In this occasional series we record the views and personal experience of people who have especially contributed to the evolution of ideas in the journal's field of interest. Ian Stolerman is best known for his work on nicotine and for his advocacy of drug discrimination methodology in the broader field of behavioural pharmacology.
Addiction (A): Could we start, as is conventional in these conversations, by asking you a little about your family background, your early life and your schooling? Where did you come from, Ian?
Ian Stollerman (IS): I went to grammar school in Brighton and then to the London School of Pharmacy (colloquially, ‘The Square’). In fact, around the age of 14–15 years, I had my first dealings with tobacco. I helped out in a family business, a retail confectionery and tobacconist's shop, during school holidays and I knew the names of every brand of cigarette, which ones had filters and which did not. As far as I can remember, most did not have filters then.
A: Those were the days of Woodbines!
IS: Woodbines and Navy Cut and Senior Service. I did sell quite a lot of these over a couple of years. I am not sure whether I was really legally allowed to be working there, doing that. I do remember that when Richard Doll's early work on smoking and cancer was headline news in the national papers, my father said: ‘This will be the end of our business. Nobody's going to smoke after this.’ Smoking as an addiction was not on the radar at that time.
A: So I guess you did science subjects at school?
IS: Physics, chemistry and biology at A-level, and a smattering of extra mathematics and geology.
A: Do you remember what it was that stimulated your interest in pharmacy?
IS: The breadth of coverage of the course, ranging through biological to physical sciences.
A: And so your undergraduate degree at the School of Pharmacy in London, tell us about that.
IS: It was a small college, very strong in research but rather lacking as a broader, intellectually stimulating environment. I realized that when I went to University College London (UCL) for postgraduate studies. Nevertheless, the quality of the teaching at The Square was very high and its excellence in pharmacology stimulated my interest. I discussed studying for a PhD with Mike Rand, then a lecturer, and he suggested that I think about psychopharmacology. It was remarkable that Rand had a PhD student, Mike Clark, who was conducting a project on nicotine that involved both human and animal work; I was a non-smoker control subject in one of his experiments. What was quite extraordinary was his work on both oral and intravenous self-administration of nicotine in rats; he reported that both these experiments were successful. Only an abstract was published .
A: That is in the prehistory of nicotine behavioural research.
IS: Yes. Those studies probably would not meet present-day criteria, but nevertheless they were noteworthy, and the work was supported by the tobacco industry whose documents refer to ‘early work on animals pressing levers to be rewarded with nicotine, and the view that the general conclusion of Dr Clarke (sic) was that there was much evidence to support the assumption that smokers smoked in order to obtain the pharmacological effects of nicotine in the tobacco’ (Legacy Tobacco Documents Library, http://legacy.library.ucsf.edu/tid/cxl55a99/pdf, University of California San Francisco). That conclusion was subsequently denied by many companies.
A: This was the Mike Rand who developed one of the first blood nicotine assays?
IS: Yes, that was after he went back to Australia to take up the chair of pharmacology in Melbourne. Mike Clark eventually went into the pharmaceutical industry and 30 years later, in the mid-1990s, he and I got together again. Due to his support, Smith Kline and Beecham part-sponsored a PhD studentship held by N. R. ‘Max’ Mirza on the cognitive enhancing effects of nicotine. That was my entrée into an area that became a major line of work in my laboratory. I suppose we should deal with the conclusion of the Mike Rand story.
A: Yes, because he ran into repeated ethical difficulties.
IS: He was a terrifically stimulating teacher who was much feared by most of the students because he would ask difficult questions. Sadly, he became wrapped up with the tobacco industry, as I became aware at a conference that took place near Montreal around 1993, where I presented a paper arguing the case for nicotine being an addictive substance, based on a review  that was in preparation. Rand presented the chairman's summary and said that he found the concept of nicotine addiction to be ludicrous. He did not actually refer to any evidence that he thought was invalid and it was painful for me to hear such remarks from someone to whom I owed a great deal, not least because it was an abuse of the chair's position.
A: He had gone to the dark side?
