It was mentioned by Jack Henningfield that my career in tobacco research, which was very short-lived, occurred in the 1960s. To start, I would like to review some of my early pharmacological research on cigarette smoking behaviour.

During the 1960s, it was not clear that cigarettes acted as a delivery device for the psychoactive substance nicotine. Rather, psychoanalytic theories of the aetiological basis of cigarette use stressed oral gratification. In order to look more closely at the pharmacological effect of nicotine on humans, five human subjects (referred to then simply as ‘smokers’), all of whom were dependent on tobacco, were recruited for a study supported by the American Medical Association (Lucchesi, Schuster and Emley, 1967).¹ Ben Lucchesi, a cardiovascular pharmacologist and physician, and I looked at what would happen over a 6-hour period to cigarette smoking frequency if smokers, who believed they were being studied for an unrelated purpose, were infused with nicotine.

Subjects were 21- to 30-year-old male and female volunteers. They were studied for 15 consecutive days, and completed a 6-hour experimental session daily. A Y-adapter was used to infuse intravenously 0.9% sodium chloride continuously, and either nicotine bitartrate or saline solution, randomly. The subjects were unaware, at all times, of the order of infusion. Both the number of cigarettes consumed during each session and the weight of the unsmoked portion of the cigarettes was measured and recorded. Only subjects who were capable of tolerating a 4 mg/h dose of nicotine without subjective responses were included in this study.

It was found that Subject 1 smoked 17.9 cigarettes on average across seven sessions in a 6-h period, with very little variance, and a standard deviation of only 0.72. The rest of the subjects showed the same type of regularity from session to session. As a matter of …