Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Thomas A. Ban’s Interview of Philip B. Bradley – Recording Electrical Activity from Cerebral Cortex and Subcortical Structures in Conscious Cats
In 1948 Philip B. Bradley (1919–2009) joined Joel Elkes’ team in Alistair Frazer’s Department of Pharmacology at the University of Birmingham in England. He graduated that year with an honors degree in zoology with chemistry as an additional subject (Bradley 2000).
Bradley’s assignment on Elkes’ team was to study the effects of drugs on the electrical activity in the brain of animals in order to elucidate their mode of action. To prepare him for his assignment, Bradley was sent to the Burden Neurological Institute to learn from Grey Walter (1910-1977) EEG techniques. Upon return he setup his own laboratory in which his initial projects on animals also provided the material for his doctoral thesis (Bradley 1952). Reflecting on these early days about half a century later, Joel Elkes (1919 -2009) in his own autobiographical account wrote: “(Bradley) quickly established reference points for a pharmacology of the brainin as much as it related to behavior. I still treasure a copy of Philip’s thesis completed in October 1952” (Elkes 1998).
When reviewing the literature on the effects of drugs on the EEG in animals Bradley concluded that the findings are of little value in the analysis of drug action unless accompanied by concomitant observations of their effects on behavior. To meet the needs, in the early 1950s he devised, in collaboration with Joel Elkes, a technique for recording the electrical activity of the cerebral cortex together with various subcortical structures in unrestrained conscious animals (cats).When experimenting with drugs with the employment of their new technique, the animals were placed in a “constant environment chamber” from which extraneous visual, auditory and electrical stimuli were excluded (Bradley and Elkes 1953a).
At the time (in the early 1950s), there was little known about synaptic transmission in the brain, but it was already recognized that acetylcholine was the transmitter at neuromuscular junctions. Hence, Bradley and Elkes began their exploration of the pharmacology of the brain with drugs which affected cholinergic transmission in the periphery (Bradley and Elkes 1953b; Bradley and Elkes 1954). Simultaneously with their research in animals, they also studiedthe effects of lysergic acid diethylamide (LSD-25) and amphetamine on the EEG in normal subjects (Bradley, Elkes and Elkes 1953).
Several years later, in 1957 Bradley, in collaboration with PM Jeavons, conducted research with the employment of EEG parameters on the effects of chlorpromazine and reserpine on sedation and convulsive threshold in patients with schizophrenia (Bradley and Jeavons 1957).
In his autobiographic account, published in 2000, Bradley notes that while writing his “thesis” he became aware of two publications relevant to his interest: one was Moruzzi and Magoun’s classic paper on the reticular formation of the brain and its role on arousal; and the other was a publication of Abraham Wikler describing “pharmacologic dissociation” between the effects of some drugs on behavior and on the EEG (Moruzzi and Magoun 1948; Wikler 1952). Bradley was able to relate his findings to both (Bradley 2000).
In keeping with Wikler’s “pharmacological dissociation” Bradley and Elkes found that atropine in relatively large doses produced sleep-like activity on the electrocorticogram without the appearance of behavioral sleep and physostigmine, in doses which were not sufficient to produce peripheral parasympathetic stimulation, induced fast activity on the electrocorticogram resembling wakefulness although the animals were not behaviorally awake. They also noted that some of the other drugs they studied, e.g., amphetamine, CPZ, LSD-25, did not affect the correlation (Bradley and Elkes 1953a,b,c).
Wikler’s “pharmacological dissociation” was brought to a new light by Moruzzi and Magoun’s (1948) demonstration that lesions of the midbrain blocked arousal response to stimulation of the reticular formation. With consideration of the effects of midbrain lesions on the arousal response, in the mid-1950s Bradley and Elkes hypothesized that drugs which produce effects on the EEG that correlate with behavior are acting at the midbrain level, either directly or indirectly on the reticular formation, whereas those which produce dissociation of EEG activity and behavior are reacting probably more diffusely (Bradley and Elkes 1954).
Subsequently, in the late 1950s, in collaboration with Brian Key, Bradley studied the effects of drugs on arousal responses produced either by direct stimulation of the brainstem reticular formation or by peripheral auditory stimulation. Findings in these studies indicated that depressant drugs, such as the barbiturates, and central stimulants, such as the amphetamines, were likely to be acting directly or indirectly on arousal mechanisms located at the brain stem level, whereas CPZ and LSD-25 probably had their actions on the afferent collaterals which influenced arousal mechanisms indirectly (Bradley and Key1958).
In the late 1950s Bradley extended the scope of his research to studies in which he used “floating microelectrodes.” Theyenabled him to record activity from a single neuron in the brain stem for relatively long periods of time. With the employment of “microelectrodes” he studied the effects of adrenaline, noradrenaline and acetylcholine, injected intravenously or directly into the carotid artery, on the activity of single neurons in the reticular formation (Bradley and Mollica 1958)
By thelate1950s Bradley’s research was recognized internationally. In 1957, at an International Symposium dedicated to the Reticular Formation of the Brain, Bradley presented a paper, “On the central action of certain drugs in relation to the reticular formation of the brain” (Bradley 1957b), and at another symposium dedicated to Psychotropic Drugs, he presented two papers: one, “On the effects of drugs on the electrical activity of the brain and behavior” (Bradley 1957c), and the other, “Microelectrode approach to the neuropharmacology of the reticular formation” (Bradley 1957a).
Towards the end of the 1980s Bradley published his “Introduction to Neuropharmacology” (Bradley 1899) and towards the end of the 20th century he co-authored a proposed classification of opioid receptors (Dhawan et al.1996).
Philip B. Bradley was interviewed by Thomas A. Ban for ACNP’s Oral History series and his interview was published in Volume Two of the series (Ban 2011; Bradley 2011; Fink 2011).
Ban TA. Preface. In: Fin M, editor. Neurophysiology. (In: Ban TA, editor. An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews. Volume Two). Budapest: Animula; 2011, p. x – xxii.
Bradley PB. Observations on the effects of drugs on the electrical activity of the brain. Doctoral Thesis. University of Birmingham, England, 1952.
Bradley P. Effect of drugs on electrical activity of the brain and behavior. In Garattini S, Ghetti V, eds. Psychotropic Drugs. Amsterdam: Elsevier; 1957a, p. 21.
Bradley P. Microelectrode approach to the neuropharmacology of the reticular formation. In Garattini S, Ghetti V, eds. Psychotropic Drugs. Amsterdam: Elsevier; 1957b, p. 207 – 16.
Bradley PB. On the central action of certain drugs in relation to the reticular formation of the brain. In Jasper HH, Proctor LD, Knighton RS, Noshay WC, Costello RT, eds. Reticular Formation of the Brain. New York: Little Brown; 1957c, p. 123 – 49.
Bradley PB. An Introduction to Neuropharmacology.London:Jon Wright;1989.
Bradley PB. A personal reminiscence of the birth of psychopharmacology. In Ban TA, Healy D, Shorter E, eds. The Triumph of Psychopharmacology and the Story of CINP. Budapest: Animula; 2000, p.25 – 32.
Bradley PB interviewed by Thomas A. Ban. In Fink M, editor. Neurophysiology. (In Ban TA, editor. An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews. Volume Two). Budapest: Animula; 2011, p. 123 – 58.
Bradley PB, Elkes J. A technique for recording the electrical activity of the brain in the conscious animal EEG ClinNeurophysiol 1953a; 5: 451-6.
Bradley PB, Elkes J. The effect of amphetamine and D-lysergic acid diethylamide (LSD-25) on the electrical activity of the brain of the conscious cat. J Physiol (London) 1953b; 120: 13.
Bradley PB, Elkes J. The effect of atropine, hyosciamine, physostigmine and neostigmine on the electrical activity of the brain of the conscious cat. J Physiol (London) 1953c; 120: 14 -5.
Bradley PB, Elkes J. The effect of some drugs on the electrical activity of the brain. Brain. Brain1954; 80: 77 -0117.
Bradley PB, Elkes C, Elkes J. On some effects of lysergic acid diethylamide (LSD-25) on normal volunteers. J Physiol (London) 1953; 121: 50.
Bradley PB, Jeavons PM. The effect of chlorpromazine and reserpine on sedation and convulsive threshold in schizophrenicpatients. EEG ClinNeurophysiol 1957; 9: 661-72.
Bradley PB, Kay BJ. The effect of drugs on arousal responses produced by direct electrical stimulation of the reticular formation of the brain. EEG ClinNeurophysiol 1958; 10: 97 -110.
Bradley PB, Mollica A. The effect of adrenaline and acetylcholineon single unit activity in the reticular formation of decerebrated cat. Arch Ital Biol 1958; 96: 168 – 86.
Dhawan BN, Cessilin F, Raghabir R, Reisine T, Bradley PB, Porthogese PS, Hamon M. International Union of Pharmacology. XII. Classification of Opioid Receptors. Pharmacol Rev. 1996; 48: 567 -92.
Elkes C, Elkes J. Effects of chlorpromazine on the behavior of chronically overactive psychotic patients. Brit Med J 1954; 2: 560.
Elkes J. Towards footing of a science: Personal beginning in psychopharmacology in the forties and fifties. In Ban TA, Healy D, Shorter E, The Rise of Psychopharmacology and the Story of CINP. Budapest: Animula; 1998, p. 15 – 25
Fink M. Introduction and dramatis personae. In: Fink M, editor. Neurophysiology. (In: Ban TA, editor. An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews. Volume Two). Brentwood: American College of Neuropsychopharmacology; 2011, p. xxxii – xlvii.
Morruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. EEG ClinNeurophysiol 1949; 1: 455.
Wikler A. Pharmacologic dissociation of behavior and “sleep pattern”in dogs: morphine, n-allylnormorphine and atropine. Proc SocExp Biol1952; 79: 261 - 4.
