m / z was M β c + 9 + H + = 536 + 9 + 1 = m / z 546) ( 23 ). This labeled Golden Rice β -carotene produces retinol with a most abundant peak mass at the ionized retinol plus 5 mass units derived from deuterium minus water (the result of ionization in the mass ionization chamber).

Chromatogram of Golden Rice carotenoids. Each labeled chromatographic peak represents an identified carotenoid compound: 1, lutein; 2, anhydrolutein; 3, zeaxanthin; 4, cryptoxanthin; 5, 13- cis β -carotene; 6, all - trans β -carotene; 7, 9- cis β -carotene.

Deuterium enrichment profile of Golden Rice β -carotene analyzed by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (positive ion mode). Hydroponic labeling does not produce uniform enrichment, but rather a range of isotopomers. The vertical axis represents the signal intensity. The horizontal axis represents the mass ( M + H + = mass plus hydrogen atom with positive charge) of the isotopomers. Unlabeled β -carotene is shown with a mass of 537. The most abundant isotopomer of labeled β -carotene (with 9 deuterium atoms) is represented by an m/z of 546. The enrichment of Golden Rice β -carotene is 86%.

Characteristics of volunteers

Five healthy nonsmokers (2 men and 3 women; age: 41–70 y; BMI: 22–29) were recruited as study volunteers. The characteristics of these subjects are presented in Table 1 . Concentrations of carotenoids and retinoids in serum samples collected at baseline and analyzed by using HPLC ( 22 ) are presented in Table 2 . These data showed that the vitamin A and carotenoid concentrations of the volunteers were in the normal range.

Characteristics of the 5 study subjects

Carotenoid and retinol concentrations in the serum of each subject at the beginning of the study 1

Blood response to a Golden Rice meal

Retinols labeled at M retinol + 5 or M retinol + 10 ( M retinol = m / z 268, representing unlabeled endogenous retinol) were detected in serum extracts, as shown in the middle and bottom panels of Figure 5 . The mass distribution of circulating retinol at baseline (day 1 at 0 h before the reference dose; top panel), the enrichment of M retinol + 10 = m / z 278 from the reference dose [ 13 C]retinyl acetate (day 1 at 13 h after the dose; middle panel), and the enrichment of M retinol + 5 = m / z 273 and M retinol + 10 = m / z 278 retinol (day 9 at 0 or 24 h after the Golden Rice meal; bottom panel) are shown in the figure. The kinetic responses of labeled M retinol + 5 = m / z 273 and M retinol + 10 = m / z 278 retinol up to 32 d from one subject are presented in Figure 6 .

Enrichment mass spectrometric profile of serum retinol samples collected from one subject. Top panel: profile obtained before ingestion of the labeled dose; data are an average of 11.3–11.6 min on the gas chromatography–mass spectrometry (GC/MS) chromatogram for a sample collected on day 1, 0 h. Middle panel: profile obtained after ingestion of the reference dose; data are an average of 13.7–13.8 min on the GC/MS chromatogram for a sample collected on day 1, 13 h after the [ 13 C 10 ]retinyl acetate dose. Bottom panel: profile obtained after ingestion of the labeled Golden Rice dose; data are an average of 11.3–11.6 min on the GC/MS chromatogram for a sample collected on day 9, 24 h after the Golden Rice meal. Arrows indicate signal intensities that were greater than the abundance values on the y axis.

Calculated labeled retinol species in the circulation of a representative volunteer, throughout the course of the study, after consumption of [ 13 C 10 ]retinyl acetate on day 1 and after a deuterium-labeled Golden Rice β -carotene dose on day 8.

The responses of the volunteers who consumed a reference dose on day 1 and a labeled Golden Rice dose (130 or 200 g cooked weight containing 0.99 or 1.53 mg labeled β -carotene, respectively) on day 8, together with 10 g butter, are presented in Table 3 .

Subject responses to a reference dose of [ 13 C 10 ]retinyl acetate and a Golden Rice meal with [ 2 H 9 ] β -carotene 1

For Golden Rice β -carotene, analysis of serum samples by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry ( 23 ) showed that the labeled β -carotene was absorbed intact after consumption of the cooked Golden Rice. Serum response kinetics of intact β -carotene are presented in Figure 7 .

Serial measurements of deuterium-labeled β -carotene in the circulation of a representative volunteer. Values are presented for the 25 d of monitoring after the oral dose of labeled Golden Rice.

