[Congressional Record Volume 141, Number 121 (Tuesday, July 25, 1995)]
[House]
[Pages H7646-H7683]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]


                      TOBACCO AND AMERICA'S YOUTH

  [Additional statements to Mr. Waxman's Testimony, in the Record of 
Monday, July 24, 1995.]

     January 8, 1969.


                       Objectives and Plans--1600

                [By Dr. P.A. Eichorn and W.L. Dunn, Jr.]


                              Objective 1

       To establish different thresholds for menthol level in 
     cigarettes and identify optimum menthol level or levels.
     Plan
       Complete study already initiated by April 1.


                              Objective 2

       Attempt to develop research addressed to following 
     questions:
       (a) How much reduction in TPM delivery can we expect the 
     typical smoker to tolerate over the next five years?
       (b) Can we forecast the stabilization level in the 
     percentage of the U.S. population who smoke cigarettes?
       (c) Is there any product that can potentially replace the 
     cigarette in need-gratification?
     Plan
       Non-schedulable. The task is one of problem solution in 
     research design.


                              Objective 3

       To develop instrumentation and procedures for monitoring 
     the psychophysiological state and responsivity of the free-
     roaming human and apply this technology to a study of the 
     psychophysiological state and/or responsivity of cigarette 
     smokers relative to non-smokers.
     Plan
       (1) Instrument acquisition and calibration by May 1, 1969.
       (2) Hard-line preliminary runs with human subjects 
     completed by December 31, 1969.


                              Objection 4

       To attempt to teach a rat to seek the inhalation of 
     cigarette smoke.
     Plan
       An informal small-scale (no budget) exploration in which 
     principles of operant conditioning will be applied to 
     teaching the rat to inhale smoke first through reinforcement 
     of the act by food or shock avoidant reward and ultimately 
     through the reinforcing effect of the psychopharmacological 
     effects of the inhaled smoke. No definite conclusion 
     anticipated in 1969.
                                 ______

     To: Dr. H. Wakeham
     From: W. L. Dunn, Jr.
     Date: August 1, 1969
     Subject: A Trip Report--Discussions with Prof. Lazarsfeld on 
         the Study of Discontinuing Smokers
       I spent six hours with Dr. Paul Lazarsfeld on Wednesday. 
     Following lunch together, I sat with him in his office in the 
     Sociology Dept. of Columbia University, later attending as 
     his guest a status conference on the on-going drug addiction 
     study for New York State. The conference was held in the off-
     campus building housing the Bureau of Applied Social 
     Research. I met several of his doctoral staff members and 
     observed the graduate student interviewing staff as they 
     participated in the conference proceedings. I was favorably 
     impressed.
       We have made great strides towards initiating the 
     exploratory study of the experiences of smokers in their 
     efforts to discontinue the habit. The agreed upon calendar of 
     events calls for Dr. Lazarsfeld to submit a proposal to P.M. 
     R&D prior to August 15. In turn I agreed to make immediately 
     available to him copies of pertinent articles from the R&D 
     Smoking and Health library, to be followed by a background 
     bibliography of broader scope. Thereafter, pending acceptance 
     of his proposal, dialogue between P.M. R&D and BASR staff 
     will be addressed to the development of interview format and 
     content.
       I anticipate that his proposal will consist of a study of 
     recidivists and cohort groups of abstainers, the latter 
     consisting of one month, three-month, six-month and one-year 
     abstainers. Subjects will be selected on a post-hoc basis, 
     that is, their efforts to abstain will precede their entry 
     into the study. Interviews will be retrospective probings 
     into their daily lives during the period from the date of 
     discontinuation to the date of the interview. The initial 
     interviews will be loosely structured, with subsequent waves 
     increasingly structured and focused. The progressive 
     sharpening of the interview is to the achieved through Prof. 
     Lazarsfeld's characteristic research style; a series of 
     conferences in which interview material from new batches of 
     interviews is studied in great detail for clues to pay-dirt, 
     with subsequent interviews altered accordingly. I saw this 
     approach in operation in the drug-addiction conference. In 
     its current application it appears to be highly effective. I 
     can see no reason why It should not be as effective for the 
     proposed study.
       We also discussed the idea of a steering committee. We 
     noted the various forms this might take:
       1. An unstructured group of consultants to Prof. Lazarsfeld 
     as principle investigator.
       2. A formally structured advisory group to the project.
       3. The Board of the Stress Institute (in this case the 
     Stress Institute would likely be the sponsor of the project).
       He seemed equally amenable to all three, though expressing 
     fascination with the third alternative. He pointed out that 
     the task of creating an institute would require heavy 
     commitment of time on someone's part over a period of many 
     months.
       As men of repute to advise, he is agreeable to Hans Selye 
     (whom he does not know) and he suggested Prof. Stanley 
     Schacter, a social psychologist of Columbia University who 
     has recently been studying the effects of adrenalin on 
     perceptual processes. We further agreed upon the wisdom of an 
     additional psychologist closer to the physiological front. I 
     named Dr. Frank Finger of the University of Virginia, widely 
     known among psychologists and active in various governing 
     bodies of the American Psychological Association. Another 
     prospect that just occurred to me is Joseph D. Matarazzo, 
     Chairman, Dept. of Medical Psychology, University of Oregon 
     Medical School and writer of the source review of smoking 
     psychology in 1960.
       He displayed pleased surprise at our interest in the 
     development of theory, although at this point it would be 
     difficult to say whether this was diplomacy or genuine 
     interest.
       I also met and spoke briefly with George Brooks, his staff 
     man formerly with Elmo Roper, confidante of Jet Lincoln, and 
     key man in the series of smoker attitude surveys conducted in 
     the early '60's by Roper for Philip Morris.
                                 ______

  Ryan/Dunn Alternate--Third Version of Board Presentation--Delivered 
                  With Only Minor Changes (Fall 1969)

     Gentlemen of the Board and guests:
       Once again it is my pleasure to appear before you and to 
     make this traditional annual presentation of Philip Morris 
     Research Center activities. Before talking about that 
     particular aspect of the program that I have selected for 
     this year's presentation, let me 

[[Page H 7647]]
     make a few remarks about the Research Center in general. You have 
     before you a new brochure on Research at Philip Morris. In it 
     are details about our people and the facility, but here are 
     some figures I think you will find of interest. Our present 
     staff numbers about 330 persons. We occupy 125,000 ft. of 
     floor space. Our budget for this year is $6 million, of which 
     about 25 percent goes into research, 50 percent into product 
     development and 25 percent into technical services to other 
     departments.
       I have selected our psychology program to talk about this 
     year. In terms of people and budget it is relatively 
     inconsequential, which partly explains why it has never been 
     mentioned before. We are proud of the fact that we are the 
     only company in the industry that has the discipline of 
     psychology represented amongst its research staff; and we 
     think it only proper, in view of the climate of the times, 
     that we concern ourselves with the topic of the psychology of 
     smoking.
       In order to bring you up to date, let me first review the 
     highlights of accomplishments on this front during the past 
     few years.
       1. We have established a consumer research facility called 
     our Product Opinion Laboratory. This consists of about 
     fourteen people, mostly pretty girls, who have as their chief 
     task the collecting of opinions and judgments about our new 
     products. The judgments are made by different types of 
     people, depending on the stage of product development and the 
     degree of expertise required. Thus, preliminary taste and 
     flavor profiles are supplied our chemists and development 
     engineers by three small groups of highly trained experts. 
     Products slightly further along the development trail are 
     evaluated by a larger groups of less expert Research Center 
     employees, supplemented by a group of about eighty Richmond 
     housewives who smoke cigarettes in an office near a shopping 
     center. Further screening is available from about 1500 
     members of civic clubs and community organizations who are 
     called on when we want a quick test from a more 
     representative group of non-experts. And finally, products 
     approaching the test market stage of development are 
     evaluated by a national cross section of American consumers, 
     chosen from some 35,000 people who represent 15,000 families.
       So, funneled through our little group of consumer research 
     people, there is a continuous flow of consumer responses to 
     guide the Research Center and Marketing people of making 
     product decisions.
       Apart from their routine product testing, they have also 
     reported a number of interesting findings that are worthy of 
     mentioning.
       2. Some Highlights:
       A. One study has demonstrated that a cigarette manufacturer 
     presumably P.M.--can increase the reconstituted-tobacco 
     component of the cigarette blend to 30 percent without 
     significantly altering the taste and subjective properties of 
     the smoke. The implications of dollar savings here are 
     obvious.
       B. Another study demonstrated rather dramatically that the 
     menthol coolness ascribable to our competitor's Kool 
     cigarette is attributable to its name and brand image rather 
     than to the taste of the smoke, per se. When the Kool 
     cigarette was compared to our Marlboro Menthol with the brand 
     identify concealed, menthol smokers, including regular Kool 
     smokers, could not tell the difference. When these same 
     smokers smoked these same cigarettes in their regular 
     packages, most of the menthol smokers chose the Kool 
     cigarette to be the cooler smoking.
       C. In a third study a thousand smokers were asked to 
     compare cigarettes made of aged tobacco with cigarettes of 
     unaged tobaccos. They had no preference, suggesting that the 
     aging process does not significantly alter the taste of the 
     cigarette from the consumer's point of view. This means we 
     have more latitude in maintaining a tobacco inventory than 
     was heretofore appreciated.
       D. All the medical research on how much people smoke has 
     used the smoker's estimate of how many cigarettes he smokes a 
     day. We've always known this to be a crude measure, but a 
     recent P.M. study has made it possible to show how very crude 
     it is. Our chemists have developed a means of measuring 
     residual nicotine in the filter of a cigarette. From this can 
     be precisely calculated how much TPM passed through the 
     filter and into the smoker's mouth. We had 2500 filter 
     smokers save their butts for us for one week, and from the 
     residual nicotine measurements, obtained an average daily TPM 
     intake value for each smoker: The slide before you shows the 
     relationship of the daily intake value with the smoker's 
     estimate of how many cigarettes he smokes per day.
       There are two important political as well as scientific 
     implications from this study.
       1. The index of smoking level in health surveys as 
     determined by the number of cigarettes people say they smoke 
     is a very unreliable measure of actual smoke intake, and
       2. The prediction of smoker intake from the FTC tar value 
     for the brand smoked is also very unreliable.
       E. From the study of smoke intake we developed the 
     hypothesis that a smoker will tend to seek his own level of 
     smoke intake whether he smokes filter cigarettes, long 
     cigarettes or skinny cigarettes. A study to test this 
     hypothesis has just been completed. We had about 150 filter 
     smokers volunteer to smoke only the cigarettes we gave them 
     for six weeks. For the first two weeks they all received 
     cigarettes delivering 20 mg of TPM. Beginning the third week, 
     half the group were supplied with cigarettes delivering 25 mg 
     and the other half were given cigarettes delivering 15 mg. 
     They were not informed of the switch nor did they know 
     anything about the purpose of the study. They were kept on 
     the high and low TPM cigarettes for four weeks. During the 
     entire six weeks they saved their butts. Daily intake values 
     were calculated from the residual nicotine in the butted 
     filters.
       The slide tells the story. Initially there was an increase 
     in daily intake for those shifted to the 25 mg cigarette, and 
     a decrease for those shifted to the 15 mg cigarette. But 
     notice that they returned toward their original level of 
     intake after 2 weeks on the new cigarette. It would appear 
     that smokers do modify their smoking habits in order to 
     maintain a preferred intake level. [Illegible]
       So much for the past. Recently the psychology program has 
     added a new emphasis. Most of our attention in the past has 
     been focused upon the cigarette. Now we are beginning to 
     concentrate on the smoker himself. We are addressing 
     ourselves to that simple but fundamental question, ``Why do 
     people smoke?''
       I must admit to some embarrassment when I say I don't know 
     the answer to this question. It is even more embarrassing to 
     the psychologists on my staff. But I can tell you this . . . 
     . despite the voluminous research and pseudo-sophisticated 
     theories, there is not a scientist alive who can give an 
     explanation backed up by fact.
       First we have to break the question into its two parts: (1) 
     Why does one begin to smoke? and (2) Why does one continue to 
     smoke?
       There is general agreement on the answer to the first part. 
     The 16 to 20 year-old begins smoking for psychosocial 
     reasons. The act of smoking is symbolic; it signifies 
     adulthood, he smokes to enhance his image in the eyes of his 
     peers.
       But the psychosocial motive is not enough to explain 
     continued smoking. Some other motive force takes over to make 
     smoking rewarding in its own right. Long after adolescent 
     preoccupation with self-image has subsided, the cigarette 
     will even preempt food in times of scarcity on the smoker's 
     priority list. The question is ``Why?''
       One of the obvious ways to approach the problem is to ask 
     the smoker himself why he smokes: When you do this (and Leo 
     Burnett did this about 10 years ago for P.M.) the smoker will 
     either parrot an advertising slogan or give you one of these 
     responses: (1) It relaxes me.
       (2) It stimulates me.
       One way to interpret this is to conclude that different 
     people are affected in different ways by the inhalation of 
     smoke. We are inclined, however, to ascribe this apparent 
     duality of effect to an inability on the part of the smoker 
     to describe smoke-produced sensations.
       Another obvious way to approach the problem is to search 
     for differences between smokers and non-smokers. This 
     strategy has been more fruitful. The research effort in 
     England and the U.S. over the past 15 years has yielded the 
     following findings:
       A. Personality Differences--Smokers are:
       (1) More gregarious.
       (2) More extroverted.
       (3) More business oriented.
       (4) Greater sense of time urgency.
       (5) More competitive.
       (6) More mobile (jobs, residences).
       Generally more aggressive and risk oriented.
       B. Physiological Differences:
       (1) Smokers have faster heart rate.
       (2) Eat more.
       (3) Drink more--beer, whiskey, coffee.
       (4) Have higher oxygen metabolism.
       (5) Weigh less.
       Generally more active, faster living.
       C. Psychological Differences--Smokers exhibit:
       (1) More anxiety.
       (2) More emotional disturbance.
       (3) Higher accident and injury rate.
       (4) More suicide.
       (5) Lower grades in school.
       Generally more tense and emotional.
       A third way to approach the question is to search for the 
     immediate effects of smoke inhalation upon the smoker. This 
     approach also has been fruitful. Here are the changes in 
     human body function which follow smoke inhalation. All of 
     these changes have been reported by at least two independent 
     researchers:
       Cigarette smoke effects:
       Increased pulse rate; Increased cardiac output and coronary 
     flow; Lowered skin temperature in hands and feet; Adrenalin 
     released into blood stream; Increased blood flow in skeletal 
     musculature; Reduction in pattellare reflex magnitude; Nerve 
     impulse transmission facilitated through autonomic nervous 
     system; Arousal center in brain stem excited, causing arousal 
     patterns in the electrical activity of the cortex; Blood 
     sugar level increases.
       Now what can be said about all of these findings?
     As for the differences between smokers and non-smokers, one 
     might summarize with these three general observations:
       1. Cigarette smoking is more often a habit among more 
     responsive, more arousable, more anxious people than among 
     the less responsive or more tranquil people.
       2. More cigarette smoking is to be found among people whose 
     life careers expose them to pressures and crises.
       3. A smoker smokes more during the more stressful moments 
     of his day or during stressful period of his life.

[[Page H 7648]]

       One might expect from these differences to find that people 
     are attracted to smoking because it acts as a tranquilizer in 
     a stressful situation, as some told Leo Burnett. Indeed this 
     reason for smoking has been hypothesized by a number of other 
     investigators. But in our experimentation whenever we have 
     attempted to confirm this hypothesis, we have found exactly 
     the opposite effect. For example, in studies using excessive 
     muscle tension as a measure of psychological arousal we have 
     observed that smoking increases rather than decreases muscle 
     tension.
       We are of the conviction, in view of the foregoing, that 
     the ultimate explanation for the perpetuated cigarette habit 
     resides in the pharmacological effect of smoke upon the body 
     of the smoker, the effect being most rewarding to the 
     individual under stress.
       We cannot view the smoke as a tranquilizer; most of its 
     effects on body function suggest arousal. We can see on all 
     the benefits of smoking when bored, not yet fully awake, 
     etc.--it arouses you when you need to be aroused. However, we 
     do not yet understand how an additional source of stimulation 
     could be rewarding to an aroused person in a stress 
     situation. We are beginning to work on this problem.
       Currently we are making exploratory measures of bodily 
     indices of emotion and arousal. We are measuring heart rate, 
     respiratory rate, the electrical resistance of the skin and 
     muscle tension. At the moment our subjects are wired to a 
     polygraph recorder; we plan to develop the techniques and 
     instrumentation to measure these indices remotely by radio 
     signal.
       Our ultimate intent is to monitor the smoker under real 
     life conditions, under conditions of experimentally induced 
     stress and under conditions of tobacco-deprivation.
       This is basic exploratory research, but we would hope for 
     fallout in the way of information applicable to the design of 
     our smoking products and also information that could be used 
     in a public relations program to counter that of the American 
     Cancer Society.
                                 ______

     To: W.L. Dunn, Jr.
     From: F.J. Ryan
     Date: December 23, 1969.
     Subject: Proposed Research Project: Smoking and Anxiety
       It seems likely that cigarette smoking is affected by 
     stressful situations, but we have little experimental 
     evidence of such a relation. We reason that stressful 
     situations produce states of anxiety within the smoker, and 
     know that he seeks anxiety-reducing palliatives in order to 
     feel more comfortable. Smoking may be one of these 
     palliatives. However, not only are the mechanisms by which 
     tobacco smoke might serve as a palliative not completely 
     clear, but we do not even know whether people smoke more 
     under stress than under nonstress. We wish to conduct the 
     research outlined below in order to clarify the matter and 
     lay the ground work for later study. It is discouraging to 
     realize that we have so little data available that we must 
     start at the very beginning but start we must.
       Title: Smoking Under Conditions of Shock Produced Anxiety
       Purpose: To show cigarette smoking is more probable in 
     stress situations than in nonstress situations.
       Importance: Most research in smoking emphasizes its 
     negative qualities. This project is interested in one of the 
     advantages of smoking, its use as an anxiety reducer.
       Nontechnical Summary: We will warn people that they're 
     going to get a harmless but annoying shock while we note 
     changes in (a) amount of smoking, compared to no shock days 
     and in (b) frequency of puffs during the interval between 
     warning and shock. The smoking, the warning, and the shock 
     will all be embedded in a simple discrimination task. Our 
     cover story will be that we are interested in ``smoking and 
     judgment.'' (We need to disguise our real interests in order 
     to prevent subjects from telling us what they think we want 
     to know.)
       Predicted Results: (a) Number of puffs on cigarettes will 
     be highest on days when shock is administered, lowest on days 
     when shock is not administered. (b) The distribution of puffs 
     on shock days should be different from the distribution of 
     puffs on no shock days. E.g., either a greater percentage of 
     puffs may occur between the warning and the shock on shock 
     days than in a similar interval on no shock days, or it may 
     be that we will find puffing is postponed until after shock 
     administration.
       The Subjects: We prefer to use non-employees for this 
     research. A ready supply of college age subjects can be had 
     from VCU and the University of Richmond. We will pay for the 
     services of both males and females, all volunteers over 21 
     years old. Each subject will be asked to sign a paper stating 
     that he understands the general conditions of the experiment, 
     and it will be made clear that the subject can withdraw from 
     the experiment at any time, including the middle of a 
     session. They will be paid $2 for participating in each 
     session, plus about $1.50 in rewards for correct responding. 
     In the course of several sessions they can earn $15, 
     including a bonus for completing a series of sessions.
       Shock Intensity: Shock intensity will be adjusted for each 
     subject according to the subject's pain threshold. The shock 
     will be painful, but tolerable. Depending on the subject, 
     this will require shock currents of from half a milliamp up 
     to three and a half milliamps. Shock administration will be 
     via a constant amperage shock source controlled by relay 
     equipment. Safety precautions include (1) an isolation 
     transformer, (2) fuses in both shock leads, and (3) a limited 
     time of administration through the contacts of a 
     precautionary timer. The latter unit would limit shock 
     duration to T1 seconds in case the shock administration 
     circuit should fuse shut.
       The Discrimination Task: A series of slides containing 
     different shapes will be presented by a modified Carousel 
     projector. Odd numbered slides will contain a single shape, 
     even numbered slides two shapes. The subject's task will be 
     to decide which of the two shapes presented on the even 
     numbered slide most closely resembles the shape shown on the 
     preceding odd numbered slide. (The shapes can be varied in 
     number of enclosed dots, number of sides, color, area, etc., 
     and there may or may not be irrelevant characteristics also 
     present.) Whenever the correct choice is made, the subject 
     will be rewarded with a token. At the conclusion of the 
     session the accumulated tokens can be exchanged for money 
     over and above the amount paid for participation. Whenever an 
     incorrect choice is made, a warning tone will sound. The tone 
     will last for T2 seconds. Tone offset will, on shock 
     trials, be accompanied by a brief presentation of shock to 
     the subject's fingers.
       Noshock-day Procedures: On days when the subject is to 
     receive no shock he will be treated exactly as on shock days, 
     but he will be told truthfully that he will receive no shock. 
     No pretesting shocks will be administered on these days, and 
     incorrect choices will produce only the tone.
       Shock-day Procedures: The subject will receive pre-test 
     shock to find his appropriate shock intensity. His incorrect 
     responses will produce the warning tone. The probability, p, 
     that the tone will terminate in shock will always be above 
     zero, but need not be 1.00 (certainty). It might be more 
     anxiety producing to have p values of less than 1.00, for we 
     suspect that uncertainty of punishment may be more disturbing 
     than certainty of punishment. Accordingly, we will have two 
     different shock-day procedures, one of which p=1.00 and one 
     in which p=.50, or some other value less than 1.00.
       The Subject's Response: The subject's overt task is to 
     throw a left switch or a right switch to indicate that the 
     left or right stimulus is most like the previous stimulus. 
     Action of these switches will produce electrical impulses 
     which in turn will deliver shock or reward, depending on the 
     state of other routing switches. The routing switches will be 
     set by photocell relays, operated by lights shining through 
     holes in the plastic slide mounts of the modified Carousel 
     projector. The relays and switches will start and stop 
     various timers, which will in turn control the sequence of 
     events. Subjects will be asked to abstain from smoking for a 
     period of time prior to the test session, and will be asked 
     to smoke during the test session. Puffing will be observed by 
     the monitoring experimenter, who will throw a switch to mark 
     each puff. The placement of puffs within the intervals 
     between other events can be read directly off a polygraph 
     record. (If a satisfactory puff monitor can be produced by 
     the electrical engineers at U. Va. then its output can 
     replace the experimenter/observer's switch.)
       Later Research Plans: It is possible for us to monitor a 
     number of concurrent physiological variables during the test 
     session, such as Heart Rate, GSR, perhaps EMG, depending on 
     our developing interests.
                                 ______

     Charge Number: 1600
     Program Title: Consumer Psychology
     Program Leader: W. L. Dunn, Jr.
     Period Covered: September 16--October 15, 1971
     Project Title: Psychology of Smoking
     Project Leader: W. L. Dunn, Jr.

       The Conference on Motivation in Cigarette Smoking is on 
     schedule.

     Project Title: Miller Brewing Work
     Project Leader: Anne Ferguson

       A new augmenting smoking panel is being selected and the 
     beer panel is receiving refresher instruction. Both 
     activities are being undertaken with the consultative 
     assistance of Barbara Hall Ellis.

     Project Title: Methods Studies
     Project Leader: W. L. Dunn, Jr.

       Replication of SIC-1 (preference justification effect) is 
     in the field. The study of alternative field test designs was 
     mailed out but has been aborted and will be rerun due to 
     package coding errors.

     Project Title: Smoking Profiles: A Pilot Study
     Project Leader: Frank Ryan

       Several improvements in the puff monitoring system have 
     made it less obtrusive. Some preliminary measures have been 
     made on college students in the shock research project, and 
     additional measures have been made on R & D personnel to aid 
     in calibration of the system. When five additional models are 
     made, they will have slightly different specifications. The 
     range of flow rates by the orifice is such that we will have 
     to use different models for different smokers, but we should 
     be able to handle 9/10 of the smokers we are likely to meet. 
     (See the reports of the Program on Human Smoking Simulation, 
     Charge Number 4008)

     Project Titles: Shock I, II, III, and IV
     Project Leader: Frank Ryan
       We continue to gather data on the puffing behavior of local 
     college students (Shock 

[[Page H 7649]]
     IV). The first study of this type (Shock I) indicated that personality 
     affected the puff rates of the 16 students in a shock and 
     heart rate experiment. The second study (Shock II) replicated 
     the procedures of the first but omitted the heart rate 
     measures. Assigning 21 new students to one of three groups on 
     the basis of their personality scores and the data of the 
     first study, we predicted that the three groups would rank 
     low, moderate, and high in number of puffs. The data 
     supported the hypothesis, the means being 9.1, 10.6 and 12.0 
     puffs for the three groups.
       At third variation (Shock III) of the procedures has now 
     been completed and the data analyzed for 23 new students. The 
     results suggest that personality factors, particularly the 
     Anxiety factor, account for most of the puffing in our test 
     situation under our tests conditions (note the qualifiers.) 
     The correlation between the personality factors and puff rate 
     is very high, and further research will undoubtedly lead to 
     lower but more stable figures.
       We are very much encouraged by the tend of these findings, 
     because they bear on the hypothesis that different types of 
     people have different tar and nicotine intakes.

     Project Title: Preferred Tar Reduction Procedure
     Project Leader: Frank Ryan
       Planning is underway for a study of consumer preferences 
     among the different procedures which lower FTC Tar delivery. 
     Cigarette models will be chosen in November, and mailout 
     target date is February 20, 1972.

     Project Title: Cigarette TPM Difference Limens
     Project Leader: T.R. Schori
       Twenty R & D employees have been run as subjects in this 
     study which was designed to determine what constitutes a 
     just-noticeable-difference in cigarette TMP. The data suggest 
     that smokers are very poor at making such discriminations. We 
     are instigating a slight change in our approach to the 
     problem to see whether our procedure is insensitive or 
     whether in fact smokers are unable to discriminate.
                                 ______

     Charge Number: 1600
     Program Title: Consumer Psychology
     Period Covered: January 15-February 15, 1972

     Project Title: Preferred Delivery Reduction
     Written by: Frank Ryan
       We are comparing five cigarettes, each delivering about 14 
     mg. tar from a Marlboro 85 blend. Each achieves its tar 
     reduction in a different fashion. The models are: No air 
     dilution, high RTD; moderate air dilution, moderate RTD; high 
     air dilution, low RTD; a paper/CA filter; and an extended 
     tipping paper. Prototypes have been made which are reasonably 
     homogeneous and close to the 14 mg. target, and mailout 
     cigarettes have been ordered. Panelists will be selected from 
     known Marlboro smokers after POL National repolling is 
     complete.

     Project Title: Shock V
     Written by: Frank Ryan
       (a) Additional subjects will be screened to test our 
     personality-puff rate data with new slides.
       (b) We plan to reintroduce electric shock in studies this 
     spring.
       (c) The apparatus is currently tied up in the smoking 
     profiles pilot work.

     Project Title: Smoking Profiles Pilot Study
     Written by: Frank Ryan
       Students with known puffing patterns (e.g., number of puffs 
     and puff intervals) are evaluating the difficulty of the 
     slides used in Shock I-V while smoking with the human smoking 
     recorder. We are looking for differences in puff behavior 
     attributable to the cigarette holder mouthpiece, tubes, 
     recorders system, etc.
       The first test we plan to run with this apparatus will 
     compare puffing behavior on two different types of very 
     different cigarettes. Our present plans are first to test a 
     high delivery 85 mm against a low delivery 85 mm vs. 100 mm 
     of comparable draw.

     Project Title: Puffing vs. Judgment
     Written by: Frank Ryan
       We will ask our students to rate two vastly different 
     experimental cigarettes, using standard SEF callots, to see 
     whether those who take many puffs are as responsive to smoke 
     characteristics as those who take few.

     Project Title: Perceived Attributes of Cigarettes
     Written by: T.R. Schori
       This study was designed to determine major cigarette 
     characteristics as perceived by smokers by means of a factor 
     analytic technique. Ballots are in process of being mailed to 
     a representative panel of 800 smokers.

     Project Title: Smoking and Low Delivery Cigarettes
     Written by: T. R. Schori
       This is a two part study. Cigarettes for Part 1 (TNT-2) are 
     in the process of being mailed out. Cigarettes for Part 2 
     (TNT-3) are currently being developed.

     Project Title: A Comparison of the Effect of Caffeine and 
         Cigarette Smoking
     Written by: T. R. Schori
       Smokers were tested in each of 3 conditions: placebo, 
     caffeine, and cigarette smoking. Eleven measures of arousal 
     were collected. A discriminant analysis indicated that these 
     three groups differed from one another in terms of the eleven 
     measures considered simultaneously. A report will be written 
     shortly.
                                 ______

     Dr. P.A. Eichorn
     W.L. Dunn, Jr.
     Quarterly Report--Projects 1600 and 2302
     October 5, 1972


                                sex-iii

       Twelve hundred of the original 2400 filter smokers who 
     participated in the SEX-I study in 1968 are, at the time of 
     this writing, saving butts for R&D analysis. We will be 
     attempting to relate change in smoke intake to other 
     variables, notably change in available TPM in the cigarette 
     smoked.
       Publication of Smoking Behavior: Motives and Incentives.--
     Because of editing difficulties with one author, the volume 
     is now likely to be delayed until January, 1973.
       Participation in Ford Motors Keep-Well Campaign.--The 
     Medical Department of Ford Motor Co. will be launching an 
     exploratory study of a Prophylactic Program to Reduce 
     Cardiovascular Illness among Employees. We will collaborate 
     in the design and data collection. The study is in the early 
     planning stage.
       Miller Brewing.--We are providing ongoing consultation and 
     testing services to this subsidiary in the evaluation of its 
     beer products.
       The Schachter Studies.--We are collaborating closely with 
     this investigator and providing technical support to the 
     research activities in the Psychology Dept. of Columbia 
     University. A significant theoretical contribution to the 
     understanding of cigarette smoking is believed imminent from 
     this effort.
       Puffing Behavior.--We have begun gathering puffing data 
     among student college smoking various brands of cigarettes 
     and little cigars. Intake variables (puff frequency, 
     interpuffing intervals, puff volume, etc.) should prove 
     related to product preferences, FTC tar and nicotine 
     delivery, etc. The human smoking recorder is used to monitor 
     the puffing while subjects watch slides.
       Personality and Puffing.--We continue to observe 
     differences in puffing behavior related to personality 
     variables. The effect seems clearer among male subjects than 
     among females.
       Shock and Smoking.--Data collection will resume in October 
     at a new location (POL). We need to develop a different 
     stressor as fear of shock is scaring away some of our more 
     valuable subjects.
       Sustained-Performance and Smoking.--In this two-part study, 
     we are evaluating psychomotor performance of smokers, 
     deprived smokers, and nonsmokers over time (3 hours). Part 1, 
     concerned with complex task performance, has been completed. 
     The subject's task consisted of five subtasks which had to be 
     performed simultaneously. These subtasks were: a meter 
     monitoring subtask (6 meters), a light monitoring subtask (4 
     lights), a visual choice reaction time subtask, an auditory 
     choice reaction time subtask, and a mental arithmetic 
     subtask.
       In terms of all five subtasks, the subjects showed 
     significant improvements in performance over time. No 
     significant differences in performance were found between the 
     three smoking conditions except in the auditory subtask where 
     smokers displayed the best performance. This latter finding 
     suggests the possibility that smoking enhances auditory 
     sensitivity and we are currently looking into this 
     possibility. As we had found in previous studies, smokers had 
     fewer significant mood changes (as measured by the Nowlis 
     Mood Scale--a paper and pencil device to measure transient 
     mood states) than did nonsmokers or deprived smokers. This 
     suggests that smokers are more emotionally stable in this 
     sort of test situation than are nonsmokers or deprived 
     smoker.


  multiple discriminant Analysis: A repeated Measures Design Virginia 
Journal of Science, 23, 62-63, Summer, 1972. Schori, T.R., and Tindall, 
                                  J.E.

       Menthol Cigarette Studies.--Two menthol cigarette studies 
     are underway. The first is designed to delineate the images 
     possessed by various of the menthol cigarettes currently on 
     the market. This is a questionnaire type study using national 
     roster panelists.
       The second type is a smoking test. It is designed to 
     identify nicotine and menthol parameters which make for 
     optimal acceptability of menthol cigarettes. This study has a 
     three-stage design. The first stage is designed to identify 
     those nicotine delivery levels which we might reasonably wish 
     to consider for menthol cigarettes. Having identified these 
     nicotine delivery levels, in stage 2 we will determine 
     combinations of nicotine and menthol which make for optimal 
     acceptability. And then in stage 3, cigarettes with these 
     combinations will be tested against current brands of known 
     quality and sales potential.
       Bay Area Study.--Marketing, for the past few months, has 
     been trying to improve the image of Multifilter in the San 
     Francisco Bay Area and San Jose. In this study, we are trying 
     to determine whether this attempt to improve Multifilter's 
     image has been successful. We are doing this by means of a 
     mailout to smokers in these areas.
       Tar and Nicotine Studies.--We have done a number of 
     nicotine to tar ratio studies. Development is continuing to 
     try to make cigarette models with various levels of tar and 
     nicotine using our low nicotine tobacco. When we get 
     successful models, we will go out to a national panel in an 
     attempt to determine combinations of tar and nicotine which 
     make for optimal acceptability.
       In addition, a local panel of smokers will test these 
     cigarettes for nine weeks in order to determine the effect of 
     tar and nicotine on cigarette consumption when both tar and 

[[Page H 7650]]
     nicotine deviate downward from that to which the smokers are 
     accustomed. This is a follow-up of TNT-1.
                                 ______

     Dr. P. A. Eichorn
     W. L. Dunn, Jr.
     Five-year Objectives and Plans for Project 1600
     September 25, 197


                              objective I

       Identify as many as possible of the short-term 
     psychological and psychophysiological phenomena attendant 
     upon the smoking of a cigarette.
       Plans.--To expand the scope of the present psychology 
     research program to include studies of the immediate, short-
     term effects of cigarette smoking as manifested through 
     changes in autonomic, perceptual, cognitive and central 
     nervous system processes and motor performance.


                              objective II

       Advance scientific knowledge of the motivation sustaining 
     the cigarette smoking habit.
       Plans.--(1) To further observe the smoking-induced changes 
     identified under Objective I under varying degrees of 
     psychological tension, from relaxed calmness to anxiety, in 
     order to study the interaction effects of smoking and tension 
     upon psychological function.
       (2) To conduct studies in which the dependent variable is 
     rate of smoking and the independent variable is a situational 
     factor affecting the smoker's level of vigilance or tension, 
     testing the hypothesis that rate of smoking is a function of 
     vigilance or tension level.
       (3) To research the question, ``Can the smoking habit be 
     sustained in the absence of nicotine?'' Other strategies may 
     be developed, but one now being explored is to attempt to 
     identify which components of the smoke, in gross fractions, 
     effect the heart rate change associated with inhalation of 
     whole smoke.
       (4) To coordinate the industry-sponsored conference on the 
     motivational mechanisms of cigarette smoking scheduled for 
     January, 1972.
       (5) To prepare a review paper on the psychodynamics of 
     cigarette smoking.


                             objective III

       Forecast trends in cigarette smoking behavior and 
     preferences for guidance in cigarette development.
       Plans.--(1) To design a test for determining the smoker's 
     tolerance for reduction in tar delivery over time in terms of 
     rate, increments and limits of reduction.
       (2) To elucidate the role of nicotine as a factor in 
     determining cigarette acceptability in terms of absolute 
     levels and relative to other smoke components.
       (3) To more systematically observe puffing profiles of 
     smokers across various cigarettes via use of the mobile 
     recording system developed for P.M. by the Engineering School 
     of the University of Virginia.


                              objective IV

       Establish the psychological units of detectable difference 
     for the basic dimensions of cigarette smoking including tar, 
     nicotine, RTD, menthol and TFP.
       Plans.--Since methodological obstacles have severely 
     limited our progress on this front to date, we must 
     concentrate on devising research procedures for circumventing 
     these obstacles.


                              objective v

       Improve the validity and reliability of our standard 
     product testing procedures, and reduce the lagtime between 
     service request and report of findings.
       Plans.--(1) Continue, as in the past, to test out new 
     research designs and procedures.
       (2) Incorporate data retrieval, processing and reporting 
     innovations into our routine procedures as they become 
     available and appropriate.
                                 ______

     Charge Number: 1600
     Program Title: Consumer Psychology
     Program Leader: W.L. Dunn, Jr.
     Period Covered: October 16-November 15, 1971

     Project Title: Psychology of Smoking
     Project Leader: W.L. Dunn, Jr.
       The Conference on Motivation in Cigarette Smoking is 
     continuing on schedule.

     Project Title: Methods Studies
     Project Leader: W.L. Dunn, Jr.
       The study of alternative field test designs (TRI-2) is in 
     the field. SIC-2 (preference justification effect) is now in 
     analysis.

     Project Title: Shock IV
     Project Leader: Frank Ryan
       Data collection continues in this series of experiments on 
     student smoking behavior. Nearly 100 students have been 
     tested in the four series to date. We are seeking additional 
     tasks for them to perform in order to broaden the scope and 
     generality of our findings.

     Project Title: Desire to Smoke
     Project Leader: Frank Ryan
       All available college subjects will fill out a 
     questionnaire rating their desire to smoke in each of 22 
     hypothetical situations. One of Eysenck's colleagues has 
     postulated that there are two types of smokers: one smoker 
     smokes in quiet situations to raise the level of his central 
     nervous system arousal, a second smokes in tense situations 
     in order to reduce their arousal level. The published data 
     suggest that males had their highest desire in quiet 
     situations, females in stressful situations. This may be 
     related to male extroversion and female introversion factors, 
     so Eysenck has suggested that extroverts smoke to increase 
     arousal, while introverts smoke to reduce arousal. We'll 
     compare the rated desire to smoke with our existing 
     personality profiles of these students to check out the 
     hypothesis.
                                 ______

     Dr. P.A. Eichorn
     W.L. Dunn, Jr.
     Quarterly Report--Projects 1600 and 2302
     January 5, 1973
       SEX-III--Data collection completed. Analysis in progress. 
     Preliminary analysis reveals a 10% reduction from 1968 to 
     1972 in available tar among cigarettes smoked and 
     commensurate reduction in mean daily intake.
       Ford Motor's Keep-Well Campaign.--No progress to report. 
     The study at Ford has been delayed.
       The Schachter Studies.--A pilot study at the Columbia 
     University laboratory has revealed a 30% increase in 
     cigarette consumption (number smoked) over normal consumption 
     when on a regimen of high level Vitamin C dosage. A 
     comparable regimen with sodium bicarbonate did not result in 
     the predicted reduction in consumption.
       The Neal Miller Studies.--A pilot study at the Rockefeller 
     University laboratory suggests that the elicited attack 
     behavior in cats is markedly moderated when the animal has 
     been injected with nicotine. The high nicotine dosage level, 
     however, demands caution in any interpretation.
       Puffing Patterns.--Data continues to be collected on 
     puffing behavior relative to the type cigarette being smoked.
       Bay Area Study.--Discontinued. The study was judged to be 
     of a non-R&D nature and Marketing Research funds were not 
     available for its support.
       The Effects of Smoking on Heart Rate Variability.--Three 
     studies are in the initial stages for determining what 
     effect, if any, smoking has upon the magnitude of shifts in 
     arousal level, with heart rate being used as the index of 
     this psycho-physiological state. The study involving the 
     telemetry of heart rate, delayed because of technical 
     problems and laboratory relocation, is about to enter the 
     recording phase. Heart rates of R&D smokers, under smoking 
     and abstention conditions, will be sampled over working 
     hours. A second study is being initiated in which a small 
     sample of R&D employees will record their heart rates on 
     portable tape units while driving to and from work under 
     smoking and extended abstention conditions. A third study is 
     being formulated in which volunteer subjects will be 
     subjected to intensive and varied activity programs designed 
     to be fatiguing and/or frustrating and extending over a 24-
     hour period in which no sleep will be permitted. The effects 
     of deprivation of food, of water and of smoking will be 
     observed in terms of heart rate measures and performance 
     efficiency. The scheduling of these latter two studies is 
     contingent upon the assembly of the portable heart rate 
     recording device, the critical element of which is the 
     sensor-transducer component. The critical measure is the 
     variance of heart rate over time.
       Tar & Nicotine Studies.--Cigarettes are scheduled to become 
     available for these studies in January.
       Fourteen Choice.--There are various ways for lowering TPM 
     to 14 mg. Which yields the preferred cigarette? After 
     extensive experimentation, adequately controlled samples of 
     the six selected cigarettes have been provided in sufficient 
     quantity for local testing. This testing will begin in 
     January, to be followed by national field testing.
       Black Menthol Panels.--Recruitment of both local and 
     national black menthol smokers is underway.
       Menthol-tar Combinations.--Experimental models of the 
     cigarettes needed for this study are being made. When the 
     specifications are met, the cigarettes will be produced and 
     the study initiated.
       Tar-nicotine Combinations.--Here also the execution of the 
     study is contingent upon the design and production of 
     cigarettes which meet the specifications demanded.
                                 ______

     Charge Number: 1600
     Program Title: Smoker Psychology
     Project Leader: W. L. Dunn, Jr.
     Period Covered: January 1--January 31, 1973
     Date of Report: February 9, 1973

     Project Title: Smoking and Rate of Learning Alpha Control (A 
         new study)
     Written by: W. L. Dunn
       Alpha brain wave (8-12Hz) dominance is associated with 
     states of tranquility and meditation. Alpha is recordable 
     with appropriate electronic circuitry (EEG) and can be used 
     to trigger auditory or visual stimuli as signals of alpha 
     presence above predetermined threshold levels. These 
     biofeedback signals can facilitate the learning of alpha 
     control in human subjects.
       As part of our continuing search for the motivationally 
     relevant effects of smoking, we are investigating the 
     influence of smoking upon the rate of acquisition of alpha 
     wave control. Using smoking subjects and alternating smoking 
     and non-smoking learning sessions (daily sessions of 3 to 5 
     minutes) we will test for differences between the two 
     conditions in terms of cumulative time of alpha dominance.

     Project Title: Richmond Product Placement Panel
     Written by: M. E. Johnston
       Plans for establishing a local roster of 1500 to 2000 
     smokers, including much needed Marlboro, hi-fi and black 
     menthol smokers, are being put into effect.


[[Page H 7651]]

     Project Title: The Delivery of Inhalation Impact via Other 
         Vehicles than Nicotine
     Written by: W. L. Dunn
       It has been observed that when the filler of a commercial 
     type cigarette is denicotinized, the inhalation impact of 
     that cigarette is lost. In collaboration with Hind and 
     Gellatly, we are investigating the capability of a 
     denicotinized 100% uncased burley cigarette to deliver 
     impact. If there is found to be residual impact, we will 
     attempt to build an acceptable cigarette around denicotinized 
     uncased burley.

