Reports that Matter

United States v. Philip Morris USA Inc.: Amended Final Opinion

Defendants Concealed and Suppressed Research Data and Other

Section 55 of 129

Defendants Concealed and Suppressed Research Data and Other

Evidence that Nicotine Is Addictive 1266. As demonstrated, Defendants' internal documents reflect a sophisticated

understanding of nicotine and its role in creating smoking addiction -- an understanding that is totally inconsistent with their long-standing public denials that nicotine is addictive. In addition, it is clear that Defendants intentionally withheld from public dissemination, from the public health community, and from government authorities, accurate and important information regarding the addictiveness of nicotine in cigarettes. Henningfield WD, 87:10-88:20, 161:23-167:6.

  1. Defendants suppressed their own extensive research findings discussed in Section V(B)(3), supra, supporting the conclusion that nicotine is addictive, and fostered controversy about the extent of scientific knowledge concerning nicotine and its addictive effects that was publicly available. Henningfield WD, 134:23-136:9, 161:23-167:6.

  2. As that evidence shows, Defendants themselves possessed, from their own in-house and external research, information that led them to conclude, long before public health bodies did, that the primary reason people keep smoking cigarettes is to obtain the drug nicotine, which is addictive. Defendants intentionally withheld this data (including many of studies on the physiological effects of nicotine in animals and humans, and much of their research on the determinants of nicotine dosing in cigarettes) when there were major public efforts to review and synthesize all available information. This occurred with the preparation of both the 1964 and 1985 Surgeon General's Reports and numerous congressional investigations. Defendants also engaged in a decades-long, elaborate, sophisticated, well-funded public relations offensive, denying and attacking the consensus conclusion they had long ago reached internally, but that the less well-funded public health community was belatedly reaching, that smoking is addictive primarily because cigarettes effectively deliver nicotine. Henningfield WD, 87:10-103:13, 104:14-110:8, 134:23- 136:1, 150:14-159:8, 161:23-167:6. See also 490010042-0044 at 0043 (US 79285) (presenting "Addiction Statement," prepared by Shook, Hardy & Bacon, deciding the company's position must be that smoking is not addictive and that, "Statements in company documents cannot refute this conclusion.").

510
  1. A September 9, 1980 Tobacco Institute internal memorandum revealed the recognition by the member companies that a public admission that nicotine was addictive would undermine their litigation defense that a person's decision to smoke is a "free choice":

[T]he entire matter of addiction is the most potent weapon a prosecuting attorney could have in a lung cancer/cigarette case. We can't defend continued smoking as "free choice" if the person was "addicted."

TIMN0107822-7823 at 7823 (US 21275).

  1. A second reason Defendants denied addiction was to avoid regulation by the FDA. None of the companies' internal research and evidence about addiction was submitted in 1996 when the FDA sought to assert jurisdiction over cigarettes as drug (nicotine) delivery devices. Instead, Defendants vigorously denied every aspect of addiction. 25055597781-7998G (US 23028*).

  2. The following are examples of the actions Defendants undertook to either block or limit the nature and dissemination of nicotine-related research, as well as any evidence suggesting addiction.

511

  1. As already discussed, Philip Morris intensively studied nicotine and both its pharmacological and physiological effects on smokers (sometimes called addictive, dependence-producing, or reinforcing effects) in an effort to increase its market share within the industry. However, Philip Morris withheld from the public its internal knowledge and acceptance that smoking, because of nicotine, was addictive. Similarly, Philip Morris's research demonstrating the addictive impact of nicotine on the bodies of animals and humans was suppressed, and in some cases terminated.

  2. In a 1992 memorandum titled "Philip Morris Behavioral Research Program," the company's long-time outside counsel, Shook, Hardy & Bacon, reviewed and summarized much of Philip Morris's nicotine research conducted from 1969 to 1984 under the direction of Principal Scientist William L. Dunn. The research into nervous system effects and smoking behavior was conducted both internally (by scientists such as Dunn, Berntson, Gullotta, DeNoble and others) and by outside researchers (including scientists Hutchinson, Abood, Egle and others). 2021423403-3497 at 3406-3409 (US 36743).