IS: When I was dipping into subsequently published tobacco industry papers I found that he had strong links with the industry whose report on the meeting stated: ‘His closing remarks at the symposium were very much in agreement with the views of the tobacco industry. He does not believe that smoking causes lung cancer or cardiovascular diseases. He said that it was ludicrous to equate heroin and cocaine with nicotine’ (Legacy Tobacco Documents Library, 1993, http://legacy.library.ucsf.edu/tid/zxy38d00/pdf, University of California San Francisco).
A: Still, he helped develop your career by making, pointing you in the right direction, and your next port of call was the pharmacology department at UCL.
IS: He pointed me towards UCL where I conducted my PhD studies in the pharmacology department headed by Heinz (pA2) Schild under the supervision of Hannah Steinberg, who became the first professor of psychopharmacology in the United Kingdom. My interest in psychology came about even while I was in Brighton, when I started reading popular books about experimental psychology, such as those by Hans Eysenck (Uses and Abuses of Psychology and Sense and Nonsense in Psychology). Then, after discovering Aldous Huxley's The Doors of Perception, it was a natural step to write an undergraduate dissertation on hallucinogens in relation to schizophrenia. There was little interest in psychopharmacology at The Square, although there was one lecture on addiction. I have never forgotten the speaker's opening comment to the effect that it was a disreputable area and we should steer clear of it if making a career in pharmacology.
‘There was little interest in psychopharmacology at The Square, although there was one lecture on addiction. I have never forgotten the speaker's opening comment to the effect that it was a disreputable area and we should steer clear of it if making a career in pharmacology.’
A: Now this would have been about 1963. I think what is coming across to me is that behavioural studies of addiction and even behavioural pharmacology were both somewhat in their infancy as academic research disciplines. Would you agree?
IS: That is certainly true. Although there were important studies in behavioural pharmacology published in the 1950s, it was a long time before it received much recognition; so it was notable that Hannah Steinberg had the opportunity to work within a pharmacology department. The group was spread between pharmacology and psychology in UCL, as well as part of the adjoining Birkbeck College.
A: I seem to remember seeing the young Channi Kumar and yourself in the pharmacology department around about 1969.
IS: We both completed our PhDs there, and collaboration with Channi was immensely important because we provided much-needed mutual support. We also learned our trade from diverse others around the place. David Colquhoun (who later held the A. J. Clark Chair of Pharmacology at UCL) was then a junior lecturer and was looked up to by younger members of the department because he owned a Mercedes sports car. It was from him, a neurophysiologist, that I learnt about statistics because he taught statistics in fairly plain English for medical students. At a later date I was asked to teach about disinfectants in the same department! I arrived with little knowledge of psychology and Hannah encouraged me to go to a course run by A. R. Jonckheere (noted for a statistical test for trends). I found his lectures on experimental design very helpful, covering, for example, the controls needed before you could say that something was a conditioned phenomenon. He was talking mainly about worms, but the general principles were there.
A: Your PhD?
IS: My PhD, like Channi Kumar's, had nothing to do with drug dependence, but we attended a lecture by the pathologist Francis Camps; he talked about intravenous drug use and showed horrific slides of heroin users who had overdosed. Channi and I realized that it was an area in which behavioural issues had received little attention. We were aware of a few reports on drug self-administration from American laboratories and we persuaded Hannah to let us conduct some studies on oral morphine intake in rats. We made some progress, and it became quite a significant line of work in the department. I was much more interested in that than in my PhD. Travis Thompson, from Minneapolis, was spending some time in England and he told us about his then unpublished, pioneering work with Roy Pickens on intravenous cocaine self-administration. It was immensely encouraging and helpful to have him around. Being a PhD student in Hannah's group was exciting in other ways which we did not recognize at the time. Apart from Channi Kumar, other students included Roger Porsolt, who subsequently developed a classic screening test for antidepressants, and David Sanger, who became President of the European Behavioural Pharmacology Society. Malcolm Lader held a post-doctoral position in pharmacology and I met his student, Martin Jarvis. Although I did not have much professional contact with Martin for a long time afterwards, we did both end up working in the nicotine area and we wrote a much-cited article together .
A: At UCL you were awarded your PhD, you acquired some skills as a behavioural pharmacologist and then it was time to move on.