Conversion factor of Golden Rice β -carotene to vitamin A

The AUC response of vitamin A ( M retinol + 5) formed from the dose of labeled Golden Rice β -carotene was compared with the AUC of the reference [ 13 C 10 ]vitamin A, up to 21 d ( Table 3 ). The Golden Rice containing 0.99 mg β -carotene provided 0.24–0.51 mg retinol, and the Golden Rice containing 1.53 mg β -carotene provided 0.24–0.94 mg retinol. It should be noted that at these physiologic doses (0.99–1.53 mg β -carotene), it is unlikely that the differences in dose would influence the outcome of retinol equivalence per milligram of β -carotene. Acknowledging that we had a limited number of subjects ( n = 5), statistical analysis showed that there was no difference in the calculated conversion factors between subjects taking 0.99 or 1.53 mg Golden Rice β -carotene. Altogether, our results show that the conversion factor of Golden Rice β -carotene to retinol is 3.8 ± 1.7 (mean ± SD) to 1 with a range of 1.9–6.4 to 1 by weight, or 2.0 ± 0.9 to 1 with a range of 1.0–3.4 to 1 by mol, as presented in Table 3 . The conversion factors between men ( n = 2) and women ( n = 3) were not different. In addition, in these 5 subjects, there was no correlation between the conversion factors and BMIs.

Golden Rice is a bioengineered crop with yellow-colored endosperm that contains β -carotene (provitamin A). To produce Golden Rice, 2 enzymes are introduced into the endosperm [phytoene synthase (psy) and phytoene desaturase (crtl)] via an endosperm-specific glutelin (Gtl) promoter ( 15 ), to establish a β -carotene biosynthetic pathway in the rice grains. This is the first study on the vitamin A value of Golden Rice in humans, and our analysis showed a very efficient bioconversion of β -carotene to vitamin A ( Table 3 ). Using a conversion factor in which 3.8 μ g Golden Rice β -carotene provides 1 μ g retinol, along with the level of Golden Rice β -carotene being 20–30 μ g/g uncooked rice, we project that 100 g uncooked rice provides 500–800 μ g retinol. This represents 80–100% of the estimated average requirement (EAR) for men and women and 55–70% of the Recommended Dietary Allowance (RDA, derived from the EAR) for men and women, as set by the US National Academy of Science ( 24 ). In the United States, the EAR and RDA for vitamin A were set based on the amount needed to provide 4 mo of vitamin A storage in the body. For children, additional study of Golden Rice β -carotene conversion to retinol is needed. However, we speculate that 50 g uncooked Golden Rice, which is a reasonable serving size for children aged 4–8 y in rice-eating regions, who eat ≈130–200 g rice/d ( 25 ), would be able to provide >90% of vitamin A EAR (275 μ g retinol/d) or >60% of the RDA (400 μ g retinol/d) ( 24 ).

In this study, we used a combination of state-of-the-art approaches to determine the vitamin A equivalence of Golden Rice in humans. Plants were grown hydroponically in heavy water to intrinsically label Golden Rice β -carotene with deuterium. The subjects were fed both the labeled rice and a reference dose of differently labeled retinol. Sensitive mass spectrometry approaches were used to analyze both β -carotene and retinol enrichment in serum with stable isotope labeling, which allowed us to easily discern Golden Rice and reference dose molecules from preexisting, endogenous β -carotene and retinol. Our subsequent results, based on a small number of US volunteers, showed the effective conversion of Golden Rice β -carotene, even though all individuals were of normal vitamin A status. Whether this conversion efficiency is a good approximation for rice-eating populations with marginal-to-severe vitamin A deficiency, or perhaps is a conservative underestimate, has yet to be determined. To provide information for public health or public policy purposes, a larger long-term trial targeting individuals with marginal vitamin A status is needed. For instance, an isotope dilution approach could be used to evaluate changes in whole-body vitamin A stores ( 26 ) after an extended feeding period of Golden Rice with incorporation of the rice into daily diets.

The food matrix plays an important role in determining the bioavailability of vitamin A from provitamin A carotenoids in a particular food. Rice has a simple and easily digestible food matrix, which allows for a high bioavailability and bioconversion of β -carotene to vitamin A. Similarly, spirulina, with its simple food matrix, has also shown a highly efficient conversion factor for β -carotene to vitamin A of 4.5 to 1 by weight in humans ( 27 ). To combat vitamin A deficiency, consumption of locally available vegetables, fruit, and other plant foods, such as algae products, should be encouraged. Each of these plant foods can contribute to vitamin A nutrition, although the conversion of the provitamin A carotenoids within them may not be equivalent. Conversion factors for provitamin A carotenoids from various plants have been reported as 12 to 1 for fruit ( 14 , 28 ), 13 to 1 for sweet potato ( 15 ), 15 to 1 for carrots ( 16 ), and 10 to 1 ( 15 ), 21 to 1 ( 16 ), 26 to 1 ( 14 ), 27 to 1 ( 13 ), and 28 to 1 ( 28 ) for green leafy vegetables. Thus, comparatively speaking, Golden Rice has a very favorable conversion ratio.

