Cornered

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Cornered Page 11

by Peter Pringle


  The brain cells quickly adapt to having sites blocked by nicotine by generating more sites. When the nicotine eventually unblocks these sites, there are then more sites available than normal and the result is overstimulation, which causes a person to become irritable and cranky—a symptom of nicotine withdrawal. When smokers say smoking “relaxes” them, what they are actually saying is that the new nicotine “hit” from a fresh cigarette is treating their nicotine withdrawal symptoms.

  The paradox of the nicotine “fix” is that it can be either a “high” or a “low”: nicotine can act as a stimulant, increasing attentiveness, heart rate, and blood pressure, but it can also act as a depressant, inhibiting the flow of information between nerve cells.

  As the nervous system adapts to nicotine, a smoker slowly increases the number of cigarettes smoked and hence the level of nicotine in the blood—until the number of sites stimulated and blocked by nicotine is balanced by the new sites made available by the neurotransmitters. The smoker has reached a “target level,” which he then needs to maintain by keeping up his level of nicotine.

  When the smoker goes to sleep, the nicotine level drops dramatically—about forty-five minutes after a cigarette is smoked the concentration of nicotine in the blood is half what it was—which is why smokers often talk about the first cigarette in the morning being the best. The length of time between a smoker waking up and his first cigarette is a measure of the severity of his dependence. More than one-third of smokers reach for their first cigarette within ten minutes of waking; nearly two-thirds within the first half hour. When a smoker stops smoking, it takes one or two weeks for his brain chemistry to return to normal. Some studies suggest long-term smoking can make near-permanent changes in the brain.

  * * *

  SO, WHY DID the 1964 Surgeon General’s report say smoking was a nicotine “habit,” not an “addiction”? At the time, the two nongovernmental authorities then charged with classifying drugs—the World Health Organization and the American Psychiatric Association—used two categories, “habituating” and “addicting.” Drug “addiction,” said the WHO, was a state of periodic or chronic intoxication produced by the repeated consumption of a drug that creates an overpowering need, or compulsion, to increase the dose and a psychological dependence, with detrimental effect on the individual and society. Included in this group were the opiates and barbiturates. “Habituation,” on the other hand, was a desire but not a compulsion, with little or no tendency to increase the dose, some degree of dependence but no withdrawal symptoms, and with possible detrimental effects on the individual but not on society. Cocaine, amphetamines, and nicotine were included in this group.

  In the 1964 report, the section dealing with nicotine addictiveness was a mere five pages out of a 387-page review of the scientific literature on smoking and health. Dr. Terry had made a point of inviting the tobacco companies to submit names of experts so that the report should be seen to be fair. The addiction section was written by Maurice Seevers, chairman of the pharmacology department at the University of Michigan, whose name had been put forward to the Surgeon General by the tobacco companies.

  Seevers was an expert on habit-forming drugs. From the start, he dismayed some of his colleagues on the committee writing the report by refusing to label nicotine an addictive substance, but they had to concede they did not have his expertise. As one of them acknowledged subsequently, he was “one tough hombre,” who would not even concede that the issue of the effects of nicotine was controversial.

  The key distinction, according to Seevers, was that hard-drug takers can harm society; nicotine only affects the individual. Seevers relied on the then generally accepted view of psychiatrists that addiction to potent drugs is based upon personality defects; true addicts are abnormal. A smoker in withdrawal from nicotine was not likely to become a burden on society. (Of course, he could find his fix at the local store. Seevers did not discuss the most obvious difference between hard drugs and tobacco—that the first are illegal, and tobacco is not.) Seevers’s report did not explore another aspect of addiction: while some tobacco smokers were able to quit with seeming ease, others could not give up—much like any addict. Indeed, roughly two-thirds of current tobacco smokers have tried at least once, and one-third try in any given year. The relapse rate for tobacco use is remarkably similar to that of heroin. But apparently Seevers wanted a clear distinction between habit forming and addictiveness. The tobacco companies could not have wished for a better result.