Philip B. Bradley, interviewed by Thomas A. Ban
London, England, January 21, 2002
First published in Volume Two
(Neuropharmacology, edited by Max Fink) of
An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews, a series edited by Thomas A. Ban
(Brentwood: American College of Neuropsychopharmacology; 2011, p. 329 - 54)
TB: This will be an interview with Professor Philip Bradley, for the Archives of the American College of Neuropsychopharmacology. We are in London, England. It is January 21, 2002. I am Thomas Ban. Let us start from the very beginning. If you could tell us first where and when were you born? Say something about your childhood, early interests and education.
PB: Well, I was born in Bristol in 1919. My parents were quite poor; it was just after the end of the First World War. I had three brothers and two sisters, all of whom were considerably older than me, so I was the baby of the family. I went to a number of schools in Bristol. None of them would be well known, except possibly Cotham Grammar School where I took my matriculation examination before moving to Bristol University to study Zoology and Chemistry. For financial reasons, I could only get a place at university because I was given a grant from the Ministry of Education, which committed me to take a teaching post after graduation for four years. However, the Second World War intervened, and because I failed a chemistry examination, I was obliged to join the army. At the time science students were exempt from military service, but because I had failed this exam, I was no longer exempt.
I spent six years in the army, and at one time I was posted to Brighton Technical College as an army instructor to teach electronics, which was a rather strange thing as I knew very little about it! I thought afterwards it might have been because I had studied Physics for my Higher School Certificate. So, I was teaching electronics to army students and had to learn it very quickly. After two years, I went on to various other posts in the army which involved working on radar repairs and maintenance and being in charge of radar and wireless workshops. Eventually I went back to Bristol to complete my degree. Because of this wartime experience in electronics, I then became interested in electrophysiology and my research project in zoology was to record nerve potentials in insects.
TB: So, you continued your studies in zoology after you got out from the army?
PB: Yes, I went back to finish my degree in zoology and chemistry.
TB: What year did you get your degree in zoology?
PB: That was in 1948, and I was then looking for employment. I was offered a post with the Colonial Service to work as an entomologist in East Africa. But before I accepted that offer, I heard about a vacancy at the University of Birmingham in the Department of Pharmacology. They were looking for someone with my experience and I had an interview with Joel Elkes and Alistair Frazier, who was then head of the Pharmacology Department. They offered me a post as a Research Fellow that I accepted. I was to work with Joel and study the effects of drugs on the brain, using electrophysiological techniques.
Because of this, I took a course in electroencephalography (EEG) at the Burden Neurological Institute in Bristol with Dr. Grey Walter who, with Lord Adrian, had developed electroencephalography in England. When I arrived in Birmingham, I started work on recording the electrical activity of the brain in animals and studying the effects of drugs on the EEG. At that time, there were not many drugs available with known actions on the central nervous system. So, I worked with atropine and physostigmine, which were used clinically at the time. The only treatment then for schizophrenia seemed to be sedatives and surprisingly, amphetamine, which had a dramatic effect on catatonic stupor.
Shortly afterwards new drugs appeared. The first was, I think, LSD-25, and then we heard about chlorpromazine being used in Paris. This was a very exciting time, because we received samples of chlorpromazine and Joel Elkes and his wife Charmian did the first clinical trial of chlorpromazine in the UK on schizophrenic patients and I was a member of the team, doing the EEGs. My own work was primarily on animals. The idea was to develop techniques for recording the EEG in conscious, unrestrained animals, which at that time I do not think had been done. It was Joel’s idea for me to do the EEG course at the Burden, so that I would have some expertise in human EEG and I used that subsequently.
After taking part in the clinical trial of chlorpromazine in schizophrenic patients, I worked in collaboration with another psychiatrist in Birmingham, Peter Jeavons. We studied the sedation threshold in schizophrenic patients, using the EEG. I was also invited to work with the neurosurgeons in Birmingham, who realized that recording the electrical activity directly from the cerebral cortex would be helpful in delineating tumors and epileptic foci on the exposed cerebral cortex. They did not have suitable equipment of their own, and I used to trundle my equipment across to the hospital where we sterilized the electrodes and other bits of equipment that came into contact with the patients. Occasionally, I accompanied Eric Turner, the neurosurgeon I was working with, to London to watch neurosurgical operations performed at the Maudsley Hospital. I also worked in collaboration with the Professor of Neurosurgery, Professor Brodie Hughes, recording the activity of single cells in the caudate nucleus, using stereotactic techniques. Brodie Hughes was interested in Parkinson’s disease, and at the time, the condition was relieved by lesions of the caudate nucleus. It may sound illogical, but that’s what we were doing. So, I did have some experience using the electrophysiological techniques I had learned at Burden, and I think that was quite valuable.
TB: Did you by that time develop your technique for recording electrical activity of the brain in unrestrained conscious animals?
PB: Yes, I had to develop the technology for animals as up to then recordings had been made in anesthetized animals, and apart from the effects of the anesthetic obscuring changes in the EEG, we also wanted to see the effects of the drugs on behavior. Therefore, I developed techniques for implanting electrodes in animals, in order to record the activity of the brain at the same time as observing the behavior. This was the work I did for my PhD.
TB: So, your PhD was in neuropharmacology.
PB: No, it was in pharmacology, neuropharmacology as a subject did not exist then.
TB: Then, you got your DSc, your Doctor of Science?
PB: That was later, and that was in Neuropharmacology. I got my PhD in 1952, at the time when Joel Elkes went off to spend a year to Washington. When he came back, he established a new department called Experimental Psychiatry, in which he took responsibility for the clinical work of the department and I was in charge of the basic research, which also included neurochemistry.
TB: When did you do the research with barbiturates and amphetamines?
PB: That was in my PhD work.
TB: So, it was done between 1948 and 1952?
PB: That sounds about right. I worked initially with the drugs that were available at the time, i.e., atropine and physostigmine, to modify cholinergic function in the brain, and amphetamine and barbiturates to modify levels of consciousness. Later, when chlorpromazine and LSD became available, I studied those as well. In 1949, after Moruzzi and Magoun published their seminal paper on the reticular formation of the brain, I devised a series of acute experiments using lesions at different levels in the brain.
TB: Before telling us about your findings with lesions could you elaborate on Moruzzi and Magoun’s influential paper?
PB: They showed that stimulating the reticular formation, a diffuse structure in the tegmental region of the brain stem – comprising mainly short axon neurones and distinct from the main afferent pathways and the cranial nerve nuclei – with a relatively high frequency electrical stimulus (300 c/s,) produced an arousal response as observed by changes in the electrical activity of the cerebral cortex.
TB: What did you find with lesions?
PB: We were able to show that a lesion which transected the midbrain cutting off the ascending influence of the reticular formation blocked the stimulant effects of amphetamine; whilst, on the other hand, the effects of drugs with actions related to cholinergic mechanisms in the brain were unaffected by this lesion. So, we made some rather naïve predictions about the possible site of action of these drugs.
TB: At what levels did you have the lesions?
PB: I adopted the techniques of the Belgian physiologist, Bremer. One of the lesions was at the C-1 level in the spinal cord, which produced what he called the encéphaleisolé, an isolated brain but with an intact blood supply. This preparation showed periods of wakefulness and sleep, as judged by the activity of the cerebral cortex and responses to sensory stimuli. Another lesion was at the midbrain level which resulted in the cerveauisolé, or isolated cerebrum and this preparation showed permanent sleep activity, presumably as the result of the removal of the ascending influence of the reticular formation. Our studies in these acute animal preparations showed that both transsections of the spinal cord and of the midbrain did not modify the effect of cholinergic drugs, physostigmine producing an alert pattern of activity in the EEG and atropine, sleep-like activity, i.e., the reverse. However, transsection at the spinal cord level appeared to block the alerting effect of LSD, and lesions of the midbrain blocked the alerting effect of amphetamine.
TB: What about chlorpromazine?
PB: Chlorpromazine seemed to have very little effect in these experiments and we were unable at the time to localize its effects to the brain stem.
TB: Didn’t you find that chlorpromazine interfered with the response to afferent stimulation?
PB: Yes. With my colleague Brian Key who was a PhD student at the time, we devised an experiment in which we measured the threshold for arousal to electrical stimulation of the reticular formation and the threshold for arousal produced by afferent, auditory stimulation. This work was done with acute encéphaleisolé preparations and was supported financially by the US Air Force. We found that sedative drugs, such as the barbiturates, blocked the effect of the stimulation in the brain stem very quickly, whereas amphetamine had the opposite effect: it reduced the threshold although this was very difficult to measure.
We also tested the arousal response to afferent stimulation and found that chlorpromazine had little effect on the threshold for arousal produced by brain stem stimulation, but depressed afferent-induced arousal. LSD on the other hand had the opposite effect, facilitating the afferent-induced arousal. So, we put forward the hypothesis that drugs which affect levels of consciousness probably act directly on the reticular formation either by stimulating or depressing it, whereas others, such as chlorpromazine and LSD seemed to have less direct effect on the reticular formation but influenced the effects of afferent stimulation either by depression, as chlorpromazine, or stimulation, as LSD.
TB: Was anyone else at the time involved in similar research?
PB: Well, I think that some of the experiments that the Killams were doing in Los Angeles at the time might have been similar.
TB: How did the scientific community respond to your findings?
PB: Not very well, I must say. My recollection of presenting papers to the Physiological Society in London was that they were met with quiet acceptance, without much discussion. What we were doing was probably not considered proper physiology. On the other hand, because of my training in electroencephalography I was a member of the EEG Society and I gave papers at their meetings. These were received quite well by the audience, which consisted largely of psychiatrists and neurologists, and even some physiologists.
TB: You mentioned before that while doing your research for your PhD you worked with drugs like atropine and physostigmine. Did you do the research with anticholinergics that showed dissociation between the changes in the EEG and behavior, before or after Wikler published his findings?
PB: I would say that it was about the same time, because I met Wikler and we discussed his work on dogs where he showed the dissociation of the EEG from behavior, and we were able to demonstrate a similar phenomenon in other species, cats and later on rhesus monkeys.
TB: So, you showed that some drugs would produce dissociation between behavior and EEG in the cat?
PB: That’s right. The most striking dissociation was with atropine, but large doses of the drug were needed. It wasn’t what you would regard as a normal dose of atropine in either animals or man for that matter but we noticed no untoward effects.
