Conversation with Joseph V. Brady

Abstract

AddictionVolume 100, Issue 12 p. 1805-1812 Free Access Conversation with Joseph V. Brady First published: 23 November 2005 https://doi.org/10.1111/j.1360-0443.2005.01246.xCitations: 4AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Figure 1Open in figure viewerPowerPoint In this occasional series we record the views and personal experience of people who have specially contributed to the evolution of ideas in the journal's field of interest. Joseph V. Brady is Professor of Behavioral Biology, Director of the Behavioral Biology Research Center, and Professor of Neuroscience at the Johns Hopkins University School of Medicine in Baltimore, Maryland. He is one of the founders of the field of behavioral pharmacology. Addiction (A): Joe, you are well known as one of the founders of behavioral pharmacology. Were you interested in psychology and behavior from an early age? Joseph V. Brady (JVB): Oh, no. My early home and school years were strongly influenced by the Catholic parochial school system of Brooklyn, New York, and by a Xaverian and Jesuit secondary and college education. When I entered Fordham, a Jesuit college, in 1940, everybody took philosophy, logic, epistemology, and for the first couple of years there was no specialization. Even through college I had no objectives in that direction at all. I knew that I would have to go into the military, so I joined the Reserve Officers Training Corps (ROTC) while I was at Fordham. By 1942–43, the ROTC was activated, so Fordham compressed the course work and I graduated in less than 3 years. Then I was sent off to officers’ training school, commissioned as Second Lieutenant and served as an infantry platoon leader. I was in Berlin by the end of the war, when orders came from European Headquarters in Frankfurt reassigning me to the 317th Station Hospital in Wiesbaden, Germany, which had just been designated as the Neuropsychiatric Center of the European Command, and that is what changed my life. A: How so? JVB: The 317th Station Hospital had been a Luftwaffe hospital, and it obviously had some psychiatric focus because one of the things we found there were huge wards with tubs. Remember, this was the 1940s. What were the treatments available at that time? There were the tubs, there was insulin, there was electroconvulsive shock, and there was psychoanalysis. Everybody who was admitted to that hospital on the psychiatric ward, along with his bathrobe and slippers, got a set of electrodes. This was a very effective way to keep the closed ward calm. When I reported in to that hospital, the Commanding General sent me over to the Chief of the Psychiatry Service, who greeted me with, ‘Am I glad you’re here. I’ve got a Major General up on the 2nd floor. I need a Rorschach on him right away.’ Now, when you’re a Lieutenant in the Infantry and a Major tells you to do something, there is no other answer but, ‘Yes, Sir!’ So I said, ‘Yes, Sir’, and ran off to the hospital library. They had a reasonably good library, auf Deutsch for the most part, where I found a couple of books on the Rorschach, translated them as best I could, memorized them as if they were an Army Field Manual, and came back the next morning to administer the first of some 500 Rorschachs that I would give over the next couple of years. I also learned the Wechsler Bellevue, the Thematic Apperception Test, the Bender Gestalt—I mean I mastered the whole repertoire. A: How did you do that? JVB: I read. I read a lot of books. Well, the whole psychiatric/medical staff was at about the same level of sophistication in their field. We would teach one another. We were like the blind leading the blind. That went on for a little more than a year. Then the Army sent several of us back the United States, me to the University of Chicago, to get some training to bring us up to date. So, to go back to the point of what I thought I would do when I was in college (and while I was still in the Army), I thought I would get out and go to law school. My father was a lawyer, and my brother. But here came an opportunity to go to school at the Army's expense. By that time I had been made a Captain, and I had a couple of kids. So I went off to the Department of Psychology at the University of Chicago. They had a new chairman at that time, James Grier Miller, and Miller had a brand new bright idea. We were to review the whole of psychology in 9 months and then take comprehensive examinations for the PhD, and have selected a specialty area. This was rather unusual. I was planning to get a degree in clinical psychology. But there was also another requirement. You also had to pick an experiment from the literature and replicate it. I picked an experiment that Estes and Skinner had published in 1942 [1] on conditioned anxiety, and I went over to see Howard Hunt, who had just come from Stanford to the University of Chicago