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In this occasional series we record views and personal experience of people who have specially contributed to the evolution of ideas in the Journal's field of interest. Roger Meyer is an American psychiatrist who, throughout a long and fruitful career as addictions researcher and research center director, has exemplified an interdisciplinary view. He has helped to position clinical research in the broad field.

A (Addiction): Can you tell us something about your personal background and early years?

Roger E. Meyer (REM) reply: In terms of my personal background, I was born and raised in New York City in a mixed Irish, Italian and Jewish neighborhood. My father had come to the United States from Germany in 1929 at the age of 23, having survived a childhood of lost parents, the stresses of World War I and the devastation caused by the massive postwar inflation in Germany. His extended family included a number of distinguished academic physicians in pediatrics, dermatology and public health, but my dad and his older brother were largely treated as orphans while being raised by both grandmothers. It was probably the grimness of his past, coupled with the possibility of a new beginning in America, that enabled my dad to leave his family in Germany—thus avoiding the events that followed in the 1930s.

My mother was born in New York to immigrant parents from eastern Europe. Her parents came to these shores as children, and never had the opportunity for an education. My mother trained as a commercial artist, but the talent in her gene pool was not transmitted to her sons. My dad was in and out of work through the early and mid-1930s; my parents were married in 1935; my dad found permanent employment in 1937, and I was born in 1938 (after which my mother worked as a contract artist part-time from home). Like so many sons of that time, I felt much riding on my talents and intellect in terms of charting a future for myself and a respected place for my family in America.

As was not uncommon in the 1940s, I went through the first six grades of elementary school in 4½ years. Following a less than stellar experience in junior high school, I was admitted by competitive examination to one of the finest high schools in the city (Stuyvesant). The student body (all male) was populated by some of the brightest people that I have ever known, and the competition was intense. I performed well enough, but, with my parents' encouragement, I chose a small liberal arts college in upstate New York for my next stop on the educational ladder. Hobart College was as different from my earlier years as one might imagine. New York State's drinking age was 18. I was 16, and had never had an alcoholic beverage. The drinking on the campus led to the deaths of several of my schoolmates from auto accidents and/or accidental overdose. For the most part, fraternities were the major drinking venue, and I was very much outside of that orbit. Apart from this social mismatch, Hobart College turned out to be the best possible choice for me in all respects, and I was admitted to Harvard Medical School upon graduation.

A: How did you become involved in research on the addictions?

REM: I discovered psychiatry as a medical student, observing the revolutionary changes then taking place in psychopharmacology and in community-based treatments. For me, these changes heralded a transformation in the practice of psychiatry, and a path towards understanding the causes of mental illness. I saw psychoanalysis as reactionary, with an institutional structure that impeded inquiry. I saw psychiatry as an opportunity to do research, particularly clinical research. I completed an intensive medical internship in Seattle in 1963 and came out of the experience feeling like a physician. I then began a psychiatric residency back at Harvard in a very psychoanalytical environment. In my second year, I chose to do research in psychopharmacology, and in my last year I completed a 1-year advanced program in community mental health that had previously been at the Harvard School of Public Health.

A: So you found your way to addictions research through research in psychopharmacology and training in community mental health?

REM: Yes, during my first year of residency, I met Dr Gerald Klerman (my first role model in psychiatry). Gerry was an encyclopedia of information about psychiatry, psychopharmacology and the history of medicine. I had been accepted into the US Public Health Service (PHS) as an alternative to mandatory military service; and, with Gerry's support, I was invited to work in the addictions program at the National Institute of Mental Health (NIMH), which I saw as an opportunity to link my interests in public health and psychopharmacology, and I decided to accept the position.

CHANCE FAVORS A PREPARED MIND

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References

A: What was your experience at NIMH?

REM: My first 6 months at NIMH were a combination of a crash course in addictions, introductions to the leading figures in the field, and an orientation to government. I came under the influence of Mitchell Balter, a social psychologist, who became my first mentor in the addictions field. Mitch's interest in epidemiology led me to the rich literature in drug and alcohol addiction. Later, a site visit to the Addiction Research Center at Lexington introduced me to some of the greats of that time and place: Harris Isbell, William Martin, Nathan B. Eddy, Jack O'Donnell and, most importantly, Abraham Wikler (perhaps the most creative psychiatrist of his generation, and largely unknown to most of his contemporaries in the United States). In December 1966, in connection with my role in government, I attended a meeting of the Association for Research in Nervous and Mental Disease in New York where I encountered state of the art science across the addictions field. I was hooked! I could now see a career path following models already laid out by the likes of Abe Wikler, Jack Mendelson and Jerome Jaffe; three psychiatrists who were able to conduct translational research, a rarity in psychiatry to this day.

‘I could now see a career path following models already laid out by the likes of Abe Wikler, Jack Mendelson and Jerome Jaffe . . .’

A: And the next step?

REM: By January 1967, I was in the Center for Studies of Narcotics and Drug Abuse, part of a new Division of Special Mental Health Programs that also included the National Center on Alcoholism headed by Jack Mendelson. Our Center Director died within 3 months of assuming office. So, at the tender age of 29, I was named Acting Director of the Center, a program that, 7 years later, evolved into the National Institute on Drug Abuse (NIDA).

