The hidden hunger affecting billions
BY MICHAEL MARSHALL
Two billion people do not get enough micronutrients in their diets, which can lead to severe health conditions. New kinds of crops could help to create better, more nutritious foods to beat these deficiencies.When children do not get enough iron in their food, the results are heartbreaking. They are slower to acquire language, struggle with short-term memory, have poor attention spans and ultimately do less well at school.

“They can never live up to their full physical and mental potential,” says Wolfgang Pfeiffer, director of research and development at HarvestPlus, an organisation that develops nutritionally improved crops in Washington DC. “If they are deficient in their childhood, they learn 20% less as adults.”

In the poorest parts of India and China, millions of children have their lives stunted through lack of iron. In South Asia, an estimated 50% of pregnant women have iron deficiency, and it is also prevalent in South America and sub-Saharan Africa.

But iron is only one small part of the story. There are several dozen other “micronutrients” – substances that we need to consume, in small quantities but regularly, to remain healthy. They include zinc, copper, vitamins and folates such as folic acid and vitamin B9.

An estimated two billion people – 30% of the global population – lack one or more crucial micronutrients. Many people suffer serious and life-long health problems as a result.

As the world’s population continues to grow rapidly, it becomes more pressing not just to increase the quantity but to improve the quality of foods. Without adequate levels of micronutrients, health problems like stunting, birth defects and blindness become a greater risk.

But new ways to tackle micronutrient deficiencies, such as the lack of iron, are starting to change the picture. In 2012, HarvestPlus released a new version of pearl millet, a staple crop in India. Known as Dhanashakti, the millet has been bred to have much higher levels of iron (link to: http://oar.icrisat.org/8602/). By 2017 it had been marketed to over 70,000 farmers, mostly in Maharashtra state where many people rely on pearl millet. Tens of thousands of Indian children are now eating this iron-rich pearl millet.

The results have been “fantastic”, says Pfeiffer. “The iron improved the iron status and the physical and cognitive performance of adolescents,” he says. The popularity of the Dhanashakti pearl millet could ensure that thousands of children grow up with healthy bodies and brains, with a better chance of reaching their full potential.

The enhanced pearl millet is one of dozens of new crops that HarvestPlus and other research groups are creating. These crops are being carefully bred, or genetically engineered or edited to contain more vital nutrients, to resist diseases and to survive extreme weather like droughts and heatwaves.

The goal is to improve the health and wellbeing of the world’s poorest, most vulnerable people.

The traditional solution to micronutrient deficiencies has been to add more micronutrients to common foods, or to supply pills. For example, pregnant women in many countries are encouraged to take folic acid supplements to ensure they get enough folates. Many breakfast cereals are “fortified” with iron and vitamins, while some countries add iodine to salt to ensure people get enough.

But these strategies have limits. If people can’t afford pills or don’t have access to a pharmacy, they may still not get enough micronutrients. What’s more, adding micronutrients to food is a constant process: every batch of breakfast cereal has to be artificially dosed with iron and vitamins.

A much simpler approach would be to go back to the crop plant from which the cereal is made, and ensure that it packs itself full of the micronutrient in the first place.

This is the thinking behind “biofortification”, the process of creating crops that have unusually high levels of micronutrients like iron. HarvestPlus was founded in 2003 by economist Howarth Bouis, after a decade of lobbying and raising money to create biofortified crops and make them available where they are needed. Today HarvestPlus has members in more than 20 countries and has biofortified over a dozen crops, from rice to sweet potatoes.

“By now we have more than 300 varieties of all those crops, released in more than 35 countries,” says Pfeiffer. “More than 50 million people are already consuming those crops.”

To make a biofortified crop, HarvestPlus must answer three questions, says Pfeiffer. First, is it even possible to breed a crop with higher levels of a desired nutrient, without harming other traits like productivity or resilience to drought?

Second, can people eating the new crop actually absorb the extra nutrients, and does this improve their health? This cannot be taken for granted: “superfoods” are often marketed as being unusually rich in a particular nutrient, but that doesn’t mean your body can take it all in.

And third, are farmers and consumers willing to adopt the biofortified crop? Here, cultural factors can be crucial. If the new crop is a different colour or shape to the familiar one, people may be wary of it. Rejecting a healthy food because of its appearance may seem silly, but we all do it: many people are reluctant to eat black pasta, for instance.

Some of HarvestPlus’s biggest successes have been tackling vitamin A deficiency in Africa. There are several versions of vitamin A, and HarvestPlus has succeeded in breeding crops enriched with one form, known as beta-carotene. This is the orange-red pigment found in carrots, pumpkins and mangoes.