  3. The funding for the Behavioral Research Program, or Nicotine Program as it was sometimes called, was terminated without explanation in 1984. 2025768108-8166 at 8113 (US 36743).

  4. Discussing Philip Morris's research into the pharmacological effects of nicotine, Dr. Dunn wrote the following in a "CONFIDENTIAL" memorandum to Research & Development Vice President Helmut Wakeham on February 19, 1969: '[D]o we really want to tout cigarette smoke as a drug? It is, of course, but there are dangerous F.D.A. implications to having such a conceptualization go beyond these walls." 1003289921-9922 at 9921 (US 20167).

512

  1. Dunn wrote a "CONFIDENTIAL" memorandum dated October 19, 1977 titled "Smoker Psychology Program Review" summarizing his program for Tom Osdene. Dunn made three observations that represented the Philip Morris position on smoker behavior and nicotine research. First, the mission of the Philip Morris program was to "study the psychology of the smoker in search of information that can increase corporate profits." Second, Dunn admitted that while "[t]here is a general realm of psychological inquiry that would not make our lawyers nervous were the findings to be made public," there is "legal concern" with any scientific inquiry into the dependency-producing compound, or "reinforcing mechanism," of smoking. Third, Dunn stated that his research assumed that nicotine was the compound in question, a compound without which "the cigarette market would collapse, P.M. would collapse, and we'd all lose our jobs and consulting fees." 1000046538-6546 at 6538-6542 (US 26074); 2021423403-3497 at 3488 (US 36743).

  2. Dunn also compared smokers seeking nicotine to Pavlov's dogs and to hungry laboratory rats who press levers seeking food pellet "rewards":

Consider the smoker. Smoking the cigarette is the lever press. The effect of that smoking act upon the person is the reward. That effect reinforces the smoking act. He comes to push the smoking lever 10 to 60 times per day.

1000046538-6546 at 6543 (US 26074); 2021423403-3497 at 3485 (US 36743).

  1. Shortly thereafter, in a November 3, 1977 memorandum, Dunn revealed his strategy for concealing any unfavorable nicotine research results. Regarding a proposed study of nicotine withdrawal in rats to be undertaken by Philip Morris scientist Carolyn Levy, Dunn stated that he approved it. However, he cautioned that, "If she is able to demonstrate, as she anticipates, no withdrawal effects of nicotine, we will want to pursue this with some vigor. If, however, the results with nicotine are similar to those gotten with morphine and caffeine, we will want to bury it." 1003293588-3588 (US 20168).
513

  1. The terms of Levy's "Proposed Study of Nicotine Withdrawal in Rats" are contained in a November 1, 1977 memorandum from her to Dunn, where Levy states her hypothesis that her research would show that there are no withdrawal symptoms associated with nicotine. Levy intended to compare known morphine and caffeine withdrawal symptoms to nicotine's effects. Levy stated, however, that while she predicted favorable results, she understood that "it is dangerous to set out to prove the null hypothesis." 1003293589-3591 (US 21421).

  2. Robert Seligman, Vice President of Research & Development at Philip Morris, wrote a memorandum to company general counsel Alex Holtzman dated June 27, 1978, attaching Dunn's report of a conference Seligman and Dunn attended called "Cigarette Smoking as a Dependence Process." The conference was apparently put on by the National Institute on Drug Abuse. Seligman prophetically warned Holtzman that:

It is my impression that at some time in the future, nicotine will be listed as a dependency drug (or smoking will be listed as a dependence process). Thus, it might be wise to contemplate the future legal ramifications of such an inevitability. Additionally, you might want to consider some mode of action which might forestall such a designation by the drug abuse community.

1003726420-6420 (US 85384) (emphasis in original).