It should be noted that we closely monitored our subjects for any possible adverse effects after the consumption of Golden Rice and found no evidence of any problems, including allergic reactions or gastrointestinal disturbance. Although this attests to the probable safety of Golden Rice, we acknowledge that only a single serving was fed to each study subject. A much longer exposure with a larger cumulative consumption of Golden Rice would be needed to make definitive assertions regarding the inherent safety of this food for human use.

Staple foods should not only provide energy but also nutrients in a bioavailable form. Thus, Golden Rice may be a cost-effective staple food for combating vitamin A deficiency in rice-eating populations ( 29 ). Other provitamin A–containing staple foods, such as corn, cassava, sweet potato, and sorghum should be developed to serve other vitamin A–deficient populations with different food cultures.

Acknowledgments

We thank the Metabolic Research Unit of the Jean Mayer USDA Human Nutrition Research Center on Aging for recruiting our volunteers and for performing the human study procedures and David Dworak and Chee-Ming Li of the USDA/ARS Children's Nutrition Research Center for helping to label and produce the Golden Rice.

The authors' responsibilities were as follows—GT: designed the study, supervised the data collection, analyzed the data, and wrote the manuscript; JQ: collected and analyzed the samples; GGD: supervised the mass spectrometric analysis and revised the manuscript; RMR: supervised the human study as the study physician and revised the manuscript; and MAG: designed the production methods for the labeled Golden Rice, harvested the labeled Golden Rice for the study, and revised the manuscript. No financial benefit was obtained from this research study.

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Five Questions with Professor Stanley Kowalski: The Enduring “Golden Rice” Case Study

Forging connections between intellectual property, global health, food security, and biotechnology

Published by Prof. Stanley Kowalski twenty years ago in the final issue of the renowned peer-reviewed Franklin Pierce Law Center journal, RISK: Health, Safety & Environment , and one of the most popular downloads in UNH Franklin Pierce’s IP library, “Golden Rice: A Case Study in Intellectual Property Management and International Capacity Building”, has now been included in the prestigious Elgar compendium , Intellectual Property and Agriculture .  This compendium is a collection of articles from the past century which have had significant impact in the field of intellectual property and agriculture. 

Please provide a brief description of what your article is about and why you wrote it when you did. Why was it relevant then?

The Golden Rice RISK article has not only endured, but it has also gained scholarly momentum, as evidenced by numerous citations and over a thousand downloads.  It is more topical now than when first published two decades ago.  This remarkable endurance illustrates the continuing legacy of the Franklin Pierce Law Center, from its bold pioneering origin five decades ago to the present powerhouse, with Dean Megan Carpenter continuing to forge forward, opening new vistas, and creating new opportunities. 

Golden Rice, genetically engineered rice which accumulates β-carotene (provitamin A) in the endosperm, is a harbinger of bio-innovation sorely needed to address looming global challenges in this century.  As a complex agricultural biotechnological product comprising multiple inputs and processes, Golden Rice, required correspondingly sophisticated intellectual property management to reach those who most need it in their diets, that is, malnourished children suffering from vitamin-A deficiency, e.g., blindness, chronic illness, and mortality.  The intellectual property embedded in Golden Rice was identified, analyzed, and then strategically accessed via creative licensing and technology transfer.  Thus, the saga of Golden Rice represents a concise illustrative case study of how intellectual property and technology transfer can address and abate critical global issues in health, nutrition, and food security. 

Why do you think it continues to be relevant today and is such a popular download in the IP library?

By forging connections between intellectual property, global health, food security and biotechnology, all in the context of international development, the article illustrates the power of merging intellectual property and the public interest.  Specifically, the article has a key message: the importance of strategic management of intellectual property to accelerate research, development, assembly, and global access to critical bio-innovation in health and agriculture.  Such bio-innovation includes improved crop varieties, green energy, medicines, and vaccines.

What are your thoughts on the growth of IP during the time between the two publications of this article—what’s different and what’s the same?

Over the past two decades, globalization has moved from being a somewhat arcane concept to a pressing reality.  The coronavirus pandemic, climate change and biodiversity destruction illustrate this principle clearly and loudly.  The RISK Golden Rice article provides a practical roadmap for meeting these challenges, that is, a systematic methodology to strategically manage intellectual property in order to accelerate global access to critical innovations in agriculture, green energy, and health.  The problems of twenty years ago have simply magnified, and thus the relevance of the article has likewise increased. 