     Project Title: Optimum Mode of Tar Reduction
     Written by: Frank Ryan
       A five-pack handout is now in local distribution. Results 
     will be used to determine feasibility of national mailout.

     Project Title: Arousal and Smoking
     Written by: Frank Ryan
       The effect of smoking or non-smoking on the arousal 
     mechanisms of the central nervous system is being monitored 
     throughout the day by measuring heart rate activity. Samples 
     of activity are taken throughout a week of smoking, and then 
     throughout a week of non-smoking. Several employees have 
     volunteered to quit smoking for a week and then resume, but 
     not all will be usable.
       In addition, heart-rate recordings while commuting to work 
     will be collected under smoking and extended abstention 
     conditions.

     Project Title: Puffing Behavior on Different Brands
     Written by: Frank Ryan
       Final subjects are now being run. Preliminary data 
     indicates puffing at little cigars is different from puffing 
     at cigarettes and that Marlboro and Winston are smoked 
     similarly. This appears to be a useful procedure, but it 
     takes a long time to gather any significant amount of data. 
     We may change our standard task to enable us to use the same 
     smokers more often.

     Project Title: Cigarette Variability
     Written by: Frank Ryan
       A pack handout will be made in late February to test the 
     effect of cigarette variability on consumer response. Warren 
     Claflin's group has provided the cigarettes.

     Project Title: Personality and Puffing Behavior
     Written by: Frank Ryan
       A report is being prepared on this topic covering progress 
     to date.

     Project Title: Smoking and Spare Mental Capacity
     Written by: T. R. Schori
       This is a study in which we are looking for differences in 
     spare mental capacity between smokers, smokers-deprived, and 
     nonsmokers using a cross-adaptive loading task technique. 
     With this technique, subsidiary task difficulty is dependent 
     upon primary task performance in such fashion that primary 
     task performance is made comparable over groups while 
     subsidiary task performance becomes an indication of spare 
     mental capacity.

     Project Title: SEX-III Analysis
     Written by: T. R. Schori
       Data analysis continues. The first draft of the report will 
     be complete February 14.

     Project Title: JND-2
     Written by: T. R. Schori
       This is a follow-up of JND-1 in which we are interested in 
     whether smokers can detect differences in two cigarettes 
     varying in tar delivery by 5 mg. They were unable to do so in 
     the original study. The cigarettes are in the field. Ballots 
     are starting to trickle in.

     Project Title: Smoking and Sustained Performance
     Written by: T. R. Schori
       Report in progress.

     Project Title: Menthol Cigarette Image (HN-1)
     Written by: T. R. Schori
       Report in progress.

     Project Title: Acceptability and Low Delivery Cigarettes (II)
     Written by: T. R. Schori
       Awaiting cigarettes.

     Project Title: Economic Analyses
     Written by: Myron Johnston
       The following analyses were completed:
       1. Projections of Weighted Average Tar Deliveries 
     (requested by Steve Fountaine). Extrapolations of trend lines 
     of weighted average tar deliveries basedoon three different 
     time periods and two methods of computation (logarithmic and 
     arithmetic).
       2. Weighted average tar deliveries of 85mm and 100mm filter 
     cigarettes calculated separately (requested by Al Udow).
       3. Calculation of simple average tar delivery and range of 
     delivery levels available to the American public, 1954-1972 
     (requested by Dr. Wakeham).
       4. Percent who smoke cigarettes by occupation and age 
     (requested by Dr. Fagan and Mr. J. Lincoln).
       5. Attitudes of R&D professionals to the speakers at the 
     evening seminars for the past two years (requested by Dr. 
     Fagan for the Evening Seminar Committee).

     Project Title: Smoking Patterns as Related to Status 
         Inconsistency
     Written by: Myron Johnston
       Several computer runs have been made and we are in the 
     process of analyzing and writing up the results of our 
     findings to date. Status inconsistent smokers report higher 
     consumption rates than status consistent smokers according to 
     preliminary data. Our panel data confirms the findings of 
     other studies that smoking is inversely related to income, 
     occupation and educational attainment (the components of 
     socio-economic class).

     Project Title: Acquisition of Marlboro Smokers from Market 
         Research Department
     Written by: Myron Johnston
       HTI has been having computer problems but we have been 
     promised delivery of the names and addresses of 500 Marlboro 
     smokers by February 12.

     Project Title: Product Usage--Pipe Tobacco (requested by 
         Marketing Department through Bill Corsover).
     Written by: M.E. Johnston
       Several computer tabulations have been run and I am ready 
     to begin the analysis of the data.
                                 ______

     Charge Number: 1600
     Program Title: Smoker Psychology
     Project Leader: W.L. Dunn, Jr.
     Period Covered: May 1-31, 1974
     Date of Report: June 10, 1974

     Project Title: Alpha Brain Waves and Smoking
     Written by: W.L. Dunn
       Data collection complete. Analysis in progress.

     Project Title: Inhalation Controls
     Written by: W.L. Dunn
       Instrumentation is nearly complete. Electronic problems 
     have been resolved and mechanical valving of airways appears 
     to be in working order. The nose mask is causing some delay 
     in that we recently became aware of a shrinkage problem with 
     the silicon rubber material used in fabricating the mask. An 
     alternate curing agent (on order) is supposed to solve the 
     problem.

     Project Title: Puffing Behavior
     Written by: F.J. Ryan
       We have begun gathering data on the effects of 
     intercigarette interval on puffing behavior. Students smoke 
     cigarettes either 10 or 60 minutes apart while working on 
     paper and pencil tasks and reading into the delayed feedback 
     tape recorder. We expect to see differences in behavior as a 
     function of the intercigarette interval. It is not clear 
     whether these differences will be in average puff volumes, 
     durations, and flows, or in number of puffs, total puff 
     volume, and interval between puffs. Our previous research 
     suggests that average puff volume, puff duration, and flow 
     rate of the smoke are relatively insensitive to external 
     conditions, each smoker having his own preferred response 
     pattern which interacts with the physical characteristics of 
     the cigarette rod at the time of the puff to determine the 
     puff volumes, etc. Therefore we suspect that the major 
     differences will appear in the number of puffs taken, 
     interpuff interval, and total volume of smoke.

     Project Title: Relationship Between Smoking and Personality
     Written by: F.J. Ryan
       Some children are so active (or ``hyperkinetic'') that they 
     are unable to sit quietly in school and concentrate on what 
     is being taught. In recent years it has been found that 
     amphetamines, which are strong stimulants, have the anomalous 
     effect of quieting these children down and enabling them to 
     concentrate in the face of distractions which otherwise would 
     have disrupted their attention. Many children are therefore 
     regularly administered amphetamines throughout grade school 
     years. The wisdom of such prescription is open to question, 
     and some published reports have suggested that caffeine, in 
     the form of coffee or tea for breakfast, would produce the 
     same end result. We wonder whether such children may not 
     eventually become cigarette smokers in their teenage years as 
     they discover the advantage of self-stimulation via nicotine. 
     We have already collaborated with a local school system in 
     identifying some such children presently in the third grade; 
     we are reviewing the available literature on the topic; and 
     we may propose a prospective study of this relationship. It 
     would be good to show that smoking is an advantage to at 
     least one subgroup of the population. Needless to say, we 
     will not propose giving cigarettes to children.

     Project Title: Smoking and Mental Concentration
     Written by: F.J. Ryan
       Embedded in the puffing behavior study mentioned above is 
     the study of the effects of smoking on performance with the 
     delayed feedback tape recorder. The students read passages 
     into a microphone connected to a tape recorder while hearing 
     their own voice over earphones either as they say each word 
     or slightly after they say each word. The latter (delay) 
     condition disrupts normal speech patterns, sometimes causing 
     stuttering, word blocking, slurring, dropped final word-
     endings, etc., and seems to slow reading rate by 15% of more. 
     One strategy adopted by readers under delay circumstances is 
     to ignore the sound of their own voices and hence to pay no 
     attention to what they are reading. We test for this by 
     asking questions about the material read. To the extent that 
     smoking aids in concentration we should see performance 
     improvement when reading in the delay condition after having 
     had a cigarette compared to reading when no cigarette has 
     been smoked for an hour.

     Project Title: DL-2
     Written by: T.R. Schori
       Panelists smoked a Marlboro Control and three low delivery 
     cigarettes, averaging less than 10 mg tar, at three levels of 
     RTD varying upwards from 4.8 inches. The most interesting 
     finding was that these low delivery 

[[Page H 7652]]
     cigarettes were as acceptable as the Marlboro Control. A report is 
     being written.

     Project Title: Smoking, Arousal, and Mood
     Written by: T.R. Schori
       The data acquisition phase of this study is nearly over.

     Project Title: MN-3
     Written by: T.R. Schori
       This is the second in a series of studies designed to 
     determine what nicotine and menthol parameters will optimize 
     consumer acceptability (of various subsets of the menthol 
     smoker population) of menthol cigarettes. These cigarettes 
     are ready to go out to a national panel.
                                 ______

     Charge Number: 1600
     Program Title: Smoker Psychology
     Project Leader: W.L. Dunn, Jr.
     Period Covered: February 1-28, 1975
     Date of Report: March 10, 1975

     Project Title: DTR-2
     Written by: W.L. Dunn
       A dual field study of RTD/tar interaction and assessment of 
     three modes of presentation. Data in analysis.

     Project Title: Inhalation II
     Written by: W.L. Dunn
       An attempt to monitor all of the behavioral mechanisms 
     available to the smoker for regulating exposure to smoke 
     under conditions of varied delivery levels. The study will 
     require the simultaneous recording of (a) the puff profile, 
     (b) nose/mouth inhalation ratio, (c) total inhalation volume 
     and (d) retention time. We are engaged in solving the 
     instrumentation problems.

     Project Title: Puffing Following Deprivation
     Written by: Frank Ryan
       Data collection continues, will end this month.

     Project Title: Constant Volume Puffing
     Written by: Frank Ryan
       To see what cues govern the size of puffs we will ask 
     smokers to attempt to take puffs of identical volume at 
     different places on the rod, while manipulating delivery and 
     RTD of the products being smoked.

     Project Title: Hyperkinesis as a Precursor of Smoking
     Written by: Frank Ryan
       The size of our prospective study should be increased to a 
     base of about 6,000 children when a local school system 
     extends its student evaluations three more grades this 
     spring.

     Project Title: Annual Monitoring of Cigarette Acceptability
     Written by: Frank Ryan
       The tentative design of this study is as follows: once a 
     year we will have five different products evaluated by a 
     large panel of smokers.
       The evaluation will be on a 9-point acceptability scale, 
     ranging from Dislike Extremely to Like Extremely.
       The products will range from 8 mg FTC tar to 20 mg FTC tar 
     in 3 mg steps. All will be nonmenthol.
       The panelists will be chosen from the POL National Roster. 
     Both sexes and a wide variety of ages will be used, with 
     over-sampling of younger smokers whose preference criteria 
     may not yet be well established. We do not have data on the 
     number of years panelists have been smoking, so we will ask 
     that question on the ballots, and then make analyses by age, 
     number of years smoking, as well as delivery range of current 
     own product. Myron Johnston is cross tabulating the POL panel 
     now to get us up-to-date information on the number of 
     panelists in different age and sex categories in the 
     available subject population. (Nonfiltered menthol smokers 
     will be excluded.)
       Test is tentatively scheduled for late October to early 
     November.

     Project Title: Smoking and Risk-taking in a Simulated Driving 
         Task
     Written by: T.R. Schori
       The data acquisition phase is complete. We have started to 
     analyze the data.

     Project Title: The Betta Study
     Written by: T.R. Schori
       Having gotten our first group of fish, we are preparing to 
     determine nicotine dosage effects. Subsequently, we plan to 
     test 30 Bettas at each of 3 nicotine levels (the lowest being 
     0 nicotine). We will make observations of exploratory 
     activity and hooding behavior (aggressive behavior) on each 
     Betta at each dosage on several occasions.

     Project Title: Miscellaneous
     Written by: T.R. Schori
       Menthol Cigarette Preferences of Blacks: cigarettes are in 
     storage awaiting the availability of the RP Black menthol 
     panel. Low Delivery Cigarettes: Another Look at the Influence 
     of Delivery Information on Subjective Evaluations: cigarettes 
     are ready and should go out shortly to a National POL panel. 
     There are two conditions in this study. In the first 
     panelists will make blind ratings of a Marlboro control and a 
     9 mg tar cigarette while in the second condition the 
     cigarettes will be identified as to their tar and nicotine 
     deliveries.
                                 ______

   Philip Morris Research Center--Behavioral Research Annual Report 
Approved by W.L. Dunn & distributed to H. Wakeham et al.--July 18, 1975

       We have arranged the 1600 activities for this report into 
     the three status sections: Completed, In Progress and 
     Planned.
       Under each status section the individual studies are 
     grouped under the three objectives of the Behavioral Research 
     Laboratory: I. To learn more about why people smoke. II. To 
     learn more about how people smoke. III. To further identify 
     what people want to smoke.


                           completed studies

     I. The effect of smoking on risk-taking in a simulated 
         driving task (Jones and Schori)
       Smokers are reported to have more traffic accidents than 
     nonsmokers. There are several possible explanations. First, 
     the studies that have been conducted have made no attempt to 
     control certain important extraneous variables. For 
     meaningful comparisons of smokers and nonsmokers, it is 
     essential that quantity and quality of driving exposure be 
     considered. The higher alcohol consumption of smokers is 
     another example of an uncontrolled variable that could 
     influence accident data. Second, it could be that smoking 
     adversely affects driving performance. The results of studies 
     in this area are not conclusive. Furthermore, it is not known 
     whether inferior motor performance significantly increases 
     accident rates. Our interest has been in a third possibility: 
     That smokers are more willing to take risks than nonsmokers, 
     resulting in higher accident rates among smokers. Therefore, 
     an investigation was conducted to determine experimentally 
     whether smoking condition (smoking, smoking-deprivation and 
     nonsmoking) affects an individual's degree of willingness to 
     take risks. The task used was designed to simulate an actual 
     car passing situation, varied as to the degree of risk 
     involved in making the pass.
       The subject was seated in front of a panel on which lights 
     represented the movement of cars in the inner and outer lanes 
     of a race track. The subject's task was to pass the car ahead 
     of his car (lead car) without crashing into an approaching 
     car. It was emphasized to the subject that in order to do 
     well on the task it was necessary to take risks. The 
     necessity of risk-taking was increased by the random 
     increases in the speed of the approaching car. A performance 
     contingent monetary bonus was used to motivate the subject to 
     perform well on the task.
       There were 15 college students subject in each of the three 
     smoking conditions. Smokers were randomly assigned to either 
     the smoker or smoker-deprived condition. Performance data 
     were collected on the following dependent variables: response 
     latency, number of pass attempts, number of backout attempts, 
     number of successful passes, number of crashes, and amount of 
     good time (the amount of time not immediately behind the lead 
     vehicle or in a crash condition).
       The performance data were analyzed by means of a two-way 
     multivariate analysis of variance in which both Smoking 
     Condition and Trials were treated as independent variables. 
     We analyzed for treatment effects in terms of all dependent 
     variables simultaneously while taking into consideration 
     their interrelationships.
       Significant differences were detected as a function of 
     trials. The nature of the trials effect was such that it can 
     be concluded that the accuracy with which subjects evaluated 
     potential risk improved with practice, a finding which may 
     have practical implications for driver training programs. 
     However, no differences were detected as a function of 
     smoking condition or the smoking condition trials 
     interaction. Thus, it can be concluded that in this simulated 
     car passing task nonsmokers, smokers-deprived, and smokers 
     did not differ in their willingness to take risks.
     I. Delayed audio feedback (Ryan and Lieser)
       In the last annual report we commented briefly on a then 
     recent study not yet completely analyzed. It had been 
     undertaken to see whether cigarette smoking, which should 
     have stimulating and frustration reducing characteristics, 
     would improve vocal performance under conditions of delayed 
     audio-feedback.
       In delayed audio feedback subjects speak or read aloud into 
     a microphone connected to a special tape recorder. The 
     subject's voice is relayed to his earphones either as he 
     speaks (immediate feedback) or a fraction of a second after 
     he has spoken (delayed feedback). Most people are unaware of 
     the fact that our speech behavior depends in part on hearing 
     what we are saying as we say it. Even fraction of a second 
     delays can therefore cause stammering, speech blockage, 
     slurred words, slower speech, louder speech, etc.
       The speech problems cause speakers to become more tense, 
     and the extra tension seems to make the problem even worse.
       We reasoned that smoking cigarettes might reduce tension 
     and speed up behavior, so that after a smoke speakers would 
     read faster and make fewer errors under delayed feedback than 
     they made before smoking.
       We found that as expected:
       (1) smoking increased post-cigarette speech rate (by about 
     8%) under both feedback conditions; and (2) smoking decreased 
     the total number of speech errors under the delayed feedback 
     condition, but (3) the magnitude of the effect was not great 
     because (4) our headphone speaker volume was not loud enough.
       Because this is an easy experiment to conduct, we will 
     replicate it piecemeal in the future (at higher output 
     volumes) using as subjects college students who have come to 
     the laboratory to participate in other projects and have 
     either finished earlier than expected or have been excused 
     from participation because of apparatus failures.
     II. Smoking behavior following deprivation (Ryan and Lieser)
       This study was conducted to answer two question: What 
     effect does short-term smoke 

[[Page H 7653]]
     deprivation have on number of cigarettes subsequently consumed? and 
     What effect does short-term smoke deprivation have on 
     subsequent puffing behavior?
       By ``short-term deprivation'' we mean being in a No Smoking 
     condition for two hours when smoking would otherwise be an 
     appropriate act. Thus we are indirectly testing the effects 
     of various state laws, local ordinances, and business 
     establishment decisions which forbid smoking in various 
     places: buses, stores, theatres, waiting rooms, schools, etc.
       Our subjects were 20 college students who visited the 
     Research Center on two separate days during each of which 
     they spent 4 hours taking multiple-choice tests, memorizing 
     facts, free associating to nonsense words, filling out 
     personality tests, and (less frequently) talking with the 
     experimenter about miscellaneous topical matters during a 15-
     minute break period which split the 4-hour session into two 
     2-hour parts. The situation was therefore like that of study 
     and testing periods, although it required more concentrated 
     work than most students normally perform.
       A dozen other students were tested in portions of this 
     study, either in a pilot work or during the project itself, 
     but were excluded from the results here presented either 
     because we suspected they were not smokers or at best very 
     light smokers, or because we made slight changes in 
     procedure. All these omitted subjects followed the same 
     general smoking patters reported here.
       On one of the days the students were allowed to smoke as 
     often and as much as they wished (ad lib) from a free supply 
     of their own brand of cigarettes placed prominently on the 
     table before them.
       On the other day they were forbidden to smoke during the 
     first 2 hours (deprivation) and then allowed to smoke ad lib 
     during the next 2 hours. Prior to the beginning of each 4-
     hour period, they smoked one of their own brand cigarettes 
     through a PM Human Smoking Recorder system. The computer 
     output describing these two smokings was used to calculate 
     the 2-day average puff volume on nonlighting puffs for each 
     smoker. No other cigarettes were monitored by recorder, but 
     number of cigarettes smoked, interval between cigarettes, 
     number of puffs, taken, and interval between puffs were noted 
     by observer(s) in an adjoining room watching the subject via 
     closed circuit TV. From the nominal nicotine delivery of a 35 
     cc puff on each brand listed in CI reports, given the size of 
     an average puff from the recorder output, and having counted 
     the number of puffs taken during the session, we were able to 
     approximate nicotine intake during the sessions.
       This also assumes that puffs outside the recorder are like 
     recorded puffs, and that deprivation does not affect puff 
     volume. We can't do anything about the first assumption, but 
     in a prior study in which effects of one hour of deprivation 
     on a subsequent single cigarette was evaluated, we saw no 
     volume change after deprivation although there was an effect 
     on number of puffs and interpuff interval which explains the 
     choice of variable in the present work.
       Twelve of the students were males, eight were families, and 
     half of each gender group smoked menthol.
       The results are summarized in Tables 1, 2 and 3 and in 
     Figs. 1 and 2.

 TABLE 1--EFFECTS OF DEPRIVATION ON NUMBER OF CIGARETTES SMOKED, NUMBER 
       OF PUFFS TAKEN, AND ESTIMATED NICOTINE INTAKE (ALL SMOKERS)      
------------------------------------------------------------------------
                                                              Estimated 
                                    Number of    Total No.      group   
                                    cigarettes    of puffs     nicotine 
                                                             intake (mg)
------------------------------------------------------------------------
First 2 hours ad lib.............           79          621        79.73
Second 2 hours ad lib............           74          608        78.74
2 hours post deprivation.........           95          832       106.50
------------------------------------------------------------------------


          TABLE 2--EFFECTS OF DEPRIVATION ON SUBGROUPS: MENTHOL VERSUS NONMENTHOL; MALES VERSUS FEMALES         
----------------------------------------------------------------------------------------------------------------
                                      Number of cigarettes       Total No. of puffs     Estimated group nicotine
                                   ----------------------------------------------------        intake (mg)      
                                                                                       -------------------------
                                      Menthol    Non-menthol    Menthol    Non-menthol    Menthol    Non-menthol
----------------------------------------------------------------------------------------------------------------
First 2 hours ad lib..............           43           36          340          281        43.75        35.98
Second 2 hours ad lib.............           39           35          323          285        42.43        36.31
2 hours post deprivation..........           47           48          415          417        54.10        52.40
----------------------------------------------------------------------------------------------------------------


----------------------------------------------------------------------------------------------------------------
                                      12 Males    8 Females     12 Males    8 Females     12 Males    8 Females 
----------------------------------------------------------------------------------------------------------------
First 2 hours ad lib..............           45           34          321          300        42.09        37.64
Second 2 hours ad lib.............           44           30          341          267        45.13        33.61
2 hours post deprivation..........           56           39          459          373        59.68        46.82
----------------------------------------------------------------------------------------------------------------


 TABLE 3--CONSUMPTION POST-DEPRIVATION AS A PERCENT OF SECOND TWO HOURS AD LIB AND OF TOTAL 4-HOUR AD LIB DATA; 
             WITH SECOND TWO HOURS AD LIB COMPARED WITH FIRST TWO HOURS AD LIB TO SHOW THE CONTRAST             
                                                  [In percent]                                                  
----------------------------------------------------------------------------------------------------------------
                                                                                                Estimated group 
                                                             Number of       Total number of    nicotine intake 
                                                             cigarettes           puffs               (mg)      
----------------------------------------------------------------------------------------------------------------
Post deprivation vs. second    All Smokers.............                128                137                135
 two hours ad lib.                                                                                              
  ...........................  Menthol.................                121                128                127
  ...........................  Non-menthol.............                137                146                144
  ...........................  Males...................                127                135                132
  ...........................  Females.................                130                140                139
Post deprivation vs. all four  All Smokers.............                 62                 68                 67
 hours ad lib.                                                                                                  
  ...........................  Menthol.................                 57                 64                 63
  ...........................  Non-menthol.............                 58                 74                 73
  ...........................  Males...................                 63                 70                 68
  ...........................  Females.................                 61                 66                 66
Second two hours ad lib vs.    All Smokers.............                 94                 98                 99
 first two hours ad lib.                                                                                        
  ...........................  Menthol.................                 91                 95                 97
  ...........................  Non-menthol.............                 97                101                101
  ...........................  Males...................                 98                106                197
  ...........................  Females.................                 88                 89                 89
----------------------------------------------------------------------------------------------------------------

       Tables 1 and 2 show that behavior and nicotine intake were 
     strikingly similar during each of the two sessions of the ad 
     lib smoking day. This similarity is stressed further at the 
     bottom of Table 3, which shows the second two hours' behavior 
     as a percentage of the first. We shall consider these two 
     periods as essentially equal in their effect. However, 
     because the design suggests that the post-deprivation period 
     should be compared to a comparable period of free smoking, we 
     concentrate our attention on the difference between the post-
     deprivation measures and those of the second two hours of the 
     ad lib smoking day.
       The data in the tables show that number of cigarettes 
     consumed increased 28% from 74 to 95, that number of puffs 
     taken increased 37% from 608 to 832, and that total estimated 
     nicotine intake increased 35% from 78.74 to 106.50 mg after 
     the deprivation period.
       The effect of No Smoking situations of 2-hour durations is 
     to increase subsequent consumption by anywhere from 28% to 
     37% depending on the measure taken.
       On the other hand, in only a two-hour period smokers do not 
     make up the entire smoke deficit created by a No Smoking 
     situation. Comparing their consumption during the combined 
     deprivation-smoking period of one day with their normal 4-
     hour smoking behavior, (see second block of entries in Table 
     3) they only take about \2/3\ the puffs and \3/5\ of the 
     cigarettes they would normally have taken.

                                                                                                                

[[Page H 7654]]
 TABLE 4.--MEAN NUMBER OF PUFFS FOR 9 ``LIGHT'' SMOKERS (1 PACK OR LESS)
                          AND ``HEAVY'' SMOKERS                         
                          [Over one pack a day]                         
------------------------------------------------------------------------
                                                        Light     Heavy 
------------------------------------------------------------------------
First 2 hours ad lib.................................     22.7     37.9 
Second 2 hours ad lib................................     21.6     37.6 
Post Deprivation.....................................     36.1     46.1 
                                                      ------------------
Increase Post Deprivation in percent.................       67       23 
------------------------------------------------------------------------


       The effects of the deprivation were not the same on all 
     smokers. They were proportionally much stronger on the light 
     smokers than on the heavy smokers. That is because the 
     heavier smokers spent so much time smoking that they could 
     not increase their consumption as much as the light smokers 
     could. There are several ways to classify the smokers of this 
     study as ``light'' or ``heavy''; they all show the same type 
     of effect. In Table 4 we show the number of puffs taken by 
     light and heavy smokers classified by their answers to the 
     question ``How many cigarettes do you smoke each day?'' On 
     the consent form which all subjects filled out. Those nine 
     who smoked a pack or less increased the number of puffs they 
     took by 67% following deprivation, while for the eight who 
     report smoking more than a pack a day the increase was only 
     23%.
       A second-and perhaps more objective--way to classify the 
     subjects is by the number of cigarettes they smoked during 
     the first two hours of the ad lib day. Breaking these into 
     three groups, who smoked less than four, four, or more than 
     four cigarettes during the first two hours we make the 
     interesting observation that after deprivation the light 
     smokers smoked as moderate smokers normally do and the 
     moderate smokers smoked as heavy smokers normally do (Table 
     5).
       To overgeneralize from small samples is always dangerous, 
     but it is tempting to suggest that establishing a No Smoking 
     situation-with the well-intentioned (?) goal of cutting back 
     smoke consumption makes people heavier smokers than they 
     would otherwise be. (It must be understood, however, that 
     there is a net reduction, and that the data for the increase 
     are based on only two hours of observation. This is not a 
     slogan that can be used without reservation.)

  TABLE 5.--MEAN NUMBER OF PUFFS FOR LIGHT, MODERATE, AND HEAVY SMOKERS 
 CLASSIFIED BY NUMBER OF CIGARETTES SMOKED DURING FIRST TWO HOURS OF AD 
                                 LIB DAY                                
------------------------------------------------------------------------
                                     Mean number of puffs/              
                                            smoker                      
                                  --------------------------  Percent of
                                    Second two     Post-       increase 
                                      hours     deprivation             
------------------------------------------------------------------------
8 Light (less than 4 cigts.).....         20.6         33.9           65
7 Moderate (4 cigts.)............         33.7         44.3           31
5 Heavy (more than 4 cigts.).....         41.4         50.2           21
------------------------------------------------------------------------

       Will the increased smoking rate following deprivation be 
     continued beyond the two-hour period? This is an important 
     question, and it is impossible to answer based on the data 
     obtained. However, we have some clues which are suggestive.
       Plotting the cumulative total smoke volume (in ccs) across 
     the four-hour ad lib period we see that intake accumulates in 
     a near linear fashion across time, an observation we have 
     already made in a different form by noting that first and 
     second two-hour behavior was almost identical. Similarly we 
     see a near linear accumulation of smoke volume during the 
     two-hour deprivation period. The slope of the post-
     deprivation line is steeper than that of the control day * * 
     *
       Assuming the linearity to continue, then we can project 
     both lines to an intersection point which represents equal 
     volumes accumulated under the two condition. For the present 
     data this intersection occurs about 7\1/2\ hours after our 
     observations stopped, implying that it will take a smoker 
     9\1/2\ hours to make up the intake he loses because of two 
     hours of deprivation. It therefore seems unlikely that a 
     group of smokers would be able to make up their deficit 
     during a day, and would undoubtedly not be able to make up 
     deficits which occurred late in the afternoon or early 
     evening.
       Personality Differences.--Examining the personality scores 
     of our subjects we note that those who are high in anxiety 
     tend to take more puffs than those who are low in anxiety. 
     The correlation between the two variables is +.58. Given the 
     obvious relation between puffs and nicotine delivery, it is 
     not surprising that anxiety was also positively related to 
     nicotine intake: r=+.56. Both these correlations are 
     significant at the .05 level.
     III A Comparative Evaluation of Three Methods For Field 
         Testing Cigarettes--Accession Number 75-105 (Dunn and 
         Martin)
       Recently the New Cigarette Products Division demonstrated 
     that they could provide any tar delivery and RTD combination 
     within the 12 mg to 20 mg tar delivery range and 4" to 6" RTD 
     range, and do so with good approximation to target 
     specifications. This achievement made possible a critical 
     comparative study of several alternative field test methods. 
     Using high and low tar delivery levels, and high and low RTD 
     levels, we tested the four combinations (High-High, Low-Low, 
     Low-High and High-Low) against a control, middle-of-the-
     array, Marlboro-like cigarette, using three field testing 
     methods.
       The design of the study permitted a comparative assessment 
     of the three methods and gave information about the influence 
     of tar delivery and RTD changes on subjective response to 
     cigarettes.
       The most significant finding was that a method which 
     permitted the testing of as many as four experimental 
     cigarettes on a single mailout, with judgment based upon a 2-
     pack sample, was as sensitive and as potentially useful in 
     cigarette testing as the standard field testing procedure. 
     Recommendations for further investigation of the technique 
     are made in this report, with proposals for data treatment 
     that promise to yield additional useful information from 
     field tests.
       We also concluded that a 5 mg reduction from the 17 mg tar 
     delivery norm is clearly detectable to the average regular 
     filter smoker, but he is tolerant of this reduction. He is 
     not so tolerant of tar delivery increases.
       RTD changes of 1" from the 5" norm appear to 
     have little influence upon overall acceptability. The 1" 
     increase is clearly detectable; that 1" decrease did not 
     appear to be so.
     III. Further evaluation of delivery information influence on 
         subjective acceptability of a low delivery cigarette 
         (Martin and Schori)
       Cigarettes at two delivery levels (15 mg and 8 mg) were 
     rated on acceptability and strength by National POL 
     nonmenthol smokers. One panel of 500 rated the cigarettes 
     with no delivery informatioon supplied. A second panel of 500 
     rated the cigarettes with tar and nicotine delivery levels 
     clearly marked on the packs and on the ballots. The purpose 
     of the test was to determine the effect of delivery 
     information upon the subjective ratings of cigarettes at two 
     distinctively different delivery levels.
       With no information provided, the strength difference was 
     clearly detected and the higher delivery cigarette was rated 
     more acceptable.
       The judgment of those panelists who were given delivery 
     information contrasted sharply with the judgments of the no-
     information group. The low delivery cigarette was rated the 
     more acceptable. The difference between the strength ratings 
     of the two cigarettes, so evident under the no-information 
     condition, was wiped out under the information condition, 
     such that the two cigarettes were rated as being of equal 
     strength, despite the fact that the panelists were told that 
     the higher delivery cigarette delivered 80% more tar and 
     nicotine.
       We see two phenomena at work in these results:
       (1) Given a cigarette ``blind,'' a smoker will judge it 
     largely on its own merits--given vital information along with 
     the cigarette, the smoker's hedonic judgment of the cigarette 
     will be confounded by socially learned value judgments, e.g. 
     ``low delivery is healthy and good.''
       (2) The smoker will move his rating on a physical attribute 
     scale toward that end of the scale that corroborates his 
     hedonic judgment, e.g., the cigarette rated more acceptable 
     will be rated toward the ``strong'' rather than the ``weak'' 
     end of the strength scale. This is the halo effect, a force 
     we believe to be so pervasive in product testing that the 
     validity of any judgment of the physical attributes of a 
     product rendered in company with a preference or 
     acceptability judgment of that product must be held suspect.
       The practical implication of these findings is that a real 
     marketing advantage is gained by calling attention to the 
     delivery values of low delivery values of low delivery 
     cigarettes, the effect being greatest among those smokers 
     most likely to buy the low delivery cigarette anyway.
     III. Menthol cigarette characteristics as perceived by blacks 
         and whites (Martin, Jones and Schori)
       The black menthol smoker is an important segment of the 
     menthol market, yet all of the PM national field tests of 
     menthol cigarettes have been conducted with virtually all 
     white panels. What with some 500 black menthol smokers having 
     become available with the advent of the RP \3\ panel, the 
     opportunity was afforded to study the black response to 
     menthol cigarettes. We were interested in determining whether 
     the two loosely defined ethnic groups differed in their 
     assessments of variations in two important parameters of 
     menthol cigarettes.
       The study consisted of two runs, the second intended to be 
     a partial replication. Because of unintended significant 
     differences in the menthol levels of the two sets of 
     cigarettes, the results of the two runs cannot be pooled but 
     must be treated separately. Table 6 contains the critical 
     values for the cigarettes.

  TABLE 6.--THE CIGARETTE SPECIFICATIONS IN THE TWO BLACK MENTHOL RUNS  
------------------------------------------------------------------------
                                                    Nicotine/Menthol    
                                               -------------------------
                                                 First Run    Second Run
------------------------------------------------------------------------
Low Nicotine Low Menthol......................      .84/.48      .85/.48
Low Nicotine High Menthol.....................      .82/.62      .71/.62
High Nicotine Low Menthol.....................     1.08/.48     1.17/.36
High Nicotine High Menthol....................     1.12/.76     1.12/.80
Control.......................................      .92/.46      .70/.36
------------------------------------------------------------------------

       Table 7 gives the essential information about the 
     panelists. Note that in the second run only black respondents 
     were used.

       TABLE 7.--THE PANELISTS USED IN THE TWO BLACK MENTHOL RUNS       
         [The parenthesized value is the percent useable return]        
------------------------------------------------------------------------
                              First Run                Second Run       
                     ---------------------------------------------------
                         Black        White        Black        White   
------------------------------------------------------------------------
Number..............     250 (36)     350 (50)     405 (54)            0
Source..............       RP \3\                                       
                          Menthol     Nat. POL                          
                                       Menthol       RP \3\             
                                                    Menthol  ...........
------------------------------------------------------------------------


[[Page H 7655]]

       Two packs of each of the five cigarettes were provided in a 
     carton mailout in both runs.
       The ballots were identical in both runs, with ratings 
     obtained for each cigarette on Acceptability, Strength and 
     Menthol Level.
       In the first run, where both white and black smokers were 
     responding, the two groups were apparently detecting the 
     menthol level differences among the cigarettes. It is to be 
     noted, however, that black males and black Kool smokers were 
     apparently not detecting these differences.
       In the second run, with slightly larger differences in the 
     menthol levels, all of the black subgroups were 
     differentiating in terms of menthol levels.
       There is some evidence that the blacks were less sensitive 
     to ``strength'' differences than the whites. But the strength 
     rating is of itself interesting in that panelists were 
     reacting to menthol level as well as tar level when recording 
     their strength ratings, i.e. menthol level ratings and 
     strength ratings are probably not meaningfully 
     distinguishable as discrete subjective variables in menthol 
     cigarette tests. Also of interest is the observation that the 
     variation in nicotine delivery level had no influence upon 
     strength ratings.
       Both groups of panelists in the first run were responding 
     more favorably (higher acceptability ratings) to the lower 
     level of menthol. These findings were not supported, however, 
     in the second run, for here we find the black smokers were 
     finding all of the cigarettes equally acceptable, despite the 
     fact that the menthol differences among the cigarettes were 
     greater than in the first run.
       Thus the first run finding that a lower menthol delivery is 
     more acceptable among menthol smokers is made equivocal, 
     especially for the black smoker.
       What with the observation that the response of blacks may 
     be less differentiating than whites and what with the 
     questionable representativeness of a Virginia sample for the 
     national market, it would seem feasible to establish a 
     larger, national roster of black smokers especially for the 
     evaluation of menthol candidates:
     III. Mixed pack study (Ryan)
       As deliveries drop we reasoned that eventually they could 
     reach a point where all the cigarettes in a pack would be 
     unsatisfying. The inclusion of some high delivery cigarettes 
     in a pack would therefore give the smokers at least 
     occasional feelings of satisfaction and should lead to a 
     preference for a mixed pack over a homogeneous pack with the 
     same tar and nicotine delivery per pack. Pilot testing with 
     RP \3\ subjects twice indicated slight preferences for a 
     mixture. Therefore a POL national field test of two different 
     packs of 11 mg tar cigarettes was conducted in which one pack 
     consisted of 20 cigarettes each delivering about 11 mg and 
     the other pack was half made up of 8 mg and half of 14 mg 
     cigarettes.
       A total of 309 respondents (most of whom were low delivery 
     smokers) answered the usual ballot questions giving a 9-point 
     rating of each pack type, a preference, and so on. Observed 
     rating and preference differences favoring the homogeneous 
     pack did not reach statistical significance; but since we 
     began the study hoping to show that the mixed pack would be 
     preferred and get higher ratings, we have concluded that this 
     idea should be rejected. this may, of course, be because the 
     smokers found either the 14 or 8 mg model in the mixed pack 
     unacceptable in flavor after taste, or in some other 
     characteristic such as satisfaction.
       There were a few interesting inversions in the ratings by 
     242 HiFi and 67 other than HiFi smokers: For example, the 
     HiFi smokers thought the mixed pack stronger than the 
     homogeneous (responding to the 14 mg?) and the non-HiFi 
     smokers thought the homogeneous stronger than the mix 
     (responding to the 8 mg?).
       No one commented on the fact that the mixed pack consisted 
     of different cigarettes.
       In general the panelists rated all the cigarettes rather 
     high--5.3 for the mix and 5.6 for the homogeneous pack--but 
     many complained about them all burning too rapidly, being 
     dry, and having a long filter. Several noted that the two-
     part paper filter broke or came apart.
       The idea may still be feasible, but not with the cigarettes 
     we used at the levels we tested.


