A cacophony of comment greeted last year's announcement of the human genome's sequencing. Response to the Jan. 26 announcement that the rice genome has been mapped has been a comparative whisper. That's understandable, because in Western countries, rice is an also-ran grain. Yet rice is the staple for half the planet--three billion people. It is mankind's single most important food. So a lot of people around the world will be watching very closely what Syngenta--the Swiss-based agribusiness company that owns the genome data--will do.

Syngenta asserts proprietary rights over its data, and will require academic as well as commercial researchers to sign a contract acknowledging its rights. Since free exchange of data is a fundamental principle of academic science, some researchers are considering taking a pass and waiting for a public rice genome initiative scheduled to finish in 2003. (An earlier "working draft" of the rice genome completed for Monsanto has been made available to the International Rice Genome Sequence Project.)

Syngenta is committed to helping subsistence farmers, including providing improved rice already available, such as the "golden rice" genetically modified to provide more Vitamin A, says Steve Briggs, president of the Torrey Mesa Research Institute, Syngenta's San Diego-based research center. Syngenta earlier made 100,000 rice genome sequence fragments publicly available on the Web. "All the technology that's required to bring improved varieties to the hands of subsistence farmers is being donated free of cost or royalties," Briggs says. The genome sequence itself is highly reliable, he adds. "It's a complete genome sequence. It's high quality. The coverage is greater than 99 percent, compared to the human genome that's only 90 to 95 percent. The accuracy is higher, so it's a lot better map than (that of) the Human Genome Project. We refer to it the agricultural equivalent of the Human Genome Project, but in fact it's a higher quality project." Few would dispute the significance of Syngenta's accomplishment, done in collaboration with Myriad Genetics (Salt Lake City, UT) and Clemson University in South Carolina.

"Completing the rice genome is a major landmark in our advancement in plant biotechnology," says C.S. Prakash, professor in plant molecular genetics and director of the Center for Plant Biotechnology Research at Tuskegee University. "Not only is it the most important food crop in the world, we expect we'll need to be producing 60 percent more rice in the next 20 years, with less land, less water, and perhaps less chemicals. Understanding the rice genome will bring us one step further toward achieving that goal."

However, recent history shows that many activist groups won't be mollified by these promised gains, because they reject much of what agricultural biotechnology has to offer, or at least the corporations that want to be its vehicle. Last year's introduction of "golden rice" was opposed by activists such as Greenpeace because it was developed through their bęte noir of transgenic engineering and because it helps modern agribusiness. So the genome mapping of rice by a private company unleashes all the elements of a socio-economic drama: the tension between rich and poor countries, old cultural traditions vs. modern biotechnology, and the search for corporate profits.

Small Genome, Big Prize

Despite its secondary role in Western countries, agbiotech focused on rice first because its genome is the smallest of major cereals--six times smaller than that of corn and 37 times smaller than that of wheat. So given the close homology already known to exist between rice genes and those of other cereals, knowing the rice genome automatically means one has a rough guide to where genes in the other genomes might be. And Syngenta is looking at using conventional breeding, along with more controversial transgenic technology, to take advantage of this knowledge. "

"There's not only similarity, but co-linearity," Prakash says. "Even the arrangement of genes, how they're scattered on the chromosomes, tends to be fairly similar among crop plants.

One of the most urgent needs in rice cultivation is to increase the yield to keep up with a booming global population. The annual increase in yield of rice has dropped in the last 40 years, says Christopher R. Somerville, director of the Carnegie Institute of Washington's department of plant biology at Stanford University in California. Up until 1960, the rate of increase was four percent, while today it's stuck at one percent per year. "That's all that can be achieved by breeding, and it's heading toward zero," Somerville says. Knowing the genome map should speed up genetic work in rice and other cereals by a factor of 50, Somerville says. A specialist in arabidopsis, Somerville says that's how much research speed has increased since that workhorse plant's genome was made public at the end of last year.

"My lab cloned the first plant gene by map-based cloning in 1992," Somerville says. "That took us 6 person-years in arabidopsis. Now we can do it in 6 weeks. As that rice sequence becomes available to researchers, it greatly reduces the cost and time to find the genetic basis for a trait. It brings it down to the level where you don't have to have big, heavily funded mechanized research labs. Individuals now, working all over the world can do it without huge research support .. Things that people just knew they couldn't do in the past, because students didn't have long enough in their whole career to carry out one of the projects, now they can be undertaken." Somerville says that examining cultivated varieties will unravel how they grow and why some plants are small and slow-growing, and others large and grow quickly. Because of the similarity across the cereal grasses, Somerville says the findings in rice should be transferable to wheat, oats, and other crops.

"Gene discovery of location and function happens faster in a model system," says Mark E. Sorrells, a professor of plant breeding at Cornell University. "It will always happen faster in model systems than in species that have large, complex genomes and are polyploid. The idea is to take advantage of that faster rate of gene discovery by transferring that information to other species."

As head of the Small Grains Breeding Project, Sorrells is looking for ways to improve tef, a grain that is a major staple in famine-plagued Ethiopia. Tef has a high protein content and is drought-tolerant, and the Small Grains Breeding Project is looking for ways to increase tef yield. The rice genome will be more useful than that of arabidopsis for comparative analysis of tef, Sorrells said, because arabidopsis is only a distant cousin to the grains.

"We're looking for genes in the rice genome that have been characterized, both in terms of their effect on the phenotype and in their metabolic pathway function," Sorrells says. "Then we can utilize that information by finding the same gene in tef, and hopefully it matches up with a phenotype or a QTL (quantitative trait locus) that we've characterized in a test population."

