Martin w. Adler

Interviewed by Larry Stein

San Juan, Puerto Rico, December 12, 1996
LS: I am Larry Stein and it’s my very great pleasure to have this conversation with a most distinguished pharmacologist, Dr. Martin Adler.^ I think we want to call each other Marty and Larry because we’ve known each other so long. I should say, for the sake of the record, that many of the years in my early career I spent in Philadelphia, where Marty has spent a lot of his career. We know each other well, personally. Both of us have done a lot of work in the field of drug abuse, so we are also familiar with each other’s activity in science. But, nevertheless, Marty, I would be interested in how you got started in science and in pharmacology.

MA: I needed a job. Actually, I always wanted to be a physician and my interest was really very strong in the history of medicine. In high school, I did a lot of reading on ancient Egyptian medicine, and it was something I really enjoyed. When I started college at New York University (NYU) in 1946 virtually everyone was a bit older. I was not yet seventeen at the time. Most of the other students had been in the army. When I graduated from NYU and applied to medical school, I was an alternate at some schools, but was not accepted. In fact, only one or two out of three hundred of the non-veterans got into medical school that year. So, I was looking for something else and somebody had suggested pharmacy school to me, so I applied to pharmacy school. I remember going on my interview and they asked me, “What do you want to do”? And, I said, “I want to do medical research”. And, they said, “Well, first of all this isn’t a medical school”. And, I said, “I know that”. And, they said, “Well, we don’t do too much in research”. I said, “Well, I figure it’s a pretty good background for me to go into research”. Anyway, I got admitted. I was going to finish at NYU, as I said, with a Bachelor of Arts and I started pharmacy school.

LS: This was which school?

MA: Brooklyn College of Pharmacy. As it turned out, someone who had been my lab instructor in biology at NYU was now a faculty member at Brooklyn College of Pharmacy, teaching pharmacology, but, frankly, I didn’t know what pharmacology was. His name was Jim Ingalls. He started a group of five students, who wanted to do research, all of whom had a Bachelor’s degree before coming to pharmacy school. We were doing research in Pharmacology and we all had teaching fellowships and I was teaching organic chemistry, and, so on. When finished there I did not want to practice pharmacy, but Uncle Sam reared his ugly head and I got drafted and ended up in Korea. I used to try to call my wife every month if I could and I’d hitch a ride down to Seoul to try to get through. One October I remember, I got through and she said, “How would you like to go back to school”? I said, “What are you talking about”? She said, “I talked to Jim Ingalls. He called me and asked if you’d like to go back to school to Columbia”. I said, “Gee, I don’t know; I haven’t thought about it”. I said, “To study what?” She said, “Pharmacology, of course”. I said I would think about it. The following month, when I called her, I said I would go and Jim Ingalls and Toby, my wife, set up everything for me. I was accepted with a full fellowship and that’s sort of how I got into pharmacology.

LS: There were some great pharmacologists at Columbia at the time.

MA: Yes, I was at the pharmacy school where I was teaching and doing research. My course work was all up at the medical school at Columbia. There were some wonderful people there at the time.

LS: Who was the Chair at Columbia at that time?

MA: I can’t even remember, but one of the people I interacted with was Wong, who was a neurophysiologist. He did a lot work on the vomiting center with Herb Borison and I had thought about staying on with him for doing my PhD. This might not be the most political thing to say, but I was turned off by Columbia. The PhDs were looked down upon. I took a course in biochemistry and there was one of these huge laboratories, you know 150 students or so and in the last row were the graduate students. The instructors would walk down to that last rows but never get to the last row. They’d turn around and walk back. I decided that this was not the attitude I wanted.

LS: So, the curriculum was really designed for the medical students. The PhDs became much more prominent and important to the faculty in later years as research got more significant and the role of the graduate students in research became decisive, I would assume.

MA: Absolutely, but it…

LS: I think, what I’m hearing, Marty, is that you got your first peek into CNS pharmacology with in work in the pons and medulla and you have ended up in higher regions of the brain in terms of drug addiction, learning and memory and these kinds of things, but, at least, there was a pharmacology of the brain that you saw.