as an associate professor and wanted to start a laboratory. So we built some rat boxes and things of that sort, and got rats pressing a lever for sugar water, and we superimposed upon this intermittent schedule of reinforcement 3 minutes of a clicking noise followed by a shock to the feet. When I tried this, nothing much happened; I didn’t get any change in behavior, so I increased the shock level. The bottom line is, not only did I not reproduce the Skinner and Estes paper, but I got real suppression. When I turned on my clicker, not only did the rats stop pressing the lever, they had piloerection, crapped and crouched in the box, took the shock, and then went right back to work again. I said, Wow! That is real conditioned anxiety. At the end of 9 months, I had completed my comprehensive examinations and had four rats trained so that I could measure their conditioned anxiety levels by the changes in the rate at which they performed their ongoing lever-pressing business. It occurred to me that this was really a very good model of psychiatric disorders expressed as a change in a person's rate of performance. I said perhaps electroconvulsive shock (ECS) could reverse the conditioned anxiety in these rats, so we produced full-blown tonic clonic convulsions in the animals. After 7 days of treatment animals who received three ECS per day for 7 days worked right through the clicker. We had literally ‘cured’ these animals with the electroconvulsive shock. And I was changed in terms of what I was going to do for the rest of my life. It was perfectly clear [2]. So with all the critical course work and the dissertation done, I spent a year with Carl Rogers. I spent some time in clinics, but most of my time was spent in the laboratory. A: You wrote this up and gained your doctorate? JVB: Oh yes, within 2 years. By that time the Army had assigned me to Walter Reed Army Hospital, in Washington, DC, and sent me back to the clinical service conducting Rorschachs again. The Army did not have a place for somebody who plugged rats into light circuits! A: There was no experimental branch at Walter Reed at the time? JVB: None whatsoever, not until David Rioch came along. Within a year after my arrival at Walter Reed, Dave Rioch was hired by what was then called the Army Medical Research Institute, which was in the grounds at Walter Reed but was separate from the hospital. The military found that they lost more man-hours per annum during that 1940–45 war from behavioral or psychiatric problems than from all other medical problems put together, but they had no research in that area at all. This was in 1951, shortly after the National Institute of Mental Health was established, and before anyone else had thought of interdisciplinary neuropsychiatric research. The idea of bringing together all these different disciplines at one place was Dave Rioch’s, and Walter Reed was the first interdisciplinary neuropsychiatric research institute. Then Seymour Kety and Joel Elkes, who had been at St Elizabeth's Hospital and were Rioch's friends, put the idea into place at the National Institutes of Health (NIH). Then NIH started awarding grants for such research—a somewhat novel idea at the time. The major story is Walter Reed Army Hospital, where I was on the clinical service. Bob Galambos, the neurophysiologist that Dave hired first, asked me to come and give a talk to him and Rioch. And with fire in my belly, I gave them the story about the electroconvulsive shock and how it was the only experiment that I knew of in psychology that every time you replicate it, it comes out the same way. I became the first ‘Chief’ of the department of experimental psychology in the neuropsychiatry division. That is one of the reasons why I have always thought of myself as the beneficiary of a fortuitous environment! Just about this time, the substantive part of the research program in behavioral pharmacology started. The first thing that happened was the appearance of the psychotropic drugs. The major tranquilizers—chlorpromazine, reserpine—appeared on the scene during the early 1950s. Murray Sidman and I decided that as everyone was raving about reserpine, for example, we would give reserpine to all the animals in the laboratory; but we did not know anything about dosing at the time. The interesting thing is that most histories of science in this area subscribe to a ‘creationist’ view. They all emphasize the great men who produced the advances in the field. In a lecture I gave at last year's meeting of the Federated American Societies of Experimental Biology, when the American Society of Pharmacology and Experimental Therapeutics gave me the Dews Award for life-time contributions to research, I told them that I was going to present a revisionist history of behavioral pharmacology—that is, the ‘great men’ approach is not the way to look at the evolution of the field. This field should