For example, in Zambia HarvestPlus has released vitamin A maize. Pfeiffer was initially wary of this plan, because the enhanced maize might well be yellow, a colour that had become associated with the poor-quality maize imported during food shortages.

“They only like white maize,” he says. “They had a real aversion against yellow maize.”

To get around this, HarvestPlus bred the new maize to be orange, which studies showed people were happy to grow and eat. In 2015 the biofortified maize went on sale in Zambia. Children who eat the new maize have more responsive pupils than those who don’t, suggesting it is helping to protect them against future eyesight problems.

Similarly, farmers in Rwanda now grow iron-fortified beans devised by HarvestPlus. Laura Murray-Kolb of Pennsylvania State University has helped show that these beans reduce iron deficiency within 128 days.

Food basket
In South America, the deficiency challenge is more complex than in Africa or Asia, says Marilia Regini Nuti, HarvestPlus’s regional director for Latin America. The issue is that there is not a single staple crop that the vast majority of people rely on, as is the case in Zambia with maize.

Instead people eat a mix of rice, beans, cassava, maize and a host of other foods – and the mixture varies drastically even within countries. So Nuti and her team have developed a “food basket approach”, in which they biofortify multiple crops through selective breeding to have as big an influence on people’s diets as possible.

One lesser-known crop that has proved to be crucial is cowpea, which is related to peas and beans. It is a legume, which means it hosts bacteria in its roots that “fix” nitrogen from the air. As a result, cowpea beans are high in protein. There are a lot of cultivated varieties, of which perhaps the most famous are black-eyed peas.

“Cowpea is very important for Brazil because cowpea grows in arid soil, where beans cannot grow,” says Nuti. This makes cowpeas a crucial staple in the poor, dry north-east of the country, so boosting their iron and zinc content looked like a good approach. A 2011 study revealed considerable variation in iron and zinc levels in different strains of cowpea, so the breeding programme had plenty of raw material to work with.

The Brazilian breeding efforts were led by Embrapa, a research organisation owned by the Brazilian government. They have bred and released three new varieties of cowpea, with up to 40% higher iron levels.

But there is a further complication in South America. People living in cities often have micronutrient deficiencies too – unlike other parts of the world, where such deficiencies are largely confined to rural areas.

To help tackle micronutrient deficiencies in cities, Nuti is working on crops that can be used by the food industry. For instance, in Colombia she has helped launch maize biofortified with zinc. The next step is to use flour from this maize to make arepas: circular flatbread-like foods that look a bit like English muffins.

“You put butter on it,” says Nuti. “It’s something the population eats a lot.”

Working with a food company, her team is developing zinc-enhanced arepas that can be sold in cities. It’s hoped that focusing on ready-made foods can help improve the nutrition of urban populations in ways that only biofortifying individual crops cannot.

Cooked and processed foods have a reputation for being low in micronutrients, but this is not necessarily true. For instance, Fabiana de Moura, now at the US Food and Drug Administration, has shown that people get just as much iron from cooked bananas as from raw bananas.

Leonardo Silva Boiteux of Embrapa is also developing biofortified crops that can be used in processed food. He has spent decades developing new varieties of tomato for use in products like ketchup. Boiteux aims both to improve their nutritional content and to make them more resilient to threats like drought and disease.

Boiteux’s main focus on the nutritional side is the amount of lycopene in the tomatoes. Lycopene is the red pigment that gives tomatoes their colour and is chemically similar to vitamin A.

It has been suggested that eating lots of lycopene might help protect against both cancer and heart disease. It was initially believed lycopene acted as an antioxidant that can mop up highly reactive chemicals called free radicals, which would otherwise damage cells. However, research suggests that taking antioxidant supplements has very few benefits and may even be harmful if eaten in excess. So simply being an antioxidant does not mean lycopene is good for us.

But, as with much of the complex science of nutrition, the jury is still out. A 2016 review concluded that lycopene might help protect our hearts after all, albeit by other mechanisms such as reducing inflammation. Similarly, a 2015 meta-analysis concluded that men who eat more lycopene have a reduced risk of prostate cancer.

Boiteux has developed a series of tomato varieties with excess lycopene: one strain with 104 micrograms of lycopene per gram, and more recently another one known as the Zamir strain, with 144 micrograms per gram. The Zamir strain also incorporates a newly-discovered gene variant called bif, which Boiteux and his colleagues found in tomatoes from the Galapagos Islands. The bif variant causes a massive increase in branching and thus in the number of tomatoes per plant.

“The number of fruits increased 3.3 times,” says Boiteux. Boiteux’s team also bred in strong resistance to powdery leaf mildew, which is a major disease of cultivated tomatoes.

