December, 1997

Iron is the most commonly deficient micronutrient in the human diet and iron deficiency affects an estimated 1-2 billion people. Anemia characterized by low hemoglobin is the most widely recognized symptom of iron deficiency, but there are other serious problems such as impaired learning ability in children, increased susceptibility to infection and reduced work capacity. Women of child-bearing age are especially prone to iron deficiency and suffer from tragic consequences such as premature child birth, babies with low birth weight and even greater risk of death.

Worldwide, an estimated 40% of women suffer from iron deficiency, with proportionally higher rates in developing countries. Iron deficiency is not an acute problem in many industrialized countries thanks to food fortification and diverse diets that include significant amounts of meat.

Increasing the iron content in rice is an appealing strategy to supply the mineral inexpensively and effortlessly to a large sector of the world's disadvantaged population. Rice feeds half of the world, and is eaten every day in those parts of the world where iron deficiency is most prevalent. Two research groups from Japan and Switzerland are working to develop rice plants with increased iron content; the results of their ongoing research were presented at the recent International Congress of Plant Molecular Biology in Singapore.

A research group led by Toshihiro Yoshihara and Fumiyuki Goto at the Central Research Institute of Electric Power Industry in Japan employed the gene for ferritin, an iron-rich soybean storage protein, under the control of an endosperm-specific promoter. Grains from transgenic rice plants contained three times more iron than normal rice. Another group, led by Ingo Potrykus and his Ph.D. student Paola Lucca at the Institute of Plant Sciences in Zurich, has developed similar transgenic rice with the ferritin gene from beans, and the plants are now being evaluated.

In conversation at the Singapore meeting, Yoshihara commented that although his group has successfully developed rice with elevated iron levels, more research is needed to further increase the iron content in the grain. He plans to focus on iron transport within the plant. Potrykus agreed that the success of the Japanese group "is an encouraging first step forward" to combat iron deficiency, but believes that there are more important problems of iron bioavailability that need to be considered.

Seeds store the phosphorous needed for germination in the form of phytate, a sugar alcohol molecule having six phosphate groups attached. In terms of food and feed, though, phytate is an anti-nutrient because it strongly chelates iron, calcium, zinc and other divalent mineral ions, making them unavailable for uptake.

Potrykus and his group have developed a series of transgenic rice lines designed to deal with this problem. One approach has been to reduce the phytate in rice endosperm by introducing a gene from the fungus Aspergillus niger that encodes phytase, an enzyme that breaks down phytate.

To counter phytate from other sources in the diet, the Swiss group is using another gene that encodes for a heat-stable phytase from Aspergillus fumigatus. This enzyme can survive boiling and has two pH optima - acidic for the stomach and alkaline for the intestine. To further promote the resorption of iron, a gene for a metallothionein-like protein has also been engineered. Potrykus commented that all these transgenics will soon be tested and eventually the traits will be combined into a multiply-engineered line.

Yoshihara supports the elaborate strategies of the Potrykus group, but suggests that iron uptake can also be enhanced by the use of chelators such as ascorbic acid (vitamin C). Addition of vitamin C-rich vegetables like collard greens to rice meal has been known to improve iron absorption in the body. But Potrykus points out that the diet of poor people in developing countries often lacks vitamin C.

Fortification of wheat flour with iron has been a successful strategy to ameliorate iron deficiency in the developed countries. As such fortification is not possible with rice, "genetically engineered fortification is the only possible solution" says Potrykus. Even if successful, it is unlikely that 'iron-fortified' rice would be widely available and may be selectively targeted to segments of population at greatest risk of iron deficiency such as infants, school children and pregnant mothers. This is because of the concerns that individuals with high iron stores have a higher risk of cancer and heart disease.

The ferritin gene, in addition to improving the nutritional content, appears also to help the plant in dealing with its own iron nutrient problems. Either too much or too little iron in the soil can cause decreased plant productivity. Yoshihara's group found that tobacco plants expressing the ferritin gene grew well under conditions of wide ranging iron concentrations in the soil.

C. S. Prakash
Center for Plant Biotechnology Research
Tuskegee University