MA: Absolutely. But we’ll backtrack for a second. The research I did for my Master’s degree at Columbia was on stress. I was very interested in it and I thought I’d continue in that field for the PhD. When I decided I wanted to leave Columbia, I went to Einstein where I was interviewed by Al Gilman. I was accepted by him and started with him. However, they had nobody doing work on stress. So, he said, “You can choose any other area you want, but not stress”. That’s when I started working with Murray Jarvik and got into the learning and memory field, the effects of drugs on delayed response and visual discrimination in monkeys. And, as you know, Larry, what got me out of that area, was that I had discovered the monkeys were much smarter than I was. When Murray and I would set up these programs we would design and build the circuits for the visual discrimination and delayed response tests in old refrigerators. I would set one up for Murray and he would set one up for me and we’d each sit in the refrigerator and see how long it would take us to solve the task. If we could do it in a reasonably short period of time, we’d figure the monkey could too. One time he designed something and I sat in that blasted box for an hour and couldn’t solve it. When Wwe put a monkey in there and inside of two minutes, the monkey had it solved, I said to Murray, “I’m finished”!

LS Back to the stress research.

MA: That’s right, but we, also, were working with some monkeys that had brain damage. Mort Mishkin had done the lesions in the animals.

LS: Was Mishkin at Albert Einstein?

MA: No he was at NIH and he had done some of these for Murray. I don’t even know why they were done and we started using them. I saw some changes in those animals compared to the normals and that’s what got me interested. I decided to get out of the learning and memory field and got interested in the brain lesion work. I started with rats. Seth Sharpless was doing some work with rats. I decided that I wanted to see what would happen with brain damage, what sort of recovery of function we could see after brain damage.

LS: You got your PhD in Pharmacology from Einstein?

MA: PhD in Pharmacology from Einstein.

LS: And, your mentor was Jarvik?

MA: Yes, Jarvik and Sharpless.

LS: Jarvik and Sharpless were both your mentors?

MA: Right and, actually, I was the first PhD studdent from Einstein in anything, as it turns out.

LS: You were the first PhD to graduate from Albert Einstein? Now, that’s very interesting

MA: The difference between Einstein and what turned me on to research as compared to the situation at Columbia, was the fact that the graduate students were treated well. Let me give you an example. I took Pathology at Einstein. Laboratory classes were in small groups of 12. Three of us were graduate students and the rest were medical students. The first day of the class the Head of Pathology, Angrist, walked in and said, “I understand there are some graduate students in here”. And, I said, “Oh, blankety-blank, here we go again”, you know. And, he turns around to the medical students and he says, “I want you to take a look at these people. That’s the future of knowledge and the future of science”. And he gave us a job where we helped set things up and the attitude was one towards the advancement of knowledge.

LS: So, the student was treated a little bit more as a junior colleague?

MA: Absolutely, and we were fully integrated into the medical class. We took courses that were mostly medical school courses, with a few exceptions, and included some of the clinical courses, as well.

LS: You had already done your army service, so now that you had your PhD, you were free to take your first job and what was that?

MA: At Temple, where I still am.

LS: Ah, so your first and current job, forty years later?

MA: Almost. It is thirty-six years.

LS: Almost forty years. So, we will trace your research and your Temple career, simultaneously. I take it you were recruited as a young faculty member at Temple in the Department of Pharmacology. Off you went to Philadelphia, where you had grown up?

MA: I really grew up in New York. I was born in Philadelphia, but my family moved to New York when I was six.

LS: What was Temple like when you joined the faculty?

MA: Well, I was the fourth member of the Department of Pharmacology. I was, only, the third person in the school who did any neuroresearch of any sort. The Head of Physiology did some neurophysiological research. Ernst Spiegel was at Temple, and for those who don’t know, Ernst designed the first instrument for using stereotactic surgery, which is in the Smithsonian. He was a great man, really. But, nobody else was there in the neuro-field, I mean, there were some clinical neurologists, but nobody in terms of people doing research. The Psychiatry Department was doing traditional psychoanalytic type of research. There was no interest in biological psychiatry, let alone research going on

LS: For a resourceful and dynamic self-starter that you are this represented a little bit of an opportunity to form a group without the distraction of others. So, what was the first project that interested you as a faculty member and at what point do we enter the world of grants? We might be interested in learning how that early research was funded and what were the circumstances of your first grant? By the way I am asking that because one of Marty’s important contributions to pharmacology is that he has been Chair of the Pharmacology Study Section for many, many years and he has made important contributions to the funding of research in pharmacology. But I am interested to hear how that activity originally started and, perhaps, the story of the first grant, which may have shaped your attitudes as a study section chairman.

