COLUMN ONE : Tobacco Lab: Science and Silence : When the smoking wars heated up, Philip Morris put Victor DeNoble’s nicotine experiments on ice. His story is part of the wider drama involving the industry and its researchers.

It wasn’t like entering the Peace Corps, but Victor DeNoble hoped to do some good when he joined the tobacco industry.

The year was 1980 and DeNoble, then a 30-year-old Ph.D. in experimental psychology, accepted an offer to run a secret pharmacology lab for Philip Morris Inc., maker of Marlboro and the world’s largest cigarette manufacturer.

DeNoble was to do research on nicotine’s effects on the behavior of rats. But the ultimate goal, he said, was the development of synthetic forms of nicotine that would give smokers a buzz while avoiding the chemical’s injurious effects on the heart.

Neither a smoker nor particular fan of the tobacco industry, DeNoble nonetheless said he was intrigued by the chance “to study a very mysterious drug” and make a contribution to society. There would always be millions of smokers, he believed, so it made sense to reduce their risk of cardiovascular disease--which kills more smokers than lung cancer.

But, within a few years, the tobacco wars invaded DeNoble’s cloister at the Philip Morris research center in Richmond, Va.

Like the other U.S. tobacco giants, Philip Morris suddenly found itself facing a wave of smoker-death claims. And as it girded for legal battle, DeNoble’s research loomed as a serious liability.

DeNoble had joined an industry deeply ambivalent about such research--and fearful of what might happen should word of it get out. Plaintiffs’ lawyers might seize upon the work as a tacit admission that smoking was addictive and dangerous. Having disputed these contentions for decades, the industry could not afford to be caught acting as if it believed them.

Philip Morris--which declined to respond to questions about DeNoble’s research or otherwise discuss this story--abruptly shut the lab in April, 1984. DeNoble was called in, congratulated on his fine work and told to turn in his badge.

Returning to retrieve something a few days later, DeNoble was amazed to find no sign the lab had ever existed.

“Everything was gone,” he recalled. “The cages were gone, the animals were gone, all the data was gone. It was empty rooms.”

During several months of job-hunting, Philip Morris graciously carried DeNoble and fellow scientist Paul C. Mele on its payroll. But the company also muzzled them, threatening legal action should they publish their research.

A decade passed, and the episode might have been buried forever, had word not reached the House of Representatives’ health and environment subcommittee, chaired by tobacco foe Rep. Henry A. Waxman (D-Los Angeles).

When DeNoble and Mele appeared before the panel April 28, Rep. Ron Wyden (D-Ore.) said: “Americans ought to be troubled by what we are going to learn today, which is that when the tobacco industry does research and the results hurt them, the investigators and their data are buttoned up tight.”

Then DeNoble and Mele told their story--opening a window on an industry that painted itself into a corner and did not know how to get out.

*

Despite their unstinting attacks on the evidence against smoking, cigarette makers have behaved in private as if they knew better. Internal documents produced in lawsuits and leaked from tobacco company files reveal a preoccupation with developing “safe”--or at least much safer--cigarettes.

It was this quest that brought DeNoble and Mele to Philip Morris.

Besides the obvious health advantages, a safer cigarette made good business sense. After all, smokers who quit or die cease to be good customers. But what the industry would do if it found what it sought was a bit problematic. Here, tobacco company scientists and lawyers were not always on the same wavelength.

Industry lawyers knew that the “safe” cigarette, if one could be developed, was a legal and financial minefield. What if they found one but it bombed in the marketplace? Would health agencies or Congress, seeing safer smokes were possible, nevertheless require the companies to modify their top-selling brands?

And what of the lawsuits that threatened to engulf the industry? As part of their successful defense, the cigarette makers had contended there was no scientific proof that smoking was dangerous and that any risks that might exist were inherent in the product and beyond their control. A “safe” cigarette would appear to contradict such claims.

Still, internal documents show the companies busily sought the magic bullet.

During the 1960s, ‘70s, and ‘80s, they investigated various additives, catalysts and tobacco substitutes. Some of these proved superior to regular cigarettes in the standard cancer test, which involved painting the skin of mice with tars from tobacco smoke. The experimental cigarettes were euphemistically described as having reduced “biological activity”--meaning they produced fewer tumors on the skin of the mice than commercial brands.

Some advances were not meant to be offered to consumers, unless political or competitive pressures required them. In a 1985 memo, a Brown & Williamson Tobacco Corp. vice president said a prototype cigarette that delivered less carbon monoxide had been kept “ready . . . in the event of a marketing need for such product.” But, he wrote, “right now, we do not see any pressures coming from either government agencies or consumer groups.”

Brown & Williamson officials declined comment.

Hardly any of these projects made it to market. The rejects included “Chemosol,” an additive meant to reduce cancer-causing benzopyrene in cigarette smoke. Dr. Perry B. Hudson, who tried unsuccessfully to sell the industry on the product in the 1960s, said in an interview that he was beaten from the start.