Rice itself has several defects as a human food. Its cultivation depends upon a plentiful water supply, and it's vulnerable to some serious diseases such rice blast. Aside from that, the grain is deficient in Vitamin A and iron. Rice actually produces a chelating compound, phytic acid, that takes iron out of the diet, Somerville says. And rice is far from the only water hog; it takes 17,000 pounds of water to produce one pound of cotton, Somerville says, and the ratio is similar for grains. Many of rice's shortcomings can be corrected without transgenic technology, Prakash says, by delving within the genome to make better use of what's already there. For example, golden rice was developed using a daffodil gene, but rice already produces provitamin A. The trouble is that it's in the husk, which is removed when rice is processed. With knowledge of the genome, it should be possible to coax this gene to produce provitamin A in the seed--without using controversial transgenic technologies. "That technique, called chimeraplasty, is already available," Prakash says. "We could make minor changes within a gene in a plant without introducing a foreign gene--more targeted, directed changes. This is just one of the applications. There's already research at putting iron genes into rice, and we could perhaps expedite that and make iron in a form that is bioavailable."

Somerville says the iron deficiency could be attacked by searching for all the genes that make phytic acid, so they can be either removed or modified, "probably by conventional mutation breeding." Although Syngenta is also planning to use conventional breeding, Briggs says the company isn't dropping transgenic crops; rather, it views breeding and transgenics as each having appropriate roles in crop development, with decisions made case by case.

"Our point of view is they're not substitutes for each other," Briggs says. "Whole genome recombination that breeding makes possible is extremely powerful. Now that we can observe all of the genes and their recombinations in unlimited detail, we can extract, for example, a rice blast gene that may already be present in exotic rice but not in germplasm that's used by breeders. I think this breeding application will be not only the fastest to marketplace, but also an ongoing and major way to improve varieties. And then (transgenics) deals more with discrete traits, and they can often be applied across crops species, not limited to one…both are important."

Briggs acknowledged that Syngenta will tailor its product development to the demands of its markets, including those that don't want transgenic crops. For example, Briggs says Syngenta is looking into the possibility of making a non-transgenic golden rice. "Now that we have a rice genome map, we can ask what are all the genes required for carotinoid synthesis, and then we can set up a diagnostic for each of those, and use that to screen the thousands of rice varieties that are not used in breeding programs," Briggs says. "We can perhaps find an old variety that maybe has one step in the carotinoid pathway that's highly expressed, and a different variety that has the second step, and so on, and pull them together through conventional breeding, until we recombine the pathway." This knowledge will help recapture genetic diversity lost in the development of these crops, Briggs adds. "When humans domesticated these crops, they did it with a very small fraction of the genetic diversity in the species, so all of our breeding material represents 1 percent, let's say, of the genetic potential that already exists in that species ... it opens up the genetic potential of the traditional unused varieties."

Academic qualms

Syngenta plans to work in a collaborative model with those who wish to use the rice genome information, Briggs says. "If in the collaboration itself, a commercially useful invention is made, we would expect at least the opportunity to share in that," he states. "In some cases we would pursue that, in others we wouldn't." Prakash says he hasn't yet looked at the contract Syngenta is proffering researchers, but isn't too concerned, as the limitation appears to apply to commercial uses and to the developed world. "For using in developing countries, for use on rice for poor farmers, I don't think there will be any problem," Prakash says.

Scott Jackson, a plant geneticist at the University of Minnesota, has registered to look at the Syngenta rice map. Jackson, a postdoctoral scientist in the department of agronomy and plant genetics, is researching the genetic characteristics of wild rice, recently found against conventional wisdom to be closely related to cultivated rice, the two having 80-05 percent gene co-linearity. Wild rice has some superior nutritional traits to cultivated rice, but yield is harmed by its tendency to shatter, or drop seeds from the head before harvest. Knowing the cultivated rice genome might yield genes controlling shatter that would apply to wild rice. Conversely, wild rice has traits that might be useful in cultivated rice. Native to northern Minnesota, wild rice is cold-hardy. But Jeffrey L. Bennetzen, a professor in the department of department of biological sciences at Purdue University, says he's not interested in signing up for data if he's restricted from sharing it. "There's always, when an industrial group makes a contribution, an initial statement that this will be available to the public with relatively few strings attached," Bennetzen says. "In the end, that's usually not the case. Often they make it so [highly restricted that] the public researchers are unwilling to use that resource."

For example, Bennetzen says, Monsanto's release of the draft rice genome sequence last year "wasn't of any value to me, because I wasn't willing to give up what I needed to give to get access that information." And there's a lot more to research than raw genomic data alone, he adds. "My research as a public scientist is funded by the U.S. government, by the citizens of this country. And when…10 percent of what I need [comes] from industry, whereas the other 90 percent is funded by federal dollars, and now the industry has complete rights over what I've done, I've really given away a whole lot of public value for a minor gain," Bennetzen says.

Sorrells says he has not applied to use the Syngenta data, and is still considering what effect the company's restrictions might have on his research. In addition, partial sequences are available from other sources such as Monsanto, albeit also with restrictions, Sorrells noted.

Somerville, of the Carnegie Institute of Washington, doesn't need the rice genome because he specializes in arabidopsis, whose genome is already in the public domain. However, he says those who work on rice need a public domain map such as that now being worked on. A public genome map will tend to make purveyors of privately held genome information offer better terms than if they alone held that information. "I don't think we can have sole sources for these really important sequences," Somerville says.

** NOTICE: In accordance with Title 17 U.S.C. Section 107, this material is distributed for research and educational purposes only. **