On a Wednesday evening in early April, David Kessler is telling the story of The Tobacco Wars to a room full of about 50 people. The account is equal parts public health analysis, investigative journalism and detective story, with a few elements that are decidedly cloak-and-dagger: an informant code-named Cigarette, industry documents leaked in a plain white envelope, and painstaking searches through patents and customs declarations.

The opening chapter takes place in Washington, where as Food and Drug Administration commissioner in 1991, Dr. Kessler asked his staff why the FDA did not regulate tobacco. After all, it was clearly an addictive substance responsible for as many as 400,000 deaths a year in the United States alone. Why not try to prevent illness and death? Because 90 percent of smokers started in their teens, he also saw it as a pediatric health concern. Why not try to prevent young people from starting? The answer was direct, he recalls. “ 'Because that's one industry you can't take on. It's too powerful.' ”

Seven years later, the conventional wisdom has changed. The tobacco companies have offered to pay $368.5 billion to settle a series of class-action lawsuits (a deal that subsequently fell apart as Congress sought a higher amount and curbs on immunity from future litigation). Dr. Kessler has left Washington to become dean of the School of Medicine, remaining vocal on the issue and advocating, along with former surgeon general C. Everett Koop, for a tough settlement.

Tonight, Dr. Kessler talks about the tobacco wars as a faculty member engaging a class. “How do you look at the problem?” he asks the audience at the Slifka Center for Jewish Life at Yale. “What do you have to show?” From a regulatory standpoint, the problem was to define tobacco as a drug and place it under FDA jurisdiction. What stymied regulators was the definition of a drug as an article other than food that is intended to affect the function or structure of the body.

“It took us two years to think through the question of how to approach that definition. What we concluded, and it was a subtle difference that made all the difference in the world, was that the article was the nicotine,” Dr. Kessler says, noting that one of the definition's key words is intended. “The physiological effects of nicotine on the central nervous system certainly are sufficient to affect the structure and function of the body. You have to show intent, the manufacturer's intent. How do you go about doing that?”

The search began with industry patents to develop nicotine substitutes and add nicotine to wrappings and filters. Although the industry officials insisted they were not manipulating nicotine, a study of low-tar cigarettes suggested otherwise. The industry said that nicotine was linked to tar. If tar levels were high, nicotine levels would be high, the industry claimed. But the FDA found that one maker's ultralight cigarettes, for example, had more nicotine than the same brand's regular cigarettes. “I would argue that can't happen without some degree of manipulation,” Dr. Kessler says.

But a theory is not proof. An important bit of evidence came from a surprising source, a tobacco lobbyist bragging at a Washington reception that the FDA was looking in the wrong places. “What he said was, 'It all begins in the fields,' ” Dr. Kessler says. “What he didn't realize was that the person standing next to him would call us the next day.”

That information and another tip led the FDA to foreign patents and to Brazil, where an American company was developing genetically engineered tobacco with twice the normal concentration of nicotine. The industry claimed the new tobacco was simply a blending device.

“The strongest evidence was yet to come and it focused on industry knowledge of tobacco products,” Dr. Kessler says. Documents from the 1960s proved that tobacco officials knew nicotine was addictive. Others from the 1970s proved the tobacco industry was marketing to young people. “Realistically,” reads an industry memo, “if our company is to survive and prosper over the long term we must get our share of the youth market.”

In 1996, the FDA declared nicotine a drug and placed restrictions on tobacco ads and sales. A year later, the industry struck a deal with 41 state attorneys general who were suing to recover smoking-related health care costs. The industry would agree to pay $368.5 billion over 25 years to settle the claims, but would be immune from future class-action suits. Dr. Kessler and Dr. Koop, a visiting professor of public health at Yale last year, called that deal too weak. Sen. John McCain, an Arizona Republican who chairs the Senate Commerce Com-mittee, proposed tougher restrictions including a $1.10-per-pack price hike to be phased in over five years; a $516 billion payment from the industry; no ban on lawsuits; and additional penalties if companies failed to reduce youth smoking. That proposal, approved by the commerce committee in a 19-1 vote, led the tobacco industry to walk out on the previous settlement.

Dr. Kessler learned of the walkout a few hours before giving his talk at the Slifka Center. “Congress,” he tells the audience, “does not have to ask the industry for permission to act.” Congressional efforts to craft some type of settlement fell apart, however, leaving states to negotiate individually with the tobacco industry.

He closes his talk with the recollection of the question that was considered naïve. “Everyone at that time said it was a fool's errand,” Dr. Kessler says. Tonight, this once-invincible industry is on the defense, hard-pressed even to find candidates who will accept its campaign contributions. In Dr. Kessler's eyes, it was persistence and preparation–as well as imagination–that made the difference. “Sometimes, just sometimes,” he says, “you can take on the impossible.”