A POST-DOCTORAL POSITION IN NEW YORK
IS: Much of the psychopharmacology research that interested me had originated in the United States and I secured a postdoctoral position with Murray Jarvik at the Albert Einstein College of Medicine in New York. Murray had been extremely active in the psychopharmacology of learning and memory, but in 1971 his nicotine work was at a relatively early stage. I had wanted to go there because of the studies on learning and memory. I did not see myself as a drug dependence researcher. I was somebody interested in the behavioural effects of drugs but not especially in the addictive aspect, despite the fact that I had carried out some work on it, but Murray had an opening on the nicotine project. The first thing was to get there, and then to get into the learning and memory work! However, when I arrived at Einstein I found I found the nicotine area to be quite challenging, and I became absorbed in it. One of the benefits of that era was that the literature was smaller, there was time to read around the subject very thoroughly, and I did not have to write grant applications. I had spoken previously about nicotine with two prominent pharmacologists in Britain. The first said my plans would be a waste of time because nicotine does not do very much and people do not smoke to gain drug effects. Then I spoke with the second person, who also said that it would be a waste of time, because it had already been established that nicotine was what smoking was about. So these two people reflected very well the perceptions of nicotine psychopharmacology at the time.
A: It was either uninteresting or passé. In fact, you contributed to a truly seminal study on modulating the central effects of nicotine with mecamylamine and its effects on smoking.
‘. . . you contributed to a truly seminal study on modulating the central effects of nicotine with mecamylamine and its effects on smoking’.
IS: I would like to tell you how that study  came to be performed. Shortly before I arrived at Einstein, Murray's group had published a report that mecamylamine stopped rhesus monkeys smoking in a model situation that they had developed. I read the paper and although it was in Nature, I was not convinced by it. I was too nervous to express this view to Murray just a week after I arrived. By then work had moved on to studies in which a small number of human volunteers would take mecamylamine and report their smoking behaviour while they were in their normal environments, at home, on holiday, or at work. It was not a smoking cessation trial, but a matter of seeing whether the substance would simply stop people smoking. It did not. We discussed the next step, and I thought it was important to work in a better-controlled environment and also to determine whether the mecamylamine was actually blocking nicotine. I proposed an adaptation of the experimental situation used by Hannah Steinberg for studies of amphetamine–barbiturate mixtures , where experimental subjects sat around a table work in pairs carrying out psychomotor tests and each one would score the performance of the other. The psychomotor tests were there in part to disguise the main purpose of the work, which was to score smoking behaviour. We selected tests to include some that might be sensitive to nicotine and nicotine antagonists; and we allowed subjects to smoke their usual cigarettes in the laboratory in the medical school, for which we did not have to gain approval at that time.
A: You would not be able to do it now!
IS: There would be problems now, and those of us who did not smoke had to put up with the smoke. We very quickly found that subjects were smoking more cigarettes when they had mecamylamine and when we gave pentolinium instead, which did not penetrate to the central nervous system (CNS), we did not see the effect . It was a happy experience for me because, in addition to Murray Jarvik's strong support, I had a superb collaborator, Tony Goldfarb.
A: That was really your first nicotine research and, thinking back, can you remember now what your take was on smoking and nicotine at that time? It was then a very unfashionable area.
IS: There was little known about the role of nicotine in smoking. Murray repeatedly raised that question and stated the objective of finding out whether people were smoking to get nicotine. One of the things I learned from Murray was the need to have a research question that does not need an hour-and-a-half to define.
A: It is as if you are pitching a Hollywood movie idea, it has to be expressed in 30 seconds or less.
IS: If the idea is so obscure and complicated that it cannot be explained fairly quickly, then how important is it going to be? Murray stuck with that theme, which guided the direction of work during my year in New York and also at the University of California at Los Angeles (UCLA), to which the group moved. The year at the Albert Einstein College was also wonderful because it had been a centre for drug dependence researchers, including Seth Sharpless and Jerry Jaffe. The department was headed by Alfred Gilman (editor of the classic pharmacology textbook), and I shared an office with Eliot Gardner who, like me, did not envisage making a career in drug dependence research. I saw the nicotine work as a short-term diversion. It was a good many years later that Eliot carried out his important work on cannabinoids and the dopamine system at the National Institute on Drug Abuse in Baltimore.
A: Jerry was about to become Nixon's first drug czar.