  The distinction was dropped shortly after Dr. Terry’s report. To move the whole debate away from the moral and social issues associated with the term addiction, a new term, “dependence,” was adopted. The key change for the American Psychiatric Association was the new medical description of nicotine-withdrawal syndrome, which included the craving for the drug, irritability, frustration or anger, anxiety, difficulty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain.

  Twenty-four years later, the report of the then Surgeon General of the United States, Dr. C. Everett Koop, stated boldly that nicotine was addictive and the “pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.”

  In the preface to his 639-page report, Dr. Koop wrote, “Some people may have difficulty in accepting the notion that tobacco is addicting because it is a legal product. The word ‘addiction’ is strongly associated with illegal drugs such as cocaine and heroin. However … the [biological] processes that determine tobacco addiction are similar to those that determine addiction to other drugs, including illegal drugs.”

  The central element of all forms of drug addiction, he said, was that the user’s behavior is largely controlled by a psychoactive (mood changing) substance. Other criteria included compulsive use of the drug, repeated self-administration, “reinforcement” because of the drug’s rewarding properties, and “tolerance,” whereby a given dose of a drug produces less effect or increasing doses are required to achieve a specified intensity of response. Finally, absence of the drug produces withdrawal symptoms. Nicotine was such a drug, the report concluded.

  The industry immediately claimed the change was motivated by politics, not science. Dr. Koop had “moved the goal posts,” complained R. J. Reynolds. But the problem for the tobacco companies was that virtually the entire medical science and psychiatric community supported Koop’s conclusions.

  The tobacco companies were left with a handful of psychologists who had been promoting the idea that people smoked according to their personality or their genetic makeup and not because of a chemical addiction to nicotine. Extroverts smoke, introverts tend not to, was the message. To call nicotine addictive merely on medical science criteria of what happens to the brain was not a meaningful statement, merely a hypothesis, according to these researchers. In place of the “addiction hypothesis,” a small group of psychologists proposed what they called the “resource hypothesis”: that smokers use cigarettes primarily as a “tool” or “resource” that provides them with psychological benefits, such as increased mental alertness, reduced anxiety, and an ability to cope with stress.

  The legal departments of the tobacco companies had often relied on the work of a British behavioral psychologist, Hans Eysenck, who argued that smoking and lung cancer were related to genetic makeup: that people were cancer-prone because of their genes, and their genes also somehow caused them to smoke. The companies also relied on the provocative writings of another English psychologist, David Warburton of the University of Reading. Attacking Koop’s 1988 report, Warburton argued that nicotine fit only a few of the new criteria agreed upon by the American Psychiatric Association and the WHO. Koop, he charged, was ignoring “the discrepancies in his enthusiasm to find criteria to compare nicotine with heroin and cocaine use.”

  Two R. J. Reynolds scientists, John Robinson and Walter Pritchard, working at the company’s behavioral research and development cent
er in Winston-Salem, North Carolina, joined the attack on Koop. They concentrated on the addiction criterion of intoxication—as their boss James Johnston would do at the Waxman hearings. If a drug did not result in intoxication, it could not be termed addictive, they said. Intoxication should be the key point in distinguishing between habituating and addicting drugs. They also argued that nicotine did not fit the “compulsive use” criterion since many smokers can do without a cigarette for long periods.

  Most importantly, however, they said, “Common sense tells us that nicotine is not [their italics] like heroin, cocaine or any other ‘classic’ addicting drug.… One does not have to be a trained behavioral scientist to come to this conclusion. Simply ask, and honestly answer, the question as to how many people would board a plane piloted by someone who had just consumed an addicting drug (alcohol, cocaine, barbiturates) versus a plane piloted by someone who had just had a cup of coffee and smoked a cigarette.” (Johnston would use the same words in his congressional testimony.)

