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Obituaries

CINP would like to express the highest gratitude to former members with outstanding contribution in the field of psychopharmacology, who unfortunately have left us in the past years.

They showed us the societal usefulness and importance of basic neuropsychopharmacological expertise and were known all loyal supporters, who contributed to our scientific and educational programs over the years. May your memory be honored forever.

Arvid Carlsson, MD, PhD (1923-2018)

by Johan WingborgArvid Carlsson was born in 1923 and grew up in Lund where he also studied medicine. His thesis, which he defended in 1951, was on calcium and bone tissue, but a brief stay at the laboratory of the legendary Bernard Brodie at NIH made him change his field of interest to that of brain neurotransmitters. In 1959, he became professor of pharmacology at the University of Gothenburg where he came to stay for the rest of his career. Among his many awards are the Nobel Prize, the Japan Prize, the Wolf Prize and the Jahre Prize. He was married to Ulla-Lisa, also MD, who throughout his career provided strong support for him in his work, and had five children.

When Carlsson entered the field of neuropsychopharmacology, the discipline was still in its very infancy. After long-standing reluctance, the concept of chemical transmission taking place in the brain had recently achieved acceptance, but virtually nothing was known with respect to the identity of the transmitters used for this purpose. When visiting Brodie’s laboratory, which also hosted future Nobel Laureate Julius Axelrod, Carlsson was asked to explore the possible influence of reserpine, known to exert antipsychotic activity, on the release of serotonin. He suggested that one should also examine the possible influence of reserpine on catecholamines, but as this was beyond the interest of Brodie, Carlsson decided to conduct these experiments when back in Sweden. To this end, he established close collaboration with histologist Nils-Åke Hillarp, later recognized for the invention of the Falck-Hillarp immunofluorescence technique by means of which brain monoaminergic neurons could be mapped.

Without any knowledge of the vesicular monoamine transporter, which we now know is the molecular target of reserpine, Carlsson and Hillarp could confirm that the drug effectively depletes catecholamines by interfering with the storage of the monoamines. Moreover, Carlsson showed that the loss of normal motor activity displayed by rabbits after treatment with reserpine was dramatically reversed upon administration of the catecholamine precursor levodopa, and that this effect was not, as he had assumed, caused by the restoration of brain levels of noradrenaline, but closely related to the formation of dopamine. Highly controversial when it was first presented, this was the main discovery for which he was subsequently awarded the Nobel Prize.

Needless to say, Carlsson’s reports on these pivotal experiments, conducted in Lund in the late 50’s, had an enormous impact on the development of the field. First, they suggested that dopamine, by the time regarded merely as an intermediary in the formation of noradrenaline in the peripheral nervous system, was a brain neurotransmitter. Second, they constituted the first confirmation of the feasibility of the mode of thinking that has since then dominated neuropsychopharmacology, i.e. that behavioural aberrations may be caused by more or less specific transmitter aberrations and treated with drugs normalizing transmitter activity. Third, they paved the way for the subsequent introduction by George Cotzias of the use of levodopa as treatment of Parkinson’s disease. Fifty years later, there is still no more effective drug for this disabling condition.

In the 60´s, when Carlsson had moved to Gothenburg, he made another seminal discovery related to dopamine. The observations that reserpine is an antipsychotic drug, and that it reduces brain dopamine levels, had prompted several groups to explore the possibility that also other antipsychotic drugs, the recently discovered chlorpromazine and haloperidol, might reduce dopamine levels, but without obtaining support for this suggestion. Analysing transmitter turnover rather than merely transmitter levels, Carlsson however noted that these drugs elicits an increase in catecholamine turnover, and concluded that they may act as receptor antagonists, the increase in turnover most likely being an adaptive response mediated by a yet unidentified feed-back mechanism. Given that one, at the time, knew very little about synaptic regulation, including the existence of the kind of receptor Carlsson later named autoreceptor, and that receptor antagonism was far from an established mechanism of action for drugs influencing the brain, the conclusion drawn by Carlsson was a brave yet logical one, that has since then been confirmed in numerous studies.