MA: It did. In fact, it’s one of my favorite stories. I won’t mention the name of the person who site visited me. I put in for a grant right away. It wasn’t a huge grant. I asked for eighty-two hundred dollars a year, which covered the full cost of a full time technician, as well as all of my research costs. I applied for the grant, and, as you well know at that time, essentially everybody was site visited. A site-visitor came up, we sat and we talked about baseball and we talked about football and he met the chairman of the department and we had a cup of coffee. I had tea; he had coffee. And, he said, “Well, I have to leave. I have an appointment”. And, I said, “Don’t you want to talk about the research”? And, he said, “Why should I, you got your degree with Murray Jarvik, Seth Sharpless and Al Gilman. What am I going to ask you”? And, I got the grant.

LS: Times have changed.

MA: But, it’s very important in my thinking, because what I would like to see is some way of getting young people, who have good educational pedigree and are thought well of by the people that they train, get started. That’s what we can’t do now.

LS: You found that in terms of funding, it was relatively easy to get started.

MA: Yes, no problem.

LS: And, so you have made efforts, throughout your career, to try to get young investigators started and that’s been one of your important contributions. Your first grant was on what subject matter?

MA: Brain lesions. Recovery of function in brain damage, primarily involved with seizure mechanisms. That was the area that I was involved in most of my work and in my thesis. I also did some work with amphetamine and locomotor activity. But, I focused mostly on brain damage. I got into my present work strictly by fluke.

LS: Are you referring to your drug abuse research area? It will be interesting to hear the transition from brain lesions to drug abuse.

MA: That was an interesting experience, although, very traumatic at the time. I was up for my second renewal of the grant in 1966 and I was site visited, as was common at the time. One of the visitors felt that the work had no basis in fact, because the test that I was using was empirical. I was using chemically induced seizures and electrically induced seizures and he asked about the mechanisms, how does it work? And, I said, “I don’t know. The fact is that it works. It’s a useful test”. And he said, “If you don’t know it’s not a worthwhile project and it shouldn’t be funded”. Despite, the fighting by the other two site visitors, one of whom was very prominent in ACNP and backed the research, it didn’t go well in the study section. And, so I was without a grant but, happily, that’s the only time in my thirty-six years in research that I’ve been without grant. I was thinking, what am I going to do? How am I going to get a grant? Then I met Joe Cochin on a bus going to and from some hotel at a meeting and we started talking about research and I told him about my interest in seizures and the brain lesions. He said, “Well, why don’t you use morphine”? I said, “What in the world would I want to use morphine for”? He said, “Well, morphine causes seizures”. He said, “Just do the same thing, only do it with morphine”. Well, all right, I’ll do that. And, I submitted a grant application for it.

LS: To what agency?

MA: It was to NIMH.

LS: Before NIDA?

MA: It was before NIDA. This was in 1966. That did very well and I got funded. And, so, I started working with morphine and one of the things we found is that the literature was wrong. Morphine was anticonvulsant. We kept going along those lines but, then, something interesting happened.

LS: I’d be interested, but I think it’s very important, particularly, for young scientists to understand that a surprising result, in general, is more useful than an expected result. You got your grant and you knew that you were expected to do some work with morphine, which you had heard would produce seizures and you made your early observations that, in fact, it was anticonvulsant. What went through your mind at the time?

MA: Well, the first thing, obviously, was that we did something wrong. We sat down and we looked at the data and we said, “Well, this is right. OK, something’s wrong with the animals”. So we took another batch of...

LS: There was a dose-effect function there?