“They couldn’t say to the public, in effect, ‘These diseases we’ve been lying to you about we now can help you with.’ ”

Scientists and consultants for Liggett Group Inc., maker of Chesterfield and other brands, poured more than 20 years into developing a catalyst--made of palladium and magnesium nitrate--that purportedly destroyed cancer-causing compounds in cigarette smoke, according to testimony in a New Jersey wrongful-death case.

But project TAME, as it was known inside the company, was abandoned about 1979 because of litigation fears, according to testimony by Liggett’s former assistant research director, James D. Mold. “They felt that such a cigarette if put on the market would seriously indict them for having sold other types of cigarettes,” according to Mold, who said in a deposition that he, too, was forbidden to publish his research on the subject.

A lawyer for a top industry law firm elaborated on this theme in 1987 in a memo bemoaning the launching of “Premier”--a virtually smokeless cigarette described by its manufacturer, R. J. Reynolds Tobacco Co., as the world’s “cleanest” brand.

Premier--which delivered nicotine and cigarette flavor by heating rather than burning tobacco--could “have significant effects on the tobacco industry’s joint defense efforts,” warned the memo by William S. Ohlmeyer of Shook, Hardy & Bacon, lawyers for Philip Morris and other firms.

“The industry position has always been that there is no alternative design for a cigarette as we know them,” Ohlmeyer wrote in the leaked memo. “Unfortunately, the Reynolds announcement . . . seriously undercuts this component of industry’s defense.”

If Premier struck Ohlmeyer as a foolish gamble, its fate seemed to underscore the point. Smokers hated Premier, and it quickly disappeared. All that legal exposure, and the thing didn’t even make money.

*

By the time Victor DeNoble arrived in Richmond, tobacco companies understood the importance of nicotine to their business. “They (Philip Morris) clearly believed that nicotine was a psychopharmacological agent, and it was the main reason that people smoked,” DeNoble said in an interview.

In fact, many in the industry had known this for a very long time. Sir Charles Ellis, scientific adviser to the board of directors of British-American Tobacco, declared: “We are in a nicotine rather than a tobacco industry,” according to a 1967 document leaked from Brown & Williamson and recently cited before Congress.

In a colorful memo in 1972, Philip Morris psychologist William J. Dunn Jr.--who eight years later would be DeNoble’s supervisor--was equally blunt. “Think of the cigarette pack as a storage container for a day’s supply of nicotine,” Dunn wrote. “Think of the cigarette as a dispenser for a dose unit of nicotine.”

Apart from its habit-forming properties, however, nicotine also was a health hazard. “The Cardiovascular Effects in smoke are believed to be mainly due to nicotine and have been thoroughly explored in literature,” said a 1963 memo by Philip Morris research director Helmut Wakeham--which, like the Dunn memo, later was introduced in court.

So Philip Morris set about developing nicotine analogues--compounds that would have the effects on the brain of nicotine without the cardiovascular effects.

DeNoble’s role was to study nicotine’s effects on the behavior of rats. These results would guide the testing of the analogue compounds. He recruited Mele, a behavioral pharmacologist.

They found that nicotine met two hallmarks of potential addiction--”self-administration,” in that rats would press levers to inject themselves with a nicotine solution, and “tolerance,” in that a given dose of nicotine over time had a reduced effect.

The work was to remain secret even from fellow Philip Morris scientists, DeNoble said; test animals were delivered at dawn and brought from the loading dock to the lab under cover.

Still, it seemed as though “the company was truly interested in investigating their product (and) improving it,” Mele recalled in an interview. “They seemed to want to know about it with a kind of no-holds-barred attitude.”

That changed by 1983.

Several wrongful death claims had been filed against tobacco companies, and dozens more were on the way. Nicotine dependence was a crucial issue in these cases. Although tobacco lawyers argued that smokers had ignored warning labels and accepted the risk, plaintiffs claimed they were hooked. The U.S. surgeon general would pronounce nicotine addictive, but that was five years away.

With the litigation heating up, DeNoble was called to Philip Morris’ New York headquarters in June, 1983, to brief top executives on his work.

He recalled one asking, “ ‘Why should I risk a billion-dollar industry on rats pressing levers for nicotine?’ My comment was, ‘I have no idea,’ ” DeNoble said.

Still, one of DeNoble’s associates told him he thought the meeting went well. On the return flight to Richmond on the corporate jet, DeNoble remembered thinking, “ ‘Boy, these guys can really play poker,’ because I couldn’t read the emotions of the day.”

Soon, however, company lawyers were prowling the lab and reviewing research notebooks. “We were told the data we were generating . . . could be dangerous to the company,” DeNoble said.

There was talk of killing the research or moving it outside so the company would be freer to disavow the results. One scenario had DeNoble and Mele leaving the payroll and continuing as contractors, DeNoble testified to Congress. Another involved shifting the work to a lab in Switzerland.

Earlier that year, the company had approved DeNoble’s and Mele’s request to publish some of their data; their paper had been accepted by the journal Psychopharmacology. But DeNoble was told in August to withdraw the article, which he did with a letter to journal Editor Herbert Barry III.

“The company didn’t want their own scientists to be publishing information that would indicate that nicotine was an addictive drug (or) that it was harmful in any way,” Barry recalled.