A: And what were some of the tasks that confronted you on taking up that job?

REM: During the summer of 1967, I was asked to get a better sense of the public health consequences of hallucinogenic drug use in San Francisco. Later in the year, our Center was asked about rumors of carcinogenicity and teratogenicity of hallucinogens. We convened an expert, multi-disciplinary panel and its output became my first monograph [1].

A: What else did this job entail?

REM: Our Center also had responsibility for funding extramural research, including Avram Goldstein's early work on the opiate receptor, reviewing a broad portfolio of clinical and basic research, and approving the use of hallucinogenic drugs in research. We were given the responsibility to develop the national marijuana program. We were also asked to develop community-based treatment programs for heroin addicts. Although it was strongly recommended that we focus our support for the latter effort through the nascent community mental health centers, we believed that this was not the right strategy because the vast majority of these centers lacked expertise in addiction. We ultimately selected six programs for funding, including those in New Haven (Herbert Kleber), Chicago (Jerome Jaffe) and New York City (Efren Ramirez). The national marihuana research program was developed with the extraordinary help of a former executive of Mead Johnson Pharmaceuticals (Coy Waller) who volunteered his services (without cost) to our program. Together, we established a plantation growing marijuana in Mississippi, and we acquired the necessary precursor molecules to synthesize delta-9-tetrahydrocannabinol.

A: Exciting times?

REM: It was a heady time: I testified before the Congress and was invited to advise the Pentagon on marihuana use in Vietnam, and our programs were well funded. Despite strong urging from NIMH leadership to remain Center Director, I decided (with strong support from my wife) that the best next step would be to learn about addiction at the ground level and not from the heights of government. In my training as a resident in psychiatry, I had never worked with an alcoholic or an addict; and I was intrigued by the possibilities for productive translational research on addictive disorders. I felt that I had acquired an excellent working knowledge of the contributions that multiple disciplines were making to advance our understanding of the pathways into and out of addiction and the implications for treatment and prevention. It made me more aware that the basic sciences underlying psychiatry were much broader than psychoanalysis and must necessarily involve non-psychiatrists who were skilled in research methodology. That understanding has been at the heart of my passion for the addictions field, and it guided me throughout my subsequent career as a researcher and research center director.

A: What did you do after you left the Center in 1968?

REM: I went to work at Boston University (BU) as the Deputy Director for Research Training in Psychiatry, a position that was funded by an NIMH training grant. I wanted to create a research program in addictive disorders. My overarching goals were to develop animal models of opiate addiction that could be used to screen new medications; and, to adapt the biobehavioral clinical research methods developed in the alcohol field by Jack Mendelson and Nancy Mello to my own studies of addiction.

EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References

A: So you went back to Boston with the intention of developing a more empirically validated model of addiction?

REM: Yes, at BU I began my original research with Dr Steven Mirin (who was my first mentee) on the reactions of heavy and casual marijuana smokers to marijuana in a laboratory setting [2,3]. At that time, I also began studies of oral etonitazene self-administration in a two-bottle free-choice drinking paradigm in mice in Joseph Cochin's laboratory in pharmacology. The animal studies were an important stage in my own scientific development [4,5], and in the later development of my first research center grant award.

A: How did you make the transition to biobehavioral clinical studies?

REM: While I was still in the Department of Psychiatry at BU, Jack Mendelson relocated from NIMH to become Chair of the Department of Psychiatry at Harvard's unit at Boston City Hospital, which was right next door to the BU Medical Center. The National Commission on Marihuana and Drug Abuse (the Commission), an advisory group empanelled by the Congress and the White House, had just released a Request for Applications for a study of the effects of chronic marihuana smoking on heavy and casual users. Although the funds were very limited, Jack suggested that we apply jointly to conduct the study at Boston City Hospital. Building upon the paradigm that he had applied to drinking behavior of alcoholics, we undertook a study of free choice marijuana smoking among 10 daily heavy marijuana smokers (compared with 10 casual users) over 21 days on an in-patient research unit. We assessed the differential reinforcing potency of cannabis in these two groups [6].

A: These individuals were given ad libitum access?

REM: Yes, but they had to work for the access; in essence to ‘purchase’ each cigarette using points generated on a hand counter. It was clear that marijuana smoking did not have the same urgency for the smokers, even the heavy smokers, that Jack had observed for alcohol in alcoholics.

Participation in the study launched a 7-year collaboration and life-long friendship with Jack, a long collaboration with Tom Babor at Harvard and then at the University of Connecticut, and my first hands-on experience with a behavioral analysis model of addictive behavior in humans that would lend itself to multi-disciplinary collaboration. With Jack Mendelson's strong encouragement, I left the department of psychiatry at BU and became associate professor of psychiatry at Harvard and Boston City Hospital. With the support of Joseph Cochin, I was able to continue my animal studies in the department of pharmacology at BU. Both Jack and Joe were very generous mentors, who shared their insights and their resources, and encouraged me to pursue my research interests and activities.

A: What happened next?