The report on the mechanism of action of antipsychotics was published in a Scandinavian journal, Acta Pharmacologica et Toxicologica, and was for several years rarely cited; when the dopamine hypothesis of schizophrenia had gained acceptance, it however became a citation classic. It is of note that Carlsson never cared much for the prestige of journals, or their impact factor, reasoning that a finding of sufficient importance would sooner or laterbecome well-known, regardless of where it was published. He even suggested that it might be advantageous to publish in modest journals so that one could do the obvious follow-up experiments without too much of a competition from other groups.

Carlsson remained interested in the role of dopamine in schizophrenia for the rest of his career. Impressed by the vast physiological importance of dopamine transmission, he regarded blocking the dopamine D2 receptors in patients with schizophrenia being too drastic an interference, and suggested that partial D2 agonists, such as (-)-3-PPP, which was developed in his own laboratory, may have a more tolerable profile; he was hence one of the first proponents of the mode of action today exerted by aripiprazole and several other recently developed second-generation antipsychotics. However, in recent years he came to believe that there are even more effective ways of stabilizing dopaminergic activity than partial agonism. Active until the very end of his life, Carlsson hence, together with his daughter Maria, spent his last years developing a new kind of dopamine stabilizer, OSU6162, which had been shown to enhance the activity of low-activity animals and reduce it in those being hyperactive; at the age of 95, he published his last paper on this compound in the same month that he passed away. It is saddening that Carlsson did not live long enough to witness the outcome of the ongoing clinical trials where this intriguing drug is being evaluated for its proposed effect on mental fatigue.

Carlsson also made important contributions to the field of antidepressants. After the serendipitous discovery by Roland Kuhn in 1957 of an antidepressant effect of the tricyclic drug imipramine, it had been reported by Julius Axelrod, in 1962, that this compound blocks the reuptake of noradrenaline, and suggested by Joseph Schildkraut, in 1965, that facilitation of noradrenergic transmission be a common denominator for antidepressants. In the late 60’s, Carlsson however showed that tricyclic antidepressants also inhibit serotonin reuptake in brain and proposed that this effect may contribute to their antidepressant properties. He suggested to Ivan Östholm, head of research at a small, nearby drug company, Hässle AB, which was a subsidiary of Astra, that they together should develop a reuptake inhibitor influencing serotonin but not noradrenaline, the result of this endeavour being zimelidine, the first of the selective serotonin reuptake inhibitors (SSRIs). Whereas clinical trials with this drug provided proof of the concept that depression may be treated by drugs selectively influencing serotonin, zimelidine unfortunately had to be withdrawn from the market because of a rare and reversible Guillain-Barré-like side effect. Needless to say, the suggestion that selective serotonin reuptake inhibition be a feasible mechanism for treating depression however did survive, the followers of zimelidine still being first line of treatment not only for depressed mood but also for a number of anxiety disorders, obsessive compulsive disorder and premenstrual dysphoric disorder.

Asked why he had become so successful, Carlsson often underlined that he had been lucky, arriving to exactly the right place (Brodie’s lab) at exactly the right time, i.e. in the very infancy of a field that soon was to expand enormously, and also, after having returned to Sweden, having the opportunity to collaborate with a scientist with exactly the right complementary competence, Nils-Åke Hillarp. But while luck may have a played a significant role for a researcher making one important discovery, it can hardly be the major factor for someone who, like Carlsson, has made a string of seminal discoveries. Instead Carlsson’s achievements must be explained by a unique talent for scientific thinking: like few others, he could select the most promising leads from many possible alternatives, mobilize the required rethinking to interpret puzzling results in an unconventional way, and recognize a pattern, invisible to others, from a number of disparate observations. He also displayed an entrepreneurial ability to get things done, and – not least – such a genuine interest in the scientific problems that he, throughout his 70-year-long career, always avoided leading positions within the faculty as well as prestigious but time-consuming honorary assignments. His focus was always on solving scientific problems.