                          studies in progress

     I. Nicotine as a modulator of CNS arousal (Dunn, Martin and 
         Jones)
       Several investigators participating in the 1973 St. Martin 
     Conference on ``Motivation in Smoking'' reported data 
     suggesting that smoking in humans or nicotine injection in 
     animals may have the effects of reducing aggressivity in 
     overt behavior. Schachter also reported at that conference a 
     greater tolerance for pain among smokers when allowed to 
     smoke. There is also the readily observable, commonly 
     acknowledged fact that smokers at a greater rate when under 
     stress. These and other observations imply the influence of 
     nicotine upon some control mechanism governing affective 
     responsivity, the net effect upon overt behavior being to 
     reduce the intensity of the emotionally-toned response, or 
     raise the threshold for the elicitation of that response.
       We have singled out aggressive behavior for study quite 
     frankly because of the practical significance of the 
     suspected effect of nicotine. If indeed, nicotine lowers the 
     intensity or raises the threshold for a form of socially 
     unsanctioned behavior, such as aggression, to demonstrate 
     that effect could be of considerable consequence to the 
     smoker and his protagonists.
       We have a trio of studies in progress, all aimed at 
     observing the effect of nicotine upon aggressive behavior in 
     subhuman species. The species, or the individual animals, 
     have been selected for their innate aggressivity in a form 
     readily elicitable and readily quantifiable. The aggressive 
     pattern is observed in the normal state of the animal and 
     following the administration of nicotine. With proper 
     controls, and with no change in baseline behaviors, (i.e. 
     frequently recurring behaviors other than aggressive), any 
     reduction in the aggressive responses can be attributed to 
     the nicotinic effect specific to the aggressivity.
       This rationale is common to all three of the studies. At 
     the Laboratory of Comparative and Physiological Psychology at 
     Ohio State University we have had a guiding hand in designing 
     studies of the influence of injected nicotine upon the 
     predatory attack of cats upon mice. At the Psychology 
     Department of Rockefeller University, the influence of 
     injected nicotine upon the predatory attack of rats upon mice 
     is being investigated at our request. And at R&D we are 
     observing for the influence of low concentrations of nicotine 
     in the ambient water of male Betta fish upon their mirror 
     display behavior.
       Only preliminary observations are available, but in the two 
     extra-R&D studies these are encouraging. The cats and rats 
     are ceasing their attacks. Whether the base-line behaviors 
     are remaining unchanged is now the subject of greatest 
     interest as the data is being gathered.
       In house, the toxicity phase of the Betta testing has been 
     completed. We established that the LC50 was greater than 
     10 ppm and less than 100 ppm v/v, using distilled nicotine 
     base. The S in the 10 ppm solution was almost completely 
     inactive, but would respond to prodding. The S in the 100 ppm 
     solution was dead within 2 minutes. A possible avoidance 
     pattern to the stimulus was noticed at 1 ppm. This will be 
     the solution used as the higher concentration in the effects 
     study. The lower concentration will be 0.1 ppm. These 
     preliminary observations have indicated a possible 
     differential effect of nicotine, whereby aggressive display 
     is decreased and other base-line behaviors (e.g. air gulping) 
     remain the same.
       Thirty male Bettas of approximately the same age are being 
     established in a housing tank for approximately one month. 
     The fish will be calibrated (base line air gulping and 
     display activity) before the effects study starts. Each fish 
     will be in each of the three solutions for three test 
     periods. Test days and solutions will be randomized. 
     Measurements to be made will be number of times gill erection 
     occurs, duration of gill erection and number of air gulps.
     I. Personality, smoking, and stimulus deprivation (Ryan and 
         Lieser)
       We are interested in the problem of why some people smoke 
     and others do not. The personality research of Hans Eysenck 
     offers one clue. Eysenck points out that the level of 
     activity in our central nervous system affects our 
     performance efficiency. If it is too low or too high we 
     perform inefficiently. Somewhere in between high and low 
     there is an optimal point at which our bodies work at their 
     best. This optimal point is markedly higher for some people 
     than for the average man, while for still other people it is 
     much lower than it is for the average. He hypothesized that 
     in order to maintain optimal efficiency a person who is 
     chronically below optimum level will seek to increase his CNS 
     activity level. One way to do this is by seeking out 
     stimulating situations--such as parties, music, sporting 
     events, etc. which increase the amount of social and 
     environmental stimulation to which he is exposed. These 
     probably increase the amount of adrenalin in the system, 
     which increases the CNS activity. Another way to increase CNS 
     activity would be to consume socially approved chemicals 
     which would have a similar effect on the body--such as the 
     stimulant drugs caffeine and nicotine.
       In fact it has been reported that people who 
     (theoretically) seek out such stimulation, called extraverts 
     because they are outward directed, are also more apt to be 
     smokers than are those who avoid such stimulation, called 
     introverts because they are inner directed.
       In our next project we are testing this hypothesis by 
     placing extraverts in a stimulus deficient environment (a 
     dark, very quiet room) and watching to see whether they will 
     seek stimulation (by working to turn on flashing lights and 
     sounds) than will a group of introverts. Extraverted smokers 
     who are smoke-deprived (or nicotine deprived) should be more 
     in need of stimulation than those who have just finished 
     smoking several cigarettes.
       Similarly the hypothesis that introverted smokers will be 
     less likely to work for stimulation after smoking cigarettes 
     than when smoke deprived, for the extra input from smoke will 
     tend to bring them close to the point where any extra 
     environmental stimulation would make them feel uncomfortable. 
     Hence they would be content with the status quo.
       Thus an extension of the existing hypothesis predicts one 
     type of difference in behavior for one group of people and 
     the opposite type of behavior for another group--which always 
     makes a nice study. (Actually we're 

[[Page H 7656]]
     not as convinced of the effect on the introverts as the foregoing 
     suggests. They may respond similarly whether smoking or not, 
     depending on how content they are with the quiet dark 
     situation.)
     I. Hyperkinetic child as a prospective smoker (Ryan)
       We hypothesize that the characteristics of smokers and 
     hyperkinetic children so closely resemble each other that in 
     the past hyperkinetics were almost sure to become smokers. 
     Thus we could account for some of the differences between 
     smokers and nonsmokers by the disproportionate representation 
     of this special subgroup in the adult smoking population 
     compared to the adult nonsmoking population.
       We have undertaken a long term prospective study to 
     identify the hyperkinetic and borderline hyperkinetic 
     youngsters in the Chesterfield County school system, and to 
     see whether they become smokers. All the children in one 
     grade level were tested last year but the school system did 
     not continue their testing this year to include extra grades. 
     This was due to the reorganization of the system by a new 
     superintendent with its concomitant personnel and morale 
     problems and readjustment of priorities. Because school 
     systems must (under Virginia law) identify all problem 
     children of all types, we expect to greatly expand the data 
     base next year.
       We did manage to check the reliability of last year's pupil 
     ratings by having new teachers rerate a previously rated 
     subsample. The correlation was satisfactorily high (+.86), 
     suggesting that teachers agree on what constitutes problem 
     behavior as defined by the questionnaire used.
     I. Smoking and aggression (Jones)
       The simulated driving test used in the risk-taking study 
     has been modified so that college student subjects will 
     receive inaccurate feedback regarding their performance on 
     the task. It is expected that a student who is being paid for 
     successful passing will respond aggressively if his 
     successful passes are incorrectly recorded as crashes.
       There will be 30 subjects tested in each of the three 
     smoking conditions (nonsmoker, smoker-deprived, and smoker). 
     Both groups of smokers will be instructed not to smoke at all 
     the day they are to report to the laboratory. They will be 
     told that urine samples will be taken to verify their 
     abstinence. All subjects will be in the laboratory for at 
     least an hour before the actual testing session begins, 
     during which time they will fill out information forms, take 
     a personality test and complete a Nowlis Mood Scale. Those in 
     the smoker group will be permitted to smoke ad lib during 
     this period and will be required to smoke one cigarette 
     before each trial of the driving task. Smokers-deprived, 
     however, will not be permitted to smoke until the entire 
     experiment has been completed.
       All subjects will have a 10-minute practice session before 
     beginning two 20-minute trials. The first trial will be with 
     accurate feedback so that baseline measurements may be 
     obtained before inaccurate feedback is introduced. The 
     smoker-deprived group will be given a third trial with 
     inaccurate feedback. The group will be divided, with half of 
     the subjects remaining deprived and the other half being 
     permitted to smoke. All subjects will be given a Nowlis Mood 
     Scale after each trial.
       Subjects will be observed through a one-way mirror, verbal 
     behavior will be coded, and the force with which they push 
     the response buttons will be recorded as a measure of 
     aggressive behavior. College student pilot subjects will be 
     brought in so that observational techniques can be perfected.
     III. Lowe delivery cigarettes and increased nicotine/tar 
         ratios, a replication (Jones and Martin)
       This test is a replication of a study (74-088) in which a 
     10.7 mg tar cigarette with a .12 nicotine/tar (N/T) ratio was 
     found to be comparable to a Marlboro control in both 
     subjective acceptability and strength. The three experimental 
     cigarettes deliver approximately 10 mg tar with N/T ratios of 
     .07, .10 and .13.
       These cigarettes and a Marlboro control have been sent out 
     to 300 RP3 smokers and returns are beginning to arrive. 
     Panelists were asked to smoke the four cigarettes in any 
     order they wish and to rate each cigarette on a acceptability 
     scale and a strength scale before beginning to smoke the next 
     cigarette code. In the event that the panelists smoke the 
     cigarettes in the order suggested by the rating scales, all 
     possible presentations of the rating scales for the four 
     cigarettes will have been used an equal number of times.
     III. A low delivery cigarette with impact and flavor (Jones 
         and Martin)
       This is the first study in the 5-6 mg tar delivery program 
     being carried out in collaboration with Paul Gauvin, Barbro 
     Goodman, and Willie Houck. The purpose is to evaluate the 
     relative influences of blend (Standard Marlboro blend vs 50% 
     burley blend), burley spray (100% vs. 50%), and filter system 
     (cellulose acetate filter vs. paper/cellulose acetate filter) 
     on smoke impact and acceptability of cigarettes in the 5 to 6 
     mg tar range.
       Panelists will be asked to smoke the eight experimental 
     cigarettes and a Marlboro control in any order they wish and 
     to rate each coded cigarette on an impact scale and an 
     acceptability scale before beginning to smoke another 
     cigarette code. The cigarettes have been released and should 
     go out shortly to 400 RP3 smokers.
                            planned studies

     I. Conference on the regulatory influence of nicotine on 
         human behavior (Dunn)
       An international conference on the regulatory influence of 
     nicotine upon behavior has been proposed to the cigarette 
     industry. We would hope that these studies on aggression 
     could be reported at that conference, as well as studies of 
     the influence of smoking upon other emotionally toned 
     response patterns. The interest of prospective sponsors has 
     yet to become great enough to provide the impetus for 
     approval and support.
     I. Is learning affected by nicotine? (Ryan and Lieser)
       Some reports in the animal literature suggest that nicotine 
     facilitates at least some aspects of the learning process. 
     Recently Andersson and Post have reported that nicotine 
     interferes with human learning in at least one task 
     situation--the learning of a long list of nonsense syllables. 
     We are unhappy with this report and unconvinced by its 
     evidence, which appears to have some internal inconsistencies 
     (e.g. a first nicotine cigarette slows learning, a second 
     speeds it up); as well as some flaws in design (e.g. the 
     control nicotine free cigarette used was Bravo--we prefer 
     denicotinized tobacco); the ``smokers'' were very low intake 
     people whom we would not classify as regular smokers (we 
     prefer heavier smokers); both cigarettes smoked were the same 
     type (we would have included switch groups); the list of 
     syllables was very difficult (we would prefer a difficult and 
     an easy list); only a few smokers were used; total smoke 
     intake was unmeasured, etc. We're repeating the study (In 
     part because we have student subjects already on hand in the 
     lab who are participating in the Personality, Smoking and 
     Stimulus deprivation study) essentially as run together with 
     some of the corrections suggested above. We feel a 
     responsibility to see that the published report is corrected 
     if it is in fact wrong. The smoking studies in psychology 
     journals contain too much unchallenged and unreplicated junk 
     which has passed editorial review because the findings 
     conform to editorial biases against tobacco. Sooner or later 
     the accumulation of this unchallenged sloppy work will be 
     used against us. We aren't interested in picking fights, but 
     . . . .
     II. Inhalation patterns (Dunn and Levy)
       Following our preliminary run reported at the November 
     Project Review, we decided to continue this work. In the 
     preliminary runs we measured gas volume drawn in through the 
     nose upon smoke inhalation, as well as that drawn in through 
     the mouth. We did not measure puff volume, nor retention 
     time, two measures that we now view as essential. We have 
     also come to believe that the smoking of our subjects must be 
     monitored over a period of many hours rather than during the 
     smoking of a single cigarette. These two decisions force the 
     experimentation into a new realm of complexity in terms of 
     instrumentation and logistics. We have installed an 
     observation room that permits complete control of sensory 
     input. We plan to have our subjects remain in this room for 
     four to eight-hour periods, measuring all parameters of 
     smoking behavior throughout the period while varying factors 
     suspected to be determinative of dosage. Some preliminary 
     work on the additional instrumentation has been accomplished, 
     but full scale resumption of the work has been delayed until 
     the arrival in September of the new member of our staff, a 
     physiological psychologist.
       Our objective in this part of our program is to demonstrate 
     the degree to which the smoker's absorption of smoke 
     components is a function of his smoking behavior as opposed 
     to his absorption being a function of what is made available 
     to him in the cigarette smoke.
     III. Annual cigarette monitoring (Ryan)
       Cigarettes with tar and nicotine deliveries only a few 
     years ago though much too low for public acceptance are now 
     selling in the billions. Is the public's taste actually 
     changing, so that even lower delivery cigarettes may soon 
     become acceptable?
       We lack data on the relative acceptability of cigarettes of 
     different delivery evaluated by the same smokers. No broad 
     studies of this type have ever been conducted here. To fill 
     the data gap we have had Marlboro rods attached to five 
     different filter systems to produce 85 mm nonmenthol 
     cigarettes with nominal deliveries of 20, 17, 14, 11, and 8 
     mg tar, which we will ask a National POL panel to evaluate 
     annually. The filter systems, whose characteristics were 
     chosen by W. Houck and W. Claflin, represent the draw and 
     other characteristics of typical cigarettes now marketed at 
     these delivery levels.
       The actual deliveries are: 19.6, 17.6, 14.3, 10.5, and 7.9 
     mg tar; 1.22, 1.10, 0.93, 0.74, and 0.59 mg nicotine per 
     cigarette, respectively.
       Smokers will be asked only to rate the acceptability (on a 
     labeled scale from 1-9) of the five products in a blind test, 
     basing their evaluation on two packs of each type sent them 
     as a carton mailout. A variety of possible outcomes can be 
     foreseen. In any given year different acceptabilities are 
     expected for the five cigarettes, with the most acceptable 
     being the one which most resembles and the lowest being the 
     one which least resembles the smoker's own brand--if the 
     smoker bases the acceptability of the unbranded models on 
     cues based on their resemblance to his own brand. To the 
     extent that he has some other criterion, then the evaluations 


[[Page H 7657]]
     will differ from this model. For example, if he likes taste but has 
     chosen to smoke a low taste cigarette for obscure reasons 
     (e.g. health? advertising campaigns? imitating his friends?) 
     then he should give higher acceptability ratings to the high 
     delivery models than to the low delivery models, no matter 
     what his own brand is. The reader can speculate for himself 
     on how other possible demographic or smoking history 
     variables might be expected to affect the acceptability 
     ratings.
       To be sure that a wide variety of demographic 
     characteristics are present we will poll a large sample from 
     the POL National panel, oversampling young subgroups to 
     insure reasonable returns.
       Although basic information of interest can be gathered from 
     the returns of any given year, our principal interest will be 
     in the acceptability change from year to year.
     III. Low delivery cigarettes and RTD (Jones)
       A study is being planned in collaboration with some people 
     in Development in which the question of the influence of RTD 
     level upon acceptability and strength ratings of low delivery 
     cigarettes will be further explored. Based upon the 
     recommendations given in a previous report (75-105), the 
     multiple monadic testing procedure will be used. After 
     cigarette models are designed and cigarettes made, they will 
     be sent out to a large panel of National POL smokers.
     III. Perceived attributes of cigarettes, a replication 
         (Jones)
       Two studies have been conducted concerning smoker 
     perceptions of regular filter (72-088) and menthol (73-027) 
     cigarettes. It seems that with the recent interest in longer 
     (120 mm) cigarettes, smokers' ideas about cigarettes may have 
     shifted such that they place more emphasis on length than 
     they did previously. In addition to possible changes in what 
     cigarette attributes are considered important, there have 
     been brands introduced since the previous studies were 
     completed (e.g. Marlboro Lights, Winston Lights, Kool Milds) 
     which may have filled what at that time appeared to be gaps 
     in the market (e.g. low in delivery, high in flavor). 
     Therefore, plans are being made to replicate the perceived 
     attributes studies.
                                 ______

     Charge Number: 1600
     Program Title: Smoker Psychology
     Project Leader: W.L. Dunn, Jr.
     Period Covered: April 1-30, 1977
     Date of Report: May 13, 1977

     Project Title: Regulator Identification Project
     Written by: C.J. Levy
       Twenty-five college student smokers have been smoking high 
     and low delivery cigarettes for two weeks at home. These 
     students are now coming in to our Franklin Street office on 
     four separate occasions to smoke under more controlled 
     conditions.

     Project Title: Low Nicotine Cigarettes
     Written by: C.J. Levy
       Forty-eight R&D smokers compared two types of cigarettes in 
     a booth test. Both cigarettes were made from tobacco which 
     had been treated with steam and ammonia by Fran Utsch's 
     group. The cigarettes (control and experimental) delivered 
     20.0 mg tar, 0.40 mg nicotine and 19.9 mg tar, 0.87 mg 
     nicotine, respectively. The nicotine delivery of the 
     experimental cigarettes was increased using nicotine citrate. 
     No significant differences were found between the two 
     cigarettes in this test.
       Eighteen (out of 23) smokers who previously identified the 
     experimental cigarette as producing more inhalation impact 
     than the control were subsequently asked to smoke the 
     cigarettes on three more occasions. Only three of these 
     smokers consistently identified the experimental cigarette as 
     producing more inhalation impact. Eight identified it twice 
     and seven identified it only once.
       We conclude from these tests that there are no dramatic 
     differences between the cigarettes when tested using a paired 
     comparison methods, even through the experimental cigarette 
     delivers twice as much nicotine.

     Project Title: Measurement of Smoke Inhalation
     Written by: C.J. Levy
       (a) We are continuing to collect chest expansion data using 
     a mercury strain gauge. We are currently working out 
     calibration procedures with the assistance of Dr. Farone.
       (b) In another approach we have brought in Dr. Eli Fromm of 
     Drexel University as a consultant to advise in the 
     development of a device for unobtrusively monitoring smoke 
     inhalation under normal smoking conditions.

     Project Title: Annual Monitoring
     Written by: F.J. Ryan
       We sent cigarettes to 4,000 panelists. All but 128 were 
     delivered. Ballots have been returned from 2,953 people, a 
     return of 76%. Not all of these will be usable. At least 197 
     (or 6.7%) have incomplete data or will be voided for various 
     reasons: being smoked through an extra filter, or by a smoker 
     who had a cold, or by a nonsmoker, etc. At least 125 more 
     ballots (or 4.2%) were returned by people who had switched to 
     menthol brands since last being polled.
       Ballots are now being coded and a preliminary report should 
     be ready by mid-June.

     Project Title: Verbal Learning and Smoking
     Written by: F.J. Ryan
       Only two more subjects are needed to complete the data 
     gathering phase of this study.

     Project Title: Perceived Smoke Strength and Interpuff 
         Interval
     Written by: F.J. Ryan
       We have screened 25 R&D smokers to find 20 who can detect 
     differences in strength between cigarettes of widely varying 
     delivery. They will be asked to rate the apparent strength of 
     a 9 mg cigarette smoked at long or short interpuff intervals. 
     If short interpuff intervals increase apparent strength, then 
     we may be able to account for the increased puff count 
     sometimes observed on low delivery products.

     Project Title: Hyperactivity
     Written by: F.J. Ryan
       To test our hypothesis that hyperactive children are more 
     likely to become cigarette smokers than nonhyperactives, we 
     have begun pilot research for two prospective studies in 
     collaboration with others interested in hyperactivity. 
     Together with Dr. Ron David, a pediatric neurologist at MCV, 
     we are identifying a group of his patients who are known to 
     have their hyperactive or impulsive behaviors reduced by 
     drugs (e.g. Ritalin) and a group which does not respond to 
     drugs. Together with Dr. Al Finch, research psychologist at 
     the Virginia Treatment Center, and Dr. Howard Garner, VCU, we 
     are identifying a group of patients treated with Ritalin or 
     other stimulants, and a group of controls with nonhyperactive 
     behavior problems. In both cases we will later contact the 
     children to see whether they have become smokers, comparing 
     the incidence of smoking among these groups with the 
     incidence in the nonhyperactive school population.
       In return for access to their files we are helping our 
     colleagues find (1) the variables which account for drug-
     responding and non-responding (Dr. David) and (2) the effect 
     of miscellaneous treatments on later adjustment to school and 
     society (Drs. Finch and Garner). Neither of these colleagues 
     is being financially supported.

     Project Title: Patterned Cigarette Paper
     Written by: E.C. Gay
       A second consumer evaluation of patterned papers was 
     conducted using eight designs printed in green. A clear 
     winner emerged as top choice of respondents across and within 
     all subgroups. It has a ``light'' overall appearance, with a 
     ``small'' ``plain'' design according to panelists. Additional 
     evaluations are programmed to evaluate still other patterns, 
     with first and second choices from each heat to compete in a 
     final runoff evaluation later.
                                 ______

     Charge Number: 1600
     Project Title: Smoker Psychology
     Period Covered: February 1-28, 1978
     Project Leader: W.L. Dunn
     Date of Report: March 10, 1978

     Project Title: Smoking and Learned Helplessness
     Written by: C.J. Levy
       We continue to collect data. We are having some difficulty 
     recruiting the male smokers needed to complete the study.

     Project Title: Smoking of Low Nicotine-Cigarettes
     Written by: C.J. Levy
       We have received the analytical data on our experimental 
     cigarette. The nicotine-fortified cigarette delivers 1.34 mg 
     of nicotine, and the low-nicotine cigarette delivers 0.14 mg 
     of nicotine. We are currently recruiting R&D smokers for our 
     study.

     Project Title: Smoking Parameters Study
     Written by: F.P. Gullotta
       A follow-up on the completed heart rate study is being 
     implemented. In addition to heart rate, respiration and puff 
     measures will also be recorded. Data collection will begin in 
     one to two weeks and the study should be completed in five to 
     six weeks.

     Project Title: EEG
     Written by: F.P. Gullotta
       Neither the EEG/Polygraph nor the computer has arrived. The 
     EEG will be shipped from Quincy, MA this week. It is 
     anticipated that the computer will arrive within a month.
       A meeting has been arranged with Mr. D. Derr of Coulbourn 
     Instruments to discuss the purchase of auditory and 
     somatosensory evoked potential modules to be used in studies 
     planned for the second half of 1978.

     Project Title: Smoking Diary Study
     Written by: F.J. Ryan
       Butt collection is complete. Although 33 students completed 
     the study, we expect to discard a few because their results 
     appear affected by influenza or chronic unreliability. We 
     have switched full-flavor smokers to low delivery and back, 
     or switched low-delivery smokers to full flavor and back. The 
     data consist of butt counts, butt lengths, nicotine in filler 
     analyses, time of day each cigarette was smoked, and 
     proportion of day spent in various activities.
       We are interested in the extent to which smoking behavior 
     changed when cigarette delivery changed. We are seeking (1) 
     to find the extent to which nicotine need governed behavior 
     and (2) to find the extent to which stimulus situations 
     controlled the behavior. Data evaluation will be a lengthy 
     process.

     Project Title: Hyperkinetic Children
     Written by: F.J. Ryan
       Obstacles presented by school systems and physicians 
     concerned with the various ``privacy acts'' passed by state 
     and national legislatures have made it very difficult for us 
     to conduct studies using school and medical records of 
     minors. Therefore we have stopped our activities in this 
     area.

     Project Title: Annual Monitoring

[[Page H 7658]]

     Written by: F.J. Ryan
       The second ``mailout'' of the annual monitoring cigarettes 
     is now firmly scheduled for the end of March. Ballots are 
     essentially the same as last year. We will contact about 2700 
     of last year's panelists, plus 1300 supplementary people who 
     smoke full-flavor or low-delivery nonmenthol filter 
     cigarettes. Ballots are to be returned on or before April 21.

     Project Title: Exit Brand Cigarettes
     Written by: F.J. Ryan
       A report has been written outlining the findings of the 
     Exit-Brand Study.
                                 ______

Philip Morris Research Center--Behavioral Research Annual Report (Part 
II) Approved by T.S. Osdene & Distributed to H. Wakeham et al.--Nov. 1, 
                                  1974

       This is the second of a two-part annual report covering the 
     research activities under Charge No. 1600. The first part was 
     prepared by Frank Ryan in August, 1974, and included 
     accomplishments by him. This second part has been prepared by 
     Tom Schori and Bill Dunn and summarizes accomplishments in 
     their respective areas:


                               Objectives

       Our objectives under 1600 are threefold:
       I. To learn more about why people smoke.
       II. To learn more about how people smoke.
       III. To further identify what people want to smoke.
       For each of these objectives we have formulated hypotheses 
     which guide our research effort. For the sake of clarity, the 
     studies being reported on are designated by a three-part 
     prefix. The first symbol is a Roman numeral designating the 
     objective being pursued, the second symbol is a letter of the 
     alphabet identifying the hypothesis being tested and the 
     third symbol is an Arabic number which identifies the study.
       Below we set forth in sequence the three objectives and 
     list the working hypotheses under each objective:
       I. To learn more about why people smoke.
       IA. Cigarette smoke improves efficiency in the performance 
     of complex psychological tasks.
       IB. Cigarette smoking attenuates, modulates or otherwise 
     influences emotional arousal such as to be gratifying or 
     rewarding to the smoker, thus reinforcing the smoking act.
       II. To learn more about how people smoke.
       IIA. Smoking patterns vary as a function of changes in 
     cigarette and the smoke it generates.
       IIB. Dose-control continues even after the puff of smoke is 
     drawn into the mouth.
       III. To further identify what people want to smoke.
       IIIA. There are optimum combinations of critical variables 
     in smoke composition.
       IIIB. Deterioration in cigarette acceptability can be 
     minimized when reducing tar deliveries by not reducing or 
     changing other critical properties.
       IIIC. More effective ways can be developed for obtaining 
     consumer response to cigarettes.
       From this point on we will present the individual studies 
     of 1600, grouping them by progress status in three sections:
       1. Completed
       2. Data Being Collected
       3. Preinvestigative (conceptualization and instrumentation)
       The Ryan studies will be cited with page references to his 
     portion of the annual report.


                   completed studies since july, 1973

     IAI--(Dunn and Martin)--THE INFLUENCE OF CIGARETTE SMOKING 
         UPON THE VOLUNTARY CONTROL OF ALPHA TYPE 
         ELECTROENCEPHALOGRAPHIC ACTIVITY (Accession No. 74-075)
       Observations suggest that there are links-between brain 
     wave frequencies and psychological levels of alertness. The 
     highly aroused human will display brain activity at the upper 
     end of the 1-30 Hz range. When drowsy or sleeping, the 
     dominant activity will be at the low end of the spectrum. The 
     1-30 Hz range has been divided somewhat arbitrarily into four 
     bands, each band associated with a reasonably circumscribable 
     psychological state. The beta band, including all signals 
     exceeding 13 Hz, is linked to the state of alert 
     responsiveness to external stimulation. Those ranging from 8 
     to 4 Hz, the theta waves, correspond to the drowsy, sleepy 
     states of mind. Delta, less than 4 Hz, is seen in deep sleep 
     states. The alpha waves (8-13 Hz) are the most interesting in 
     that these appear to be dominant when the subject is in a 
     relaxed but awake meditative state, not unlike the states 
     thought to characterize the meditating Indian yogi.
       Thus, if one seeks to induce the ``alpha state'' in 
     oneself, the effort can be facilitated by the auditory signal 
     linked to a dominant alpha frequency. It is not clear how the 
     gradual increase in control occurs, but it is a matter of 
     observation that the increase does occur and that the 
     feedback signal is facilitative.
       In that we here at P.M. R&D are intent upon identifying 
     psychological changes induced by smoke inhalation, it 
     occurred to us that we should determine whether smoking has 
     an influence upon achieving the alpha state. We considered it 
     not unreasonable to anticipate a smoking effect upon rate of 
     learning of the control of alpha activity, or even more 
     likely an effect upon time on target during a fixed period of 
     observation. We did not arrive at this position by way of a 
     conceptual model, at any rate not in any formal, deductive 
     manner. Perhaps at some pre- or sub-conceptual state there is 
     an intuitive belief that we should be paying attention to the 
     more subtle psychological functions having to do with 
     alertness and concentration as possible points at which we 
     may find smoke inhalation having some facilitative effect. In 
     any event we had no preconceptions as to what effect, if any, 
     smoking might have upon the acquisition and maintenance of 
     the alpha-state. Long inured to the elusiveness of smoke 
     inhalation effects upon psychological state or function, we 
     have come to proceed in a pragmatic way by sinking shafts 
     here and there for signs of smoke-induced change. Either 
     facilitory or inhibitory effect would be a welcome clue.
       Nineteen R&D smokers, with sensing electrodes and 
     headphones in place, sat in daily 10-minute sessions learning 
     to keep the auditory tone on by maintaining a dominant alpha 
     brain wave pattern. These sessions were continued until on-
     target time had plateaued. Nine subjects were allowed to 
     smoke freely prior to session, and ten abstained from the 
     preceding evening's bedtime. This was Phase I for which we 
     had the following objectives:
       1. To bring all subjects to a plateau level in maintaining 
     the alpha state.
       2. To observe for differences in learning rate between 
     those smoking prior to the observation period and those 
     abstaining from smoking.
       3. To observe for differences in learning rate between 
     introverts and extroverts.
       4. To observe for correlations between certain measures of 
     personality traits and acquisition rate in maintaining a 
     dominant alpha pattern.
       Mean time-on-target in the first session was 69%, with a 
     range from 15% to 93%. The high base line of 69% for the 
     first session was a surprise. It was also an unanticipated 
     constraint on the study in that little latitude was left for 
     improvement in performance. Mean time-on-target at plateau 
     was 82%. Introverts performed better than extroverts, both 
     initially and at plateau. We concluded after a thorough 
     analysis that whether or not a smoker smoked immediately 
     preceding observation had no discernible effect upon 
     acquisition rate, not initial, nor final performance levels. 
     Certain personality traits, as measured by the Cattell 16 PF 
     Scales were found to be correlated with performance 
     improvement, but these are of little interest for our 
     purposes here. (See Table 4 of Accession No. 74-075.)
       Having plateaued, a subject entered Phase II. Sixteen of 
     the original 19 subjects completed Phase II. All subjects 
     were pooled, each serving as his own control. There was a 5-
     minute pretreatment, 3-minute treatment and 5-minute post-
     treatment sequences. The pre- and post-treatment periods were 
     alpha time-on-target periods. The 3-minute treatment period 
     was a cigarette smoking and a dry-puffing period on alternate 
     days. Each subject went through six such days, 3 experimental 
     (smoking) and 3 control (dry-puffing).
       Although there was a 2 to 1 tendency for introverts to 
     improve and a 2 to 1 tendency for extroverts to worsen as a 
     result of smoking, our numbers are simply too small and our 
     performance values too variable to allow us to draw any 
     inferences other than that all of the differences observed 
     were but the result of change fluctuations.
       Thus we have been unable to relate any of the measures 
     pertaining to alpha control to cigarette smoking. Note that 
     we did not look for differences between smokers and 
     nonsmokers, since our interest was in the immediate effect of 
     smoke inhalation.
       We did make the passing observation in Phase II that there 
     appeared to be some disruption during the initial part of the 
     post-treatment (smoking) five minutes of observation. Not 
     anticipating such transient, short-lived effect, we were not 
     prepared to record anything other than cumulative performance 
     over the whole of the five minutes. So we plan to follow up 
     on this observation by running a few subjects under 
     conditions in which we can record time-on-target for briefer 
     time intervals. The results of this briefer study will be 
     reported separately.
     IA2--(Ryan and Lieser)--Effects of smoking and delayed audio-
         feedback on speech behavior
       (See pp. 6-8--Behavioral Research Annual Report, Part I, 
     Accession No. 74-065)
     IA3--(Schori and Jones)--Smoking and attentional capabilities
       Smokers, smokers-deprived, and nonsmokers performed a 
     tracking task while simultaneously performing a cross-
     adaptive loading task. The loading task automatically varied 
     in difficulty such that it utilized that portion of the 
     subject's total attentional capacity which was not needed for 
     satisfactory tracking performance, i.e., his spare 
     attentional capacity. In this fashion, the size of the total 
     work load (tracking and loading tasks combined) was 
     individually tailored to utilize each subject's entire 
     attentional capacity. No differences were found among groups 
     either in tracking or loading task performance. Therefore, it 
     was concluded that smokers, smokers-deprived, and nonsmokers 
     expended similar amounts of attentional effort in performing 
     the tracking task and, thus, smoking condition did not affect 
     the size of the workload which could be handled. Reference: 
     73-123, September, 1973.

[[Page H 7659]]

     IB1--(Ryan and Dunn)--Heart rate change under arousal 
         conditions among smokers and nonsmokers
       The Emory-Ryan hypothesis predicts reduction in magnitude 
     of heart rate increment under smoking conditions. We did an 
     exploratory study in which arousal was induced by physical 
     exercise, using smokers and nonsmokers whose heart rates were 
     radio-telemetered to a nearby recorder. The study was aborted 
     when we observed no difference in heart rate increments for 
     the two group of subjects.
     IB2--(Schori and Jones)--Smoking, arousal, and mood change
       In this study smokers, smokers-deprived, and nonsmokers 
     were required to solve multiple choice problems (mathematical 
     problems adapted from the College Boards and the Graduate 
     Record Examination) which were rear-projected onto a screen. 
     When the subject had solved a problem, he indicated his 
     response by pressing the button--just below the rear-
     projection screen--that corresponded to the alternative he 
     had chosen. Each subject, on different days, performed the 
     task at 3 problem presentation rates, i.e., slow-paced, self-
     paced, and fast-paced. Performance of smokers-deprived was 
     definitely better (that is, they responded both more quickly 
     and more accurately to the problems presented) than either 
     nonsmokers or smokers--the latter two groups exhibiting 
     comparable performance. That the smokers-deprived performed 
     better, without going into detail, was explained in terms of 
     two factors in combination: (1) simply being deprived of 
     cigarettes; and (2) the nature of the task itself.
       No differences in personality profiles were found between 
     nonsmokers and smokers (which for this analysis included 
     smokers-deprived). This may not be too surprising. When 
     personality differences between nonsmokers and smokers have 
     been reported, it has generally been based upon large scale 
     samplings of heterogeneous populations--not from small 
     relatively homogeneous populations such as our college 
     student sample. Furthermore, even when large heterogeneous 
     populations are sampled, differences in personality 
     characteristics that have been reported are very slight. In 
     agreement with most literature on the topic, heart rates of 
     smokers were substantially higher than those for nonsmokers 
     and smokers-deprived, viz., an increase in heart rate of 10-
     11 beats/min. could be attributed to smoking.
       We had expected that mood change would be more prevalent 
     under the slow and fast-paced conditions than under this 
     self-paced condition. However, this is not what we observed. 
     Instead, mood change, i.e., changes in affect, was much more 
     prevalent (more significant mood changes occurred) under the 
     self-paced condition. Smokers, though, did experience less 
     mood change than did nonsmokers or smokers-deprived--which in 
     agreement with similar findings of other investigators does 
     suggest that smoking actually may act to temper emotional 
     reactivity. Draft manuscript, October, 1974--the technical 
     report should be out shortly.
     IIA1--(Ryan)--Puff three--Chained puffing (see p. 1, 
         Accession No. 74-065)
     IIA2--(Ryan)--Puff four--Puffing behavior at 30-and 60-second 
         puff intervals (see p. 2, Accession No. 74-065)
     IIA3--(Ryan)--Puff five--Puffing behavior changes on 
         cigarette cut to different lengths (see pp. 2-4, 
         Accession No. 74-065 )
     IIA4--(Schori and Jones)--Does the smoker compensate for 
         changes in delivery in order to regulate intake? (TNT-4)
       Winston smokers from the RP\3\ panel smoked 7 different 
     cigarettes each for 1 week. There were 6 experimental 
     cigarettes, with tar ranging from 8.2 to 14.6 mg and nicotine 
     ranging from .28 to .90 mg, and a Marlboro control. The 
     number of cigarettes smoked/day and the amount of rod 
     consumed per cigarette (mm) were recorded from saved butts. 
     If the smoker does change the number of cigarettes smoked or 
     amount of rod consumed to maintain relatively constant intake 
     as changes in cigarette deliveries occur, this should be 
     evident as deliveries both increases and decrease from his 
     accustomed levels. However, we found no evidence of any such 
     regulatory behavior, i.e., they failed to compensate for the 
     decreased availability of tar and nicotine by changing either 
     the number of cigarettes which they smoked or the amount of 
     rod consumed from each cigarette. In the face of mounting 
     evidence (of which this study is an instance) that smokers do 
     not alter consumption rates sufficiently to support the 
     intake constancy hypothesis, this hypothesis must be viewed 
     with skepticism unless some other mechanism for regulating 
     intake can be discovered. Reference: 74-078, August, 1974.
     IIIB1--(Schori and Jones)--Smoking and low delivery 
         cigarettes (TNT-3)
       Smokers from the POL National Panel were required to smoke 
     14 mg tar cigarettes at .30, .75 and 1.20 mg nicotine, 11 and 
     8 mg tar cigarettes at .30 and .75 mg nicotine, and a 
     Marlboro control. The 14 mg tar/.75 mg nicotine cigarette (a 
     cigarette with proportional reductions in nicotine and tar) 
     was accorded an acceptability rating equivalent to that of 
     the Marlboro control. The other experimental cigarettes, 
     however, did not compare very favorably to Marlboro in 
     acceptability. Reference 73-129, October, 1973.
     IIIB2--(Schori and Martin)--Low delivery cigarettes and 
         increased RTD (DL-2)
       Smokers in an R&D handout test and in an RP\3\ test smoked 
     a Marlboro control and three low delivery cigarettes--
     averaging less than 10 mg tar--with RTDs varying upwards from 
     4.8 in. We has predicted, based upon earlier data, that 
     increasing the RTDs of low delivery cigarettes would make 
     them subjectively appear stronger. However, this is not what 
     we found The Marlboro control was given the highest mean 
     strength rating. The next highest strength rating was 
     ascribed to the low delivery cigarette with the 4.8 in RTD 
     while the lowest mean strength rating was given to the low 
     delivery cigarette having the highest RTD. Although there can 
     be other interpretations of this finding, it appears most 
     likely that the variations in strength ratings among the low 
     delivery cigarettes reflect their variations in RTD.
       The most interesting finding had nothing to do with the 
     relationship between RTD and cigarette strength. It was the 
     fact that the Marlboro control, in comparison to the low 
     delivery cigarettes was not the most acceptable cigarette to 
     the smokers. Thus, it may be possible to make cigarettes 
     delivering less than 10 mg tar which will be just as 
     acceptable to high delivery smokers as a standard Marlboro--a 
     finding similar to those that we have reported earlier in 
     conjunction with studies of smoker response to cigarettes of 
     somewhat higher deliveries than those of the present study. 
     Reference: 74-054, June, 1974.
     IIIB3--(Schori and Martin)--Low Delivery Cigarettes and 
         Increased Nicotine/Tar Ratios (DL-1)
       In this study, we compared 3 low delivery cigarettes (in 
     the 10 mg tar range) to a Marlboro control. One of these 
     cigarettes, i.e., the 10.7 mg tar, .12 nicotine to tar (N/T) 
     ratio cigarette, was comparable to the Marlboro in terms of 
     both subjective acceptability and strength. In other words, 
     that cigarette was perceived to be a full-flavored low 
     delivery cigarette. Although we previously have had 
     cigarettes, in this tar delivery range, which achieved parity 
     with Marlboro in acceptability, this is the first time that 
     such a cigarette has achieved parity in both acceptability 
     and strength. However, we cannot be certain whether the high 
     N/T ratio was an essential factor in that cigarette being 
     perceived as a full-flavored cigarette. And obviously we do 
     not wish to increase N/T ratios unless it is absolutely 
     necessary to do so in order to make full-flavored low 
     delivery cigarettes. Reference: 74-088, September, 1974.
     IIIC1--(Schori and Jones)--A Method for Field Testing a 
         Distinctively Flavored Candidate
       In response to a specific need, we developed a general 
     testing methodology for consumer tests of novel cigarette 
     products. The methodology itself is currently being evaluated 
     in an actual product test. Reference: Memo to Filosa, April, 
     1974.
     IIIC2--(Schori)--Analyzing Descriptive Panel Data
       Having recommended a different approach for analyzing 
     descriptive panel data, we continue to do these descriptive 
     panel analyses on a regular basis.
     IIIC3--(Schori and Jones)--A Procedure to Identify Gaps in an 
         Existing Product Market
       We prepared this paper to present at the ASTM Symposium 
     this fall (based upon an earlier report--72-088, June, 1972). 
     However, it was felt that the material covered in the paper 
     was of a proprietary nature and, therefore, was not suitable 
     for outside release. Reference: Unpublished manuscript, 
     September, 1974.


                         outside publications:

       Schori, T.R. & Jones, B.W. Smoking and multiple-task 
     performance. Virginia Journal of Science, in press.
       Schari, T.R. & Jones, B.W. Smoking and work load. Journal 
     of Motor Behavior, in press.


                         data being collected:

     IA4--(Schori and Jones)--The Relationship Between Smoking and 
         Risk-Taking Behavior
       It has often been suggested that smokers take more risks 
     than do nonsmokers. This notion, though, has been based upon 
     non-experimental data (e.g., the fact that smokers have more 
     traffic accidents than nonsmokers). And such data do not take 
     into consideration certain critical factors. For instance, 
     they do not take into consideration possible differences in 
     exposure between smokers and nonsmokers which could explain 
     their differential traffic accident rates. Therefore, the 
     present investigation was designed to determine 
     experimentally whether smoking condition (i.e., smoking, 
     smoking-deprivation, and nonsmoking) actually does affect the 
     individual's degree of willingness to take risks. The task 
     itself is a simulated driving task.
     IIA4--(Ryan and Lieser)--Puff six-Puffing behavior following 
         long and short intervals (see pp. 8-9, Accession No. 74-
         065)
     IIA5--(Ryan and Lieser)--Smoking following cigarette 
         deprivation
       We want to know whether smokers who are deprived of smoke--
     by being in a ``no-smoking'' area or situation--will make up 
     for this smoke deficit when they leave the ``no smoking'' 
     area.
       We will observe number of puffs and number of cigarettes 
     smoked in a two-hour control period, and compare these 
     figures with those observed in a two-hour period following 
     two hours of smoke deprivation.
     