REM: Those collaborations with Jack, and with Joe Cochin, and Conan Kornetsky at BU came together in a research center grant that I submitted for federal funding. The clinical core of the center grant involved biobehavioral studies of volunteer heroin addicts given 10 days' access to heroin while under treatment with a narcotic blocking drug or placebo on a research ward.

A: What were some of the challenges that you faced in launching the clinical studies?

REM: Prior to our own work, interdisciplinary clinical research in the United States was largely limited to fixed-dose, fixed-interval, clinical experiments utilizing prisoner addicts at the Addiction Research Center at Lexington Kentucky.

‘Prior to our own work, interdisciplinary clinical research in the United States was largely limited to . . . experiments utilizing prisoner addicts . . .’

A: What were some of the most important ethical and methodological issues that you needed to address?

REM: All our subjects were men who volunteered with no promise of special treatment in the criminal justice system and they were paid only for the time spent participating in the research. The subjects had to be over the age of 22, with at least a 2-year history of heroin addiction and at least two unsuccessful attempts at drug rehabilitation. Prospective subjects met with a recruitment counselor over a number of weeks to establish their eligibility to participate in the program and to ensure that they understood all aspects of the research and the follow-up treatment that was offered. Research subjects' confidentiality was protected under rules established by the federal government. Before admission to the unit, the hospital attorney interviewed each subject to obtain informed consent.

We built a unit that had a major therapeutic component to it. All subjects were offered state-of-the-art treatment with naltrexone and counseling during aftercare and the opportunity to prepare themselves for aftercare during the research ward stay. The Advisory Board of the Commonwealth of Massachusetts Division of Drug Abuse Treatment reviewed the program and concluded that the research program was not only ethical, but was among the best treatment programs in the State at that time. Some argue that exposing addicts to their drug of choice leads to relapse. In our heroin studies, there was no difference in outcome on naltrexone at follow-up in the community between subjects who had received naltrexone on the unit (blocking the effects of heroin) and those who experienced unblocked heroin during 10 days of access [7]. Subsequently, our studies in alcoholics given an alcohol challenge and followed-up in the community showed no effect on compliance with the medication disulfiram [8] or on treatment outcome [9], compared with subjects who had not participated in the research.

A: What was the focus of the studies of heroin use by heroin addicts?

REM: The studies were designed to test Wikler's hypothesis that an individual treated with a narcotic blocking drug who is allowed to administer heroin will repeatedly challenge the narcotic blockade, exponentially increasing the behavior, until there is behavioral extinction.

We saw no evidence of operant patterns of extinction as had been postulated by Abe Wikler. Importantly, in spite of the fact that others on the unit were getting high, craving in the naltrexone-treated subjects remained low, and none chose to leave the unit, despite their exposure to powerful drug cues. For many years, I have cited these results to argue that ‘cue reactivity’ is not a sufficient laboratory model for situational craving unless drug self-administration is possible.

A: So the subjective report of craving actually mirrored drug self-administration behavior?

REM: Yes. While this series of studies [7] included many interesting findings, the results on ‘craving’, validated by actual behavior, really excited my interest. While there is no question that conditioned abstinence can be generated in the animal laboratory [10] and in clinical studies [11], we failed to find any evidence of withdrawal-like phenomena in relationship to ‘craving’ or actual drug self-administration. What was clear was that the anticipatory subjective state (‘craving’) was associated with the expectancy of drug ‘availability’; and the subjective state was ‘rewarding’ and not aversive. Recent research in animal models has appeared to confirm the rewarding properties of the anticipatory state [12,13].

A: What else stands out in terms of the heroin/naltrexone studies?

REM: Laboratory models of drug self-administration behavior are an optimal proof of concept paradigm to test the efficacy of pharmacotherapy in addiction treatment. By examining the efficacy of naltrexone in our subjects given 10 days of access to heroin, we could anticipate a number of issues with regard to out-patient follow-up. Naltrexone would be effective if the patient actually took it. The challenge was in getting the patient to take it, by simplifying access and by rewarding medication adherence under observation. With a modest monetary payment ($1), in association with medication administration at the pharmacy, we demonstrated improvement in short-term medication adherence.

A: In your biobehavioural work it is abundantly evident that you met all possible ethical expectations. You have referred very positively to the Lexington researchers and research tradition. Within the expectations of the time do you think that Lexington researchers were ethical when they administered addictive drugs to prisoners and observed the acute and chronic effects of these drugs, as well as any withdrawal effects?

REM: Your question really merits another entire interview. By today's standards, the research program at Lexington would be considered unethical because of its reliance on prisoners who participated in studies that lacked standards of informed consent, or were in violation of the recommendations of the Declaration of Helsinki. However, the research program at Lexington needs to be considered in the context of the then current practice in the United States. Prison-based research did occur before World War II in the United States, but during the war and until the early 1970s it became the bedrock of clinical research in this country. By 1972, more than 90% of all investigational drugs were first tested for safety in research subjects who were prisoners. Indeed, until that decade, the principal objections to prisoner-based research were based upon a concern that these individuals would be given special privileges or early parole.

‘By today's standards, the research program at Lexington would be considered unethical . . .’