MA: Yes, there was a dose-effect function and it was crystal clear…

LS: It was clear-cut what was happening?

MA: And, we ended up repeating it a number of times.

LS: Had the field confused withdrawal with the direct effects of the morphine?

MA: No, I don’t think that was it. What happened was that people quoted a paper that Bill Martin had written about this and quoted it incorrectly. They said that morphine causes seizures in rats and it wasn’t rats. The experiment was done in rabbits and rabbits react entirely differently. Gus Maynert, from Hopkins, was one of my site visitors. And, afterwards we started collaborating on this topic and that’s when we began to work with serotonin and norepinephrine with regard to the seizures.

LS: That’s interesting. That admonition was in your mind about looking at the mechanisms.

MA: Oh, sure.

LS: So, you had remembered that and when the opportunity arrived to examine the mechanism of the seizures you were there.

MA: Yes, but I wouldn’t say that the turndown of my grant application had a positive effect in anything except that it made me angry. I mean, being trained in pharmacology...

LS: And, it might have been motivating.

MA: Oh, absolutely, there’s no question about it. My experience is that you get two types of responses when you get turned down on the grant. Unfortunately, it’s becoming more and more common. Either, you get angry and you try and answer it and you fight harder for the grant or you say, “These people who are doing the reviews are crazy. They don’t know what they’re talking about and to say, to hell with them”. And you give up. I know people that have done both. If I mention the names of the ones that gave up, you would know because they’re not doing any research. But, the ones who fought are generally successful if they keep fighting.

LS: So, there’s an evolutionary biology operating here with natural selection. Persistence is what the Darwin of the grant world reinforces.

MA: Yes, it does.

LS: So, now you’re into morphine and still organizing your research in the seizure field. When did you turn to drug abuse?

MA: Well, it was in the seizure field because that was the primary end-point we used in looking at recovery from brain damage. And, in fact, we were the first to use the term, denervation supersensitivity in the central nervous system. Just using the term from the peripheral nervous system, we applied it to the central nervous system that led to a huge fight with the editor of JPET who said that I have no proof that it’s the same mechanism. I said I was using “denervation supersensitivity” as an operational term and I threatened to withdraw my paper when they said, “What a miserable young guy this is”. And, we got it in. So, it was the first use of the term and that’s what we were interested in. What is the time course of the recovery from the damage? What leads to the supersensitivity or to the lack of supersensitivity? And, now, of course, we know tons more about it than we did then. But, to answer your question about getting into the drug abuse area, it really was the golden era of research and support, because at that point NIDA or drug abuse research was spun off from NIMH changing from a section to form a separate institute. I received a call from the people at NIDA saying, “We have money. Would you like to do some research in the field of drug abuse because you are working with morphine”?

LS: Was this the Psychopharmacology Center with Dan Efron as Executive sSecretary, was he in charge?

MA: To tell you the truth, I really don’t remember at this point.

LS: That might have been the precursor of the Center.

MA: It was the precursor. I put together a group of six faculty members at Temple and we put together a grant application for the study of “Narcotic Receptors in Addicted and Non-Addicted States.” That was in 1970. Opiate receptors hadn’t been discovered yet, but being a pharmacologist I had to think in terms of receptors and we did know of a couple of antagonists of opium and, therefore, it met the criteria for receptors, as we knew it at that time. That’s what got us started in the field. We spanned a pretty wide and diverse area within pharmacology, everything from work that Ron Tallarida, who is still a collaborator of mine, does in terms of the mathematical constructs and theoretical pharmacology, to a biomedical engineer. And, a whole group of us were doing that sort of work; four of us are still there and working on this project.

LS: With the focus on opiate drugs at the time?

MA: Yes, the focus was on opiates. We received the usual site visit and Bill Martin was one of the site visitors and Saul Schanberg was also a site visitor. At that time when money was more plentiful, it was much easier for a young person to get help in trying to get funding and Bill Martin was superb. I had proposed eight endpoints to use and determine how they all hooked up together. After we each presented our work he called me aside and said, “I want to tell you something”. And, the person from NIDA said, “But Bill you are not allowed to say that”. But he proceeded to say: “Pick four”. So, I asked, “Dr. Martin, what do you mean, to pick four”? He says, “Pick four, because if you get to learn about even four, you are going to be a wonderful success.” So, he says, “Think about it and write it up and send it to us”. And, I did that.

