**6. Biofortification: Pioneers and the future**

The creation of what became known as Golden Rice was announced by Ingo Potrykus at the XVI International Botanical Congress in St. Louis in early August 1999, a very large meeting involving 20,000 room nights and 4700 delegates from 85 countries [72], and published in "Science" in January 14, 2000 [73]. Golden Rice was widely reported, including on the front covers of the American and Asian (but not European) editions of Time Magazine on July 31, 2000.

The Second CGIAR-wide conference on Nutrition was held at the International Rice Research Institute in October 1999, organized by Howarth Bouis. On January 1, 2000 "Food and Nutrition Bulletin" ("intended for healthcare professionals") published 41 papers of this conference: "Improving human nutrition through agriculture: the role of international agricultural research", many of them anticipating feeding trials to be started soon [74].

The conference summary and recommendations were written by Dr. Bouis, subsequently Director, and then Emeritus Fellow, of Harvest Plus and a World Food Prize Laureate 2016. In his Abstract of the conference proceedings, Dr. Bouis recorded "The need for a shift in emphasis from protein-energy malnutrition to micronutrient malnutrition was recognized" [75].

The summary included comments by the then First Lady of the Philippines (a medical doctor), reporting her, and President Estrada's commitment to medical and relief missions, particularly to poor communities that are not reached by regular public health and medical centers. The "Wheat flour Fortification with vitamin A Project" was one of the first major activities of the Estrada administration in its first 100 days. She encouraged the development of more nutrient-dense crops especially rice, corn and root crops. She also encouraged the production of micronutrient-rich food products, including livestock, poultry, fish and certain vegetables and fruits, especially those that can be easily raised in backyards and community gardens [75].

Also included in the summary were comments by Muhiuddin Khan Alamgir, the then State Minister for Planning, Bangladesh. He commented that Bangladesh's Constitution recognizes "raising the level of nutrition and improvement of public health" as "among primary duties" of the state. He called for improvement in food grain quality and listed genetic engineering and technology as of special importance [75].

In 2002, the term "Biofortification" was first used [76] and in 2004, it was first defined as "a word coined to refer to increasing the bioavailable micronutrient

#### *Golden Rice, VAD, Covid and Public Health: Saving Lives and Money DOI: http://dx.doi.org/10.5772/intechopen.101535*

content of food crops through genetic selection via plant breeding" [77]. In the 2004 paper, it is made clear that the human nutrition definition of "micronutrients" will apply encompassing both minerals and vitamins.

Incidentally, in crop breeding for minerals such as "high iron" or "high-zinc" varieties, what is selected are plants that have the capacity to accumulate these minerals from suitable soils. The crop varieties cannot synthesize the minerals. In the case of Golden Rice, beta-carotene is organically synthesized within the plant, independent of the soil type. The same is true of folate rice [78].

It is clear that a lot of thinking was being applied to nutritional improvement of crops at the beginning of this century, and the high public profile of Golden Rice put staple crop biofortification with micronutrients on the donor map in 2000. Harvest Plus, starting in 2003, has now tested or released 400 biofortified staple crop varieties in 63 countries as a result. They are being grown by more than 10 million households globally [79]. All have been produced through conventional, selective breeding improving existing crop varieties.

For those crops where conventional breeding cannot biofortify sufficiently, genetic engineering is necessary, and progress has been slower. Not only Golden Rice, but GMO-biofortified rice with iron and zinc [80], and with folate [78] (eventually it is hoped they will be combined in one multi-biofortified Golden Rice). In 2005, the Bill and Melinda Gates Foundation created Grand Challenge #9 and, following competitive grant allocation, funded further research into genetically engineered biofortified rice (with Peter Beyer—Golden Rice's co-creator—as Principal Investigator) as well as genetically engineered biofortified plantain/ banana and cassava, and sorghum. All or some will be successfully and beneficially adopted with huge welfare and economic benefits to poor societies.

All of the successes of Harvest Plus are with single nutrients in each case—all so far conventionally bred. In the case of iron and zinc, biofortification of rice Harvest Plus has found that genetic engineering can achieve levels unattainable by conventional breeding [80]. As proposed above already for Bangladesh, the combination of delivery mechanisms—conventional and existing transgenic crops being conventionally bred together—can quite easily produce, for example, "High Zinc Golden Rice" identified by its color.