IS: That is right, Jerry had recently left Einstein but came back to lecture to the medical students. I went to the lecture and it was really brilliant. He had a big impact upon me, and we talked about the work on nicotine tolerance that I was doing that year, as well as the studies with mecamylamine in humans. Murray gave me a very free hand to conduct the studies on tolerance in rodents. Again, I used a method adapted from Hannah Steinberg's work. This was a Y-shaped runway, the so-called ‘Y-maze’, for recording the locomotor activity of rats, and we found a rapidly developing and long-lasting tolerance to nicotine. The main paper  became my most highly cited article, although it was about nicotine tolerance only because we did not succeed with the objective of detecting nicotine withdrawal signs. That needed more complex techniques . Nevertheless the Y-maze paradigm was adapted for mice by Alan Collins at the Institute for Behavioral Genetics in Boulder, Colorado , and used in a very extensive programme on genetic determinants of sensitivity to nicotine.
A: You liked New York?
IS: New York was a wonderfully stimulating environment because of the exciting atmosphere and cultural life of the city, and because of the interesting people that I met. I then had the opportunity to join Murray at the early stages of his work at UCLA, and that was a continuation of the golden era where I was working on good projects without needing to write grants.
A: The UCLA group under Murray obviously became one of the main dynamos of behavioural nicotine research.
IS: There were at least two very strong groups at the time. One of them was Michael Russell's group here, at the Institute of Psychiatry in London. Murray's group at UCLA was a great one to be in and I developed long-lasting friendships with several of its members, notably Ellen Gritz and Nina Schneider who, like me, built careers from the smoking work. Ron Siegel was conducting remarkably innovative studies on hallucinogens and cannabis and was another stimulating colleague.
A: And Saul Shiffman.
IS: Murray recruited Saul about a year after I moved to UCLA and he was one of several younger people who went on to develop strong careers. Saul was notable even at that time for his incisive and original comments on literature which made us change our ideas about some published work.
A: Saul has continued to be a very insightful and creative researcher throughout his career.
IS: He is a person whose work I have much respected. My laboratory at UCLA was in the newly built psychology building (Franz Hall), and much stimulation came from discussions with others in that department. John Liebeskind was soon to begin his remarkable work with naloxone and placebo effects, and John Garcia, the father of conditioned taste aversions, had joined the department. An immensely beneficial aspect of my 3 years in the United States was the many other contacts made with drug dependence researchers.
A: By the end of that period, were you starting to think of yourself as a drug dependence researcher?
IS: Yes, I saw that area as my main, but not exclusive, future line of work. One of the most significant happenings while I was in Murray's group was meeting Steve Goldberg, with whom I collaborated on several projects, including the joint editing of Behavioral Analysis of Drug Dependence. In that book we brought together many of the different areas of research that in the 1960s and 1970s marked the broadening of pharmacology research from tolerance and withdrawal phenomena to embrace drug-taking behaviour .
A: That was before Goldberg conducted his work on self-administration of nicotine in squirrel monkeys?
IS: It was well before that. He was working on cocaine and opioid self-administration and other topics. I must also mention Abraham Wikler, one of the very first people to discuss the role of conditioning and learning in drug dependence. His orientation was much more towards classical than operant conditioning, but he did perform oral intake studies with opioids. He seemed to take me under his wing and I learned much from him.
A: That was your very formative period in the United States, where you got to know the aristocracy of behavioural drug dependence researchers, and then you came back to the United Kingdom to further your career over here. Had you got married by then, or was that later on?
BACK TO ENGLAND AND A DRUG DEPENDENCE CAREER
IS: I was entering a stage of contemplation about marriage; but it was not until 1978, about 5 years after I came back to England to join the ill-fated Medical Research Council (MRC) Neuropharmacology Unit in Birmingham, that I met Suad, my future wife. We married a year later, by which time I was planning a move back to London.
A: That period in Birmingham was not one of the high points of your career. It was a little under threat right from the moment you came there, wasn't it?
