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PHOTO BY DON MANNING *IR.winter97 w/bleeds 6/25/97 11:19 AM Page 12 Illinois Research 12 Volume 1, Number 1, 1997 *IR.winter97 w/bleeds 6/25/97 11:19 AM Page 13 genetic journey “We are witnesses to and participants in a watershed of human history... in all of this there are promises to ponder, both realistic and inflated, and dangers to consider, both real and imagined. We have already entered the doorway of the Gene Future.” Thomas F. Lee, Gene Future By Doug Peterson Illinois Research 13 Volume 1, Number 1, 1997 *IR.winter97 w/bleeds 6/25/97 11:20 AM Page 14 I n 1878, a young horticulturist stopped at a monastery to see the gardens cultivated by a modest Moravian monk named Gregor Mendel. When the horticulturist asked the monk how he had man- aged to “reshape” several beds of green peas to reach certain heights and display certain characteristics, Mendel reportedly said, “It is just a little trick, but there is a long story connected with it which would take too long to tell.” A long story, indeed. As it came to be, Mendel’s “little tricks” with green peas established several revolutionary laws of heredity and earned him the title of “the father of genetics.” Mendel had presented a paper about his hybrid work on peas in 1865, but his research went unnoticed until 1900—after the monk had died. The history of genetics has not only been a long story. It has been a long journey, tracing back thousands of years. Mendel’s work was one of the major milestones along this path, and it set the stage for dramatic plant-breeding successes in the twentieth century. Today, the path for this genetic journey is something of a superhighway, as research progresses at accelerating speed. In agriculture, revolutionary new technologies now allow the direct transfer of genes from one organism to another—what people normally think of when they hear the term “genetic engineering.” For instance, Bt corn has been genetically engineered to contain a toxin made by Bacillus thuringiensis (Bt), a bacterium that is nontoxic to humans but controls European corn borers. “Out in the field, that’s all that people want to talk to me about,” says University of Illinois entomologist Kevin Steffey. If the gene revolution fulfills its promises in agriculture, it couldn’t be better timed. Jerry Nelson, a U of I agricultural economist, says that yields on farmers’ fields and research plots began to stagnate in the late 1980s. In fact, by the early 1990s, the rate of growth in agricultural productivity fell for the first time below the rate of growth in the worldwide demand for some important food crops. Pressures on the food supply are coming from both poverty and affluence, Nelson says. The poorest people tend to be concentrated on fragile land, straining the limits of soil and water. Meanwhile, a rising middle class throughout the world, particularly in Asia, is increasing the demand for meat. (See Perspectives, p. 2). As an added twist to the scenario, Americans are putting greater emphasis on a diet that meets specific qualities— food higher in nutrition, lower in fat, and increasingly safe. To meet these varied demands, the focus of genetic research is not just about boosting yields. It’s also about controlling insects and diseases and boosting food’s nutritional value. At the U of I, genetic research on plants and animals reflects this broad focus, as the following five stories demonstrate. These stories describe just a part of the genetic work going on in three critical areas—soybeans, corn, and animals. And at the heart of each story are those tightly coiled strands of DNA—the genes that make up chromosomes and that hold the blueprints for genetic traits. “Genes are the central core of plant and animal research,” says Ted Hymowitz, U of I plant geneticist. “It all begins with the DNA.” Harris Lewin, professor of animal sciences, reviews an autoradiogram with student, PHOTO BY DAVID RIECKS Shelley Fisher. Lewin found a link between certain genes and the resistance of cows to the Bovine Leukemia Virus. Illinois Research 14 Volume 1, Number 1, 1997 *IR.winter97 w/bleeds 6/25/97 11:20 AM Page 15 “Genes are the central core of plant and animal research. It all begins with the DNA.” mapping the animal genome arris Lewin’s lifelong fascination with farming began while growing up in the most urban of locales—New York City. He was probably one of the few five-year-olds in the city to get up at 5:30 on Saturday mornings to watch Modern Farmer on television. This same fascination drives Lewin’s research today as he works to map those genes that control important traits for cattle. Lewin, a University of Illinois professor of animal science and director of the university’s Biotechnology Center, is one of the leaders behind the National Animal Genome Research Program, a less-publicized counterpart to the Human Genome Project. The project is striving to develop genome maps for the most important agricultural animal species—pigs, cattle, poultry, and sheep. “Think of a gene map in the same way as an ordinary road map, depicting a very complex highway system composed of many different ‘roads’ that intersect and cross each other,” Lewin H says. “A gene map shows you the signposts along the way, telling your location on a chromosome.” Researchers look for signposts— called “gene markers”—that will direct them to the genes