be viewed as the product of an interaction between methodological developments and conceptual changes [3]. And you can start right there with the tranquilizers. Up until that time, the kinds of effects that you produced with drugs such as reserpine and chlorpromazine had been regarded as unwanted side effects that were enough to keep a drug off the market. Reserpine, for example, turned up at the CIBA laboratories in New Jersey, where they were looking for a cardiovascular drug, and they discovered that when they dosed the rhesus monkeys, generally pretty hostile and aggressive animals, they could put their fingers safely in the monkey's mouth. The monkey was awake but had lost all his aggression. From that point on, we went to work screening for those tranquilizing effects of drugs and thus witnessed one of the major conceptual changes in the behavioral pharmacology field. At that time, I also had an academic appointment at the College Park campus of the University of Maryland, where I established a laboratory and applied for the first behavioral pharmacology program project grant from NIH. The first person I put in charge of that laboratory was Richard Herrnstein (later to become Chairman of Psychology at Harvard), who also was still on active duty as an Army officer at Walter Reed and was quite amenable to an assignment to get the laboratory started at College Park. A: How did you, as an Army officer on active duty, come to be setting up a laboratory at a university? JVB: This all came about as a result of a meeting of the first psychopharmacology study section at NIH. It was a very informal study section scheduled shortly after the appearance of the first tranquilizers—and after Congress had appropriated $2 million for psychopharmacology research in the NIH budget. A small meeting was called, about a half dozen of us, including Lou Goodman, Ed Evarts, Seymour Kety, Jonathan Cole, myself. We met for a day or two trying to decide how best to spend the $2 million that Congress had just appropriated. We had before us for review six invited proposals and decided that none of them were worthy of being supported. When we informed Phil Sapir, the Executive Secretary of the study section, accordingly and suggested that the money would best be returned to the taxpayers—that is how naive we were at the time—he informed us that if we did that, the Surgeon General of the Public Health Service would have to resign, because that would be a clear indication that he could not do the job to which he was assigned. So we decided we would all go home and do our best to save the Surgeon General's job by writing our own proposals. That is when I wrote the program project grant application from the College Park Laboratory at the University of Maryland asking for a quarter of a million dollars. As you can well imagine, that was a lot of money in the early 1950s. The reviewers ultimately agreed that the science was good and the research necessary, so they approved the first behavioral pharmacology program project grant from NIH for 3 years! A: That laboratory turned out to be an incubator for some of the early drug abuse researchers. What can you tell us about that? JVB: Heading a laboratory at the University of Maryland gave me my first chance to bring in other people on the academic track. I received an inquiry from Len Cook, at Smith-Kline & French in Philadelphia, asking me if I would be interested in taking on one of his young assistants who wanted to gain a graduate degree. That was Charles R. (Bob) Schuster; so Bob was my first predoctoral student. He came down to College Park and brought a tremendous amount of pharmacological sophistication into the laboratory. Then my mentor in Chicago had a trainee, Travis Thompson, who wanted to take a postdoctoral fellowship, so I took Thompson on. When Schuster and Thompson [4] fell in together in the laboratory, it was the start of a life-time relationship. They wrote the first behavioral pharmacology textbook, and so forth. It was Schuster fooling around with trying to teach a monkey to use an infusion of a drug as an SD for pressing a lever that was essentially the preamble to drug discrimination, but we did not know it at the time. We just wanted to see whether the animal could discriminate that something inside him changed so he should do something outside. What Schuster and Thomson discovered was that for some reason the animal was pressing the lever to obtain the infusion. I said, ‘Why don’t we try a drug?’