A: While you published many papers on your opiate studies, you presented many major findings in the book that you wrote and edited, with Steve Mirin, The Heroin Stimulus [7]

REM: I really felt that the complexity of the work could not be communicated well in any one article or series of articles. Naively or grandiosely, we also hoped that the book would more clearly convey the interdisciplinary perspective that formed the basis of our research. For example, behavioral pharmacologists tended to prefer small sample studies, and seldom applied statistics to their results. We applied multivariate statistics to look at the different variables that might account for observed behavior. Reinforcement is obviously important, but behaviorists regarded the concept of ‘craving’ as unnecessary, and they tended to minimize host differences in the development and maintenance of addiction—explaining the entire phenomenon in Skinnerian terms. We felt that the information that we gathered on the subjective state (‘craving’) could best be validated by observed and quantified behavior, but that the behavior in the absence of information on the antecedent subjective state would merely reify operant theory without advancing science beyond the extant animal models.

A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References

A: After your success at Harvard and Boston University, at the age of 39, you left Boston to become the Chairman of Psychiatry at the University of Connecticut.

REM: In 1972, before we could actually begin our research, all of the clinical departments at Boston City Hospital were consolidated under the Boston University School of Medicine. As a Harvard faculty member, I was offered the opportunity to transfer my clinical research to McLean Hospital, one of the two major psychiatric teaching hospitals at Harvard. The McLean administration was most gracious in welcoming me, and 9 months later Jack Mendelson, and in rapidly renovating a research unit for my studies. But the major problem about McLean, from my perspective, was that the culture of the hospital was overwhelmingly psychoanalytical and the emphasis of the treatment model involved long-term in-patient hospital care with intensive psychotherapy. Starting in 1975, I was approached by a number of medical schools to become a candidate for chair of psychiatry. I hoped that by taking on major administrative responsibility, I would be better able to build and sustain a research program and to avoid the marginalization that I felt at McLean. At the University of Connecticut (UConn) I saw a magnificent facility and a virtually empty hospital. Incredibly, psychiatry was on the first floor, not hidden away somewhere. They also had an in-patient alcoholism treatment unit. I obtained a commitment from the Dean that our department would always be able to retain 10 alcoholism treatment beds in the hospital, for what I envisioned to be a first class treatment, research and educational program. Applying some of the lessons learned in the heroin/naltrexone work, I felt that I could make an important contribution to alcoholism research and treatment; and, as a department head, I could help to bring addictions into the mainstream of psychiatry and of medical education.

A: Did you imagine that you would be able to create an interdisciplinary research center at a relatively small medical school that was still in the formative stages, and was not in close proximity to the relevant basic biological, behavioral and social science faculty?

REM: In January 1977, I started to commute 2 days a week from Boston to Farmington, Connecticut to begin my tenure as Chair, while transitioning out of McLean and preparing the manuscript for our book. During this time, there was an announcement that the National Institute on Alcohol Abuse and Alcoholism (NIAAA) would fund its first research centers. Tom Babor, whom I had recruited to McLean as part of the clinical research program, and I sketched out a vision for an alcohol center consisting of three parts. The first part, which actually became the typology study, was an effort to characterize alcoholics in treatment and to follow them to identify characteristics at the onset of treatment that might have predictive value over a 3-year course. We believed that if we could enroll more than 300 patients over the first 18 months, we could begin to analyze data that would inform subsequent studies of treatment interventions. Tom agreed to be a long-distance participant in our Center (he had just started his McLean-based Research Career Investigator award from NIAAA).

The second area of research emphasis was biobehavioral studies in alcoholic patients. Based upon my naltrexone studies in heroin addicts, I felt that we might be able to differentiate gradations of severity of alcohol dependence by assessing physiological and subjective responses to placebo and real beer. A psychophysiologist at the Institute of Living in Hartford, Charles Stroebel, had some very creative ideas on measurement. He and his boss and mentor (Bernard Glueck Jr) were eager to collaborate with us.

A: I would guess that genetics was the third piece.

REM: Right. Jim Stabenau, who had been the first Chair of Psychiatry at UConn, had a strong background in the genetics of schizophrenia. He suggested that we develop studies in sons of alcoholics and that we follow the cohort through the age of risk. We were able to obtain what we needed to establish feasibility and to process the grant application; but, in that first round, we did not get funded.

We were encouraged to re-apply. The good news was that we were then funded; the difficult news was that the grants were each capped at $200 000 (direct and indirect costs) per year; and we were expected to complete our projected studies which had been budgeted for costs that were more than double this amount.

A: Definitely a challenge!

REM: Yes, but the start-up problems (compared with the challenges of our heroin project) seemed manageable, if I could find the right people. I called Lee Robins at Washington University for some suggestions about candidates for local direction of the Typology project. Lee recommended Victor Hesselbrock. Tom and I visited him in St Louis during our first Center Directors meeting and we were very impressed. His wife, Michie Hesselbrock (also a Washington University PhD), had been coordinating Lee Robins' projects. We hired Michie to be the site leader of the Typology project, while Victor launched the study in sons of alcoholics when Jim Stabenau developed health problems.

A: Other recruitments?