[[Page H 7660]]

     IIBI--(Dunn and Martin)--Patterns of smoke inhalation
       We are investigating the manner in which the puff of smoke 
     in the mouth is introduced further into the respiratory 
     system.
       We became interested in this aspect of smoking behavior 
     through earlier work on the problem of dose control. Since 
     1968 when we undertook SEX-I, an extensive field study of the 
     quantity of smoke taken into the mouth, we have been 
     investigating the extent to which the smoker regulates intake 
     and the manner in which he regulates intake.
       A general premise in our theoretical model of the cigarette 
     smoker is that the smoking habit is maintained by the 
     reinforcing effects of the pharmacologically active 
     components of smoke. A corollary to this premise is that the 
     smoker will regulate his smoke intake so as to achieve his 
     habitual quota of the pharmacological action. As 
     circumstances and body state vary, so will vary the desired 
     level of action. Also as the concentration of the active 
     agents in the smoke varies, so will vary the amount of smoke 
     taken in.
       Seeking confirmation of our model, since 1968 we have been 
     measuring intake levels while systematically varying 
     circumstances, body state and smoke composition. We have 
     observed changes in the predicted directions, but the 
     magnitude of the changes has always fallen far short of that 
     change necessary to infer that the smoker is exercising quota 
     regulation of intake. Others have reported similar 
     investigations with similar findings.
       Recent observations have led us to question whether the 
     indices of intake which have been investigated to date are, 
     in fact, the appropriate indices to be measuring. We have 
     counted the number of cigarettes smoked, we have counted the 
     number of puffs taken, we have measured amount of rod 
     consumed and we have obtained reasonably accurate estimates 
     of how much smoke is actually taken into the mouth over 
     extended periods of time.
       All of these measures fall short of determining the amount 
     of smoke brought into contact with the absorbing surfaces 
     within the lungs. We now have evidence that with some smokers 
     a good portion of the smoke of a given puff never goes beyond 
     the mouth, it being retained in the mouth to be expulsed 
     ahead of that portion which was inhaled. Furthermore, we have 
     good evidence that the gas inhaled following the drawing of a 
     puff from the cigarette is not exclusively the air/smoke 
     mixture introduced through the mouth. A greater or lesser 
     amount of air is introduced through the nose, mixing at the 
     pharyngeal junction of the nose and mouth with the air/smoke 
     mixture being swept in from and through the mouth.
       These observations have made us aware of a heretofore 
     unnoticed mechanism that has the potential of affording the 
     smoker a wide latitude of control over the amount of smoke he 
     brings into contact with the absorption sites.
       It has been our purpose in this, the first of an 
     anticipated serie of studies, to systematically observe the 
     inhalation patterns of smokers. We are measuring flow rates 
     and volumes of air drawn through the mouth and air drawn 
     through the nose while varying tar and nicotine levels in the 
     mainstream smoke. If the smoker is seeking his quota of the 
     pharmacologically active ingredients, and the regulatory 
     mechanisms available at the post-puff levels are being used 
     toward this end, then we would expect to find directional 
     changes in the ratio of air drawn in through the nose and the 
     air/smoke mixture being drawn in through the mouth, and/or 
     changes in the total inhalation volume.
       The problem has required the fabrication of novel 
     apparatus. With much trial and error we have devised a means 
     of independently measuring the rate and volume of air drawn 
     in through the two orifices as the smoker inhales immediately 
     following the drawing of a puff of smoke into his mouth. We 
     have designed and constructed a face mask of silicon rubber 
     which contains a cavity for the nose and a cavity for the 
     mouth. These cavities are sealed off from ambient air and 
     from each other when the subject's face is in position. The 
     mask is rather massive and self supporting, yet flexible 
     enough to effect a good seal with a face. The mask is rigidly 
     mounted on a plexiglass sheet. Leading off behind the 
     plexiglass sheet are two \3/8\'' i.d. tygon tubes, one 
     connecting the mouth cavity to a flow rate sensor and the 
     other connecting the nose cavity to a second flow rate 
     sensor.
       The sensors responding to flow rate are hot wire 
     anemometers. The voltage changes in these sensors reflecting 
     air flow are processed through electronic circuitry to be 
     finally recorded on polygraph paper in terms of flow rate and 
     air volume. The system is calibrated such that quantified 
     flow rates and volumes in cc can be read directly from pen 
     deflections.
       Seated before the apparatus, the subject takes a puff from 
     his cigarette inserts his face into the mask, inhales, 
     withdraws from the mask and exhales in normal fashion. The 
     only part of the sequence occurring with face in mask is the 
     inhalation.
       We have used twelve volunteer R&D pack-a-day-plus smoker of 
     regular filter cigarettes. Each subject smoked one cigarette 
     at the mask in the morning and afternoon of each workday. The 
     study ran for three weeks. On the first week they smoked 
     their regular cigarettes. On the second and third weeks they 
     smoked Commanders and Carltons, with a split-group balanced 
     order. The cigarette designated for a given week was smoked 
     continuously by the subject from the first session on Monday 
     to the last session on Friday.
       Data collections has been completed and the analysis is 
     underway. The results available at the time will be reported 
     at Project Review on November 8.
       Data collection has been completed and the analysis is 
     underway. The results available at the time will be reported 
     at Project Review on November 8.
     IIIA1--(Schori, Jones and Martin)--Menthol cigarette 
         preferences of Blacks and whites (MN-3)
       Black menthol smokers have generally been inadequately 
     represented in our National menthol cigarette tests. In fact, 
     our National POL Panel, for all practical purposes, is a 
     White panel since nonwhite returns from product tests 
     probably rarely exceed 3% of the total returns. Since there 
     is considerable evidence which suggests that Blacks and 
     Whites may differ in their likes and dislikes in menthol 
     cigarettes, the present investigation was designed to 
     identify Black and White preferences for menthol and nicotine 
     deliveries in Alpine-like cigarettes. Accordingly, Black 
     menthol smokers (from RP\3\) and White menthol smokers 
     (National POL panelists) were required to smoke and rate 4 
     experimental Alpine-like cigarettes (which delivered two 
     levels of nicotine at each of two levels of menthol) and an 
     Alpine control. The lower level of nicotine, for the 
     experimental cigarettes, was slightly lower than Alpine. The 
     lower level of menthol was comparable to that of Alpine.
       The results from the first run of this test have been 
     analyzed, but questions have been raised about the 
     reliability of the data. The study is to be replicated before 
     the report is finalized.
     IIIB/C1--(Dunn and Martin)--A field test of systematically 
         varied tar and RTD levels in which three methods of 
         cigarette presentation are compared
       This study has been in process since November of last year, 
     its execution being delayed by difficulties in fabricating 
     cigarettes with the required tar/RTD combinations. The proper 
     combinations have recently been achieved by Messrs Houck and 
     Claflin, and the test is awaiting its turn on the RP\3\ 
     panel.


                 studies in the preinvestigative phase:

       A Prefatory Note: It has been well established that one of 
     the differences between smokers and nonsmokers is that 
     smokers will tend as a group to display more aggressivity. 
     There have recently been some suggestions in the literature 
     that those individuals prone to aggression may have learned 
     that smoking facilitates the control of these tendencies; and 
     that it is for this reason that one finds a higher incidence 
     of aggression prone individuals within a smoking population 
     than within a nonsmoking population.
       If this interpretation is correct, then one would expect to 
     find that when the smoker is allowed to smoke freely, his 
     display of aggression in an aggression-inciting situation 
     will be at a level comparable to that of nonsmokers, but when 
     deprived of the opportunity to smoke for a period of time 
     before and during observation, his display of aggression will 
     be manifestly higher than that of nonsmokers.
       We recognize, however, that any observed increase in 
     aggressivity when deprived of cigarettes may be as readily 
     explained as the emergence of reactions to deprivation, not 
     unlike those to be observed upon withdrawal from any of a 
     number of habituating pharmacological agents.
       The Behavioral Research Laboratory is initiating a series 
     of studies on aggression in smokers. Collectively, the 
     studies will be aimed at (1) observing for differential 
     aggressivity under free-smoking vs. deprived smoking 
     conditions and (2) if increased aggression under deprivation 
     is observed, differentiating between personality-related 
     aggression and deprivation-induced aggression.
       Our strategy for distinguishing between the personality-
     related and deprivation-induced aggression is premised upon 
     the logic that if the aggression is personality related, then 
     it should be observable (1) among prospective smokers, and 
     (2) among abstaining smokers whose period of abstention has 
     extended beyond the withdrawal period.
       Study IB1 (Schori and Jones) is designed to induce 
     aggressivity in order to determine if, indeed, differential 
     aggressivity under free-smoking and deprived smoking 
     conditions is observable. Study IB2 (Dunn and Martin) is 
     designed to observe for aggressivity the abstaining smoker 
     whose abstention has extended beyond the period in which 
     deprivation-induced behaviors are likely to be present. Study 
     IB3 (Ryan and Lieser) is a longitudinal study attempt to 
     observe for personality-related or trait aggressivity in the 
     prospective smoker.
     IB1--(Schori an Jones)--Smoking and aggression
       This study is designed to evaluate the influence of smoking 
     condition on both aggression and performance in a complex 
     task situation at 3-levels of failure-induced frustration. 
     The task is a slightly modified version of the simulated 
     driving task that is being used in the ``Smoking and Risk-
     taking'' study.
     
[[Page H 7661]]

     IB2--(Dunn and Martin)--Bruxism suppressed by smoking
       Bruxism in medical cryptology, is but the habitual act of 
     grinding the teeth. In a recent experiment aimed at treating 
     the habit through the application of biofeedback principles, 
     an enterprising psychologist at Claremont Graduate School, 
     Dr. John Rugh, devised an unobtrusive, totable electronic 
     package which emitted an audible signal whenever the tension 
     in jaw muscles exceeded a preset threshold level. The package 
     embodied a sensor whose output voltage correlated with the 
     electrical activity of the muscles over which it was placed, 
     an IC amplifier and the auditory signal generator. Without 
     the device teeth grinding has been occurring at a 
     subconscious level. The buzzer brought the behavior to the 
     subject's attention, making it more accessible to voluntary 
     control. Daily use of the device proved effective in the 
     reduction of teeth grinding.
       Our interest in this investigation is two fold: The 
     relationship between jaw muscle contraction and psychological 
     tension has relevance to smoking dynamics. Hutchinson used 
     the measure of jaw muscle tension as an index of 
     psychological tension in a 1970 study funding by P.M. R&O. 
     The measure was more specifically interpreted by this 
     investigator as an index of covert aggressive responsivity. 
     Hutchinson put smokers into frustrating task situations and 
     recorded the EMG signals at the jaw. He reported less muscle 
     tension (ergo, less anger) under smoking than under 
     abstaining conditions.
       Secondly, it occurred to us that the total package may have 
     another application to our continuing study of the 
     motivational factors in cigarette smoking. It may make it 
     possible to circumvent a methodological problem over which we 
     have agonized for some time.
       The problem is this: In order to properly assess the 
     influence or cigarette smoking upon some specified behavior 
     one must observe that behavior in the same subject 
     undersmoking and nonsmoking conditions. If, for example, one 
     wished to determine whether smoking influences visual 
     accuracy, one would obtain measures of the subject's acuity 
     immediately following the smoking of a cigarette and at some 
     other time obtain the same measures following a period of 
     abstention from smoking, the period being sufficiently long 
     to clear the organism of the pharmacological effects of the 
     smoke. Any observed difference, one might argue, would be a 
     function of the effect of the smoke upon the smoker. But such 
     an argument assumes that the abstaining smoker is in his 
     normal, i.e., non-smoke-influenced state. This assumption is 
     open to challenge. The counter argument is that, if the 
     period of abstention is sufficiently long to allow for the 
     metabolic clearing of the agents taken in from cigarette 
     smoke, then that period has been sufficiently long also for 
     the onset of any deprivation effects.
       Our methodological problem lies in our inability to 
     distinguish between those behavioral changes that reflect 
     return to some non-smoke-influenced baseline on the one hand 
     and those changes which are the individual's response to 
     smoke deprivation on the other hand. Thus Hutchinson's 
     reported increase in jaw muscle tension in abstaining smokers 
     could as readily be the emergence of behavior which had been 
     suppressed by smoking or the onset of behavior specific to 
     the smoke-deprived state. We need some means of 
     distinguishing between these two possible classes of response 
     to cessation of smoking.
       We would expect behavior specific to smoke deprivation to 
     peak rapidly following cessation of smoking and diminish 
     gradually thereafter, dropping out entirely at some later 
     point in time as the former smoker's system accommodated to a 
     nonsmoking regimen.
       On the other hand, if the observed behavioral change is due 
     to the re-emergence of patterns suppressed by smoking, we 
     would expect the behavioral change to peak fairly rapidly 
     following discontinuations, as in the case of deprivation-
     specific behavior, but then plateau at peak and remain 
     constant.
       Here, then, are two distinctive time-related patterns. Were 
     we able to continuously monitor the behavior beginning a week 
     before ceasing to smoke and continuing for a month or more 
     thereafter, the data should allow us to confirm or refute the 
     Hutchinson observation that the jaw clenching rate is altered 
     by ceasing to smoke and further, if confirmed, classify the 
     altered rate as either withdrawal-specific behavior or 
     baseline behavior characteristic of the individual when not 
     smoking.
       If we were to establish that the behavior is characteristic 
     of the smoker when not smoking and not merely a transient 
     response to deprivation, the implications are profound. 
     Following Hutchinson's interpretation of jaw clenching as a 
     covert manifestation of anger, we would have in hand our 
     first clear-cut positive effect of cigarette smoking--the 
     inhibition of anger.
       If, on the other hand, the alteration were to prove to be 
     limited only to the time period immediately following 
     cessation, the implications would not be so profound but 
     there would remain the possibility of some important 
     inferences. The duration of the altered rate would reflect 
     the duration of the deprivation period. The determination of 
     the time interval would establish how long observations must 
     be delayed following ceasing to smoke in order to study the 
     uncontaminated non-smoke-influenced behaviors for comparisons 
     with smoke-influenced behaviors.
       The totable EMG unit lends itself nicely to the collection 
     of the data. After substituting an electronic counter for the 
     signal generator, we will be able to record either 
     continuously, or by periodic sampling, the frequency with 
     which jaw clenching occurs. A simple graphic plotting of jaw 
     clenching rate over time should make it possible to evaluate 
     the pattern of change and thus establish the nature of the 
     altered behavior.
       Our major problem will be to recruit enough regular smokers 
     willing and able to abstain from smoking over the five or 
     more weeks required.
       We are corresponding with two laboratories (in the 
     Psychology Departments of Harvard University and Claremount 
     Graduate School) on the details of instrumentation.
     IB3--(Ryan and Lieser)--The hyperactive child as prospective 
         smoker (see pp. 9-12, Accession No. 74-065)
       This is an intriguing theoretical derivation of an 
     hypothesis which predicts that today's hyperactive child is 
     tomorrow's smoker.
       A Final Note to the Series of Aggression Studies: We are 
     considering modest financial support to two university 
     laboratories whose programs include studies immediately 
     relevant to the question of the influence of smoking upon 
     aggression. Neal Miller's laboratory at Rockefeller 
     University is prepared to investigate further the nicotinic 
     mechanisms in the brain of the rat, there being already some 
     evidence that nicotine does reduce irritability and 
     aggression while its withdrawal has the opposite effect.
       At Ohio State University two psychologists are eager to 
     follow up leads pointing to the inhibitory influence of 
     central nicotinic systems on the aggressive behavior in cats.
     IB4--(Dunn and Martin)--The influence of smoke inhalation 
         upon accommodating to distracting stimulation, using the 
         control of brain wave patterns as an index of 
         accommodation
       A group of investigators at Melbourne University in 
     Australia have reported that smokers accommodate (or become 
     inured) to distracting stimulation more rapidly while smoking 
     than while deprived. Maintenance of alpha brain wave 
     dominance in the face of such stimulation was used as the 
     index of accommodation. When not accommodated, alpha 
     dominance was lost when distracting stimulation was 
     presented. When accommodated, alpha dominance was not 
     disrupted by the stimulation. The reported observation is 
     exciting because of its theoretical significance and because, 
     as reported, it was a very clean effect induced by smoking. 
     We are displeased with the lack of rigor in the design of 
     their experiment, so our purpose is to replicate the 
     experiment with better controls and improved conditions of 
     observation.
     IIIB4--(Schori and Jones)--Manipulating smoke impact in very 
         low (<8 mg tar) delivery cigarettes
       How can we achieve full-flavored very low delivery 
     cigarettes? We feel that the main hinderance to doing so is 
     our inability to achieve sufficient smoke impact in very low 
     delivery cigarettes. Therefore, although ultimately we would 
     like to develop a marketable one, this study (which is being 
     conducted in cooperation with Willie Houck and Paul Gauvin) 
     is designed to assess the relative influences of various 
     factors on smoke impact in very low delivery cigarettes. 
     Specifically, the relative influenced of blend (standard 
     Marlboro blend vs. 50% burley blend), burley-spray (100% vs. 
     50%), and filter system (cellulose acetate filter plus high 
     dilution vs. paper/cellulose acetate filter plus zero 
     dilution) on smoke impact in cigarettes within the 5 to 6 mg 
     tar range).
     IIIB5--(Schori and Jones)--A low delivery full-flavored 
         candidate (Opus I)
       In an earlier study (74-053, June, 1974), three low 
     delivery cigarettes, averaging less than 10 mg tar, were 
     found to be comparable in acceptability to the Marlboro 
     control. Because of the obvious practical significance of 
     that finding, we felt that it was necessary to follow up that 
     study in order to determine whether with our current 
     capabilities we can reliably make low delivery cigarettes 
     which are just as acceptable to the smoker as Marlboro. 
     Accordingly, we attempted to remake the most promising low 
     delivery candidate from the earlier study. That candidate is 
     to be compared to a Marlboro control by high delivery 
     RP3 smokers.
     IIIB6--(Schori and Jones)--A low delivery full-flavored 
         cigarette (Opus 2)
       In an earlier study (74-088 and IIIB3 above) a low delivery 
     cigarette which delivered 10.7 mg tar--with a nicotine to tar 
     ratio (N/T) of .12--was found to be comparable to a Marlboro 
     both in acceptability and strength, i.e., this cigarette was 
     perceived to be a full-flavored cigarette. We were not 
     positive however, that the high N/T ratio was the primary 
     determinant of the smokers' favorable perceptions of this 
     cigarette. Therefore in this study we will make three 10 mg 
     tar cigarettes with N/T ratios of .07, 110, and .13--insuring 
     that tar is constant over cigarettes--and a Marlboro control. 
     From this test, we will be able to determine: (1) whether we 
     can reliably make full-flavored cigarettes in the 10 mg tar 
     range; and (2) whether a relatively high N/T ratio is 
     essential in order to do so.
     
[[Page H 7662]]

     IIB2--(Dunn and Martin)--Continuation of the investigation of 
         inhalation patterns
       A number of questions have been raised by the initial 
     inhalation study. We plan to continue these observations in 
     order to determine what, if any, aspect of the inhalation 
     pattern is relatable to smoker characteristics and cigarette 
     characteristics.
       ``PME Research: 1972-1974'' Gustafson & Haisch
       * * * [Indicate deleted material]
       HUMAN SMOKING HABITS--(or: the impact of our products on 
     the smokers)
       The thoughts on cigarette design which we have developed so 
     far and which we are realizing in the trials of the Teams of 
     ``Thermodynamics of Adsorption Processes,'' ``Intersection of 
     smoke with Cysteine,'' and ``Product Research'' are our 
     response to developing trends and public pressures.
       Further input into this research is provided by the wants, 
     references and needs of the smoker. Under the direction of 
     Mr. Bourquin we have planned, executed and analyzed several 
     studies on human smoking habits.
       At the planning stage, the objectives and goals as well as 
     the scope and depth of the study were set by asking some 
     relevant questions. The answers to these questions are needed 
     to match consumer profiles and product relevance, to provide 
     information on certain aspects of ``Smoking and Health'', and 
     for future prototype development.
       How much nicotine does the smoker want?
       2. Does the smoker compensate for nicotine delivery in a 
     low nicotine cigarette?
       3. What are the actual delivery levels of important brands?
       4. Does nicotine delivery depend on the social situation of 
     the smoker?
       5. Do well defined classes of cigarettes fit well defined 
     classes of smokers?
       6. How can an increased smoke impact be achieved with a low 
     delivery product?
       The first study was executed with the cooperation of the 
     marketing department in Germany. The stumps of 27 major 
     brands were collected at various locations and offices. To 
     calculate filter efficiency and nicotine consumption the 
     nicotine deposit in the filter was measured. (The German 
     study must be regarded as incomplete as the pilot study was 
     never followed-up by a proper scale investigation.)
       The results and conclusions gave us possible solutions to 
     some marketing problems and set the limits for product 
     modifications.
       The most frequent nicotine yield was 0.4 to 0.5 mg of 
     nicotine per cigarette. This yield is not dependent upon the 
     nicotine content of the tobacco and is not related to the 
     nicotine yield under Coresta (machine) smoking conditions. 
     The difference between nicotine yields obtained under 
     standard laboratory procedures and yields obtained under 
     ``real'' smoking conditions is explained by the existence of 
     a compensation mechanism in the smoker. This compensation 
     mechanism seems to be in operation for a proportion of the 
     consumer population to adjust the nicotine yield to their 
     needs or liking.
       * * * [Indicate deleted material]
                [From Philip Morris, Richmond, Virginia]

     To: Dr. T.S. Osdene
     From: W.L. Dunn
     Subject: Quarterly Report--January 1-March 31, 1995
     Date: March 25, 1975

       Inhalation Studies.--All work has been held up for the 
     installation of the sound- and electromagnetically-insulated 
     room. The room has arrived and is to be in April.
       A Field Test of RTD and Tar Influences on Acceptability 
     with Three Methods of Cigarette Presentation.--Analysis is 
     underway.
       Conference on the Regulatory Influence of Nicotine on Human 
     Behavior.--Proposal has been presented to the industry. 
     Awaiting decision to proceed.


                          frank ryan's report

       Puffing Following Cigarette Deprivation (Puff Seven).--
     Ongoing. We are observing number of cigarettes smoked and 
     total puffs taken by college students smoking their own 
     brands during a critical two-hour period. Preliminary data 
     suggest that more cigarettes are smoked and more puffs taken 
     when the observations follow a two-hour deprivation period 
     than following two hours when smoking is permitted.
       Mixed Pack Study.--Ongoing.--A national mailout is 
     scheduled for early April in which High Filtration panelists 
     will compare a 10 mg cigarette to a mixture of 7 and 13 mg 
     cigarettes. The object of the test is to see whether the 
     intentional inclusion of some more flavorful cigarettes in a 
     pack of low delivery cigarettes will affect product ratings.
       Personality, Arousal and Smoking.--Planning.--Following 
     Eysenck's suggestion that smokers seek stimulation to 
     increase the arousal level of their central nervous system 
     whereas introverts avoid stimulation, we will look at the 
     effects of smoke deprivation on extroverted smokers in a 
     sensory stimulation deprived situation and compared to 
     nondeprived and nonsmoker groups, as well as to introverts.
       Equal Puff Volumes.--Planning.--In this smoke recorder 
     study smokes will be instructed to take either puffs of a 
     constant volume or constant duration. Cigarette 
     characteristics will be changed from time to time to see if 
     volume changes follow. The purpose of the study is to find 
     some of the cues which control puff volume changes.


                          tom schori's report

       The Effect of Smoking on Risk-taking in a Simulated Passing 
     Task.--Data analysis is complete. The report is in 
     preparation.
       Smoking, Arousal, and Mood.--A manuscript for publication 
     has been prepared.
       The Influence of Nicotine on Aggression in Fish.--This is a 
     new study in which the Beta, an innately aggressive fish, is 
     to be treated with varying concentrations of nicotine in tank 
     water. We will be observing for differential effects upon 
     aggressive display behavior and some control behavior which 
     is to serve as an index of general activity level.
       Menthol Cigarette Preference of Blacks.--Cigarettes with 
     two nicotine and two menthol levels have gone out to 350 
     Black RP \3\ menthol smokers. This is a modified form of the 
     original study, the results of which proved difficult to 
     interpret.
       Low Delivery Cigarettes: The Influence of Delivery 
     Information on Subjective Evaluations (II).--Cigarettes are 
     ready and should go out shortly to 2 National POL panels. 
     This is a follow-up on a smaller scale study (RP \3\) the 
     results of which suggested that smokers responded favorably 
     to being provided the information that the cigarettes were 
     low delivery.
       A Low Delivery Cigarette with Impact and Flavor.--The 5-6 
     mg tar delivery program being carried out in collaboration 
     with P. Gauvin is proceeding nicely. Models for the 8 
     experimental cigarettes have been developed and the 
     cigarettes are now being made.
                                 ______

                                                September 8, 1975.
     Prof. Stanley Schachter,
     Dept. of Psychology, Columbia University, Schermerhorn Hall, 
         New York, NY.
       Dear Stan: Welcome back and thanks for your letter. And 
     thanks for your solicitation of my critique of your 
     manuscripts. I'd be delighted. I wouldn't view it as an 
     imposition because, after all, I am responsible for the 
     Company having provided you with those modest sums and 
     therefore have vested interest as well as personal interest 
     in your output.
       As for your Marlboro question, we've tracked sales vs. 
     nicotine over the past five years and have concluded that 
     there is no discernible relationship. Interestingly, the 
     concern grew from an hypothesis antithetical to your own. 
     Market Research is burdened with attempting to explain a 
     slipping sales increment. The robust 15% annual increase 
     which we'd come to view as the norm became 10% from 1973 to 
     1974 and recent figures are of the order of 7%, if my memory 
     serves me well.
       Some have interpreted this as the inevitable leveling off. 
     Although we cannot fit any kind of explanatory equation using 
     nicotine as a predictor, we cannot of course rule out the 
     possibility that the Marlboro smoker is responding to 
     nicotine reduction by switching to other brands. But your 
     manner of putting the question implies that you would have 
     predicted a sales increase. You neglected to take into 
     account that the smoker has other options than merely 
     increasing the number smoked.
       My own prejudice is that the smoker is oblivious at the 
     conscious level to major changes in the composition of his 
     smoke, but not wholly unresponsive. I am more of the belief 
     that we have many ways in which to accommodate to a variable 
     smoke, and perhaps the least of these is to smoke more 
     cigarettes. For too long investigators have relied on 
     measures relatable to the cigarette (number of cigarettes, 
     number of puffs, butt length) as consumption rate indices. 
     True enough, the number smoked is an infallible index of 
     cigarette consumption, but we should be thinking more in 
     terms of cigarette consumption. Cumulated puff volume tells 
     us more, but even this is but a measure of smoke taken into 
     the mouth. The ultimate index is how much passes over into 
     the bloodstream, a not so readily monitored phenomenon. We're 
     now looking at the fate of the smoke entering the mouth; how 
     much goes down, how much comes back out, and related 
     behavioral events that we anticipate finding to be dose-
     regulating mechanisms of remarkable precision and 
     sensitivity.
       Thus to accommodate to the 15 percent reduction in 
     available Marlboro nicotine, the smoker who was getting 50 
     percent of the available nicotine over into his blood from 
     the Marlboro delivering 1.1 mg of nicotine into a smoking 
     machine now must get 59 percent of what the current Marlboro 
     offers him. He can take bigger puffs, or inhale more from the 
     supply drawn into the mouth (we have varying quantities of 
     residual smoke in the mouth at the end of an inhalation) or 
     for more efficient extraction of the goodies, he can draw it 
     in deeper or hold it longer.
       So we're looking at respiratory behaviors. I have a 
     physiological psychologist joining the staff this month. 
     Instrumentation is the big challenge at the moment.
       Send the manuscripts.
           Regards,
                                             William L. Dunn, Jr.,
                                              Principal Scientist.
                                 ______

     Charge Number: 1600
     Program Title: Smoker Psychology
     Project Leader: W.L. Dunn, Jr.
     Period Covered: January 1-31, 1976
     Date of Report: February 10, 1976

     Project Title: Smoke Inhalation Study
     Written by: Carolyn Levy
       Our new apparatus which allows the subject to puff on a 
     cigarette while his face is in the mask is almost 
     operational. We are remaking the rubber masks in order to 
     give the subjects better access to the mouthpiece.
       In order to determine if the delivery of a cigarette is 
     reduced by the new apparatus, two Marlboro monitors were 
     smoked through the apparatus on the twenty-port smoking 

[[Page H 7663]]
     machine. For comparison purposes, two monitors were also smoke through 
     the regular smoking profile recorder mouthpiece. The TPM 
     deliveries (17 puffs) were 38.2 and 38.4 mg. Thus, we get 
     comparable deliveries with the two different pieces of 
     apparatus. In addition, these deliveries are not appreciably 
     different from what would be expected from smoking the 
     monitors in the regular fashion on the smoking machine.
       Our next study will again use R&D smokers. Cigarettes 
     delivering 18, 15.7 and 13.3 mg of tar have been made, 
     holding puff counts and RTD's approximately constant.

     Project Title: Regulatory Identification Program
     Written by: Carolyn Levy
       We are ready to begin our first attempt to identify 
     nicotine regulators and non-regulators among our smoking 
     student population. In selecting our initial subjects we 
     hypothesized that those who smoke more than 30 cigarettes per 
     day of a high delivery brand (>15 mg tar) would more likely 
     to regular than those who smoked less than 10 cigarettes per 
     day of a comparable brand. Thus we have two groups: likely 
     regulators and likely non-regulators.
       In order to measure daily nicotine intakes, the subjects 
     will smoke at home and save butts for three weeks. During 
     Week 1 they will smoke their own brands. During Weeks 2 & 3 
     they will smoke high and low delivery products in a 
     counterbalanced order. The relevant dependent variables are 
     number smoked per day and the nicotine residual in the butts. 
     We expect that daily nicotine intakes will be more product-
     dependent for non-regulators and more product independent for 
     regulators.
       After this butt saving period, the smokers will come to the 
     lab for four sessions. Session 1 will be used to familiarize 
     the subjects with procedures and apparatus. During Sessions 
     2-4 we will measure their smoking behavior while smoking own 
     brand, high and low delivery products. In order to reduce the 
     number of variables that are free to vary in the smoking 
     situation, we will tell our subjects when they will smoke a 
     cigarette, how many puffs they may take, and where along the 
     rod these puffs will be taken. We want to find out if we can 
     ``force'' our potential regulators to modify their puff 
     volumes, inhalation volumes, and/or smoke retention times in 
     order to obtain their usual nicotine dose. On the other hand, 
     we do not expect the potential non-regulators to modify their 
     smoking behavior under these circumstances. When not smoking, 
     all subjects will be occupied with time filling tasks.
       This initial study will enable us to assess the relevance 
     of consumption data to regulation. That is, are heavy smokers 
     more likely to regulate than light smokers? In addition, we 
     would like to determine other factors that are correlated 
     with regulation so as to improve our ability to predict which 
     smokers will be regulators.

     Project Title: Smoking of Nicotine Free Cigarettes
     Written by: Carolyn Levy
       Due to a delay in equipment set-up, we have been unable to 
     obtain denicotinized tobacco. Hopefully we can begin this 
     study in one or two months.
       As an alternative to denicotinized tobacco, we have look 
     into the possibility of having cigarettes made from a strain 
     of tobacco that is naturally low in nicotine. Our comparison 
     cigarette would also be made of this tobacco with nicotine 
     citrate added to bring the nicotine content up to ``normal.'' 
     This tobacco should be available by the end of February.

     Project Title: Annual Monitoring of Cigarette Preferences
     Written by: F.J. Ryan
       As a preliminary test of our ballot and procedures, five 
     non-menthol cigarettes--delivering 8, 11, 14, 17, and 40 mg 
     of tar and .6, .7, .8, 1.0, and 1.2 mg nicotine--were sent to 
     300 RP \3\ panelists who rated them for acceptability. Usable 
     replies were received from 232 (77%) of the panel.
       A preliminary analysis of returns based on incomplete data 
     suggests that the differences in ratings were small, as seen 
     in Table 1, but illustrative.
       * * * [Insert notation for deleted material]
                                 ______

                   [From Philip Morris, New York, NY

     To: Mr. J.J. Morgan
     From: Al Udow
     Subject: Why People Start To Smoke
                                                Date: June 2, 1976
       At the end of last week I gave you some material intended 
     to answer Cliff Goldsmith's question on why people start to 
     smoke. Because we should have this information at our 
     disposal, this document summarizes the data available, and 
     cites references.
       There are surprisingly few hard facts on the question of 
     the initiation of smoking. Most of those who write on the 
     subject of smoking tend to rely on the statistical work of 
     Daniel Horn and the National Clearinghouse for Smoking and 
     Health. Others offer opinions without sources or data to back 
     them up.
       The best summary of the situation may be an entry by 
     Matarazzo. Joseph D. Matarazzo, of the University of Oregon 
     Medical School has written widely on smoking. He is the 
     primary author of the entry on smoking in The International 
     Encyclopedia of the Social Sciences (1968).
       His summary of the factors involved in the initiation of 
     smoking is as follows:
       These studies consistently have identified parental smoking 
     as one of the most important predisposing factors in smoking 
     among school-age children. As mentioned above, most smokers 
     appear to have begun smoking between the ages of 10 and 18. 
     If both parents smoke, the probability that their children 
     will begin to smoke is several times that of children with 
     nonsmoking parents. When only one parent smokes, the 
     incidence of smoking among the offspring falls midway between 
     that of the other two groups. Published data also suggest a 
     higher frequency of smoking among children with older 
     siblings who smoke.
       The relationship of some other sociopersonal factors to 
     initiation of the smoking habit is less clear-cut. In 
     general, the studies suggest that youngsters' beginning to 
     smoke is related to: (a) curiosity about smoking; (b) 
     conformity pressures among adolescents; (c) need for status 
     among peers, including self-perceived failure to achieve 
     peer-group status or satisfaction; (d) the need for self-
     assurance; and (e) striving for adult status (see the reviews 
     by Hochbaum 1964; Horn 1963). However, it is difficult to 
     measure the strength of such needs, as well as their relative 
     influence, and therefore these relationships should be 
     considered tentative.
       The basis for his, and many other statements is a 
     publication of the National Clearinghouse of Smoking and 
     Health (1972) which reported on two surveys of teenagers, 
     numbering 4931 and 1968 and 2640 in 1972. Their conclusions 
     are based largely on statistical inference.
       The report concludes:
       While there are many factors in the environment of the 
     child that influence his taking up, or not taking up, the 
     smoking habit, the one that has by far the most influence is 
     the smoking behavior of those around him . . .
       In households where both parents are present, the teenager 
     is much more likely to be smoker if the parents smoke. In 
     fact, if both parents smoke the teenager has about twice the 
     likelihood of being a smoker than if neither parent smokes, 
     the rates are 18.4%and 9.8% respectively. Those with one 
     parent who smokes fall in between, with a rate of 13.8%
       We find a striking relationship between the behavior of the 
     older members of the family and that of the younger members. 
     In homes where both parents are present, boys with an older 
     brother or sister are twice as likely to smoke if one or more 
     of the older siblings smoke than if none smoke (30.0% and 
     13.1%). The relationship is even stronger among girls, with a 
     four to one ratio; 24.8% of girls with one or more smoking 
     older siblings are smokers while only 5.6% of those with 
     older siblings, none of whom smoke, have taken up the habit.
       When the combined effect of smoking of parents and older 
     siblings is considered, the concept of family patterns is 
     reinforced. The lowest level of smoking is found among 
     teenagers who live in households where both parents are 
     present and neither smokes, and who have older siblings, none 
     of whom smoke. Less than one in twenty have become regular 
     smokers (4.2%). This compares with one in four (24.9%) in 
     families with at least one parent and one older sibling who 
     smoke. The older sibling, as would be expected, is more 
     likely to smoke if he has a parent who smokes. It is 
     impossible to determine precisely what are the relative 
     effects of parental and sibling smoking on the teenager. 
     However, we do see that he is more likely to smoke if the 
     older sibling smokes and the parent does not than if the 
     parent smokes and the older sibling does not. We cannot 
     discount the influence of either; they interact with each 
     other, and as they do, the family pattern is established.
       [Not legible]
       Harold S. Diehl, M.D. (1969), of the American Cancer 
     Society quotes liberally from David Horn of the National 
     Clearinghouse for Smoking and Health. Much of what he says is 
     stated authoritatively without source or supporting data.
       ``For children who see their parents, teachers, other 
     adults, and older brothers and sisters smoking, the desire to 
     be like them, to be grown-up, constitutes a strong incentive 
     to try it themselves. Studies show that children are much 
     more likely to smoke if their parents smoke.'' (No source 
     given)
       ``Many boys and girls start smoking to show their 
     independence, as a symbol of revolt against authority, to 
     feel sophisticated and grown-up, to be ``one of the crowd'', 
     to gain social status, to have something to do.'' (No source 
     given)
       ``The advertisers of cigarettes exploit this urge by 
     creating an image of a smoker as an outstanding athlete; a 
     handsome, virile outdoor man; nonchalant campus leader; a man 
     who succeeds; a sophisticated, charming young woman.'' (No 
     source given)
       ``For some smokers the motions and movements associated 
     with smoking seem to have a soothing, pleasurable effect, 
     similar to the chewing of tasteless objects such as pencils, 
     straws, or chewing gum after the flavor is gone. It also 
     seems that some of the satisfaction derived from smoking--
     particulary of pipes and cigars--is related to watching the 
     smoke. Few people enjoy smoking in the dark, and blind men 
     rarely smoke.
       For persons who are self-conscious and insecure smoking 
     provides an activity and something to do with their hands 
     that takes their minds off themselves. Many accept the image 
     created by cigarette advertisements of cigarette smoking as a 
     symbol of poise, self-confidence, and social success. But 
     once one 

[[Page H 7664]]
     becomes dependent upon cigarettes, habituation or addiction are 
     impelling drives to continue.'' (No source given)
       Dr. Daniel Horn, Director of the National Clearinghouse for 
     Smoking and Health, says that people smoke cigarettes for one 
     or more of the following reasons: (1) for stimulation, such 
     as to get started in the morning; (2) because of addiction; 
     this smoker ``must have'' a cigarette after a certain amount 
     of time has elapsed; (3) to reduce negative feelings, such as 
     distress, anger, or fear; (4) out of habit--a behavior 
     pattern followed almost involuntarily; (5) for oral 
     gratification--the satisfaction derived from something in the 
     mouth; and (6) for pleasurable relaxation--to enhance 
     positive feelings, such as after a good dinner.
       A paper by Meyer, Friedman and Lazarsfeld (1972) given 
     before the Conference on Motivation Mechanism of Cigarette 
     Smoking provides some qualitative insight into the initiation 
     of smoking which may be abstracted as follows:
       Many smokers, particularly ``white collar'' started in 
     rebellion against their parents. Another theme is that of 
     emulating friends and relatives. Peers provide especially 
     important role models to emulate and partners with whom to 
     rebel.
       The theory is offered that when youngsters of smokers start 
     to smoke, they are helping to deny that their parents are in 
     danger. Also, when offspring of smokers take up the practice 
     themselves, they are striking back at their parents' 
     hypocrisy, and at the same time, making a connection with 
     them.
       The Encyclopedia Americana (1969) says that the way smoking 
     begins is not fully understood and then attempts to explain 
     it:
       The beginning of smoking and the processes by which it 
     becomes a habit are complex and not fully understood. In 
     large part, the habit stems from psychological and social 
     drives; the individual smoker does what others around him do. 
     Physiological and possibly constitutional factors may play a 
     lesser role. There is little doubt that the physiological 
     effects strengthen the habit. Nicotine, one of the many 
     substances pharmacologically active in tobacco smoke, exerts 
     its effects on the heart and the nervous system in 
     particular. Smoking of one or two cigarettes causes an 
     increase in the heart rate and a slight rise in blood 
     pressure. The effect on the nervous system is predominantly 
     tranquilizing and relaxing.
       Relationships between smoking and a number of psychosocial 
     and economic variables are apparent, but no simple 
     explanation is evident. It is obvious, however, that smoking 
     as a behavior has become interwoven with the complex culture 
     and environment of modern society.
       Start of the Habit. The smoking pattern is established 
     relatively early. Before 12 years of age less than 5 percent 
     of boys and 1 percent of girls smoke, but soon thereafter a 
     steady increase begins. In the 12th grade, from 40 to 55 
     percent of children are smokers, and by the age of 25 years 
     about 60 percent of men and 36 percent of women have acquired 
     the habit. The increase in the percentage of smokers 
     continues into the fourth decade of life.
       Among the reasons why children take up the habit are their 
     desire for adult status and their need to conform to social 
     pressures exerted by other children. In striving for status 
     and self-assurance, children may imitate their parents or 
     famous people. The association between the smoking habits of 
     parents and children is strong and many-sided. More children 
     smoke in families where both parents smoke than in families 
     where neither parent smokes. In adolescent and adult life, 
     similar factors involving the individual's need and his 
     environment appear to play a role in the beginning of 
     smoking.
       Although no differences in intelligence between smoking and 
     nonsmoking children have been established, smokers are more 
     frequent among those who fall behind in scholastic 
     achievement.
       Personality and Other Factors. No clearly defined 
     ``smoker's personality'' has been established. Furthermore, 
     no personality characteristic is found exclusively in either 
     the smoker or the nonsmoker. Certain personality factors--
     among them extroversion, neuroticism, and increased 
     psychosomatic complaints--have been found to be slightly more 
     common in smokers.
       Stressful situations occurring in an environment favorable 
     to smoking may contribute to the starting of the smoking 
     habit, as well as to its continuation. For instance, some men 
     begin smoking in the tense days of their first job. Smokers 
     consistently report that they tend to smoke more when under 
     tension.
       Both more smokers and more early starters are found in the 
     unskilled working classes. White collar, professional, 
     managerial, and technical occupations contain fewer smokers 
     than craftsmen, sales persons, and laborers. Smokers are 
     reported to change jobs more often than nonsmokers. Another 
     socioeconomic factor, income does not seem to be as 
     consistently and positively related to prevalence of smoking 
     as to the quantity of cigarettes consumed. A relationship 
     does exist between smoking and educational level, but it 
     seems likely that this relationship is really based on 
     occupation, because those occupations associated with higher 
     education usually show a smaller prevalence of smokers.
       Social pressures undoubtedly delayed the acquisition of the 
     smoking habit by women. Increased cigarette consumption by 
     women began in the 1920's, and the rate rose rapidly during 
     and after World War II. Although the habit has been prevalent 
     among women for a shorter period, the percentage of women who 
     smoke has been increasing faster than the percentage of men 
     who smoke.
       Kozlowski and Harford (unpublished) cite a 1959 British 
     study by Bynner based on 5601 adolescent school boys in Great 
     Britain which concludes that the important influences that 
     lead to the initiation of smoking are: (1) number of friends 
     who smoke (2) anticipation of adulthood (3) parental 
     permissiveness toward smoking (4) whether or not deterred 
     from smoking by danger of lung cancer.
       The Yankelovich organization (1976) undertook a study for 
     the American Cancer Society by means of interviews with 826 
     teenagers and young women.
       Their conclusions about the teenage smoker suggest some 
     correlates (though not exactly reasons) of the beginning of 
     smoking. They say:
       The Profile of the Teen-age Girl Smoker: The profile of the 
     teen-age girl smoker counters the image of a socially ill-at-
     ease youngster turning to cigarettes as a means of being 
     thought of as more sophisticated or as a needed prop for 
     handling social situations. Instead, it is the teen-age girl 
     smoker who is at ease socially, very put together, and with 
     full confidence in herself. Parties and social gatherings are 
     her metier. One measure of both her sophistication and her 
     value structure is the fact that 31% have already had sexual 
     relations.
       It is instead the nonsmoker who tends to be quieter, far 
     less self-assured, more involved with athletics, school 
     activities and clubs--but more likely in her spare time to be 
     reading or watching television.
       Rebelliousness and Smoking: Cigarette smoking among teenage 
     girls, however, does appear to be highly identified with an 
     antiauthority rebellious syndrome. Among teen-age girls who 
     smoke 25% use marijuana regularly compared to 3% of the 
     nonsmokers; 81% of the smokers drink and 32% drink at times 
     to get drunk compared to 42% of the nonsmokers who drink or 
     4% who drink to get drunk. One out of four teenage girl 
     smokers have run away from home compared to 10% of the 
     nonsmokers. Despite the widespread acceptance of cigarettes, 
     and the acknowledgement of smoking by parents and school 
     authorities, the old ``wood shed'' image of cigarette smoking 
     lingers on--while the concept of not smoking of nonconformity 
     or rebellion against advertising, big business, society, has 
     not yet caught on.
       Teen-age Girl Smokers and Peer Relationships: Peer 
     relationships, long identified as a major factor in teen-age 
     smoking, continue to operate as a dominant influence. Teen-
     age smokers flock together and have more respect for the 
     opinions of their own peers than for authorities. There is, 
     however, an opposite side to the story as well. For the 
     current study indicates that all teen-age girl nonsmokers are 
     not homogeneous but rather divide into two almost equal 
     groups. It is easy to explain why over half of the nonsmokers 
     (55%) do not smoke--for they are not influenced by the new 
     values, but are very traditional in their views and outlook. 
     They are strongly religious and respectful of authority and 
     they shy away from their peers who smoke, use marijuana and 
     are part of the new values. The other group of nonsmoking 
     teenagers are very different for they share many of the same 
     values as the smokers--and are highly exposed to the total 
     smoking environment. We call them the ``Vulnerables'' for, on 
     the surface, they appear to be ready candidates for the next 
     wave of new smokers. One out of two of the ``Vulnerables'' 
     report that half or more of their male friends smoke; a third 
     indicate that most of the girl friends smoke. A majority have 
     one or more parents who smoke. They see more women smoking 
     now than in the past. Yet they do not smoke. Instead they 
     have found consciously or unconsciously, some strong barriers 
     to smoking. These are the importance of being in control of 
     one's own life; and emphasis on physical fitness and well-
     being; concern about the addictive nature of cigarettes, and 
     perhaps most of all, by becoming militant antismokers--people 
     who are angered by other smokers, upset by smoke filled rooms 
     and ready for increased regulation of smoking. In other 
     words, they are finding a cause--and a new peer 
     identification.
       Information on the motivation that leads to a continuation 
     of smoking comes from a special study done for Philip Morris 
     (Brand, 1971). Smokers first answered the question ``Why do 
     you smoke'' with platitudes such as:
       --gives me something to do with my hands
       --relieves tensions
       --goes well with a social drink
       --settles my stomach after a heavy meal
       --helps me to relax
       --just an automatic habit
       --keeps my weight down
       But on deeper probing, the circumstances in which smoking 
     occurs may be generalized as follows:
       1. As a narcotic, tranquilizer, or sedative. Smokers 
     regularly use cigarettes at times of stress.
       2. At the beginning or ending of a basic activity. This 
     would cover such activities as entering or leaving a room, 
     starting or finishing a job, going into a party or leaving 
     one, starting a telephone conversation or a personal visit.
       3. Automatic smoking behavior. Heavy smokers, particularly, 
     light up at intervals without much thought, and often without 
     realizing what they are doing.

