MANNER

In the years that followed, according to M. Lance Reynolds, former Director of Product Development and Director of Research, B&W "did a lot of work on trying to develop a quote, low-tar, normal nicotine, closed quote, cigarette." Dr. Reynolds stated that from the beginning of his career at B&W in 1968, the company and other BAT Group member companies had "projects to try and increase nicotine delivery with respect to tar, for many years." Reynolds PD, Minnesota, 9/30/97, 137:10-137:15; 777125397-5403 at 5398 (US 54625).
The importance of nicotine was also emphasized in the B&W Research and Development Department. In a November 28, 1977 memorandum by researcher G. E. Stungis titled "Long-Term Product Development Strategy," one of the overarching stated objectives was that "products must provide the appropriate levels of nicotine. . . ." 501011512-1515 at 1513 (US 85309) (emphasis in original). Moreover, a significant part of the overall B&W strategy was the ability to:

Recognize that nicotine is a vital component to overall smoker satisfaction. Methods to optimize the mainstream smoke nicotine delivery with respect to pharmacological effects will be explored/developed.

¶Id. at 1513.

An August 24, 1978 B&W memorandum to M. J. McQue from Assistant Brand Manager H. David Steele titled "Future Consumer Reaction to Nicotine" stated: "Very few consumers are aware of the effects of nicotine, i.e., its addictive nature and that nicotine is a poison." 665043966-3966 (US 21485); 776078962-8962 (US 87137).

Is there not some way open now to use the knowledge we have gained in this area of tobacco and smoke research to give B&W a competitive advantage over its competition? It appears that we have sufficient expertise available to "build" a lowered mg tar cigarette which will deliver as much "free nicotine" as a Marlboro, Winston,

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or Kent without increasing the total nicotine delivery above that of a "Light" product.

¶654005805-5807 at 5806 (US 85447).

B&W scientist Tilford Riehl, who later became Vice President of Research and Development, received Gregory's "file note" and commented on an alternative to Gregory's proposal to increase "free" nicotine to boost "physiological satisfaction." While accepting Gregory's data and concept, Riehl proposed maximizing the effects of nicotine on smokers in a different way. Riehl wrote in the margin:

Several of us have proposed an alternative (almost opposite) approach -- design a low tar cig with high total nicotine/low to moderate % free nic. Theory: provide cig with "appropriate" level of sensory satisfaction/higher than usual "pharmacological" satisfaction. (emphasis in original)

¶510000667-0670 (US 51496).

B&W was given a November 1995 document prepared by Shook, Hardy & Bacon compiling and quoting from company materials that admitted nicotine manipulation by increasing "free" or "bioavailable" nicotine delivered by cigarettes. The report commented on the two 1980 documents written by Gregory and Riehl, documents that supported accusations by the FDA that B&W (and the other cigarette manufacturers) intentionally made and marketed cigarettes with nicotine effects greater than the FTC machine-measured yields:

Gregory appears to be urging that B&W engage in a manufacturing and marketing practice of which the FDA accuses the company -- that accusation being that the company designs, manufactures and markets cigarettes with a pharmacological impact which is greater than FTC yields imply. Thus, Gregory's comments are of interest in the regulatory and litigation context.

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With respect to Riehl's written comments on Gregory's memorandum urging a low tar product with high total nicotine with moderate "free" nicotine, the Shook, Hardy & Bacon report stated that: "[T]his marginalia comment, of course, raises an issue of the motivations of the company in designing cigarettes to provide 'pharmacological satisfaction' to smokers." Id. at 1754.
In February 1980, BATUS, Inc. (B&W's holding company, also located in Louisville, Kentucky) commissioned a detailed marketing plan for a "less hazardous cigarette" tentatively named "Limit." The proposal reflected the company's belief that smoking was both hazardous and addictive. The new cigarette would address the problem of addiction by offering "higher nicotine content to satisfy smokers' needs with fewer cigarettes . . . thus less potential harm." The report proposed advertising to physicians that, "Recent studies show that even under optimal conditions, it is unlikely you will persuade more than 5% of smokers to quit. So for the other 95%, do the next best thing. Switch them to new LIMIT." 501025519-5609 at 5564-65 (US 85310).
The background research underlying the 1980 BATUS marketing proposal found that physicians had a "little or no success in getting patients to stop smoking cigarettes" and even suggested that providing the smoker with a less harmful cigarette product is equivalent to providing a heroin addict methadone. The less harmful cigarette, like methadone, was referred to as the "lesser evil," a "compromise" for the smoker who cannot quit the addiction. The writers asked rhetorically, "Why won't we help a cigarette addict get his 'fix' in the least damaging way possible?" It was proposed that the "Limit" product would be made available only through pharmacies and would be introduced via physicians "in the same way that a new drug is presented." Id. at 5544-45, 5573.
The 1980 BATUS proposal specifically recognized and emphasized the smoker's "physical need," "withdrawal" effects, and the high rates of recidivism. A sample promotion letter to physicians instructed that, "Low nicotine cigarettes are not a viable compromise. Studies have shown . . . that when patients switch to low nicotine brands, they usually increase the number of cigarettes they smoke daily. . . . Finally there is an alternative . . . for those patients whose sincere and dedicated efforts to stop have ended, again and again, in frustration, self-deprecation, and recidivism[.]" Id. at 5560-5561.

