June 21, 2005

Researchers: Tobacco may be good for you

by K.C. Jaehnig


Caption follows story

CARBONDALE, Ill. -- Tobacco could be good for you.

A research team led by Southern Illinois University Carbondale biotechnologist David A. Lightfoot has found that tobacco equipped with an extra gene can produce markedly larger amounts of 159 chemical compounds. Fourteen of these could become the drugs of tomorrow, fighting off tumors, treating epilepsy and Parkinson's disease - maybe even curing the common cold.

The team includes Rajsree Mungur, a former SIUC graduate student now at Germany's Max Planck Institute in Potsdam, A.D.M. "Tony" Glass from the University of British Columbia in Canada and Dayan B. Goodenow from Phenomenome Discoveries Inc., a Canadian company based in Saskatoon, Saskatchewan. Details of this project, funded by the Illinois Council on Food and Agriculture Research, appear in this month's issue of the Journal of Biomedicine and Biotechnology.

"It's strange to think of tobacco having good things in it, but all plants do - as long as you don't set fire to them and inhale the smoke!" said Lightfoot, who developed the transgenic tobacco.

The key to tobacco's transformation from scourge to savior lies in the extra gene. Taken from a microbe that lives in the soil and altered to work in plants, this gene helps plant roots capture and use nearly all the nitrogen in today's cheap, popular, ammonium-based fertilizers.

"The original idea was that if we could beef up the nitrogen assimilation in crops like corn and tobacco, we could keep it from being flushed out of Midwest soils into the Mississippi River, into our drinking supplies," Lightfoot said.

"We started with tobacco because it's easier and cheaper to transform than corn, and we wanted to make sure the gene worked."

Lightfoot found it worked just as well in corn, but he hadn't reckoned on the storm of protest over genetically modified organisms, or GMOs, that swept through Europe in the late 1990s. Despite its environmental friendliness, the outlook for a food crop with an extra gene suddenly didn't seem so bright.

But while the practical prospects looked dim, the gene's "pure science" aspect intrigued Lightfoot.

"What bothered me was that I knew it worked, but I didn't understand why it worked," he said.

While looking for those "whys, "Lightfoot discovered some astonishing new "whats." In the years since he first started tinkering with his nitrogen-loving gene, scientists had come up with quick, cheap ways of measuring all the chemicals cells contain. Analysis of the transgenic tobacco detected some 3,000 chemicals, with nearly 2,400 of them different from those found in ordinary tobacco plants.

Using a new, advanced form of mass spectrometry, the research team determined each of those chemicals' precise weights. And because precise weights can predict chemical structure, the researchers could use a specialized federal database to match structures with names - a task that would have taken years using older techniques.

"Fifty-eight percent of these chemicals were entirely new - they'd never been described before - but we were able to name 41 compounds in the leaves and 117 in the roots," Lightfoot said.

One of the 14 compounds that eventually could become a drug is scopolepin, which increased in the transgenic tobacco by 250 percent.

"Scopolepin can inhibit E. coli O157 (the cause of several fatal food poisoning outbreaks in recent years)," Lightfoot said.

"It's also an anti-viral, so it might help knock down everything from the common cold to HIV, and it's an anti-inflammatory that's five times more effective than aspirin."

Other possible drugs include ptilocaulin, an anti-tumor agent; decanamide, which works against a particular enzyme active in Parkinson's disease; and diethadione, which may help prevent epileptic attacks. Ptilocaulin increased 294 percent, decanamide increased 435 percent, and diethadione increased 270 percent.

Nicotine, one of tobacco's less desirable compounds, increased, too, but in the roots, not in the leaves - an important difference.

"Normally, it's made in the roots and transported to the leaves, but we have mucked that up so it stays in the roots - killing insects instead of addicting humans," Lightfoot said.

A compound called swainsonine also increased in the roots - by 500 percent.

"This is a cancer therapy - it can inhibit an enzyme that cancer cells use to grow really quickly - but if you dig up the roots, you lose the leaves, so it's not of great use in tobacco," Lightfoot said.

"But the gene technology works in all sorts of root plants, such as potatoes. Wouldn't it be better to eat fries to cure cancer than to have chemotherapy and surgery as the norm?"

Tobacco's switch from harmful to helpful won't happen soon. Commercial producers likely would raise a hybrid form - a mix of the transgenic plant and the traditional burley used in cigarettes - and that kind of crossbreeding takes time. Further, to grow tobacco as a medicinal crop would require approval by the Food and Drug Administration - a notoriously slow process.

This potential new use likely comes too late to save the bulk of tobacco farms, many of which have ceased production since Congress ended price supports last year. But because a single plant would produce a lot of the desirable chemicals, it could well help those farms that survive.

"It's not the sort of technology that's going to give new uses to thousands of acres, but a two- to three-fold increase in the market for tobacco may keep growers in the Midwest in the business of growing a crop they're already very good at, "Lightfoot said.

Leading in research, creative and scholarly activities is among the goals of Southern at 150: Building Excellence Through Commitment, the blueprint for the development of the University by the time it celebrates its 150th anniversary in 2019.

(Caption: Cross examination -- In his laboratory at Southern Illinois University Carbondale, biotechnologist David A. Lightfoot crosses a genetically modified tobacco (left) he developed with a standard burley variety. Both the leaves and the roots of this transgenic plant contain high levels of chemical compounds that may someday become helpful drugs.)

Photo by Steve Buhman