[[Page H 7665]]

       It should be noted that there was scarcely any unprompted 
     reference to smoking for ``taste'', or ``flavor'', until it 
     was suggested--and then everyone agreed that it was the major 
     element in smoking satisfaction.
                                 ______

                [From Philip Morris, Richmond Virginia]

     To: Dr. T. S. Osdene
     From: W. L. Dunn
     Subject: Rationale for Investigating the Effects of Smoking 
         upon Electroencephalographic Phenomena
     Date: December 22, 1976
       The pharmacology of nicotine and tobacco smoking is very 
     complex (Larson et al., 1961; DiPalma, 1971; Goodman & 
     Gilman, 1970), Nicotine acts on the cardiovascular nervous 
     gastrointestinal and endocrine systems. Armitage, Hall, and 
     Morrison (1968) and Jarvik (1970) have provided evidence for 
     nicotine as the pharmacological basis of tobacco smoking. It 
     is obvious that we need much more research to unravel the 
     relative importance of the multiple actions of nicotine in 
     doses inhaled during tobacco smoking. In agreement with these 
     investigators, it is my basic premise that one of the many 
     reasons people smoke tobacco is that it contains nicotine. An 
     extension of that premise is that the doses of nicotine 
     inhaled produce definite, mild, and transient neuro-
     phychopharmacological effects which are positively 
     reinforcing and thus promote repetition of smoking. These 
     effects include: (a) modulation of conditioned behavior; (b) 
     mixed depression and facilitation of the neural substrates of 
     reward; (c) transient (in minutes) EEG and behavioral arousal 
     crudely reminiscent of d-amphetamine but pharmacologically 
     quite different; and at the same time (d) skeletal muscle 
     relaxation. Edward F. Domino, in Dunn (Ed.) Smoking Behavior: 
     Motives and Incentives, 1973.
       In addition to the four classes of 
     neuropsychopharmacological effects cited by Domino, there has 
     more recently been added a fifth class: modulation of 
     unconditioned, innate aggressivity. Philip Morris, one can 
     remark in passing, funded the research establishing this 
     fifth class (R. Hutchinson at Fort Custer State Home, 
     Michigan; G. Berntson at the Ohio State University; and 
     Robert Waldbilling at Rockefeller University).
       It is important to note that all of these effects are 
     attributed to the action of smoke components on the central 
     nervous system. It is also essential to know that it is the 
     consensus of investigators that the reinforcement of the 
     smoking act is the effect of smoke component action in the 
     central nervous system. It behooves us, therefore, to-seek an 
     ultimate, explanation of cigarette smoking among the 
     nicotine- or smoke component-related events of the central 
     nervous system.
       These effects can be studied in various ways. One way is to 
     observe the post-treatment behavior of both animals and 
     humans, such as we have been doing for some years with humans 
     in the Behavioral Research Laboratory. Another way is to 
     monitor treatment effects as they occur within the brain via 
     the monitoring of the electrical activity of the brain. Such 
     monitoring can be done in a passive, nonobtrusive manner by 
     means of the electroencephalograph. This instrument is 
     essentially an array of micro-sensitive sensors attached to a 
     multi-channel recording device. EEG technology, combined with 
     the analytic capabilities of the computer, now permits some 
     localization of signal source and the differentiation of 
     complex wave patterns into their simpler component elements. 
     The smoke effects of EEG patterns were reported as early as 
     1958 (Hauser, H., et al., EEG changes related to smoking. 
     Electroencephalography and Clinical Peurophysiology, 1958, 
     10, 576). Barbara Brown, in Dunn (Ed.) Smoking Behavior: 
     Motives and Incentives, 1973, reviewed this literature.
       The continually improving technology has recently led to 
     the isolation of an intriguing wave pattern which appears to 
     be the c.n.s. correlate of the psychological state of 
     anticipatory alertness. This is a vaguely defined concept 
     because of the difficulty of reducing it to operational 
     terms. Attempts have been made to more accurately delineate 
     the state by resorting to such terms as vigilance; arousal, 
     readiness to respond, etc., but it has remained an elusive, 
     though undeniably real variable in psychology. The 
     identification of an observable and quantifiable correlate of 
     this immensely important psychological factor is, indeed, a 
     welcome development. This EEG phenomenon has been labeled the 
     contingent negative variation (CNV). First observed by Walter 
     Grey in 1964, the CNV has been found to occur most intensely 
     in an expectancy situation (having been given an alerting 
     signal, ready to respond to execution signal).
       During the past two years Prof. John W. Thompson, and Dr. 
     Heather Ashton at the University of Newcastle Upon Tyne have 
     been observing the effects of smoking upon the CNV. At the 
     Zurich Conference in September 1976 they reported observable, 
     replicable changes in the CNV upon smoke inhalation and 
     nicotine injection (papers available in manuscript form). 
     They relate these changes to the subjectively reported 
     stimulating and relaxing effects of smoking, but with 
     speculative inferences. The association of smoking and CNV 
     patterning appears to be real, but further study is needed. 
     Judgmentally, however, the area has great potential for 
     yielding up observations related to why people smoke 
     cigarettes. The Research Center of B.A.T. in Southampton, 
     England, has already established an EEG laboratory to study 
     the relationship.
       EEG research is not usually considered to be the domain of 
     the psychologist. On the other hand, it is not the 
     proprietary domain of any existing discipline. Psychologists 
     are as prevalent, however, as any other specialists as users 
     of the instrument, as they have pursued their investigations 
     of sleep, dreaming, hypnosis, behavioral responses to 
     exogenous agents, psychopathology, intelligence, learning, 
     etc. It is inappropriate to think in terms of EEG research, 
     except in those not so frequent instances of pure research 
     into the nature of the phenomenon. More properly, 
     electroencephalography should be viewed as a technology for 
     monitoring otherwise unmonitorable events of direct 
     psychological significance. Since we have already 
     hypothesized a relationship between smoking and arousal (my 
     paper at the Zurich Conference), and since the CNV is 
     apparently the neural correlate of arousal, to initiate 
     studies which entail the monitoring of the CNV seems mandated 
     by our corporate and scientific responsibility.
       Accordingly, we have in our plans for 1977 the creation of 
     an EEG facility. The leading contender for the open position 
     in the Behavioral Research Laboratory is a man specialized in 
     the field, having already established two such units. He 
     estimates the cost to be $35,000, this including the required 
     dedicated computer. The required observation chamber with 
     Faraday cage is already in service.
                                 ______

     Charge Number: 1600
     Project Title: Smoker Psychology
     Period Covered: October 1-31, 1977
     Project Leader: W.L. Dunn, Jr.
     Date of Report: November 11, 1977

     Project Title: Psychophysiology of Smoking
     Written by: F.P. Gullotta
       Initial data gathering has been completed in the study on 
     the effects of cigarette smoking on heart rate. Statistical 
     analysis is now in progress. Additional data will be obtained 
     when the new experimental cigarettes which are being 
     manufactured for Dr. Levy are received.

     Project Title: Smoking and Learned Helplessness
     Written by: C.J. Levy
       Complete data have been collected on 41 subjects thus far. 
     We hope to finish data collection by February.

     Project Title: Smoking of Low Nicotine Cigarettes
     Written by: C.J. Levy
       We are still awaiting our new batch of cigarettes.

     Project Title: Habit and Need Cigarettes
     Written by: F.J. Ryan
       Although nicotine intake appears a critical mainstay of 
     tobacco consumption, not all people smoke for nicotine on all 
     occasions. Many of a smoker's cigarettes are undoubtedly 
     smoked to be sociable, to occupy his hands, to give him an 
     excuse to rest, or for some other nonnicotinic reason. Such 
     cigarettes are smoked not because of some internal cues 
     triggered by the nicotine level in the smoker's body but 
     because of the presence of external cues which have in the 
     past been associated with smoking.
       To the extent that these external cues tend to occur 
     regularly in the smoker's day, many of his cigarettes will be 
     smoked out of habit (i.e., will be conditioned responses 
     triggered by external cues) rather than out of any nicotine 
     need (i.e., will be conditioned responses triggered by 
     internal cues). All these cigarettes contribute to the total 
     nicotine in the system, so that a cigarette smoked out of 
     habit will delay the time until a cigarette is smoked out of 
     need.
       When a smoker switches from a high nicotine cigarette to a 
     low nicotine cigarette, or vice versa, it is the nicotine 
     input of these habit cigarettes which makes it impossible for 
     us to predict what changes in consumption will occur from our 
     knowledge of the deliveries of the two products. If many 
     cigarettes have been smoked out of habit, then the past 
     nicotine intake may have been higher than needed, so that 
     lowering delivery may still not lower it enough to cause 
     extra cigarettes to be smoked. Similarly, if nicotine 
     delivery is increased, because many cigarettes will continue 
     to be smoked out of habit, the increased nicotine will not 
     cause many fewer cigarettes to be smoked.
       It stands to reason, therefore, that two groups of 
     smokers--one which smokes many cigarettes out of habit and 
     few out of need and a second which smokes few out of habit 
     and many out of need--would respond differently to shifts in 
     nicotine delivery.
       To test the reasoning of this argument we are beginning a 
     two-part project. The first seeks to distinguish those 
     smokers who smoke many cigarettes from habit and few from 
     need from their opposites. The second part will switch the 
     two groups from high (or low) nicotine-cigarettes to low (or 
     high) nicotine cigarettes. The smokers who smoke mainly from 
     habit should show little or no compensation (titration), 
     whereas those smokers who smoke mainly from need should show 
     relatively more compensation.
       Groups will be identified by the regularity with which 
     critical stimulus situations elicit smoking--which means by 
     the extent to which they are ``habit'' smokers. Nonhabit 
     smokers will be assured to be ``need'' smokers.
       Regularity of behavior will be evaluated from a diary kept 
     by each smoker, showing the time of day when each cigarette 
     was 

[[Page H 7666]]
     smoked and the events taking place at the time. Nicotine intake will be 
     determined from butt residues.
       VCU students will serve as subjects, making regular visits 
     to our Franklin St. quarters to leave butts and pick up 
     cigarettes. We will seek as many smokers as possible, and 
     then try to use the extremes to make up the two groups.
                                 ______

     To: Dr. T.S. Osdene
     From: W.L. Dunn
     Subject: Behavioral Research Accomplishments--1977
     Date: December 19, 1977
     A Summary of 1977 Accomplishments
       Making reference to the Plans and Objectives for 1977 as 
     written December 1, 1976, we have succeeded some and failed 
     some; happily more of the former than the latter.
       Our successes: We have--
       (1) Acquired a third principal researcher.
       (2) Structured the group into three delineable programs 
     each headed by a principal investigator.
       (3) Established an EEG facility (to be fully instrumental 
     during the first quarter of 1978).
       (4) Moved aggressively into comparative behavior studies.
       (5) Nearly completed an extensive study of learned 
     helplessness.
       (6) Reported the first run of the Annual Monitoring 
     Program.
       (7) Done an analysis of quitting as a function of brand 
     last smoked.
       (8) Shown that we can distinguish between regulator and 
     nonregulator smokers and that after being deprived, the 
     regulators do indeed try to make up for lost intake.
       (9) Shown that acute, but not chronic, administration of 
     nicotine will alter an animal's behavior consistent with the 
     Berntson hypothesis that nicotine raises the pain threshold 
     in rats.
       (10) Gotten preliminary indications that we can use a 
     nicotine/saline discrimination task as a tool for studying 
     central nervous system mechanisms associated with smoking.
       (11) Acquired a consultant.
       (12) Completed a study of stimulus-seeking among introvert 
     vs. extravert smokers.
       (13) Completed a study of smoking effects upon learning 
     nonsense syllables.
       (14) Effected an arrangement with a university affiliated 
     hospital for injecting nicotine in humans for discrimination 
     studies.
       Our failures: We have not (1) Developed a workable 
     technique for unobtrusive monitoring of smoke inhalation 
     patterns. (2) Obtained satisfactory batches of low nicotine 
     and nicotine fortified cigarettes for a more definitive study 
     of smoke intake regulation. (3) Carried out investigation of 
     nicotine self-administration in rats. (4) Gotten completion 
     reports of funded work by Dr. Robert Weldbillig. (5) 
     Articulated the two-factor theory of smoking behavior.
     Behavioral Research Accomplishments in Detail
     Smoking and Learned Helplessness--Levy
       Hiroto and Seligman (1975) have reported that college 
     students who were subjected to inescapable loud noise or 
     unsolvable discrimination problems showed deficits in 
     performing subsequent tasks involving escape from loud noise 
     or anagram solution; they were helpless.
       Those experimental situations which are effective in 
     producing helplessness are frustrating and stressful. We 
     contend that smoking helps smokers cope with stressful 
     situations; such that smokers perform better in high arousal 
     situations than nonsmokers or deprived smokers. We therefore 
     have hypothesized that smokers will be affected less by a 
     situation devised to induce helplessness than nonsmokers or 
     deprived smokers.
       Before beginning data collection using smokers as well as 
     nonsmokers, we conducted a series of pilot studies using 
     approximately sixty nonsmokers. The purpose of the pilot 
     studies was to verify that we could induce helpless behavior 
     in our lab using local college students. As a result of the 
     pilot studies, we modified our procedures considerably. In 
     the final pilot study we had usable data on 23 subjects (12 
     males and 11 females). The results are summarized below:

------------------------------------------------------------------------
                                                           Treatment    
                  Decandent Measures                  ------------------
                                                       Helpless  Control
------------------------------------------------------------------------
X Latency to solution (sac.).........................     47.5   \1\ 28.
                                                                       9
X No. of failures to solve...........................      6.3   \1\ 4.1
X Trials to criterion................................     14.2   \1\ 10.
                                                                       0
------------------------------------------------------------------------
\1\ <.05, one tailed t test                                             

       Subjects in the helpless group took longer to solve the 
     anagrams, failed to solve more anagrams and ``caught on'' to 
     the pattern later in the task when compared to the control 
     subjects. Therefore, we were successful in producing a 
     helplessness effect in our lab.
       In March we began collecting data on smokers and nonsmokers 
     and now have complete data on 43 subjects. We anticipate 
     completing this study by February, 1978. One problem that has 
     slowed data collection considerably is our requirement that 
     subjects must score at least 115/150 on the Ammons & Ammons 
     Quick Test (a short IQ test). In our pilot work we determined 
     that this cutoff was necessary since subjects with poor 
     verbal skills find it difficult to solve the anagrams used in 
     this study.
     Smoke Inhalation Studies--Levy & Dunn
       During the past year we have been trying to devise a 
     technique by which we can unobtrusively monitor smoke 
     inhalation. Our initial attempt was to have Frank Watson's 
     group construct a piece of equipment modeled after one 
     described in a June, 1967, issue of Science. This apparatus 
     sensed changes in the antero/posterior diameters of the rib 
     cage and abdomen to estimate changes in lung volume. 
     Unfortunately design problems forced us to abandon this 
     approach.
       In cooperation with Dr. Farone, we explored the alternative 
     of using a mercury strain gauge to measure chest expansion 
     during smoke inhalation. We found that chest expansion 
     correlates quite well with volume of inhaled air (r=+0.95). 
     We can improve this correlation by adding in a correction 
     factor which takes the person's chest expansion just prior to 
     inhalation into account. A major shortcoming of the strain 
     gauge is its relative insensitivity.
       Having not found a workable technique for monitoring smoke 
     inhalation patterns unobtrusively, we called in Dr. Eli 
     Fromm, a bioelectronics expert from Orexel University. Dr. 
     Fromm proposed using an impedance pneumograph, involving pot-
     holder-like woven silver electrodes placed in sub-axillary 
     positions on the chest. These electrodes are part of an 
     impedance sensing electronic circuit. Previous work by Fromm 
     and others had established that the volumetric changes 
     associated with respiration altered the thoracic impedance. 
     We have been unable to develop this technique to even an 
     evaluative stage, since the voltage change, although 
     discernible, has not been sufficiently distinguishable from 
     background noise.
       We continue to actively search for usable technology.
     Regulator Identification Program--Levy
       We have hypothesized that some people smoke for nicotine, 
     and that these people try to obtain a relatively constant 
     amount of nicotine from their cigarettes. On the other hand, 
     people who do not smoke for nicotine would not be expected to 
     regulate. We have been conducting studies to identify those 
     people who are nicotine regulators among our smoking student 
     population.
       In our most recent study we wanted to determine if 
     regulators and nonregulators would respond differently to 
     smoke deprivation. After smoking high and low delivery 
     cigarettes at home for two weeks, fifteen smokers came to our 
     lab on four separate occasions. Each subject smoked the high 
     and low delivery cigarettes under nondeprived and overnight 
     deprived conditions. Based upon ``at home'' smoking data, 11 
     of the smokers were determined to be regulators, while 4 were 
     nonregulators. When these subjects came to the lab and smoked 
     under more controlled conditions, we found that 9 of the 
     regulators obtained more nicotine from their cigarettes when 
     overnight deprived than when nondeprived. On the other hand, 
     only 1 of the 4 nonregulators responded to smoke deprivation 
     by obtaining more nicotine from their cigarettes. Thus it 
     appears that regulators and nonregulators do respond 
     differently to smoke deprivation.
     Smoking of Low Nicotine Cigarettes--Levy
       We have been trying to obtain cigarettes made from 
     denicotinized tobacco to use in a study which will look for 
     changes in people's smoking behavior when they're shifted to 
     a low nicotine cigarette, with tar delivery held constant. We 
     plan to use a nicotine fortified cigarette made from 
     denicotinized tobacco as our comparison cigarette. We have 
     had problems in getting the nicotine level of the nicotine 
     fortified cigarettes back up to normal.
       As part of this study we are trying to see if smokers can 
     easily discriminate the nicotine fortified cigarettes from 
     the low nicotine cigarettes. Forty-eight R&O smokers compared 
     two of these cigarettes, one delivering .40 mg nicotine and 
     the other .87 mg nicotine. Over all smokers no significant 
     differences were found between the two cigarettes. Only three 
     smokers were able to identify unequivocally the nicotine 
     fortified cigarette as producing more inhalation impact. We 
     concluded that there were no dramatic organoleptic 
     differences between these two cigarettes, even though the 
     nicotine fortified cigarette delivered twice as much 
     nicotine.
     Nicotine as a Mitagator of Stress--Levy
       During the past several months we have been looking at the 
     effects of nicotine on post-stress learning deficiencies in 
     rats. In one study using 24 rats we found that an injection 
     of nicotine (.2 mg/kg) five minutes prior to a shock 
     avoidance task in a shuttle box significantly increased the 
     rats' latencies (in seconds) to cross the barrier if they had 
     been stressed with a cold swim thirty minutes before. A 
     control condition, identical to the experimental condition 
     except for a warm rather than cold swim, produced no such 
     latency difference. These results are consistent with Gary 
     Berntson's finding that nicotine increases the pain threshold 
     in rats as measured by the tail flick test.
       In a second study we looked at the effect of chronic 
     nicotine treatment on rats' shuttle box performance following 
     cold swim stress. We had hypothesized that injecting rats 
     with nicotine hydrogen tartrate (.5 mg/kg) four times daily 
     for six weeks would enhance their ability to cope with 
     stress. In order to test this hypothesis we chronically 
     injected twenty-two rats with either nicotine or saline for 
     six weeks. On test day six rats from each injection condition 
     were stressed with a four-minute cold swim (2 deg.C) and five 
     from each injection condition were given a four-minute warm 
     swim (28 deg.C). Thirty minutes post-swim each rat was tested 
     in a shock avoidance task. Rats that were stressed with the 
     cold swim took significantly longer to cross the barrier in 
     the shuttle box than rats 

[[Page H 7667]]
     given the nonstressful warm swim. Rats chronically injected with 
     nicotine that were stressed with a cold swim did not perform 
     better than the saline injected cold swim rats. In addition, 
     the behavior of saline- and nicotine-injected warm swim rats 
     did not differ. Thus the latency effect produced by nicotine 
     under acute conditions was not produced under chronic 
     conditions.
     Nicotine Discrimination Learning by Rats--Levy
       During the past few months we have been exploring the 
     feasibility of using a nicotine-saline discrimination task as 
     a tool for studying the central nervous system effects of 
     nicotine. To date, seven rats have been trained to 
     discriminate a nicotine injection (.2 mg/kg) from an 
     injection of isotonic saline. These rats are currently being 
     tested with R-(+)=nicotine (.2mg/kg and 2 mg/kg) as the 
     bartrate salt to see if the central nervous system effects of 
     R-(+)-nicotine are similar to those of S-(-)-nicotine. Our 
     data suggest that R-(+)-nicotine at a dose of .2 mg/kg is 
     more like saline than S-(-)-nicotine. However, at a dose of 2 
     mg/kg the R-(+)-nicotine is similar to S-(-)-nicotine.
       Another group of eight rats is currently being trained to 
     discriminate nicotine (.4 mg/kg) from saline and will be 
     tested using tobacco alkaloids such as anabasine and 
     nornicotine.
     The Annual Monitoring Study--Ryan
       We completed first Annual Monitoring study, providing the 
     baseline data with which later Monitoring studies will be 
     compared. This research asked a large national panel (N-2711) 
     to rate five cigarette models for strength and acceptability. 
     The cigarettes tested had nominal deliveries of 5, 9, 16, 17, 
     and 21 mg FTC tar, with commensurate nicotine values.
       The 13 and 17 mg models had the highest acceptability 
     ratings, the 5 mg model had the lowest acceptability rating, 
     the 9 and 21 mg models being of near-equal, intermediate 
     acceptability. The strength ratings increased with delivery, 
     the 5 mg being rated weakest and the 21 mg rated strongest.
       Of greatest immediate interest was the observation that 
     relative acceptability was dependent on the delivery of the 
     smoker's own brand. Thus, the ultra-low delivery brand 
     smokers (Now and Carlton) gave high acceptability ratings to 
     the lowest test brand, with systematically declining ratings 
     to higher delivery brands; the Merit and Kent Golden Light 
     smokers gave their highest rating to the 9 mg model, with 
     systematically declining acceptability to the higher delivery 
     models, and the full flavor smokers top rated the 19 mg 
     model, with declining ratings to the lower delivery models.
       It is impossible to decide from this single test whether 
     smokers have assorted themselves into brand loyalties on the 
     basis of preexisting tastes (i.e.--people who like weak 
     cigarettes gravitate towards weak cigarettes by trying 
     available brands until they meet one that fits their taste, 
     while people who like full flavor sample until they end up 
     with a full flavor brand) or whether having been smokers of a 
     certain brand for some time for unspecified reasons they 
     consider other deliveries less acceptable to the extent that 
     they differ from their accustomed brand's delivery.
     Stimulus Seeking Among Smoker and Nonsmoker Introverts and 
         Extraverts--Ryan
       We completed study of stimulation-seeking behavior among 
     smoker and nonsmoker introverts and extraverts. The data 
     suggest that nonsmoker extraverts seek more stimulation than 
     nonsmoker introverts as Eysenck has suggested. It had been 
     hoped that smoke extraverts would respond differentially when 
     allowed to smoke and when smoke deprived, in that the effects 
     of nicotine in the system would cut down on the smoker's need 
     for external stimulation, but the differences were 
     inconsequential. Whether allowed to smoke or deprived of 
     smoke, the smoker extraverts sought about as much stimulation 
     as the nonsmoker extraverts.
     Smoking Effects Upon Learning Nonsense Syllables--Ryan
       We completed study of effects of smoking low nicotine and 
     moderate nicotine cigarettes on the learning of nonsense 
     syllables and words. The data fail to substantiate the 
     hypotheses that smokers would be worse than nonsmokers, or 
     that smoking moderate delivery cigarettes would retard rote 
     learning more than smoking low delivery cigarettes. The 
     observed smoke differences are best attributed to chance.
     A Theoretical Model of Cigarette Smoker Motivation--Ryan
       We developed theoretical position relating total daily 
     cigarette consumption to two types of stimuli: internal 
     stimuli caused by deficits or surfelts of nicotine (or some 
     unknown smoke components) and external stimuli which 
     habitually trigger or inhibit smoking regardless of internal 
     cues.
       The adoption of this point of view by members of the staff 
     will lead us to recognize that apparent failures of nicotine 
     compensation model may not in fact be failures at all, and 
     that nicotine compensation is a real phenomenon which is 
     masked by the fact that smokers smoke many cigarettes out of 
     habit rather than need. We began testing the theoretical 
     model to determine the extent to which situational cues 
     rather than nicotine need determine the smoking behavior of 
     college students. This study is in progress.
     Establishment of an Electroenceonalographic Laboratory--
         Gullotta
       The major objective this year has been to set up a 
     functioning psychophysiology laboratory. Setting up the 
     physical work space was relatively easy, since it merely 
     required the modification of the existing sound-attenuated 
     chamber.
       Selecting and acquiring the equipment is taking more time. 
     A Grass model 780, EEG machine, with eight EEG channels and 
     five polygraph channels was selected. This instrument will be 
     capable of monitoring many physiologic functions including 
     EEG, EMG, heart rate, respiration, temperature, etc. It is 
     scheduled to be delivered in mid-January 1978. Grass has 
     loaned us a machine for the interim. A research model 
     photostimulator has also been ordered from Grass. It will be 
     used in visual evoked response studies.
       A techtranix-5111-storage-oscilloscope and a-C-5A 
     ascilascope camera has been received. They will be used both 
     for general laboratory procedures and to provide graphics for 
     the computer system.
       A computer system has been decided upon and ordered. After 
     a great deal of investigation, thought and discussion, a Data 
     General Micro Nova system was selected. It will be interfaced 
     with the Level 6 and Sigma 9 systems and will provide the 
     capability for planned investigations.
       We have developed and obtained legal approval for an 
     informed consent form. This was necessary in order to bring 
     students into the laboratory for experiments involving 
     psychophysiological monitoring.
       Periodic trips to the EEG laboratory at MCV were undertaken 
     to gain experience in recording the EEG patterns in humans. 
     The staff at MCV has proven extremely cooperative and helpful 
     in this regard. It is also anticipated that this source will 
     be of potential use on future research projects.
       To date, over twenty EEG recordings have been performed on 
     approximately a dozen PM R&O employees as preliminary work.
     A Heart Rate Study--Gullotta
       This study was undertaken to assess the effects of two 
     experimental cigarettes on heart rate. The two cigarettes 
     were both denicotinized Marlboro-like blends, the 
     experimental version having had nicotine citrate sprayed on 
     before making. The control delivered approximately 0.3 mg and 
     the experimental 0.7 mg of nicotine. Tar content and RTO did 
     not vary.
       R&D employees were used as subjects. In the experiment, 
     they smoked the two experimental cigarettes and regular 
     Marlboros. In addition, controls consisting of puffing on an 
     unlit cigarette and not inhaling a lit cigarette were 
     employed.
       With 10 subjects, the heart rate changes were seen to be 
     positively related to available inspired nicotine; the 
     greatest increment occurred on smoking regular Marlboros, the 
     least change occurred under control (no smoke) conditions and 
     an intermediate change occurred with the 0.3 mg nicotine 
     cigarette. Results with the 0.7 mg nicotine experimental 
     cigarette were ambiguous. Additional data are being 
     collected.
     Exit Cigarette Brands--Ryan
       Available data based upon the exit brand (last brand 
     smoked) of people who have quit smoking (nonmenthol filter 
     cigarettes within a year prior to being polled, suggest that 
     the proportion of such quitters who smoked low delivery 
     brands is about twice as great as the market share of those 
     cigarettes would indicate.
       Our data do not enable us to determine whether this means 
     that low delivery cigarettes enable smokers to wean 
     themselves from nicotine, or whether it means only that 
     people who are concerned about their health (and so smoke low 
     delivery, ``safer'' cigarettes) are more likely to quit 
     smoking than are those who are not concerned about their 
     health. The study, rather than providing answers, prompts us 
     to ask more specific questions.
     Acquisition of a Behavioral Research Consultant
       Prof. Gary Berntson of Ohio State University has become 
     affiliated with our program as a consultant. Prof. Berntson's 
     own research program has been partially funded by PM R&O for 
     several years.
     Other Extra PM Work Promoted by PM R&O
       (A) Dr. Rosecrans at MCV--With protracted intervals between 
     steps, we reached the point in November of granting a nominal 
     sum of money to underwrite a study of human ability to 
     discriminate between nicotine and no-nicotine bodily states. 
     The delays have resulted from the reluctance of the MCV 
     Ethics Committee to approve the infection of nicotine in 
     human studies. The initial study will be of smoke inhalation 
     where control and experimental cigarettes are minimally 
     distinguishable organoleptically although differing in 
     nicotine deliveries.
       (B) Prof. Bernston at Ohio State--With supportive PM R&D 
     funding, this investigator has completed two studies in 1977. 
     He reported to the Annual Meeting of the Psychonomic Society 
     that nicotine (O. 16-0.50 mg/kg) greatly reduced pain 
     sensitivity to thermal stimulation in the rat as measured by 
     the tail-flick test and the hot-plate test. This finding and 
     preliminary findings of other studies suggest that nicotine 
     may selectively reduce visceral pain without reducing somatic 
     sensitivity.
       Prof. Bernston has obtained authorization by the Ohio State 
     University Ethics Committee to pursue this line of 
     investigation 

[[Page H 7668]]
     with humans, with implicit approval to inject nicotine. We are 
     requesting that he conduct the nicotine discrimination work 
     originally discussed with Rosecrans, in view of his 
     capability of injecting nicotine in humans.
       In a study with cats he found evidence that the basic 
     sensory sensitivity of the animals remained unaltered by 
     nicotine, as well as their motor responsivity, such that 
     previously reported changes in aggressivity induced by 
     nicotine now appear more clearly to be centrally mediated.
       (c) Or Kazlowski at Wesleyan-University--This investigator 
     reported completion of a study partially supported by PM R&D 
     funds (1976) in which he observed no changes in puffing 
     behavior as a function of experimentally induced changes in 
     buccal pH.
                                 ______

     To: Dr. T. S. Osdene
     From: J. I. Seeman
     Subject: Nicotine Program
     Date: March 15, 1978
       This summary and evaluation represent the cumulative 
     influences of a number of discussions with Carolyn Levy and 
     Ted Sanders and myself. However, these conclusions may not in 
     every respect correspond directly to the ideas of CL and TS.
       An effective nicotine program must include both peripheral 
     and CNS bioassays. The former are being preferred under 
     contract, and we must await the full reports before being 
     able to make conclusions either about the results or the 
     testing program itself. It is clear that CNS studies 
     represent the most complex, state-of-the-art concepts. 
     Ultimately, the isolation and characterization of the 
     nicotine CNS receptors are the major goal. Many steps must 
     come first. These include (1) pharmacological location of 
     sites of nicotinic action using both cannulae and various 
     tissue sections; measurement of electrochemical activity 
     following drug administration; (3) various techniques 
     including photoaffinity labeling and binding studies as aids 
     at receptor isolation (4) receptor identification and 
     characterization (against and antagonist activity).
       Currently, Abood has begun work involving a ``prostration 
     syndrome.'' He is initiating synthetic work aimed at 
     preparing suitable photoaffinity labels. Goldstein, at the 
     present, has not applied his ``bag of opiate tricks'' in the 
     nicotine area and is doing only T-maze behavioral studies. He 
     is unquestionably going to pursue the nicotine-receptor 
     question vigorously.
       Ultimately, we and others (perhaps we have not considered 
     in detail ``the others'' except for Abood and Goldstein) will 
     be successful in the ``steps.'' What can be requested at the 
     present in terms of ``outside help'' is clearly limited by 
     what is available.
       I believe that we should rely on C.L. for all behavorial 
     studies. This will undoubtedly require more rats and testing 
     equipment. However, the behavorial work is key to the testing 
     program.
       Binding studies with DeVries at MCV can be initiated. He is 
     currently interested in a variety of nicotine CNS receptors. 
     Metabolism work which Castagnoli would give use information 
     with respect to biological stability of any analogues.
       For the present, I cannot believe that ``we should cancel'' 
     any opportunities with Goldstein who is clearly by-far the 
     most sophisticated experimentalist and theoretician of the 
     outside investigators. I have some suggestions relative to 
     our initial response to his current request for materials.
       In summary, I believe that the key note in this memo is 
     that we must devise not a shopping list for todays needs but 
     a policy for the program as a whole.
                                 ______

     To: Dr. T. S. Osdene
     From: J. I. Seeman, C. J. Levy, and E. B. Sanders Nicotine 
         Program: Specific Implementations
     Date: March 31, 1978
       The memo of March 21, 1978 to you from us outlined in 
     detail the long-term nicotine program, including sections on 
     (a) receptor isolation, identification and characterization; 
     (b) pharmacokinetics; (c) CNS testing (behavorial aspects); 
     (d) peripheral bioassays; (e) synthetic organic chemistry; 
     (f) chemical property evaluations; and (g) smoking studies.
       The purpose of this memo is to specifically detail the 
     additional experiments needed in the immediate future, with 
     the assumption that projects already in progress will 
     continue at their present rate.
     A. CNS Behavorial Testing
       Nicotine discrimination, self-administration and tolerance 
     studies will enable us to examine the cueing and reinforcing 
     properties of nicotine and nicotine analogues in rats. These 
     are the state-of-the-art biossays for central nervous system 
     activity which we believe will serve as useful models of 
     human smoking behavior. Implementation will require an 
     additional 400-500 sq. ft. of laboratory space for animal 
     housing and testing facilities, one-half technician, one B.A. 
     professional, and $15,000-20,000 of capital expenditure for 
     housing and testing purposes.
                                 ______

     T. S. Osdene
     Nicotine Program: Specific Implementations
     March 31, 1978
     Page 2
     B. Molecular Basis of Nicotine Pharmacology
       We must begin to gain expertise in experimentation dealing 
     with nicotine receptor technology. Initial studies will 
     involve the determination of nicotine and nicotine analogue 
     binding with various biological membranes. Studies of this 
     type are currently being performed at a number of academic 
     institutions. For example, Prof. George DeVries has contacted 
     us suggesting a possible collaboration along these lines; he 
     will conduct the biological studies on our nicotine 
     analogues. In this particular case, no request for financial 
     support has been made. It is possible that other 
     collaborations may require such aid. We suggest initiating 
     these experiments on a modest scale through the aid of 
     outside collaborations. Should results be particularly 
     interesting and important, we can then consider in-house 
     experimentation.
     C. Nicotine Analogue Preparation and Chemical Evaluation
       This work involves the preparation of the analogues and 
     physical and chemical evaluation of their properties. 
     Significant continued reliance on the Analytical Division is 
     necessary, and in certain areas, increased responsibilities 
     by them will be necessary. A.B.S. professional is necessary 
     to serve as back-up to this work.
       Please note that surgical procedures will be required for 
     certain of the behavorial studies.
       It is important to reemphasize that better communications 
     with the peripheral bioassay evaluation group in Germany must 
     be established, and that shorter response time for our 
     questions and our bioassays is essential. Additional and/or 
     replacement bioassays must be required by this group.
       Finally a decision with regard to collaboration with Dr. 
     Abood is in order.
           Research and Development Five Year Plan--1979-1983

September 1978

                           *   *   *   *   *


     IV. Fundamental studies of the product and its users
       Fundamental research at R&D consists of long-range 
     investigations aimed at discovering basic scientific 
     principles about the nature of our product, its components 
     and its users. We seek essential knowledge which can be 
     applied to the practical problems of cigarette design.

------------------------------------------------------------------------
             Objectives                           Strategies            
------------------------------------------------------------------------
To extend our knowledge of nature    Continue to study the precursor/   
 of tobacco and smoke.                product relationships in tobacco  
                                      and smoke                         
                                     Analyze the chemical interactions  
                                      of smoke on physiological systems 
                                     Study the relationship of cigarette
                                      paper composition to smoke        
                                      delivery, principally carbon      
                                      monoxide and nitrogen oxides      
                                     Continue to study smoke flavor and 
                                      how to manipulate it to achieve   
                                      desired subjective response       
                                     Investigate tobacco characteristics
                                      that affect expandability         
                                     Refine analytical methods for      
                                      tobacco and smoke components,     
                                      using the most advanced           
                                      instrumentation possible          
To extend our knowledge of the       Evaluate changes in tobacco        
 nature of water in tobacco.          expandability and filling power as
                                      a function of moisture-absorbing  
                                      utility                           
To extend our knowledge of the       Refine models of cigarette         
 nature of combustion and pyrolysis.  combustion                        
                                     Apply cigarette combustion and     
                                      pyrolysis models to the design of 
                                      cigarettes                        
To control gas phase constituents..  Continue research on control of gas
                                      phase constituents including      
                                      carbon monoxide, nitrogen oxides, 
                                      hydrogen cyanide, and acrolein    
                                     Learn more about smoke aerosol and 
                                      how to manipulate it to improve   
                                      product quality                   
To identify the smoke components     Monitor changes in smoking behavior
 sustaining cigarette smoking and     as a function of changes in the   
 describe the motivational            composition of smoke              
 mechanism.                                                             
------------------------------------------------------------------------

       We will continue to coordinate multidisciplinary research 
     to determine the role of water in tobacco filling power. 
     Specifically, we hope to learn how to manipulate the water in 
     tobacco in order to change and control filling power. 
     Emphasis will be placed on water exchange processes which 
     occur in ordering, reordering and expansion. Information 
     developed from this program will be applied to improve the 
     economics of our manufacturing processes.
       In our program on cigarette pyrolysis and combustion, we 
     seek knowledge which will contribute to the design of 
     cigarettes with controlled delivery. We are investigating the 
     mechanics of how specific compounds are formed in smoke. 
     Experiments are being conducted in the kinetics of smoke 
     generation as a function of the physical and chemical 
     properties of the cigarette.
       We have recently intensified investigations of the physical 
     and chemical properties of smoke aerosol. This work is 
     relevant to filtering specific tar elements and modifying 
     subjective response to smoke. By altering filter geometry, we 
     have noted a change in subjective response without changing 
     tar delivery. We will continue to explore ways of changing 
     filter design and hence the pattern of mainstream smoke.
       Nicotine may be the physiologically active component of 
     smoke having the greatest consequence to the consumer. 
     Therefore, we are studying the differences in physiological 
     effects between nicotine and its analogues to determine the 
     mode of nicotine action. If acquired, this knowledge may lead 
     to a substance which will produce the known desirable 
     nicotine effects and greatly diminish any physiological 
     effects of no benefit to the consumer.
      Fundamental Studies of the Product and Its Users (continued)
                [From Philip Morris, Richmond, Virginia]

     To: Dr. T.S. Osdene
     From: W.L. Dunn

[[Page H 7669]]