TB: Do you remember the research you did immediately after you got your PhD?
PB: I did some work on the effects of DFP, diisopropylfluorophosphate, an irreversible cholinesterase inhibitor. I had a student working with me then and we became interested in a technique developed by Feldberg for injecting drugs into the ventricles of the brain. These experiments produced some interesting results but their interpretation was difficult especially as it became apparent that the CSF-brain barrier was as potent as the blood-brain barrier.
TB: Could we review again briefly your findings on the effects of drugs? Barbiturates and amphetamines have . . .
PB: A direct action on the reticular formation on the brain stem, barbiturates depressing and amphetamine stimulating.
TB: LSD and chlorpromazine?
PB: Well, it seemed from our experiments with the measuring of thresholds for arousal to afferent auditory stimulation, compared to thresholds for arousal to direct electrical stimulation of the reticular formation, that the effects of LSD and chlorpromazine were more likely to be related to the afferent inputs, i.e., afferent collaterals, into the brain stem, this being the mechanism by which afferent stimuli produce arousal. At a meeting in Geneva in 1964 I proposed the hypothesis that chlorpromazine had an action in the brain stem similar to that of de-afferentation, and this could explain its clinical actions but it did not arouse much interest.
TB: This was the first hypothesis about the mode of action of chlorpromazine?
PB: I think it might have been, but I’m not sure.
TB: It was an important discovery because it showed that the mode of action of chlorpromazine is different from the old sedatives. It also showed that the mode of action of LSD is different from the mode of action of anticholinergics.
PB: Yes, the hypothesis was that the anticholinergics and cholinergic agonists act more diffusely. Their actions are not restricted to a particular area as you would expect from the distribution of cholinergic receptors in the brain, based on studies of the distribution of the enzymes choline acetylase and acetylcholinesterase, which showed a fairly even distribution throughout the brain.
TB: You were also one of the first to show dissociation between behavior and electrical activity in the brain after the administration of anticholinergics.
PB: We observed the phenomenon in the cat and also in primates, rhesus monkeys, whereas Wikler’s observations, which I think were concurrent with ours, were in dogs. So, it seems the dissociation is not species-specific. I have to say that my friend Vincenzo Longo, working in Rome, never agreed that the dissociation existed, and I think he tried to disprove it at the CINP Meeting in Tarragona in 1968, but I couldn’t be bothered to get into a dispute as I had then moved on to other things. I thought it was the sort of thing anybody could reproduce if they wished to.
TB: The finding about the dissociation has kept lingering on for a long time.
PB: I suppose so, because nobody has ever really examined the phenomenon in detail, and we still do not know what it means. It seems strange that an organism can show sleep-like activity in the EEG while it is fully alert. You could say it shows the irrelevance of the electrocorticogram to behavior, but I don’t think that’s the sort of generalization we should make. But it is clear that the electrocorticogram is not always a good indicator of the behavioral state of the animal in terms of wakefulness and sleep. I believe other examples of dissociation have been found more recently.
TB: Let’s get back to your activities after you got your PhD. Did you become involved in teaching?
PB: My first involvement in teaching was, strangely enough in neurology. The head of Pharmacology, Alistair Frazer, was of the opinion that only medically qualified staff should teach medical students. Those ideas did not last very long. There were some aspects of neurology I did not know very well, and again I had to learn quickly. However, I was able to give lectures on the reticular formation and on the EEG where I also gave demonstrations, using student volunteers.
TB: Any other important events in those years?
PB: There was the Neurochemistry Conference in Oxford in 1954, which Joel Elkes organized and I assisted with the administration. That was my first involvement in organizing meetings and the experience proved useful in later years, particularly with the early CINP meetings. It was an enjoyable experience and I met some interesting people.
TB: Can you tell us something about the Oxford meeting?
PB: It was a very mixed group, mainly biochemists, some physiologists and anatomists. I can’t tell you much about the scientific aspects of the meeting as I was working behind the scenes and looking after people’s problems. One of the problems I had was that the organizers had invited a number of speakers from the Soviet Union but had received no response. Then, half way through the meeting, this group of Russians arrived and I had to receive them, as everyone else was busy. They had an interpreter with them, a lady, but I subsequently found that they could all speak English, so the role of the interpreter was not quite what we thought. Everybody was staying in the colleges, Magdalen College being the main one, but the Russians refused to stay in a college and we had to find them a hotel!
TB: They were probably obliged by their government to stay in hotels.
PB: I think that is true, but it all ended amicably; they were very friendly and participated well in the meeting.
TB: Was that the first International Congress of Neurochemistry?
PB: I think it was. After the meeting it was decided to set up the International Society for Neurochemistry, and later on there was a Journal. Brian Ansell, who subsequently joined me in Birmingham, was one of the founders. He also became Chief Editor.
TB: It was held at the time when emphasis on the transmission of impulses in the brain began to shift from electrical to chemical.
PB: Yes, the person who was most influential was the physiologist Sir John Eccles who had been a strong proponent of electrical synaptic transmission, but in a series of lectures in Oxford described, somewhat dramatically, how he was converted to a belief in chemical transmission, i.e., that the nerve impulse crossed the synaptic junction as a result of the release of a chemical. It was about the time that the physiologists Hodgkin and Huxley were studying transmission in peripheral nerves and the neuromuscular junction. That was a very active period, but those working on peripheral nerve transmission didn’t think about the brain. I have a feeling they didn’t want to think about the brain because it was an extra complication.
TB: It was in those years that the presence of norepinephrine was detected in the brain.
PB: That was the work of Marthe Vogt and von Euler. Marthe Vogt published an important paper in 1953 on the levels of adrenaline and noradrenaline in the brain, showing that these substances were concentrated in the midbrain and brain stem regions, which fitted in nicely with our theories. But there were other things happening at that time. Joel went off to America in the early 1950s and when he came back he established this Department of Experimental Psychiatry; I was appointed to a Lectureship in Electrophysiology and joined him.
TB: It was the first Department of Experimental Psychiatry in the world.
PB: Probably so. Sometime later, I was offered a Fellowship by the Rockefeller Foundation of New York and told I could choose where to study. The options were the Department of Anatomy at UCLA with Magoun or the Institute of Physiology at the University of Pisa with Moruzzi.
TB: And you chose Pisa.
PB: It was a difficult choice, but in the end, I went to Pisa because they had developed a technique for recording the activity of single neurons using microelectrodes. My feeling was that analyzing EEGs was probably not going to get us very far and that further advances were likely to be made by studying the activity of single neurons in the brain and how their activity was affected by drugs.
TB: Before continuing with your experiences in Pisa could you tell us something about the Department of Experimental Psychiatry. Where did the support come from?
PB: There was support from a number of places and there seemed to be a lot of money available. The main source was the Rockefeller Foundation which provided my Fellowship. There was government money from the Ministry of Health and there was a mental health research organization, subsequently taken over by the Medical Research Council. But all these were grants for a limited period. I was not aware of any funding from the pharmaceutical industry at that time.
TB: Was it an independent department?
PB: Yes, it was an independent department of the University.
TB: Who were the people in the department?
PB: Joel’s wife, of course, Charmian, and there was a psychiatrist, Felix Letemandia. There was also a psychologist, Tony Harris, and an experimental psychologist, Malcolm Piercey. In addition, there was a biochemist, John Crammer.
TB: How many people were in the department, about half a dozen?
PB: Probably more. In the basic research section there was a biochemist named Archie Todrick, and a pharmacologist, Heinz Ginzel. There were also people on short-term contracts.
TB: Wasn’t Mayer-Gross a member of the team?
PB: Mayer-Gross had worked at the Creighton Royal Hospital, in Dumfries, Scotland. He had already retired when Joel consulted him about recruiting a fairly senior person to take charge of the clinical work of the department. I was told that when Joel asked Mayer-Gross whom he would recommend, Mayer-Gross said “What about me”?
TB: Can you tell us something about Mayer-Gross?
PB: He had been Professor of Psychiatry at Heidelberg University in Germany and left in the 1930s for Scotland. He was co-author of a textbook of psychiatry but I didn’t see a lot of him in Birmingham.
TB: But you had some interactions with him, didn’t you?
PB: Yes. That was when I returned from Italy in September 1957. Joel had already left and things were pretty chaotic as there was no one in charge. Mayer-Gross and I did not see eye-to-eye; he did not approve of what I was doing.
TB: But he was on the team.
PB: Yes, he was one of the team.
TB: There was also Brian Key.
PB: He was one of my PhD students. He did most of the experiments on measuring thresholds and we published that work in the EEG Journal and the British Journal of Pharmacology.
TB: Was he your first PhD student?
PB: No, my first PhD student was a man named Jim Hance. He was a zoologist, as was Key. They were both Birmingham graduates; in fact, the Professor of Zoology, Otto Lowenstein, was very helpful in finding students for me. Hance did the experiments with intraventricular cannulae, injecting drugs into the cerebral ventricles and observing the effects on the EEG and behavior. This was work for his PhD. After I came back from Pisa, I attended a meeting in Brussels. Magoun was there and invited me to work in his laboratory, but as I’d just had a year off and things in Birmingham were a little difficult, to say the least, I had to decline. But I ended by saying there was someone from my laboratory who could be interested. So Hance went in my place and stayed. He worked with the Killamsand moved to Stanford with them and then on to Davis. I visited him and his wife Ann in Los Angeles, and later on he helped me to find a house to rent on the Stanford campus. Then they moved to Davis and I saw him again when I visited the Killams. After that I am afraid we lost touch.
TB: Actually, Keith Killam died. Eva Killam is still around. I saw her at the last ACNP meeting.
PB: Oh, dear. I did not know about Keith. I last saw them both at the Pharmacology Congress in London when we had dinner together.
TB: Where was the Experimental Psychiatry department located?
PB: The department was housed at the University of Birmingham Medical School. The Medical School and the general hospital, the Queen Elizabeth Hospital, were on the same site. Most of the clinical work of the department went on at the mental hospital, All Saints, which was some distance away and that is where I used to do EEG recordings on patients. There were psychiatrists at the Queen Elizabeth Hospital but I don't think there was a University Department of Psychiatry.
