Chantal Sempach

“Fighting Hidden Hunger”. This is how ETH Zurich advertises its self-developed rice variety: the golden rice. A plant that is said to be cheap and easily available and gives sight to children from poor backgrounds. What can one have against such a miracle plant?

Night blindness and skin diseases

Vitamin A is an important chemical compound that must be absorbed by the human body through food. It is important for eyes and skin as well as for bones and teeth. Symptoms of a deficiency phenomenon can be night blindness, dry skin and infections. Complete blindness often occurs. [1] Vitamin A not only prevents such visual disturbances, but also plays an important role in cell differentiation and morphogenesis and probably also influences blood formation, since a deficiency is often associated with anaemia. [2] Vitamin A deficiency is one of the most common health problems worldwide. Especially women and children in developing countries are affected. Although vitamin A only needs to be taken in small amounts, according to the World Health Organization (WHO), an estimated 250,000 to 500,000 children suffer from the consequences of a vitamin A deficiency. About half of them die from it every year.

Vitamin A is mainly found in animal foods such as fish, eggs and dairy products. In plant foods it is found in the form of beta-carotene, a provitamin A. Especially carrots are known for their high beta-carotene content, but the daily requirement can also be covered by other fruits or vegetables such as spinach, peppers, tomatoes, broccoli or apricots. Deficiency symptoms therefore occur mainly in countries where these foods are scarce. That’s why many Asian countries, which have rice as their staple food, are affected. [1] Unskinned rice contains small amounts of beta-carotene in the husk, but this fatty cover is removed to prevent the grains from becoming rancid during storage. The husked rice, i.e. the remaining endosperm, therefore, no longer contains any vitamins. In industrialized countries, despite an abundant supply of animal and plant products, about 20-50% of vitamin A is consumed in the form of food additives. [2]

The transformation

Along with maize and wheat, rice is one of the most important crops in the world: around half of the world’s population feeds mainly on rice. It is cultivated in over 100 countries on a total of about 150 million hectares. More than 90% of this area is located in Asia. Despite classical breeding, which considerably improves the resistance of the rice, about half of the harvest still falls victim to diseases and pests. Therefore, there is still a great need for breeding improvements to this plant. The development of a rice variety with beta-carotene containing endosperm is undoubtedly a sensible strategy to guarantee a sufficient supply of vitamin A via the daily, accustomed diet in Asia.

In 1990, Swapan Datta was the first researcher to succeed in producing transgenic farmed rice. He also invented a new transformation method that allowed DNA to be introduced into plant parts without having to remove the cell wall.  In this way, entire plant parts, as in the case of rice, embryos can be used for transformation. Some of the plant cells stably incorporate the DNA into their genome and can regenerate back into plants. Since only a small fraction of the cells is successfully transformed, marker genes must be used for their identification. These allow transformed cells to selectively multiply and regenerate while untransformed cells die.

Thanks to this new method, a project to increase the vitamin A content in rice was started in the early 1990s in the laboratory of Ingo Potrykus at ETH Zurich. But initial investigations were sobering. It turned out that the rice endosperm lacked the four last enzymes of the beta-carotene synthesis pathway. At that time, it seemed completely impossible to transform four individual genes, whose enzymes would then be able to carry out a biochemical synthesis. Thanks to the financial support of the ETH, the Rockefeller Foundation, the EU and the Swiss National Science Foundation, the working group decided not to put the project on ice and started the transformations with the gene for the first of the missing enzymes, the phytoene synthesis. These first transgenic rice plants already fulfilled the researchers’ hopes, because in the endosperm they synthesized a precursor of beta-carotene, the phytoene. This was a great success, because it was possible to divert an existing synthesis pathway without affecting another vital function of the rice plant. In a next step, the other three genes were to be transformed individually in order to subsequently cross the transgenic plants with each other and thus combine the entire synthesis pathway in a rice plant. However, the attempt to regenerate a plant that expresses another enzyme of the beta-carotene synthesis pathway was unsuccessful for more than a year.

The success came with Xudong Ye, who took over the project in 1998 and decided to take a completely new approach. He used the bacterium Agrobacterium tumefaciens for the transformation. This soil bacterium possesses a tumour-inducing plasmid with genes for transferring a DNA fragment. Therefore, it has the ability to transfer DNA into plants. Modern genetic engineering has taken advantage of this bacterium by modifying the plasmids in such a way that no more bacterial genes are transferred, but only the desired useful genes. Using this method, all four genes for carotene synthesis could be transferred into the plant in a single transformation. Biochemical analyses showed a beta-carotene content of up to 1.6 µg carotene/g endosperm, a level that was close to the target of 2 µg/g. With 300 g of this rice, which took on a golden colour due to the carotene, about 10 to 20% of the daily vitamin A requirement could be covered. [2]

Abb. 1: Patrick Moore, former Greenpeace activist, turns against his organization and fights for the spread of the genetically modified rice. (transgen.de, 2020)

Golden rice and dead children

Since golden rice was developed expressly for the Third World, it is often used as a positive example of genetically modified plants. The provitamin A rice fulfils many of the requirements that are today placed on an ideal transgenic plant: On the one hand, it is cheap to buy for small farmers in poor conditions. On the other hand, it is not a hybrid seed, which means that farmers do not become dependent on the sellers. Finally, no negative health side effects have been observed so far. Nevertheless, many smaller NGOs are still vehemently opposed to the use of provitamin A rice. First of all, Greenpeace. They fear that this rice, as a “Trojan horse”, will increase the acceptance of genetically modified plants and that this will lead to further applications of genetic engineering in the field of agriculture in developing countries. [2]

In addition, Greenpeace justifies its reluctance by pointing out that golden rice was developed over 20 years ago and has since failed to demonstrate its ability to address the vitamin A deficiency problem. During this time, millions of dollars have been invested in this prestigious agro-genetic engineering project, which would have been much better invested elsewhere. Measures to combat vitamin A deficiency that have long been available and functioning, for example in the form of tablets, could have been supported in this way and the deaths of thousands of children could have been prevented. Furthermore, Greenpeace believes that it would have been better to rely on a wide range of organic products. In the long term, only the sustainable production of high-quality food in locally adapted systems will solve the problems. It is becoming increasingly obvious that, especially in tropical countries, success can only be achieved with methods of organic farming. In addition, a balanced diet would also prevent other diseases. It is therefore irresponsible and wrong to present golden rice as the only quick solution. [3]

It is uncertain whether golden rice will ever achieve the desired success in developing countries and thus lead to a reduction in health problems. Nevertheless, the rice is already a scientific breakthrough. On the one hand, it shows what cooperation between industry and science could look like and how developing countries can benefit from this modern research. On the other hand it shows the progress made in genetic engineering. Whether this is positive or negative remains a matter of opinion. But it could become necessary in any case.

[1] WHO, Micronutrient deficiencies, (2013), retrieved from https://www.who.int/nutrition/topics/vad/en/

[2] Frey, P., Golden Rice Entwicklung und Bedeutung der bekanntesten Reispflanze, (2001), retrieved from https://www.forschung-leben.ch/publikationen/biofokus/golden-rice/

[3] Zimmermann, D., “Golden rice” und tote Kinder, (2013), retrieved from https://www.greenpeace.de/themen/landwirtschaft/gentechnik/golden-rice-und-tote-kinder