Genetic engineering can also produce combination traits: rice with beta-carotene, and simultaneously, the ability to accumulate high iron and high zinc has been developed experimentally [81]. However, with current regulatory constraints and costs it would be preferable to first register and then introgress, the different traits individually.

Gene editing has been used to construct beta-carotene rice [82], but as the construct introduced foreign genes, it was anyway a "GMO." As Beyer and Potrykus have commented, gene editing may be useful to delete function in crop plants, but with current levels of genetic knowledge, to add function requires adding genes, which makes GMO crops [83], with associated regulatory challenges under current rules.

The safety for consumption of Golden Rice has been confirmed by the regulatory authorities of Australia, Canada, New Zealand, the Philippines and the USA [40]. That cultivation is also safe has received official endorsement by regulators in the Philippines. On a separate occasion, the Philippine Secretary of Agriculture, Dr. William D Dar said of Golden Rice: "It smells and tastes the same as ordinary rice, except it is colored yellow. But I will choose 'Golden Rice' over white rice, because it has more health benefits." The Golden Rice-tasting event was part of the inauguration of the Philippines Department of Agriculture Crops and Biotechnology Center, and launch of Golden Rice, on September 30, 2021 ([84], Video 1). In an accompanying press release, Dr. Dar commented that "The recent *[September 2021]* UN Food Systems Summit held in New York, USA, underscored the important role of biotechnology and other scientific innovations in attaining food security by all countries" [85].

GMO-produced insulin was commercialized from 1979 with no opposition, and genetic modification techniques are commonly employed in discovery and manufacture of pharmaceuticals, and beer, wine, cheese and bread are manufactured using genetically modified enzymes. Hundreds of millions of people in the United States and elsewhere and billions of farm animals have been consuming since 1997 products from genetically modified crops using the same techniques employed by Beyer and Potrykus to create Golden Rice. The European production of pork and chicken, the whole market in Europe, would collapse if it were not for imported GMO-maize and GMO-soy meal. Imported because, with very small exceptions, the Europeans will not allow cultivation. Yet, not a single case of any disease or other difficulty associated with genetically modified crops has been verifiably recorded in any human or other animal.

Every single academy of science in the world has attested to the fact that there is no scientifically valid reason for assuming that GMOs could cause harm [47]. Additionally, the European Food Safety Authority, stated, in 2010, that "The main conclusion to be drawn from the efforts of more than 130 research projects, covering a period of more than 25 years of research and involving more than 500 independent research groups, is that biotechnology, and in particular GMOs, are not per se more risky than, for example, conventional plant breeding technologies" [86].

The technology—of conventionally bred as well as genetically engineered biofortified crops—is in the seed and breeds true season to season. The biofortified traits are only introduced into modern, high-yielding crop varieties and can be easily transferred by plant breeders to new varieties as they become popular.

It is time to embrace all available tools, both forms of biofortification as well as chemical fortification, to improve the nutritional quality of staple foods by the incorporation of micronutrients, together with the macronutrients that have been the focus of plant breeding for the previous millennia since humans stopped being hunter gatherers.

These tools are complementary to other public health interventions, education, vaccination, supplementation, home gardens, breast feeding and economic development all important to population welfare.

Not only are all these tools required. Also required are all functions of the private, public, NGO and especially government sectors, working across silos of expertise to support each other's objective of improving societal public health.

Other countries should follow the Philippines example. Bangladesh is poised to do so. India has a huge VAD problem [2], equivalent to the total of the VAD of the 28 sub-Saharan African countries [21]. India has been held back from vitamin A supplementation, because "the issue of vitamin A has commercial overtones": "[W] e must look to our farmers, not to pharmaceutical companies, to protect the health of our children. The main solution to vitamin A deficiency should not be drugbased, but food-based." [21].

Golden Rice is "food based" and there are no "commercial overtones." Golden Rice does depend on farmers, first and foremost to grow it before it can be consumed, especially by their communities, as an additional intervention for vitamin A deficiency.

All the biofortification tools, and related biofortified crops described here and developed by the public sector are available without cost for use of governments, growers and consumers, as by the time of introduction the development costs have been paid.

On World Food Day, October 16, 2020—during the Covid-19 pandemic—Indian Prime Minister Narendra Modi gave a strong endorsement to staple crop biofortification as a sustainable and cost-effective solution to alleviate malnutrition [87].

The World Bank has recommended that micronutrient biofortification of staple crops, including specifically Golden Rice, should be the norm and not the exception in crop breeding [88].

The movement to common sense and reality has now become unstoppable.