controlling important traits, such as disease resistance. Cattle have the same number of chromosomes, and the genes are ordered in the same way on those chromosomes. Scientists are looking for differences in the genes themselves that give one cow an advantage over another. Lewin has worked extensively on the BoLA system of genes—the master genes of the mammalian immune system. He found a link between certain BoLA genes and the resistance of cows to the Bovine Leukemia Virus (BLV). About 50 percent of the dairy cows in the United States are infected with BLV, and about 30 percent of the infected cows develop “persistent lymphocytosis”—a serious ailment that reduces milk production. By identifying the BoLA genes that offer resistance to persistent lymphocytosis, producers can breed for that disease-resistant quality, saving millions of dollars nationwide. Illinois Research 15 Volume 1, Number 1, 1997 According to Lewin, global food production will be a major issue in the next century. But he believes that significant increases in the quantity and quality of plant and animal products will require an understanding of the genes behind economically important traits. To further such genetic research, the Biotechnology Center, working closely with the College of Agricultural, Consumer and Environmental Sciences and other colleges on campus, is developing plans for a Center for Comparative Genome Science. The center will feature a large lab with several automated “DNA sequencers” for researchers studying organisms with agricultural significance—plants, animals, and even microbial life. This technology was first used in agriculture earlier in the 1990s, and the first genetically engineered plant species are just now becoming available. “Equipment in the new center will do the work much faster,” Lewin says. “That’s why there is so much excitement.” *IR.winter97 w/bleeds 6/25/97 11:21 AM Page 16 developing thoroughbred corn stalking the wild soybean or nearly 20 years, Ted Hymowitz has traveled across the world in search of genetic treasure. And along the way, he has faced serious injuries, foreign prisons, policemen wielding machine guns, and termite soup—not to mention the sand traps and mudholes that have stymied his vehicles. Hymowitz, a U of I plant geneticist, has been searching for distant relatives of the soybean—wild species with a wealth of genetic traits that offer promise to soybean breeders. It’s a hunt that has taken him to over one hundred countries, including such far-flung locations as Fiji, Tonga, Papua New Guinea, Taiwan, Japan, Indonesia, and most recently the outback of Australia. “The whole idea behind the project is that wild relatives of cultivated plants have much to offer in terms of genetic diversity,” Hymowitz says. “Wild plants have developed under completely different conditions than cultivated plants, so you can expect genetic differences.” Some of these genetic differences offer hope of disease and insect resistance—as long as the traits can be passed on to the cultivated soybean. Since 1976, Hymowitz and his colleagues have discovered and collected ten new wild perennial relatives of the soybean, bringing the total to sixteen. They also have discovered that among the sixteen wild species, there is genetic resistance to the most economically damaging diseases of the soybean, including major ones such as soybean cyst nematode, soybean rust, and white mold. The research team is now taking the next big step—determining whether these traits can be passed on to the cultivated soybean plant. The first results should be back within a year, Hymowitz says. Reaching this step, however, has taken a lot of vigorous, basic research. “To make use of this wild material, someone has to go out and get it,” he says. “And it’s not found in London, Rome, or Paris. First, we have to get to know the environment of the plants we are looking for. We must know the ecology and do a lot of map work so we can narrow the search. And we must build on experience.” Put an emphasis on the word “experience.” Hymowitz has had his share of singular experiences, including the time he fell down a mountainside in Vanuatu (formerly New Hebrides), injuring his arm and leg. Three days later, when he finally reached a hospital, gangrene had set in, but an Australian doctor managed to save his arm and leg. After being discharged from the hospital, with his leg still swollen, he immediately rented a car and returned to the hunt. Hymowitz has also been shot at by smugglers who thought he was police, and he has been detained by police, who thought he was a smuggler. “This kind of work takes resources, money, the right personnel, and a little faith,” Hymowitz says. “It’s like that with any basic research. This stage of research is not putting money into anyone’s pocket, but it will have economic benefits down the line.” From such work also comes some unexpected spin-offs. For instance, Hymowitz and his colleagues ended up mapping the soybean’s chromosomes in 1988—something that had been achieved with other crops, but never with soybeans. As Hymowitz observes, “You never know where basic research will lead.” F Illinois Research 16 orbert Rocheford is looking for a few good genes. He and his fellow U of I “gene jockeys” are searching for and mapping genes that control key qualities of the corn kernel. But it’s a painstaking process, because each chromosome in corn