REM: I felt strongly that we needed to bring in additional senior faculty. I invited Jerry Jaffe to visit our department as a consultant in connection with a State of Connecticut drug and alcohol treatment program. From that consult, Jerry indicated that if we could find appropriate resources, he would be interested in joining our department. At that juncture, the new Medical Director of our affiliated Veterans Administration Hospital approached me with a request to build a stronger research, clinical and teaching presence in psychiatry at the hospital. In addition to Jerry Jaffe, we were able to recruit Ovide Pomerleau from the University of Pennsylvania, Dominic Ciraulo from Tufts and Alexander Nies from West Virginia University. All had a strong commitment in the addictions area. Ovide revitalized the psychology training program. As always, Jerry was a fount of ideas and with Dom Ciraulo, he began studies on the effects of antidepressants in the treatment of depressed alcoholics.

In addition to his own work, Ovide was a great resource to me in the recruitment of a post-doc (Richard Kaplan), and in working with Richard and me on the studies of conditioning factors in alcoholics, which demonstrated that more severely dependent alcoholics were more likely to experience the conditioned effects of alcohol when drinking placebo beer than less dependent subjects or non-alcoholics [14].

RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References

A: So by 1982, you had put together an impressive group of researchers and a significant research infrastructure.

REM: By 1980, we had also applied successfully for a post-doctoral training grant that extended our resources by enabling us to recruit some very bright young people to alcoholism research—and we had the senior faculty committed to their education. Of the four centers that were funded in 1978 we were the only one renewed in 1982. By 1982, Tom Babor had agreed to relocate to UConn with the renewal of the Center Grant.

A: An unusual aspect of the program at UConn was its recognition of young faculty and post-docs. Can you elaborate on that?

REM: Yes, in the early days of the Center, some senior faculty felt that their names should be on every paper, even remotely related to their research. I appointed a committee of junior and senior faculty that Tom Babor chaired. The committee recommended that we follow the American Psychological Association criteria, which required serious involvement in the preparation of the manuscript and the research in order to claim authorship. That tradition has continued at UConn, and has recently become more common in academic medicine in the United States.

‘we . . . required serious involvement in the preparation of the manuscript and the research in order to claim authorship.’

A: What happened next?

REM: 1982 was really the best of times. Our Center grant application had received a very high priority score in the review, and we were looking forward to 5 very productive years. During the summer of 1982, we were privileged to host a mini-sabbatical for Professor Griffith Edwards. Tom, Victor and I wrote about the organization of the Center at that time in a paper published in 2005 [15], but by the date of publication the dynamic had changed. In early 1983, the Director of the Institute of Living stepped down and a national search was initiated for his replacement. I heard from my some of my senior colleagues around the country that candidates were being invited to the Institute with an offer from the School of Medicine to include the UConn Chair of Psychiatry. When I confronted the Dean (who had recruited me) about the rumor, he indicated that if I were a loyal faculty member I would hand in my resignation as Chair. I told him that I would not resign; and I pointed out that our Center had just been renewed with a very high priority score. We had been the first federally funded research center at the school. He commented that there was no future for federally funded research centers. With the aid of one of our faculty (James O'Brien), who was well connected to the Governor, I worked very hard on a political front to delay any action by our medical center administration; but the fate of our clinical facilities was determined elsewhere, when the United States Congress authorized the implementation of a program to reduce lengths of stay for medical and surgical patients. Psychiatric beds were exempt. Health insurers followed suit, and pretty soon psychiatric beds became a much more valuable commodity for hospitals facing empty medical and surgical beds. The Institute of Living's board, to its credit, decided that it did not want to integrate its program with the State of Connecticut; but the period of uncertainty, combined with broken promises from our VA administration, led to the departure of Jerry Jaffe, Ovide Pomerleau, Alex Nies and Dominic Ciraulo by 1985.

THE NEED TO REBUILD

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References

A: So what steps did you take to reinvigorate the department?

REM: First, I had to reinvigorate my own research interest. During the summer of 1984, I spent a mini-sabbatical with Griffith Edwards at the Maudsley Hospital in London. The experience energized me and focused my interests on the Alcohol Dependence Syndrome and possible markers of severity [16]. The results of the work that I had conducted with Richard Kaplan supported the importance of the severity of alcohol dependence in the conditioning phenomena that we observed. I was still interested in ‘craving’ as a response to alcohol availability and the craving that followed beverage consumption. In my view, the latter was the basis for alcoholics' impaired control over drinking. I saw rich possibilities in neuroendocrine correlates of ‘craving’ as one of the foci for the Center grant renewal application that was scheduled for submission at the end of 1986. To examine parallel paths in human and animal studies, we recruited Bill Shoemaker from Scripps to head our animal model work.

Ovide Pomerleau had meanwhile recruited an extraordinary group of fellows and faculty (Ned Cooney, Mark Litt and Ron Kadden) who were interested in disaggregating craving, by stimulating positive and negative moods in the presence of an alcohol stimulus. They shared a strong interest in cognitive behavioral therapy. With Tom Babor's and my encouragement, they assessed alcohol dependence severity across some established scales [17].

A: So considerable rebuilding was achieved?