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A January 1982 B&W market analysis of smokers of its Belair brand reported in the section titled "Smoking Behavior and Attitudes" that: "Overall, the evidence shows that Belair smokers are extremely addicted to smoking and they know it." Belair also scored very high in factors indicative of dependency and "[a]ddiction." In fact, 94% of Belair smokers surveyed agreed with the statement, "I get a real urge for a cigarette when I haven't smoked for a while." (emphasis in original) 514107196-7249 at 7225, 7228 (US 85311).
In a similar January 1982 B&W market analysis for its Viceroy brand of cigarettes, the company was told that, "Smokers of brands in Viceroy's competitive set are more addicted to smoking than smokers in general." 514107251-7302 at 7281 (US 85312).
Later, in 1982, B&W carried out a "Smoker Personality Study" that segmented the cigarette market in terms of the level of addiction of the smokers. The stated purpose of the study was to provide the company "new insights helpful in the development and positioning of new and/or established brands." With respect to the market segments, smokers who fit into Segment IV were described as "somewhat addicted" and smokers in Segment VI were described as "addicted to smoking and often wished they never started." Smokers in Segment VIII, however, were described as "heavily addicted to smoking. To run out of cigarettes would be a real problem for them . . . from the moment they wake up they smoke." 514107303-7417 at 7336, 7350, 7364 (US 85313).

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B&W Group Product Director A.J. Mellman wrote a project memorandum on March 25, 1983, to other industry executives, including Senior Vice President for Marketing R.A. Blott, stating explicitly that nicotine is "addicting." The memorandum proposed several project ideas for the company, including a low tar cigarette with free nicotine added to the filter, based on the underlying premise that:

Nicotine is the addicting agent in cigarettes. It, therefore, seems reasonable that when people switch brands, if they have a certain smoking pattern (i.e. number of sticks/day), they will switch to a brand at the same nicotine level. I am currently examining all brands by nicotine level and by nicotine/tar ratio levels, comparing those correlations to switching patterns.

¶514110006-0009 at 0007 (US 21745) .

According to the record of a January 4 and 5, 1988 meeting in New York, B&W scientists Tilford Riehl and Lance Reynolds met with scientists from BATCo's other affiliates to discuss the progress of internal company nicotine research code-named "Project GREENDOT" and "Project AIRBUS," and to chart the course of the research for the 1990s. "Project AIRBUS" sought to develop a device similar to a non-combustible nicotine delivery product manufactured by RJR. "Project GREENDOT" sought "to produce a highly modified cigarette which maintains the delivery of nicotine to the smoker whilst reducing the delivery of tar." The goal of "GREENDOT" was to modify a 10mg tar / 0.8 mg nicotine cigarette to deliver 1mg tar / 0.8 mg nicotine. 620208779-8784 at 8782-8783 (US 85317).
BATCo regularly forwarded its nicotine research reports to the B&W Research and Development Department and the company library for use by the company and its employees. The critical importance of nicotine to the companies is evident in the titles and content of these reports. See, e.g., "Preparation and Properties of Nicotine Analogues - Part II," October 11, 1973, 657006301-6327 (US 53532); "Alpha Waves and Smoking: The Effect of Cigarette Smoking on the Alpha Density of Subjects," December 6, 1974, 657007342-7416 (US 53535); "The Effect of Smoking Deprivation on Smoking Behaviour," September 11, 1975, 650014873-4901 (US 53405); "Compensation for Changed Delivery," January 30, 1976, 650008449-8480 (US 76192); Dr. M.A.H. Russell's "Safer Cigarette" Study Report No. RD. 1652 (Restricted), March 1, 1979, 650010157- 0193 (US 85292); "Preparation and Properties of Nicotine Analogues - Part III," June 20, 1979, 657006435-6487 (US 53534); "A Comparison of Smoking Surveys Separated by Four Years," June 28, 1979, 650008946-8960 (US 85318); "Method for Nicotine and Cotinine in Blood and Urine," May 21, 1980, 6650032386-2428 (US 53430); "Nicotine Studies: A Second Report, Estimation of Whole Body Nicotine Dose by Urinary Nicotine and Cotinine Measurements," March 31, 1981, 650030769-0802 (US 53428) ; "Receptors for Nicotine in the Central Nervous System," March 22, 1984, 650000996-1034 (US 53388); "The Functional Significance of Smoking in Everyday Life," April 24, 1984, 650000563-0740 (US 85393).

