The world population is expected to increase by about 2.5 billion by 2050, from its present 6.8 billion. By far the greatest rate of population growth is expected in Africa, especially sub-Saharan Africa. Yet 94 percent of all arable land on Earth is already being cultivated. To get enough food, it is becoming increasingly necessary to raise better crops.

Cassava and sorghum are called "food security crops" because they grow where little else will. Subsistence farmers in Africa grow these crops to feed themselves and their families. Unfortunately, the nutrition obtained from these foods is poor. They supply inadequate protein, few vitamins and not enough of the so-called micronutrients (minerals) like iron and zinc.

A group of St. Louis scientists, most from the Donald Danforth Plant Science Center, are working to improve the yield and nutritional value of these foods. As participants in two massive nonprofit international projects funded by the Bill and Melinda Gates Foundation, their goal is to improve nutrition in a sustainable way, using products developed by biotechnology.

"We have been committed to these goals since our beginning," said Roger Beachy, Danforth Center president. Nearly one-third of all ongoing research at the center is concerned with bettering nutrition and agriculture in the developing world.

To be successful, the scientists must develop plants that can be grown, at least in the beginning, using techniques already used by subsistence farmers. The plants must also look and taste largely the same as those being eaten on a daily basis. Otherwise they may be shunned by consumers.

What is cassava?

Cassava is a shrub harvested for its large tuberous roots that store carbohydrates in a dense, potato-like form. One hundred and five countries grow cassava, according to Claude Fauquet, director of the International Laboratory for Tropical Biotechnology at the Danforth Center. It is the third source of calories in the developing world, behind rice and corn.

In parts of Africa, cassava makes up more than 75 percent of the diet. With rising food prices and increasing population, an even higher percentage of the African diet may be tied to that one staple root.

We know cassava in its processed form as tapioca.

Professors Kenneth Olsen and Barbara Schaal of Washington University have traced cassava's origins to the southern border of the Amazon River basin in Brazil. From there it was taken to other parts of the world by Portuguese explorers. At least 600 million people now depend upon cassava as a main source of calories.

In the course of its world travels, cassava has adapted to different environments by developing a great number of localized varieties, called cultivars. As explained by the Danforth Center's Nigel Taylor, also of ILTAB, a cultivar will be specific to a certain location, and the farmers who grow and eat the local cassava will prefer its taste over other cultivars.

Farmers propagate cassava by cutting its stems around protuberances called nodes, and simply sticking the cutting into the ground. The cutting will develop roots and leaves and then grow into a full sized shrub.

What is sorghum?

Sorghum

David Seigler, www.life.uiuc.edu/ ib/363/image/Sorghum.jpeg

Field of sorghum.

Sorghum is a grain, mostly eaten as porridge or fermented into beer. It is the fifth most important cereal worldwide and the second most important, after corn, in Africa.

One hundred million Africans depend on sorghum for survival because it grows in the dry areas surrounding moister areas where corn can grow, according to Paul Anderson, head of international programs at the Danforth Center. Two hundred million more Africans have a significant amount of sorghum in their diet.

United States farmers grow sorghum for animal feed, but African farmers often eat sorghum at every meal.

Nutritional Goals

Although achieving goals takes different paths for both crops, they are the same. The enriched crops will have

• More and higher quality protein
• Increased vitamins, especially vitamins A and E
• More available micronutrients (minerals)

Dr. Mark Manary, a pediatrician with the Washington University School of Medicine, is part of the team. He advises the lab scientists about which needs are most pressing in different areas. In coastal areas, for example, where protein from fish is available, enhancing vitamin or mineral content might be a priority.

All the goals are being approached using techniques of molecular biology. It is hoped that biotechnology will develop new products more quickly and more effectively than conventional genetic cross breeding.

The problems, and how they are solved for each crop.

Low Protein

Protein deficiency can lead to various health problems, including susceptibility to infectious diseases and muscular weakness. The effects are especially obvious in children after they are weaned. After weaning, if children eat a low protein diet, such as cassava, they often fail to grow properly. They may never fully recover from effects of protein deprivation between the ages of 2 and 5.

Cassava: Cassava roots contain approximately 1 percent protein on a dry weight basis. Thus, a 2,000 calorie diet of only cassava provides only about 20 protein calories. The Danforth Center and other scientists in the Gates BioCassava Plus project have added high quality storage protein genes from bean sources to experimental plants and have been able to increase the protein concentration to 10-11 percent dry weight. With these a 2,000 calorie cassava root diet would provide 200 or more protein calories.

Cassava makes so little protein because it diverts most of the nitrogen usually used for protein synthesis into cyanide-producing compounds. (Sugar and starch do not contain nitrogen. Amino acids do.) Cultures that eat cassava are aware of the toxicity of these compounds and treat the root to remove the cyanide before it is eaten. Part of the protein enrichment effort has been to redirect the nitrogen into protein instead of cyanide-producing molecules. The work on the cyanide-protein connection was done in the laboratories of Richard Sayre, chairman of the BioCassava Plus program. Sayre, who is at Ohio State University, will join the Danforth Center on Sept. 1.