IS: Marriage was the high point of the period! I think we did some good, well-recognized work there, but overall it was a less happy time. Philip Bradley, the Director of the unit, was very supportive and from him and Ian Martin I learned a little about the pluses and minuses of some neurophysiological and neurochemical techniques. Our behavioural studies proceeded well; even in the first year during which my laboratory was being constructed, I began a collaboration with members of the Psychology Department (David Booth and his post-doctoral researcher, the late Charles Pilcher). We were successful in demonstrating strong conditioned taste aversions induced by amphetamine and by opioid antagonists with an elegant paradigm that David had devised. We had just completed the first experiments in my newly built laboratory when there was an MRC site visit aimed at building a case for closing down the unit, on which a firm decision was made a couple of years later.
A: Then you visited the University of Maryland?
IS: The taste aversion work inter alia demonstrated its impact on operant responding ; this led to an invitation to make a lengthy visit to the University of Maryland in College Park, a strong centre for behavioural pharmacology research due to the presence of Lew Gollub and Jim Barrett. The visit served as an extended honeymoon, because it took place only a few months after Suad and I were married. In all we spent about 6 months in the United States. I did not have any firm place to come back to until, while still in Maryland, I received a one-word telegram from Channi Kumar. The word was Gaudeamus, referring to the successful outcome of our joint application for an MRC project grant. The project was on nicotine and it enabled me to join the MRC External Scientific Staff and move to the Institute of Psychiatry in London.
‘, . . . I received a one-word telegram from Channi Kumar. The word was Gaudeamus, referring to the successful outcome of our joint application for an MRC project grant.’
SETTING UP WITH AN MRC PROJECT GRANT IN LONDON
A: Have you heard of the one-word Latin telegram, peccavi, sent by British General Sir Charles Napier after annexing the Indian province of Sind in the 19th century, meaning ‘I have sinned’. Enough of one-word Latin. And so you came to the Institute in 1980?
IS: That is right, and while in Birmingham, I had worked with the two techniques that formed the core of the initial studies we used in London, these being drug discrimination and conditioned taste aversions.
A: Drug discrimination was an incredibly important technique.
IS: It was well established in the literature by the time I came to use it. It employs operant conditioning to train either animal or human subjects to report whether or not they have been given a particular drug, which we refer to as the training drug. Humans might report by saying ‘yes, I had the drug today’ or they might press one button to indicate ‘yes, I had the drug’ or another button to say ‘I didn't get the drug’. Similarly, animals can be rewarded for choosing which lever to press, according to whether or not they have been given a drug. They learn this remarkably quickly, as easily as they learn to discriminate lights or sounds. I had been interested in this area of psychopharmacology ever since the first reports from Don Overton in the 1960s. The techniques improved a great deal, and by the early 1970s the quality of the data from some laboratories was so striking that I thought we really had to use it. We used this approach as a behavioural assay for CNS effects of amphetamine and cocaine while I was in Birmingham. This technique was at the core of my MRC and National Institute on Drug Abuse (NIDA)-supported work for many years afterwards, despite a comment (now in the public domain) from a grant reviewer expressing a hope that I would not continue with this method for very long.
A: It is a very productive way of asking animals questions about how they perceive drug effects.
IS: It had appealing methodological advantages such as the feasibility of essential control tests, the quality of dose–response curves and reproducibility of findings. The method is very useful for characterizing the pharmacology of a substance and is recommended for use in the United States and Europe for assessing abuse liability. We used it for identifying the receptors and neurotransmitters through which drugs produced behavioural effects and in studies of abused drug mixtures. In 2002 we collaborated with Jean-Pierre Changeux (Pasteur Institute, Paris) to study the role of the β2 subunit of nicotinic receptors in the first study of drug discrimination in knock-out mice ; but in 1980, it was one of the very few methods in rodents that could generate clear strong dose–response curves for smoking-level doses of nicotine via actions on nicotinic receptors in the CNS. That situation has changed over the years through the development of, for example, self-administration studies.
A: It was a very important research tool for at least 15–20 or so years and provided many insights.
IS: After Bill Corrigall developed a nicotine self-administration procedure for rodents it ceased to be the best way of determining dependence-related effects of nicotine in rats, although it is still a useful supplementary method.
A: Shall we get on to your return to the Institute, actually in the same institution where Mike Russell and his group were based? That is where you really spent the rest of your career, very productively, so tell us about how things developed at the Institute.