Carlsson showed impressive creativity also with respect to how to conduct preclinical, academic research. For example, having a group of synthesis chemists working at his laboratory, providing him with novel molecules, was an unconventional but highly successful move. Several pharmacological tools resulting from this endeavour have been tremendously useful for neuropsychopharmacologists around the world, including the prototype 5-HT1A agonist 8-OH-DPAT. Moreover, as an external advisor, he prompted the above-mentioned company, Hässle AB, to profoundly change its modus operandi, hence playing a key role for its spectacular success in the 1970’s, when it developed, e.g. metoprolol for hypertension and omeprazole for peptic ulcer. Carlsson was also an atypical preclinical neuroscientist in the sense that he early on realised the importance of continual interaction with clinicians, as illustrated, e.g. by his involvement in clinical trials suggesting antipsychotic effects of the dopamine synthesis inhibitor alpha-methyl-p-tyrosine and the partial agonist (-)-3-PPP, respectively. Thus, he was a pioneer also with respect to being translational in his research.

Having good self-esteem, and firmly believing in his ideas, Carlsson often defended his stance in scientific matters with considerable stringency and vigour. He also possessed a significant personal integrity that prompted him, now and then, to make authoritative contributions to the public debate, mainly on issues of research politics. But while he could be feared as opponent in a debate, he was friendly and easy-going in private encounters, conversations with him often being interleaved with joke and laughter. And although he was probably the most internationally renowned researcher in his field, he never showed the slightest trace of conceit. Thus, throughout his professional life, the intellectual issues at stake – never prestige or position – remained central for him. Young PhD students who turned to Carlsson to discuss scientific issues were encouraged and inspired by such encounters, not least because he seemed to put as much value on them as the junior interlocutor did. Numerous colleagues throughout the world have similar experiences.

A preclinical pharmacologist with strong interest also in clinical matters, Carlsson can be said to personalize the spirit of CINP, of which he was a great friend and supporter. He usually attended the CINP congresses, was CINP President in 1978-80, hosted the CINP World Congress in Gothenburg in 1980, presented the final keynote lecture at the CINP World Congress 2012 in Stockholm and was named Honorary President in 2012. While it is sad that this pioneer in neuropsychopharmacology, and true friend of CINP, has now left us, we should be pleased that he, throughout his long professional life, had the fortune of making such important contributions for millions of patients around the world. Like no one else, Carlsson has showed us the societal usefulness and importance of basic neuropsychopharmacological research.

by Elias Eriksson & Torgny H Svensson

Oldřich Vinař, MD, PhD (1925-2018)

Oldřich Vinař was born on 9. 12. 1925 in Brno, the Moravian Metropolis of the Czech Republic. He studied Faculty of Medicine Charles University in Prague and graduated in 1949. He was the only Czech member and correspondent of the ACNP (American College of Neuro-Psychopharmacology) and co-founder of the CINP.

Oldřich Vinař was one of the founders of the Czech Neuropsychopharmacological Society and the organizer of the oldest conference on this issue in the world, the Czech-Slovak Psychopharmacological Conferences in Jeseník Spa. The first one of these took place 6 months before the first CINP conference in the 1970. Oldřich Vinař contributed to the fact that the Czechoslovak school left an indelible mark in the field of the world’s psychopharmacology. He worked closely with the team of the Research Institute of Pharmacy and Biochemistry in Prague and this collaboration led to the clinical testing and introduction of original Czechoslovak psychotropic drugs. Oldřich Vinař established the system of continuous performance of controlled studies. With a considerable advance ahead of the development in the world, he understood that, together with the development of new drugs, it is necessary to compare their effects, and he created the original Czech scales that were used in the Czech Republic before these methods arrived from abroad.

Oldřich Vinař was a visionary, able to look ahead foretelling the evolution of psychiatry and he overtook the time with an array of his claims (e.g. the effect of smoking and gender differences on the effect of psychotropic drugs). His doctoral thesis (1991) was dedicated to the possibilities of predicting the effect of psychotropic drugs. The prediction was based not only on clinical signs but also on biological parameters including electroencephalography and concentration of catecholamine metabolites. How close was he to the current efforts for a personalized medicine!