TB: And the director of the Department of Experimental Psychiatry was Joel. I read somewhere that at the time there was no other Professor of Psychiatry in Birmingham.
PB: That's right. There was no Professor of Psychiatry but there was certainly a Professor of Neurology, Philip Cloake, whom I knew very well. However, there were two psychiatrists in the hospital who were consultants. I was with them at a meeting, and after giving my paper, one of them said it didn’t matter how a drug worked as long as it had an effect on the patient. I think their attitude was one reason for Joel deciding to leave. I don’t know what he would say about this but certainly it wasn’t lack of financial support. There were other psychiatrists in Birmingham who were more supportive. There was a day hospital in Moseley, Uffculme Clinic, which was an outpost of All Saints Hospital where the medical superintendent, Dr. O’Reilly was very helpful and provided Joel with facilities for clinical trials. I believe the MRC Unit would, at least partially, have been established at Uffculme Clinic.
TB: Do you remember the visit of Ernst Rothlin?
PB: I remember it very well. Rothlin was Professor of Pharmacology at the University of Basel and Director of Research at Sandoz where LSD had been discovered by Albert Hofmann. Rothlin gave a lecture on LSD which I found quite fascinating although not much was known about its pharmacology at the time. Also, Rothlin had brought us a sample of LSD, and perhaps foolishly, we did experiments on a group of about 12 normal volunteers, including ourselves and other members of staff of the Medical School and All Saints Hospital. The experiments were supervised by Joel’s wife, Charmian, and I did the EEGs; we recorded everything we could think of, including manual dexterity and reactions to various images. The results weren’t very striking, but were, I suppose, pioneering, because it was the first experiment in normal subjects, apart from those of Hoffman and Stoll. There were changes in perception but the EEG changes were relatively slight, in the direction of increased alertness. The drug appeared to exaggerate underlying personality traits in subjects, so people who were slightly obsessive became more so, and subjects who were slightly paranoid showed increased symptoms. Personally, I think it was a mistake to use colleagues and friends as subjects in these experiments. Perhaps medical student volunteers might have been preferable although this could have had its dangers as some years later I was approached by a medical student who said he understood we were studying LSD and he could supply some! I thanked him and said “No” as by then possession of the drug was illegal and I had the only legitimate supply.
TB: Did you encounter depression in any of the subjects?
PB: No, but we did encounter some severe reactions. There was one colleague who did not seem to be responding to a dose of 25 micrograms. Joel came in and Charmian asked if we should give him some more but Joel said “No.” So we waited and soon after he got a very strong reaction, which went on for two days. People who were still showing the effects of LSD after the experiment had finished were given a small dose of a sedative, usually chlorpromazine. However, this particular subject’s wife was a doctor and she said, “Nobody is going to treat my husband,” so she refused the sedative and the effects of LSD persisted for two days. So, these were interesting times.
TB: Could you tell us something about Rothlin?
PB: Ernst Rothlin was a very nice man and I got on well with him. During his visit we discussed the idea of a new international organization devoted to Neuropharmacology and both Joel and I said that we would be enthusiastic supporters. Rothlin said he would discuss the proposal elsewhere and let us know the results.
TB: You were instrumental in opening up the field of Neuropharmacology?
PB: Somebody referred to me once as the “Father of Neuropharmacology” but I do not think that’s true and it was probably just a joke.
TB: You pioneered research in neuropharmacology, using microelectrode techniques.
PB: Yes, but I thought of neuropharmacology as a branch of pharmacology.
TB: Still, you were one of those who opened development in neuropsychopharmacological research.
PB: That is probably true, and I think I held the first formal appointment as a Neuropharmacologist in 1958; that was the year I was awarded my DSc for studies in the field of Neuropharmacology. I did think it was unnecessary to have both, “psycho” and “neur” in the name of the new organization, CINP, because what is “psycho” if it isn’t also “neuro”? However, some people, such as psychologists, would prefer to have both in the name.
TB: What would you have preferred?
PB: Just Neuropharmacology, but then others would prefer just Psychopharmacology, and I am a Founder Member of the British Association for Psychopharmacology. I think the combination Neuropsycho is a bit cumbersome but we all have to compromise.
TB: I think it was during Rothlin’s visit to Birmingham that the idea of having an organization in neuropsychopharmacology was first discussed.
PB: It was, and I believe Joel pursued the idea and talked to other people. In fact, Rothlin might have asked him to do so. A lot of people seem to have suggested it was their idea.
TB: Am I correct that the night before you went to Pisa, Joel told you that he might be leaving?
PB: That’s true. How do you know this?
TB: I learned it from one of your or his publications.
PB: It wouldn’t have been in any of my papers. He’d been back in Birmingham for some years but was still visiting Washington frequently, and it was the night before I was due to leave for Pisa we had dinner at the Cafe Royal in London when he broke the news and said he hoped I might eventually join him. I had been attending a meeting at the Institute of Psychiatry at the Maudsley Hospital and Denis Hill, who was in charge of the EEG Department there, offered me a job. I was in turmoil and didn’t know what to do. I thought the department in Birmingham might break up. Anyway, I turned down the job at the Maudsley as I knew it wasn’t a very happy place. I knew Sir Aubrey Lewis quite well as I had been advising him on setting up a new laboratory for electrophysiological research. There had been occasions when I was lunching with Aubrey Lewis in the refectory and other people whom I knew would come in but would not join us. It seems petty but I did not think there was a very good atmosphere at the Maudsley Hospital so I turned down the job and went to Pisa and continued with my research. I subsequently had my opinion of the atmosphere at the Maudsley confirmed by others.
TB: When did you go to Pisa?
PB: It was in 1956. I went by train on a first-class sleeper from Paris and it was a pleasant journey. I had taken a supply of drugs and was a bit worried about going through Customs. It was fortunate I did take them as there was nothing at the Institute of Physiology in Pisa. My purpose in going there was to learn to use the technique of the floating microelectrode, with which they were recording the activity of single cells in the brain. I thought it would be very complicated, but it was not. Essentially it consisted of a piece of fine enameled wire, pushed gently into the brain until the activity of a single neuron was picked up. The other end of the wire was clamped but a loop was formed so that the recording tip was floating and would follow movements of the brain. I learned this technique very quickly and worked with an Italian, Dr. A. Mollica, who was Moruzzi’s first assistant. We worked hard, including on Saturdays which was the system in Italy, and we obtained some very interesting results which were published in Moruzzi's journal, the Archives Italiennes de Biologie (Archives of Italian Biology). I believe it was the first time such experiments had been performed. However, we were injecting the drugs intravenously and since there were changes in blood pressure when the drugs were injected, we could not decide whether the effects observed were due to an action of the drug on the neuron, or some indirect effect via a change in blood pressure. I realized that this technique wasn’t going to get us very far and began to think about alternatives. Nevertheless, I persevered for my year in Pisa and enjoyed the Italian sunshine and the culture.
Two events occurred during my stay in Pisa, both of which were important. The first was an invitation to attend and present a paper at a symposium, The Reticular Formation of the Brain, at the Henry Ford Hospital in Detroit in March 1957. It was a great experience and my presentation was well received. There were only two other participants from the UK, Geoffrey Harris from London and the neurosurgeon, Sir Geoffrey Jefferson, both of whom I got to know well. It was also an opportunity to visit other centers in the US, including Harold Himwich’s at Galesburg, and Magoun's laboratory in Los Angeles. I also visited Washington where I was offered a post in Joel’s laboratory at St. Elizabeths Hospital. The second event was an invitation to attend and present a paper at a meeting on Psychotropic Drugs to be held in Milan in May 1957.
TB: Could you tell us something about that meeting?
PB: The meeting was sponsored by the Institute of Pharmacology in Milan, the head of which was Professor Emilio Trabucchi. But Trabucchi was a retiring kind of person and liked to remain in the background so the meeting was organized by Silvio Garattini, whom I already knew, and Vittorio Ghetti.
TB: Later on, Silvio published the proceedings of that symposium with Ghetti.
PB: I had my first wife and two children with me in Pisa, and we all went to Milan and stayed in a very nice hotel. There was also a visit to La Scala, where I heard the tenor Guiseppi de Stefano for the first time. Scientifically the meeting was a great success with an opportunity to meet people working the same or related fields. During the meeting I received an invitation from Rothlin to attend an informal meeting to discuss the proposed organization on Neuropharmacology.
TB: How many people participated?
PB: I think about a dozen.
TB: Can you remember who was present?
PB: Rothlin, Radouco-Thomas, de Boor, Denber and others whom I can't remember.
TB: In the records of the CINP history committee, both Corneille Radouco-Thomas and Wolfgang de Boor independently suggested to Trabucchi prior to that meeting the founding of an international society in Neuropsychopharmacology.
PB: I don’t think that’s true but I am not sure. Trabucchi was a very modest, retiring man. I think he liked to facilitate things and gave his support to the meeting, but I am not sure of who proposed it. Personally, I do not think it is important who had the original idea. We all have ideas from time to time and do not pursue them, and then someone else takes them up. As far as I am concerned, I first heard mention of an organization which eventually became the CINP, in Birmingham in 1954 or 1955 during Rothlin’s visit, not in Milan in 1957.
TB: The question is whether it was Trabucchi or Rothlin who initiated that meeting during the Milan symposium and whether it was Trabucchi or Rothlin who chaired it?
PB: As far as I know, it was Rothlin, and it was certainly Rothlin who chaired it.
TB: Do you remember anyone else who participated? I think Hanns Hippius was there.
PB: He might have been there, although he was not a participant in the Symposium. But I know Rothlin chaired the meeting that led to the founding of the CINP.
TB: What about Deniker?
PB: Deniker was there and also Denber and I think Bente. We had quite a long discussion but the decision to found the CINP was deferred in Milan until the Second Congress of Psychiatry in Zurich, which was to take place in September 1957. In my opinion, this was not a good idea because most of the people who would become members of the organization were already in Milan and, apart from psychiatrists, very few were likely to attend the meeting in Zurich. However, Rothlin maintained that as pharmacology would be included in the title, it would be wise to consult the International Union of Pharmacology (IUPHAR) and get their approval; it would be a bad move to go ahead without their agreement and he was probably right. There was also discussion about a journal, which turned out to be Psychopharmacologia. Rothlin had been in discussions with a publisher but did not disclose very much information.
