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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.

Hanns Hippius, MD, PhD (1925 - 2021)

We bid farewell to our friend Hanns Hippius, who passed away peacefully surrounded by his family on August 21, 2021, at the age of 96. We mourn the loss of a great man who was a founding member (1957) and President of the International College of Neuropsychopharmacology (CINP) from 1972 to 1974. Despite his advanced age, he was still full of vitality and intellect in the final years of his life. Unsurprisingly to those who knew his strong personality and positive attitude, he endured increasing physical limitations without complaint.

Hanns Hippius was for many years Medical Director (1971-1994) of the Department of Psychiatry and Psychotherapy at the Ludwig Maximilian University in Munich. He was an outstanding physician and scientist who shaped the field of psychiatry with his extraordinary mind and exemplary commitment, not only in Germany, but also worldwide, as few German psychiatrists of his generation did.

Hanns Hippius was born on April 18, 1925, in Mühlhausen in Thuringia, Germany. He studied medicine and chemistry at the universities of Freiburg in Breisgau, Marburg an der Lahn and at the Free University of Berlin. In 1950, he received his doctorate in medicine (Dr. med.) from the Free University of Berlin and subsequently became an assistant at the Institute for Experimental Therapy "Emil von Behring" in Marburg an der Lahn. His interest in neurobiochemical processes in mental diseases grew out of the combination of his chemistry studies, which complemented his medical studies, and an intensive study of psychiatry during his medical studies. Psychiatry and neurology were also the focus of his clinical work, first as a research assistant and later as a senior physician in Berlin. After his postdoctoral qualification in psychiatry and neurology (1963), he was full professor of psychiatry and director of the Psychiatric Hospital of the Free University of Berlin from 1968 to 1970. From 1971 to 1994 he was full professor of psychiatry at the Ludwig Maximilian University of Munich and medical director of the Psychiatric University Hospital Munich.

Between 1972 and 1974 he served as President of the German Society for Psychiatry and Neurology (DGPN). He was a founding member (1957) of the International College of Neuropsychopharmacology (CINP), where he served as president from 1972 to 1974. He was also a founding member of the Association of European Psychiatrists (AEP), now the European Psychiatric Association (EPA), in 1983. He was a member of the German Academy of Sciences Leopoldina. He was an honorary member of many professional societies and received numerous other honors, including the Wilhelm Griesinger Medal of the German Society for Psychiatry and Neurology (DGPN), the Ernst Jung Medal for Medicine, the Bavarian Order of Merit and the Federal Cross of Merit.

Hanns Hippius was deeply committed to improving the care of people with mental illness in Germany. His patients knew him as an empathetic and caring physician who strongly advocated the destigmatization of the mentally ill.

In research, Hanns Hippius focused on two main scientific areas: psychopharmacological therapy and neuroscientific psychiatry. By establishing a large neurobiochemical laboratory under the direction of Norbert Matussek, Hanns Hippius made important contributions to the biochemical and immunological, and later also molecular-biological and psychiatric-genetic research that developed from it. In addition, he initiated further important developments in the field of psychiatry at a very early stage: For example, he promoted research directions such as electrophysiology and cranial imaging (with CT, SPECT and MRI) at the Psychiatric Hospital in Munich. In order to do justice to the increasing breadth of the subject (today's name: psychiatry and psychotherapy), he established new professorships for neuropsychology and for psychosomatics/psychotherapy. All this provided the basis for the acquisition of large research projects funded by the DFG or by federal ministries. It was also on this basis that the Munich hospital was selected as a WHO Collaborative Center.  As author/co-author of numerous important publications on the above-mentioned research areas, Hanns Hippius gained great national and international recognition as a scientist.

A very important aspect must not be forgotten in this context. German psychiatry had fallen into an outsider's position after the terrible events of the Nazi era (euthanasia, abuse of genetic research, etc.). This understandable discrimination was felt especially by the international professional societies. As one of the few German professors, Hanns Hippius succeeded in restoring German psychiatry's worldwide reputation through his high professional competence, his international relations and his diplomatic skills.

All of these accomplishments earned the Munich Hospital he headed a high reputation in Germany and internationally as a university psychiatric research and care institution. As one of the largest and most important psychiatric university hospitals, Hanns Hippius had a formative effect on the development of psychiatry in Germany, and in doing so, he conveyed psychopharmacotherapy and neuroscientific research as central areas of psychiatry at a time when most psychiatric university hospitals in Germany were still primarily oriented toward descriptive psychopathology. His influence in this regard can be seen, among other places, in the increasing number of psychiatrists with this scientific specialization who were appointed to chairs of psychiatry in Germany. Also, many of his students were appointed medical directors of large psychiatric care hospitals.