Withdrawal of the paper coincided with the filing of the landmark Cipollone lawsuit in New Jersey on Aug. 1, 1983. A longtime smoker, Rose Cipollone had contracted lung cancer. Before her death at 58, she sued Philip Morris and two other firms whose brands she smoked.

The case ultimately produced the first verdict against a tobacco company--a $400,000 judgment against Liggett in 1988 that was overturned on appeal.

Philip Morris and Lorillard Inc. were found not liable--in part because jurors did not believe allegations that Cipollone was hooked or that the cigarette makers had deliberately concealed information about nicotine addiction.

Whether or not it might have affected the outcome, the DeNoble-Mele paper could have helped the Cipollone family’s case.

“I can certainly see why they (Philip Morris) would be worried about having this published,” Cynthia Walters, one of the Cipollone lawyers, said in a recent interview. “The jury didn’t buy addiction as to Rose Cipollone. . . . They didn’t believe that she couldn’t stop smoking, so any additional information that it (smoking) is addictive would have been helpful.”

Despite withdrawal of the paper, DeNoble’s and Mele’s work continued, and for a while it seemed that the storm had passed.

Then in early April, 1984, DeNoble said, he was called into the office of his boss, Jim Charles, manager of biochemical research. DeNoble previously had been promoted to associate senior scientist, and when Charles began by extolling his work, DeNoble thought he was about to be promoted again.

Then the bombshell: It was strictly a business decision, but the lab would be closed.

In the world of scientific research, good jobs are hard to come by, and the first concern of DeNoble and Mele was how to make a living. Fortunately, Philip Morris paid their salaries for months until they found new jobs.

Over time, however, the men grew frustrated and angry about suppression of their data.

On arriving at Philip Morris, each had signed an agreement to seek permission before disclosing their research. They knew that Philip Morris, or any company, might have a legitimate need to hold back information about new products. But in the realm of science, publication is the key to advancement--of knowledge and careers. And they believed Philip Morris’ veto had nothing to do with competitive needs.

So DeNoble and Mele began planning ways to get their data out. In April, 1986, they made a presentation at a meeting in St. Louis of the Federation of American Societies for Experimental Biology.

Philip Morris found out, and a company lawyer sent a scolding letter. “In the future,” it said, “you are expected to comply with the terms of the agreement.”

That August, they gave another presentation at a meeting of the American Psychological Assn. in Washington. Frank Ryan, a former colleague, was sent by Philip Morris to snap their pictures--after which the three men went out for supper and beers.

But Philip Morris wasn’t fooling around. “The Company cannot tolerate this type of conduct,” warned a second letter from assistant general counsel Eric A. Taussig. “Any further breach of your agreement will result in action being taken.”

Knowing they would be overwhelmed by legal bills in a fight with Philip Morris, DeNoble and Mele backed down. They told Taussig that they had resubmitted the 1983 paper to Psychopharmacology, and that it soon would be published. Taussig told them to withdraw it, and they did.

“You’ve got to realize that I’m looking at a very large corporation . . . telling me that they’re going to tie me up in court for a long time,” DeNoble said recently. “I got scared, bottom line.”

*

Years passed, and the story might never have been publicly revealed. But it came to light earlier this year, when the Food and Drug Administration announced it was considering regulating nicotine as a drug.

Jack Henningfield, chief of clinical pharmacology for the National Institute on Drug Abuse, belonged to some of the same professional societies as DeNoble and had been told in 1983 about the squelching of the data. In March, when FDA Commissioner Dr. David A. Kessler mentioned a rumor that a tobacco company had done nicotine self-administration studies with rats, Henningfield recalled the incident and told Kessler about it. Kessler and Henningfield provided details to the Waxman panel in an appearance later that month.

At the subcommittee’s request, Philip Morris waived the secrecy requirement, and DeNoble and Mele agreed to appear. Their testimony helped fan the firestorm of criticism that has engulfed the industry this year.

Mele, 45, and DeNoble, 44, have gone on to other things. Mele is a researcher at the Armed Forces Radiobiology Research Institute in Bethesda, Md. DeNoble is a behavioral analyst in Delaware’s Department of Mental Retardation. But for both the appearance was cathartic--providing a sense of vindication and of closure.

It proved to be “a good way to let the (scientific) community know what was going on at Philip Morris, without getting on ’60 Minutes’ or anything like that,” Mele said. “We weren’t interested in being on a soapbox and trying to make them look bad.”

How Smoking Kills

In the 1980s, Victor DeNoble was part of a Philip Morris research project aimed at developing a nicotine substitute--a chemical that would give smokers a jolt without subjecting them to the cardiovascular effects of nicotine. Health experts say that cardiovascular disease not cancer--is the No. 1 killer associated with smoking. Chart shows estimates of smoking-related deaths in the United States in 1990.

Cardiovascular Disease, including ischemic heart disease--179,820; (43%)

Cancer, including lung cancer--151,322; (36%)

Chronic Obstructive Pulmonary Disease, including emphysema--84,475; (20%)

Other: 3,073 (1%)

Source: Office on Smoking & Health, Centers for Disease Control & Prevention