By David N. Leff

Malaria, the most notorious tropical disease, kills some 2 million victims each year, most of them children. They die of a co-conspiracy between the malarial parasite, Plasmodium, and its airborne delivery vehicle, the anopheles mosquito.

Just as deadly is a tropical disease of a different kind - vitamin A deficiency. No parasite is to blame for this worldwide malady, which inflicts blindness and other physical mayhem, before wreaking its fatalities. Paradoxically, the culprit is the planet's principal foodstuff - rice (Oryza sativa). Half the world's population consumes this cereal grain daily - more than any other foodstuff on earth.

As we know from our grocery shelves, rice comes in two colors - white and brown. But out in the poorer, Third World, where rice is the main subsistence food, the brown outer coat - although rich in beta-carotene, the precursor to fat-soluble vitamin A - is milled off, leaving the white endosperm for consumption. The reason for this removal is that the brown cover would go bad in storage, rendering the white inner grain inedible.

The scientific synonym for vitamin A is retinol - which recalls that lack of this vitamin in the diet attacks the retina of the eye, where it affects the rhodopsin photoreceptors. Shortage of retinol's provitamin degrades or destroys eyesight - from night blindness to total blindness. An estimated 124 million children in the world suffer from avitaminosis-A, and 1 million to 2 million of them die every year from its effects.

The celebrated Green Revolution, sponsored by the Rockefeller Foundation a generation ago, could not escape the trap that discarding the brown integument left behind white rice of dangerously poor nutritive value.

Rockefeller Buys Into Carotene Restoration Vision

That's about to change, thanks to a Swiss field plant biologist, Ingo Potrykus, who heads a molecular genetics laboratory at the Swiss Federal Institute of Technology's Plant Sciences Institute in Zurich. Potrykus is senior author of a paper in today's issue of Science, dated Jan. 14, 2000, titled: "Engineering the provitamin A (b-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm."

"This work started nine years ago," Potrykus told BioWorld Today." At that time, in the early '90s, I proposed to the Rockefeller Foundation that it try, in the framework of its rice biotechnology program, to finance a project working toward restoring beta-carotene to rice.

"In early '91, the Rockefeller started to fund this approach, and with this money over the following eight years we were able to put all the necessary genes together and do the genetic engineering and biochemical analysis"

Here is how Potrykus described this feat of recombinant genetic engineering:

"We needed four genes to do the job," he recounted. "Three to promote the biosynthetic pathway, and one to select for the transgenic material. We achieved this selection by using the hygromycin antibiotic-resistance gene. The beta-carotene biochemical pathway was reached by introducing three transgenes.

"The first gene expressed phytoene synthase (psy), the second bacterial desaturase (crtI), and the final one, lycopene beta-cyclase (lcy). To introduce those four genes into the rice genome," Potrykus continued, "we made two constructs. The first contained the psy and crtI sequences, which we inserted in a strain of Agrobacterium tumefaciens. The second construct contained the hygromycin resistance gene with the lcy, which we introduced into a different A. tumefaciens strain.

"Then we mixed both constructs, and offered them to rice-plant cells. In the transgenic offspring from this experiment we identified a series of rice plants containing and expressing the beta-carotene biosynthetic pathway genes. Both biochemical and visual analysis showed that these genes had activated the entire biosynthetic pathway leading to beta-carotene." The newly restored rice in neither white nor brown, but golden in color, reflecting carotene's pigmentation.

Where things stand at present, Potrykus stated, "is that scientifically the project is complete. To complete it agronomically, we have arranged with 10 public rice research institutions all over the world - two each in Southeast Asia, China, India, Africa and Latin America - to take over this material, and by traditional breeding develop it into the agronomically best-performing lines of rice, but having in addition the new nutritional character." He estimates this will take about two years.

"At the same time," Potrykus went on" the necessary assessment studies - ecological, socioeconomic and foodstuff evaluation - will be done in parallel, and there the Australian government's science and industry research organization will take a leading part."

Will Firms Free Up Patents For Free Rice Distribution?

"Further," he pointed out, "we are giving our technology free to subsistence farmers in developing countries for noncommercial use. But we have of course used lots of existing technology, which is patented, and constitute the intellectual property rights [IPR] of lots of different companies. Accordingly, two institutions are doing IPR audits to find out who all may have rights on tiny parts of this technology. They would have to be asked to give it away free."

Potrykus foresees, "By the end of two years from now, there is a realistic chance that new, agronomically high-performing rice varieties will be ready for distribution free of charge in all rice-growing countries for noncommercial use.

"I am still leading all of this work," he observed. "The material is still in my hands, and we are continuing on the same lines. We have recently produced rice that will improve nutritional iron bioavailability. Our manuscript reporting this development is going to Nature Biotechnology the beginning of next week. And we are working on inserting additional vitamins in rice, as well as essential amino acids. Also, we are starting collaborations to transfer the same trait to wheat, banana, cassava and sweet potato. So we are quite busy," he concluded, "in further exploiting this scientific breakthrough."

In a commentary titled "The Green Revolution Strikes Gold," molecular biologist Mary Lou Guerinot, at Dartmouth College in Hanover, Mass., made this sociological point: "The fact that rice plants normally do make cartenoids should go a long way toward calming fears about 'Frankenfoods.'"