     Subject: Plans and Objectives--1979
     Date: December 6, 1978
       All of the effort of the Behavioral Research Laboratory is 
     aimed at achieving this objective: To understand the 
     psychological reward the smoker gets from smoking, to 
     understand the physchophysiology underlying this reward, and 
     to relate this reward to the constituents in smoke.
       The rationale for the program rests on the premise that 
     such knowledge will strengthen Philip Morris R&D capability 
     in developing new and improved smoking products.
       In pursuit of this knowledge, three somewhat independent 
     lines of investigation are underway:
       1. The effects on nicotine and nicotine-like compounds upon 
     animal behavior.
       2. The effects of smoke and smoke constituents upon the 
     electrical activity in the human brain.
       3. The effects of changes in smoke composition upon puffing 
     behavior, inhalation behavior and descriptive statements by 
     the smoker.
     Animal Behavior Studies (Levy, Young and Rowsey)
       A major objective of the comparative research effort is to 
     develop behavioral tests which are sensitive to the effects 
     of nicotine and can be used to screen nicotine analogues for 
     central nervous system (CNS) activity. The studies which aim 
     to meet this objective as well as the objective of learning 
     more about the reinforcing properties of nicotine are 
     described below.
       1. Nicotine Discrimination. In this test rats are trained 
     to discriminate nicotine injections from saline injections 
     based upon the CNS effects of the injections. We have been 
     using this test to screen a variety of nicotine analogues and 
     plan to continue doing so during 1979. This test is important 
     because it allows us to determine if test compounds produce 
     cues (subjective effects?) similar to those of nicotine.
       2. Tail Flick. Nicotine has been shown to have analgesic 
     properties as measured by the tail flick test, and apparently 
     this effect is centrally mediated (Sakley and Berntson, 
     1977). We have completed some tests using this procedure and 
     will continue doing so in an effort to determine if it can be 
     used as a preliminary quick and objective screen for 
     analogues.
       3. Monitoring of Motor Activity. Stolerman, Fink and Jarvik 
     (1973) have reported that the depression of spontaneous 
     locomotor activity can be used to monitor the development of 
     tolerance to nicotine in rats. We plan to explore the 
     feasibility of using a similar test to screen analogues for 
     nicotinic activity and also to evaluate cross tolerance 
     between nicotine and nicotine analogues.
       4. Prostration Syndrome. A prostration syndrome in rats has 
     been described by Abood, Lowy, Tometsko and Booth (1978) 
     which appears to be mediated by central noncholinergic 
     nicotinic receptors. This simple behavioral response is 
     elicited by the intraventricular administration of 2-10 
     g of (-) nicotine bitartrate. We plan to implant 
     rats with cannulae in the lateral ventricles and then inject 
     a variety of nicotine analogues into the brain to determine 
     if they elicit the prostration syndrome.
       5. Nicotine Self-Administration. A few recent studies have 
     demonstrated that intravenous nicotine is reinforcing to rats 
     since they can be taught to self-administer it. (Hanson, 
     Ivester and Morton, 1977; Lang, Latiff, McQueen and Singer, 
     1977). We plan to replicate these studies to determine a) if 
     this behavior can be blocked by cholinergic antagonists, b) 
     if it is dose-responsive and c) if it will extinguish rapidly 
     when saline is substituted for nicotine. We feel that this 
     paradigm may be a useful animal model of human smoking 
     behavior.
       6. Rat EEG. If time permits, we plan to collect some 
     preliminary data in which the dependent variable will be the 
     rat's ongoing EEG activity. The purpose of this type of study 
     will be to a) compare the effects of nicotine on the rat and 
     the human brain and b) determine if we could use data of this 
     type to evaluate the nicotinic properties of nicotine 
     analogues.
      Electroencephalographic Studies (Gullotta and Spilman)
       The major objective of all of the studies to be conducted 
     in the neuropsychology laboratory is to understand the 
     interrelationships between cigarette smoking and the human 
     brain. In so doing, we hope to further elucidate how and why 
     people smoke. The studies outlined below are directed toward 
     achieving these goals.
       1. The Effects of Cigarette Smoking on the Early, Late and 
     After-Discharge Components of the Visually Evoked Response. 
     To date data accumulation is approximately eighty percent 
     completed. We should finish running subjects in January. 
     Statistical analysis of the results will be a lengthy 
     process, but it is anticipated that the analyses will be 
     completed by the end of the first quarter of 1979. A 
     completion report will be written at that time.
       2. A Search for Other Evoked Responses which are Sensitive 
     to Cigarette Smoking. We wish to identify a number of 
     dependent measures which change following cigarette smoking. 
     Evoked responses seem to be a fruitful area of research. The 
     precise nature of the research we will engage in will depend 
     on the results of the current VER study; however, three 
     avenues of investigation seem likely:
       A. Visually Evoked Responses from Association Cortex. We 
     are currently studying VERs recorded from the primary sensory 
     cortex. However, VERs may also be recorded from other areas 
     of the brain, including the ``association cortex.'' Evoked 
     responses recorded from association areas are particularly 
     sensitive to and modifiable by behavioral variables such as 
     attention, learning and cognition. Since cigarette smoking 
     has been suggested to influence these variables, association 
     VERs might provide important information about the neuronal 
     circuitry involved.
       B. The Auditory Evoked Response. The evoked response to 
     pure tones delivered to the auditory system is quite 
     sensitive to pharmacological intervention. Several studies on 
     the effects of cigarette smoking or nicotine administration 
     on the AER has been done, but the results are ambiguous. Some 
     researchers find no changes in AERs following smoking or 
     nicotine administration, whereas others report decreases. It 
     is important to know whether and how this measure is 
     influenced by cigarette smoking.
       C. The Somatosensory Evoked Response. Very little evidence 
     exists regarding the effects of cigarette smoking or nicotine 
     administration on the somatosensory evoked response to either 
     electrical or vibratory stimulation. This response, however, 
     seems to be very sensitive to many classes of pharmacologic 
     agents and behavioral states. It is possible, therefore, that 
     the SER might be a very responsive index of cigarette 
     smoking.
       3. The Effects of Cigarette Smoking on the 
     Electroencephalogram. Numerous studies have shown that both 
     cigarette smoking and nicotine administration result in EEG 
     activation, followed at various intervals, by EEG 
     synchronization. However, those studies employing cigarette 
     smoking as the independent variable have certain 
     methodological shortcomings which need to be rectified. We 
     propose replications of these studies using more appropriate 
     controls.
       4. Long-Term Smoke Deprivation and the Electrical Activity 
     of the Brain. In terms of the electrical activity of the 
     brain, there can be little doubt that smokers and nonsmokers 
     are very different. It is also true that the brains of 
     deprived smokers are quite different from the brains of both 
     nondeprived smokers and nonsmokers.
       Were the brains of smokers always different from 
     nonsmokers, or did the brains change in some fashion 
     following experience with tobacco? These are difficult 
     questions to answer. Yet, some insight into these questions 
     might be gained by a study which followed quitters over long 
     intervals. Such a study would necessarily be a long-term 
     longitudinal endeavor. We would need to solicit volunteers 
     who were intending to quit, accumulate prequitting baseline 
     CNS measures, then restudy these individuals periodically for 
     as long (within reason) as they remain quitters.
       5. A Comparison of Three Routes of Nicotine Administration 
     on Physiologic Function. We have discussed this study with 
     Dr. Arthur Ryan and he has agreed to lend us the medical 
     personnel necessary to carry out this study. In addition he 
     has agreed to be available for consultation as needed.
       In essence, this study involves a comparison of three 
     different methods of nicotine administration: inhalation, 
     ingestion, and intravenous injection. The dependent measures 
     would probably be the EEG, VER, heart-rate, blood pressure, 
     and blood nicotine levels. A small group (five or six) of 
     subjects will be used and will be brought into the laboratory 
     between six and eight times. Dependent variables will be 
     measured prior to and at several intervals, subsequent to 
     nicotine administration.
       This experiment should help answer several important 
     questions. For example, what is the relationship between 
     blood nicotine levels and CNS activity? How soon following a 
     given method of nicotine administration are effects seen in 
     the CNS, and for how long? How are the human studies 
     employing cigarette smoking similar to or different from 
     animal studies employing nicotine injection?
     Smoking Behavior Studies (Ryan and Eaust)
       The focused objective of this area of study is to relate 
     the intake of nicotine and its presence in the body to the 
     occurrence of other behaviors, including subsequent smoking 
     behavior.
       Question 1. To what extent is the presence of nicotine in 
     smoke detectable by smokers? To answer this question we need 
     to conduct two types of studies and make two types of 
     measurement. The study types will be (A) an absolute 
     threshold study, in which smokers will be given ``nicotine-
     free'' and very low nicotine cigarettes and asked whether 
     they contain nicotine. The subjects' ability to verbalize the 
     presence of nicotine is the first type of measurement. As a 
     second type of measurement we will look for a change in heart 
     rate (HR), which is customarily associated with nicotine 
     intake in most deprived smokers. It is possible that there 
     would be a physiological (HR) effect at a level different 
     from the level at which verbalization takes place.
       Study (B) will be a difference threshold study, in which we 
     try to find how small an increment (or a decrement) of 
     nicotine in smoke can be detected as an increase (or a 
     decrease) by the smoker. If the just noticeable difference 
     (JNO) is small, the nicotine delivery of cigarettes may be 
     expected to play a more important role in the evaluation of 
     cigarette acceptability than if the just noticeable 
     difference is large. Again we will 

[[Page H 7670]]
     make 2 types of measure--subject ratings that this cigarette has more 
     nicotine than that cigarette, and a monitoring of heart rate. 
     The heart rate changes should not be important in this case, 
     for the subjects will be getting nicotine from each 
     cigarette. However, we may see differential HR increases 
     while smoking the first of the two cigarettes being compared.
       Question 2. To what extent is the ability to detect the 
     presence of nicotine in smoke masked by other smoke 
     components? There are three ways to answer this question: One 
     is to present the nicotine without the smoke, a second is to 
     hold the nicotine delivery constant while varying the 
     quantitative amount of other smoke components (e.g. FTC tar), 
     and the third is to add qualitatively different smoke 
     components (e.g. menthol or anise flavoring). Since all three 
     approaches involve novel manipulations in the smoke (aerosol) 
     delivered to the smoker, we anticipate that the year's 
     efforts devoted to this question will be consumed in the 
     experimentation required to develop the cigarettes.
       Question 3. To what extent does the presence of detectably 
     more or detectably less nicotine in smoke affect the 
     acceptability of low delivery cigarettes? This question is 
     related to the optimal nicotine/tar ratio, a problem we have 
     addressed before at higher delivery levels. Implicit in the 
     second question was the assumption that nicotine's effect may 
     be different at different tar deliveries, for its 
     detectability is expected to be different depending upon the 
     masking effect of the tar borne flavors. Consider the 
     following table of 85 mm brands arranged by FTC tar delivery:

------------------------------------------------------------------------
                                                               Nicotine/
                Product                   Nicotine   FTC Tar      Tar   
------------------------------------------------------------------------
Carlton................................        .20        1.5       .125
Now....................................        .22        1.8       .122
True...................................        .44        4.8       .092
Decade.................................        .45        4.9       .092
L&M....................................        .64        7.4       .086
Tareyton Light.........................        .71        7.6       .093
(Kent) Golden Light....................        .71        7.7       .092
Spirit.................................        .90        8.0       .112
Merit*.................................        .66        8.3       .080
Viceroy Xtra Mild......................        .86        9.1       .095
Real...................................        .87        9.1       .096
Raleigh Lights.........................        .86        9.2       .093
Parliament*............................        .78        9.3       .084
Camel Light............................        .97       10.0       .097
Vantage................................        .87       10.7       .081
Marlboro Light*........................        .82       11.4       .072
Kent...................................       1.04       12.6       .083
Winston Light..........................       1.11       13.5       .082
Doral..................................       1.13       13.8       .082
L&M....................................       1.01       14.7       .069
Tareyton...............................       1.01       14.8       .068
Raleigh................................       1.02       15.6       .065
Lark...................................       1.26       17.4       .072
Marlboro*..............................       1.12       17.8       .063
Camel..................................       1.38       18.8       .073
Winston................................       1.41       19.6       .072
------------------------------------------------------------------------

       The table suggests that Philip Morris brands (asterisked) 
     have lower nicotine/tar ratios than do other brands with 
     about the same FTC tar delivery. Marlboro has the lowest 
     ratio on the list, Marlboro Lights has the lowest ratio among 
     brands delivering less than 14.0 mg tar, and Parliament has 
     the second lowest and Merit the lowest ratio among brands 
     delivering less than 10 mg tar. The table also suggests that 
     nicotine/tar ratios go up as tar goes down, and that our 
     competitors' brands such as Golden Light, Now and Spirit (in 
     test market) seem to be higher in nicotine delivery than we 
     would otherwise expect from our own experience with low 
     delivery cigarettes. The reason for the low PM ratios seems 
     to lie in tobacco processing procedures. The reason for the 
     high ratios at low tar may be that high efficiency filters 
     catch relatively more tar than nicotine when compared to low 
     efficiency filters, and that this effect is enhanced by air 
     dilution. We suspect that in some cigarettes the use of high 
     alkaloid blends may also be an important contribution to the 
     higher ratios.
       It appears therefore that the mechanics of cigarette 
     engineering and the deliberate decisions of our competitors 
     are such as to suggest that high nicotine/tar ratios be used 
     at ultra low tar levels. But traditionally our brands have 
     been successful with low ratios. Whether this will bear true 
     at a very low FTC tar delivery as it has been heretofore at 
     higher deliveries, we do not know. We have heard some people 
     suggest that low tar cigarettes may need nicotine supplements 
     to be rated acceptable. On the other hand, we have heard 
     others suggest that people who smoke low tar products want as 
     little tar and nicotine as they can get, which suggests that 
     a low nicotine/tar ratio might be preferred. Still others 
     feel that ratio size won't make any difference at all, that 
     ``all you have to do'' is get the smoker accustomed to a 
     cigarette and he'll come to call its characteristics his 
     preferred characteristics.
       To shed further light on this problem we will evaluate low 
     delivery experimental cigarettes in the 5-7 mg FTC tar range 
     but with nicotine levels which are discernibly higher than, 
     equal to, and lower than the typical level expected of 
     cigarettes in this range (which would be .53 mg). To 
     determine how much higher or lower we must go, we'll consult 
     the results of the JNO study and the absolute threshold 
     study.
       One of the reasons for conducting the JNO study now becomes 
     apparent, for it would make no sense to ask smokers whether 
     they preferred cigarette A or cigarette B if A and B could 
     not be told apart.
       Question 4. Tar delivery being the same, what are the 
     behavioral consequences of smoking low nicotine rather than 
     high nicotine cigarettes?
       This question will be answered by conducting a series of 
     shift studies using cigarettes of similar low tar but 
     differential nicotine deliveries. The low nicotine delivery 
     will ensure that total nicotine in the system remains at or 
     near the nicotine need threshold, thus maximizing the 
     proportion of the day's cigarette consumption which is smoked 
     out of need and minimizing the nicotine augmentation from 
     those cigarettes which are smoked out of habit.
       The results may shed light on the manner by which nicotine 
     control is achieved.
       Question 5. To what extent do ``mouthfeel'' factors affect 
     the taste and acceptability of cigarettes? We begin to answer 
     this broad question by asking a narrower one: To what extent 
     does salivation affect the taste of cigarettes?
       We ask the question because low tar triers often complain 
     that low tar products taste ``hot and dry.'' This may mean 
     that the smoke is in fact hot and dry, but it is more likely 
     to mean that the smoker's mouth is hot and dry--which 
     suggests that salivation could affect the sensation.
       We will investigate this by sampling the saliva quantity 
     present in the mouth during and after smoking cigarettes of 
     differential delivery. Both nonmethols and menthols will be 
     used as it is possible that menthol may affect salivation.
       If saliva flow is found to be relatable to delivery, then 
     we can investigate compounds which may counter the effect.
       Annual Monitoring Study. We have twice presented a large 
     national panel with five widely differing types of cigarettes 
     to be rated on acceptability, seeking to find whether low 
     delivery cigarettes are becoming more acceptable. So far the 
     evidence, based on the changes from 1977 to 1978, is slim. We 
     will repeat that test in the spring of 1979, examining 
     changes since '78 and since baseline data in '77.
       Diary Study. We will finish our first diary study during 
     January, '79. Only data analysis and final writing remains to 
     be done. It is possible that we will employ this technique 
     again, but with fewer subjects selected from a nonstudent 
     population.
     Inhalation Studies (Dunn)
       We have failed to find convincing evidence of regulation of 
     smoke intake when observing number of cigarettes smoked, 
     puffing patterns, etc. Nor have we found such evidence when 
     looking at inhalation measures in the laboratory. 
     Nevertheless there are compelling reasons to suspect that the 
     smoker does accommodate his smoking behavior to smoke 
     composition. We suspect that the regulation occurs in 
     inhalation patterns and that the regulation was obscured by 
     the laboratory conditions under which we made our earlier 
     observations. We did, in fact, establish that the smoker has 
     great latitude in altering intake at the inhalation level. 
     Inhalation is the final volitional act whereby the smoke is 
     transported from the mouth to the site where smoke 
     constituents cross the tissue barrier to enter the 
     bloodstream.
       Our working hypothesis remains that the smoker does alter 
     inhalation in response to cues of smoke composition and that 
     these alterations can be observed under natural smoking 
     conditions if recording procedures are made sufficiently 
     unobtrusive.
       Our objectives for 1979 are two-fold:
       1. To complete development of an electronic recording 
     device for continuous, unobtrusive monitoring of smoke 
     inhalation (collaborative with Electrical Engineering).
       2. To apply the recording device to the investigation of 
     smoke inhalation patterns and those variables which influence 
     them.
       We have established the following criteria to be satisfied 
     before the device is judged acceptable:
       1. Measures are demonstrated linear within operating range.
       2. Measures can be calibrated with spirometer.
       3. Baseline drift over 6 hr. period controlled or 
     compensated.
       4. Extraneous variables controlled.
       5. Monitoring can run continuously for 6 hours.
       6. Body movement error minimized and residual effect 
     randomized.
       7. Smoke laden inhalation peak is labeled.
       8. Obtrusiveness judgementally not distorting smoking 
     behavior.

       We will initiate the following sequence when the device 
     becomes available:
     Preliminary Exercises
       Procedural refinements and development of criteria for 
     subject's habituation to device.
     Study 1 (N=4)
       Establish Smoker's Inhalation Profile in terms of:
       1. Inhalation volume
       2. Retention time
       3. Depth (Volume/Vital Capacity)
       4.  daily inhalation volume
       5. Puff interval
       6. cigarette interval
     Study 2 (N=4)
       Investigation of state variables influencing profile 
     parameters:
       1. Heart rate
       2. Heart rate 
       3. Preceding cigarette interval (controlled and 
     uncontrolled)
     Study 3 (N=4)
       Inhalation profile changes as a function of smoke 
     composition changes:
       1. Nicotine varied--tar constant
       2. Tar varied--nicotine constant
     To: Dr. T.S. Osdene
     From: W.L. Dunn
     Subject: Plans and Objectives--1980
     Date: January 7, 1980

[[Page H 7671]]

       In our 1979 Plans and Objectives report we stated that 
     there were three somewhat independent lines of investigation 
     underway. These were:
       1. The Comparative Psychology Program--Studies of the 
     effects of nicotine and nicotine-like compounds upon animal 
     behavior.
       2. The Electroencephalography Program--Studies of the 
     effects of smoke and smoke-constituents upon the electrical 
     activity of the human brain.
       3. The Experimental Psychology Program--Studies of the 
     effects of changes in smoke composition upon puffing 
     behavior, inhalation behavior and the judgmental statements 
     of smokers reacting to those changes.
       These three programs are being continued through 1980.
       We are adding a fourth area of investigation this year:
       4. The Social Psychology Program--Studies of cigarette 
     smoking as a psychosocial phenomenon. Sandra Dunn, Ph.D., 
     Research Psychologist, will be responsible for this new 
     program.
       Our aim in this new program will be to contribute to the 
     understanding of how cigarette smoking and the social process 
     influence one another. We will be interested, for example, in 
     how social change effects changes in the behavior, attitudes 
     and self-perception of the smoker, and how, conversely, 
     cigarette smoking can have psychosocial consequences through 
     its manifest involvement in the social situation, and also 
     through its central-nervous-system-mediated effects upon the 
     coping abilities of the smoking social participant.
       Details of the three original lines of investigation 
     follow. It is premature to set down concrete plans for the 
     social psychology program. Our initial efforts in 1980 will 
     be to formulate those plans.
     I. The Comparative Psychology Program--Levy Replacement, 
         Carron and Allen
       The two major objectives of the comparative psychology 
     program are 1) to develop and use animal behavior tests to 
     screen nicotine analogues and 2) to learn more about the 
     reinforcing properties of nicotine. Studies designed to meet 
     these objectives are described below.
       Nicotine Discrimination
       In this test rats are trained to discriminate nicotine 
     injections from saline injections based upon the CNS effects 
     of the injections. We have been using this test to screen 
     nicotine analogues and plan to continue doing so during 1980 
     because it has proven to be an extremely sensitive and 
     reliable test.
       Tail Flick
       Nicotine has analgesic properties as measured by the tail 
     flick test (Sahley and Berntson, 1977). We have done 
     extensive testing of (-)- and (+)-nicotine using this test. 
     Unfortunately the data were highly variable due to the rats' 
     severe agitation after the nicotine injections. During 1980 
     we plan to administer nicotine and nicotine analogues 
     intraventricularly in an effort to obtain more reliable data.
       Prostration Syndrome
       A prostration syndrome in rats has been described by Abood 
     and his coworkers (1978). This response is elicited by rapid 
     intraventricular administration of 2-10 g of 
     nicotine. We have begun to routinely administer nicotine and 
     nicotine analogues intraventricularly and to rate the 
     resultant prostration. During 1980 we plan to continue using 
     this test to screen analogues. In addition we plan to begin 
     video taping the test sessions, and (in collaboration with F. 
     Gullotta) record from the dorsal hippocampus during testing.
       Place Preference
       Mucha and Van der Kooy (1979) have reported that a place 
     preference paradigm may be used to demonstrate the rewarding 
     properties of morphine. We plan to use a similar paradigm to 
     examine the rewarding effects of nicotine. Rats will be given 
     nicotine injections in one distinctive environment and saline 
     injections in another distinctive environment for several 
     days. Following this training procedure, the rats will be 
     given a choice between the two environments, and the time 
     they spend in each will be the dependent variable. If the 
     rats spend more time in the environment paired with the 
     nicotine injections, this will suggest that the nicotine was 
     reinforcing to them.
       Nicotine Self-Administration
       If the reinforcing properties of nicotine cannot be readily 
     demonstrated using the place preference paradigm described 
     above, we will try to get rats to self-administer nicotine 
     through indwelling intravenous catheters using a procedure 
     similar to that of Hanson and his coworkers (1977). If we are 
     successful if getting rats to self-inject nicotine, we plan 
     to determine a) if this behavior can be blocked by 
     cholinergic antagonists, b) if it is dose-responsive and c) 
     if it extinguishes when saline is substituted for nicotine.
     II. Electrophysiological Program--Gullotta and Frankovitch
       We hypothesize for this program that the smoking act is 
     perpetuated by the salutory effect of smoke inhalation upon 
     certain discrete as yet unspecified neural functions. We take 
     as a premise that the effect will be present and observable 
     in the EEG correlates of these neural functions. Our 
     objectives in all of the following proposed studies therefore 
     are to determine 1) if the effect is discernible in any of 
     the various monitorable EEG patterns and if so 2) whether 
     further knowledge of the nature of the effect can be inferred 
     from its EEG manifestation.
       Auditory Evoked Potentials and Cigarette Smoking
       This study was begun in late 1979 and should be competed 
     during the first quarter of 1980. It was initiated by reports 
     in the literature which suggest that both nicotine 
     administration and cigarette smoking may influence auditory 
     evoked responses.
       In a study using cats as subjects (Guha & Pradhan, 1976) it 
     was found that low doses of nicotine enhanced auditory EPs, 
     while high doses depressed them. In a study using humans as 
     subjects (Friedman, et al., 1974) it was found that cigarette 
     smoking tended to depress auditory EPs. It is extremely 
     important to further investigate the effects of cigarette 
     smoking on auditory EPs. If cigarette smoking does, in fact, 
     depress auditory EPs, this would imply that nicotine has 
     selective effects on the CNS (recall that several reports 
     have indicated that cigarette smoking enhances visual EPs).
       Cigarette Smoking and the Standard Electroencephalogram
       Numerous studies have shown that both cigarette smoking and 
     smoke deprivation affect the EEG. Cigarette smoking results 
     in EEG changes associated with arousal, while smoke 
     deprivation results in the high amplitude, low frequency 
     waves associated with drowsiness.
       The EEG studies that have been reported thus far generally 
     fail on one or two accounts. First, most studies have only 
     examined EEG changes occurring over very few cortical areas. 
     Second, the majority of these studies have used rather crude 
     data analysis techniques.
       As part of our ongoing program, we have placed electrodes 
     over central, posterior and temporal brain areas and have 
     recorded ongoing EEG activity. We are now in the process of 
     developing a spectral analysis program, which will allow us 
     to perform power spectral density analyses of ongoing EEG 
     data from a number of brain loci under varying conditions of 
     smoking and smoke deprivation.
       Central Gating and Cigarette Smoking
       Cigarette smoking appears to have opposite effects on 
     visual and auditory evoked potentials. While visual EPs are 
     enhanced by smoking, auditory EPs appear to be depressed. 
     First, nicotine, rather than being a general stimulant, may 
     be exerting a selective influence on brain structures. 
     Second, perhaps nicotine somehow participates in the gating 
     of information by the brain. This gating phenomenon was 
     eloquently demonstrated in 1959 by Hernandez-Peon and has 
     been often replicated. It could be that visual EPs are 
     enhanced at the expense of auditory EPs.
       It is possible that cigarette smoking (via nicotine) allows 
     for selective attention in the visual mode by damping input 
     from other sensory modes. We propose to investigate this 
     possible relationship by using cross-modal evoked potentials. 
     Visual and auditory EPs will be recorded in the same 
     experiment, while attention is varied by instructional set.
       Cigarette Smoking and Learning by the Brain
       A number of studies have shown that cigarette smoking may 
     facilitate certain types of learning. The mechanisms by which 
     this facilitation is accomplished remain to be clarified. The 
     following study may shed light on this problem.
       When a dim flash of light is presented to a subject, an 
     evoked response is recorded over specific visual projection 
     areas. No responses are recorded from the auditory cortex. 
     If, however, the dim flash of light is repeatedly paired with 
     a tone, an evoked response to the flash alone will gradually 
     develop at the auditory cortex. This type of learning is 
     called classical conditioning and it is the fundamental 
     building block of many ``higher'' forms of learning.
       We propose to study the effects of cigarette smoking on the 
     rate at which an EP develops at the auditory cortex to light 
     flash. If smoking accelerates the rate at which conditioning 
     occurs, these data would help explain why smoking facilitates 
     certain types of learning.
       Cigarette Smoking and Somatosensory Evoked Potentials
       We have two reasons for wanting to investigate the effects 
     of cigarette smoking on somatosensory evoked potentials. 
     First, we wish to find out whether smoking influences this 
     response. No literature currently exists on this topic. Any 
     data gathered would increase our understanding of how 
     cigarette smoking influences brain systems mediating 
     behavior. Second, and more importantly, we wish to 
     investigate the proposed analgesic properties of nicotine.
       Animal studies from our laboratory (Levy) and other 
     (Berntson) suggest that nicotine may have analgesic effects 
     on certain types of pain. Analgesics affect somatosensory EPs 
     in known ways. If cigarette smoking influences these EPs in a 
     similar fashion, this would be correlative evidence for 
     cigarette smoking possessing analgesic properties in humans.
     III. The Experimental Psychology Program--Ryan and Jones
       Objective 1: To gain better understanding of the role of 
     nicotine in smoking.
       First Approach: To further evaluate the smoker's ability to 
     detect nicotine differences among cigarettes.--The first 
     phase 

[[Page H 7672]]
     of this research was conducted in 1979, when we found that 9 of 10 
     smokers could detect nicotine differences (at 6 mg tar 
     levels) if nicotine deliveries differed by 50%. In the second 
     phase of this research we will extend the investigation to 
     cigarettes at the 12 and 17 mg tar levels. These cigarettes 
     have been ordered and should be made in January. We are 
     looking into the possibility of a third phase, in which 
     nicotine detectability is examined at near zero tar levels.
       Second Approach: Examine smoker preference for nicotine 
     delivery in very low tar cigarettes.--The first phase of this 
     project consists of having consumers rate the strength and 
     acceptability of 6 mg tar cigarettes with detectably 
     different nicotine contents above and below the levels found 
     in normal 6 mg models. Should it be possible to make ultra 
     low tar models with markedly different nicotine deliveries 
     (see above) then a second phase investigation will examine 
     acceptability and strength ratings for cigarettes with 
     detectably different nicotine deliveries at near zero tar. 
     (We understand that M.A.H. Russell is engaged in similar 
     research in England.)
       Third Approach: Examine the changes in body nicotine 
     content pre and post smoking.--Our theorizing on the role of 
     nicotine suggests that cigarettes will be smoked whenever 
     body nicotine content drops below a certain (unknown) level. 
     We can detect nicotine's presence in saliva, where its 
     concentration probably reflects its concentration in blood 
     and tissues.
       We are engaged in systematic investigation of the changes 
     in salivary nicotine content as a function of the time since 
     smoking and magnitude of intake. Our first goal is to find 
     the growth and decay curve of salivary nicotine 
     concentrations after different amounts of smoking. As a 
     second step, we will relate the salivary concentrations to 
     the concentration of nicotine in the blood. We have had 
     preliminary discussion of the latter problem with Dr. Arthur 
     Ryan, in our medical Department, and, depending on our 
     ability to identify the salivary growth and decay date, will 
     make a series of blood and saliva concentration measures 
     later in the year. The exact procedure is as yet undecided, 
     but the data will be gathered from a few volunteer subjects 
     under medical supervision.
       Assuming that salivary nicotine concentrations will reflect 
     blood nicotine concentrations, we can then proceed to a 
     fourth stage in the research, relating the easily obtained 
     salivary concentrations to the urge to smoke.
       Fourth Approach: Identification of two smoking population 
     subgroups, one of which has greater nicotine needs than the 
     other.--We have described these people in the past as 
     compensators and noncompensators, and attempted to define 
     them by their consumption changes when nicotine deliveries 
     were moderately shifted. However, we've had no great success 
     in the identification to date. Now we may have two extra 
     tools to use: commercial PM cigarettes of ultra low tar and 
     nicotine, and salivary nicotine concentrations. Others, 
     principally at Columbia University, have suggested that 
     shifts to ultra low nicotine cigarettes produce the same type 
     of psychological stress behaviors as quitting. We therefore 
     propose a shift study in which smokers are shifted to an 
     ultra low brand, and the key dependent variable becomes the 
     presence or absence of the withdrawal syndrome. Those who 
     show evidence of nicotine dependence and those who do not can 
     then be used to test our hypotheses on the relationship of 
     salivary concentration to smoking behavior.
       Objective 2: To better understand the mechanisms 
     controlling cigarette acceptability.
       First Approach: We will continue the Annual Monitoring of 
     Cigarette Acceptability for a fourth year. This will exhaust 
     our supply of available cigarettes at 5, 9, 13, 17, and 21 mg 
     tar. It would seem reasonable to change this project slightly 
     in 1981 by adding a 1 mg tar cigarette and dropping the 21 mg 
     model when the next batch of cigarettes is made.
       Second Approach: We have noted that some cigarettes produce 
     a greater saliva flow than other cigarettes. This may in part 
     be attributed to the role of nicotine and in part to PTO but 
     it appears also in part related to the presence of other 
     flavorings in the smoke (e.g. menthol). We intend to 
     investigate this phenomenon more systematically, examining 
     the effects of RTD, menthol, WS, etc.
     Inhalation Studies--Jones
       A method for monitoring respiration has been developed to 
     permit further research on the nicotine titration hypothesis. 
     The question has been asked: When given cigarettes with 
     differing nicotine deliveries, do smokers alter their smoking 
     behavior to regulate or ``titrate'' the amount of nicotine 
     taken up via inspiration of smoke? The Respitrace Calibrator 
     will be used to address this question, investigating whether 
     smokers alter inhalation patterns when smoking cigarettes 
     with differing nicotine deliveries.
       In a series of preliminary trials using 5 subjects, 
     respiratory transducer recordings have been shown to 
     correlate with spirometer readings on the order of .92+, 
     including readings taken up to five hours after calibration. 
     The relationship consistently has been identified as linear. 
     We have isolated several variables which influence the 
     accuracy of the measurements, and they are being controlled--
     positioning of the tunic on the abdomen and rib cage, posture 
     when taking the readings, slippage of the tunic, etc.
       Several other variables are currently under investigation.
       Plans for 1980 are as follows:
       1. Further procedural refinement of the present system. A 
     study of the sensitivity of the calibrator to gain values is 
     planned, as well as development of criteria for the subject's 
     habituation to the device.
       2. Procedural refinement for the mobile apparatus which is 
     on order for spring of 1980. These investigations will 
     parallel the work that has been done on the present system, 
     determining the accuracy of the recordings as compared with a 
     standard, identifying extraneous variables and working toward 
     their control, investigating baseline drift across a single 
     day and the variability between days.
       3. Application of the mobile Respitrace to research on the 
     nicotine titration hypothesis as detailed in Plans and 
     Objectives, 1979.
                                 ______

     Dr. T. S. Osdene
     M. C. Bourlas distributed to R. Seligman et al.--
     Analytical Research Division--1980 Plans and Objectives
     Date: January 16, 1980
       A summary of the major Plans and Objectives for the 
     Analytical Research Division is presented below. A more 
     detailed description may be found in the accompanying memos.
       The establishment of basic, fundamental research programs 
     and the continuation of these programs to the applied and 
     development stages will be a primary goal for the Analytical 
     Research Division. In addition and of equal importance will 
     be the continuation of providing technical service to the 
     Research and Development staff, the PM Leaf Department as 
     well as PM International whenever our services are required.
     I. NUCLEAR AND RADIOCHEMISTRY
       The Nuclear and Radiochemistry Group has been charged with 
     the responsibility for the use of radioisotopes and radiation 
     to study how cigarette smoke is formed and is transported out 
     of the cigarette. In order to accomplish this task, the group 
     will be investigating mechanisms of smoke formation by being 
     engaged in labelled precursor-product studies, labelled 
     tracer studies, neutron activation analyses and radiation 
     effects research. The group will continue to maintain the 
     Health Physics responsibility which includes environmental 
     monitoring of the natural radioisotopes. The preparation of 
     labelled tobacco via biosynthesis will also continue in order 
     to accomplish our isotopic studies.
       Distribution of effort--fundamental studies, 80 percent; 
     technical services 20.
     II. FOURIER TRANSFORM INFRARED EVOLVED GAS ANALYSIS (FT-IR-
         EGA) SYSTEM
       The study of smoke constituents generated during pyrolysis 
     or combustion is important if cigarette deliveries are to be 
     manipulated and controlled. These studies involve 
     establishing the conditions when smoke products form, the 
     rate at which they form, and the effects of secondary 
     factors, such as heating rate and oxygen content, on their 
     formation. For this purpose a FT-IR-EGA System has been 
     developed. The technique will be employed to examine gases 
     generated during tobacco decomposition.
       This computer controlled system permits the simultaneous 
     determination of major gas phase constituents and the effects 
     of tobacco processing, expansion and blending. The system 
     will be used to evaluate the denitration processes, effects 
     of oxygen on the thermal degradation of tobacco and, in 
     general, various physicochemical approaches to reduce gas 
     phase components.
Distribution of effort:                                         Percent
Fundamental Studies..................................................50
New Product Development..............................................25
Technical Services...................................................25
     III. TUNABLE DIODE LASER (TDL) SYSTEM
       While a clear picture of the thermal behavior of tobacco is 
     being obtained with the EGA System (above), the TDL System is 
     being developed to monitor both mainstream and sidestream gas 
     phase components under actual smoking conditions.
       The increased resolution and sensitivity of the TDL System 
     will permit us to investigate two major areas: 1. The first 
     involves monitoring certain gas phase components in 
     mainstream and, 2. The second is the profiling of gases 
     within a single puff.
       In the area of filtration and filter development, changes 
     in dilution as a function of puff number become important. 
     With the TDL system puff-by-puff profiles of many gas phase 
     constituents can be obtained for evaluation of the effect of 
     dilution on gas phase reduction.
       A clear understanding of dilution of filtration mechanisms 
     can be greatly facilitated by a detailed knowledge of the 
     rate of delivery of a smoke component within an individual 
     puff. Because of limited detector response time, the profile 
     within a single puff of smoke could not be investigated 
     utilizing conventional infrared instrumentation. Using 
     tunable diode lasers a method will be developed which will 
     allow puff-by-puff variations and the single puff profile of 
     gas phase constituents to be simultaneously recorded.
       Major gases which will be monitored included NH3, 
     acrolein, CO, NO, NO2 and HCN.
Distribution of Effort:                                         Percent
Fundamental Studies..................................................50
Cost Savings.........................................................20
New Product Development..............................................20
Technical Services...................................................10

[[Page H 7673]]

     77. PATTERN RECOGNITION ANALYSIS (PRA)/CHEMOMETRIC 
         CHARACTERIZATION OF TOBACCO
       The ability to recognize and measure differences in 
     competitor's cigarettes is essential in the design of our own 
     products and in maintaining a clear view of the changes in 
     the cigarette market. The approach taken to obtain the 
     required analytical information has been to develop the 
     necessary methodology to quantitatively measure individual 
     components of tobacco and smoke. This single parameter 
     approach (tar, nicotine, water, PG, RTD, etc.) has permitted 
     us to establish a significantly large data base for 
     comparison purposes. However, the complexity of tobacco 
     processing, changes in filter design, application of new 
     flavors, changes in cigarette dilution, and various 
     alterations made to the tobacco (expansion, denitration) have 
     required that approaches be established and employed to 
     characterize and differentiate between various tobaccos and 
     tobacco blends. Multi-variate data analysis in the form of 
     pattern recognition analysis (PRA) is a versatile tool for 
     extracting information from a well defined data base and is 
     in fact the approach which will be taken to classify 
     tobaccos.
       The long-range goal for PRA is to interrelate flavor 
     quality, that is, subjective responses, with analytical data. 
     In our attempts to achieve this goal, computer manipulation 
     techniques and sampling procedures are currently being tested 
     and refined.
Distribution of Effort:                                         Percent
Fundamental Studies..................................................20
Cost Savings.........................................................20
Methods Development..................................................40
Technical Services...................................................20
     V. NUCLEAR MAGNETIC RESONANCE (NMR) LABORATORY
       Conformational analysis of tobacco and smoke components and 
     those organic compounds which have either flavor or 
     biological implications will continue to occupy the bulk of 
     the activities in the nuclear magnetic resonance laboratory. 
     To this end, strategies have been designed and computer 
     programs written in order to extend the 13 C T1 
     analysis already completed for nicotine to other compounds. 
     This analysis will yield information regarding internal and 
     overall motion a well as conformational details. An extension 
     of these investigations will be to study a variety of menthol 
     derivatives to establish both the conformation and relative 
     configuration at asymmetric centers.
Distribution of Effort:                                         Percent
Fundamental Studies..................................................60
Technical Services...................................................40
     VI. MECHANISMS OF TOBACCO EXPANSION--CHARGE NO. 8204
       Project No. 8204 will concentrate its efforts on the 
     changes occurring in the non-water fraction of tobacco as a 
     function of expansion. Investigations to date have emphasized 
     the water fraction and its changes upon expansion, however, 
     this has not yielded the complete picture with regard to the 
     mechanism of expansion. Our involvement in this project will 
     be to coordinate efforts in four major areas--
       (A) Investigations into the interactions of salts and their 
     distribution within the tobacco cell wall with expansion. 
     Particular attention will be given to calcium. The method of 
     investigation will be the measurement of the rates of cation 
     extraction with various solvent systems using atomic 
     absorption techniques.
       (B) FT-IR evolved gas analysis of the various expanded 
     samples, to study the changes in specific tobacco components 
     upon expansion (i.e., sugars, cellulose, pectin, etc.).
       (C) EPR studies of the free radical content of expanded 
     samples to gain insight into the effects of heat and air on 
     the tobacco constituents.
       (D) SEM microstructural studies in order to access physical 
     cell wall damage as a function of the method of expansion.
       These investigations are in various stages of completion at 
     the present time and will be continued throughout 1980.
Distribution of effort:                                         Percent
Fundamental Studies..................................................70
Cost Savings.........................................................10
Methods Development..................................................20
     VII. ANALYTICAL RESEARCH NECESSITATED BY LOW TAR CIGARETTES
       A. Significance and Use of Gas Phase (OGPP) Data
       As our products aim toward lowered tar deliveries, gas 
     phase delivery assumes a role of greater importance. The 
     techniques employed in the chromatographic separation of 
     tobacco and smoke constituents and subsequent chemometric 
     characterization of tobacco have been shown to provide data 
     that his previously been inaccessible. This data will be 
     correlated with cigarette variables such as blend 
     composition, filter effectiveness, paper types and flavor 
     systems.
       B. Significance and Use of Profiling Whole Smoke by Gas 
           Chromatography
       The techniques developed for production of high resolution 
     gas chromatographic separation of gas phase components will 
     be applied to whole smoke, especially for the ultra-low tar 
     delivery models.
       C. Analytical Procedures Developed for Low Tar Cigarettes
       Efforts will be made to develop analytical procedures for 
     the evaluation of low tar cigarettes since the procedures now 
     in use were developed for cigarettes yielding relatively 
     gross amounts of tar. These new procedures will be directly 
     correlatable with the FTC tar number.
       An automated computerized technique towards this end is 
     being investigated using the 2-propanol extract of TPM needed 
     for the nicotine and water determination.
Distribution of Effort:                                         Percent
Fundamental Studies..................................................40
Methods Development..................................................40
Technical Services...................................................20
     VIII. SUPPORT EFFORTS
       A. Leaf
       Support in this area will be given as a cooperative 
     function with other divisions of R&D as well as areas outside 
     R&D. The changes in the chemistry of aging tobacco as well as 
     chemical changes caused by cultural practices and storage 
     variation will be monitored. In addition to established 
     analytical procedures, some methods development and/or 
     modification will be necessary.
       B. Manufacturing
       Support will continue to be given to Manufacturing to 
     assist them in problem areas involving tobacco processing. 
     Particular effort is anticipated in the area of tipping paper 
     problems. A great deal of effort will be expended to develop 
     an on-line optical porosity monitor which will be interfaced 
     with the existing laser perforator.
       C. International
       Support for International is expected to continue. This 
     requested support will be in the form of on-site education 
     and training in the operation of instrumentation as well as 
     troubleshooting. Significant in these areas is the automated 
     determination of TPM, H2O, nicotine and tar.
                                 ______

    Nuclear and Radiochemistry of Smoke--Plans and Objectives (1980)

     I. PRECURSOR-PRODUCT STUDIES
       These studies are divided into two broad areas--A. 
     Naturally occurring materials present in the finished 
     cigarette. Examples are the following: 1. What are the major 
     smoke products from tobacco polyphenols? 2. Is nicotine 
     transferred at the same rate from bright, burley, ET, stems, 
     etc.? 3. How much CO is formed from each ingredient in the 
     cigarette? Do the various tobaccos contribute their equal 
     shares to the CO? Does the calcium carbonate in the paper 
     contribute to the CO formed? How much do the sugars, 
     humectants, etc., contribute?
       B. Added materials and their contribution to smoke. These 
     are broken down into several areas.
       1. Flavor release compounds--Selected candidates will be 
     prepared, labelled and the contribution of each part of the 
     compound to smoke determined. This type of study must be 
     conducted for every new material added to our cigarettes in 
     order to insure that we know what is produced in the smoke 
     stream.
       2. Distillable flavors/additives--These materials must also 
     be studied to determine their contributions to smoke in order 
     to ascertain what products are derived from the precursors 
     added.
     II. LABELLED TRACER STUDIES
       This area will be divided into research and service A. 
     Service--In this area, efforts will be in the use of labelled 
     compounds to determine isolation schemes and recoveries from 
     ours and other projects' research studies. Examples are:
       1. The use of \14\C-NNN to determine recoveries and to 
     calculate absolute amounts delivered.
       2. The use of labelled rutin to establish recoveries (if 
     any) from smoke.
       3. The use of neutron activation analysis (NAA) to 
     determine Br and C1 levels in submitted samples.
       B. Research 1. Labelled materials will be selectively 
     placed within the cigarette at known locations, and these 
     used to determine smoke formation mechanisms, dilutions and 
     deliveries. 2. Neutron Activation Analysis will be used to 
     follow the fate of the inorganics during smoke formation, 
     i.e., how are the inorganics transferred into smoke, and how 
     do they affect smoke formation?
     III. SMOKE FORMATION AND COMPOSITION STUDIES
       A. Smoke Aerosol Studies--It has already been demonstrated 
     that the chemical composition of MS nonvolatile smoke is 
     different for different smoke particle sizes. This has 
     important considerations in giving the smoker maximum impact. 
     If the desired flavors can be enriched into those particle 
     sizes which have maximum lung retention (or mouth retention 
     if desired), overall concentration in the total smoke can be 
     kept to a minimum. The data will allow us to accurately state 
     just how much of each smoke component in each particle size 
     range comes from each labelled cigarette constituent.
       B. Use basic smoke formation knowledge to regulate the 
     delivery of selected smoke constituents. Examples are 1. The 
     use of selected flavor components on the cigarette periphery 
     to give ``enriched'' TPM in the MS. 2. The use of solid 
     center tobacco cores to ``block'' the formation and transfer 
     of CO to the MS smoke.
     IV. ENVIRONMENTAL RADIOLOGICAL MONITORING
       A. Monitor all naturally occurring radioisotopes in our 
     tobaccos and finished cigarettes. These data will be used to 
     monitor any increase in naturally occurring materials in our 
     future tobaccos due to environmental factors similar to Three 
     Mile Island.
       B. Conduct all defensive studies regarding naturally 
     occurring isotopes, i.e., the 210Pb-210Po problems 
     of the past, etc.
     