IS: The original plan was to conduct combined human and animal research on nicotine in collaboration with Channi Kumar and Malcolm Lader, whom I knew from UCL and who was well established with a large research group at the Institute at that time. We had applied for an MRC grant combining human and animal work that was turned down, with a criticism that it was really two separate lines of work that should be supported independently. Channi Kumar and I then applied for a grant to conduct the animal studies, which led to the Gaudeamus telegram. Contacts with Mike Russell and members of his group were immensely beneficial, but we never carried out joint research. My group collaborated with the Department of Neurology, where there was expertise in ligand-binding techniques. Two outstanding postdoctoral researchers joined my group from neurology, Charlie Reavill and Judy Pratt (now Professor of Systems Neuroscience in Glasgow, Scotland).
A: You collaborated with Mike Russell on a book.
IS: Our ideas and concepts were often very similar, which made the book , edited together with Susan Wonnacott (University of Bath), an enjoyable venture. I have also had a number of research collaborations with Susan. In fact my nicotine research was supported by a series of 3- and 5-year grants upon which my own position was entirely dependent.
‘. . . my nicotine research was supported by a series of 3- and 5-year grants upon which my own position was entirely dependent’.
A: You were living hand-to-mouth, really, as a researcher with, however, no security of tenure over quite a long period.
IS: In a sense there was security, because I had what MRC described as an appointment of unlimited duration, but the terms of the appointment would be breached if I was deemed to be working at reduced efficiency. The definition of reduced efficiency included failure to win an MRC grant.
A: It sounds a little like catch-22.
IS: It was anxiety-provoking, particularly as I was married and we had young children. There were some advantages, in terms of greater independence to pursue my own direction in a full-time research job, with very limited administrative duties. The Institute was extremely supportive and, for example, funded the building of a new laboratory for me around 1988; so I continued working with Channi Kumar, who was gradually moving out of behavioural pharmacology and starting up his very successful work in perinatal psychiatry. Work on nicotine was at the core of studies in the section of Behavioural Pharmacology that I took over from Channi. Paul Clarke (now a Professor of Pharmacology at McGill) was finishing his PhD on nicotine in rodents and so he used to ask me lots of questions, and I soon found out that he knew more than I did about the most of the topics that we discussed. Later students and post-doctoral researchers who joined the group and then pursued research careers included Max Mirza, Mohammed Shoaib, Chris Chandler, Nimish Sidhpura, Britta Hahn and Emma Childs. Shoaib, for example, was immensely productive and started our studies on glutamatergic mechanisms and on self-administration. It makes me a little sad that a third or more of the students and post-doctoral researchers who came through the group are now working overseas.
A: The central thrust of your work at this time?
IS: The work in my group was about nicotine's mode of action and aimed to identify the types of nicotinic receptors and neurotransmitters through which it acted to produce behavioural effects and dependence. That was the core of our activity, but other lines of research were developing as well. We had also started studies on the discriminative stimulus effects of drug mixtures. As we were the first to train with the benzodiazepine midazolam in drug discrimination experiments, it was a natural step to go on to use mixtures of nicotine and midazolam as prototypical discriminable drugs for this work. The studies aimed to aid understanding of how single drugs with multiple effects were discriminated, with possible applications to abused drug mixtures. Jeevi Mariathasan, Harbach Garcha, Sherelle Chamberlain and Julie-Anne White were among the many colleagues who put much effort into these investigations. Fortunately I was able to obtain a series of NIDA grants to support the development of the work from 1987 onwards, after MRC rejected it. The studies showed how associative processes such as blocking and overshadowing could influence drug effects and could account for some influences of behavioural history on pharmacological response . The ideas put forward had broad applicability in the discrimination area and informed the work of Kathy Grant's group in South Carolina on that very well-known drug with multiple actions—alcohol.
A: Can I just ask you about your view of nicotine, because by 1985, many other people were thinking of you as definitely a nicotine researcher. This was an area which had evolved greatly since you first became involved in it in 1971, and many things were changing. There was an explosion of scientific knowledge, but also the politics of nicotine had changed greatly, so I wonder if you can give us a perspective on how you lived through all that and your own views on nicotine use as an addiction and the role of the industry in trying to shape opinion.