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B&W's law firm, Shook, Hardy & Bacon, prepared a document titled "B&W -- Addiction Notebook" for the company. The Addiction Notebook identifies numerous company documents (both B&W documents and documents sent to B&W by BATCo) admitting that (1) smoking is addictive, (2) nicotine is the primary addictive drug responsible for making smoking addictive, and (3) BATCo and B&W conducted and funded research over decades into the physiological and pharmacological properties of nicotine as a drug, as an essential element of smoking, and as a commercial element necessary to the profitability of the cigarette industry.

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e. Lorillard 1118. Many internal documents show that Lorillard also has also been aware for decades

¶of nicotine's addictive properties and the importance of nicotine to cigarette smokers.

In an August 1964 national survey titled "A Market Target -- Buying Incentive Study of Cigarette Market," Lorillard found that 66% of qualified respondents gave habit/addiction as a reason for continuing to smoke. 03492841-3067 at 2884 (US 21432).
In an August 7, 1964 memorandum regarding "Potassium Carbonate," H.D. Anderson told Lorillard's legal counsel that "[t]here seems no doubt that the 'kick' of a cigarette is due to the concentration of nicotine in the blood-stream which . . . is a product of the quantity of nicotine in the smoke and the speed of transfer of that nicotine from the smoke to the blood-stream." 100059066- 9067 at 9067 (US 20102).
Like the other cigarette manufacturer Defendants in the 1970s and 1980s, Lorillard knew that the issue was not only nicotine, but the amount of "free" nicotine actually delivered to smokers. In a February 8, 1973 report to research department executives, Lorillard scientist A. M. Ihrig concluded that nicotine in alkaline smoke (high pH) is absorbed in the mouth and lungs far more rapidly than nicotine in low pH smoke, and that this phenomenon was due to the fact that "free," or readily absorbable, nicotine increased dramatically with pH. According to Ihrig, "a change in pH from 5.7 to 8.0 results in an increase of free nicotine from 0.69% to 58.3%." 00776238-6250

467

Ihrig also noted the importance of "free" nicotine to the company's financial success: "Furthermore, the cigarette brands which are enjoying the largest sales increase generally have smoke pHs in the 6.5-7.0 range." He later adds that, "The smoke pH for Kool and Marlboro are 7.12 and 6.98, respectively, confirming the relationship between high smoke pH and cigarette sales increase." 00776238-6250 at 6239, 6245 (US 21477).
Alexander Spears, Lorillard's Vice President of Research and later Lorillard Chairman and CEO, wrote a paper on the "elements of product acceptance" dated November 13, 1973. In his paper, Dr. Spears stated that one of the main elements of cigarette acceptance was "Physiological, being comprised largely of the nicotine-induced stimulation and thought coordination effects." Dr. Spears then stated that "it would be useful to have a wider range of control over nicotine than now exists," and that "[i]t is our present intent to develop low nicotine brands, with the maximum physiological impact, within the next year." 80634635-4642 (US 21063).
Lorillard knew that nicotine was distinct from and not essential to the taste of a cigarette. In a March 2, 1976 presentation, the Will Graham Company advised Lorillard that "the taste of tobacco may be one of the least significant reasons why a person smokes," adding that, "it certainly ranks well below the impact of nicotine" for smokers. 01771073-1207 at 1079 (US 20052).
A 1976 Lorillard internal review of nicotine scientific literature by H.S. Tong reported the following with respect to smoker compensation:

A review has been made of the literature on the pharmacology of smoke-dose nicotine with the goal of discovering some indications of threshold dose and optimum doses of nicotine in the average cigarette smokers. . . . It seems that, within limits, smokers can and do control their nicotine intake from smoke by varying their smoking techniques. Nicotine has numerous sites of action and the response is an algebraic sum of its actions. . . . It seems that smokers smoke

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for both calming and stimulant effects. In a subjective study, test subjects reported that they found cigarettes of 0.8 mg to be acceptable.