What scholarship are you working on now?

Currently I am in the very early stages of researching and outlining a study which explores the interconnectedness of biodiversity and genetic resources, bio-innovation, intellectual property, and conservation.  This study is in the context of the international treaty, the Convention on Biological Diversity (CBD), which aspires to balance access, use and conservation of genetic resources.  This, of course, is related to climate change, emerging global health challenges and food security.  It is both compelling and complex, to put it mildly.  Management of intellectual property assets and strategic technology transfer will be key to developing sustainable systems. And as the case study of Golden Rice exemplifies, the urgency of such system development will increase as we traverse this century. 

Anything else you’d like to share?

The RISK article on Golden Rice which I authored nearly two decades ago in a sense epitomizes the legacy of the Franklin Piece Law Center, and what it was so well known for: a pioneer, years ahead of all the rest, innovative, inclusive, interdisciplinary, and globally focused, tackling critical issues at the intersection of intellectual property, international development, and the public interest.  And this tradition continues in new and exciting ways; it’s in our DNA.  Under the visionary leadership of Dean Carpenter, the Franklin Pierce School of Law remains an innovative leader, with exciting programs, renowned faculty, and a forward-looking perspective.  As a dynamic thought leader in the field of legal education and intellectual property, Dean Carpenter’s outside of the box approach has fostered a plethora of awesome and cutting-edge programs, decades ahead of the rest, innovative, bold, and courageous.  Indeed, it is a safe prediction that scholarship that is current now, as the RISK Golden Rice article had been decades ago, will be even more impactful decades into the future, for example the Deflategate controversy (Prof. McCann), the “Slants” offensive, scandalous, and immoral trademark litigation (Prof. Roberts), and the intersection of copyright, pornography, and feminist legal theory (Prof. Bartow).  All told, the pioneering legacy of the Franklin Pierce Law Center lives on in the Powerhouse. 

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CASE STUDY: GOLDEN RICE

Related Papers

International Journal of Social Science and Interdisciplinary Research

Dr.Basil B Mathew

The improvement of plants and livestock for food production and the use of different conservation techniques have been practice as long as the human kind stopped migrating relying on agriculture for survival. With the quest to grow more food to meet the demand of our fast growing population, genetic engineering of crops has become a new platform in addition to plant breeding. Golden rice is a variety of rice produced through genetic engineering to biosynthesis beta-carotene, a precursor of vitamin A. The research of the golden rice was conducted with the goal of producing a fortified food to be grown and consumed in areas with the shortage of dietary vitamin A. Here we explore the debate surrounding golden rice and the politics of Genetic modified organism and the concerns and challenges.

Gary L Comstock , Kristen Hessler , J. Fletcher , Ross Whetten

An interactive classroom exercise for guiding discussions of ethical concerns about agricultural biotechnology.

Scott Kaplan

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H.P.S. Sachdev

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Malaysian Journal of …

MOHAMAD RAIS MUSTAQIM HARON

Golden rice was developed by the insertion of carrot gene into rice to solve vitamin A deficiency problem. Past studies have shown that consumer acceptance of genetically modified (GM) food is driven by many factors, of which moral aspects was found to be an ...

Kym Anderson

The first generation of genetically modified (GM) crop varieties sought to increase farmer profitability through cost reductions or higher yields. The next generation of GM food research is focusing also on breeding for attributes of interest to consumers, beginning with ‘golden rice’, which has been genetically engineered to contain a higher level of vitamin A and thereby boost the health

Shambu Prasad Chebrolu

Environment and Development Economics

david zilberman , J. Wesseler

Golden Rice contains the genes essential to activate the biochemical pathway for the production pro-vitamin A. Thus this biochemical pathway is activated especially in the endosperm. The intensity of the “golden colour” represents the concentration of pro-vitamin A. In developing countries, 500,000 people become blind each year and up to 6,000 die per day from vitamin A-malnutrition. This is despite enormous efforts from public and philanthropic institutions to reduce this medical problem with the help of traditional interventions such as supplementation, fortification, encouragement for diet diversification, etc. This heavy toll that poor people in developing countries are deprived of the basic nutrition needed to sustain life. Biotechnology is one of the several means to achieve and sustain food security, equitable access to health services, a safe environment, and industry development. In agriculture, biotechnology can be applied in many different ways, and one of the most well-known and talked-about is through the development of genetically modified (GM) crops. Farmers and consumers benefit from rice genetic research because it leads to new rice varieties that have higher yield, higher quality, and are more resistant to pests, diseases, and the effects of climate change. The potential benefits of GM rice are also important, particularly around improving nutrition. Once Golden Rice varieties have passed the national bio-safety procedures, it will be made available to subsistence farmers free of cost It will become the property of the farmers so that they can grow it year after year and use part of their harvest for the next sowing without additional costs. The farmers will use their traditional farming systems which do not require any additional agronomic inputs.