After his retirement, he focused with great commitment on taking care of his large family (4 children, 5 grandchildren), to which he felt he had not always been able to devote enough time during the professional phase of his life. His wife's dementia overshadowed many years of this phase of his life to a considerable extent. It was admirable how Hanns Hippius lovingly cared for his wife, first at home and later in a nursing home. One could regretfully observe how much he, who always loved to be among people, was thus closed off from the outside world and how much of his strength this task demanded. Nevertheless, when he himself became increasingly in need of care due to old age, he decided to bring his wife home and live with her in the house with the help of caregivers until her death. Hans-Jürgen Möller always remembers with pleasure the phone call when Hanns Hippius told him full of joy: "I have brought Waltraud home again". This act of special humanity made a particularly deep impression on him.

We will remember Hanns Hippius as a great personality and a highly honored friend.

Hans-Jürgen Möller, Peter Falkai, Siegfried Kasper

Oleh Hornykiewicz, MD, PhD (1926-2020)

A Tribute to Oleh Hornykiewicz (by Christian Pifl and Harald H. Sitte)

Pharmacology and neuroscience have lost a great man, to whom we owe the only firmly established pharmacotherapy of a neurodegenerative disease: Oleh Hornykiewicz, Emeritus and Chairman of the Institute of Biochemical Pharmacology, Vienna, Austria, passed away on 26 May 2020. He was renowned for his discovery of the neuropathological and functional basis of Parkinson’s disease, the striatal loss of dopamine, and its treatment with the dopamine precursor, L-DOPA.

From Eastern to Central Europe

Oleh Hornykiewicz was born on 17 November 1926 in Sychiw near Lviv/Lemberg in Eastern Galicia, which is western Ukraine today. In 1939, with the outbreak of the Second World War, his father, a Catholic-Ukrainian priest and teacher of Catholic doctrine and philosophy of religion at Lemberg Gymnasia, moved to Vienna with his family. Oleh, then 13 years old, started to attend secondary school in Vienna, followed in 1945, by medical studies at the University of Vienna. After obtaining his MD in 1951, he became a ‘voluntary research assistant’ at the Pharmacological Institute of the University of Vienna under the directorship of Franz von Brücke, a charismatic teacher and dean of the Medical Faculty of Vienna. Von Brücke became an important mentor and their relationship was characterized by mutual esteem. Even after von Brücke’s death, Hornykiewicz remained friends with von Brücke’s son Thomas, a neurologist.

Focus on Dopamine

In 1956, Oleh applied for a Scholarship of the British Council and joined the Department of Pharmacology at Oxford University in the laboratory of Herman Blaschko, one of the leading researchers in the field of the biosynthesis, storage, and inactivation of biogenic amines, especially noradrenaline and adrenaline. At that time, dopamine was considered as a mere intermediate in the synthesis of noradrenaline, but Blaschko had conceived the idea that dopamine had some regulating functions of its own. Indeed, Hornykiewicz was able to show a decrease in blood pressure triggered by dopamine in the guinea pig, independently of noradrenaline, and demonstrated that L-dopa, the amino acid from which dopamine is formed in the brain, behaved exactly like dopamine.

Breakthrough in Parkinson’s

In 1958, Oleh returned to Vienna and obtained a position as a research assistant at the Institute of Pharmacology of the University of Vienna. The observation of Bertler and Rosengren (1959) that dopamine, by contrast to noradrenaline, was highly concentrated in the dog corpus striatum, and their assumption, based on earlier work on the brain dopamine-depleting and parkinsonism-inducing effect of reserpine, that dopamine is connected with the function of the striatum and, thus, with the control of movement, prompted Hornykiewicz to study dopamine in the brain of patients with Parkinson’s disease or other extrapyramidal disorders and in the brains of non-neurological controls. He found that only the six patients with Parkinson’s disease cases had a severe loss of dopamine in the caudate nucleus and putamen. Remembering his previous research on dopamine/L-dopa in Oxford, the enthusiastic young pharmacologist became obsessed by the idea that motor deficits of Parkinson’s disease could be improved by replacing the missing brain dopamine. Within a short time, he succeeded in motivating Walther Birkmayer, an experienced neurologist and head of the Neurology Ward of the Municipal Home ‘Wien Lainz’, to substitute the loss in striatal dopamine of his Parkinson patients by injecting its precursor L-DOPA. From animal experiments, it was already known that L-DOPA was capable of increasing brain dopamine levels. In 1961, Birkmayer and Hornykiewicz reported on the first 20 patients injected intravenously with up to 150 mg L-DOPA. They observed a dramatic improvement of Parkinsonian symptoms with comparably few adverse effects (modest increases in blood pressure, vomiting, and sweating) and the action was enhanced and prolonged by the additional application of Marplan, a monoamine oxidase inhibitor.