REM: The rebuilding job of replacing three full professors and one very successful assistant professor was still a major challenge. The core of our nascent pharmacotherapy program at the VA Hospital was at risk. I began some strategic conversations with Herb Kleber, the director of the addiction research, training and clinical programs at Yale. The emphasis at Yale was on drug abuse, which complemented our alcohol research center. Herb and I saw the tremendous opportunities in a full collaboration, and we asked Tom Babor and Bruce Rounsaville from Yale to chart some promising opportunities. Bruce and colleagues offered to work with us in the development of pharmacotherapy trials and to provide mentorship to a young psychiatrist, Hank Kranzler, to develop a pharmacotherapy program focused on buspirone at the UConn site. Stephanie O'Malley, who was transitioning to faculty status at Yale, was his counterpart in a study of fluoxetine in New Haven.

A: What other developments were there?

REM: We had completed our initial studies in sons of alcoholics. With an unrestricted donation from Heublein Corporation, we were able to build and staff a neurodynamics laboratory headed by Sean O'Connor, an electrical engineer and psychiatrist. He and Victor Hesselbrock sought to determine whether the results from Henri Begleiter's laboratory showing the relationship between the P300 component of the evoked potential and risk of alcoholism was specific to that disorder or linked to an externalizing personality disorder.

A: Other developments?

REM: Most importantly, our program had expanded out beyond the Center grant to investigator initiated grants and major collaborations. Tom Babor and his team directed the project development and data analysis for Project MATCH, the largest psychotherapy/behavioral therapy project ever conducted. The Center's Typology study results informed the treatment matching design and methodology. Ron Kadden, Ned Cooney and Mark Litt directed the UConn clinical site in Project MATCH based on their work on the enhancement of coping skills. Victor and his team became a critical component in the Collaborative Study on the Genetics of Alcoholism, a landmark project that was the dream of Henri Begleiter and T. K Li. Our Center's work on the P300 in sons of alcoholics, and the rigorous assessment battery that Victor and his colleagues developed, made the UConn site and investigators a key part of the network.

A: Any other important developments at this time?

REM: Before our pharmacotherapy studies could get under way, the manufacturer of fluoxetine notified us that they would not provide the drug for out-patient studies in alcoholics. We were forced to go in a different direction. Based on the effects of naltrexone in a rodent model of drinking behavior, and exciting preliminary data from the University of Pennsylvania on its effects on drinking in alcoholics, we were encouraged by Chuck O'Brien, the Director of the research center at Penn to attempt to replicate their work—which is how Stephanie O'Malley and colleagues ended up studying naltrexone. Together, data from our two centers (Penn and UConn/Yale) led to the FDA approval for naltrexone to treat alcohol dependence. Having completed my studies of naltrexone in heroin addicts a decade earlier, I felt a certain a connection between the new results and my previous work that was a mixture of emotional and intellectual excitement.

A: It seems that the developments that began with the renewal process for the 1987 Center grant resubmission have stood the test of time!

REM: Between 1987 and 1992, I think the Center really thrived. People collaborated well with each other and with investigators at other universities. There was a sense that the Center mattered, and that young investigators and post-docs were valued highly and deserved serious mentorship. Our now senior faculty had come of age, and contributed exciting ideas for research.

‘Between 1987 and 1992, . . . the Center really thrived . . . There was a sense that the Center mattered . . .’

In 1986, our new Dean announced to me that the school had been given a significant sum of money from the privatization of a non-profit health system in Connecticut. He insisted that the psychiatry department be given one of these four positions and I was named Physicians Health Services Professor as an endowed Chair. The Chair was tied to our research focus. In 1987, the Dean asked me to add the responsibility for the medical school's faculty practice plan to my administrative portfolio.

A: You had become a very senior figure in the field by this time, and your new responsibilities must have been helpful in securing your clinical and research base at UConn.

REM: By the late 1980s, in the alcohol field, among the psychiatry chairs, and in the broader world of psychopharmacology, I sensed myself moving from young Turk to elder statesman within what seemed like a blink of time. When I was elected President of the Chairs group in psychiatry in 1990 and President of the American College of Neuropsychopharmacology in 1992 (the first alcohol clinical researcher in either role), I felt that perhaps alcohol research was going ‘mainstream’. By 1992, our Center grant was renewed for a fourth cycle, and the psychiatry department had become the top research department, on a per capita basis (in terms of NIH support) at UConn. And, when the school faced another crisis, the Dean asked me to add the role of Executive Dean to my jobs as Chair and Center Director.

A: That sounds like a superhuman work-load. How did you do it?

REM: Both the psychiatry department and the alcohol research center were running well, with solid administrative support. I was able to recruit separate administrative staff to support my role in the Dean's office. I cut back on clinical time, and I was no longer able to be directly involved in the day-to-day aspects of my research on craving. Even with these changes, by 1992, my three administrative jobs at UConn had worn me down a bit. In the fall of that year, I started a year-long sabbatical at the Center for Advanced Study in the Behavioral Sciences at Stanford. I was able to lead our grant renewal application in the year before the sabbatical, and I was able to negotiate an agreement with the medical school administration to provide new support for Center faculty as a demonstration to NIAAA of the value of the program to the medical school.