Oldřich Vinař also belonged to those enlightened psychiatrists who tried to offer the colleagues from other disciplines and the laity an insight to the issue of mental disorders, showing them from a human and comprehensible point of view. With increasing age, he focused on philosophical themes that were always of his interest. The entire generation of Czech psychiatrists studied psychopharmacology from his textbooks “Psychopharmacs I and II”. The psychiatric community used to know Oldřich as a master of brilliant and often provocative discussions with an excellent memory. His professional attitudes and messages have never been forget.

Dear Oldřich, may your memory be honored forever.

Pamela Sklar, MD, PhD (1959-2017)

CINP mourns the passing on November 20, 2017 of Pamela Sklar, M.D., Ph.D., a member of the CINP Council. At the time of her passing, Dr. Sklar was Chair of the Department of Genetics and Genomic Sciences and professor of psychiatry, neuroscience, and genetic and genomic sciences at the Icahn School of Medicine at Mount Sinai (New York, USA). She was also chief of the Division of Psychiatric Genomics at the Icahn School of Medicine at Mount Sinai.

Dr. Sklar was a pioneering psychiatric geneticist and a principal investigator of the Psychiatric Genomics Consortium. She was known for her pioneering contributions to large scale genetics initiatives that identified rare gene variants that had a relatively large effect on schizophrenia risk as well as some of the first replicable findings on the impact of numerous common gene variants that contribute to the risk for schizophrenia and mood disorders.

A polymath, Dr. Sklar completed her bachelor’s degree in classics and philosophy at St. John’s College in 1981. She then completed her M.D. and Ph.D. (Neuroscience) degrees in neuroscience at Johns Hopkins School of Medicine. She completed her Ph.D. in the laboratory of Lasker Prize recipient, Solomon Snyder. She then completed psychiatry residency and post-doctoral research training at Columbia University. Her post-doctoral work was conducted in the laboratory of Nobel laureate, Richard Axel. While working at the Broad Institute, a joint Harvard-MIT initiative, she co-founded the Stanley Center for Psychiatric Research. In 2011, she moved to the Icahn School of Medicine at Mount Sinai.

Dr. Sklar was the recipient of numerous honors and distinctions that included the Brain and Behavior Research Foundation Colvin Prize for Outstanding Achievement in Mood Disorders Research, the Lifetime Achievement Award from the International Society of Psychiatric Genetics, and election to the U.S. National Academy of Medicine.

Dr. Sklar is survived by her husband, Andrew Chess, MD, Professor of Genetics and Genomic Sciences; Cell, Developmental and Regenerative Biology; and Neuroscience, at the Icahn School of Medicine at Mount Sinai; and their children, Michael Sklar Chess and Isabel Sklar Chess.

Dr. John Krystal, former president of CINP, wrote, “I was thrilled to see that Pamela had been elected to the CINP Council. She would have brought so much to our College, as she has to our field. I am deeply saddened by her passing. On behalf of CINP, I send our deepest condolences to her family, friends, and colleagues.”

Graham D Burrows, MD (1938-2016)

Graham Burrows, of the Department of Psychiatry, University of Melbourne, unexpectedly passed away in January 2016 following an accident in his home.

The sudden death of Graham was a shock to all his many friends and colleagues in CINP. Graham was an enthusiastic supporter of our organisation for over 30 years and an active participant in our symposiums. Indeed he participated as a speaker in our congress in Vancouver in 2014 and had every intention to join us in Seoul this year.

Graham had a most distinguished academic and professional career, not only as a clinical researcher in mood disorders, pain and addictive behaviours, which resulted in over 700 international publications, but also in public life as chairman of the Mental Health Association of Australia. In this position he was particularly active in fighting stigma and educating the public in the treatment of mental disorders. He was also a member of the Ministerial Advisory Committee on mental health. For his distinguished contributions to medicine, Graham received one of the highest awards, the Order of Australia, in 1989, which was followed by Australian knighthoods (KSJ and KCSJ) a few years later.

However, despite all the honours bestowed on him over the years, Graham always maintained a down-to-earth sense of humour and a warm regard for his friends and colleagues. As departmental head he always supported and encouraged the success of his younger colleagues and researchers.

The CINP has lost a loyal supporter who contributed much to our scientific and educational programmes over the years. His friends and colleagues will miss him for his warmth, his enjoyment of life and for his many contributions to all that is best in our organisation. He will be deeply missed not only by his grieving family but also by his many friends in the CINP. May he rest in peace!