Active on Two Continents

In 1964, Hornykiewicz was awarded tenure as ‘Dozent’ for Pharmacology and Toxicology at the University of Vienna. Although his success story ‘from brain homogenates to treatment’ did not immediately establish the role of brain dopamine in brain function, his seminal article in Pharmacological Reviews in 1966 finally contributed to the recognition of dopamine as an independent neurotransmitter with specific functions in the central nervous system (CNS). In 1967, he was offered a position as full professor in pharmacology at the University of Toronto and head of the Department of Psychopharmacology of the Clarke Institute; in 1973, he also became a full professor in the Department of Psychiatry, University of Toronto. In these scientifically fruitful years in Canada, his work gave insights into crucial questions regarding the concept of replacement therapy in Parkinson’s disease. Most importantly, for the first time, tyrosine hydroxylase and DOPA decarboxylase activities could be measured in postmortem basal ganglia, and were found to be reduced in Parkinson patients and striatal dopamine levels were found to be increased in Parkinson patients who received L-DOPA Hornykiewicz’s demonstration of the unique research value of frozen human postmortem brain material triggered the establishment of human brain tissue banks worldwide.

In 1976, Hornykiewicz was offered the position of professor and chairman in the newly founded Institute of Biochemical Pharmacology in Vienna. Most of his work here was devoted to neurotoxins, with the search for mechanisms of neurodegeneration. He had three main focuses: the excitotoxin kainic acid; the cholinergic toxin AF64A; and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP not only allowed a detailed study of monoamine neurotransmitter loss in rhesus monkeys, thanks to Hornykiewicz’s remarkable skills in meticulous dissection by hand of sliced frozen brains, but also revived his passion for translational research. As a result, in cooperation with Günther Schingnitz at Boehringer-Ingelheim’s CNS Pharmacology and Walter Kobinger and Ludwig Pichler from the Boehringer Research Institute, Vienna, a new class of (nonergoline) direct dopamine agonists (B-HT 920, talipexol, in Japan; the chemically closely related pramipexol in the Western Hemisphere) was profiled by Hornykiewicz in this primate model of Parkinson’s disease.

During this time, Professor Hornykiewicz continued as a visiting professor of the University of Toronto and, in 1978, established the Human Brain Laboratory at the Clarke Institute of Psychiatry. His collaborator in the Clarke Institute was Dr Stephen Kish, a creative researcher who had spent one year (1981) as a postdoctoral fellow in Oleh’s lab in Vienna to learn the HPLC method with electrochemical detection, which was already established there. Their collaboration led to numerous well-recognized papers on the neurochemistry of Down’s syndrome, Lesch–Nyhan syndrome, Huntington’s disease, and other neurological conditions and disorders. Most important was the highly cited study on the inter- and subregional neurochemical patterns of Parkinson’s disease, which formed the base for the in vivo diagnosis of the disease by positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging methods, and in vivo grafting studies.

Honors and Contributions to the Scientific Community

Numerous were the honors and awards that Professor Hornykiewicz received over the years. In 1979, together with Arvid Carlsson, he was awarded the Wolf Prize, for opening a new approach to the control of Parkinson's disease by L-DOPA. This award from Israel’s Wolf Foundation ranks among the most prestigious scientific awards. In fact, many Wolf Award winners had also gone on to win the Nobel Prize, including Arvid Carlsson, who won in 2000, together with Paul Greengard and Eric Kandel, for their discoveries in the field of signal transduction in the nervous system. In an open letter to the Nobel Committee for Physiology and Medicine, written in 2001, more than 230 scientists expressed that Oleh Hornykiewicz should have been included in the Award.