Despite the lack of definitive knowledge, it seems probable that smokers choose cigarette smoking for sensual, psychological, social, cultural, and pharmacological effects. The pharmacological effects are most likely due to the action of nicotine since the presence of a variety of other chemical components in the smoke in all probability is below their threshold level. . . . It is well known that the pharmacologic effects of nicotine at various sites are dependent on the dose, the dose schedule, and duration of exposure. Smoke dose nicotine has a stimulant action. It stimulates ganglia, and, therefore, it activates both the sympathetic and parasympathetic nervous systems simultaneously, the ultimate effects are the algebraic sum of its actions. Research in drug addiction indicates that the CNS [central nervous system] is the prime site of drug action. In order to understand the precise action of nicotine in the smoke habit, the CNS should be the logical site for study. . . .

The purpose of this review is to determine if there were data which would indicate a threshold dose and an optimum satisfaction dose of nicotine for the majority of smokers.

¶83250863-0873 at 0863-0865 (US 55673).

In a June 16, 1976 Lorillard memorandum titled "Progress Report on Nicotine

¶Augmentation Project," H. J. Minnemeyer, the lead researcher on the company's nicotine augmentation programs, updated Spears on the progress of efforts to solve "the problem of delivering more nicotine in the smoke of low tar cigarettes." The memorandum described the various research projects being conducted by Defendants as well as the medical and scientific research articles that had been published on the subject. 95539652-9655 (US 56825).

A July 16, 1976 Lorillard research proposal memorandum to H.J. Minnemeyer from

¶M. S. Ireland, titled "Research Proposal -- Development of Assay for Free Nicotine," again acknowledged the scientific consensus that nicotine was the source of the addiction to smoking:

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Cigarette sales are made for one reason. The customer is satisfied with the product either from the taste or the physiological satisfaction derived from the smoke. The consensus of opinion derived from a review of the literature on the subjects indicates that the most probable reason for the addictive properties of the smoke is the nicotine. Indications are that the smoker adjusts his smoking habits to satisfy the desire of nicotine either by frequent or large puffs on the cigarette, or smoking a large number of cigarettes. . . . [I]t is generally agreed at this time that a "small" amount of free nicotine is more desirable than a "large" amount of bound nicotine.

¶82396938-6939 at 6938 (US 22012).

In the mid-1970s, Lorillard embarked on another project called the "Lowered Nicotine

¶Project." According to a November 9, 1976 memorandum from company Vice President for

¶Marketing R.E. Smith to the research department, the project was abandoned. However, the memorandum disclosed that, despite Lorillard's contrary public declarations, the company was well aware of the importance of nicotine in sustaining smoking:

After discussing the 50% Lower Nicotine Project with Dr. Spears, I agree that we should discontinue work. We all understand that this concept has considerable consumer trial appeal; as quantified by the NPSS concept study. However, it is our judgment that a cigarette with substantially lowered nicotine could not deliver the smoking satisfaction to sustain consumer purchase.

¶01244504-4504 (US 20042).

Lorillard knew that nicotine shared attributes of opiates, and sought to use this knowledge to its advantage. A March 16, 1978 memorandum by Lorillard scientist R.S. Marmor summarized a lecture given at Lorillard by industry-funded scientist Leo Abood titled "In Search of a Site and Mechanism for Nicotine's Action on the Brain." Marmor reported that:

Prof. Abood's lecture here on "In Search of a Site and Mechanism for Nicotine's Action on the Brain" was well attended and well received. . . . Theorizing that nicotine's activity is due to an

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accidental mimicry of some normally present but as yet unknown brain peptide (analogous entirely to the recent opiate-enkephalin research findings), it might be possible to determine the structure of this peptide from information about the receptor site. In any case, information we gain on the mechanism of nicotine activity may be useful in determining how to adjust physiological impact in our cigarettes. We intend to support Prof. Abood by supplying samples and performing some synthetic and computer work.