LS: You had to look hard at that list.

MA: I certainly did and I’m still working on some of those four. He’s an absolutely brilliant man, a remarkably strong influence on me and many other young scientists.

LS: So, we’re starting to identify factors in successful research, particularly, nationally funded research. The first you mentioned was persistence and the second you mentioned is focus. We will accumulate this list as we examine your career. So, you’ve got endpoints for your opiate research and you’ve got the funding. You’ve put together a rather large group and the other thing that impresses me is that, as a pharmacologist, you have understood that the concept of receptor is almost everything. So the title of the project has receptor prominently in it and you’re thinking it’s organized around receptor mechanisms. This must have been very refreshing to an emerging field, as drug abuse was at that time, to bring real science to the challenge of drug abuse. So, how did that evolve?

MA: I think it’s a natural course of events. If you’ve been trained in the scientific method in experimentation, it’s almost irrelevant what you’re going after. In the sense that you have any understanding of the current state of knowledge, you can design a proper experiment. Larry, when you evaluate a grant or you look at a paper that’s sent in for review, I’m sure, and I don’t want to insult you, you don’t understand all the nuances of the technology that’s involved with this specific project, but you can tell very easily whether it’s in animals, one species or another, human or whatever, whether there’s a proper design to the experiment, whether you have correct control groups, whether the end point is correct, whether the conclusions that you reach are based upon the facts. And, if you want to go out on a limb, you are at least justified in saying, “OK, I’m going to take a wild guess but, based on what I have, this is almost the beginning of a hypothesis”.

LS: Right.

MA: You can do that to every aspect of an area, so the grounding has to be in proper scientific methodology. And, I don’t care if it is psychology, pharmacology, biochemistry, anatomy or what have you, it’s almost immaterial. But, I’ll also say that one of the strongest influences on me was the fact that I did work with MDs during my thesis. I did work with them in subsequent years and still do and I took a number of clinical courses. I’ll branch off into something for a second, if you don’t mind. I think we train our students too narrowly. It’s fine to get into a new technology, help develop that technology. It’s fine, but if you can’t see past that technology, your contributions are really limited and I think you have to think beyond that. And, in order to do that, you need a broader exposure. Too many of our medical schools, today, are forcing the students to become narrow at much too young of age. We all become narrower as we go along.

LS: Would you like to see broader and, even especially, clinical questions being asked?

MA: Yes, I would.

LS: And, that the research should, at least, start to provide the early leads towards solution to problems and disease?

MA: I would. Every one of my pre-doc students is required to take a course, although a shortened course, in pathology. I’m the only one in my department who requires that.

LS: And, would I be correct in saying then that, given those attitudes, you then looked at the question of drug abuse in a medical model and said, “Can this be construed as a disease and if it is a disease, how does one deal with the problem and how does one elucidate it”?

MA: Absolutely. That’s certainly the basis, no ifs, ands or buts. But, now I do something a little bit different. After years of doing nothing but chronic experiments where you’re waiting a year until you see if you have anything, there’s a certain attraction to doing acute experiments.

LS: There’s a lot of work in a chronic experiment. Was your thinking that these chronic experiments were vital experiments at the time that you were doing them?

MA: Well, are you talking about some of the brain lesion work, are you talking about the research with morphine?

LS: Well, that could be construed as a general question, but I was actually thinking of the drug abuse problem and why you focused on it. We will hear about the short-cut acute experiments, as well, but I’m interested as to why you said, “Hey, this is a chronic disease and we need to do chronic drug experiments in order to understand it”.