  Other behavioral psychologists, however, agreed with the new definition of nicotine as a dependence-producing, or addictive, drug. Intoxication was not central to dependence, they argued. In the end, it was a matter of the industry’s out-of-date, scientifically frivolous, “common sense” public position against basic biology. The companies knew the difference, of course.

  * * *

  THE MERRELL WILLIAMS PAPERS told plaintiffs’ lawyers like Gauthier that in private, three decades ago, the company scientists had never bothered with the semantic distinction between habituation and addiction. Sir Charles Ellis, the chief scientist at BAT, the Brown & Williamson parent company, had said in a 1962 in-house conference that smoking “is a habit of addiction…” A 1963 BAT research paper entitled “The Fate of Nicotine in the Body” begins, “[Nicotine] appears to be intimately involved with the phenomena of tobacco habituation (tolerance) and/or addiction.” Brown & Williamson’s own chief counsel, Addison Yeaman, wrote in a 1963 memo, “We are, then, in the business of selling nicotine, an addictive product.”

  But toward the end of the ’60s there were hints that company legal departments were at work. In a draft report of a 1967 BAT research conference, company scientists listed some “main” assumptions—among them, “There is a minimum level of nicotine. Smoking is an addictive habit attributable to nicotine.…” The draft notes that these assumptions were made “without any attempt to justify them [or] to agree on their correctness at this time,” and then a handwritten edit on the document changes the phrase “an addictive habit” to “a habit.”

  While the companies in public used the words “taste,” “satisfaction,” and “impact” to describe the effects of nicotine, in their private research papers they talked about the pharmacology of nicotine, its effects on the brain, and the “need” of the smoker for those effects. People smoked primarily for their dose of nicotine. “The cigarette should be conceived not as a product but as a package. The product is nicotine.… Think of the cigarette as a storage container for one day’s supply of nicotine,” wrote William Dunn, Philip Morris’s research scientist, in 1972. “As with eating and copulating, so it is with smoking,” Dunn wrote. “The physiological effect serves as the primary incentive; all other incentives are secondary.” Another BAT study in 1976 referred to “Low Need” and “High Need” nicotine smokers. “The indications are that cigarettes delivering around 1.0 to 1.5 mg [of nicotine] are better suited to Low Need clusters, while cigarettes delivering 1.5 to 2.0 are better suited to High Need clusters.”

  In the early ’70s, the tobacco companies explored the possibility of finding a replacement for nicotine that would not cause health problems. For example, the companies were aware of the harmful effects of nicotine on the cardiovascular system—it increases pulse rate and contracts blood vessels—and they would try to find a chemical substitute, a so-called analogue, that would mimic the effects of the drug on the brain without affecting the blood supply.

  In 1980, a young behavioral psychologist named Victor DeNoble went to work for Philip Morris at the company’s research labs in Richmond, Virginia. His job was to find that analogue, and he and his coworker, Paul Mele, set up a series of experiments on rats. They linked the rats to a catheter so that if they pressed a lever they would get a shot of nicotine directly into the heart. The rats kept pressing the lever, showing that nicotine acted as a “reinforcer”; that one dose was pleasurable enough for them to want another. In fact, the rats would press the lever several times for one injection, showing how great was their need. The rats also developed the condition known as “tolerance” to the drug; as time went on, they needed more nicotine to achieve the same effect. The work was not duplicated in outside laboratories until 1989.

  The implications of the study for Philip Morris were immense—even though, as DeNoble was the first to point out, it was a single observation in rats and it was not possible to project the results to humans with any scientific certainty. All one could say was that nicotine had what behaviorists like DeNoble call “an abuse liability.” But Philip Morris didn’t want to take any chances. Security at DeNoble’s lab was tightened. Fresh supplies of animals would be brought in at night, or early in the morning, to minimize questions about the work from other technicians. DeNoble and Mele were not allowed to discuss their work at the company’s research committee meetings. In the fall of 1982, DeNoble and Mele wanted to publish their results. They submitted a paper (“Nicotine as a Positive Reinforcer in Rats”) to their superiors for permission to publish. Approval was given and they sent a draft to the journal Psychopharmacology. They also sent an abstract to a meeting of the American Psychological Association. At the time, Rose Cipollone had just filed her product liability suit against three cigarette makers, including Philip Morris, charging them with failing to warn her properly of the addictive nature of nicotine and other harmful effects of smoking.