Oleh was the acting Chairman of the Institute for Biochemical Pharmacology, Vienna when, during the late 1980s, the idea of a Vienna Brain Research Institute emerged that would bring together four existing Institutes dealing with various aspects of neuroscience, including biochemical pharmacology, into one multidisciplinary Brain Research Center. Hornykiewicz’s personal efforts and his international standing became instrumental in this project and, in 1999, the Brain Research Institute (now known as the Center for Brain Research of the Medical University of Vienna) opened its doors.

Life after Retirement

Professor Hornykiewicz retired from the University of Toronto in 1992 and from the University of Vienna in 1995 as ‘Professor Emeritus’. From then until his recent death, he remained intellectually fit and interested in science. As a result, Oleh authored more than 50 scientific papers since his retirement, the last ones in 2017, including one on L-DOPA. Even up until 91 years of age, he spent most weekdays at his office in the Center for Brain Research of the Medical University of Vienna. He vividly discussed his ideas on various topics in neuroscience on a high scientific level, with unbroken and highly contagious enthusiasm for his field of research. It was only in 2017, 3 months after the death of his beloved Christina (who had become his wife in 1962 and was the mother of his four children), that he stopped going to the lab. During his last years, his interest in history increased and, when we visited him, we discussed scientific topics as well as history and humanities.

Torgny Svensson, MD, PhD (1945-2020)

Torgny Svensson, a superb mind and an inspiring colleague

Torgny Svensson, Professor emeritus of Pharmacology at Karolinska Institutet, succumbed to Covid-19 on Friday June 12, 2020, at the age of 75.  He is grieved by his wife Louise and their children Martin, Jenny and Michael, and missed by many friends and colleagues in Sweden and around the world.

Torgny Svensson was born on May 15, 1945, in Gothenburg, where he grew up and studied medicine. He received his MD in 1970 and defended his PhD thesis in 1971 at the Department of Pharmacology, Gothenburg University, with Arvid Carlsson, the Nobel Laureate, as the supervisor. In 1975 he became a licensed physician.

Torgny, contrasting most Swedish PhD students at that time, then moved to the United States for postdoctoral studies, spending two years (1973-1974) at Yale University working with George Aghajanian and colleagues – a period that strongly shaped his scientific approach, thinking and life, and that resulted, e.g., in a seminal paper demonstrating the autoreceptor-mediated reduction in the firing of noradrenergic neurons obtained with clonidine. After returning to Gothenburg, he formed his own research group and established the single cell recording technique that he had picked up at Aghajanian´s lab – a technique that at that time was still not used much by psychopharmacologists. A number of important papers followed, e.g. on the physiological regulation of catecholaminergic neurons – and on how the activity of these nerve cells may be influenced by psychoactive drugs – that rapidly made him a leading authority in this field of research. After a period as visiting scientist at The Salk Institute (1981-1982) working with Floyd Bloom and George Koob, he was appointed professor of pharmacology at Karolinska Institutet in 1983, where he served as Chair and Vice-Chair during the period 1987-2004, and on the Nobel Assembly for almost two decades (1993-2010). In 1989 he was visiting professor at the Université de Lyon in France.

Torgny’s research centered, from the beginning, on monoamines, which is no wonder since he had Arvid Carlsson as supervisor and was highly influenced by his thinking. Among the many areas where Torgny made important contributions may be mentioned the involvement of locus coeruleus noradrenergic neurons in arousal and anxiety, the feed-back influence of antidepressant reuptake inhibitors on these nerve cells, the possible functional relevance of different firing patterns of dopaminergic neurons, the influence of nicotine and nicotine withdrawal on brain monoaminergic transmission, and possible mechanisms underlying the unique features of clozapine. In recent years, his explorations of interactions between monoaminergic and glutamatergic neurons in the prefrontal cortex provided intriguing support for how the efficacy of both antidepressant and antipsychotic drugs may be augmented by the use of various drug combinations. He published over 300 peer reviewed papers and is the inventor of a number of patents. As a recognition of his seminal work he received several international awards, including the ECNP Neuroscience Award, the Kraepelin-Alzheimer Medal of the Ludwig Maximilian University of Munich and just recently in 2020 the prestigious CINP Pioneer Award. It is sad that he never had the opportunity to formally receive the latter.

Combining a clinical understanding and the pharmacological competence required for drug development, Torgny was a scientist much in demand by pharmaceutical companies, and collaborated with many of these. This competence also made him a much sought-after and inspiring lecturer at symposia and big meetings. He had a huge international network of friends and collaborators and was a faithful attendant at the CINP, ECNP and ACNP congresses, where he enthusiastically took part both in advanced scientific discussions and in cheerful joking and gossiping.