MA: Well, because that’s part of the human equation. That’s what happens in real life and I think that’s where the influence of the clinical courses has been. As much as I am a basic scientist I don’t want to lose track of the fact that what we’re out to do is find things that answer the problems and the questions that come up in life. And, certainly, when we talk about drug abuse, we’re talking about the chronic administration of drugs. You’re not talking about somebody who tries a drug once. Has that person abused the drug? Yes. Is that person a drug abuser? Not in my book. So, we’re talking about the chronic effects of drugs or the effects of chronic administration of drugs. And, I guess, my career has really been shaped by the fact that I’ve been interested in what happens in human disease and I’ve always considered that drug abuse is much more than something like “just say, no”, which is a nice phrase and sure, it’s helpful to have that, but that’s not the answer to the problem. That it’s a very complex series of events that have occurred, not the least of which are the pharmacological properties of the drugs, certainly the environment, the genetics, socioeconomics, behavior and everything else that goes into it.

LS: And, the long-term changes that chronic administration produces in the body’s physiology?

MA: Yes, and this led us to some of the work that we do now with the acute…

LS: And, of course, many other workers, particularly some of the molecular people, are very interested in and distinguish clearly, between the acute reinforcing effects of drugs of abuse and the long-term chronic changes they may produce, particularly, in the brain.

MA: Absolutely.

LS: And, with your contributions with the chronic studies and the emphasis upon that, that puts us in this happier state of affairs, I think.

MA: You know, I think it’s a mix. What’s nice in science is that you don’t get overwhelmed with your own importance and your own contributions, because lots of people get similar ideas at the same time. Science reaches a certain point where you have a natural outgrowth of ideas and people begin to work on them. Some of our studies led us to conclude that there must be strong influences of the various neurotransmitters involved in that and the neurotransmitters must change with time, as a result of it. We became interested in what the endogenous opioids do and, so, we tried to...

LS: So, you were fascinated at the time with the discovery that the brain has its own natural opiate system. This, immediately, had an important impact on your research?

MA: Absolutely.

LS: And, you were a believer real early, because there were skeptics real early. So it might be worth hearing a little bit about that, about your reaction to the Hughes and Kosterlitz claim. Well, first there were opiate receptors, but you had talked about drug receptors for a long time.

MA: Right.

LS: So, that was not a big stretch.

MA: No, especially some of the work of Dr. Bill Martin…

LS: But, the fact that there were endogenous opioids must have been interesting to you and I am curious as to what your state of credibility was when you first learned of this work.

MA: Well, I had no doubts that there were endogenous opioids. I don’t believe you had receptors sitting there. They weren’t waiting there for somebody to use the poppy plant. They had to be doing something. They interacted with some endogenous system. But, in studying it and studying some of the endogenous opioids and trying to look at their function, you begin to look at endogenously administered drugs to get some idea, so you give them morphine or you give GABA agonist or whatever. And, then you say, well, these aren’t acting by themselves, so it leads you to the next level of complexity. And, people have looked at the neurotransmitters dopamine, serotonin, etc. In this regard, we chose a slightly different path. We decided to look at the neuropeptides and how they interact. So, we’ve been studying CCK, Substance P, neurotensin and TRH, and so on. And, we pick up new techniques as we go along. We now know a lot about how you get release of these compounds and what release is in terms of the opioids, what can block them and then you begin to ask questions. How does that play in? What’s the initiating event vs. the reaction event? Which peptides are involved? So, you find out for acute drug administartion and then you say, “Well, that’s all well and good, but what happens in chronic drug administrtaion”? And, that’s something we’ve started more recently. But, then new things come up. And, the newest thing that we’re involved in, and I’m using this as an example of new things that come up, it was recently discovered that cytokines exist in the brain and that they are produced by the glial cells. And, for most years, as you well know, the glial cells were there. What did they do? They outnumbered the neurons nine to one or ten to one.

LS: There was a guy at Walter Reed, who wanted to glorify the glial cells and he got shot down by his boss, who was an anatomist who considered that a heresy.

MA: There was a guy named Dick Orkand at Penn, who proposed that glial cells are involved in sodium-potassium balance and I was struck by, whatever happened to him. But, now, we know there were cytokines and some of the work that we’re doing indicates that they not only interact with the opioid system in the brain, but some of their effects, in terms of fever, for example, can be blocked by an opioid antagonist. So the complexities are always there but at different levels. When I first started in the whole field of psychopharmacology, it was Hess’ theory of the ergotropic and trophotropic systems, and you had acetylcholine…

LS: That might burn up Brodie.