[[Page H 7674]]

     V. GREENHOUSE FACILITY
       The greenhouse facility will provide support in the 
     following areas:
       A. Establish the techniques and produce labelled plant 
     materials which will provide the major source for all of the 
     labelled smoke studies at R&D.
       B. Provide fresh green tobacco plant materials to all 
     Research & Development projects and other PM departments, as 
     requested.
       C. Provide a liaison with R&D , the Leaf Department, 
     Tobacco Industry Committees, commercial companies, Federal 
     and State Agricultural Research agencies, and growers, on a 
     cooperative basis, to test and evaluate any necessary 
     materials and/or tobacco deemed in the best interest of the 
     company.
       D. The preparation of all experimental labelled cigarettes 
     in support of all ongoing research studies utilizing Carbon-
     14 and Nitrogen-15.
     VI. MASS SPECTROMETRY LABORATORY
       The existing mass spectrometers will be utilized in support 
     of both ongoing and planned Research programs. These programs 
     include the MC Materials Evaluation Program, the synthesis of 
     tobacco flavorants and the evolved gas analysis program which 
     entails the determination of the gases evolved from thermally 
     degraded tobacco. Particular emphasis will be placed using 
     mass spectrometry in tobacco product/precursor studies and 
     especially the nitrogen containing components.
       Since the present hardware and software are nearly fully 
     extended, the primary activities over the coming year will be 
     in the area of system investigations. Continuing studies 
     include the denitration, and expansion processes, cellulase 
     treatment, and baseline studies on individual tobacco 
     constituents. The baseline data will also be used in 
     correlation studies on the effects of physical factors 
     (heating rate, flow rate, etc.) on constituent 
     decompositions. Other planned investigations include the 
     effect of genotype and fertilizer application on ammonia and 
     other nitrogenous materials in burley tobacco. Also, the 
     correlation between formic acid evolution and molecular 
     weight of cellulose will be explored further.
                                 ______

                  Spectroscopy/Chromatography Section

       I. Tobacco and Filler
       A. Tobacco Expansion
       OBJECTIVE: Develop data base designed for defining tobacco 
     expansion as functions of physical and chemical parameters
       ACTIVITIES:
       (1) Investigate salts' interactions and their distribution 
     within the tobacco cell wall using atomic absorption
       (2) Study changes in tobacco components using FT-IR and 
     Evolved Gas Analysis
       (3) Coordinate efforts of Charge No. 8204
       B. Blend Composition
       OBJECTIVE: Quantitative discrimination of cigarette blend 
     components
       ACTIVITIES:
       (1) Investigate and determine optimum methods for sample 
     preparation and analysis by (GC) \2\
       (2) Establish degree of difference of total blend 
     components
       (3) Apply chemometric techniques
       II. Smoke
       A. Chromatographic/Chemometric Characterization
       OBJECTIVE: Application of chemometric techniques in 
     extraction of information from smoke analyses
       ACTIVITIES:
       (1) Develop procedures for profiling wholesmoke
       (2) Investigate use of mass spectral data as a ``third 
     dimension'' in GC smoke profiling
       (3) Apply ARTHUR to profiled data for correlation with 
     sensory evaluations.
       B. Tunable Diode Laser (TDL)
       OBJECTIVE: Application of TDL to understanding of 
     parameters affecting smoke component formation and delivery
       ACTIVITIES:
       (1) Determine mechanism of incorporation of water oxygen 
     atoms in nitric oxide
       (2) Quantitate NH3, NO2, NO, and acrolein in 
     whole smoke
       (3) Develop programs for on-line dedicated computer 
     processing of TDL data
       (4) Construct single puff profile (within puff) monitors 
     for CO
       (5) Develop infrared laser monitor for routine puff-by-puff 
     quantitation of NH3
       III. Other
       A. Optical Porosity Monitor
       OBJECTIVE: Provide accurate on-line measurement of porosity 
     of laser perforated tipping paper
       ACTIVITIES:
       (1) Design and build prototype laser monitors for optically 
     measuring porosity of tipping paper
       (3) Develop system for tracking perforations as to 
     positioning of holes.
       B. Automation
       OBJECTIVE: Increase accuracy and capacity for routine GC 
     analyses
       ACTIVITY: Apply automaton to routine GC analyses with 
     dedicated or time-shared on-line data collection and report 
     generation
       C. Flavor Release Compounds--NMR Studies
       OBJECTIVE: Increased understanding of the synthesis and 
     reactions of potential flavor release compounds (in 
     collaboration with Yoram Houminer)'
       ACTIVITIES:
       (1) Determine stability of methyl pyrazine anions through 
     NMR studies of deuterium exchange kinetics of methyl protons
       (2) Examine the conformation of pyrazine ethanols by 
     coupling constant analysis and by studying the effects of 
     various substituents on proton chemical shifts
       (3) Assign 13C and 1H spectra of alkyl pyrazines 
     using coupling constant measurements and lanthanide shift 
     reagents
       D. Conformation of and Kinetics of Internal Rotation in 2, 
     4-dimethyl Nicotine
       OBJECTIVE: Understanding the energetic factors which 
     determine the solution conformation of tobacco alkaloids
       ACTIVITY: Measure the rotational barriers on 2, 4-dimethyl 
     nicotine by 13C NMR lineshape analysis; analyze 
     conformation from coupling constants and Nuclear Overhauser 
     effects
                                 ______

                         Special Investigations

       The following is a list of plans and capital 
     instrumentation needed by the above section in 1980.
       I. Tobacco and Filler
       A. Complete Development of HPLC Determination of Solonesol 
     in Tobacco and/or Smoke
       OBJECTIVE: To assist the flavor transfer group in their 
     evaluation of the lipid portion of the blend for flavor 
     characteristics.
       Project Chiefly Concerned--2306
       B. HPLC Study on Turkish Tobacco
       OBJECTIVE: To do a cumulative collection of selected HPLC 
     peaks from Turkish tobacco extracts for reconstitution into 
     cigarettes. The cigarettes will be subjectively evaluated and 
     the peaks of interest will be identified. This will be a 
     cooperative effort with development.
       Project Chiefly Concerned--2306
       C. Liquid CO2 Extraction of Tobacco
       OBJECTIVE: To investigate the utility of the apparatus for 
     analytical extractions, particularly for the lipid portion of 
     tobacco. To do HPLC on the extracted material and compare it 
     with other extraction techniques.
       Projects Chiefly Concerned--1901, 1503, 8401, 2306
       D. Amino Acid Analysis
       OBJECTIVE: To determine individual amino acids and peptides 
     on samples of green leaf, cured leaf, expressed juices and 
     protein hydrolysates. The Dionix amino acid analyzer will be 
     used to replace the long tedious gas chromatographic 
     procedure.
       Projects Chiefly Concerned--8205, 1503, 1901
                                 ______

       E. Organic Acids in Tobacco by HPLC
       OBJECTIVE: To develop an HPLC procedure for the 
     determination of organic acids in tobacco. The procedure 
     could replace the tedious extraction and derivatization steps 
     required before the gas chromatographic readout. A 0.5% 
     dicyclohexylamine ion-pairing agent will be the eluting 
     solvent and a C18 column will be used.
       Projects Chiefly Concerned--1503, 1901
       F. Tobacco Protein Analysis
       OBJECTIVE: To investigate the proteins in tobacco and 
     smoke. Emphasis initially would be directed toward the 
     separation of tobacco glycoprotein by GPC and HPLC.
       Projects Chiefly Concerned--6900, 6906, 6908
       G. Amino Sugars in Tobacco and Reaction Flavor Mixtures
       OBJECTIVE: To determine the amino sugars formed from the 
     reaction of sugars and amino acids and/or ammonia. The 
     approach will be investigation of the reaction of ninhydrin 
     with amino sugar, making appropriate correction for amino 
     acids.
       Projects Chiefly Concerned--8401, 2305
       H. Fluoride Selective Ion Electrode for Ionizable Fluoride
       OBJECTIVE: This method will be developed in response to a 
     request from Park 500 for a fluoride determination in 
     potassium nitrate crystals isolated from CEL.
       Project Chiefly Concerned--8205
       I. Evaluation of the Microwave Moisture Meter for Leaf
       OBJECTIVE: To assist the Engineering Department in the 
     evaluation of their prototype microwave moisture.
       Project Chiefly Concerned--8204
       II. Smoke
       A. Aldehydes in Smoke
       OBJECTIVE: To extend the isocratic HPLC determination of 
     aldehydes in smoke with the gradient capability of the new 
     Hewlett-Packard HPLC to achieve better resolution of the 
     peaks.
       Projects Chiefly Concerned--8101, 6908
       B. FTC Tar by TPM Fluorescence
       OBJECTIVE: FTC tar measurement by fluorescence will be made 
     for the study of filter efficiency, sidestream/mainstream 
     ratios and puff X puff data on low delivery cigarettes.
       Project Chiefly Concerned--8101
       C. Electrochemical Analytical Techniques for Smoke Analysis
       OBJECTIVE: These techniques should be investigated as a 
     quick and selective way of determining aldehydes, ketones, 
     alcohols, acids, volatile metals or any material capable of 
     oxidation or reduction.
       Projects Chiefly Concerned--6908, 1503, 1901
       D. Gel Permeation on Whole Smoke Condensate
       OBJECTIVE: To make a comparison of GPC profiles of WSC from 
     cigarette types. The feasibility could be determined on the 
     Waters 202 HPLC using microstyrogel columns and THF solvent. 
     Possibly the isolated PAH fraction could thus be enriched 
     making easier any future analytical determinations of PAH's.
       Project Chiefly Concerned--6908
       III. Cigarette Paper
       A. Completion of Tipping Paper Ink/Adhesion Problem
       OBJECTIVE: To determine from one lot of paper to another 
     and to be able to correlate these differences with 
     performance on the cigarette maker.

[[Page H 7675]]

       Project Chiefly Concerned--8205
       B. Citric Acid in Cigarette Paper
       OBJECTIVE: To develop a simple HPLC procedure for citrates 
     in cigarette paper to replace the present gas chromatographic 
     procedure. The procedure will be developed on the new 
     Hewlett-Packard 1084b HPLC. The old DuPont 820 HPLC will be 
     dedicated for this determination.
       Project Chiefly Concerned--8101
                                 ______

                      General Analytical Chemistry

       I. General
       A. Provide accurate, precise analytical service as needed 
     to personnel of R&D and other PM departments with a target 
     turnaround time of seven work days or less per request.
       B. Consult with the above personnel in order to advise them 
     on ways of obtaining meaningful analytical data to aid them 
     in meeting current and future project objectives.
       II. Tobacco Leaf, Filler, Reconstituted Materials and 
     Process Slurries
       A. Investigate HPLC methods for separation and/or 
     quantitation of (in order of priority):
       1. Polyphenols
       2. Major and minor alkaloids
       3. Sorbate salts and sorbic acid in filler
       B. Incorporate a nitrite nitrogen procedure into the 
     nitrate nitrogen method.
       C. Conduct a rigorous investigation into all aspects of the 
     petroleum ether solubles method in order to develop a more 
     efficient procedure.
       D. Adapt the rapid procedure for hot water solubles to the 
     determination of cold water solubles.
       E. Develop a rapid accurate direct method for low levels of 
     insoluble solids in process slurries to aid in improving 
     accuracy of material balance studies.
       F. Improve precision, accuracy and sensitivity of the 
     sorbic acid method.
       G. Total Nitrogen Determination
       1. Maintain contacts with the manufacturer of the LECO NP-
     28 to lower maintenance requirements and reduce downtime.
       2. Investigate the feasibility of the determination of 
     insoluble nitrogen on the LECO NP-28.
       3. Investigate other methods of total nitrogen 
     determination, such as pyrolysis-chemiluminesence.
       4. Do a critical study of the effect of conditions such as 
     the salt concentration of digests on the values obtained in 
     the Kjeldahl total nitrogen method using the Technicon block 
     digestor.
       H. Investigate conditions which affect the reproducibility 
     of barium sulfate crystal formation in the turbidometric 
     sulfate method.
       III. Smoke
       Evaluate the method for NH3 in mainstream wholesmoke 
     by comparison with values obtained by the infrared 
     spectroscopy group on the diode laser IR spectrometer, with 
     the development of a low cost diode laser instrument capable 
     of routine operation as a goal.
       IV. Miscellaneous
       A. Methods Manual
       1. Document all methods in routine use in the General 
     Analytical Section.
       2. Consider ways of evaluating circulated manuals for 
     accuracy of content.
       3. Utilize computer capabilities for manual indexing and 
     updating.
       B. Computer/Microprossor Applications
       1. Utilize the existing microprossor or the computer for 
     the automation of the weighing of petroleum ether 
     extractables.
       2. Expand the availability of computer-generated hard copy 
     reports.
       C. Instrumentation
       1. Keep abreast of new developments in HPLC technology to 
     update present equipment, especially new detection systems.
       2. Optimize all AutoAnalyzer systems to increase speed and 
     accuracy and decrease reagent use.
       D. Personnel Education
       1. Continue rotation and cross-training of professionals 
     and technicians.
       2. Develop a training program for technicians providing 
     instruction in laboratory skills (complete with written 
     material) necessary in our laboratory.
       3. Develop a program of education of both the analyst and 
     submitter so that work performed is both meaningful and 
     necessary.
       E. Conduct an extensive study of laboratory organization to 
     determine what changes (e.g., flex time) might result in more 
     efficient operation, then implement those changes.
       F. Assume responsibility during the first quarter of 1980 
     for the receiving, coding, collating and transmittal of 
     samples and data from sources outside of R&D.
                                 ______

                          Biochemical Research

     To: Dr. T.S. Osdene
     From: W.F. Kuhn
     Subject: Plans and Objectives for 1980--Biochemical Research 
         Division
     Date: January 7, 1980
       The attached documents are the Plans and Objectives 
     prepared by the individual project leaders in the Biochemical 
     Research Division. These reports represent the areas of 
     research to be explored in 1980 under each charge number. 
     Each project leader prepared his report from the input he 
     received from his colleagues coupled with his own goals for 
     the coming year.
       The overall objectives of the Division are threefold and 
     remain essentially the same as outlined in previous reports. 
     First, develop an integrated program for control of insects 
     which infest stored tobacco, processed filler and finished 
     cigarettes. Second, establish a matrix or battery of in 
     vitro* bioassays for the evaluation of the biological effects 
     of smoke products and apply these assays for the 
     investigation of biological, chemical, and physical 
     parameters of cigarette smoke. Third, develop methods for the 
     collection, isolation, identification and quantitation of 
     tobacco and cigarette smoke components which affect the in 
     vivo and/or in vitro bioactivity. The main areas of endeavor 
     are highlighted below.
     CHARGE NUMBER 1101--ENTOMOLOGICAL RESEARCH
       Our effort on cigarette beetle physiological studies will 
     be continued. This emphasis stems from the trend to eliminate 
     the use of highly toxic or residual pesticides as control 
     agents and increase the use of mechanical and physical 
     methods to achieve the desired result. This effort will be 
     focused on: (1) the effect of relative humidity and low 
     temperatures toward beetle growth; (2) the investigation of 
     the comparative attractiveness to the beetle of various 
     colors from the visible spectrum; (3) the initiation of 
     studies on the use of feeding inhibitors; e.g., Neem nut 
     extracts, as possible repellents; (4) the efficacy of 
     pyrethrin alone as a larvicide; and (5) the evaluation of 
     commercially available sex pheromones of the cigarette beetle 
     and the tobacco moth. (Japanese scientists have published the 
     synthesis of a chemical reported to be the sex pheromone of 
     the cigarette beetle.)
       The research program on the application of an insect growth 
     regulator, methoprene, was highly successful. These results 
     led to the initiation of a large commercial application trial 
     (16,000 hogsheads) of KABAT--5% methoprene in ethanol--to 
     strip and stem. We will monitor the treated tobacco materials 
     for the presence of cigarette beetles and methoprene residue. 
     These hogsheads will be used to evaluate the effects of 
     various control practices (methoprene only, methoprene+DDVP 
     fogging and methoprene+DDVP fogging+PH3 fumigation) in 
     separate warehouses. The HTI results of both methoprene 
     treated Marlboro filler and Benson & Hedges filler in 
     relation to appropriate controls will be completed. We will 
     assist in the transfer of KABAT application techniques to 
     Stemmery personnel as the use of material is more widely used 
     throughout Philip Morris, U.S.A.
       We will continue to provide consultation and technical 
     service to other Departments within the Company. Such effort 
     will focus on the efficacy of DDVP fogging in warehouses, 
     methyl bromide vacuum fumigation at lower dosages and on-site 
     examinations within PM, USA and upon request.
Distribution of effort:                                         Percent
Fundamental studies..................................................30
Cost savings.........................................................45
Technical services...................................................25
     CHARGE NUMBER 6906--BIOLOGICAL EFFECTS OF SMOKE
       In the coming year, the goals of this group reflect our 
     decision to learn more about the existing, developed assays 
     rather than focus our attention on the interests of the 
     company to emphasize the former at the expense of the latter. 
     Since our resources are finite, we cannot engage in both 
     endeavors and adequately contribute to the understanding of 
     effects of smoke components in biological systems.
       MAMMALIAN CELL SYSTEMS
       The principal goal of the L5178Y mouse cell (thymidine 
     kinase mutation) assay will be to define parameters which 
     determine the activity of whole smoke condensate (WSC). To 
     accomplish this goal, three lines of investigation will be 
     pursued. First, the WSC derived from cigarettes which contain 
     filler variants of the LTF-IIIA formula will be tested. 
     Second, acid, base and neutral fractions isolated from WSC 
     will be evaluated as well as the testing of fractions derived 
     from synthetic mixtures of pure compounds to define the 
     application of the exponential dose-response curves. In 
     addition, WSC will be ``spiked'' with a known chemical of 
     high activity to trace its distribution, recovery and 
     potential interaction with isolates smoke components. Third, 
     the effect of variable microsomal protein (S9) on the 
     activity of positive control chemicals and WSC will be 
     studied. The objective of this effort will be to determine 
     how the relative activities of various WSCs are influenced by 
     changes in the amount of available, exogenous mammalian 
     metabolism.
       Although investigations on the measurement of sister 
     chromatid exchange (SCE) were suspended last year, 
     investigations on this phenomenon will be resumed. Successful 
     establishment of this assay will provide a second genetic 
     endpoint in the L5178Y cell system as well as provide an 
     additional assay for evaluating the biological effects of 
     smoke products.
       Literature reports indicate that smoke products are weak 
     initiators but moderate promotors in the two-stage model of 
     carcino-genicity. By measuring the degree of metabolic 
     cooperation between tymidine kinase proficient (TK+/-) and 
     tymidine kinase deficient (TK-/-) cells in the presence of 
     trifluorothymidine, it may be feasible to develop an in vitro 
     assay for promotors with L5178Y cells. Investigations will be 
     conducted to explore this phenomenon in the coming year.
       The major goal of the baby hamster kidney (BHK) assay will 
     be to establish the system 

[[Page H 7676]]
     with positive and negative control compounds. Experiments designed to 
     identify the causes of problems encountered to date are under 
     investigation. Failure to resolve these problems in our 
     facilities may require a visit to Dr. J.A. Styles' laboratory 
     at ICI in England to gain ``hands on'' experience in 
     conducting this bioassay.
       NONMAMMALIAN SYSTEMS
       Our efforts in the E. coli differential toxicity assay will 
     be directed toward the hypothesis that aldehydes in smoke are 
     causally related to activity. This study is closely coupled 
     to the development of a method for aldehydes in smoke by 
     personnel of the smoke condensate studies group.
       The major thrust in the yeast mitotic gene conversion assay 
     will continue to refine our knowledge of the determinants of 
     WSC activity. We plan to study the activity of TPM as a 
     function of puff volume initially which may lead to 
     additional studies on activity versus puff interval and/or 
     frequency. Additionally, the water soluble and insoluble 
     fractions of WSC will be tested along with the components 
     present in the acid, base, and neutral portions of WSC. On a 
     continuing basis, the pyrolyzate formed at 620  deg.C from 
     filler of various cigarettes will be tested. In particular, 
     the higher activity of RCB versus RL is especially important.
       Various investigations involving the application of the 
     Salmonella/microsome assay continue to require about 50% of 
     the total personnel effort of this project. In this regard, 
     we plan to study the TPM activity as a function of puff 
     volume, duration and frequency. THe feasibility of testing 
     pyrolyzed materials in the assay was demonstrated in 1979. We 
     plan to continue this effort this year. Studies of whole 
     smoke and gas phase activity (direct exposure of plates in a 
     chamber) in this assay will be suspended while the principal 
     investigator is on LOA. However, some work will be done on 
     the activity of whole and gas phase smoke collected directly 
     in solvent (DMSO) filled traps. Although this study is not as 
     elaborate as the chamber-exposure technique, it should 
     provide valuable information about the activity of gas phase.
       We plan to pursue the extensive study of the base fraction, 
     acid/neutral fraction and WSC activity of 14 model cigarette 
     types. We will continue the investigation of components 
     responsible for the base fraction activity of burley 
     cigarettes. In this regard model compounds such as amino 
     - and -carbolines will be studied.
       We will continue to test potential cigarette additives and 
     WSC from new cigarette candidates as requested. We anticipate 
     that this effort will receive increased emphasis in the 
     coming year.
       Another specific goal will be to prepare an internal 
     Salmonella/microsome assay methods manual to document all 
     procedures involved with this assay.
Distribution of Effort:                                         Percent
Defensive Research...................................................90
New Produce Development..............................................10
     CHARGE NUMBER 6908--SMOKE CONDENSATE STUDIES
       The primarily defensive nature of this research effort 
     necessitates a continual monitoring of developments in the 
     literature related to the biological activity of smoke 
     components. Achievement of this project's goals require close 
     coordination of research efforts with those of charge number 
     6906 which were expressed in the previous section.
       More emphasis will be placed on condensate collection 
     studies since these methods may affect the overall research 
     effort. Collection of WSC in Elmenhorst cold traps (ECT) or 
     impaction-traps (IT) will continue, along with processing, 
     for in vivo testing. The collection of samples for in vitro 
     and chemical studies has been expanded to ECT, IT, TPM pad, 
     gas phase, and collection in liquids. Some of these 
     collection methods will require further development. We plan 
     to design and apply sidestream smoke collection systems in 
     the coming year. A longer range study of a glass cascade 
     impaction trap for a particle size profile is planned. 
     Satisfactory separation of discrete particles will lead to 
     the chemical and biological evaluation of each size fraction.
       A system will be established for controlled pyrolysis or 
     combustion of filler for chemical and/or in vitro bioassay 
     investigations. The evaluation of a series of marcs isolated 
     from flue-cured tobacco is planned.
       Major improvements in chromatographic separation procedures 
     are anticipated. Achievement of this objective will permit 
     the investigation of new areas of smoke condensate chemistry 
     as well as more thorough evaluation of studies conducted 
     previously. Toward this objective, extensive modification of 
     the PE-900 gas chromatograph (gc) for use with fused silica 
     columns is underway. A law pressure liquid chromatographic 
     (lc) system was designed and will provide a flexible 
     preparative or isocratic analytical lc system. Major emphasis 
     of this system will be directed toward the reversed phase 
     chromatographic evaluation of the base fraction from burley 
     WSC. The acquisition of a high performance liquid 
     chromatograph will provide sufficient capability to develop 
     new methods for the isolation of smoke components of 
     biological importance.
       The procedure for volatile nitrosamines is well developed 
     and will be applied to smoke products upon request. We plan 
     to apply the methodology to correlate tobacco precursors with 
     nitrosopyrrolidine in smoke. Investigation of nitrosamines in 
     sidestream smoke and processed WSC will be investigated. 
     Development of methods for the characterization of 
     nonvolatile nitrosamines will be pursued. Initial studies 
     will concentrate on mainstream smoke, but may be extended to 
     sidestream smoke later this year.
       The isolation and identification of active components in 
     the base fraction of WSC has proven difficult. However, the 
     high microsome dependent (Salmonella) activity in this 
     fraction requires our continued attention. We will pursue 
     this goal using the improved chromatographic equipment 
     described previously as well as use of model compounds for 
     enhanced improvements in fractionation and identification 
     procedures. From studies of a series of 14 cigarette types, 
     we hope to better understand the influence of filler 
     composition on base fraction activity and yield. In addition, 
     this evaluation should enhance our knowledge of the relative 
     amounts of some specific components in WSC from these various 
     tobacco types. Planned chemical studies include: pattern 
     recognition analysis of gc data versus in vivo and/or in 
     vitro bioactivity; quantitative hplc procedure for quinoline 
     in WSC will be developed and extended to additional aza-
     arenes in these fractions; a method will be developed for 
     harmane and norharmane in the base fraction as well as 
     methods for the determination of amino - and 
     -carbolines (tryptophane pyrolysis products). 
     Cigarettes have been prepared by adding proline, tryptophane 
     or pheylalanine to LTF-IIA filler. A study of the active base 
     fraction components from these simple model systems is 
     planned with emphasis on the tryptophane added sample.
       Work will continue on the fractionation of bright tobacco. 
     Increased emphasis will focus on the chemical components of 
     each marc and extract, particularly the amino acid 
     composition of protein fractions and the nature of the 
     nonprotein nitrogen components.
       There are additional areas of interest which do not fit 
     into the research endeavors discussed above and thus are of 
     lower priority. The utility of gel permeation chromatography 
     will be explored for WSCs and condensate fractions. The 
     effect of added sugars or sugar-amino acid reaction products 
     in modulating the activity arising from proteins and amino 
     acids in tobacco will be studied. It has been stated that a 
     tobacco glycoprotein may be transferred into smoke (Becker's 
     work). If so, an understanding of the parameters controlling 
     this transfer would be beneficial. A capability for isolation 
     of such material will be developed.

Distribution of Effort:                                         Percent
Defensive Research...................................................80
Fundamental Studies..................................................10
Technical Service....................................................10


     To: Mr. W. F. Kuhn
     From: R. A. Pages
     Subject: Project Charge Number 6906 (Biological Effects of 
         Smoke)--Plans and Goals for 1980
     Date: December 20, 1979
       1. INTRODUCTION
       The objectives of Project Charge Number unchanged.
       (a) To develop a battery of short-term assays to evaluate 
     the potential b effects of cigarette smoke product
       (b) To conduct research investigations to generate an 
     understanding of and control of cigarette smoke * * * in each 
     in vitro assay.
       (c) To conduct tests on potential new products or additives 
     upon request assist in the evaluation and inter * * * of the 
     results obtained.
       The original objectives of the project above) presented us 
     with a formidable challenge. * * * challenge, we developed a 
     strategy regarding the and evaluation of in vitro assays at 
     PM. Implement strategy led to the successful development to 
     sev * * * detect and measure the in vitro activity of cigar * 
     * * condensate. With that success, we first discovered 
     objective b and then came to recognize its ultimate 
     importance to our program. Thus, it became apparent that the 
     intelligent application of in vitro tests and the 
     interpretation of their results could be carried out only 
     when sufficient knowledge had been obtained about the many 
     factors (cigarette, chemical, and/or biological) which 
     together determine the level of cigarette smoke product 
     activity. This was vividly illustrated when we were faced 
     with trying to interpret the meaning of diametrically 
     opposite results obtained with the same test material in 
     different assays.
       Against this background, we will now present our plans for 
     1980. This year, as in prior years, we have had to make 
     difficult and risky decisions. This is because it is self-
     evident that: time is precious; our resources, both human and 
     material, are finite; and we cannot do everything if 
     everything we do is to be done well. Accordingly, our plans 
     reflect an imbalance between learning more about our 
     existing, developed assays and the development of additional, 
     new assays. In our judgment, it is in the best interests of 
     PM that we continue to emphasize the former at the expense of 
     the latter.
       2. PLANS AND GOALS FOR 1980
       A. L5178Y MOUSE CELLS
       1. Thymidine Kinase Mutation
       The principal goal of work with this assay in 1980 is to 
     try to define some of the parameters which determine WSC 
     activity. Although this assay system for WSC has been 
     established for almost two years, we do not yet know anything 
     about the nature of WSC activity. (Tests on the Model II and 
     URLS variant WSCs conducted during 1979 did not 

[[Page H 7677]]
     provide any new insights into this question.) We therefore propose to 
     pursue three lines of investigation in the coming year.
       (a) LTF-IIIA Variants--The Model I WSC results have 
     consistently shown that LTF-IIIA yields a WSC which is 
     significantly more active that LTF-IIA WSC. Following the 
     approach so successfully used in the Salmonella/microsome and 
     E. coli assays, we will test the WSCs derived from cigarettes 
     which contain filler variants of the LTF-IIIA formula. Enough 
     filler is already available for these studies, but it will be 
     necessary to fabricate handmade cigarettes for smoking in 
     order to standardize cigarette paper porosity and filtration 
     parameters. We intend to begin these studies no later than 
     the second quarter of 1980 and to pursue them on a continuing 
     basis thereafter. Our specific goal is to try to relate WSC 
     activity to the presence (or absence) of particular 
     precursors in the LTF-IIIA formula.
       (b) WSC Fractions--Previous studies of fractions have been 
     limited to a cursory examination of the H2O soluble and 
     insoluble portions of 2R1 WSC (both fractions were active). 
     We intend to exhaustively examine the question of activity in 
     WSC fractions on a continuing basis during 1980. These 
     studies will include: tests of the acid, basic, and neutral 
     fractions from one or more Model I WSCs; the testing of 
     fractions derived from synthetic mixtures of pure compounds 
     in order to define how to use the exponential dose-response 
     curves.
       (c) Activity as a Function of S9 Concentration--Almost all 
     prior work with this assay has involved tests conducted at a 
     single, arbitrarily selected, level of microsomal protein 
     (S9). Because it is well established that the amount of S9 
     can have a dramatic effect on the level of activity observed 
     in many short-term in vitro assays, we propose to investigate 
     this phenomenon in the L5178Y TK mutation assay. Initial 
     experiments will involve studies of the activity of our 
     positive control compounds--B(a)P and 2-acetylaminofluorene. 
     We will then investigate WSC activity versus S9. These 
     studies will necessitate the conduct of assays simultaneously 
     at different concentrations of WSC and S9. The specific goal 
     of the experiments will be to determine how the relative 
     activities of different WSCs and their respective dose-
     response curves are affected by changes in the amount of 
     exogenous mammalian metabolism. Depending on the degree of 
     success attained with testing WSC fractions at a single S9 
     level, these studies may also be extended to fractions tested 
     at multiple S9 concentrations. This work will be initiated no 
     later than the second quarter of 1980 will proceed throughout 
     the remainder of the year.
       Prior to initiating the three programs outlined above, in 
     the first quarter of 1980, we expect to conclude three 
     ongoing investigations. The first is the evaluation of the 
     utility and effectiveness of a modified cloning procedure 
     which is expected to simplify the conduct of the assay. The 
     second is the evaluation of a series of selected WSC-induced, 
     trifluorothymidine (TFT) -resistant mutants to verify that 
     they are indeed TK-deficient (TK-/-). The third is the 
     drafting of a special report to document the conclusions 
     reached after an extensive review of the data generated on 
     positive and negative control compounds over the last three 
     years. By doing this, we are hopeful of being able to 
     establish objective quality assurance criteria which can be 
     used to help us decide: when this assay is performing 
     satisfactorily; what is the acceptable level of variation; 
     and when is a test sample active or inactive in this assay.
       2. Sister Chromatid Exchange (SCE)
       Work on the development of an assay based on the 
     measurement of a second genetic endpoint, SCE, in L5178Y 
     cells was suspended in May, 1979. As time permits, we plan to 
     resume this effort on a part-time basis. Based on the 
     information gathered in recent months, we are absolutely 
     confident that we can successfully establish the SCE assay in 
     our laboratory and that we can detect WSC activity by that 
     method. If and when we are able to resume the SCE work, we 
     expect to take advantage of the advice of Dr. David Kram (G. 
     Washington University) by accepting an invitation to spend 
     several days in his laboratory to obtain ``hands on'' 
     experience with the SCE assay.
       3. Metabolic Cooperation
       As time permits, we plan to conduct studies to measure the 
     degree of metabolic cooperation between TK+/- and TK-/- cells 
     in the presence of TFT. These exploratory studies are 
     designed to examine the feasibility of the possible 
     development of an in vitro assay for promoters in L5178Y 
     cells along the lines pioneered by Trosko and co-workers 
     (Science. 206:1089-1091; 1979 November 30).
       B. BHK CELL TRANSFORMATION
       The principal goal of our efforts on this assay in 1980 (as 
     it was in 1979) is to reproducibly establish the assay system 
     with positive and negative control compounds. The results 
     obtained in 1979 were moderately encouraging in that we were 
     able to obtain several cell clones which appear promising for 
     use in the assay. Several sources of difficulty were 
     identified with the published assay protocol--some of which 
     appear to be related to the quality of sera, media, etc. 
     Major obstacles remain to be overcome, however, before 
     satisfactory responses are obtained with positive control 
     compounds and a usable assay protocol is available in our 
     laboratory. Experiments designed to further identify the 
     causes of problems and variables in this assay will be 
     continued during the first and second quarters of 1980. If 
     success has not been achieved by that time, strong 
     consideration will be given to trying to arrange a visit to 
     the laboratory of Dr. J. A. Styles at ICI in the UK in order 
     to try to get some ``hands on'' experience in one of the few 
     places that has been able to get this assay to work.
       C. E. COLI DIFFERENTIAL TOXICITY
       The principal goal for work with this assay in 1980 is to 
     definitively test the hypothesis that aldehydes in smoke are 
     causally related to activity. This is a collaborative effort 
     with various personnel of Project Charge Number 6908.
       In 1979, methodology was developed to test either whole 
     smoke or TPM and gas phase in this assay. Additionally, 
     experiments were begun to study the activity of several low 
     molecular weight aldehydes in the liquid culture version of 
     this assay. These experiments will be completed in the first 
     quarter, 1980. Concurrently, 6908 personnel are exploring 
     various possibilities for analyzing and quantitating the 
     aldehydes in cigarette smoke. The ultimate test of the 
     aldehyde hypothesis is contingent upon successfully coupling 
     analytical chemical methods with the in vitro assay on common 
     samples. Pending further progress on aldehyde method 
     development by 6908 personnel, we intend to continue to 
     investigate cigarette smoke activity as a function of 
     physical cigarette parameters which are known to affect 
     aldehydes in smoke (e.g., carbon filters). The specific goal 
     of these studies will be to accumulate additional 
     circumstantial evidence in support of the aldehyde 
     hypothesis. This will be done on a continuing basis 
     throughout 1980.
       D. YEAST MITOTIC GENE CONVERSION
       Our major goal in the yeast assay work in 1980 is to 
     continue to refine our knowledge about the determinants of 
     WSC activity. Excellent progress was made in 1979 based upon 
     the results of tests on: the Model III WSCs and TPM; WSC 
     fractions; and some cigarette filler pyrolyzates. We plan to 
     continue efforts in all of these areas in 1980. Because many 
     of the studies which are of interest in the yeast assay will 
     also be conducted in the Salmonella/microsome assay, we 
     anticipate that there will be extensive interaction and 
     coordination with other personnel within 6906 and 6908 a 
     well. Hopefully, this will minimize duplication of effort(s) 
     whenever possible.
       1. WSC/TPM Activity versus Smoking Parameters
       We intend to follow up our Model III cigarette studies by 
     measuring the activity of TPM as a function of puff volume. 
     These experiments will be conducted in the first quarter, 
     1980, and may lead to additional studies such as TPM activity 
     versus puff interval and/or frequency. Further comparisons 
     between TPM and WSC activity in the yeast assay will also be 
     conducted on additional model cigarettes.
       2. WSC Fractions (with 6908)
       We are interested in testing fractions derived from the 
     H2O soluble and insoluble portions of WSC--both of which 
     were found to be active in experiments conducted in 1979--
     particularly the base and acid/neutral fractions (Activity 
     detected in the base fractions would extend our observations 
     of an association between filler nitrogen and WSC activity in 
     this assay.) Because studies already underway in the 
     Salmonella/microsome assay involve testing the bases and 
     acids/neutrals prepared directly from various WSCs (see 
     below), our initial efforts in the first quarter, 1980 will 
     be directed toward testing some of those samples in the yeast 
     assay as well.
       3. Cigarette Filler Pyrolyzates (with 6908)
       The results of feasibility studies conducted during 1979 
     demonstrated that samples prepared by heating cigarette 
     filler in air at 620o C were active in the yeast assay 
     as well as in the Salmonella/microsome assay. Thus, the 
     acquisition of pyrolysis equipment by 6908 personnel to 
     evaluate the potential of this method of generating samples 
     for in vitro testing may also provide valuable information 
     about the filler determinants of WSC activity in the yeast 
     assay. In this connection, we are especially interested in 
     investigating the higher activity of RCB versus RL. These 
     studies will be conducted on a continuing basis throughout 
     1980.
       E. SALMONELLA/MICROSOME ASSAY
       Various investigations involving the application of this 
     assay will continue to make up about half the total efforts 
     of the personnel of the project. The majority of these 
     studies will be devoted to developing a better understanding 
     of the determinants of WSC activity, although we also 
     anticipate increased demands for testing WSCs and additives 
     at the request of J.L. Charles.
       1. TPM Activity versus Smoking Parameters
       Extension of the Model III WSC studies will be conducted by 
     testing TPM from the Model III cigarettes during the first 
     quarter, 1980. Upon completion of that work, we intend to 
     study TPM activity (unfiltered PMKRC cigarette) as a function 
     of puff volume. Depending on the results obtained, it may be 
     important to also study the effects of changes in other 
     smoking parameters such as puff interval and/or frequency. In 
     continuation of our expanded efforts to study TPM activity, 
     it may also be necessary to test the Model II cigarettes.
       2. Cigarette Filler Pyrolysis (with 6908)
       We were sufficiently encouraged by the results of extensive 
     feasibility studies conducted during 1979 to strongly urge 
     and support the acquisition of pyrolysis equipment by 6908 
     personnel. We are hopeful that this equipment will be set up 
     during the first 

[[Page H 7678]]
     quarter so that intensive studies can begin to establish the 
     relationship between various pyrolysis conditions (e.g., 
     temperature, air versus nitrogen, etc.) and activity in this 
     assay. (As indicated above, section 2.D.3, there is great 
     interest in exploring the application of this method to 
     generate samples for testing in other in vitro assays.) The 
     ultimate goal of theses investigations will be to determine 
     how pyrolysis can be used to evaluate the activity of samples 
     for which cigarette fabrication is not feasible--particularly 
     the extracts and marcs of bright tobacco and RCB feedstock. 
     Pyrolysis studies will be continued throughout 1980.
       3. Whole Smoke and Gas Phase Studies
       Studies of whole smoke activity in this assay as originally 
     conceived (exposure of prepared agar plates in a chamber) 
     will be suspended while the principal investigator is on 
     leave. However, it is likely that some work will be conducted 
     during the first and second quarters, 1980 to investigate the 
     Salmonella/microsome activity of whole smoke and gas phase 
     samples prepared by the methods developed for the E. coi 
     assay--i.e., by collection in solvent (DMSO) filled traps. 
     While not as elegant as the chamber-exposure technique, it is 
     likely that such experiments will provide valuable 
     information regarding the activity of gas phase smoke 
     components.
       4. WSC versus Base Fraction Activity (with 6908)
       Already in progress is an extensive study of the base 
     fraction, acid/neutral fraction, and WSC activity of 14 model 
     cigarette types. The study should be completed in the first 
     quarter, 1980. At that time, we expect to be able to answer 
     several important questions: What is the relationship between 
     WSC specific activity and the specific activity and 
     concentration of the base fraction? Do the components 
     recovered in the weakly active acid/neutral fraction have an 
     effect on base fraction activity; i.e., are there any 
     interactions? Does the presence of high concentrations of 
     nicotine in the base fraction (30-60% of the fraction is 
     nicotine) have any effect on the microsome-dependent activity 
     of the high activity compounds that are present in that 
     fraction?
       5. Fractionation of WSC Bases (with 6908)
       The isolation and identification of individual components 
     which may be important determinants of burley WSC activity 
     remains the specific goal of this program. Further progress 
     in this effort is dependent on the development of improved 
     separation and identification methods by 6908 personnel. 
     Plans have been formulated to investigate various separation 
     procedures in conjunction with the use of model compounds 
     such as amino- and -carbolines. In 
     addition, we also plan to study the activity of selected 
     fractions as a function of different levels of S9 to 
     ascertain if the low accountabilities of activity sometimes 
     observed is due to the use of single, nonoptimal levels of S9 
     in routine tests. All of the studies will be ongoing 
     throughout 1980. * * *
     7. Assay Standardization and Quality Assurance
       In 1979, a series of steps was taken to improve our 
     internal quality control over the conduct of the assay. These 
     included: greater interaction and coordination on a regular 
     basis between all members of the project involved in using 
     the assay; the use the common cell stocks and samples of 
     positive control compounds; standardization of assay 
     methodology of conform to the most recent recommendations of 
     Ames and co-workers; and more careful monitoring of 
     interexperiment variations of spontaneous backgrounds, cell 
     titers, and positive control activities. These efforts will 
     be continued and expanded in 1980. It is our specific goal to 
     prepare an internal, Salmonella/microsome assay methods 
     manual which will document in detail all phases of the 
     conduct of the assay at PM including data processing and 
     analysis via the R & D computer. We expect to complete the 
     initial draft of the manual in the second quarter of 1980 and 
     then to continually update it whenever changes in protocol or 
     procedures are made.
     F. PERSONNEL
       We have received authorization to hire a new person for our 
     group in 1980. In view of the rather ambitious program 
     outlined above and in keeping with our basic philosophy on 
     current priorities as outlined in the Introduction above, our 
     plans are to hire an Associate Scientist A in the second 
     quarter of 1980. The new person will be assigned to work 
     under the supervision and direction of more experienced 
     personnel in one of the assay areas outlined above. Exactly 
     which area will be decided upon at the end of the first 
     quarter of 1980.
       3. SUMMARY OF PLANS AND GOALS FOR 1980
       Assay/Activity
       A. L5178Y Mouse Cells: Time
       1. TK Mutation
       Verify WSC-induced, TFT-resistant mutants are TK: 1st 
     quarter
       Modified Cloning Procedure: 1st quarter
       Develop and publish quality assurance criteria for assay: 
     1st quarter
       LTF-IIIA variants-filler: 2nd quarter composition vs. WSC 
     activity: and continuing
       WSC fractions: 2nd quarter and continuing
       WSC activity vs. S9 concentration: 2nd quarter and 
     continuing
       2. SCE
       Establish assay: as time permits
       3. Metabolic Cooperation
       Feasibility studies: as time permits
       B. BHK Cell Transformation
       Establish assay protocol with positive and negative control 
     compounds: continuing
       C. E. coli Differential Toxicity
       Aldehydes in smoke vs. activity: continuing
       Test model compounds in liquid culture assay: 1st quarter
       Activity vs. physical cigarette parameters: 2nd quarter and 
     continuing
       Mehtod development--aldehyde analysis (by 6908 personnel): 
     continuing
       D. Yeast Mitotic Gene Conversion
       TPM activity vs.Puff volume: 1st quarter
       Base vs. acid/neutral fractions of WSC: 1st quarter and 
     continuing
       Cigarette filler pyrolyzates: continuing
       e. Salmonella/Microsome Assay
       TPM activity vs. puff volume: 1st quarter
       Cigarette filler pyrolyzates: continuing
       Whole smoke and gas phase activity of solvent trapped 
     smoke: 2nd quarter
       WSC vs. base fraction activity: 1st quarter;
       Fractionation of WSC bases: continuing
       Additive and WSC testing: as requested
       Research studies of additive testing: 2nd quarter
       Assay standardization and quality assurance Methods: 
     continuing
       Manual: 2nd quarter
                                 ______