A: Your mini-sabbatical in London in 1984 had certainly recharged your enthusiasm about alcoholism research. Were you hoping to achieve the same outcome with the sabbatical at Stanford?

REM: I felt comfortable taking the 1-year sabbatical because of the state of the department and the Center; but I was concerned about imminent changes in leadership at the Health Center. It all had taken a huge effort, and I was not sure that I had the capacity or influence necessary to continue to protect and grow our programs.

My research interests were still focused on the relationship between craving and alcohol dependence. I went to California and tried to sort out where I should focus my interests. Our youngest daughter had just left for college, and we had no urgent ties keeping us in Connecticut. At Stanford, the new Chair offered me the opportunity to come on faculty to do full-time research. I was also invited by several medical schools to consider a position as Dean of the Medical School or Vice President for Health Affairs. I chose to accept a position at George Washington University with broad responsibility for the entire enterprise (hospital, medical school and other health science schools). The job, while fraught with problems, was in Washington, a place that my wife and I had loved during the 2 years that we had spent there when I was at NIMH.

A: After an immensely contributory career in academia you tackled that new challenge—how many years were you at George Washington and what followed?

REM: I actually spent just under 2 years at George Washington. We completed the first Chair recruitments in many years, brought together an outstanding clinical, operational and financial team that generated the first ‘profit’ ($35 million) in a number of years from clinical operations, forged a research partnership with a nearby non-profit basic science center, initiated a public health school and increased the membership of our wholly owned health maintenance organization (HMO) by nearly 50%. This enabled my boss, the university president, to proclaim that as we were now profitable, we should sell off the clinical operations (hospital, clinical department faculty and the HMO). Having feared his tepid commitment to the school, I had negotiated a 5-year contract going in, so I had 3 years to chart a new path. I was offered the vice-presidency at another school in the Midwest, but my wife and I really loved Washington; so in 1997 I started a consulting business with three other partners to small and non-US-based pharmaceutical companies interested in developing central nervous system (CNS)-active drugs in the United States. I also began work as a part-time consultant to the Association of American Medical Colleges (AAMC), focused on strengthening clinical research programs at US medical schools. In 2002, as our business began to get very busy, I dropped my role at AAMC to focus on the other consulting activity.

A: And as well as giving extraordinary service to your science I believe you have enjoyed a very happy family life?

REM: The key event that has gone unmentioned so far was my good fortune in finding the right life-time partner. I was very lucky that I was ready to make a commitment to one person at the exact time that I found that person during my residency. With Sheila, over nearly 45 years now, we have been privileged to raise three daughters (each accomplished in her own right) and now to experience the joys of being grandparents. My children remind me that I never missed a breakfast or dinner with them when not on travel; and the stories that they remember from their childhoods reassure me that they felt a lot of attention and affection from their father (and mother). That is the deepest satisfaction.

A: And satisfaction in professional achievement?

REM: From a work perspective, I feel that I was privileged to enter academic medicine in the United States at a particularly good time. The research career goals that I set out to achieve as I was leaving NIMH in 1968 were achieved beyond my wildest expectations. The privilege of serving as a consultant to the White House in the Nixon and Reagan administrations (in particular) was a special opportunity to affect policy. My service as a reviewer for NIDA, NIAAA, FDA and the Department of Veterans Affairs taught me a great deal about a broad range of research topics. My friendships within the addiction research community have been very meaningful. I know of no other field of research in psychiatry where the physician researchers are as committed to a multi-disciplinary perspective or are as generous and mutually supportive. Most importantly, my former colleagues at UConn, especially my mentees, represent the real lasting contribution to the field. What was striking to me as I went off on sabbatical was how my leadership role at the Center had evolved from being the source of research ideas to a more avuncular style and status of leadership. When I took my last mini-sabbatical at the Rockefeller Foundation Center at Bellagio Italy in 2000, I reconnected with the passion that I felt about alcoholism research. I put my thoughts together in a paper that I published in Alcoholism: Clinical and Experimental Research[18]. The message of my paper was, in retrospect, a restatement and further elaboration on what I had learned at NIMH on the importance of the broad base of research across public health, clinical observation, behavioral, psychological and social science, and the multiple disciplines now grouped under the term neuroscience and genetics. On reflection I saw a continuing need to develop an interdisciplinary model of alcoholism that can only come out of models of interdisciplinary research that are perhaps yet to emerge.

‘The privilege of serving as a consultant to the White House in the Nixon and Reagan administrations . . . was a special opportunity to affect policy.’

A: If we caught you on a rare day not working, how would we find you spending your time?

REM: Enjoying time with my family, biking along the Chesapeake and Ohio Canal, playing tennis, reading history and several daily newspapers, and a recent hobby: making slide shows of trips that my wife and I have taken. The DVDs that I make include the music of the local culture as background, and my voice-over guiding the video.

A: Now a final question if I may. You are someone who has always enthusiastically accepted responsibilities toward younger colleagues. Bright young people in the United States have no shortage of career choices. If a young clinical researcher were to approach you today and say ‘Dr Meyer, you have vast experience, tell me why I should make addictions and their frequently stigmatized patients my priority choice?’ what would be your answer?