Dr. Leonard Cook (1924-2016)

One of the world’s leading psychopharmacologists passed away Saturday, January 30, 2016 at the age of 91.

He is recognized as the discoverer of several early drugs for psychiatric disorders and as a pioneer in the development of methods to identify and study drugs for treatment in psychiatry. Leonard is credited for his role in the establishment of the modern field of psychopharmacology.

Dr. Cook was born in Newark, NJ in 1924. He served as a celestial navigator in the Army Air Force during World War II. Leonard graduated from Rutgers University and then attended Yale Medical School where he earned his PhD in pharmacology in 1951. In 1952, Dr. Cook was recognized as the first pharmacologist in the United States to study and elucidate the pharmacological properties of chlorpromazine, which eventually became the “breakthrough” agent (Thorazine) for the therapy of schizophrenia. In recognition of these early and significant contributions in the field of neuropsychopharmacology, the Collegium International of Neuropsychopharmacology (CINP) Society awarded him their coveted “Pioneer Award” in 2006. In the same year, the American Society of Pharmacology and Experimental Therapeutics (ASPET) presented him with their “Lifetime Achievement Award,” recognizing his early and continuous contributions to this field.

Dr. Cook’s initial research was carried out at Smith Kline & French Laboratories in the early 1950’s, where his research team developed
“Compazine” and “Stelazine,” and discovered a compound for depression, “Parnate.” These compounds had a significant impact in the therapy of psychiatric disorders in the 1950s and 1960s. Dr. Cook’s research group was internationally recognized as the largest and most prominent behavioral pharmacology research laboratory in the world, visited by international scientists, including many from the former Soviet Union where he was referred to as the “American Pavlov.”

In 1969, he became the Director of Pharmacology at Hoffmann La Roche to lead their entire pharmacological research department, and focused on the research of new drugs in the field of anxiety to follow their initial agents of Librium and Valium. In 1982, Dr. Cook was elected President of the American College of Neuropsychopharmacology (ACNP). He was a founding member of this group in 1961 and was the first industrial scientist to serve as President of this prestigious organization. Dr. Cook also received ACNP’s prestigious “Paul Hoch Award.” In 1983, he joined DuPont Merck to build and lead their research in the Central Nervous System area for the pharmaceutical business, resulting in the discovery of agents which entered clinical trials for the potential treatment of Alzheimer’s disease. During his research career, Dr. Cook also received numerous academic appointments, including adjunct professor of pharmacology at the New Jersey School of Medicine and Temple Medical School, and adjunct professor in psychiatry at the University of Pennsylvania. He was also appointed Visiting Professor of Pharmacology at Beijing Medical School, Shanghai School of Medicine and Xian School of Medicine in China, and visiting professor at Moscow and Leningrad Schools of Medicine.
Dr. Cook served for many years as a consultant to the National Institute of Drug Abuse, particularly in their pursuit of pharmacological agents useful in treating drug abuse. He also served as a special consultant to the Pentagon. He was particularly proud of the many young scientists he trained in his neuropsychopharmacology laboratories, several of whom went on to be outstanding in this field.

Dr. Cook was predeceased by his beloved wife of 45 years, Rheva Cook and is survived by his loving children, Dr. Steven Cook (Linda), Dr. Michael Cook (Rae) and Dr. Sandra Cook Gruber (Thomas); two grandsons, Daniel Cook (Jingsi) and Peter Cook; brother, George Cook; and Len’s close and loving companion, Barbara Yalisove.

Jonathan O. Cole, MD (1925-2009)

Jonathan O. Cole, M.D.Jonathan Cole had a remarkable impact on psychiatry and psychopharmacology which should be re-evaluated to clearly establish the enormous contribution he made to the field and the people who came into contact with him. He was born on 16 August 1925. He went to Harvard College and then onto Cornell University Medical School, graduating in 1947 and continued there in psychiatric residency at Payne Whitney Clinic from 1948 to 1951. After his residency he went into the U.S. Army.

In 1953 he took a position as a Professional Associate to the committee on Psychiatry at the National Academy of Sciences in Washington, D.C. where he remained until 1956.

