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Scientists take on tobacco genome
By Adam Marcus

An effort is underway to sequence the genome of Burley tobacco, a staple of Southern U.S. farmers and plant researchers alike.

Tobacco field.

Scientists at North Carolina State University in Raleigh, are leading the Tobacco Genome Initiative, launched late last year. Philip Morris, maker of Marlboro, Virginia Slims and other top-selling cigarettes, is providing $17.6 million over 4.5 years for the project.

Tobacco is a favorite of plant biologists—and not for its recreational uses. The malleable plant is reputedly the easiest species to engineer. Scientists have already created nicotine-free tobacco strains, and researchers in the U.K. have given the plants a gene from a bacterium, Enterobacter cloacae, that can draw TNT from soil, for instance, at older munitions factories.

Tobacco plants even have the potential to become factories for therapeutic proteins and other useful substances.

"Tobacco is one of the best model systems for looking at plant-disease interactions," says Steve Lommel, professor of plant pathology and genetics at N.C. State, and a leader of the project. Lommel says the money from Philip Morris should be enough to sequence 90 percent of the tobacco genome, which has about 40 percent more base pairs than the human genome.

Jennifer Golisch, a spokeswoman for Philip Morris USA, says the company is funding the genome sequencing as part of a larger effort to produce "reduced-risk" tobacco products. "We hope that by increasing our understanding of the tobacco plant and its genetic composition we will gain a better understanding of its [ability] to produce nicotine," Golisch says.

Alec Hayes, a research scientist for Philip Morris, says the company is also looking for genetic ways of reducing levels in tobacco of heavy metals, especially the carcinogen cadmium.

Tobacco is believed to have between 25,000 and 50,000 genes in its five billion base pair genome, yet the vast bulk of its DNA doesn't encode for proteins. Rather, it consists of long stretches of repetitive DNA that scientists must weed out to find the interesting segments. To find these genes, the N.C. State researchers will be using mapping technology from Orion Genomics, of St. Louis.

Carole Cramer, a plant pathologist at Virginia Tech University in Blacksburg, wants to turn tobacco leaves into pharmaceutical mills. Tobacco is an ideal plant for generating therapeutic proteins, such as those used in vaccines or to fight cancer, Cramer says. It readily takes in foreign genes and a single plant in a greenhouse can generate up to a million seeds. Bacteria also serve as protein factories, but they require expensive 'fermenters' that make mass production costly. The only ceiling for raising tobacco is the availability of farmland.

Knowing the genome of the plant could aid her work, says Cramer. On her wish list are new ways to switch on and regulate genes, and how to make them more efficient protein producers. A roster of genes the species uses to fight disease would also be a boon, especially since densely grown plants seem to face different illnesses.

Cramer helped found a company, CropTech, to commercialize drug-making plants. The Blacksburg-based firm has yet to bring a product to clinical trials, though Cramer says it could have one within the next two years. She declined to identify the molecule or what it is intended to treat.

John Dangl, a plant biologist at the University of North Carolina, Chapel Hill, says he'd oppose a tobacco genome project that relied on public funding, which the current one does not.

"We've already made a huge investment in species of the same family, potato and tomato," says Dangl, who specializes in disease resistance in the mustard weed Arabidopsis. "Let's focus on a crop that doesn't kill people."

"Philip Morris USA Provides $17.6 Million for Tobacco Genome Mapping." Press Release, North Carolina State University, Raleigh (December 11, 2002).

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