TB: Now, the story goes that in Milan there was another important luncheon meeting relevant to the founding of the CINP in which you participated. Do you remember?
PB: I remember the meeting and that we had lunch, I think at Trabucchi's department as I remember talking to him, but precisely what it was about I can't remember. I should think it was probably a preparation for the meeting in Zurich but cannot be sure.
TB: Were you involved in the preparation of the inaugural meeting in Zurich?
PB: No, I had other problems at the time. I had received a message that Joel Elkes had already left Birmingham, so I returned from Pisa a month early, in August, to find out what was happening. Things were pretty chaotic and the finances of the department were in a mess. Then the University appointed me Acting Head of the Department and the Vice-Chancellor, Sir Robert Aitken, said to me, “This is your opportunity.” In retrospect, I have sometimes wondered if Mayer-Gross had expected to take over from Joel. I was probably lacking in experience and not very good at handling people.
The main problem was that the three staff members Joel had recently recruited, Letemendia, Harris and Crammer, who were all medically qualified, were on short-term contracts and the money was running out. I was told by the Rockefeller Foundation that they would not be renewing their grant and I knew that the people at the MRC were not very happy as they set up a Research Unit with Joel as director and with some staff, but he abandoned it at very short notice. Not many people knew about this, but I saw it written on headed notepaper about the Unit. Mayer-Gross accused me of getting rid of good people and destroying what Joel had built up, but I had no choice as the finances were in a mess. I probably did not handle Mayer-Gross very well. He was a nice man but very dominating and famous, whereas I was at the beginning of my career. There was one other factor I considered important, and that was, as I did not have a medical qualification, I did not feel I could be responsible for the work of medically-qualified staff. Perhaps Mayer-Gross and I ought to have found a way of working together but it would have been very difficult. It was probably a mistake for him to come to Birmingham after he had retired.
Another important event that year was that I was invited to meet Sir Harold Himsworth, the Secretary of the MRC in London. We had an interesting discussion as a result of which I was asked to present my research findings and future plans to the MRC's Clinical Research Board. I know that discussions went on behind the scenes with the Vice-Chancellor, and the MRC decided to establish a research unit in Birmingham, the Neuropharmacology Research Unit, with myself as Honorary Director. This was my first official appointment as a neuropharmacologist. Eventually, the university appointed a Professor of Psychiatry.
TB: Who did they appoint?
PB: Professor William Trethowan from Australia. It was clear that there could not be two departments of psychiatry and I was quite happy to change the name of mine. I would have preferred Neuropharmacology but the Professor of Pharmacology, Alistair Frazer, would not accept that so as a compromise, we became Experimental Neuropharmacology. I must say that Trethowan and I got on extremely well and he was very supportive of our research.
TB: But in spite of all the problems you had at home you went to Zurich to attend the inaugural meeting of the CINP.
PB: Yes, I went to Zurich for the 2nd World Congress of Psychiatry. I felt that as I had been involved in neuropharmacology from the beginning, I should be there.
TB: That meeting in Zurich was organized by Rothlin and included invitation to a dinner.
PB: The dinner was in the first-class restaurant at the Zurich railway station.
TB: Insofar as we know there were 33 people at that dinner, right?
PB: I think so. From the UK, apart from myself, there was Michael Shepherd, Sir Aubrey Lewis and Derek Richter. Humphrey Osmond was also there.
TB: What about Linford Rees?
PB: I don’t think he was there, but I cannot be sure.
TB: Some people say he was, but others say not. It was a very distinguished group.
PB: Probably. A lot of people felt motivated to make speeches. At the end, there was a formal proposal from Rothlin that the CINP should be founded and this was agreed unanimously. Rothlin became its first president and various people were proposed for the committee.
TB: You and Deniker became the first councilors.
PB: Yes. I was proposed by Aubrey Lewis. I think that Rothlin wanted another pharmacologist on the committee, which seemed sensible. But he also wanted a representative from the UK.
TB: Another version is that it was Denber’s suggestion that you and Deniker became councilors because of your contributions to the new field.
PB: It is possible that Denber supported my nomination but I know it was Aubrey Lewis who proposed me as he was sitting next to me. Anyway, the CINP was established and I was a member of the Council. Our immediate task was to organize the first meeting in Rome in 1958, which was in 12 months’ time. I thought it was crazy, but we did it!
TB: What was your role in organizing that congress?
PB: I was asked to organize one of the symposia. It was the first Symposium, “Methods and Analysis of Drug-induced Behavior in Animals”. As I was also the first speaker, it was chaired by Rothlin and Jules Masserman.
TB: Could you tell us who were involved in organizing the congress?
PB: Both Rothlin and Trabucchi were involved. I think Trabucchi made most of the local arrangements as Chairman of the Local Organizing Committee, whereas the program was the responsibility of the Executive Committee, chaired by Rothlin.
TB: In addition to Rothlin and Deniker could you tell us who the others were on CINP's first executive? There were two secretaries. . ..
PB: Yes, Radouco-Thomas and Denber.
TB: And the treasurer was Stoll.
PB: That’s right. It was dominated by Europeans.
TB: Could you tell us something about the Rome congress?
PB: It was a very successful meeting. We tried to put together a program which covered all the different scientific disciplines contributing to neuropsychopharmacology and I think we succeeded. Certainly, a number of people who attended told me later how successful it was. There was an excellent social program as well, although I was obliged to miss the audience with the Pope as I needed to prepare my talk. Apart from the opening symposium in which I participated, I persuaded my colleague, Brian Ansell, who had just joined me in Birmingham as Lecturer in Neurochemistry to give a lecture on “The Present State of Neurochemistry.”
TB: Didn’t you edit the proceedings?
PB: The Executive Committee met on the last day of the meeting and decided that the proceedings should be published. Myself, Deniker and Radouco-Thomas were appointed as editors. We had a difficult task as many people were already leaving and had not been asked to prepare a manuscript, and there was no publisher. However, we succeeded, and the Elsevier Publishing Company proved to be very co-operative. I think Radouco-Thomas had already been in touch with them. Inevitably some contributions were missing as we could not delay publication for too long. I think that the book was well received. This was my first venture into publishing and it prepared me for the future.
TB: How many people attended the congress?
PB: There were over five hundred. Some people came because this was something new. There weren't many from the UK at the inaugural meeting in Zurich and my impression was that the bulk of the psychiatric population in the UK wasn’t terribly interested. However, when they heard about the success of the Congress in Rome, many more became interested and eventually joined the CINP.
TB: Could you tell us something about your research after you returned from Pisa?
PB: It was some time before I could get back into experimental work. As I was in charge of a department that had been abandoned by its previous head, I had a great deal of administration to contend with and was lacking in experience. There was also a good deal of planning to do. Fortunately, research funds had not dried up completely, in spite of the Rockefeller Foundation not renewing its grant. I think that was a personal grant to Joel anyway. I still had my funding from the US Air Force which was generous, and the University provided a number of new appointments, including a Lectureship to which Brian Ansell was appointed. Eventually, the MRC established its Neuropharmacology Research Unit under my direction, occupying accommodation provided by the University.
During my absence in Italy the electrophysiological research had been kept going by two postgraduate students who were in touch with me by mail. Now I had a new student working with me making microelectrode recordings of single neurons in the brain. I had heard about iontophoresis being used by some people at University College London and I visited them. A similar technique was being used at John Eccles’ laboratory in Canberra. Then, at a meeting of the Physiological Society, I met John Wolstencroft who was working in Leeds. He was planning a visit to Moruzzi's laboratory in Pisa and wanted my advice. Our discussions led to the discovery of many mutual scientific interests and we both concluded that the use of microiontophoresis to apply active substances on single neurons in the brain, whilst recording their activity, was the way forward for both of us. I was able to persuade the MRC to create a senior appointment for John in the unit and he moved to Birmingham. This was the beginning of a very exciting time for both of us.
The equipment we were using at the time was very primitive and the experiments very time-consuming. Because of electrical interference in the Medical School during the day, although we were using a Faraday Cage, we had to work at night when the lifts could be switched off. Also, the only way we could record the action potentials was by photographing onto 35 mm film. Then, after the film was developed, one of us would take it home and count the activity usually over a 10 second period. Eventually, we designed electronic equipment for recording and counting the neuronal activity that provided a printed output. The people working with iontophoresis in London and Canberra were studying neurons in the spinal cord, and as far as we knew, no one had used the technique in the brain. We obtained some exciting results. Using putative transmitters, such as acetylcholine, noradrenaline and serotonin, we were able to classify the brain stem neurons into different types according to their responses. Thus, when acetylcholine was applied, some neurons showed a pattern of excitation whilst others were inhibited, and a third group was unaffected. A similar pattern of activity was shown by the other two substances, noradrenaline and serotonin. Furthermore, some neurons responded to just one substance, some to two and, rarely, some to all three and the pattern of responses could be a mixture of excitation and inhibition. From this complex pattern of responses, we attempted to classify neurons in the brain stem, and although this classification was somewhat crude, it was a beginning.
We then started looking at interactions with centrally acting drugs, for example chlorpromazine, LSD and amphetamine. One interesting finding was that LSD antagonized the actions of serotonin (5-HT) which supported the hypothesis put forward by Gaddum in 1956, based on studies on peripheral nerves. At the time some workers in the Physiology Department in Birmingham had isolated a substance with oxytocic properties, which was released from the cerebral cortex in response to stimulation of peripheral nerves. John Wolstencroft was very excited about this and wanted us to test it in our experiments. I was not keen as we knew nothing about the chemistry of the substance, only that it was oxytocic. Nevertheless, we did some experiments and found the substance had some activity on brain stem neurons but the results were difficult to interpret. Later on, the substance we were using was shown to be a prostaglandin, which has an important role in platelet aggregation. We also did some experiments with a “sleep-inducing” substance discovered by Monnier working at the University of Basel in Switzerland. He sent us samples and we collected them at the airport and rushed them to the lab. Again, very little activity was found and I was not pleased when I discovered that Monnier was sending us placebos as well without telling us which the active sample was and which was not.