Programmes like these can achieve a lot. However, it is not enough to simply create crops that have higher nutrient levels. Today’s crops must also be resilient in the face of extreme weather events like heatwaves and droughts, which are becoming more frequent as a result of climate change, and able to fight off diseases and pests.

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Hunting for chickpeas
One crop with enormous potential to withstand extreme conditions is the chickpea. Today chickpeas are grown throughout the tropics, and are particularly important in India and the Middle East. But they were first domesticated in Mesopotamia and many wild varieties still grow in that region.

“The extent of the diversity of the material and its origins were not understood, nor was it understood how domestication had impacted it,” says Douglas Cook, who leads the Climate Resilient Chickpea Innovation Lab at the University of California, Davis. “As a consequence, nobody had a good idea about how those wild types might be useful in agriculture. We spent the last five years answering those questions.”

The team has crossed the wild varieties with domesticated chickpeas, creating a huge resource of genetic variation that they now hope to use to enhance existing varieties. They are looking to improve a laundry list of properties, including drought tolerance, heat tolerance, disease resistance and pest resistance.

“If you’re interested in the nutritional end-product of the seed, all these things matter,” says Cook. “Drought impinges on nitrogen fixation, which drives proteins. If you have drought, protein production goes down.” In other words, chickpea plants that can’t handle drought will end up making chickpeas that are less nutritious. “These things are tied together inextricably.”

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All these biofortification schemes rely solely on conventional breeding. But crops can also be genetically engineered. This has proved controversial in Europe, where some countries have banned genetically modified crops over fears – which groups including the US’s National Academies of Sciences, Engineering and Medicine suggest are almost certainly unjustified – that they could lead to unforeseen environmental or health consequences.

In some cases, the only way to achieve a particular enhancement is through genetic engineering or modern methods of gene editing. If all the strains of a crop have about the same amount of a given nutrient, no amount of conventional breeding will boost levels of that nutrient.

That is why Dominique Van Der Straeten of Ghent University in Belgium and her colleagues resorted to genetic engineering to boost the folates content of white rice. Despite being a staple food in India and other countries, white rice contains low levels of folates.

“A pregnant woman would have to eat 12kg of boiled white rice per day to have a sufficient folate intake,” says Van Der Straeten. “Which is absolutely impossible.”

They first added two genes involved in making folates from Arabidopsis thaliana, a plant often used in laboratory studies. Then they “over-expressed” these genes, making them more active. The result was rice seeds with levels of folates up to 100 times higher than ordinary white rice.

However, this wasn’t enough because the folates broke down when the rice was stored for several months, so the team kept engineering. A combination of four genes that they tried seemed to do the trick.

“We were able to effectively stabilise the folate levels and actually reach even higher levels, because we now have prototype rice lines that contain up to 150-fold more folates than wild-type rice,” says Van Der Straeten. Pregnant women would only need to eat 150g of boiled white rice to get enough folates. “One cup of rice would bring them a sufficient amount.”

The team has attempted something similar with potatoes and has achieved a 12-fold improvement in folates levels: not as “spectacular”, says Van Der Straeten, but “not bad”. The next step is to cross the engineered varieties with local varieties that are adapted to an area’s environmental conditions, to produce a version that can be grown in India and other countries.

“Primarily, our goal is to help people who are really in need, that is, the least favoured in society,” she says.

It remains to be seen whether the high-folate rice and potatoes will prove acceptable to farmers, consumer and governments. A previous high-profile attempt at biofortification by genetic engineering, “golden rice” engineered to have high levels of vitamin A, became the subject of vociferous protests driven by Greenpeace and other campaign groups. In 2013, an experimental plot in the Philippines was stormed and uprooted by militant farmers.

Nevertheless, in February 2019 Bangladesh’s agriculture minister announced that golden rice would soon be approved for large-scale use there.

“If and when the golden rice is grown there and people really see what it is doing, that the effect is there, and that people are saved from blindness due to the golden rice consumption, then I think that would really make a statement for the entire field and hopefully improve the acceptance also in Europe,” says Van Der Straeten.

Even in the best-case scenario, nobody expects biofortification to eliminate the problem of micronutrient deficiencies. Nuti points out that governments have long given out pills to tackle deficiencies and this did not eliminate the deficiencies, because their root causes are poverty and limited access to foods.

Nevertheless, biofortification looks set to be increasingly important. As the carbon dioxide content of the atmosphere increases, crops are expected to have lower levels of protein, iron and zinc. According to a study published in August 2018, this could lead to an additional 175 million people being zinc-deficient and an extra 122 million being protein-deficient.