. And this is the idea of the interaction between methodological developments and conceptual change. What did that do when animals started self-administering drugs? The prevailing view of alcoholism and drug abuse at that time was that these were events that were largely the result of people being driven into this terrible life-style. Now all of a sudden we had monkeys pressing levers to obtain a drug. It is a perfect example of a methodological development producing a conceptual change: it was clearly the consequences, not the antecedents, that were maintaining the drug self-administration performance. A: But what about the role of the ‘great men’? JVB: Well the great men are agents. They just happened to be in the right place at the right time. Now there are good agents and bad agents, but to hang the development of a field on great individuals is misplaced in my view. I think much of it, as an environmentalist, comes as a result of fortuitous events that occur in your life. And my life-time is no better example of that than anybody I know. Think of the fortuitous events that have kept me from being a lawyer! A: When did you move your research to Johns Hopkins? JVB: These transitions are never clean. I accepted an appointment at Johns Hopkins before I left the Army. I left Walter Reed in 1971, but I kept the appointment at Maryland for a while. Joel Elkes, who had become Director of the Department of Psychiatry at Hopkins, invited me to join the department there. A: You have given quite a bit of time to various advisory committees and commissions. You served on the President's Science Advisory Committee in 1961. How did that come about? JVB: During the Kennedy years the White House put together a special panel to look at promising technologies for the future. The chairman of the committee was a professor from MIT. Fred Skinner and I were the two behavioral representatives. By and large, Skinner avoided serving on any committees, but when he was asked to serve on this Life Sciences subcommittee of the President's Science Committee, he evidently could not refuse. In the course of those proceedings, I went up to Boston and stayed with the Skinners while we spent a few days composing our contribution talking about behavioral technology. I learned something of how Skinner operated, living with him for those several days. His study was in the basement, and there was nothing on his desk except what he was working on—unlike my own desk. The object, of course, is perfectly clear. You spend a great deal of time ‘warming up’ when you have other things around, cleaning your desk and so on. Skinner would go right to work. He had a little timer which he started, and it had a red light on it. He counted the number of words, if he was writing, that he had produced that day, and plotted them on a cumulative curve on the wall. When he stopped or was interrupted he turned the timer off. But when you walked into the room and saw the timer running with the red light on you knew he was being productive and this was not a time to interrupt. He was a man who worked seriously to control his own behavior. A: In 1961/1962 the word ‘psychopharmacology’ was just coming into use to describe the new area of research that you were working on, and you were you involved with starting the American College of Neuropsychopharmacology (ACNP). Were problems of addiction of interest to that group? JVB: Yes, I was one of the ‘founding fathers’ of the ACNP. Joel Elkes was one of the moving forces behind it, I was on the first credentials committee and Harris Isbell (the Director of the Addiction Research Center at Lexington, Kentucky) was the first chairman of that committee. Abe Wikler and Bill Martin were also part of the original group. The Lexington group and addiction research were well represented. A: Not long afterward you played a central role in shaping the direction of drug abuse research for the entire country. JVB: Several years later, I served on the very first NIMH study section on drug abuse. I replaced Jerome Jaffe, who had taken a high level job in the White House and had to leave the study section. The first Chair was Eddie Way. Study sections in those days had 30–40 people on them. The drug abuse study section had anthropologists, biochemists and so forth, and we reviewed the whole range of the field; so you would have an anthropologist listening to an evaluation of biochemistry proposal, for example, and everybody voted. When Eddie Way reached the end of his term as Chair he recommended that I should step into that role, so I became the Chairman of one of those very early and very expansive drug abuse study sections that site-visited just about everything and spent a full week reviewing proposals. A: Looking back, do you see some particular point in your work that led you focus on psychopharmacology and addiction? JVB: Absolutely. The first paper I published in Science was on the effect of reserpine on CER and this was the first cumulative record to ever be published in Science; secondly, it was a single animal. Can you imagine getting away with a publication in Science with an n of one? That paper was published in the mid-1950s [5] and that was the paper that led to my helping to set up laboratories at various drug companies—Merck, Lilly, CIBA and so