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Golden Rice

An Intimate Debate Case

By Annie Prud’homme-Genereux

Share Start a Discussion

In this intimate debate case, students consider whether to support the development and use of Golden Rice as a means to alleviate vitamin A deficiency in the developing world. Since many of the arguments typically raised against genetically modified organisms (GMOs) do not apply to this particular GM crop, students are forced to analyze the facts rather than rely on what they have heard in the media. Teams of students are presented with evidence that supports either the pro or con position. Based on this information, they formulate arguments to defend their position, then present their case to another team. Each team also listens to arguments from a team defending the other position. Listening skills are developed in addition to scientific argumentation skills, since in the next phase of the debate students must defend the opposite position. This is followed by a whole-class discussion that explores broader issues and questions introduced by the case.  Developed for an introductory molecular biology undergraduate course, the case could also be used at more advanced levels.

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Date Posted

• Describe concepts associated with GMOs such as monoculture, cross-fertilization of crops, allergenicity, and patents.
• Examine the arguments supporting and opposing the use of a GMO.
• Evaluate the merits of using Golden Rice to alleviate vitamin A deficiency in developing regions.
• Consider the socio-political causes and implications of malnutrition in developing countries and propose the best strategies to remedy it in the long-term.

Golden rice; genetic engineering; genetically modified organism; GMO; vitamin A deficiency; gene patent and licensing; Potrykus; developing world; bioethics

Subject Headings

EDUCATIONAL LEVEL

High school, Undergraduate lower division, Undergraduate upper division

TOPICAL AREAS

Scientific argumentation, Social justice issues, Social issues

TYPE/METHODS

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Teaching notes are intended to help teachers select and adopt a case. They typically include a summary of the case, teaching objectives, information about the intended audience, details about how the case may be taught, and a list of references and resources.

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Why I Stopped Defending GMOs

The scientific evidence is important, but there’s more to consider..

After my first child was born, I was terrified that something bad would happen to her. I compulsively checked my stove, the locks, and my baby’s breathing in futile attempts to assuage my overwhelming fears. The parenting books, the internet forums, Dr. Oz, and the news outlets I turned to suggested that every choice could make or break my kid’s well-being. They told me that harmful chemicals lurked around every corner—in infant formula, household products, and the foods she would soon eat.

I decided to fight my fears with evidence. Over the next two years, I taught myself to read peer-reviewed scientific literature. Going straight to the primary source behind the stories, and the worries, was a desperate attempt at self-preservation. It worked to some extent. Knowledge and meds brought me out of the worst of the terror that had started with my first child in 2011 in time for the birth of my second in 2013. Eventually, I found a good behavioral therapist to help with the rest.

But I was left resentful of all of the unscientific fearmongering. I channeled the resentment into blogging, intending to arm worried parents with tools to navigate all of the scary information. Among those who exploited parents’ natural fears, the anti-GMO movement was a big one: GMOs kept popping up as the purported culprit for a gamut of problems, from obesity to infertility to the commodification of life forms in the world our children are set to inherit.

I looked at claim after claim that GMOs were harmful and found them riddled with misinformation. I learned about the financial, political, and ideological motives behind a slew of prominent players who systematically mischaracterize genetic engineering. I found, as William Saletan did in an investigation for Slate in 2015 , that the case against GMOs is full of fraud and lies.

I wanted to shout it from the rooftops. Not only were GMOs safe, they were wonderful: To me, the precise transfer of genes to confer desired traits seemed downright elegant. Papaya with an added gene is now practically vaccinated against a virus that nearly wiped it out? Potatoes and apples—like the ones I learned about on an all-expenses-paid trip to Arctic Apples orchards—that don’t brown? Well, slap an “I ♥ GMO” T-shirt on me and hand me a megaphone , I thought. That’s exactly what I did . I didn’t just wear the shirt—I became a leader in the pro-GMO movemen t .

My enthusiasm didn’t just come from my personal relief. It also felt morally correct. Among the biggest darlings of genetic modification is golden rice, engineered to be rich with beta carotene—the precursor to vitamin A—which gives the grain a yellow hue. Vitamin A deficiency (VAD) is the leading cause of preventable blindness in children globally and increases susceptibility to infectious disease. Proponents argue that this staple food— this “gift” to the developing world — could save the lives and health of millions of poor children whose diets consisted mainly of rice. As a parent who had worried so much about her own children, it felt natural to worry about other children too—children whom the GMO movement could help if only the anti-science crowd, the crowd who’d fallen for all that fearmongering, would back down. “Like most kindhearted and empathetic people, my heart breaks for those less fortunate,” I wrote in a 2014 blog post, titled “Good, Kindhearted Parents are Pro-GMO,” which used the global potential of golden rice as a case study.

