The agricultural biotechnology company Syngenta AG is featured not once, but twice, in this week's Nature journals, though officials there presumably are considerably more pleased with one article than the other.

In data published via advance online publication in Nature Biotechnology on March 27, 2005, the Geneva-based company's scientists report on the creation of improved Golden Rice, rice genetically modified to produce beta-carotene. And in a news story in the March 24, 2005, issue of Nature, that journal reports that Syngenta mistakenly sold several tons of corn that were modified with the gene Bt10, rather than the approved Bt11. Regulatory agencies did not notice the mistake until Syngenta informed the Environmental Protection Agency and the USDA late in 2004.

As part of the answer to global hunger, some scientists and policymakers long have hoped that foodstuffs could be genetically engineered to provide higher nutritional value. The scientific underpinnings of that hope received a boost this week, with the publication of the second-generation Golden Rice article.

One grain at a time, rice is the source of more calories than any other food in the world. Unfortunately, a high beta-carotene content does not rank among rice's many virtues; even whole-grain rice contains only minimal amounts of beta-carotene, and milled rice contains next to none. Beta-carotene is a precursor to vitamin A, which, in turn, is crucial for the development of the visual system. Vitamin A deficiency is the leading cause of preventable blindness in children, accounting for a quarter-million to half a million cases a year, according to World Health Organization statistics. Vitamin A also is important for immune system functioning, and about 40 percent of children under age 5 in the developing world suffer from immune system weaknesses consequent to vitamin A deficiencies.

In plants, beta-carotene is synthesized from a precursor known as geranyl geranyl diphosphate, which is transformed into beta-carotene through a series of intermediates by the sequential action of two enzymes: phytoene synthase (psy) and carotene desaturase (crtI). Because rice produces geranyl geranyl diphosphate in its endosperm and is a staple food in several areas of the world where vitamin A deficiency is a pressing problem, scientists from the Swiss Federal Institute of Technology in Zurich and the University of Freiburg in Germany decided to try to engineer the beta-carotene-synthesizing enzymes into rice.

It worked, and the technique was published in Science in 2000. Original Golden Rice contained a bacterial crtI and a psy gene from daffodils.

"The scientists involved [in the creation of original Golden Rice] purposefully chose the daffodil gene for good reasons; daffodil petals are a rich source of carotenoid" and daffodil plants share some characteristics with rice plants, Rachel Drake, research project manager at Syngenta and senior author of the paper describing Golden Rice 2, told BioWorld Today.

Original Golden Rice contained more beta-carotene than natural varieties, but the proof was in the (rice) pudding; in the end, beta-carotene levels still were insufficient to allow practical implementation in the field.

In the new work, Drake and colleagues at Syngenta screened a variety of psy genes to find ones that might allow more beta-carotene accumulation than the original Golden Rice. Psy genes from different plant species were combined with a bacterial crtI gene, and the resulting expression cassette first was used to transform corn plants, which are experimentally more tractable than rice.

And The Winner Is. . . Rice Psy, Almost

Ironically, the daffodil psy that had been used to transform the original Golden Rice was the poorest performer of the species tested, while rice psy was one of the best. The reason that wild-type rice is a poor provider of vitamin A despite its active psy gene could be summed up as "so close and yet so far."

"It is not just the presence of the DNA that is needed, the gene must also be switched on at the right time and place," Drake said. "In rice, the native rice psy is switched on in the leaves and other green parts of the plant. It is not switched on in the endosperm. The psy that we transformed is designed to switch on in the endosperm; this is necessary to make Golden Rice," Drake said.

To make Golden Rice 2, the scientists decided to use the maize psy gene. When rice plants were transformed with the maize psy plus bacterial crtI, the rice produced up to 23 times more beta-carotene than original Golden Rice.

Syngenta plans to donate the new technology to the Golden Rice Humanitarian Board, a nonprofit organization dedicated to facilitating the evaluation and eventual use of Golden Rice.

Malnutrition is not just a scientific issue, as the board noted in an editorial accompanying the scientific paper. The editorial stated that "malnutrition is rooted in political, economic and cultural issues that cannot be magically resolved by a single agricultural technology." To name just the most obvious stumbling block, to be utilized effectively beta-carotene must be eaten as part of a balanced diet that contains certain fats as well as leafy greens, and such a diet might be hard to come by for the poor who are supposed to benefit from Golden Rice.

The editorial also points out the need for field-study trials as well as the need for countries that are supposed to be the beneficiaries of the technology to evaluate Golden Rice through their own political process without being pressured to either accept or reject the technology.

But the technology itself was evaluated positively, from both a nutritional and a farming standpoint. In the editorial, the Golden Rice Humanitarian Board called the beta-carotene increase in Golden Rice 2 "an exciting advance." It also noted that "Golden Rice is compatible with farmers using traditional farming systems, without the need for additional agronomic inputs. Therefore, no new dependencies will be created. Furthermore, the Golden trait does not pose any known risk to the environment."