on. That led to training options. It was the basis for the program project grant, and that is how I ended up getting Bob Schuster as my first doctoral student. It was when Bob Schuster and Travis Thompson came to my laboratory at the University of Maryland and Schuster was interested in the way a drug could be used as a discriminative stimulus that the first drug self-administration work started. A: You continued that line of research after they left? JVB: Oh, yes. We took it to Johns Hopkins when Jack Finley and I moved there, and it became the major driver in the laboratory there. As soon as I arrived at Hopkins I began to bring in more post-docs. George Bigelow and Roland Griffiths came from Travis Thompson's laboratory at the University of Minnesota, where he had gone to teach. Scott Lukas came from Elias Kazan's laboratory at the University of Maryland School of Pharmacy, Jack Henningfield came to us from Minnesota as well, Nancy Ator came as a post-doc from Jim Barrett's laboratory at the University of Maryland in College Park, Richard Foltin and Marian Fischman came from Chicago, Tom Kelly from Minnesota and Maxine Stitzer from Michigan, among many others who have contributed importantly to the behavioral pharmacology work at Johns Hopkins over the past several decades. A: How has your abuse liability work evolved over the past 40 years? JVB: Well, the first animals we used were rhesus monkeys. Then we got a baboon at Walter Reed and we were so impressed with that animal—its hardiness, to start with, and its relative manageability compared to the rhesus monkey. We now have had some 60 baboons in these experiments and the refinements that we have made in the methodology came as a result of applying a procedure that Bill Hodos developed at Walter Reed called the progressive ratio. That is a method that made it possible to have the animals rank order the drugs with regard to their abuse liability [6]. The other direction in which that development has gone and is now being practised is extending the notion that just because a drug or a compound is self administered does not necessarily make it bad or dangerous, but it is the price the organism pays for what is administered. That is when we enter the animal psychophysics side of this, so we have developed procedures with these baboons so that we can determine their auditory and visual thresholds and then see what effect the drug at different doses has upon those measures. That is how we developed something akin to the therapeutic ratio. This was a ratio that compared the dose of the drug that would be self-administered by the baboon with the dose of the drug that produced a decrement in visual or audio thresholds [7]. Drugs differ in that regard. Some of the drugs—phencyclidines—produce changes in audio and visual thresholds at doses even below that which is self-administered. With the barbiturates, on the other hand, the minimum dose that is self-administered produces hardly any change in audio and visual thresholds, and does not do so until you push the dose well above the lowest self-administered dose. The work with the baboons has been going on for nearly 40 years now. A: You were also very much involved with the Committee on Problems of Drug Dependence (CPDD). Can you tell us how it evolved from a committee of the National Academy of Science into the College on Problems of Drug Dependence? JVB: I was Chairman of the Committee around the transition time. It was still an old boys’ club in 1980. The first meetings of the Committee that I went to were held at the National Academy of Science. I am not sure whether it had been separated from the Academy as an independent college, but it was still not a membership organization when I became Chair. I lobbied to change that, with Chuck O’Brien and Jerry Jaffe who were in favor of that idea, as were Loretta Finnegan and Mary Jeanne Kreek. As I recall, Eddie Way and Lou Harris, among others, were pretty much opposed at the time. I remember sitting with Jerry Jaffe and Harold Kalant trying to work out something that would be acceptable to this whole committee about my way of looking at substance abuse problems and arguing about why I thought the word ‘addiction’ was an absolutely useless term because it had too much surplus meaning. If you looked at the different aspects of the problem, it seemed to me that the critical events in the process were clearly divisible into two distinct categories, those that occurred before actual drug taking—roughly defining the ‘abuse’ category—and those that occurred after and as a consequence of drug taking—defining the ‘dependence’ category. Getting that committee to agree to anything as a group was very difficult, but with Jaffe and Kalant on my side, I had the necessary leverage. A: Perhaps this is a digression, but could you tell us something about your involvement in the National Commission for the