TB: You said, if I understood it correctly, that you were involved in classifying neurons according to their response to neurotransmitters, and if I remember, you also studied interactions between neurotransmitters and drugs by using iontophoresis. Could you give us an idea what you actually did?
PB: We used multi-barreled microelectrodes which consisted of glass tubing, drawn out to a fine tip. We invented a device in which the glass tubing was held vertically and a weight attached to the bottom end. In the center was a circular electrical heating element. When the current was switched on, the tubing was heated and the weight pulled out the glass to a very fine diameter. By adjusting the weight and current we were able to achieve the size of tip we needed, usually 5 microns diameter. With this size we were able to isolate single neurons in the brain stem. A number of these tubes would be glued together, usually five but I have heard of people using electrodes with up to eight barrels. The central barrel was filled with saline solution and used for recording the activity of the neuron and the other barrels were filled with aqueous solutions of the substances we wished to test. Clearly only substances that ionized in solution could be used in this way, and we were lucky that most of the substances we were interested in did so. By passing a very small electric current through the relevant barrel, the substance under test was released close to the neuron being recorded. Usually one of the barrels of the electrode was filled with saline to test the effect of the current alone on the activity of the neuron. We assumed that the amount of substance released from the tip of the electrode would be dependent on the strength of current passed.
Sometime later one of my colleagues did some tests using radio-labeled compounds to measure the quantity released with different current strengths and confirmed that our assumption was correct. We seemed to be developing a new area of CNS research and I thought it might be interesting to make it known to a wider audience. Since I was a member of the organizing committee for the 3rd CINP Congress to be held in Munich, I proposed that there should be a session on studies on single neurons and this was accepted. John and I put together a program to include those who were working in similar or related fields; these included Salmoiraghi who was working at Joel’s new unit in Washington and Krnjevic, who had worked with Eccles and was then in Cambridge. The session was held in a fairly small auditorium which we thought would be adequate, but we were completely wrong as we had people queuing at the door to get in and others listening from the corridor outside. I was pleased with the reception we received.
TB: Weren’t there some problems with the CINP in those years?
PB: I am afraid there were. Rothlin was not an impartial chairman. He would lead the discussion and expect other people to agree with him. When a topic came up for discussion, there was no way in which members of the committee could present their own views before a conclusion was reached. I think it was Denber, one of the secretaries, who objected vociferously and I felt obliged to support him although I had some sympathy for Rothlin having visited him at home and at his retreat on the top of the Rigi. I thought he did not know any other way to behave in such circumstances, and I realized that the universities in Switzerland must have been run on very autocratic lines, as were those in the UK at one time.
TB: What was it about Rothlin’s actions that created the problem?
PB: Well, it was really about the way decisions were made because Rothlin wanted to have his way in everything and it was impossible to get him to listen to reason.
TB: Was there any real issue?
PB: I don’t think so but maybe you should talk to other people who were there. Have you talked to Denber?
TB: He died.
PB: Did he? I’m sorry to hear that.
TB: I talked to him about it some time ago but he didn’t say very much.
PB: He would probably sit on the fence for diplomacy's sake.
TB: Am I correct that you supported Denber?
PB: I did, because I felt it was necessary; although I appreciated Rothlin did what he did because it was the only way he knew how and one couldn’t change that.
TB: Some people told us that it was about finances.
PB: I don’t know if that is true. However, I felt that Denber had a point. Then Seymour Kety told us to pull together, which we did.
TB: I understood from some people that it was a rather difficult situation.
PB: It seemed the CINP might collapse and it was probably saved by the intervention of Seymour Kety.
TB: Some of the founders, Denber and Radouco-Thomas resigned.
PB: Yes, but my memory isn’t terribly good, one tries to forget unpleasant things.
TB: The important thing is the CINP survived and by the 3rd congress everything was fine.
PB: Yes, it was.
TB: The fourth CINP meeting was in Birmingham. Wasn’t it?
PB: Yes, it was the meeting I hosted.
TB: It was a great meeting.
PB: Was it? Good.
TB: Yes; it was the first meeting I attended.
PB: At the end of the week, we went to a performance of Henry V in Stratford and I fell asleep during the battle scene! So, it must have been pretty exhausting.
TB: It had an excellent program. It was also interesting in terms of organization. Everyone stayed on campus in the student halls of residence.
PB: Oh yes, but we hadn’t much alternative. There wouldn’t have been enough hotel accommodation in Birmingham at that time. There probably is now. I thought it was a disaster at the time because people were in rooms without wash basins. The student accommodation was quite Spartan. It has improved considerably since.
TB: There was one bathroom for about ten rooms.
PB: Not ideal for people used to better things. However, I think the meeting was successful scientifically.
TB: I remember that Max Fink delivered one of the plenary lectures on clinical neurophysiology, on the new science, pharmaco-EEG.
PB: Yes, he did and it was well received.
TB: And there was also a lecture by the president . . .
PB: That was the Austrian, Hoff.
TB: Can you tell us something about the budget and finances of the Birmingham meeting?
PB: I believe we covered our costs. I don’t think the University was quite as helpful as it should have been although we were provided with the accommodation we needed, including a large lecture theatre for the plenary sessions. We had adequate financial support, some from the United States, and most of the pharmaceutical companies I contacted gave us generous support.
TB: So, the meeting didn’t cost CINP any money?
PB: Not as far as I am aware. I don’t think the CINP had much money at the time. There was a bank account in Basel and the subscriptions were going in but there did not seem to be much money available.
TB: So, there was no money from the CINP.
PB: No. The meetings were supposed to be self-supporting. We were able to cover our expenses and pay the speakers but there were no large grants.
TB: Is there anything else you would like to say in relation to the Birmingham meeting?
PB: During the meeting there was discussion at the Executive Committee as to who the next president might be. I thought it was time we had someone from the UK and suggested Sir John Gaddum who was Professor of Pharmacology at Edinburgh and well known internationally. Unfortunately, when I approached him he was obliged to decline the invitation as he had developed esophageal cancer. It was also in that year I had been nominated for a professorial chair. Prior to that, I had been appointed to a Readership which was the most senior non-professorial appointment in the University and was usually awarded for distinction in one's research field. However, the Vice-Chancellor said to me, “It’s time we gave you a Chair.” The appointment should have been made in October, but he pushed it forward, so that I had professorial status in time for the meeting.
TB: Before that you were Acting Head?
PB: They made me Acting Head of the Department, but without a Chair. At the time I was the only non-medical head of a department in the Faculty of Medicine but that did not seem to matter and I got on well with my colleagues.
TB: It was after the Birmingham meeting that you became treasurer of CINP.
PB: It must have been then. I had served for six years as Councilor and thought it was time for new faces on the Committee but they invited me to become treasurer and I accepted.
TB: And you continued to be treasurer for six years.
PB: Was it as long as that?
TB: I think it was.
PB: I can remember at the Washington meeting having to go to the bank to draw out a large sum of money in order to pay the speakers’ expenses. Why we had to do it in that way I don’t know and I was concerned at having to travel across Washington in a taxi with such a large amount of cash. Perhaps I should have had an escort! I made the payments from my room in the hotel. I think it was the Sheraton, wasn’t it?
TB: Yes, it was at the Sheraton.
PB: Max Fink and I were invited by the Program Committee to organize a Symposium at the Washington meeting.
TB: What was the symposium on?
PB: The topic was “Anticholinergic Drugs”.
PB: I still had an interest in that area at the time.
TB: Would you like to say something about your symposium?
PB: I think it was successful. It was certainly well attended; we invited a number of distinguished speakers, including Wikler, Votava, Herz, Longo, Domino and Jacobsen.
TB: In those years there was still interest in publishing the proceedings of meetings.
PB: I had been involved in editing the proceedings of a number of CINP meetings. I had formed a good relationship with the Elsevier Publishing Company who had a series of books, called Progress in Brain Research, which later became a journal. They proposed to Fink and I that our proceeding should be one of these volumes.
TB: I think you were involved in editing the proceedings of the 1st, 3rd, 4th and 5th congresses.
PB: Yes, but with different collaborators each time. I should have stopped but I enjoyed doing it.
TB: You co-edited the Washington proceedings with Brill,Cole, Deniker and Hippius.
PB: That’s right and that was quite a big volume, wasn’t it?
PB: They were getting too big, I think.
PB: Well, I have enjoyed all the CINP meetings I have attended.
TB: By the time of the Washington congress in 1966 you were also involved with Mimmo Costa editing a journal in the field.
PB: In the early 1960s, at a meeting in Milan on “Adrenergic Mechanisms” held at the Mario Negri Institute, Costa asked me if I would be interested in co-editing a journal with him. Before that, Elsevier, who had published all the CINP Proceedings up to then, told me that they would be willing to publish a CINP Journal, taking all responsibility, including financial. This would have meant publishing the proceedings of meetings in the journal rather than as books which were getting rather large. However, when I put the proposal to the CINP Executive Committee, it was rejected. This made me more sympathetic to Costa’s approach. It is interesting that the CINP did later start a journal and I think it has proved successful.
TB: What was the name of Costa's journal?
PB: It was the International Journal of Neuropharmacology, which had been founded a few years earlier by Radouco-Thomas and Brodie. I knew about it as Radouco-Thomas had discussed the proposal to found a journal with me. I was already a member of the Editorial Board. Later on,Costa and I thought it would be better to simplify the title so we changed it to Neuropharmacology which it still is.
TB: And you have been editor of that journal until . . .?
PB: Only until 1993.
TB: About 10 years ago.
PB: Yes, I retired from my university post in 1986 and I thought editing was something I could do in retirement. Also, Costa wanted to give up at that time, so for a while I was sole editor. Costa and I had hoped to appoint our successors as editors but that was not to be. The journal was published by Pergamon Press which was owned and run by Robert Maxwell with whom I always got on well. He stated he would never sell Pergamon Press as it was one of his earliest ventures. However, when he ran into financial difficulties shortly before his death, he did sell and the new publisher wanted to appoint his own choice of editors. So, I resigned. I think it was time, although I enjoyed doing it.