  1. A memorandum to Seligman from J.I. Seeman, dated March 18, 1980, provided additional commentary on the Philip Morris "Nicotine Receptor Program." In Seeman's memorandum, he implied that any outside scientist working with Philip Morris had to share the company's interest. He wrote that, "An additional, and perhaps fundamental, requirement was that the individual(s) chosen to work with us is acceptable from a 'political' perspective." 1003289974- 9975 (US 87078).
514

  1. Dunn wrote an internal memorandum to Seligman dated March 21, 1980, describing Philip Morris's "Nicotine Receptor Program," an internal company research program focusing on the psychopharmacology of nicotine. The research was "aimed at understanding that specific action of nicotine which causes the smoker to repeatedly introduce nicotine into his body." While Dunn stated that the nicotine research would likely produce "significant scientific developments," he noted that it was "a highly vexatious topic" that company lawyers did not want to become public because nicotine's drug properties, if known, would support regulation of tobacco by the FDA. Dunn wrote, "Yet this is where our attorneys least want us to be." Moreover, lawyers were concerned that new "knowledge of nicotine" might permit "therapeutic breakthroughs to reduce the incidence of smoking." 0000127789-7792 (US 35152).

  2. Consequently, Dunn observed that while Philip Morris would continue its research program "to study the drug nicotine, we must not be visible about it." And while the program depended on a "heavy commitment" by Philip Morris, Dunn wrote that "our attorneys, however, will likely continue to insist on a clandestine effort in order to keep nicotine the drug in low profile." Dunn mentioned Shook, Hardy & Bacon's Don Hoel and Jacob & Medinger's Ed Jacob by name in his memorandum. 0000127789-7790 (US 21794).

  3. A March 16, 1983 memorandum from researchers James Charles and Victor DeNoble concerning their critiques of the Public Health Service's Report titled "Why People Smoke" acknowledged that Philip Morris had research results with implications contrary to the company's publicly stated opinions on nicotine, but that Philip Morris had not disseminated those findings publicly: "Recent experiments in Vic's [DeNoble's] project have shown that there is a behavioral component to tolerance (a learned phenomenon), but this work has not been published." 1005061346-1346 (US 20199). This was the work, described below, led by Drs. DeNoble and Mele. Mele WD, 11:6-15:4.

515

  1. Under the guidance of Drs. DeNoble and Mele, the Philip Morris Biochemical Research Division developed an important method for demonstrating that rats press levers and will work for nicotine. Such studies had been done earlier with monkeys, but there had not previously been a good rat model. Philip Morris was one of the first to develop a valid rat model for nicotine intravenous self-administration. As outlined infra, Philip Morris prevented the publication and presentation of this important new work, claiming the methodology was flawed. Henningfield WD, 161:23-167:6; DeNoble WD, 17:1-18:6, 22:6-23:18, 39:12-45:11; Mele WD, 20:3-22:12, 28:13- 32:4.

  2. Drs. DeNoble and Mele had also demonstrated, by administering nicotine to rats, the existence of both physiological and behavioral tolerance to nicotine. Mele WD, 11:6-13:5. Behavioral tolerance -- when tolerance develops to a behavioral effect of a drug -- had not been shown prior to this research. Id. at 12:16-13:10. When Dr. Mele sought to publish this groundbreaking research in 1983, Philip Morris informed him that the tolerance study could not be published "because the study showed tolerance and physical dependence to nicotine." Id. at 14:2-10. Instead, Philip Morris would only allow Dr. Mele to write for internal consumption. Id.;

516
  1. Shook, Hardy & Bacon commented on an unpublished manuscript from Drs. DeNoble and Mele titled "Development of Behavioral Tolerance Following Chronic Nicotine Administration," that "[t]he bottom line is that the authors are maintaining that there is tolerance to nicotine, which involves both behavioral and physiological factors." The memorandum noted that such a finding would be detrimental to the cigarette industry:

It is obvious that such a report has undesirable implications for smoking and health litigation. Tolerance is frequently cited as one of the hallmarks of addiction. It is the industry's position that one of the classic criteria for addiction is tolerance, and that such has not been demonstrated in the case of nicotine. While it is true that the Mele and DeNoble paper does not discuss smoking in particular or attempt to extrapolate their experimental findings beyond the laboratory, there is nevertheless the implication simply by the fact that Philip Morris is doing this research, that it is viewing this research as relevant to smoking behavior.

2021424402-4412 at 4404-4405 (US 22847).