¶00110371-0371 (US 34404).

In a February 13, 1980 Lorillard memorandum stamped "SECRET," marketing vice president Smith described the goal of the ongoing Lorillard nicotine research project called the "RT

¶Information Task Force." The memorandum provided Lorillard executives, including Dr. Spears, details of the secret project:

Goal -- determine the minimum level of nicotine that will allow continued smoking.

We hypothesize that below some very low nicotine level, diminished physiological satisfaction cannot be compensated for by psychological satisfaction. At this point smokers will quit, or return to higher T&N [tar and nicotine] brands.

¶01394380-4381 at 4380 (US 21543).

Senior Lorillard researcher S. T. (Tom) Jones prepared a lengthy "confidential" report dated July 30, 1980, for the research leadership in Greensboro titled "Five-Year Plan Preparation," in which he reviewed current literature on the "psychology of smoking." Jones wrote in a section presenting "A Review of Behavioral and Psychopharmacological Factors in Smoking" that,

¶"Undoubtedly, nicotine serves a primary role in cigarette smoking." He also noted that, "A real problem in this whole area is the diversity of terms employed to say essentially the same thing." He later stated that:

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Considerable research in both the relative importance and mechanistic pathway of nicotine have [sic] been conducted. Although the role of nicotine is not completely understood, it is obviously one of the major factors associated with tobacco usage. Consumption of nicotine, administered either orally, intravenously, or via smoking elicits numerous responses including increased pulse rate, variations in skin temperature, and changes in brain wave patterns. Hutchinson and Emely take the position that nicotine is a powerful chemical reinforcer which reduces stressful and unpleasant stimulation.

¶01105000-5021 at 5001, 5002, 5009 (US 20030).

Lorillard scientists also knew and accepted the phenomenon of nicotine compensation. Jones concluded in his memorandum that smokers of low tar products compensated

¶("titrated") to achieve a greater "nicotine dose":

The evidence to date clearly indicates that smokers titrate or regulate their intake of nicotine, e.g. smokers of cigarettes which deliver large amounts of nicotine will adjust -- when given low nicotine cigarettes -- their smoking to get a larger nicotine dose than the machine determined values indicate. Also, smokers regulate their nicotine intake over time when smoking their regular brand.

¶Id. at 5010.

Finally, Jones summarized research findings that "withdrawal is an identifiable syndrome" characterized by "anxiety and irritability," "an inability to concentrate and an intense craving for tobacco." Id. at 5013.

¶f. American Tobacco Company

American has known since the 1940s that nicotine was essential to its products and was responsible for the physiological responses to smoking. An April 1940 document written by H. R. Hanmer, American's Director of Research, was titled "Memorandum on the Nicotine Content of

¶Lucky Strike and Other Leading Brands of Cigarettes." The document contained a section called

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¶"Importance of Nicotine in Tobacco and Tobacco Products." Hanmer observed that the following

¶"facts" were "long common knowledge" at the company:

The presence of nicotine as a universal constituent of tobacco leaf differentiates it from other plant material. Nicotine contributes to the gratification of smoking. Tobacco substitutes, devoid of nicotine, have not been accepted. . . .

That any physiological response to the constituents of smoke is due to nicotine is generally accepted and has recently been confirmed. The malaise after over-smoking is due to an excess of nicotine beyond one's individual tolerance. The pleasure, euphoria, or pacification from smoking are due to the sedative action of nicotine.

With such facts long common knowledge to the Research Staff, the incorporation of nicotine control into the selection of tobaccos was a logical development.

¶ATX300006425-6468V at 6428 (US 85324).

These "facts" and the company's ability to control nicotine were important to the development and maintenance of American's most popular brand at the time, Lucky Strike. Hanmer wrote in the same memorandum that its success was the result of the company's "nicotine control policy":

A recognition of the facts presented above led to the institution of a method of scientific control of tobacco purchased by the Company. . . .

That the favorable position of LUCKY STRIKE in comparison with other leading brands is not fortuitous but the result of a comprehensive nicotine control policy is demonstrated by the material exhibited in this memorandum.