MA: Yes. I mean you have these very simplified systems.

LS: And, then, you had serotonin, norepinephrine…

MA: Sure, sure, but the important thing is that we were right, not in the specifics but in the concept that you have a balance of systems.

LS: Yes.

MA: And, that’s never changed. So if you thought of it, not in terms of norepinephrine or serotonin, but you thought of it in terms of the balances between systems, it still holds true. And, so that’s when you and everybody else...

LS: So, you’re trained to organize your data

MA: Absolutely.

LS: I wonder if we could switch topics a little bit because your contributions have not only been in basic science fundamental research contributions but you have made very decisive contributions in administration and in support functions for research in two important areas. I’d like to discuss those with you: Firstly your experiences as chairman of a study group, and secondly, your very important role as the Executive Officer of the College on Problems of Drug Dependence. So, why don’t you talk about both of those and whether they interact with each other and what you’re trying to accomplish in your roles in both, in terms of advances in science?

MA: I was asked to show up as an ad hoc reviewer on a study section in 1976. I guess anyone who has ever been asked to do this, first time he or she is asked, feels this is a great honor before they realize the amount of work involved. But, it’s a great honor and that was in 1976. I became an official member of the committee in 1978 and became Chairman of the Biomedical Research Review Committee at NIDA in 1980. And, I’ve since gone back and chaired a number of other committees and I now chair the Center Grants Committee. Let me put it this way, it’s sort of a circular thing. I very, very much appreciated the help I got from people like Bill Martin and Saul Schanberg and Joe Cochin and some others, when I was trying to start in, what was to me, a new field. They went out of their way to be helpful rather than just critical without helpful criticism. So, when I went on the committee and then, especially when I became Chair, I felt it was my obligation to make sure that every applicant had a fair hearing. And, if the grant was lousy, it was going to be lousy, but if it was good, it was good and it wasn’t going to be nitpicked to death, because there’s no grant that can’t be nitpicked to death. And, you have to keep sight of a broader importance than just a word here or there. This, especially, holds true in my book for the young investigators. You’ve got to get people started somewhere. So, it was a very strong influence, what happened to me, and the help I got from people and giving back to others. And, that’s what I have tried to keep as my primary focus.

LS: This was recognized when you were a committee member and is the reason that you were elevated to Chairman, that you took a critical but a constructive attitude toward the grant, with a particular eye on the young investigator, knowing that is the future of the field.

MA: Yes and what made it easier was that there were a number of people at NIDA and NIDA staff, who felt the same way. I mean, you can’t be a lone voice in the wind and if you are you would never really accomplish anything. You can be a lone voice for a while, but unless additional voices join you, you’re not going to make it. And, they were receptive to it and I will mention Joe Cochin again. Joe was a strong influence on that and, in fact, CPDD has a yearly award honoring young scientists, the Joseph Cochin award, a very strong influence. And, another strong influence on that was a young executive secretary, as they were called at the time, Mike Morrison, who, unfortunately, died from malignant melanoma; he was my executive secretary. CPDD gives an award, the Michael Morrison Award every other year to somebody in scientific administration. His push was the same thing, that a fair shake on a grant review that is tough but fair, and a little bit of a boost towards the young group, people who will determine the future.

LS: Tell us how the College on Problems of Drug Dependence began and tell us about your role in directing the College.

MA: Well, the CPDD began as a committee and is actually the oldest research group on drug abuse, I think in the world, certainly in the United States. It began, I won’t go back to the whole history, as a committee of the National Academy of Sciences and it was started in 1929. It split off and became independent in 1976, and was sponsored by twelve organizations, including ACNP, The American Society for Pharmacology and Experimental Therapeutics, The American Chemical Society, the AMA and so on. It became independent but still retained the name, “Committee on Problems of Drug Dependence”. After a long series of changes, in terms of the executive committee and the board of directors and so on, the current system evolved. It became a membership organization four years ago if I’m not mistaken, with an executive committee, a board of directors and an executive officer. Joe Cochin was the executive secretary as it was called at that time and when he died in 1986, for a short period of time thereafter, Conan Kornetsky functioned in that position. Mary Jean Kreek worked on it as well and in 1986, I was elected to that position, so I’ve been in that position for ten years now. Let’s call it a very close sister organization to ACNP in many ways, with the primary concern being drug abuse, as opposed to being more general psychopharmacology. The emphasis is different, but the interests of the two organizations are very close in many ways.