     To: Mr. W.F. Kuhn
     From: R.N. Ferguson
     Subject: Plans and Objectives for 1980 (Charge Number 6908)
     Date: December 18, 1979
     I. INTRODUCTION
       The project continues to have several interrelated goals:
       (a) to develop and apply methods to identify and quantitate 
     components of cigarette smoke which relate to biological 
     activity,
       (b) to use cigarette models to relate chemical composition 
     to biological activity including precursor/product 
     relationships,
       (c) to develop or improve methods for collection of 
     cigarette smoke and apply these to collection and processing 
     of smoke condensate for in vivo, in vitro, and chemical 
     testing.
       The primarily defensive nature of this research 
     necessitates a continual monitoring of developments in the 
     literature related to the biological activity of smoke 
     components. These goals also require a close coordination of 
     our research efforts with those of Charge Number 6906--
     Biological Effects of Smoke.
       During the last year, considerable progress was made in 
     nitrosamine studies, in base fraction components, in liquid 
     and gas chromatography methods, in pyrolysis, and in an 
     aldehyde procedure. The complexity of WSC remains the major 
     challenge to advances in these areas of interest. Another 
     problem is the large number of areas requiring our attention. 
     This is due to the considerable number of potentially active 
     components known or suspected in WSC.
     II. RESEARCH PLANS
       A. Condensate Collection and Processing
       More emphasis will be put on condensate collection studies 
     since these methods are a key part of our research.
       Collection of whole smoke condensate by Elmenhorst cold 
     trap (ECT) or impaction trap (IT) procedure will continue, 
     along with processing, for in vivo testing. This involves gc 
     analysis and concentration testing on these samples. Selected 
     ECT or IT trapped and processed samples will be checked for 
     volatile and nonvolatile nitrosamines.
       The collection of samples for in vitro and chemical study 
     has been expanded to ECT, IT, TPM pad, gas phase, and 
     collection in liquids. Some of these methods will require 
     further development. In addition, design and application of 
     sidestream collection systems has begun. Considerable effort 
     will be required to develop satisfactory methodology in the 
     coming year.
       A study of volatiles not collected (IT) or lost during 
     processing (ECT) has also been initiated and will continue. A 
     longer range study of a glass cascade impaction trap for a 
     particle size profile is planned. This could be extended to 
     chemical and biological evaluation of each size fraction.
       A system will be set up in the coming year for pyrolysis or 
     combustion of filler and collection of the smoke for either 
     chemical or in vitro assay. After the equipment has been 
     obtained an extensive check of conditions will be made for 
     possible correlation of pyrolyzate and WSC biological 
     activity. The application of this methodology to evaluation 
     of a series of bright marcs is also planned.
       B. Chromatography
       Improved separation procedures will allow both the 
     investigation of new areas and more complete investigation of 
     areas previously studied.
       Extensive modification of the PE-900 for use with fused 
     silica capillary columns is progressing.
       The Sigma 3 gc, which is coupled to the du Pont 21-490 mass 
     spectrometer, has capillary capability. To permit the 
     exploitation of this feature on the 21-490 ms will require 
     considerable effort due to limitations in the ms system. 
     Acquisition of capillary capability for the gc/ms/ds, if 
     possible, will be a significant advance in our capabilities.
       A low pressure lc system has been designed and will provide 
     a flexible preparative or isocratic analytical chromatography 
     system. Major initial emphasis will be on reversed phase 
     chromatography applications to base fractions from X6D3IM 
     (burley) WSC.
       It is anticipated that a number of new hplc separations 
     will be made possible by the acquisition of a second high 
     performance, gradient analytical lc system in 1980. This will 


[[Page H 7679]]
     provide sufficient capability both to develop new methods and to put 
     developed methods into routine use on the present instrument 
     (Spectra Physics 3500B).
       Droplet counter-current chromatography is a method not 
     previously investigated for WSC fractionation. An effort 
     toward a collaborative evaluation of the methods potential in 
     areas of interest to us will be made.
       C. Nitrosamines
       The procedure for volatile nitrosamines is well developed 
     but application of this technique on new samples will 
     continue. The general method will also be applied to 
     correlation of tobacco precursors with nitro- sopyrrolidine 
     in smoke. Work with sidestream and processed WSC is also 
     planned.
       We have been delayed in development of methods for 
     nonvolatile nitrosamines by sample load but work in this area 
     will be initiated in the first quarter of 1980. Of interest 
     is N-nitroso nornicotine (NNN), 4-(N-methyl-N-nitrosoamino)-
     l-(3-pyridyl)-l-butanone (NNK), and N-nitrosanatabine (NAB). 
     A hplc has been interfaced to the thermal energy analyzer 
     (tea) for these analyses, but we also will explore the 
     possibility of using gc/tea for these so called nonvolatile 
     nitrosamines. Initial work will concentrate on mainstream 
     smoke, but extension to sidestream is possible in the future.
       D. Base Fraction of X6D3IM (burley)
       The isolation and identification of individual active base 
     fraction components has proven difficult. Nevertheless, the 
     high microsome dependent activity shown by these fractions 
     requires a further effort at identification. Of particular 
     importance will be the improve chromatography methods 
     described in section B. Further use of model compounds is 
     planned for improvement in fractionation and identification 
     procedures.
       E. Model Cigarettes: Chemical Studies versus Salmonella 
           Activity
       A series of 14 cigarettes (varying tobacco fillers) has 
     been selected for a number of chemical evaluations. In 
     addition, the Salmonella/microsome activity of each WSC and 
     base fraction will be evaluated. We hope to better understand 
     the influence of filler parameters on base fraction activity 
     and yield and also the levels of some specific components in 
     WSC from various tobacco types. Planned chemical studies 
     include: a) TMS derivatization of the WSC and capillary gc 
     profile generation. Pattern recognition analysis of data 
     versus in vivo estimated activity and/or in vitro activity. 
     Use of the gc profile method on base fractions. b) The 
     quantitative hplc procedure for quinoline in WSC will be 
     applied. The determination of additional aza-arenes in these 
     fractions is also a possibility. c) A procedure for harmane 
     and norharmane in the base fraction will be developed. This 
     hplc procedure will also be applied to the set of model WSCs. 
     d) A gc method for nicotine will be applied to the base 
     fractions. e) We hope to be able to develop an hplc method 
     for amino - and - carbolines (tryptophane 
     pyrolysis products) in the base fraction. When available, 
     this procedure will also be applied to the model WSC samples.
       In addition to these studies, cigarettes have been prepared 
     by adding proline, tryptophane, or phenylalanine to LTF-IIA 
     (nitrogen free) filler. A study of the active base fraction 
     components from these fairly simple model systems is planned 
     with emphasis on the tryptophane spiked sample.
       F. Bright Tobacco Extraction
       Work is continuing on the fractionation of bright tobacco 
     in order to study the effect of removal of various classes of 
     nitrogen containing compounds. Increased emphasis will be on 
     the chemical components of each marc and extract, 
     particularly the amino acid composition of protein fractions 
     and the nature of the nonprotein nitrogen components.
       When acceptable pyrolysis conditions are available, this 
     method will be used for evaluation of each marc.
       G. MW 288
       The positive identity of this smoke component has remained 
     unsolved, primarily due to our problems with selective 
     ozonolysis and derivatization of model compounds. A synthetic 
     approach to this compound is being pursued by Dr. Edwards. We 
     are considering the possibility of the preparation of a 
     crystalline derivative suitable for an x-ray structure study.
       The cuticular wax of bright and burley tobacco has been 
     obtained. We hope to establish that duvatrienediols produce 
     MW 288 under appropriate thermal conditions. Further, we 
     expect to find out if each isomer of duvatrienediol leads to 
     one specific MW 288 isomer.
       H. E. coli Assay and Aldehydes
       The E. coli assay has previously defied attempts to 
     determine which components of smoke are principally 
     responsible for activity. This may no longer be the case. 
     Evidence has been accumulated that some aldehydes are highly 
     active in the assay. Progress has been made in trapping and 
     derivatizing both whole smoke and gas phase smoke. An hplc 
     method for the dinitrophenyl-hydrazones of reactive carbonyl 
     components is almost finalized. We will attempt to definitely 
     establish the quantitative importance of the smoke aldehydes 
     in this assay.
       I. Additional Areas
       There are a number of additional areas of opportunity and 
     interest which do not fit into the areas already discussed or 
     are of lower priority for study. Investigation in at least 
     some of these areas is planned as time allows.
       (a) Some initial work has been done with activity in 
     fractions in the yeast assay. We wish to find the types of 
     components responsible for the activity seen in WSC by 
     fractionation studies.
       (b) LTF-IIA plus phenylalanine-continuation of gc and gc/ms 
     studies for products from phenylalanine in model cigarettes.
       (c) Develop methods for N-heterocycle analogs of PAHs in 
     smoke.
       (d) Further study of the red material formed in ECT smoke 
     of nitrate cigarettes and see if addition of NO to smoke will 
     produce this band on ECT.
       (e) Explore the utility of gel permeation chromatography 
     both for WSCs and for condensate fractions.
       (f) Explore the effect of added sugars or sugar-amino acid 
     reaction products in modulating the activity arising from 
     proteins and amino acids in tobacco.
       (g) Study the mass spectra of geometric isomers of aldehyde 
     O-methyloximes.
       (h) A tobacco glycoprotein may be transferred to smoke. If 
     so, an understanding of the parameters controlling this 
     transfer would be of great use. A capability for isolation of 
     such material will be developed.
       (i) Fluorescence is a very useful tool in a number of 
     areas. Additional evaluation of the utility of fluorescence 
     for studies of smoke components and evaluation on commercial 
     instrumentation needs to be made.
       (j) Is 3-nitro-5-(3'-pyridyl)-pyrazole formed on ECT 
     collection of smoke from high nitrate cigarettes?
       (k) Develop and apply chemical/physical indicators of 
     estimated in vivo biological activity.
     III. CONCLUSION
       These plans and objectives represent some redefinition of 
     the project's goals. There is more emphasis on the 
     development of smoke collection technology and its impact on 
     WSC chemistry. Also greater emphasis is on chemistry coupled 
     to actual in vitro (particularly Salmonella/microsome) 
     activity rather than estimated in vivo activity has been 
     dropped as a research goal. Finally, capillary gc and various 
     hplc methods have been given a high development priority in 
     our planning.
     IV. PLANS
       Activity; Timetable
       A. Condensate Collection, Preparation, Analysis
       1. Current Test Samples: Ongoing*
       2. ECT and IT for in vitro and chemical study: Ongoing
       3. Alternate collection--TPM, solvent impaction, 
     sidestream: 4th qtr., 1979 through 4th qtr. 1980
       4. Volatiles and semivolatiles lost in collection and 
     processing: complete 2nd qtr.
       5. Pyrolysis setup and experimentation: Initiate; 1st qtr.
       B. Chromatography
       1. Capillary gc on PE 900
       (a) Derivatized WSC: Complete 3rd qtr.
       (b) Fractions: Initiate 2nd qtr.
       2. Evaluation of capillary gc/ms: 1980
       3. Low pressure lc system: Assemble 1st qtr.
       4. Analytical hplc
       (a) New system installation: 1st quarter
       (b) New methods development: Ongoing
       (c) Gel Permeation: 1980?
       C. Nitrosamines
       1. Volatile nitrosamines: Ongoing
       2. Nonvolatile nitrosamines: Initiate 2nd qtr.
       D. MW 288
       1. Structure: Complete 3rd qtr.
       2. Duvatrienediols as precursors: Complete 4th qtr.
       E. Salmonella/microsome assay
       1. X6D3IM base fractions: Ongoing
       2. Base fractions from Model cigarettes
       (a) Yield and activity: Complete 1st qtr.
       (b) Chemical constituents: Initiate 1st qtr.
       3. Bright tobacco marcs and extracts: Ongoing
       4. LTF-IIA plus additives: 1980
       F. Aldehydes and E. coli activity: Complete 3rd qtr.
       G. WSC fractions and yeast assay: Initiate 1st qtr.
       H. Additional Areas
       1. Chemical predictors of EBA: In 1980 as time permits.
       2. Polycyclic nitrogen heterocycles
       3. Red bands in ECT smoke
       4. Tobacco glycoprotein
       5. Application of fluoresence
       6. Basic ms studies--oximes
       7. Sugar effect on WSC activity
       8. Droplet counter current distribution

     *Completion in 1980 is not anticipated for any ongoing 
     projects.
                                 ______

     To: Dr. E.B. Sanders
     From: J.I. Seeman
     Subject: Plans and Objectives for 1980 (Charge 2500)
     Date: January 4, 1980
       Work for 1990 will be focused in three general areas; 
     alkaloid and nicotine chemistry, flavor chemistry, and 
     flavor-release chemistry. In addition, we will continue to 
     perform assistance to other units upon request in such areas 
     as custom synthesis and general organic chemistry.
       I. Alkaloid and Nicotine Chemistry (Chavdarian, Secor, plus 
     one).
       A. Objectives
       1. To develop a fundamental understanding of the mechanisms 
     by which nicotine and other tobacco alkaloids interact with 
     peripheral and central nervous system receptors.
       2. To determine if nicotine analogues can be designed which 
     exhibit differential activity at different receptors.
     
[[Page H 7680]]

       3. To develop procedures to synthesize nicotine analogues 
     and isotopically labelled nicotine analogues.
       4. To investigate the possible correlation of structural 
     and chemical parameters with biological behavior.
       5. To perform, in a collaborative fashion, pharmacological 
     testing of nicotine and its analogues with a goal of deriving 
     structure-activity relationships.
       6. To develop an effective insecticide(s) through 
     collaborative testing of nicotine analogues; in this 
     conjunction, the mode of action(s) of these compounds will be 
     investigated.
       7. To aid other groups with problems related to tobacco 
     alkaloids.
       B. Synthetic Studies
       1. Preparation of Optically Active Nicotinoids
       a. Procedures will be developed which will allow the 
     separation of racemic nornicotine derivatives into their 
     enantiomers. This will involve the HPLC purification of, 
     a.g., nornicotine urethanes which are diastercomeric by 
     virtue of the nornicotine condensation reagent.
       b. We have already shown that 6-methylnicotine and 6-
     butylnicotine can be formed in high yield from nicotine by 
     reaction with methyllithium and butyllithium respectively. 
     This procedure will be extended to other 6-substituted 
     nicotinoids.
       c. Microbiological reduction of 3-acetylpyridine has been 
     shown to result in the optically active alcohol. Attempts to 
     convert this alcohol to the corresponding amine will be made. 
     If successful, this procedure will be applied to an 
     asymmetric norcotinine synthesis.
       d. We have found that cotinine can be alkylated and 
     carboxylated at C-4'. The products can subsequently be 
     reduced to 4'-substituted nicotinoids which are optically 
     active by virtue of asymmetry of cotinine. This work will be 
     extended to a few additional analogues.
       e. 5-(3-Pyridyl)butyrolactone, obtainable from procedure 
     I.B.1.c. above, may be convertible to active norcotinine with 
     ammonia.
       f. The microbiological reduction of imines (e.g., myosmine) 
     to saturated amines (e.g., nornicotine) may result in an 
     optically active product. There are no examples of such a 
     reduction in the literature. This will be examined.
       2. Preparation of Pyridine-Substituted Analogues
       a. 5- and 6-Substituted nicotinoids will be prepared by a 
     variety of methods, including the reaction of nicotine with 
     alkyllithium reagents (c.f. I.B.1.b.) and routes involving 
     synthesis of substituted nicotinonitriles and methyl 
     nicotinates. These will also include heterosubstituted 
     nicotinoids. Optically active 6-hydroxynicotine will be 
     prepared from microbiological oxidation of nicotine. This 
     material will be used as the key intermediate in the 
     preparation of 6-alkoxy and 6-acetoxy derivatives.
       b. Nicotine 6-carboxylic acid and nicotine 5-carboxylic 
     acid and their corresponding esters will be prepared.
       c. 2,4-Dimethylnicotine and selected deuterated analogues 
     will be prepared for mechanistic studies.
       3. Preparation of Pyrrolidine Substituted Analogues
       a. HPLC purification will be performed to purify numerous 
     isomeric methylated nicotinoids.
       b. 2'-Substituted analogues will be prepared by addition of 
     organometallic reagents to N'-methylmyosmine perchlorate.
       c. A number of N'-substituted nornicotines in their 
     enantiomeric forms (c.f. I.B.1.a.) will be prepared.
       d. 4'-Substituted nicotinoids will be prepared (c.f. 
     I.B.1.d.).
       e. Additional examples of 3'-alkylnicotines will be 
     prepared by condensation of 3-pyridinecarboxaldehyde and 
     Michael acceptors.
       f. Anatabine will be prepared from the reaction of 3-
     pyridyllithium (or 3-pyridylmagnesium bromide) and 2-cyano-
     4-piperidine.
       g. Simple syntheses of nicotyrine will be investigated, for 
     example, by the reaction of 3-pyridyllithium with a protected 
     4-hydroxypyrrolidinone.
       h. 3'-4'-Dehydronicotine will be prepared, either 
     by reduction of methylnicotyrine (c.f. I.B.3.g.) or 
     dehydration of 4'-hydroxynicotine (c.f. I.B.l.d.).
       4. Preparation of Bridged Nicotines. This type of 
     nicotinoid represents the most difficult challenge in the 
     synthesis of nicotine analogues. In the past year, one member 
     of this class has been prepared in a one-step procedure from 
     tropinone and -aminoacrolein.
       Note that the carbon atoms which have the ``bold-faced'' 
     dots can be interchanged with the pyridine nitrogen atoms of 
     these compounds to produce isomeric bridged compounds. 
     Ideally, the preparation of the ``pairs'' of compounds will 
     be successful.
       5. Ring-Ring Shifted Nicotinoids. A number of compounds 
     falling into this class have already been prepared.
       C. Mechnistic Studies
       1. Kinetic experiments and stereochemical evaluations of 
     the alkylation of a wide variety of nicotinoids with 
     iodomethane and possibly other alkylating agents will 
     continue. These experiments are aimed to allow an 
     understanding of the steric, electronic, stereoelectronic, 
     and conformational features present in these systems. 
     Implementation of the totally automated conductivity system 
     is anticipated to be a milestone in such kinetic 
     investigations.
       2. Protonation studies will continue to allow the 
     evaluation of the conformation of the N-methyl group in these 
     nicotine analogues.
       3. NMR studies will be used as in the past to derive 
     conformational information about these molecules.
       4. Theoretical calculations (INDO, Ab Initio) will be 
     performed to give information regarding conformation, 
     electron distribution, polarizability, etc., of these 
     molecules.
       5. Kinetic studies involving a-cyanoamines will be 
     performed.
       D. Microbiological Studies. In collaboration with B. Semp, 
     a number of studies involving the use of microbiological 
     techniques to perform a variety of synthetic operations will 
     be investigated (c.f.I.B.l.c.; I.B.l.e.; I.B.l.f.; I.B.2.a.). 
     Also included will be an attempted large scale preparation of 
     nornicotine from nicotine.
       E. Pharmacological.
       l. Efforts will continue to obtain peripheral and central 
     nervous system data on our compounds. Some of this will be 
     with the aid of C. Levy and her associates.
       2. Partition coefficients and pKa data are needed for 
     our compounds.
       F. Insecticidal. More racemic and optically active nicotine 
     analogues will be submitted for in-house and collaborative 
     testing.
                                 ______

     To: Those Listed Dr. T.S. Osdene, Dr. E.B. Sanders, Dr. W.L. 
         Dunn, Mr. J.L. Charles, Dr. J.I. Seeman
     From: R.B. Seligman
     Subject: Nicotine Receptor Program--University of Rochester
     Date: March 5, 1980
       As you know, we have been supporting the subject program 
     for the past year, and Dr. Abood has visited with us several 
     times during this period. I would like an independent written 
     evaluation from each of you concerning the benefits this 
     program brings to our Research Center.
       Please transmit these reports to me by March 21.
                                 ______

     To: Dr. R.B. Seligman
     From: J.L. Charles
     Subject: Nicotine Receptor Program--University of Rochester
     Date: March 18, 1980
       Nicotine is a powerful pharmacological agent with multiple 
     sites of action and may be the most important component of 
     cigarette smoke. Nicotine and an understanding of its 
     properties are important to the continued well being of our 
     cigarette business since this alkaloid has been cited often 
     as ``the reason for smoking'' and theories have been advanced 
     for ``nicotine titration'' by the smoker. Nicotine is known 
     to have effects on the central and peripheral nervous system 
     as well as influencing memory, learning, pain perception, 
     response to stress and level of arousal.
       It is not surprising that a compound with such a multitude 
     of effects would have properties which are considered 
     undesirable by the anti-smoking forces. Claims are made that 
     nicotine in cigarette smoke can induce chest pain and 
     irregularities in cardiac rhythm when a person with a 
     compromised cardiovascular system smokes or when persons with 
     cardiac disease are exposed to high concentrations of side 
     stream smoke.
       For these reasons our ability to ascertain the structural 
     features of the nicotine molecule which are responsible for 
     its various pharmacological properties can lead to the design 
     of compounds with enhanced desirable properties (central 
     nervous system effects) and minimized suspect properties 
     (peripheral nervous system effects). There are many 
     opportunities for acquiring proprietary compounds which can 
     serve as a firm foundation for new and innovative products in 
     the future.
       The above is an excerpt from an introduction to the 
     nicotine program which I wrote on 12/1/78. My views have not 
     significantly changed since that time. I believe that 
     nicotine does play an important role in the smoking process. 
     How important that role is remains to be determined. The 
     receptor program at the University of Rochester is an 
     integral part of the nicotine program and can be justified in 
     a number of ways. An initial thought was that Dr. Abood would 
     have the knowledge and techniques to perform screening of 
     nicotine analogs for CNS activity. The synthesis group has 
     created a number of interesting compounds which are now being 
     screened by Dr. Abood. In addition Dr. Abood was to carry out 
     fundamental studies on sites and mechanisms of action of 
     nicotine in the brain. That research is in progress.
       I sat in on an additional meeting with Dr. Abood and Drs. 
     Sanders, Seeman, and Chavdarian during Dr. Abood's last 
     visit. I found the discussions to be useful and felt that Dr. 
     Abood was doing some very interesting work which can 
     ultimately be of benefit to Philip Morris. I also utilized 
     Dr. Abood as a consultant during that visit and he made some 
     good suggestions and I thought the time was well spent.
       In summary, the nicotine receptor program at the University 
     of Rochester is an integral part of our overall nicotine 
     program. The combination of basic research on the 
     pharmacology of the nicotine receptor combined with the 
     capability to screen nicotine analogs for CNS activity 
     complements our internal synthetic and behavioral efforts in 
     the nicotine program. The program is justified in my view as 
     a defensive response to the anti-smoking forces criticisms of 
     nicotine and also as fundamental research into the nature of 
     our product and how it affects 

[[Page H 7681]]
     our customers, the smokers. This entire program involves complex 
     technological problems and the benefits to be derived from 
     the program will not be realized immediately. Indeed the 
     benefits will necessarily be of a long-term nature and may 
     have direct bearing on our market position in a 10-15 year 
     time frame. However, if we do not have the basic research 
     results this program will provide we will not be in a 
     position to respond if and when the pressures to change do 
     occur.
                                 ______

     To: Dr. R.B. Seligman
     From: E.B. Sanders
     Subject: Nicotine Receptor Program--University of Rochester
     Date: March 21, 1980
       Dr. Leo Abood's collaboration with the Research Center has 
     been extremely beneficial to the nicotine program. His 
     assistance has impinged on four different areas; namely, 
     direct assistance to the Behavioral Research Group, 
     assistance in interpreting peripheral testing results, 
     providing us with current information regarding work 
     concerning nicotine pharmacology at other locations, and 
     direct hands on work in setting up binding assays for 
     nicotine analogues synthesized by members of Charge Number 
     2500.
       Dr. Abood's interaction with the Behavioral Research Group 
     has been of crucial importance in establishing the 
     ``prostration syndrome'' test. The value of this particular 
     technique to the nicotine program cannot be overstated in 
     that it is the first biological response to nicotine that 
     does not appear to be mediated by a cholinergic receptor. The 
     original charge of the nicotine program was (1) to ascertain 
     if the central and peripheral effects could be ``separated'' 
     and (2) to design a nicotine analogue which would have CNS 
     activity equivalent to nicotine with little or no peripheral 
     effect. Since it has been well-established that nicotine's 
     peripheral effects are cholinergic, the discovery of a non-
     cholinergic central receptor provides us with reason to 
     believe in the ultimate success of the program.
       Future work involving the ``prostration syndrome'' must 
     unequivocally establish the non-cholinergic nature of the 
     receptor and must explore the role that the ``prostration 
     syndrome'' receptor plays in the psychology of smoking. Leo's 
     expertise, involving his experience in the necessary 
     methodology as well as his work in attempting to characterize 
     the natural neurotransmitter for this receptor, is crucial to 
     the vigorous prosecution of this work.
       For several years we have been receiving data on peripheral 
     screening of our nicotine analogues from Germany. The quality 
     of the work has been consistently of the highest calibre. On 
     the other hand, the German laboratory has been of minimal 
     assistance regarding interpretation. The problem is a 
     combination of our lack of pharmacological sophistication 
     coupled with the large distance between Richmond and Cologne. 
     We have existed with this problem for some time since it 
     would be virtually impossible to match the good service we 
     are getting elsewhere. Leo Abood's association with Philip 
     Morris has consequently filled a void. Not only have we been 
     able to get a better handle on both the meaning of a given 
     test result but possible interesting follow-up tests on 
     certain analogues as well.
       Dr. Abood has occupied a position of preeminence in 
     neuropharmacology for some time. Consequently, he has 
     contacts with virtually all of the laboratories working on 
     various aspects of nicotine pharmacology, throughout the 
     country. These contacts have benefitted us by keeping us 
     abreast of interesting current developments as well as in 
     more direct ways. The best example of the latter involves the 
     direct assistance Leo is providing us in carrying out binding 
     assays for our synthetic analogues. Leo has obtained a sample 
     of purified nicotinic receptor from Torpedo and has 
     established the experimental conditions for assaying binding 
     to the receptor. We are now in the process of sending out the 
     first set of compounds. This assay will allow us to 
     differentiate between compounds which bind to the nicotinic 
     receptor but do not activate it and those compounds which do 
     not bind. With this information we hope to get a clearer 
     picture of the nicotinic receptor.
       In summary, I feel that we have benefitted considerably 
     from Leo's association with the Research Center, and I trust 
     that this association will continue.
                                 ______

     To: Dr. T.S. Osdene
     From: W.L. Dunn
     Subject: Plans and Objectives--1981
     Date: November 26, 1980
     INTRODUCTORY NOTES
       The Behavioral Research Laboratory effort is organized into 
     programs which reflect to a large degree the subdisciplines 
     of the responsible psychologists. On the one extreme of the 
     psychological spectrum is the social psychology program of 
     Dr. Sandra Dunn. On the other extreme is the behavioral 
     pharmacology program of Dr. DeNoble. Ranging between are the 
     experimental psychology program of Mr. Ryan, the 
     electrophysiology program of Dr. Gullotta and the smoke 
     inhalation program of Miss Jan Jones. Each of these programs 
     is but a varied attach upon the overall objective of the 
     Behavioral Research program: To contribute useful knowledge 
     about the response of the smoker to the cigarette and its 
     smoke. The results may prove useful in developing a new 
     product, or improving an existing product, or in the defense 
     of the company from legislative or litigative harassment.
     ELECTROPHYSIOLOGY PROGRAM . . . Gullotta and Shultz
     Objectives:
       It is our belief that the reinforcing properties of 
     cigarette smoking are directly relatable to the effects that 
     smoking has on electrical and chemical events within the 
     central nervous system. Therefore, the goals of the 
     electrophysiology program are to: (I) Determine how cigarette 
     smoking affects the electrical activity of the brain, and 
     (II) Identify, as far as possible, the neural elements which 
     mediate cigarette smoking's reinforcing actions.
     Planned Studies


            i. spectral analysis of the electroencephalogram

       We have proposed this study in the past but, due to 
     technical problems, we have been unable to undertake it. We 
     are finally in a position to begin.
       Numerous studies have investigated the effects of cigarette 
     smoking and nicotine administration on the 
     electroencephalogram (EEG) of man and other animals. Although 
     there is some degree of concordance among the results of 
     these studies, many points are yet to be resolved. For 
     example, with regard to the human literature, an early study 
     showed that cigarette smoking produced low amplitude, fast 
     EEG activity. Another study, however, found that smoking did 
     not increase low amplitude fast activity and, indeed, slowed 
     certain EEG frequencies. A number of other examples of this 
     type can be found in the literature.
       It seems likely that most of the controversies could be 
     resolved by a more systematic analysis and quantification of 
     the EEG. Therefore, we plan to spectrally analyze EEG data 
     from a variety of electrode locations under varying smoking 
     and deprivation conditions.
       II. Animal Electrophysiology
       We have discussed with Dr. DeNoble the possibility of a 
     collaborative effort to study the effects of nicotine and 
     nicotine-like compounds on the electrical activity of the rat 
     brain. This would involve EEG recordings from surface and 
     deep structures within several experimental paradigms. It 
     would also involve the use of evoked potential technology. 
     Some technical problems must be solved before such a program 
     can be initiated. Our early efforts will be aimed at 
     addressing these technical considerations.
       III. The Effects of Cigarette Smoking on Pattern Reversal 
           Evoked Potentials
       This study is well under way and will be completed in early 
     1981.
       We have previously demonstrated that cigarette smoking 
     increases the amplitude of the late components of the visual 
     evoked potential to flash stimulation. However, since flash 
     stimulation activates nonspecific brain structures (e.g., 
     reticular formation, association cortex, etc.) as well as 
     specific structures (e.g., primary visual cortex), we were 
     unable to determine with certainty whether the enhancement we 
     observed was due specifically to increased receptivity to 
     visual information.
       Pattern stimulation avoids the problems associated with 
     flash by activating primarily visual structures. Therefore, 
     we are using pattern reversal evoked potentials to 
     checkerboard stimulation to study the effects of cigarette 
     smoking on visual information processing.
       IV. Cigarette Smoking and the Habituation of Pattern 
           Reversal Evoked Potentials
       It is commonly reported that cigarette smoking facilitates 
     one's ability to concentrate. Concentration implies sustained 
     attention to simulation. We are interested in the possibility 
     that we might gain insight into the processes involved by 
     employing evoked potential techniques.
       When, within a given session, sensory evoked potentials are 
     repeatedly measured, there is a decrement in the response 
     over trials. We interpret this decrement as a decrease in the 
     sensitivity of the system to incoming sensory information. We 
     can then ask whether cigarette smoking alters the rate at 
     which this decrement occurs. If smoking retards the rate at 
     which the evoked potential decreases in amplitude over 
     trials, we will have demonstrated one manner in which 
     concentration might be facilitated by cigarette smoking.
       We have recently been gathering pilot data on this subject 
     employing pattern reversal evoked potentials. If our data 
     look encouraging we will mount a full-scale investigation in 
     early 1981.
     V. Cigarette Smoking and the Brainstem Auditory Evoked 
         Potential
       Recently, a new class of evoked potentials have been 
     described. These are the acoustic and sematosensory brainstem 
     (far-field) evoked potentials. One of the advantages of these 
     brainstem potentials relative to the more traditional forms 
     of recording is that the neural generators of the components 
     are better known. For example, it has been shown that Peak I 
     of the auditory brainstem response is due to VIIIth nerve 
     activity, Peak II to activity of the cochlear nucleus, etc..
       In this experiment we will be employing brainstem auditory 
     evoked potentials in an attempt to ascertain sites and modes 
     of action for centrally active smoke constituents. We chose 
     the auditory potential because (1) there are nicorinic 
     cholinergic synapses within the system and (2) it has 
     recently been shown that, in rats, systemic nicotine 
     administration alters certain components of the response.
     
[[Page H 7682]]

     THE BEHAVIORAL PHARMACOLOGY PROGRAM . . . DeNoble
       Objectives
       I. To develop a better understanding of the behavioral 
     pharmacological actions of nicotine, particularly the action 
     which reinforces smoking behavior.
       II. Develop the empirical evidence which differentiates 
     nicotine from the classical abuse substances.
       III. Use behavioral pharmacological methods for evaluating 
     the nicotine-likeness of nicotine analogues.
       Planned Studies--I. Nicotine Self-administration
       A successful development of the technique for establishing 
     self-administration of nicotine in an animal has important 
     implications for all three objectives of our behavioral 
     pharmacology program.
       We have developed that technique, making it quite clear 
     that nicotine can function as a positive reinforcer for rats. 
     We will use the technique (1) in studying the reinforcing 
     action of nicotine, (2) in differentiating nicotine from the 
     classical abuse substances, and (3) in evaluating analogues.
       We will undertake as many of the following essential self-
     administration studies in 1981 as time permits:
       (1) Examine the dose-response curve under various 
     schedules.
       (2) Examine the effects of cholinergic antagonists upon 
     self-administration.
       (3) Determine substitutability of selected analogues.
       (4) Demonstrate, in pursuit of Objective III, that (a) 
     nicotine self-administration does not interfere with on-going 
     behavior and (b) that termination of nicotine availability 
     for self-administration does not produce behavior impairment, 
     or alter self-administration of other reinforcers (food, 
     water, saccharine, etc.).
       II. The Nicotine-Induced Prostration Syndrome
       The prostration syndrome, first reported by Leo Abood as a 
     gross behavioral response to the intraventricular infusion of 
     nicotine, has been used routinely for several years in our 
     program of nicotine analogue evaluation.
       Although the prostration syndrome is a reliable screen for 
     behaviorally active nicotine analogues, the rating scale 
     developed by Dr. Abood provides only descriptive 
     interpretation of the compounds' effects, and does not permit 
     a determination of possible prolonged changes in CNS 
     activity. We have begun using scheduled controlled behavior 
     to evaluate the effects of intraventricular injections, since 
     measures based upon this behavior have been shown to be more 
     sensitive than activity rating scales, and provide a more 
     stable nicotine baseline from which to evaluate CNS recovery 
     times for nicotine analogues.
       We have recently observed in conducting these studies that 
     there is a diminution of the effect of nicotine over repeated 
     administrations. Diminution will occur even with a 7 day 
     interval between the first and the second administration, and 
     observation difficult to explain simply in terms of the 
     development of metabolic tolerance. We may be observing 
     instead an instance of behavioral tolerance. We are currently 
     designing a study which should more accurately characterize 
     the development of tolerance.
       We will also be conducting studies in which the effects of 
     the selective blockade of neural structure will be reflected 
     in the behavioral components of prostration, anticipating 
     that these observations can further our knowledge about the 
     sites of action of nicotine.
       III. Discrimination Studies
       We will continue to use the now standardized discrimination 
     technique to evaluate nicotine analogues. We are currently 
     investigating a dose-response curve approach, a modest 
     variant on the standard procedure.
     THE EXPERIMENTAL PSYCHOLOGY PROGRAM
       Objectives
       1. To gain a better understanding of the role of nicotine 
     in smoking.
       2. To study basic dimensions of the cigarette as they 
     relate to cigarette acceptability.
       Planned Studies--I. Salivary Nicotine
       Speculation suggests that smokers modify smoking behavior 
     to maintain certain levels of nicotine in the blood. 
     Historically this has been the basis of nicotine titration 
     hypotheses. Knowledgeable consideration of the issue suggests 
     that the changes in level may be more important than the 
     absolute levels--that the input of nicotine from a cigarette 
     creates a ``spike'' which is the summation of the discrete 
     puff-induced spikes.
       We now have the ability to measure via gas chromatograph 
     the level of nicotine in saliva. Observations from previous 
     work with salivation and smoking suggest that systemic 
     nicotine in saliva tracks with systemic nicotine in the 
     blood. We plan to use the g.c. measure to:
       A. Monitor the appearance and decline of nicotine in saliva 
     following smoking. This will shed light on the question 
     ``Does a low systemic level of nicotine trigger the smoking 
     response.'' The question can only be answered if measures are 
     made many times. Therefore, we will:
       B. Observe changes in salivary nicotine level across time 
     and smokings, relating the changes to the delivery of 
     cigarettes smoked and the time since prior smokings. The data 
     will bear upon the issue to the extent that salivary nicotine 
     reflects tissue and blood levels of nicotine. This must be 
     confirmed by means of:
       C. A correlational study of the salivary nicotine with 
     blood nicotine. This is awkward research to perform because 
     the taking of blood samples is so intrusive and objectionable 
     to participants and because it requires medical supervision. 
     Therefore, we will postpone this segment of the research 
     until it is evident that there are some systematic changes in 
     the salivary nicotine data. We have made some preliminary 
     contacts with our medical staff, and they will support us 
     when needed.
       II. There are tentative plans for one other project in 
     which nicotine will be delivered intravenously in different 
     sized spikes of different duration, to yield a broader 
     picture of the role of the spike, the level, and the 
     reinforcement characteristics of the substance. The execution 
     of this project is contingent upon the execution of study I-C 
     above, since both involve the dosing of numerous subjects 
     with nicotine.
       III. Other smoking related research
       1. Role played by Cigarette Firmness in determining 
     cigarette acceptability. Much attention has been paid to the 
     problem of maintaining the firmness of our cigarettes at a 
     level consistent with the image of a high quality product. We 
     have recently found that a trained panel's evaluations of 
     firmness are highly correlated with the firmness data 
     provided by the Firmness-while-smoking machine and our 
     compacimeter procedures. However, we know neither the 
     relative importance of firmness to the consumer (compared to 
     other characteristics of the cigarette's appearance) nor the 
     most desirable firmness level. We will try to find out.
       IV. Support for other projects, within R & D and within 
     behavior research, will be provided, as necessary.
     SOCIAL PSYCHOLOGY PROGRAM S. Dunn
       Objectives
       I. To gain a better understanding of the role of social 
     psychological factors in shaping cigarette smoking behavior.
       II. To apply social psychology techniques to the study of 
     cigarette acceptability.
       Planned Studies--I. Exploratory Study on Psychosocial 
           Determinants of Smoking Behavior
       As an initial approach to the problem, we have designed a 
     one-on-one interview including both objective questions and 
     in-depth probes. This interview is an intensive two-hours of 
     data gathering, ranging across a spectrum of social, 
     personality, attitudinal and situational dimensions. The 
     dimensions were chosen for inclusion because of their 
     potential relevance to smoking behavior. Items included in 
     the questionnaire/interview schedule can be subsumed under 
     these headings:
       1. Emotional state and responsivity.
       2. Stress-handling mechanisms.
       3. Situational determinants and cues.
       4. Socio-cultural influences.
       5. Health concerns and smoking.
       Interviewees are being drawn from among the population of 
     45 year-old, white, college-educated, upper-middle class 
     women, half of whom smoke high-delivery cigarettes and half 
     of whom smoke ultra-low delivery cigarettes. Focus on these 
     groups will also provide data on women smokers and on the 
     factors determining choice of delivery level.
       The data obtained will be subjected to a statistical 
     analysis designed to identify the underlying higher order 
     factors. The nature of these factors, and the extent of their 
     influence upon smoking behavior will provide the basis for 
     further studies. The analysis is scheduled for completion by 
     the end of the first quarter of 1981. Upon completion of this 
     analysis we will generate hypotheses testable under rigorous, 
     laboratory-controlled conditions.
       II. The Influence of Cigarette Firmness Upon Cigarette 
           Acceptability
       Mr. Ryan has reported a study of the correlation of 
     subjective firmness with measures obtained on the Firmness-
     while-smoking machine and on the compacimeter. The question 
     has been raised as to what relevance, if any, these measures 
     have to cigarette acceptability. We are designing a study 
     that will address this question. The study will incorporate 
     interview techniques of social psychology rather than rely 
     upon conventional marketing research survey methods.
     III. THE INHALATION MONITORING PROGRAM . . . Jones
       Objective: To determine in what manner the smoker 
     altersimulation patterns in response to changes in the 
     chemical composition of cigarette smoke.
       Planned Studies--I. Instrumentation
       A. Exploratory research using the new recording system. The 
     literature on smoke-laden inhalation research is limited, and 
     that which does exist suffers from severe technological 
     constraints. Our inhalation monitoring system provides us 
     with the advanced technology necessary to acquire fundamental 
     information about inhalation behavior. We are immediately 
     concerned with establishing valid and reliable criteria for 
     determining when a subject's inhalation patterns have 

[[Page H 7683]]
     stabilized--at what point we are seeing a reproducible representation 
     of the subject's inhalation behavior. In designing our 
     experiment we must determine what would be sufficient time 
     within each period of data collection for the smoking 
     behavior to stabilize, before introducing a new experimental 
     condition. Other information which is related to experimental 
     design involves what happens to baseline behavior, 
     established on a smoker's own cigarette, following 
     experimental conditions. Is there a return to baseline 
     inhalation behavior or will the baseline readjust? Carry-over 
     effects resulting from the use of repeated measures may occur 
     and must be taken into account.
       B. Programming a dedicated minicomputer for data display 
     and analysis. The MINC/DECLAB minicomputer, expected to 
     arrive early in 1981, will be used to store and display the 
     quantities of information collected. Following our 
     programming efforts, the computer will be customized to 
     handle the high-speed analyses required for our specific 
     needs.
       II. Experiment # 11: Does the smoker demonstrate 
     compensatory inhalation behavior in response to changes in 
     the nicotine content of cigarette smoke?
       The experimental design is repeated measures with an ABACA 
     format--a powerful method for examining what happens to 
     inhalation patterns when a smoker switches between cigarettes 
     of high, low, and ultra-low nicotine delivery. Baseline 
     measures will be taken on the smoker's own low delivery 
     cigarette until we observe stable behavior. The smoker will 
     then switch to an ultra-low or high delivery experimental 
     cigarette for two weeks, the order of presentation being 
     balanced across subjects. Following each experimental 
     condition, the smoker will switch back to his own cigarette 
     to re-establish baseline behavior. Our primary interest is in 
     comparing one inhalation parameters of Condition B with 
     Condition C, demonstrating differences due to nicotine 
     delivery of the cigarette smoked. The other 3 conditions will 
     mainly serve to make this information meaningful.
       We will be collecting data for approximately 2 months on 
     each subject. The study will begin early in 1981 and is 
     expected to continue throughout the year.
     

                          ____________________