Vitamin A deficiency and Golden Rice

Today’s organism was modified over two decades ago. This topic may not be an easy topic for everyone, because today we’ll discuss the effects vitamin A deficiency can have on your body and how many children suffer from this deficiency. However, we will also talk about a silver lining: the “Golden Rice”.

International Rice Research Institute; photo licensed under CC BY 2.0.

Why do we need vitamin A?

What is vitamin A? Vitamin A is a group of fat-soluble retinoids. It is important for the immune system, cell-cell communication, growth and development, and female reproduction [1]. It also has critical roles in the normal formation of the heart, lungs, eyes, and other organs. Vitamin A is essential for the eye because it is essential for rhodopsin, the light-sensitive proteins in the eye, and it enables the normal formation and function of the cornea (curved section in front of the pupil) and conjunctiva (connecting the eyeball to the eyelids) [1].

How do humans absorb vitamin A? Like many other things, through food. However, there are two versions: preformed vitamin A, which includes retinol and retinyl esters. These are absorbed through dairy products, eggs, fish, and meat. Then there are the provitamin A carotenoids, which are absorbed through the digestion of plant pigments. These mainly include beta-carotene, alpha-carotene and beta-cryptoxanthin. Lycopene, lutein, and zeaxanthin are not among them, but seem to be helpful in the production of vitamin A [1].

Vitamin A deficiency and its consequences

Residents of industrialised countries usually do not have a problem with vitamin A deficiency, but this deficiency often occurs in developing countries [2]. Vitamin A deficiency affects more than half of all countries, many in Africa and South-East Asia. Medically, vitamin A deficiency leads to xerophthalmia, the drying of the cornea and conjunctiva. This leads to anything from milder night blindness and Bitot’s spots (foamy patches on the eyeball) to potential blindness (corneal xerosis, ulceration, necrosis) [2]. Retinol is the most abundant form of vitamin A in blood and plasma. One speaks of a subclinical vitamin A deficiency at a concentration of <0.70 µmol/L and of a severe deficiency at a concentration of <0.35 µmol/L. The worst affected are often children and pregnant women.

There are on average 250,000-500,000 children who go blind each year due to vitamin A deficiency, according to the WHO, and half of them die within 12 months of going blind. Vitamin A deficiency is also associated with high morbidity and mortality from childhood diseases and would be the biggest preventable cause of childhood blindness. It has other consequences such as increasing the risk of contracting respiratory and diarrhoeal infections, reduced growth, and slow bone development, to name a few [2].

In the first eight years of life, an average of 400 µg of retinol activity equivalents (RAE) is needed daily. One µg RAE is defined as 1 µg retinol, 2 µg beta-carotene in dietary supplementation, 12 µg beta-carotene with food or 24 µg alpha-carotene or beta-cryptoxanthin with food [1].

Golden Rice takes the stage

If vitamin A is found in so many foods, why is it such a huge problem? Many foods grow only very seasonally, need certain geographical conditions, have a rather low yield, or are too expensive to obtain by poor families. Since a lot of rice is grown in many areas where vitamin A deficiency also occurs, it would be ideal if vitamin A could be taken in through rice. Peter Beyer and Ingo Potrykus thought so as well.

**The BETA-carotene pathway introduced into Golden Rice**

They use the geranylgeranyl diphosphate (GGDP) produced in the endosperm (the rice grain) to produce beta-carotene [3]. To do this, Agrobacterium-mediated transformation (a standard plant transformation method for introducing transgenes into certain plants) was used to introduce three enzymes into the plant.

first, a phytoene synthetase (psy) from the organism Narcissus pseudonarcissus (daffodil), which converts GGDP into phytoene.
second, a bacterial phytoene desaturase (crtI) from the organism Erwinia uredovora, which catalyses 4 double bonds to convert phytoene into lycopene.
Third, lycopene beta-cyclase (lcy) also from the organism Narcissus pseudonarcissus, which converts lycopene into beta-carotene.

Here, psy was placed under the control of the endosperm-specific glutelin and crtl under the control of the constitutive CaMV (cauliflower mosaic virus) 35S promoter. Both sequences were modified with transit peptide sequences to localise the enzymes in the endosperm plastid where GGDP is actively produced. The lcy gene also has a transit peptide sequence to be imported into the plastid and was placed under the control of the rice glutelin promoter [3].

At the end of the publication, they mention that 1.6 µg/g of carotenoid is produced in endosperms, which is close to their target of at least 2 µg/g of provitamin A in endosperms. This would correspond to 100 µg retinol with a daily consumption of 300 g rice [3].

This 2000 publication was mentioned in the July 2000 issue of Time magazine [4]. The research continued and led to the publication of Golden Rice 2 by Syngenta in 2005 [5]. They found that the psy gene from maize (Zea mays) worked much more effectively than the homologue from daffodils. They were able to produce up to 37 µg/g of carotenoids in rice endosperms, which is 23 times more than the original Golden Rice. Of these 37 µg/g carotenoids, 31 µg/g are beta-carotene, so children’s daily intake would be saturated by 50% just by eating 72 g of dry Golden Rice 2 [5].

Enough biochemistry, what about real world application?

20 years old – and not yet in use?

As early as 2007, a study in collaboration with researchers living in Bangladesh, India, the Philippines, and the USA reported that the incorporation of transgenes for carotenoid synthesis did not change any significant agronomic characteristics in the rice plants[6].

However, there have been repeated criticisms that the plant would not produce enough provitamin A for it to be relevant, but this has become unnecessary with Golden Rice 2. Afterwards, there was criticism that it was not known how much beta-carotene was broken down or lost during intake. In 2009, however, a study was published proving that beta-carotene from Golden Rice is effectively converted into retinol in humans[7].

Even 159 Nobel laureates wrote a public letter in 2016 to Greenpeace, the United Nations, and governments around the world that they support “GMOs” and especially Golden Rice[8]. In this letter, they write that organisations opposing GMOs have misrepresented the risks, benefits and impact and supported the destruction of approved field trials and research projects. An opinion piece published in PNAS in December 2021 summarises the urgent need and fears regarding Golden Rice quite well [9].

Will it be used or not?

Both the Philippines and Bangladesh have given the green light for the commercial use of golden rice. In 2022, the Philippines launched its project to combat vitamin A deficiency by growing and consuming golden rice in vulnerable areas of the country. “At the policy level, the National Seed Industry Council (NSIC) has adopted a uniform policy for variety approval of all genetically modified crops, paving the way for a streamlined timeline for the introduction of golden rice,” Dar said at the Healthier Rice Project Team and Advisory Committee (HRAC) meeting [10].

Golden rice in the Philippines has been crossed with local rice, which is preferred by the citizens. The key finding here is that one gram of rice grain contains about 11 micrograms of beta-carotene, which is sufficient to provide 80-110% of the recommended daily intake of vitamin A for children and women. [11]

Massive seed production is expected to start this year and the first yields will be after the next harvest. Hopefully this is the last time you will have to read about vitamin A deficiency, because golden rice shows promise to be a cure for this widespread problem.

If you found this topic exciting or are still rather averse to it, please visit the Golden Rice Project and read up further there.