IS: At the start I saw the issue of nicotine addiction as an open question. There was some evidence but there were many gaps. Murray and I filled in one or two of the gaps, but there was still much more to be done; but in 1981 the self-administration study in primates by Goldberg & Spealman settled the issue for me ; the human work had also come a long way, and I did not think there was any doubt that nicotine induced dependence and functioned as an abused (addictive) drug. The wider recognition of that situation was triggered by the 1988 report from the US Surgeon General, which codified what most researchers within the area had believed for many years.
A: What has been your experience with the tobacco industry?
THE TOBACCO INDUSTRY
IS: When I first encountered the tobacco industry my attitude towards it, and that of my colleagues, was such that we did not see it as a major threat or in an exclusively negative way. The industry was publishing some important work on nicotine in the late 1960s, such as that by Armitage et al. , but we did not know about the work that they were not publishing. When I was with Murray Jarvik we had communications with Philip Morris (PM); it is fair to say we were no more than a little bit wary of their motives and there was a certain naiveté in that. During this period, I first became aware of the proclivity of the industry to suppress data. A researcher at PM told me that they had developed research cigarettes that differed with respect to the ratio between nicotine and tar delivery, rather than just the absolute amounts. The researcher offered some of these cigarettes for our work, because company lawyers had prohibited publication of his data. Interestingly, the results of his experiments were negative with regard to nicotine, so it seemed to me that PM did not even want it known that they took seriously the possibility that people might smoke for nicotine. The result was that we conducted a study which attempted to separate the role of nicotine and tar. It was very limited, for various reasons; for example, we did not have a nicotine blood assay and relied upon urinary nicotine, an indirect measure of the amounts taken. The results indicated that it was the nicotine rather than the tar that influenced smoking, but it was a rather low-impact paper .
A: So you realized that the industry could suppress data?
IS: That was when I first realized the industry would suppress data. At the time, issues about ethics of what is published and what is not were very unformed in our minds. Changes came about in the 1980s when I was back in London. The British American Tobacco (BAT) Company sent Sharon Boyce (formerly a benzodiazepine researcher) to visit the Institute of Psychiatry to push grants onto us. I met with her but indicated that I was not interested in applying. Her report noted accurately that I was ‘unfortunately, of the opinion that scientists who are funded by the tobacco industry lose their scientific credibility’ (Legacy Tobacco Documents Library, http://legacy.library.ucsf.edu/tid/iml00a99, University of California San Francisco). BAT did succeed in placing a grant with Professor Jeffrey Gray in our psychology department. He conducted some interesting work on the neurochemistry of nicotine actions in the CNS under this grant. What he did not know about was the view inside BAT that he was effectively silenced as a potential and powerful source of hostility. Company staff expressed this more colourfully to me in the statement: ‘this year we got Jeffrey Gray under our belt’.
A: They were right.
IS: They were right in so far as Jeffrey was deflected away from working explicitly on nicotine addiction and in time he came to question the concept.
A: He was a contrarian.
IS: He was not easily persuaded of things with which he did not agree. Whether or not there was an influence of the funding on his views is highly debatable, but his views certainly did change. That was one of the reasons why he and I never collaborated.
A: Of course, the Institute also had perhaps the most famous industry apologist of all time in Hans Eysenck, working there for many years.
IS: Hans was still here when I arrived, and he had a history of work on nicotine which I actually first encountered when I was a PhD student at UCL. He had edited a massive book on his work with drugs, but I found it to reveal fundamental misunderstandings about how drugs worked. He had major support from the tobacco industry and also wrote a book arguing against a role for tobacco smoking in the development of lung cancer. That was embarrassing for the Institute of Psychiatry, and by the late 1990s the continuation of industry support for Gray's group was becoming a further worry because of potentially unfavourable, albeit unfair, publicity. The Wellcome Trust was also ceasing to fund institutions that accepted tobacco money. The matter came to a head when a debate was provoked by an imminent broadcast of Despatches, a TV programme. I argued against acceptance of tobacco industry funding, which was proscribed from that time onwards. These events also helped to set the scene for the subsequent establishment of stricter Institute guidelines for funding from the alcohol industry.