I refuted piles of misinformation on GMOs in my writing (including in Slate ). Some of my colleagues and I launched the #Moms4GMOs campaign, which soon led to Science Moms , a crowdfunded 2017 film about vaccines, alternative medicine, and food. In 2015, I co-founded the pro-GMO March Against Myths (MAMyths) to “take science to the streets” and counterprotest the annual March Against Monsanto , which promotes the spectrum of misinformation about not only GMOs but vaccines, Bill Gates, autism, and more. We carried signs with slogans like “Biotech for the People,” and “GMO Saved the Hawaiian Papaya.” We chanted: “What do we want? Safe technology! When do we want it? We already have it!”

Soon, MAMyths chapters were active across the U.S. and around the world. My co-founders and I were featured in Food Evolution , a “pro-science” documentary that shed light on the truth about GMOs and was narrated by Neil deGrasse Tyson, whom the New York Times billed as “the most credible public scientist on the planet” in its review.

I held contempt for GMO opponents who, as I put it in a piece for Forbes, “would rather throw tantrums” than accept the safety and potential benefits of biotechnology. We were on two clear, separate sides, each with our signs, and our chants, and our polarized views. Specifically, the other side opposed solutions to the suffering and death of millions . In the summer of 2016, when none of the countries that golden rice was made to help had taken it up, more than 100 Nobel laureates published an open letter accusing Greenpeace and other activists of “crimes against humanity” for their opposition to golden rice and other humanitarian GMOs, and urging them to stop “for the sake of the developing world.” Richard Roberts, who spearheaded the letter, told me for a Forbes story that parenthood had shaped his worldview too: “Being a father makes one truly cognizant of the value of human life.”

The 2016 general election is what began to make me question belonging to the pro-GMO community, which counts everyone from farmers to environmentalists to science fans among its ranks. We had never really talked about politics, so it had been easy to assume that I’d been holding a picket sign next to people who’d oppose the presidential candidate refusing to make basic statements about believing in science and supporting social justice. Those, after all, were my reasons for being so enthusiastic about GMOs to start with. But after the election it was clear from social media that some not only supported Trump—a blatantly racist, misogynistic candidate who flouts facts—but also taunted those of us who were upset about the victory in posts on social media. It was gut-wrenching. As I stepped back from the movement a bit, I began to see its tactics as domineering, more eager to outargue the other side than have a dialogue that weighs all of the facts. In August of 2017, one of Monsanto’s communications directors suggested that high-yield GMO corn is a technology that only “fearmongers” oppose. But it’s not anti-science to question the sheer quantity of genetically modified corn grown in the U.S., I thought. Little by little, I and others, including my MAMyths co-founders, began to question being “pro-GMO.”

The last straw for me (for many of us) came in January of 2018 when Monsanto invited alt-right hero (at the time, anyway) Jordan Peterson to speak at the annual American Farm Bureau Federation conference about farming and about “allowing ideologies to grow unopposed.” I wrote a story for Slate questioning the decision to invite Peterson, noting that the “ideologies” that he opposes are what I’d consider basic levels of respect for people who are not white men—that is, people like me. Soon after the Slate story went live, GMO advocates, including farmers and scientists—the very people I’d been siding with in the GMO movement— rushed to Monsanto’s defense . I detailed the fallout in a piece for Undark . I explained that, in my view, Monsanto’s objective seemed to be to equate an opposition to GMOs with a belief in Bigfoot, something to be debunked perhaps with the tone of an exasperated parent, not engaged with in good faith. I had a new perspective: Maybe the rustling in the trees wasn’t sasquatch, but it was worth investigating.

As the pro-GMO movement broke ranks, I started paying close attention to the calls to decolonize science and decenter the views and legacies of white, European men. Writing in the Conversation in April 2018, Rohan Deb Roy, a lecturer in South Asian history, explained that “for imperialists and their modern apologists , science and medicine were among the gracious gifts from the European empires to the colonial world.” The legacy of colonialism in science is still alive and well, he explains: “When an economically weaker part of the world collaborates almost exclusively with very strong scientific partners, it can take the form of dependence, if not subordination.” I realized that this sounded a lot like the model of “gifting” GMOs. My own grandparents lived under British colonial rule in India. It was unnerving for me to realize that proponents of golden rice—including, at one point, me—suppose that less developed countries simply need a little technological help from a society that knows more than they do. It’s, well, paternalistic.