Protection of Human Subjects? JVB: Last year was the 25th anniversary of the Belmont Report, the surprisingly influential product of that Commission first published in the late 1970s and immortalized as the basis for all the ensuing Federal regulations on the use of human subjects in biomedical and behavioral research. As a result, I have been lecturing around the country a good deal over the past year at numerous anniversary celebrations of the Belmont Report [8]. The commission was established by an act of Congress. Unlike most commissions, task forces and study groups usually appointed by the President or the Executive Branch of Government, this one was established by public law. It was in response to what appeared at the time to be a growing problem with the non-ethical use of human subjects in research. A: This took place after Tuskeegee? JVB: Oh, yes. Tuskeegee was just part of that history. In response to some rather disturbing revelations about research that had been supported by NIH, Congress had passed a law that imposed severe constraints on fetal research. Then they passed the public law establishing a commission to review all of the ethical problems having to do with the use of human subjects in biomedical and behavioral research. The significance of this, of course, was the specific focus on biomedical and behavioral research to the exclusion of other areas such as education, where substantial amounts of government support was provided. The attempt to include education in the legislation was strongly resisted by very powerful educator lobbying groups apparently and they successfully avoided inclusion. A: How did you get onto that Commission? JVB: Bill Pollin [a former director of the National Institute on Drug Abuse (NIDA)] told me that he recommended me. The Secretary of Health Education and Welfare, Casper Weinberger, called me directly. The law passed by Congress required that this commission be appointed and in place by the first of September, 1974 and it was the end of August before I received the call. My work at that time was focused primarily on baboons, but Secretary Weinberger insisted that he was looking for the Brady from Johns Hopkins in Baltimore. The conversation ended with my agreeing to accept the appointment, but on the condition that I could resign if it emerged that this was not the right thing for me to be doing. Well, when I got into it and found that I had been made an instant ethicist by an act of Congress, I spent the next 5 years warming up to the task and even developing my own radical behaviorist view of ethics. It came as no surprise that this operational view of the ethics arena as being made up of two components—values and morals—was not warmly embraced by the professional philosophers and ethicists on the commission, particularly when they heard how I defined these two components. Values are simply what folks say are important to them—abstractions for the most part, such as Life, Liberty and the Pursuit of Happiness. Morals, on the other hand, are the practices that the community rewards and punishes—Mother Love and Double Parking. From a radical behaviorist perspective, it is such values and morals that define the ethics domain, including research ethics. Although this point of view was not always applauded by my pluralistic colleagues, I was able to make a reasonable contribution to the Belmont Report that soon became the basis for all the Institutional Review Board (IRB) rules and regulations that have had such a strong and continuing influence on human research ethics. A: How long did the work of that Commission last? JVB: It went on for 5 years. We met a couple of times a month. There was a plausible argument that my appointment to the Commission was based largely upon my Irish name and my Jesuit training, as the Kennedys were the broadly acknowledged authors of the Congressional legislation establishing the Commission. A: You have been involved in many other things that can best be described as public service. For example, you were the president of the Society for Behavioral Medicine, and the Society for Behavioral Pharmacology. Could you tell us about your role in those organizations? JVB: In both those cases I think the major factor was being in the right place at the right time. The Society of Behavioral Pharmacology was started because many of the people I knew who were working for the drug companies felt somewhat isolated from the academic community, so they began getting together at annual meetings. It was just the drug company people for the most part, but I was invited because I had helped many of them to get their jobs in the first place. The society grew bigger and bigger and I suppose my being present at the creation led ultimately to my becoming one of the early presidents of the Behavioral Pharmacology Society—similar to ACNP (the American College of Neuropsychopharmacolog