REM: Over the past 13 years (as a consultant to industry, government and the AAMC), I have appreciated even more that we in the addictions field have clinical research and animal models that should be the envy of our colleagues in the rest of psychiatry. The young person should understand that to really know the field, one should be able to read a multi-disciplinary literature and to think outside the box created by American psychiatry and the DSM. You should seek to collaborate with biological, behavioral and social scientists who will know more about research, but who will value what you can bring from your clinical observations and experience. You should be prepared to ‘get little respect’ from your colleagues who study schizophrenia or mood disorders. You should be capable of developing empathy for the struggles that patients and families go through in coping with addiction as a chronic relapsing disorder, and you should be able to provide hope and informed treatments (often repeatedly); applying or recommending the best evidence-based interventions that are available. There is no other area of psychiatry that has so much imminent promise.

References

  1. Top of page
  2. CHANCE FAVORS A PREPARED MIND
  3. EFFORTS TO CREATE CLINICAL AND ANIMAL BEHAVIORAL MODELS FOR TRANSLATIONAL RESEARCH
  4. A MOVE TOWARD AUTONOMY LEADS TO ADMINISTRATION
  5. RECRUITMENTS AND SUPPORT FOR YOUNG FACULTY CREATE A TEAM
  6. THE NEED TO REBUILD
  7. References
  • 1
    Meyer R. E., editor. Adverse Reactions to Hallucinogenic Drugs. Report of a Conference held at the National Institute of Mental Health, Chevy Chase, Maryland, September 1967 (with selected background papers). Bethesda, MD: National Clearinghouse for Mental Health Information; 1969.
  • 2
    Meyer R. E., Pillard R. C., Mirin S. M., Shapiro L. M. Administration of marihuana to heavy and casual marihuana users. Am J Psychiatry 1971; 128: 198204.
  • 3
    Mirin S. M., Shapiro L. M., Meyer R. E., Pillard R. C., Fisher S. Casual versus heavy use of marijuana: a redefinition of the marijuana problem. Am J Psychiatry 1971; 127: 113440.
  • 4
    Meyer R. E., Cochin J., Miller J. M., Rosow C. The relationship between aggression and host differences in vulnerability to opiate addiction in the white mouse. In: Report of the college on Problems of Drug Dependence. Philadelphia, PA: CPDD; 1970.
  • 5
    Hindman R. D., Miller J. M., Meyer R. E., Cochin J. The effect of length of exposure to etonitazene upon drug seeking behavior. Pharmacologist 1971; 13: 262.
  • 6
    Mendelson J. H., Rossi A. M., Meyer R. E. The Use of Marihuana: A Psychological and Physiological Inquiry. New York: Plenum Press; 1974.
  • 7
    Meyer R. E., Mirin S. M. The Heroin Stimulus: Implications for a Theory of Addiction. New York: Plenum; 1979.
  • 8
    Kranzler H. R., Dolinsky Z., Kaplan R. F. Giving ethanol to alcoholics in a research setting: its effect on compliance with disulfiram treatment. Br J Addict 1990; 85: 11923.
  • 9
    Dolinsky Z., Babor T. F. Ethical, scientific and clinical issues in ethanol administration research involving alcoholics as human subjects. Addiction 1976; 92: 108797.
  • 10
    Wikler A., Pescor F. T. Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and ‘relapse’ in morphine-addicted rats. Psychopharmacologia 1967; 10: 25584.
  • 11
    Wikler A. Opioid Dependence: Mechanisms and Treatment. New York: Plenum Press; 1980.
  • 12
    Weiss F., Koob G. F. The neuropharmacology of ethanol self-administration. In: MeyerR. E., KoobG. F., LewisM. J., PaulS. M., editors. Neuropharmacology of Ethanol: New Approaches. Boston, MA: Birkhauser; 1991, p. 12562.
  • 13
    Vavrousek-Jakuba E., Cohen C. A., Shoemaker W. J. Ethanol effects of CNS dopamine receptors: in vivo binding following voluntary ethanol intake in rats. In: NaranjoC. A., SellersE. M., editors. Novel Pharmacological Interventions for Alcoholism. NewYork: Springer-Verlag; 1990, p. 3724.
  • 14
    Kaplan R. F., Meyer R. E., Stroebel C. F. Alcohol dependence and responsivity to an ethanol stimulus as predictors of alcohol consumption. Br J Addict 1983; 78: 25967.
  • 15
    Babor T. F., Meyer R. E., Hesselbrock V. M. From collaboration to integration: the university of Connecticut Alcohol Research Center in concept and practice. Bull Soc Psychol Subst Abuse 1985; 4: 315.
  • 16
    Meyer R. E. Old wine, new bottle: the alcohol dependence syndrome. Psychiatr Clin North Am 1986; 9: 43553.
  • 17
    Cooney N. L., Meyer R. E., Kaplan R. F., Baker L. H. A validation study of four scales measuring the alcohol dependence syndrome. Br J Addict 1986; 81: 2239.
  • 18
    Meyer R. E. Finding paradigms for the future of alcoholism research: an interdisciplinary perspective. Alcohol Clin Exp Res 2001; 25: 1393406.