  Suddenly, DeNoble and Mele were summoned to Philip Morris corporate headquarters in New York to give a presentation of the results to their corporate bosses. They were met at the airport by one of the company’s chauffeur-driven limousines and whisked to the Park Avenue headquarters; there they gave the presentation and had lunch in the executive dining room. It all seemed to go well and on the way back in the plane, DeNoble and Mele agreed they had done a good job. Only one of the questions asked by a senior executive had bothered them. He had asked something like, “Why should I risk a billion dollar industry on rats pressing a lever to get nicotine?”

  The two researchers thought no more of the remark until a few weeks later when DeNoble was told by his superiors that his laboratory was generating information the company did not want: the results DeNoble and Mele were getting could be used against the company in lawsuits. DeNoble was told to withdraw his paper from publication, although it had already passed peer review and been accepted. He protested to no avail, and not wanting to lose his job, he complied with the company’s request.

  At the same time, three corporation lawyers moved into the room next door to DeNoble and Mele and started going through their files and photocopying their research papers. They also wanted certain words in the report changed. “I had said, you know, nicotine is a drug that is widely used … and they wanted the word drug changed to compound,” DeNoble would say later. “We were not allowed to refer to nicotine or anything in tobacco as a drug.”

  Next, Shep Pollack, the president and chief operating officer of Philip Morris, flew down from New York with his attorney to see for himself what was going on at the lab. DeNoble set up the experiment, the rats pressed levers for nicotine, Pollack peered into the cages. So did his lawyer. The lawyer asked whether this test procedure was the same one that would be used by a government agency to demonstrate addiction, and DeNoble answered that it was. The lawyer shook his head and walked away.

  A few months later, in April 1984, days before Rose Cipollone’s lawyers filed a sweeping discovery request for Philip Morris research documents, DeNoble w
as called to the office of his superior and fired. He was told to shut down his experiments, kill the rats, and clear out his office. When he turned up at the research center the next day, he couldn’t get into the building because his pass had been canceled. DeNoble and Mele were given new offices and provided with secretarial support to look for other jobs.

  A week after he was fired, DeNoble returned to the lab and was astonished to find it had literally disappeared. “The equipment was gone, the cages were gone, all the data was gone. There were empty rooms.”

  Both DeNoble and Mele eventually found other jobs and still wanted to publish their work. The problem was that, like all other employees at Philip Morris, they had signed confidentiality agreements covering the work they had done for the company. At the end of 1985, they decided to take the risk and resubmit their paper to Psychopharmacology. They also delivered a paper on rat tolerance to nicotine to the Federation of American Societies for Experimental Biology. Philip Morris found out and sent the researchers a letter warning them that they had breached their confidentiality agreement. DeNoble was told that if anything about his work at the lab was published, Philip Morris would sue.

  When DeNoble’s troubles became known in the antismoking movement, he was contacted by the Food and Drug Administration and asked to help with the agency’s own inquiries into the tobacco industry. A copy of his and Mele’s paper also found its way to Henry Waxman’s subcommittee in Washington. Waxman released the paper from his office in March 1994, in effect forcing Philip Morris to release DeNoble and Mele from the confidentiality agreements. The information about the rats was now public, and DeNoble would testify before Waxman’s committee. It sounded like a triumph over censorship, but in fact Philip Morris had achieved its aim in hiding his results. In the interim decade, several independent papers mimicking DeNoble’s experiments, and his results, had been published in medical journals. His work was now out of date.

 

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