Sorghum: Sorghum grains are composed of about 12 percent protein on the average. The problem with sorghum arises when the grain is cooked into porridge. When it is cooked, 50-60 percent of that protein becomes unavailable nutritionally.

The reason for the unavailability is that when the proteins are heated, certain chemical groups called sulfhydryls(-SH) become reactive and cross-link into extremely stable bonds called disulfides (S-S). One protein strand will cross-link with others into a sort of network. As the proteins pass through the gut, digestive enzymes are unable to break the network into peptides and amino acids small enough to be absorbed.

The group headed by Anderson applies technology developed in corn to the sorghum grain. They have learned how to eliminate some of the seed storage proteins with the highest sulfhydryl content. Then, according to Anderson, "there is a compensating increase in the levels of other proteins with better amino acid composition." In this case, "better" also means proteins that supply a greater proportion of the amino acids that the body must get from foods, known as essential amino acids.

Increasing vitamin content

For both crops, increasing vitamin A is a top priority. As Anderson put it, "Vitamin A deficiency can lead to blindness, and in Africa blindness is likely to lead to death."

In cassava, the vitamin A content has been increased about 20-fold in the Danforth Center laboratories of Ed Cahoon by inserting the gene that makes pro-vitamin A.

Increasing micronutrients (minerals)

We need iron for our red blood cells. We need zinc for many processes catalyzed by enzymes, including protein synthesis, wound healing and immune function. Both cassava and sorghum supply inadequate amounts of these micronutrients, but for different reasons.

Cassava roots do a poor job of taking micronutrients from the soil. The Danforth Center laboratory of Daniel Schachtman is learning to overexpress the proteins that act as transporters of zinc from outside to inside. Augmenting the transport of iron 4-5 fold has been accomplished in the Sayre lab without increasing the uptake of potentially poisonous metals such as cadmium. Roots from the newly developed cassava plants will thus contain more of these needed minerals.

Sorghum has a different obstacle to making zinc and iron available for human nutrition. Its seeds contain a chemical called phytic acid that contains six negatively charged phosphate groups per molecule. The zinc and iron that we need are both positively charged. Positive and negative charges get together to form a very tight bond. Thus phytic acid ties up all the available zinc and iron in sorghum grain, and the micronutrients cannot be absorbed by the digestive system.

The solution is to reduce the synthesis of phytic acid about 50 percent, leaving plenty of iron and zinc free to be used as nutrients.

Where do these projects stand?

Developing new plant strains, whether by conventional genetic cross breeding or through biotechnology is time consuming. New products must be increased in number, grown to maturity, tested in greenhouse or lab situations and extensively field tested.

At this point, much progress has been made in greenhouses. Sorghum has been enriched in lysine-containing protein and with reduced levels of phytic acid. Virus-resistant cassava as well as cassavas enriched in protein, micronutrients and vitamins A and E have all been developed.

The virus-resistant cassava and lysine-enriched sorghum are being field tested in Puerto Rico for general vigor and viability as well as biosafety.

Beginning this fall, if all goes as planned, virus resistant cassava strains will be field tested in Uganda and Kenya. "Our African partners and collaborators are very important in this process and will help make it successful," Beachy said.

The partners will grow the new products at stations much like USDA experimental stations. They will be engaged in the discussion with the public about the new products before they are released. Farmers will be invited to follow the field trials. The products will be tested exhaustively in African countries, and the regulatory process being established to judge the new crops will be like those in the United States. Researchers hope subsistence farmers will have access to at least some of the new products by 2015.

What remains?

Some of the most challenging technology still remains to be developed.

The Gates Foundation would like to have more than one enrichment in the plants the farmers will cultivate. Incorporating two new characteristics in a plant using molecular biology is a daunting technological feat. Incorporating up to four may prove to be impossible.

At this point, explains Nigel Taylor, the role of Dr. Manary, the pediatrician in the cassava project, becomes crucial. He will advise the scientists about which nutritional problems are most pressing locally.

Then, one more layer of technical complication must be overcome. Cassava cultivars grown in one location tastes different from cultivars at other locations. For the farmers to want to grow and eat the new products, the taste must be familiar.

Taylor and his co-workers are working to enrich several local cultivars. In essence, nutritionally enriched cassava will be tailored to local tastes, conditions and needs.

In the case of sorghum, Anderson and his partners in the Africa Biofortified Sorghum project hope the biotechnology developed for corn will continue to transfer successfully to the other grain.

Bottom Line

Biotechnology provides revolutionary tools to approach old problems. Products developed here in St. Louis may be instrumental in helping humans escape starvation and malnutrition.