TB: So, you kept the journal but gave up your CINP activities by the 1970s.
PB: That is correct. I was attending too many meetings and that is why I dropped out of the CINP. I used to enjoy the meetings, but I had to think about where to present my work, particularly as I was working on single cells. I was also getting involved with the British Association for Psychopharmacology and the International Union of Pharmacology.
TB: When was the British Association for Psychopharmacology founded?
PB: In the early 1970s.
TB: Aren’t you one of the founders?
PB: Yes, I was, but it was a difficult birth.
PB: Some of us in the UK had been discussing the possibility of establishing a British psychopharmacology group along the lines of the ACNP. People such as Roger Brimblecombe, Hannah Steinberg and others were encouraging me but I had too many commitments elsewhere. Then a letter appeared in the Lancet which proposed much the same thing except that it would include only people who were doing clinical work. I had no choice but to get involved. There was a meeting at the Royal College of Medicine in London where there was a somewhat heated discussion. Eventually it was accepted there were people in biochemistry, psychology and pharmacology who were making a significant contribution to psychopharmacology. Our opponents seemed to think that psychopharmacology should be purely clinical. The most difficult person was Max Hamilton, Professor of Psychiatry at Leeds. He and I had a big bust-up during the CINP meeting in Paris in 1974. But eventually we won the day and the BAP was founded along the lines of the CINP with an equal balance between clinical and non-clinical members and alternating chairmanships.
TB: So, the difficulties were resolved and the Association was founded.
TB: And some years later, you became President.
PB: Hamilton, of course, became the first President. That was inevitable. Then he was followed by Coppen, although it should have been a scientist, and I became President in 1978.
TB: Could we shift back to your research after the 1950s?
PB: As I have already indicated, I was becoming less interested in behavior and more interested in what was happening at the single cell level in the brain. I felt that I could leave behavioral studies to other people. So, I recruited a psychologist, Ian Stolerman to my department and he did psychopharmacological experiments with animals.
TB: When did you do your work on opioid receptors? Wasn’t it in the late1970s?
PB: No, it was earlier than that. I had another sabbatical when I was offered a one-year Fellowship at the Center for Advanced Studies in the Behavioral Sciences which was located on the campus of Stanford University in California.
TB: When was that?
PB: It was in1967. It may seem strange, since at that time I was relinquishing some of my interests in behavioral studies. Still, it seemed to be an opportunity not to be missed.
TB: And what did you do in Stanford?
PB: It was a “Think Tank,” where people went mainly to think and write. There were no laboratory facilities, but I could probably have arranged to work in the Department of Pharmacology at Stanford Medical Centre as I knew a number of people there, including the Killams. I decided to spend my time writing, which was what most Fellows at the Centre were doing. And, of course I received many invitations to visit other laboratories and give talks. I had been asked to write a chapter on the phenothiazines for a book which I think was the Annual Review of Pharmacology. I spent some time on that as I decided to make it as comprehensive as possible; I covered the history, chemistry, pharmacology and clinical uses. I was told later that my chapter has been useful for teaching! I also wrote another chapter for a book whilst I was at Stanford, and I started planning a book of my own.
TB: After your return to Birmingham from Stanford I suppose you were mainly involved with research.
PB: I had hoped to be, but again it was a difficult time. Having left my department in the hands of my colleague Brian Ansell for a year, with the MRC Unit being looked after by John Wolstencroft, there were many administrative matters to deal with. There was also the journal which a friend and colleague, Ted Marley at the Maudsley Hospital in London, took charge of during my absence. I was lucky to have such reliable people stand in for me, but it took time to pick up the threads. In addition, I had heard whilst I was still at Stanford that the teaching of pharmacology to medical students in Birmingham had virtually collapsed and the students were complaining. I won't go into the reasons for this but after consulting my colleagues I went to see the Dean of the Medical School and offered to put on a course in pharmacology for the preclinical medical students. My proposals were accepted and we became involved in establishing the course, bringing in people from other departments where necessary, including clinicians. I had done a limited amount of teaching from the time I received my PhD, but I had felt for some time that we should be doing more. There were also political and financial considerations. I found myself on many committees, both university and NHS, some of which had no relevance to my own subject, but as a senior academic it was considered a duty.
At the time, I was the only non-medical head of a department in the Faculty of Medicine which meant I was frequently asked to serve on NHS consultant appointment committees. They were obliged to have a university representative and I was told they preferred to have someone non-medical who would “have no axe to grind!”
TB: How much interaction did you have with the drug industry?
PB: I did some consulting but not very much. I did not find it very interesting although I made some good friends in industry.
TB: Was there any particular drug that you had been involved in consultation?
PB: No, the work was more general. I would be asked to look at particular types of research and advise whether it should continue or stop. I was attending a meeting in Basel on one occasion and received a call from Hugo Bein who was head of research at Ciba-Geigy, and also a friend. Over lunch he invited me to be a consultant at the firm and after discussing my role, I accepted. Unfortunately, before my first visit, Bein had left and new people had taken over with completely different ideas so I did not continue for very long. I also consulted from time to time with UK firms such as ICI, Wellcome and Glaxo, and supervised research workers in industry who were allowed to work for a higher degree. That was quite rewarding. I’ve always had good relations with the pharmaceutical industry and was happy to advise them from time to time on appointments.
TB: You trained many people. Would you like to mention the names of a few?
PB: Well, I have already mentioned Brian Key and Jim Hance, who eventually went to California. Brian remained in Birmingham and was a Senior Lecturer when I retired. There was Tony Nicholson, who was medically qualified and finished his PhD whilst working at the Institute of Aviation Medicine at Farnborough. During my stay in Stanford he visited me, accompanied by a senior RAF psychiatrist. I acted as their guide and accompanied them on a visit to NASA where I was allowed to try landing a 747 on the simulator! Then there was Malcolm Roberts, who went to Edinburgh to work with John Smythies and then moved to the Physiology Department in Cardiff. There was also Gill Samuels, who did research on prostaglandins for her PhD. She went into industry, ending up at Pfizer, where she became a vice-president for research and involved in the development of Viagra. Ian Phillips went to Ohio University where I visited him; he is now head of a department at the University of Orlando, Florida. Another was Andy Dray who worked on opioid receptors. Peter Keane was offered a Royal Society Fellowship to work in Lyon and stayed in France with Synthélabo. There were a number of others who went mainly into the pharmaceutical industry as academic jobs were getting hard to find.
TB: Could you tell us about your work with opioid receptors?
PB: It came about from a conversation with Hans Kosterlitz from Aberdeen. He admired our work but asked why we had not investigated morphine. I said that we thought morphine was not suitable for iontophoresis, but I was wrong and when we tried it morphine produced striking effects which we were able to antagonize with naloxone applied iontophoretically. Then came the discovery of enkephalins from the Aberdeen group which aroused world-wide interest and we received one of the first samples to test.
TB: So, the research was focused on classifying opioid receptors.
TB: Didn’t you also do some research with serotonin receptors?
PB: We worked quite a lot on serotonin receptors.
TB: What did you do?
PB: We examined the distribution of neurons that responded to the application of serotonin and its agonists and antagonists.
TB: Weren’t you doing also some research with anesthetics?
PB: We were involved in looking at some new anesthetic drugs of the Fentanyl type. They were rather strange drugs and we did not get very far with the investigations which were supported by a grant from a government department. Those drugs are extremely potent and some are now used clinically. One of them was interesting because it blocked respiration without affecting consciousness, yet respiration started again voluntarily.
TB: Any other research you did that you would like to mention?
PB: None that I can recall at the moment.
TB: It seems that by the 1980s you shifted almost completely to receptor research, right?
PB: Yes, and that continued until I retired.
TB: When did you retire?
PB: In 1986.
TB: Didn’t you publish a book around that time?
PB: Yes, it was the book I had started planning when I was at Stanford twenty years earlier but when I returned to Birmingham there was little time to finish it until after I retired.
TB: So that was in 1986?
PB: It was published in 1987.
TB: Can you tell us something about the book?
PB: It was called Introduction to Neuropharmacology. In my teaching activities, which had developed significantly and included not only medical students, but also dental students, anesthetists working for their primary exams and postgraduate toxicology students, I felt there was need for a basic text. That is what the book was intended to be, an introductory text which could also be read by the intelligent layman. Unfortunately, I was let down by my publishers. The original publishers I approached were well known for publishing medical books and very keen to have my book after consulting their advisors and staff. Sadly, they were taken over by a much larger organization, which although major publishers of science books, were not very interested although they promised to fulfill the contract. I cannot complain about the production and I was pleased with the result, but I do not think the book received adequate publicity. Not many people had seen the book or an advertisement for it. I do not think many copies were sent for review although I received some letters of congratulation including one from a professor of anesthesiology and another from a psychiatrist, both of whom said it would be useful in teaching.
TB: It sold quite well. I read somewhere it sold about 9,000 copies?
PB: I am not sure it was as many as that.
TB: If it was, that was not bad.
PB: I had expected more but it certainly wasn’t a bestseller! There was probably too much competition as everybody feels motivated to write a book these days.
TB: It was probably one of the first introductory books on neuropharmacology.
PB: I think it was.
TB: Do you think it could still be used?
PB: I would like to hope so. Some parts, in fact most, are still valid but it would have to be brought up to date and new sections added. I wouldn’t want to do that now.
TB: Was it translated into any other languages?
PB: I don't think so. As I said, the new publishers weren’t terribly interested. They fulfilled the basic contract and that was it.
TB What did you do after the book?
PB: I was still editing the journal, Neuropharmacology, and when Costa resigned I was sole Chief Editor. There was quite a lot to do as I did not have any secretarial help. Previously, I had two secretaries and an editorial assistant plus various other people to help me. Then I was asked to join a newly formed International Committee on the Classification of Drug Receptors, under the auspices of the International Union of Pharmacologists. This came about because in 1984, two years before I retired, we had a meeting of the British Pharmacological Society in Birmingham and the day before the main meeting started, I organized a Symposium on Serotonin Receptors, inviting everyone who had worked on serotonin, including its discoverers, Rapport and Erspamer, neither of whom unfortunately was able to attend. We had an excellent meeting and I arranged for the proceedings to be published as a supplement to Neuropharmacology. During the discussions, it was suggested that a small group might meet regularly to discuss receptor subtypes, including not only 5-HT but dopamine and opioid receptors.