contains thousands of genes, while only five or six of those genes may be responsible for much of the variation of a particular corn trait. Rocheford, an associate professor of plant genetics, is presently looking for “gene markers” that identify those regions of the chromosome controlling production of Vitamins E and A in corn. Being able to control Vitamin E and A levels in corn might have significant implications for both animal and human nutrition. In a 1993 study, for instance, Vitamin E supplements reduced heart disease by 41 percent among 87,000 female nurses. What’s more, Rocheford says, receiving Vitamin E naturally through the food supply seems to provide greater health benefits than taking high doses in pill form. Like Vitamin E, Vitamin A is an “antioxidant,” which means it too could help prevent heart attacks. But the data on its role as an antioxidant is more conflicting than with Vitamin E. Rocheford and his colleagues, plant genetics professors Robert Lambert and John Dudley, have just begun mapping the genes responsible for Vitamins E and A in corn, and they have done extensive mapping of other genes, such as those controlling the oil and fatty acid content of corn kernels. “If we can increase the Vitamin A and E levels in grain, the grain will be more nutritious for human consumption or as animal feed,” Rocheford says. “And if the grain being fed to animals is better, the meat will also be more nutritious.” T Volume 1, Number 1, 1997 *IR.winter97 w/bleeds 6/25/97 11:21 AM Page 17 exploring the soybean gene pool PHOTO BY MATTHEW WHEELER he gene pool that soybean breeders draw upon today might be better characterized as a wading pool in terms of its depth. Ninety-five percent of the genes in commercial soybeans today come from only 35 ancestors. Such a small gene pool could mean stagnating yields in the future, but U of I researchers are trying to guard against such an outcome. Because the modern varieties that have been derived from those 35 soybean ancestors are so high-yielding, it makes sense that plant breeders continue to use those varieties as parents in creating new varieties, says Randall Nelson, U of I associate professor of plant genetics and research geneticist with USDAAgricultural Research Service. But there is a risk involved. By using only varieties descended from these 35 ancestors, you draw from a limited gene pool; as a result, diversity is lost from that pool with each new set of varieties. Eventually, this will make it more difficult to produce new varieties with higher yields. To safeguard against stagnating yield rates, Nelson and his fellow researchers are drawing upon the 15,000 lines of soybeans in the USDA collection, which has been housed in Urbana since 1949. Compared to the beans that farmers grow, the 15,000 lines are low-yielding. But Nelson has been able to produce high-yielding experimental lines by crossing some of the low-yielding varieties with high-yielding commercial varieties. What’s more, he says, the highyielding experimental lines that result are genetically distinct from the varieties farmers use. This research demonstrates that it is possible to increase both genetic diversity and yield, which may help increase the rate of yield improvement in the future. T The most common method for transferring desirable DNA to swine is “microinjection.” The DNA is microinjected into a one-cell fertilized embryo. Eventually, the injected embryo is transferred to a suitably prepared animal. the genetic legacy of Big Al t all began with “Big Al”—the patriarch of a rapidly growing line of “transgenic” pigs. Big Al earned his fame in 1994 by becoming the first pig to receive the alpha-lactalbumin gene from a Holstein dairy cow, says Matthew Wheeler, associate professor of physiology in the U of I’s Department of Animal Sciences. Transgenic animals, he says, have had one or more genes transplanted in them from another animal. Scientists believe that animals carrying the alpha-lactalbumin gene produce greater amounts of milk—a factor that could boost the weight of piglets and increase the chances of survival for animals in each litter. If milk production would increase by as little as 10 percent, Wheeler projects that each piglet in an average litter could gain 11/2 additional pounds. This boost alone could mean 25 to 30 million additional dollars per year for the pork industry. Big Al, alas, is no longer alive, but his transgenic legacy continues in the I Illinois Research 17 Volume 1, Number 1, 1997 generations that he begat. Five of his daughters and four of his sons have carried on the alpha-lactalbumin gene. The daughters have been bred, and as their litters arrive, U of I researchers monitor their milk production. “It’s still too early to know whether milk production is increasing,” Wheeler says. “We’ll need at least 25 to 30 litters before we can have any definitive answers.” In the meantime, Wheeler is working with U of I nutritionist Sharon Donovan to create another line of transgenic pigs. This line of pigs would carry a gene that produces a specific protein to improve digestive function in piglets and thus increase their survivability. The work carries implications for people as well, because it may be possible to purify this protein out of sows’ milk and add it to human infant formula. The same genetic technique could be used to produce other proteins that benefit human health.