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Between 1940 and 1970, American sponsored 111 studies on the biological effects of cigarettes, with ninety-three, or over 80%, related to the effects of nicotine on the body. "Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and Adolescents," 1996 FDA Jurisdictional Determination, HHA 0680950-1649 (US 33031); VXA1242326-3211 (US 64323).
In a June 19, 1963 letter, American's Assistant to the President (and later company president) Robert K. Heimann labeled nicotine as "the characteristic and essential element in tobacco and tobacco smoke." Heimann asserted that the "reduction of nicotine to very low levels results in an unsatisfactory smoke." MNAT00787182-7182 (US 85325); ATC2471666-1666 (US 86691).

g. CTR 1138. Nicotine research funded by CTR also shows "that the cigarette manufacturers have

¶acted like traditional pharmaceutical companies," studying the pharmacokinetics (absorption, metabolism, and excretion) of nicotine, the pharmacodynamics (effects on body chemistry) of nicotine, and the clinical effectiveness (whether drug is effective in producing the desired effects) of nicotine. VX1242326-3211 at 2806-2087 (US 64323).

On November 22, 1977, CTR Associate Research Director Donald H. Ford stated the following in a proposal for further CTR-funded nicotine research:

[I]t now seems evident that nicotine, like narcotics, influences the CNS in multiple ways involving effects related to most known neurotransmitters. Further, the dependence which develops to tobacco in humans (and withdrawal symptoms during the cessation of smoking) and the degree of tolerance to nicotine which occurs in certain animal paradigms strongly suggest that nicotine is a habituating agent.

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Ford presented his nicotine observations and proposed research at the November 1977 CTR meeting. His proposed avenues of research related to "Receptors and sites of nicotine action," neurochemical studies, the effects of nicotine on fetal development, neuroendocrinology, and behavioral responses to nicotine. 1000036584-6590 (US 21417); 01113272-3272 (US 85329); 01113280-3284 (US 85330).
This November 1977 CTR presentation by Ford drew the concern of Philip Morris's Tom Osdene, who later wrote to Bob Seligman that the nicotine "work being taken by CTR is totally detrimental to our position and undermines the public posture we have taken to outsiders." 2022246952-6952 (US 36865).
The November 1977 CTR meeting was attended by lawyers and executives from all the member cigarette manufacturers, along with several outside counsel (Don Hoel, Janet Brown, and Ed Jacob). According to notes of the meeting taken by Philip Morris's Tom Osdene, Dr. Ford explained his nicotine research in detail. This presentation was introduced by CTR scientific director Dr. Gardner, who told the attendees that, "Opiates and nicotine may be similar in actions," and that there was a "relationship between nicotine and opiates." The notes of attendees indicate that no one questioned Dr. Ford's premise or Dr. Gardner's introductory remarks. 1000036584-6590 at 6584 (US 21417); 01113280-3284 at 3280 (US 85330).
Thereafter, as stated in the May 10, 1978 notes of the CTR Industry Technical Committee Chairman Preston Leake (also Scientific Director of American Tobacco) to American Tobacco general counsel Arnold Henson, the proposed nicotine work was "ruled out" by outside counsel Ed Jacob. Jacob claimed that the nicotine work had antitrust implications because it might be subject to "misinterpretation as product development." 955017148-7154 at 7149-7150 (US

475

A June 20, 1984 memorandum, written by Shook, Hardy & Bacon attorney Wendell

¶L. Stone, summarizes the significance of CTR-funded nicotine research for industry clients. In his memorandum, Stone conceded that:

Of the three areas pertinent to Cipollone16 (lung cancer, emphysema, and addiction) the abstracts and CTR commentary regarding addiction are the most consistently adverse. Through the years, CTR has funded psychopharmacological and neuropharmacological studies which emphasize and leave clear the points that CTR views nicotine as a "psychoactive" or "psychotropic" drug (terms which CTR has used), and that the research approach most appropriate to studying smoking behavior involves the pharmacology of nicotine. Among the undesirable research claims which appear in abstracts which acknowledge CTR support: the identification of specific central nervous system structures (nicotine receptors) at which nicotine acts; effects of nicotine on a variety of different purported neurotransmitters involved in learning, memory, etc.; various behavioral effects of nicotine from which can be inferred central nervous system effects, some of which might be used to support assertions regarding "tolerance" and "withdrawal."

¶515709297-9340 at 9298 (US 20866).

The evidence overwhelmingly shows that Defendants have for decades internally recognized that smoking is addictive and that nicotine is the key to that addiction.