I have known Jonathan Cole for the past 50 years. We first met when I was a visiting scientist at the University of Michigan and he was making a follow-up site visit with two of his junior staff, Rees Jones and the late Jerry Klerman. They were visiting the Schizophrenia and Psychopharmacology Research project that Jon had played a major role in establishing. Some of the details can give some idea of his vision and breadth of scope. The Director was Ralph W. Gerard a famous neurophysiologist from the University of Chicago, and his deputy was an American psychiatrist. The investigators were drawn from the U.S. and the rest of the world – Japan, Sweden, Britain, Germany and one from Australia. It was a 5-year centre grant and during this period other investigators came in and some moved on. We did not cure schizophrenia but produced many findings that did influence the state of the art in its infancy and most certainly its progress. This one example illustrates his goal of seeding research sites and creating in them the ability to metastasize.

Subsequent to this experience I worked in other centres in the U.S. and found that Jon Cole, the travelling salesman for psychopharmacology, had already visited and left his mark or came shortly after and helped establish a new site.

His centre of operation was as Chief, Psychopharmacology Service Center at NIMH from 1956 to 1966 and from 1966 to 1967 as Chief, Psychopharmacology Research Branch, NIMH. He was in effect the head of a worldwide Marshall plan for psychopharmacology. There was another unique aspect to his operations. They were personal and hands on. He would identify a Dr X who had special skills in one or another relevant discipline and explore whether this individual was a potential investigator in the cause, then he and his colleagues would help that person or group get a start. His personal involvement in this mission was one of his great contributions to the success of the investigator and the success of the mission. To this task he not only brought exquisite clinical skills and understanding but a charm and jolly cheerfulness that was therapeutic for new investigators.

After he left NIMH he returned to Boston, to Boston State Hospital from 1967 to 1973 and then to McLean Hospital in Boston where he was active as a psychiatrist and an investigator and was productive in carrying out clinical research and coming up with new ideas. He contributed several hundred publications to the literature, including research papers, book chapters, and books. Letters to the editor was another way for him to present interesting observations based on his exquisite clinical acumen.

His continued contribution to the development of the field was his active involvement in the developmentand growth of the ACNP and he became its President in 1965–1966. He also dedicated his efforts to support the CINP and was secretary of the organization from 1966–1969 and was awarded the CINP, Pioneers in Psychopharmacology Award in 2002.

Over the past several years he was ill and for a while restricted in his mobility, but he still attended scientific meetings and would be active in discussions and suggesting new approaches to issues under discussion.

Dimitrije P. Milovanoviæ, MD, PhD (1928-2008)

Dimitrije P. Milovanoviæ, MD, PhDDimitrije P. Milovanoviæ, emeritus member of CINP, passed away on December 1, 2008 at age 80. Born on September 9, 1928, in the village of Donje Crnatovo (Zitorada municipality, Toplica district,) Serbia, he studied medicine at the University of Belgrade, graduating  in 1953, and receiving his specialist certification in neuropsychiatry in 1960.
Milovanoviae began his professional career in 1954 in the Department of Psychiatry, Faculty of Medicine, University of Belgrade, and stayed in the Department until his retirement in 1993. In 1979 he was elected professor of neuropsychiatry at the University, and, in 1988, a member of the Serbian Academy of Sciences.

Milovaoviae’s textbook, Clinical Psychopharmacology, was first published (Gorenjski tisk, Ljubljana) in 1972. The book, now in its 5th edition, was to become the standard text in psychopharmacology in Serbia. In 1979, Milovanoviae was awarded the October Prize of the City of Belgrade for his book, Medical Ethics, now in its 4th edition. He served as President of the Association of Psychiatrists of Yugoslavia, and was the founding editor-in-chief from 1979 to 2004 of ENGRAMI, the journal of the Association. Miolvanoviae was elected a member of CINP in 1978, and became an emeritus member in 2005

In 1994, Milovaniae was elected a senior research fellow of the United Nations European and Development Center. He is considered by his peers, as expressed by Professor V. Varagic, the founder of psychopharmacology in  Serbia.

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