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Scientist Emeritus

Irwin Kopin, M.D.

9000 Rockville Pike
Bethesda MD 20892

Irwin J. Kopin, M.D.

Dr. Irwin J. Kopin was world renowned for his catecholamine research here at the NIH. Dr. Kopin led the Laboratory of Clinical Science at the National Institute of Mental Health (NIMH) during the early, exhilarating days of neuropsychopharmacology side by side with such luminaries as Drs. Julius Axelrod and Seymour Kety. His seminal research on the characteristics and metabolism of catecholamines — a class of chemicals that includes epinephrine, norepinephrine, and dopamine — provided the backbone for major clinical advances in neurological and psychiatric disorders and helped bring the NIMH international distinction in the 1960s. A Scientist Emeritus since his retirement in 1999, Dr. Kopin was well known and an active participant in the Clinical Neurocardiology Section at the NINDS. He was a radiant fixture on the NIH campus. He continued to publish papers vigorously during his retirement, as well, with the last appearing May 2017 in Cellular and Molecular Neurobiology journals.

Dr. Kopin was born in 1929 and raised in the Bronx, graduating from the famed Bronx High School of Science before attending City College in New York. He soon transferred to McGill University, where he earned a B.S. in Biochemistry in 1951 and an M.D. in 1955. During his second year of medical residency at Boston City Hospital, he joined the Public Health Service and was assigned as a statistician to work on tuberculosis, reportedly because his transcript noted he had taken mathematics courses in college. As related in the book NINDS at 50, however, when Dr. Kopin eventually revealed he wasn't a mathematician, he lost that job. And that's what brought him to the NIH circa 1957, for a research position in the Laboratory of Clinical Science at the NIMH under the direction of Dr. Seymour Kety, a renowned scientist even at this early date who was introducing basic science rigor to the field of psychiatry.

It was during this time that Dr. Kopin began what would be a long collaboration and friendship with Dr. Julius Axelrod, who shared the 1970 Nobel Prize in Physiology or Medicine for work on the release and reuptake of catecholamines. In the late 1950s, Dr. Axelrod had just discovered catechol-O-methyltransferase, an enzyme that metabolizes catecholamines. A question arose as to which was more important in terminating the action of epinephrine: COMT or monoamine oxidase. Dr. Kopin conceived and ultimately performed the study. (The answer is COMT.) Dr. Axelrod was impressed, and the two became solid collaborators soon thereafter. With Dr. Axelrod and others, Dr. Kopin published numerous original research articles that were foundational in the area of the disposition and metabolism of catecholamines. His research achievements also include reporting that MPTP produces an animal model of Parkinson's Disease. Much more of Dr. Kopin's work is detailed in the book NINDS at 50.

Dr. Kopin was Chief of the Laboratory of Clinical Science from 1969 to 1983. He then became Scientific Director of the National Institute of Neurological Disorders and Stroke (NINDS), a position in which he served with great distinction for more than a decade, until 1994. With his broad knowledge of neuroscience and medicine, Dr. Kopin strengthened both the basic and clinical neurosciences programs in NINDS. He was collaborative in his administrative duties as well, and he developed a novel and effective administrative triad with Dr. Mark Hallett as Clinical Neuroscience Director and Dr. Ernst Freese and later Dr. Hal Gainer as Basic Neuroscience Directors. Also at the NINDS, he was in charge of the Clinical Neuroscience Branch. Dr. Kopin’s awards included the PHS Distinguished Service Medal in 1980 and in 1990; honorary membership in the Royal Society of Medicine in 1993; and the Paul Hoch Award for Distinguished Service in 2004.

Throughout his career, Dr. Kopin demonstrated an unstinting commitment to the mission of the NIH and more generally to advancing medical scientific knowledge. He authored or co-authored more than 730 articles, reviews, and book chapters, including several this year. His collaborations with many leaders in the field provided the growing points that shaped the direction of much of present day knowledge about catecholamine systems, both inside and outside the brain. Scientific acumen aside, Dr. Kopin is perhaps as well known for his mentorship to scores of postdoctoral researchers, many of whom have gone on to occupy key positions in academic medicine or the pharmaceutical industry. Dr. David S. Goldstein, who leads the intramural NINDS Clinical Neurocardiology Section, was one such person touched by Dr. Kopin. In a dedication to his recent book, Principles of Autonomic Medicine, Dr. Goldstein described Dr. Kopin as "an example of intellectual rigor, productivity, perspective, and integrity, an inspiration throughout my career at the NIH."

Dr. Kopin's research career began at a time that there was great interest and an emerging series of discoveries about neurotransmitters in the brain and peripheral nervous systems. In 1957, only acetylcholine and norepinephrine were known to be neurotransmitters. Relatively little was known about their formation, mode of action, role in disease, or pharmacology.  At Dr. Kety’s urging he began studies on the metabolism and disposition of norepinephrine (NE) with Dr. Julius Axelrod and participated in the experiments that described re-uptake of NE as the means of terminating the actions of that neurotransmitter.  They discovered new metabolites and that monoamine oxidase was the main intra-neuronal pathway for NE whereas O-methylation was predominantly extra-neuronal. Compounds that resemble the chemical structure of NE were found to be capable of replacing it and being released as relatively inactive “False Transmitters”. Their formation and accumulation in sympathetic nerves account for the paradoxical hypotensive effects of MAO inhibitors. Others, labeled with positron-emitting isotopes, were developed for PET imaging of neurons that accumulate these compounds. The first patient to be described with MPTP toxicity-induced parkinsonism was reported from the laboratory.  Dr. Kopin's lab also introduced use of MPTP-toxicity as animal models of PD for testing new therapies. As well as PD, they studied other areas related to catecholamines including disorders of blood pressure regulation and dysautomias, antipsychotics, and various types of stress.

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