During Torgny´s period as a very successful president of the Scandinavian College of Neuropsychopharmacology (SCNP) from 2001 to 2005, the annual meetings of this society attracted more attendants than ever before. Illustrating his standing in the international psychopharmacological sphere, he became President of the CINP in 2006, and held this position when the society celebrated its 50 years anniversary. We still remember the 2012 CINP World Congress in Stockholm where Torgny hosted a gala dinner in the Grand Hotel with a menu copied from the first the Nobel Prize Dinner in 1901 held in the same hotel.

Torgny was a person whom you did not easily forget, if you had had the privilege to meet him on a person-to-person basis. He was a great scientist always ready to discuss experiments and his most novel ideas in detail, and he inspired and guided a large number of PhD students through their journey to a successful defense. But he also had a broad knowledge of history and other subjects, and a sometimes drastic sense of humor that brightened any interaction with him. International neuroscience and psychopharmacology have lost a leading figure and a colorful personality.

By Siegfried Kasper, Hans-Jürgen Möller, Göran Engberg, Elias Eriksson and Tomas Hökfelt.

Alec Coppen, MD, DSc (1923-2019)

Dr Alec Coppen, who has died aged 96, was a psychiatrist who was among the first to investigate the link between the neurotransmitter serotonin and clinical depression as well as carrying out early studies about the role of folate and lithium in the treatment of mood disorders.

Dr Coppen was a pioneer of the scientific study of the effects of drugs on the brain and behaviour at a time when such research was often regarded with suspicion. In 1967 he proposed that antidepressants worked by increasing the amount of norepinephrine available in the central nervous system.  However, his research then suggested that there were other neurotransmitters implicated in mood disorders, particularly serotonin.  He proposed that giving tryptophan – an amino acid which is converted to serotonin in the brain – might help those who were already on antidepressants to get better faster than those who were treated with antidepressants alone.  This theory became one of the most influential in psychopharmacology. He also went on to investigate the effects of taking antidepressants with folic acid in addition to the treatment regimen.

Dr Coppen also evaluated the merits of lithium, now widely used to treat bipolar disorder and recurring depressive illness. While several studies had indicated that lithium might protect patients from relapses, various august figures at the Institute of Psychiatry remained unconvinced. The results of Dr Coppen’s own controlled trial, published in 1971, confirmed the benefits of lithium therapy and he went on to champion its effectiveness in the treatment of both unipolar depression and bipolar depression and was one of the very first researchers to suggest that lithium was anti-suicidal, a property which has been confirmed in large scale studies.

From 1964 until his retirement in 1988 Dr Coppen was a consultant psychiatrist at West Park Hospital in Epsom, Surrey. He was a consultant for the World Health Organisation from 1970 and served as President of the International College of Neuropsychopharmacology from 1988 to 1990. Dr Coppen was a founding member of the British Association for Psychopharmacology (which he also served as President) and the first recipient of the BAP lifetime achievement award.  He was made an honorary fellow of the Royal College of Psychiatrists in 1995 and in 2000 he received the CINP Pioneer in Psychopharmacology Award.

He married, in 1952, Gunhild Andersson (she died in 2007); they had one son, Michael.

Dr Alec Coppen, born January 29 1923, died March 15 2019

Per Bech (1942-2018)

On May 9, 2018, Per Bech, a leading psychopharmacologist over four decades and an active contributing member of our International Network for the History of Neuropsychopharmacology, passed away. Born in Svendborg, Denmark, on January 12, 1942, at the time of his death, Bech was 76 years old, but still fully active as Professor of Clinical Psychiatry and Head of the Psychiatric Research Unit at the New Zealand Mental Health Center, University of Copenhagen.
A 1969 graduate of the medical school of Copenhagen University, Per Bech became involved in psychopharmacology and psychometrics during his training in psychiatry at Aarhus University in Aarhus, Denmark. Following the footsteps of Emil Kraepelin (1856 – 1926), who studied dose-effect relationships with alcohol by measuring reaction time in Wilhelm Wundt’s (1832 -1920) laboratories, Bech studied dose-effect relationships with tetrahydrocannabinol with the employment of various psychological measurements (Ban 2016). Then, in the 1970s while working in Ole Rafaelsen’s (1930 -1987) Psychochemical Institute in Copenhagen, Bech became involved in the evaluation of validity of rating scales for measuring changes in the course of treatment of depression and mania, as well as in developing new scales. His dissertation on the “clinical and psychometric validity of rating scales in depression and mania” earned him the degree of Doctor of Medical Science in 1981. In the same year, following the publication of his first book, Rating Scales for Affective Disorders: Their Validity and Consistency, he received the prestigious Anna-Monika Prize for his contributions in the field of depression. (Bech 1981).