I still craved more evidence, but this time not about the biology of GMOs. I wanted to understand the social science of the people and economies they are purportedly designed for. In the case of golden rice and other humanitarian GMOs, that evidence is pretty clear that GMO technology has not helped and has led to some objectionable consequences. “If history is any indicator, genetically-modified (GM) crops may actually render African farmers and scientists more, not less, reliant on global actors and markets,” Joeva Rock, an anthropologist at UC–Berkeley, and Rachel Schurman, a sociologist at the University of Minnesota, write of their research into the social impact of GMOs spread by Western countries. Suggesting that golden rice is a “gift,” ostensibly because it would be given free of charge to the poorest farmers, seems benevolent. But no one is putting out a pile of GMO seeds free for the taking and then just leaving the content alone. Farmers get the rice under a humanitarian license , which means there are strings attached. As Rock and Schurman explain in their latest study , Western entities that distribute GMOs abroad, like the Gates Foundation–funded African Agricultural Technology Foundation, have become embedded within governmental agencies throughout the continent. That gives these groups outsize influence in public policy. The crop isn’t truly free—it comes in exchange for reliance on and control by Western entities.

Rather than pushing GMOs like golden rice, anyone who is honestly concerned about malnutrition “would start by looking into what tools [already seem] to be effective,” Glenn Davis Stone, a professor of anthropology and environmental studies at Washington University in St. Louis, told me in an email. There have been improvements in nutrition that have nothing to do with golden rice, he explained, referring to studies showing that the prevalence of VAD has dropped from 39 percent to 29 percent globally between 1991 and 2013, and from 40 percent to 15 percent between 2003 and 2008 in the Philippines . “GM crops played no role in this,” he said. Studies suggest that these gains were achieved with vitamin supplementation, fortification of foods, nutritional education, and increasing the diversity of diets—and increasing access to those could help even more people. Too many proponents invested in GMOs like golden rice, either monetarily or emotionally, are “using the world’s poorest sickest little kids to sell it,” he says. “Talk about crimes against humanity.”

Personally, I still love a good GMO—particularly Impossible burgers, made with yeast engineered to produce a protein that mimics blood—and so do many of my justice-driven allies. But we’ve learned the hard way that people fighting for a common cause don’t always share their values. We still care about food and farming, but our focus has shifted to social and environmental justice in the food system, rather than advocating for particular technologies.

When it comes to the bigger picture, I prefer to take a more nuanced view of food systems, power dynamics, and legacies of colonialism, and look beyond the outlandish parts of opposition to science and technology to the evidence-based concerns. Sometimes solutions might involve genetic engineering, sometimes not. When it comes to golden rice, questioning its impact and the motives behind it is not “anti-science,” and it’s not up to GMO proponents to decide what’s best.

The ENVS Experience

Blake Slattengren's Student Site

Golden Rice Case Study

April 3, 2016 By Blake Slattengren

Golden Rice is a famous example of the possible benefits of genetically modified organisms. It was originally engineered in 2000 in order to produce ß-carotene to combat vitamin A deficiency world-wide (Ye 2000). This was proposed as an interesting and unique solution to a problem that effects millions of people, mainly in impoverished countries in Africa and Southeast Asia (Dawe 2002). In particular, it could help cure child blindness that plagued countries in the global South (Dawe 2002). In 2000, media attention was huge, and TIME magazine proclaimed “This Rice Could Save a Million Kids a Year” (Philpott 2016). It also held interesting implications for the the future of food consumption. If we can, should we make mass-produced food healthier, without the use of fortification? Like many technologies before it, this held promise of a bright, new future where technology saves us from some the biggest problems around. However, despite the promise of greatness, Golden Rice failed to take off and, over 15 years after its inventing, it has never been planted commercially.

This failure that Golden Rice has become has resulted from several factors. First, the Golden Rice doesn’t plant at the same yields or is as consistent as regular rice plants (What Is… 2016).  While further studies and research is being done by the International Rice Research Institute (IRRI) and the Philippine Rice Research Institute, Golden Rice is not yet at a point where is makes economic sense to instate the rice on a commercial scale (What Is… 2016).

In addition, there is backlash among many who are cautious or against the rise of GM foods. Many developing nations have adopted the Cartagena Protocol on Biosafety, a set of regulations for the cautious and limited testing of GM life (Philpott 2016). The US and other developed countries do not instate such restrictions resulting in development of GM products that is quicker and conducted with less caution. On top of this, anti-GM activists strongly oppose any research and have gone to such lengths as burning crops planted by the IRRI (Philpott 2016). These political and social barriers make it difficult for the continued research needed for the possibility of an economically feasible Golden Rice, and even then it is hard to say that the research will pay off with a superior rice.

