Behind Political Smoke, Tobacco Bioengineering Shines as Model

As biotech breakthroughs go, Brown & Williamson’s controversial efforts to genetically engineer a line of high-nicotine tobacco qualified perhaps as something out of “The Gang That Couldn’t Splice Straight.” So what’s next? Pork genetically packed with extra lipids? Oranges engineered to be free of Vitamin C?

But blow away some of the smoke and what you’ll find is an unusual case study in successful technology transfer, and a superb example of the role of serendipity in promoting biotech innovation. Now, it’s probably not wise to rely on tobacco companies for medical advice or congressional testimony, but when it comes to exploring the market potential of biotechnology, the people who make cigarettes are not slow on the draw.

By sheer happenstance, it turns out that tobacco companies have the inside track when it comes to exploiting innovations in plant genetics and biotechnology. Why? Because tobacco is the scientific standard. For decades, tobacco has been the experimental plant of choice for researchers in the biotech community. Everyone who’s anyone in plant genetics has done nicotiana tobacum .

“It’s like a mouse,” says University of Illinois plant pathologist Paul D. Shaw. “Almost everybody uses it one way or another. A lot is known about the genetics; it’s easy to construct hybrids and crosses and it’s a very easy plant to grow. The tobacco industry, whenever it has a serious disease problem--on its plants, I mean--can easily transform the plant and breed other varieties for disease resistance. It’s just a great plant to manipulate.”

“Tobacco happens to be an excellent plant to work on from a plant-biochemistry and -physiology point of view,” agrees Howard Brooks, the U.S. Department of Agriculture’s associate deputy administrator for plant sciences. “It’s extremely useful as a model plant system.”

In fact, tobacco-based research has won the Nobel Prize: Nearly 60 years ago, Rockefeller Institute scientist Wendell Stanley’s work crystallizing the tobacco mosaic virus offered powerful insight into the structural nature of viruses.

In other words, scientists probably knew more about tobacco than any other plant in existence. That was the rich research context that would lure the tobacco companies into multimillion-dollar partnerships with so many of the budding young plant biotech entrepreneurs of the 1980s; it seemed a natural match.

“In the early 1980s, we had already been using tobacco as a model system for experiments,” recalls DNA Plant Technology’s David Evans, the company’s vice president for business development. “Our interest was more in tissue culture--how to get whole plants from just a few cells--and what we did worked better on tobacco than anything else.

“But we weren’t using tobacco strains that were commercially viable. So several companies and us, we scratched our heads and said maybe we can make money off of this. I didn’t have a clue. There was just the idea that there might be a marriage there. So companies like Crop Genetics and Calgene and us all had deals with tobacco companies in the early 1980s.”

So Crop Genetics and Calgene hooked up with Philip Morris; Plant Genetic Systems went with Japan Tobacco. DNA Plant Technology became partner to the Louisville, Ky.-based, British American Tobacco-owned Brown & Williamson.

“They were among the best people we worked with,” says Evans, who recalls that his company “floundered for a couple of years” trying to figure out which collaboration would make the most sense. Brown & Williamson declines to comment.

But soon after, the tobacco giant came to DNA Plant Technology with a high-nicotine plant developed in concert with scientists at North Carolina State--an excellent example of industry-academe collaboration and technology transfer--and the company was able to use its tissue culture biotechnology to breed a “better” plant.

That plant, grown overseas, yielded the potent leaves that were dried and cured into Y-1, the high-nicotine “blending” agent that Food and Drug Administration chief Dr. David Kessler condemned as an example of improper manipulation of cigarette nicotine levels.

“My view was that we had a technical success, but the company (Brown & Williamson) wasn’t able to commercially exploit it,” Evans says. “A technology success, yes; a commercial success, no.”

Of course, there are other routes through which cigarette companies can exploit biotechnology for nicotine profit. Much as the National Institutes of Health is trying to sequence key portions of the human genome, Philip Morris is reportedly trying to map and sequence the vital parts of the tobacco genome: just which genetic instructions express themselves in the plant’s tar and nicotine levels. Like other biotech firms, Philip Morris is trying to patent those sequences. It’s far too early to say whether these approaches will be any more successful than Y-1.

Ironically, however, precisely at the moment when molecular biology and agricultural bioengineering assume even greater prominence, tobacco is dying out as the experimental plant of choice. Plant molecular biologists are flocking to arabodapsis--a relative of cabbage and canola--because it grows and reproduces faster and has a smaller and easier genetic instruction set than tobacco.

“I don’t think it will be used as much as an experimental model anymore,” says Agriculture’s Brooks. “In research, tobacco’s best days are behind it.”

But wait! DNA Plant Technology’s Evans insists that tobacco still has great potential. “Since tobacco grows so fast and is so easy to grow and manipulate,it will be used to grow alternative materials,” he says. “In five years, tobacco could be used as a medium to grow food flavoring and fragrance compounds.”

Indeed, Evans even predicts that tobacco might become a cash crop for “pharming”--plants genetically engineered to contain life-saving pharmaceuticals than can be processed after harvest. “I think that would attract an awful lot of research,” he says.

Indeed, perhaps we’ll even see a methanol-like subsidy that pays tobacco farmers to grow alternative materials just as grain farmers get one to grow crops for methanol production.

Is this the future of tobacco biotechnology? Or is the industry just blowing smoke? Don’t hold your breath. . . . Sorry.