During the 1980s pharmacotherapy with psychotropic drugs became the primary form of treatment for mental disorders and with the introduction of Third Edition of the Diagnostic and Statistical Manual of the America Psychiatric Association, in 1980, psychiatric patients were classified by diagnoses, accessible to “psychometrics” and treated with drugs developed by a methodology based on “psychometrics.” An active participant of this development, Bech broadened the scope of his research to study scales employed in a wide variety of mental disorders and in 1986 he presented his findings in a “Mini-compendium of rating scales for states of anxiety depression, mania, schizophrenia with corresponding DSM-III syndromes” written in collaboration with Marianne . Kastrup and Ole Rafaelsen.  By the 1990s, Bech’s research embraced mental health, and not only its pathology; he was developing instruments suitable for measuring also the effects of treatment on enjoyment of life and adaptation to society, as reflected in his book, Rating Scales for Psychopathology, Health Status and Quality of Life, published in 1993.

Actively involved in clinical investigations with psychotropic drugs and psychometrics throughout the years, in 2008 Bech was appointed professor of applied clinical psychometrics at Copenhagen University. Four years later, in 2012 he published Clinical Psychometrics, a tour de force,  in which he defined the field, outlined its development, summarized its progress between 1993 and 2012 and conceptualized his own  contributions to it over four decades. The two major models for testing  the  measurement aspect of rating scales, Hotelling’s Principal Component Analysis for identifying the structure of items included in a scale,  and Rasch’s  and Mokken’s Item Response Theory models for examining the “scalability” of rating scales, are given special attention. Yet,  at the heart of the monograph is Bech’s “pharmacopsychometric triangle” of which one of the angles “covers” measurements relevant to therapeutic (desired) effects, another angle covers measurements relevant to side or adverse (unwanted) effects and the third, measurements relevant to patients’ quality of life. The “psychometric triangle” is a conceptual construct for translating the therapeutic ratio of psychotropic drugs into measurable benefits of treatment in patients’ well-being, based on patients’ “subjective” experience.
While in Clinical Psychometrics Bech provides a conceptual framework for “measurement – based care of mental disorders,” in his Measurement-Based Care of Mental Disorder, published in 2016, just two years before his untimely death,  he translates theory into practice by selecting easy to use, short and valid rating scales and questionnaires for use in both: clinical research throughout the clinical development of psychotropic drugs and in daily practice in evaluating their effect in clinical practice. Adoption of the scales he selected in clinical routine would open up the possibility of an accountable clinical practice in psychiatry. It would also generate information that would allow for rational decisions whether adoption of a  particular new drug would offer any advantages in treatment. With publication of his last book Bech has opened a new horizon in which evidence-based care will be replaced by measurement-based care in psychiatry.

Per Bech’s contributions were crowned in 2010 with the “pioneer award” of the International College of Neuropsychopharmacology (CINP).

References:

  • American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. DSM-III. Washington: American Psychiatric Association; 1980.
  • Ban TA. Foreword. In Bech P. Measurement Based Care in Mental Disorders. New York: Springer; 2016.
  • Bech P. Rating scales for affective disorders: their validity and consistency. Acta Psychiatr Scand Suppl. 1981;295:1-101.
  • Bech P. Clinical Psychometrics. Oxford: Wiley – Blackwell; 2012.
  • Bech P. Measurement Based Care in Mental Disorders. New York: Springer; 2016.
  • Bech P. Rating Scales for Psychopathology, Health Status and Quality of Life. New York: Springer; 1993.
  • Bech P, Kastrup M, Rafaelsen O. Mini rating scales for states of anxiety, depression, mania, schizophrenia with corresponding  DSM-III syndromes. Acta Psychiatrica Scandinavica 1986; 326:  1 -37.

Ban TA In Celebration of Per Bech. inhn. org. Biographies (Eulogies). February 20, 2020

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.
              (by Johan Wingborg)

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 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, 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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