A: Of course, in recent years, when you took up the role of journal editor, I imagine ethical issues must have also started to play a more important role when you considered not just nicotine, but other drug dependencies as well.
IS: From a fairly early stage in my period as the associate editor of Drug and Alcohol Dependence, ethical issues about funding sources were a concern. I had to chase some authors rather hard to get them to divulge their funding source. The journal, like others, developed much stronger rules and guidelines for authors about what they had to disclose.
PRESIDENCY OF THE INTERNATIONAL SOCIETY OF ADDICTION JOURNAL EDITORS (ISAJE) AND THE EUROPEAN BEHAVIOURAL PHARMACOLOGY SOCIETY (EBPS)
A: Of course, the ISAJE organization, of which you were a prominent member, is concerned with achieving a more unified approach among different addiction journals to some of these problems.
IS: Griffith Edwards and Tom Babor founded the ISAJE. Griffith involved me in it and after a few years he persuaded me that it really was not a great deal of work to be the President of this small organization. I accepted the nomination and actually became quite pleased with the progress that the Society made. I learned that a small society can be just as much work as a larger one, because it does not have the same infrastructure and the same number of people to whom tasks can be delegated. It was by no means the first society with which I had been actively involved. Most notably, while I was at the Institute of Psychiatry Francis Colpaert and I founded EBPS, of which I became the first President. EBPS became the strongest society in the world devoted exclusively to behavioural pharmacology, and overall I am more proud of what I achieved with EBPS than with my scientific research.
A: Your career has precisely spanned the period when this discipline was developing and coming of age, and a society like that encapsulates that success.
IS: EBPS was very much needed. Behavioural pharmacology research could be presented at general pharmacology meetings or at other psychopharmacology conferences, but they were orientated toward different disciplines and the latter were often predominantly clinical. The success of EBPS was apparent from an early stage.
A: Now, of course, just in the last year you have retired from your post at the Institute of Psychiatry, so you are no longer engaged day-to-day in laboratory studies and have more time for these other kinds of professional activities. Are you planning to stay closely involved?
IS: I have continued with a collaboration involving Professor Lisiane Bizarro, a former post-doctoral researcher in my group now based in Brazil, with whom I held a grant from the Wellcome Trust. The project, on prenatal exposure to nicotine and alcohol in rats, was carried out in parallel in London and in Porto Alegre, Brazil. I also continue to work on the bibliographic database of drug self-administration and drug discrimination research. This began in 1982 without outside support and my first NIDA grant, awarded in 1986, was for supporting the database. The grant is still going after a succession of renewals, but after retiring I handed over the principal investigator role to Dick Meisch (Houston, Texas). After stepping down from the editing role in Drug and Alcohol Dependence I became editor of the Encyclopedia of Psychopharmacology, the first edition of which was published by Springer in 2010.
A: You are still remarkably busy in many fields, and it sounds as if you are going to be busy for years to come.
IS: I am busier than I expected, but I have more time for other interests, such as dabbling in photography and researching my family history. I enjoyed behavioural pharmacology; I think it was the right area for me and I do not know of any other in which I might have achieved similar success.
‘I enjoyed behavioural pharmacology; I think it was the right area for me and I do not know of any other in which I might have achieved similar success.’
A: This is an area that has an exciting scientific future, I think.
IS: In some areas we have excellent animal models and drug dependence (including nicotine) is a notable example, whereas for others, such as schizophrenia and depression, the models are much weaker. However, most of the models for dependence were designed for studying mechanisms rather than to evaluate treatments. The animals are not placed into a situation equivalent to a treatment programme. Drugs are used to assist smoking cessation, rather than as magic bullets given to people who are not prepared to make an effort to stop. People in treatment are motivated by the consequences, actual or potential, of not doing so; animals are typically not motivated to stop self-administering. That is the gap; we need appropriately motivated animals and I believe they can be developed.
A: So there is plenty for an ongoing research agenda there. Thank you very much indeed, Ian, for talking to Addiction. It has been a real pleasure.
The opinions expressed in this interview reflect the views of the interviewee and are not meant to represent the opinions or official positions of any institution or organization the interviewee serves or has served.
The opinions expressed in this interview reflect the views of the interviewee and are not meant to represent the opinions or official positions of any institution or organization the interviewee serves or has served.