LS: I think we’re at a point where we can wrap things up. Is there something, at this point, you might want to say, particularly, to the young scientists at this time when funding is as tough as it is and careers are tough but, at the same time, we recognize the need that the next generation must be trained. I wonder if you have some concluding views at a point in this field that some might be inclined to view dismally but, perhaps, you have an optimistic note.

MA: Well, I don’t know. I am both optimistic and pessimistic about it. We can’t keep growing at the rate that we have. There are no ifs, ands or buts. Jobs for new PhDs or MDs doing research are fewer and farther between. The landscape changes; whereas, probably most graduates before, in these fields, ended up in academia, today, a much larger number ending up in pharmaceutical and biotech companies. I’m talking mostly about pharmacology, obviously, but also basic sciences, in general. There are different types of opportunities available, but it’s not as easy. Somebody is not going to walk in and talk about what happened to the Philadelphia Eagles and give you a grant with a technician. And, the answer today, I think, lies more in group-research than in individual research. The techniques are too complicated. The equipment is too expensive. The space required is too great for one person to expect to be able to do it all by himself or herself, but groups, in collaborative efforts as you say, are awfully important and this causes department alarms. I’m a strong believer in departments. I think that’s our real support system but, at the same time, I recognize that no department can spread itself so thin that it will have everything one needs to do research in all fields. So, you need interdepartmental cooperation, and inter- and intra- university cooperation. And, it works.

LS: And institutes, which have to find a niche in a department-based medical school?

MA: Yes, I am totally, irrevocably against a free standing institute. It has to be department based. If it’s free standing, it’s an invitation, in my book, for disaster, but department based, it can work.

LS: Are you optimistic about dealing with the disease of drug abuse and do you foresee on the horizon that we will be dealing with cocaine abuse and opiate abuse in more effective ways?

MA: Oh, absolutely. I think as our knowledge base expands, just to give you an example, the use of knock-out mice, to look at some of these, to understand in detail the transporter system and how you might be able to block it, the contributions of molecular biology toward this are enormous. But, as long as we don’t forget that molecular biology, as crucial as that is to its understanding, can only tell us what happens in vitro and then you’ve got to go to an in vivo system and then go back to the in vitro system. That’s fine, but I, also, think that although, we’ll come out with new medications, new ways of dealing with it, we’re not going to find the magic bullet. You’re not going to be able to give the drug and say, “Ah ha, there’s no such thing as cocaine abuse; there’s no such thing as craving; there’s no such thing”. Cocaine abuse and craving will be with us, but we’ll be able to handle the problem, just as we handle lots of diseases, and I think we do have to think of it as a brain disease. I think we have to think of it as a public health issue and if we begin to put it in terms of the perspective that it deserves, that it’s with us and it always has been, only now we say, “Hey, it’s with us”. So; therefore, it’s more than it has been in the past. We recognize that we have to deal with the situation effectively and we can. I’m very optimistic about that. In my mind, there’s no question that we will. But, at the same time, there’ll be new drugs coming along that none of us can envision now, that the street pharmacologist will come up with. And, some of these street pharmacologists are awfully smart. We’re going to have the problems, but we have to learn, you know, to deal with them and we have to take that out of the closet and not deal with something, “Oh, you can’t talk about that. You know, that doesn’t exist”. And we have to get rid of the mentality that everybody can just stop when he or she wants to stop. That’s not true. They’re going to need help, whether that help is psychological, psychiatric, pharmacologic, or more likely the combination of all of those, plus some others, and I am very optimistic about that. I think there’s every reason for optimism.

LS: Well, with that positive and optimistic note, we conclude a fascinating interview with one of the pioneers in the pharmacology of drug abuse, Dr. Martin Adler.

MA: Thank you.