The implementation of Golden Rice was held back by several factors. The original implementation seemed smooth with humanitarian, free access granted to Golden Rice seeds for global farmers looking to make less than $10,000 annually (Dobson 2000). The principal inventor, Professor I ngo Potrykus, stated in 2000,‘‘I now very much hope that others having intellectual property rights used in the development of golden rice will follow the generous example of Monsanto and also provide a royalty-free license for the humanitarian use of the technology and its transfer to developing countries” (Dobson 2000). While the humanitarian intentions are clear, the development is still held back by political, social, and technological limitations.

Learning from this, it is clear that technology alone is no way to fix any problem. While the Golden Rice seemed potentially world-changing in theory, it still has yet to become a practical invention, and it may never achieve that status. A great, radical idea and tech demo are not enough to fix a wicked problem on the scale of global health concerns. The limitations of a technology and society have to be taken into consideration. However, Golden Rice is certainly not a total failure. Even if it is never commercially produced, the innovative idea has changed what is considered possible with GM foods. If not Golden Rice, maybe some other GM food will make healthier food widely accessible.

• Dawe, D., R. Robertson, and L. Unnevehr. 2002. “Golden Rice: What Role Could It Play in Alleviation of Vitamin A Deficiency?” Food Policy 27 (5–6): 541–60. doi:10.1016/S0306-9192(02)00065-9.
• Dobson, R. 2000. “Royalty-Free Licenses for Genetically Modified Rice Made Available to Developing Countries.” Bulletin of the World Health Organization 78 (10): 1281.
• Paine, Jacqueline A., Catherine A. Shipton, Sunandha Chaggar, Rhian M. Howells, Mike J. Kennedy, Gareth Vernon, Susan Y. Wright, et al. 2005. “Improving the Nutritional Value of Golden Rice through Increased pro-Vitamin A Content.” Nature Biotechnology 23 (4): 482–87. doi:10.1038/nbt1082.
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Impact of aerosol concentration changes on carbon sequestration potential of rice in a temperate monsoon climate zone during the COVID-19: a case study on the Sanjiang Plain, China

• Research Article
• Published: 06 April 2024

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• Xiaokang Zuo 1 &
• Hanxi Wang   ORCID: orcid.org/0000-0003-4130-6981 1 , 2  

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The emission reduction of atmospheric pollutants during the COVID-19 caused the change in aerosol concentration. However, there is a lack of research on the impact of changes in aerosol concentration on carbon sequestration potential. To reveal the impact mechanism of aerosols on rice carbon sequestration, the spatial differentiation characteristics of aerosol optical depth (AOD), gross primary productivity (GPP), net primary productivity (NPP), leaf area index (LAI), fraction of absorbed photosynthetically active radiation (FPAR), and meteorological factors were compared in the Sanjiang Plain. Pearson correlation analysis and geographic detector were used to analyze the main driving factors affecting the spatial heterogeneity of GPP and NPP. The study showed that the spatial distribution pattern of AOD in the rice-growing area during the epidemic was gradually decreasing from northeast to southwest with an overall decrease of 29.76%. Under the synergistic effect of multiple driving factors, both GPP and NPP increased by more than 5.0%, and the carbon sequestration capacity was improved. LAI and FPAR were the main driving factors for the spatial differentiation of rice GPP and NPP during the epidemic, followed by potential evapotranspiration and AOD. All interaction detection results showed a double-factor enhancement, which indicated that the effects of atmospheric environmental changes on rice primary productivity were the synergistic effect result of multiple factors, and AOD was the key factor that indirectly affected rice primary productivity. The synergistic effects between aerosol-radiation-meteorological factor-rice primary productivity in a typical temperate monsoon climate zone suitable for rice growth were studied, and the effects of changes in aerosol concentration on carbon sequestration potential were analyzed. The study can provide important references for the assessment of carbon sequestration potential in this climate zone.

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The authors thank the reviewers for their valuable comments, and the authors thank the editor for his efforts in this paper.

This research was funded by the High-level Talent Foundation Project of Harbin Normal University (No. 1305123005).

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Zuo, X., Wang, H. Impact of aerosol concentration changes on carbon sequestration potential of rice in a temperate monsoon climate zone during the COVID-19: a case study on the Sanjiang Plain, China. Environ Sci Pollut Res (2024). https://doi.org/10.1007/s11356-024-33149-5

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