  1. In the same memorandum, Shook, Hardy & Bacon pointed out the legal implications of the "unfavorable" Philip Morris internal nicotine research:

Research engaged in, as well as some possibly under consideration, by Philip Morris has undesirable and dangerous implications for litigation positions the industry takes in regard to smoking behavior. The pharmacological nature of the research implies strongly a view of the importance of nicotine. What is worse, research reports under Philip Morris' sponsorship contain claims of unequivocal demonstrations of reinforcement by nicotine in animals. This kind of research is a major tool of our adversaries on the addiction issue; the irony is that industry-sponsored research is honing that tool. In the final analysis, the performing and publishing of nicotine related research clearly seems ill-advised from a litigation point of view.

2021424402-4412 at 4412 (US 22847); 2021423403-3461 at 3422 (US 87038*).

517

  1. The intravenous self-administration rat model is considered a classic indicator that a substance has abuse potential. Using that model, and the same procedure that NIDA used to demonstrate abuse potential, the Philip Morris DeNoble study demonstrated the abuse potential of nicotine. DeNoble WD, 17:9-20:2; See also, 2023963269-3341 at 3312-2213 (US 20398) (DeNoble testimony at 1994 Waxman hearings).

  2. DeNoble's rat studies on self-administration and tolerance succeeded where others had failed and clearly were very significant at that point in history. DeNoble WD, 17:9-18:6. As

DeNoble explained in his testimony before the Waxman Subcommittee in 1994:

The work that we did with nicotine was clearly some years ahead of the external community, scientific community. It wasn't until 1989 that Bill Corgal (sp) demonstrated that nicotine would function as an intravenously delivered reinforcer for rats, using the same models that I used -- that Paul [Mele] and I used. The work that we did on self administration, on dependence, on tolerance, on frustration, clearly would have moved the scientific community much further along than it had been moved by that work not getting out.

2023963269-3341 at 3285 (US 20398). This assessment echoes Dr. Henningfield's view about the adverse impact that Philip Morris's concealment had on the scientific research community.

Henningfield WD, 162:10-167:6.

  1. DeNoble's research colleague at Philip Morris, Dr. Paul Mele, also agreed with this analysis in his testimony before the Waxman Subcommittee in 1994:

. . . [S]ome of these studies were the first to be done with nicotine. I have no doubt that other people would have performed these studies subsequently just as has been done recently in Toronto. But they weren't being done at the time, and to quote a recent review article in Science . . . it basically took six or seven years for the nicotine self-administration model to be developed and come out. Whereas, it would have been out much earlier had this work been allowed to go out and stay out.

518

  1. Philip Morris management fully appreciated the scientific significance of the DeNoble rat self-administration nicotine study. At first, Dr. DeNoble obtained approval to submit it to a leading peer review scientific journal, Psychopharmacology, and there were plans to present results of the study at the 1983 American Psychological Association meeting in Anaheim, California. 2023963269-3341 at 3303 (US 20398).

  2. Prior to publication, at a 1982 presentation at corporate headquarters on the activities of the behavioral pharmacology laboratory including the results of the rat self-administration nicotine study, DeNoble was asked only one question, by the President and CEO of Philip Morris, Ross Millhiser: "Why should I risk a billion-dollar industry on rats pressing a lever to get nicotine?" DeNoble WD, 24:8-25:1.

  3. The saga of the Philip Morris Nicotine Program is summarized in detail in a lengthy 1992 document prepared by outside counsel Shook, Hardy & Bacon titled "Philip Morris Behavioral Research Program." In this report, counsel describe many aspects of the program and cite specific documents showing a major internal research initiative that lasted from 1969 to 1984, involving many scientists, including DeNoble and Mele. The report makes clear that the program generated results and was still generating data in 1984 related to nicotine receptors, analogs, peripheral nervous system effects, central nervous system effects, effects on animal behavior, and differences between high nicotine delivery and low nicotine delivery cigarettes. 2021423403-3497 at 3408-3409 (US

519

  1. In a July 27, 1983 letter to the head of Philip Morris, Shook, Hardy & Bacon attorney Patrick Sigrid summarized the nicotine research being conducted by DeNoble and recommended its suppression. 2046754720-4731 (US 20476).