Subsequently, at the International Pharmacology Congress in Sydney in 1987, which I was unable to attend as I was in hospital, a proposal was made to set up an international committee on Drug Receptor Classification and I was proposed as one of the UK delegates. The committee was small at first and not very active. The chairman was not keen to continue and eventually Paul Vanhoutte took over. After that the committee expanded rapidly and became much more active, producing a series of reports. I was asked to lead a working party on the classification of opioid receptors. It took a long time and involved many people, and at one time, for health reasons, I was obliged to hand it over to someone else. Eventually, we published a comprehensive report which I think was well received. At one time the Committee was looking for somewhere to publish its reports when I was the BPS representative on the editorial board of Pharmacological Reviews. I managed to persuade them to take on the task, so that is where our report on opioid receptors was published.
TB: This was in the early 1990’s?
TB: Who were the people on the committee? Was Solomon Snyder on it?
PB: No, he wasn’t. There was Trendelenburg who worked on adrenaline.
TB: Was Sol Langer on it?
PB: Yes, he was. I used to meet him with his wife. He was moving from South America to Paris to be head of pharmacology at a drug company.
TB: Later on, he moved from France to Israel. Anyone else on that Committee you remember?
PB: There was Colin Dollery from London, Eric Barnard from Cambridge who did a lot of work isolating receptors and their constituent proteins, Pat Humphrey from Glaxo, Tom Bonner, Godfraind, Dhawan from Lucknow and RudolfoPaoletti. These are the people I remember best but there were many others and the membership of the committee changed frequently.
TB: Could you tell us something about your activities on international organizations. We already talked about the CINP. Haven’t you been involved with WHO?
PB: It must have been in the early 1960s, that I was invited by the World Health Organization to join a Working Group on the Major Tranquillizers. When I arrived in Geneva I was met by the Deputy Director of WHO, a Dr. Medvedev who took me to his apartment and plied me with vodka, after which he asked me to be the Rapporteur of the meeting. I was reluctant to accept as I had done nothing like it before but could see no way out. In the event all was well and we had a very successful meeting. I received a lot of help from the other members, including John Smythies. The only problem was that I spent every evening after dinner going through the typed transcripts of the previous day's discussions. Lehmann was the Chairman and the only other members I can remember well were Deniker and Freyhan. There was also a man named Lapin, a psychologist from Leningrad, who was very friendly and interested in my work but I never had time to talk to him as I was so busy preparing the report. I don't think Michael Shepherd was there, as I knew him well and would have remembered him. Eventually, our report was published by WHO with the recommendation that the term “Neuroleptic” should be used world-wide and I think it has been. I was on another WHO committee which was concerned with amphetamine derivatives which were being made illegally and were popular with drug users.
TB: Could you name one?
PB: One of them was ecstasy. Do you know it?
TB: Was this in the 1950’s?
PB: I think it was 1958 but it could have been later.
TB: Who was director of the mental health unit at the time?
PB: I don’t know. A Dr.Chruschiel, if that is the correct name, was working with us on one of the committees, but I don’t remember who the director of the unit was. It seemed that staff at WHO changed frequently, but I remember Nakajima who eventually became the Director. I first knew Nakajima when he was working with Thuillier in the 1950s in Paris. What happened to Thuillier?
TB: He’s still alive and writes books.
PB: I think he wrote a book on the history of psychopharmacology but I have not seen it.
TB: I think that at a certain point of time he was involved with the drug industry.
PB: He visited Birmingham on one occasion and gave a talk and showed a film of his circling mice. He had this compound which, if injected into mice, caused continuous circling. I asked him a number of times if he had had it analyzed chemically and if it was optically active but I never knew what happened. It was like Monnier’s sleep-substance in that respect. He was a very generous man and looked after me extremely well when I visited Paris to meet Delay. Thuillier was a gourmet and took me to some excellent restaurants in Paris.
TB: He was certainly a very talented person: a writer, a pharmacologist, a psychiatrist.
TB: Weren’t you also on a WHO committee on psychotomimetics?
PB: I don't remember, but I served on a British Government Committee on hallucinogenic drugs. The Chairman was Bill Paton who was Professor of Pharmacology at Oxford and both Ted Marley and I contributed to the report but what happened to it I never knew. As with so many things connected with government, there was never any feedback.
TB: In the course of your career you have been involved, in addition to research, in all kinds of other activities.
PB: Yes, writing, teaching, editing, administration and even broadcasting, both live television and radio.
TB: You had to take care of people in a rather large department.
PB: It was not that large; but we had many students. Quite a lot of the teaching involved lectures, tutorials and practical classes and there were postgraduate students to supervise.
TB: We already talked about your book that was published after you retired. Was that your last publication?
PB: My last paper was “Classification of Opioid Receptors” which was the report of the working party I had originally led for the IUPHAR Committee on Receptor Nomenclature and Drug Classification. As I was unable to continue due to ill health, the final version was written by M. Hamon who was a good friend. It was published in Pharmacological Reviews in 1996. The other thing that happened was that I was awarded the Pythagoras Prize from the University of Cattanzaro in southern Italy, which you have probably never heard of.
TB: I read about that Prize in Mimmo Costa’s autobiography.
PB: I am afraid that at first I did not take it very seriously but then I was at a meeting in London and talking to Pepeu from Florence. . ..
TB: Is he a pharmacologist who did a lot of work with cholinergics?
PB: That is right. Anyway, he said I ought to go, as did Costa who had received the prize earlier. It was a long journey but I enjoyed my visit and learned more about Pythagoras who lived in that area of Italy for some years with a group of students. He was, of course, a philosopher as well as a mathematician.
TB: What would you think was your most important contribution to neuropharmacology?
PB: It is difficult to think of any one thing. I like to think that we made a number of contributions, perhaps only minor ones, in many areas.
TB: So, you think they are equally important?
PB: I would like to think that the introduction of the microiontophoresis technique for the study of single neurons in the brain is one, and. perhaps our work with opioid receptors and their classification is another.
TB: What about your early contributions about the structures involved in the mode of action of psychotropic drugs?
PB: Yes. I think I made a contribution there, small though it was.
TB: Don’t you think that work should have been followed up?
PB: I had hoped it would be. It would have been nice if somebody had done that and I thought one of my students might do so, but people like to do their own thing, and why not?
TB: Has research in neuropsychopharmacology in the past decades moved in the direction you would have liked to see?
PB: I’m not one of those people who like to foresee what is going to happen or has plans for far ahead. I did what I thought was important at the time and what I was interested in. The main thing, I think, is to enjoy what you do.
TB: And you did enjoy it?
PB: Yes, I did. Also, I think I got on well with the people I worked with; but I don't know what they thought! When I retired, a group of my former postgraduate students entertained my wife and myself to dinner at the RAF Club in London and I shall never forget the student who, when I suggested that he should publish his latest research under his name alone, said “No,” he wanted my name on his paper in recognition of the help I had given him. I also valued my stay in Pisa, not just for the facilities and the opportunity to learn microelectrode work, but also because of my contact with Moruzzi.
TB: Could you tell us something about Moruzzi?
PB: Moruzzi was a very nice quiet man. He did not shout as so many Italians do when they get excited but was very charming and was an excellent physiologist. There was an unusual atmosphere in his institute which is difficult to describe. The Italian system involved people moving from one center to another for promotion, Rome being the pinnacle. But I don’t think Moruzzi wanted to move from Pisa as it had everything he wanted and he had an international reputation. He sometimes asked me to read his papers before sending them for publication but I found there was nothing I could contribute; his English was better than mine!
TB: Did you maintain contact after you left?
PB: For a while and then, when he was retiring, they organized a symposium for him in Pisa I attended. I met some old friends like Herbert Jasper and Mary Brazier from the early days of EEG.
TB: He was also involved in research on the reticular formation.
TB: And in conditioning.
PB: I believe so.
TB: He was working in Montreal. Didn’t you also have some contact with Ted Sourkes, the biochemist from Montreal who wrote a book on the Biochemistry of Mental Disease?
PB: Yes, I knew Ted Sourkes very well. He spent a year in Birmingham at Joel's invitation. Is he still around?
TB: Oh yes, he is retired, but has remained very active. He is editor of a journal on the history of neuroscience.
PB: That’s interesting. Ted used to tell us stories about the institute in Montreal where he worked and about Ewen Cameron.
TB: But, of all the people you were involved with, it was Joel who had the most important impact on your career?
PB: Yes. He gave me my chance; he started me off in what was then a new field, relating behavior with the electrical activity of the brain and he introduced me to a lot of people, especially at the neurochemical symposium in 1954 in Oxford. It meant that my work became known quickly, perhaps too quickly. He made suggestions from time to time but otherwise left me to get on with it. It took me a little while to get used to this way of working and we had our ups and downs. I was inexperienced and I think I resented it when I heard he was talking about my work to groups I had never heard of. However, he had a way of putting things over much better than I could have done and the support came in as a result. When he left Birmingham for Washington I felt neglected, especially as things were in a bit of a mess, but it did me good in the end and was an excellent, if traumatic, experience. Had he stayed in Birmingham, I would probably have become frustrated and moved somewhere else where the facilities I had in Birmingham would not have been available and I should have had to start again.
TB: Just one last question. Is there anything you would like to see happen in the field?
PB: There has been a trend recently to measure activity at different sites in the brain by means of blood flow. This development is both interesting and important but it would be nice to see the findings correlated with electrical activity. I had always hoped that someone would extend and improve the techniques which we developed, but so far that has not happened.
TB: On this note we conclude this interview with Professor Bradley, one of the pioneers of neuropsychopharmacology. Thank you very much, Philip for your contributions to the field and for sharing this information.
PB: I’ve enjoyed it. I didn’t expect to, but I have.
TB: Thank you.
May 17, 2018