  2. In April 1984, a few months after a top Philip Morris executive and lawyer visited the behavioral pharmacology lab, DeNoble's laboratory was suddenly, with no warning, preparation, or explanation, shut down and the animals killed. DeNoble WD, 38:4-16, 39:3-9; Mele WD, 25:19- 26:21. In DeNoble's own words, "[O]ur laboratory was terminated in one day." 2504099642-9666 at 9660 (US 22708).

  3. Subsequently, DeNoble was told by several representatives of Philip Morris management that his lab was producing information that the company did not want generated internally. As DeNoble testified at a Congressional hearing:

Apparently, at that same time, some litigation had come out, some law suits, and we were told that the data we were generating, the types of studies that we were doing would not be favorable in that litigation. . . . They just said that if the work were removed from the company connecting it back to the company would be, you know, more difficult to do than if it's being done right in the company itself.

2023963269-3341 at 3305-3306 (US 20398); See also, DeNoble WD, 38:12-14.

  1. In 1986, Dr. DeNoble and Dr. Mele presented their findings on behavioral tolerance development to nicotine in rats to the Federation of American Societies for Experimental Biology in St. Louis, Missouri. In April that year, Philip Morris Companies Assistant General Counsel Eric A. Taussig sent each scientist a letter which stated in part:

As you are aware, upon your employment at Philip Morris . . . you signed an agreement (a copy of which is enclosed) requiring you to keep confidential, unless expressly permitted otherwise, research developed while an employee of the Company. The disclosure of

520

such information as a result of your employment at Philip Morris without permission constitutes a breach of your agreement with the Company. In the future, you are expected to comply with the terms of the agreement.

DeNoble WD, 39:12-42:20; Mele WD, 28:13-30:22; 2047340350-0350 (US 22772); 2077541354- 1354 (US 44603).

  1. DeNoble perceived this letter to be a threat of future litigation. In a September 10, 1986 letter, Taussig again threatened DeNoble and Mele with litigation if they published, or presented, their findings on nicotine self-administration and brain effects, accusing DeNoble of disclosing "information relating to research on a project titled 'Brain Sites Involved in the Mediation of Behavioral Effects of Intraventricularly Administered Nicotine." Taussig wrote that Philip Morris was aware that they had on two occasions already presented the results of their nicotine research, allegedly in violation of their employment termination agreement. He informed them that "the Company cannot tolerate this type of conduct," and reiterated that "if you wish to publish or otherwise utilize research from Philip Morris, you must request and receive permission from the Company." He ended the letter by stating that "[a]ny further breach of your agreement will result in action being taken." 2023192361-2362 (US 20380). DeNoble was released from his confidentiality agreement with Philip Morris in 1994. DeNoble TT, 1/6/05, 9043:19-23.

  2. An April 1994 Shook, Hardy & Bacon report titled "Philip Morris Research of Nicotine Pharmacology and Human Smoking Behavior" pinpoints exactly which research was never made public and the relationship of that research to Philip Morris products. When describing the "Nicotine/Acetaldehyde" research conducted by DeNoble in 1982, research that showed that acetaldehyde and nicotine functioned as "positive reinforcers," the Shook, Hardy & Bacon report admitted that the research was never published:

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CAVEAT: This research has never been published. There is nothing in the literature regarding the synergistic effects of nicotine and acetaldehyde. In addition, see description below re: Frank Ryan data on predicting sales.

Upon learning that acetaldehyde functions as a positive reinforcer, they endeavored to study the combined effects of nicotine and acetaldehyde on self-administration. Results indicated that reinforcing effects of these agents are additive.

Research done by Frank Ryan indicated that acetaldehyde and nicotine data could be used to predict cigarette sales at a 96% accuracy. . . . Frank Ryan ran a program and was able to predict blindly which cigarettes would sell and which wouldn't based on the combination of nicotine and acetaldehyde delivery.

2046819241-9268 at 9249-9250 (US 85265*).

  1. In a later section of the 1994 report, Shook, Hardy & Bacon described how nicotine research undermined Philip Morris's public position denying addiction, and could invite regulation by the FDA: