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Obituary: Sydney Spector, former ASPET President, pharmacology pioneer passes away at 88

 

Sydney Spector (1923-2012)

Sydney SpectorSydney Spector, age 88, passed away October 26, 2012. Syd was an excellent athlete and really loved sports where the best of the best are described as multi-tool players. Syd was a multi tool player as well — the best of the best as an innovative scientist, caring teacher/mentor, and beloved husband, father and grandfather.

Syd’s entry into Pharmacology was delayed by his service in World War II where at the age of 20 he fought in the Normandy Invasion, the Battle of the Bulge and other European campaigns. A pioneer and worldwide leader in pharmacology, Syd’s early exposure to pharmacology occurred during a fellowship with Oliver Lowry, where he interacted with Bob Furchgott and others at Wash U in St Louis. From there with a growing family, he accepted a job in R and D in at Wyeth Pharmaceuticals. These opportunities led him to earn his PhD in Pharmacology from Jefferson Medical School in 1957. Syd participated in “the golden age of pharmacology” where he spent the early part of his career conducting research at the Heart, Lung, Blood Institute at the National Institutes of Health. Syd’s early collaborations with Bernard Brodie and colleagues were cornerstones to understanding the role and dynamics of the neurotransmitters, norepinephrine and serotonin in brain function, disease and drug action. He was among the first to study monamine oxidase inhibitors and provided key evidence for the general hypothesis that norepinephrine was usually stimulatory and serotonin inhibitory in the CNS. Syd’s work was key to pharmacology in establishing biogenic amines as a scientific foundation of affective disorders and psychoactive drug therapeutics — all accomplished within four years after his PhD; but he was just beginning.

In 1961, he began collaborating with Al Sjoerdsma and Sidney Udenfriend at the NIH and expanded his interests towards increasing biological and clinical relevance. He focused on the role of biogenic amine synthetic pathways and turnover showing that tyrosine hydroxylase was the rate limiting enzyme in catecholamine synthesis, and that alpha methyl tyrosine was a selective tyrosine hydroxylase inhibitor; and an enormously important tool to study catecholamine dynamics in disease and therapeutics. Together with his colleagues, Syd also showed that end product inhibition by catechols regulated tyrosine hydroxylase and as catechol levels increased, feedback inhibition of tyrosine hydroxylase occurred. These studies on catecholamine dynamics were among the most highly quoted and referenced scientific papers from 1965-1975.

Syd Spector was a great collaborator; and these synergistic studies with others established his leadership in the identification of important scientific questions but perhaps even more importantly, in the development and use of highly innovative methods necessary to answer those questions. Syd’s attention turned to the role of catecholamines in hypertension where he was among the first to use genetic spontaneously hypertensive rats as a model system. He defined the role of alpha methyl dopa which ultimately became clinically useful, on catecholamine synthesis and the importance of norepinephrine turnover in hypertension and the cardiovascular system.

Syd joined the Roche Institute of Molecular Biology as a founding member and department head in 1968 and added the tools of immunology to his skill set via a sabbatical with Herman Eisen at Washington University. Once again, Syd became a pioneer, opening the new important field of immunopharmacology. He developed and used highly sensitive and specific antibodies to neurotransmitters and drugs as “receptor like fishing hooks” to track and search for important compounds in the body. He conducted pioneering experiments with these antibodies including establishing their important potential use as immunotherapy for modifying drugs of abuse. Antibodies created in Syd’s lab were applied to the assay of many drugs and endogenous compounds such as barbiturates, reserpine, imipramines, morphine, naloxone, chlorpromazine, serotonin, acetylcholine, and curare — for basic research, clinical and forensic use. As diagnostic assays his methods achieved sensitivity and assay simplicity not previously possible or practical. Several of these ideas and tools were embraced by Hoffmann La Roche as products, which significantly accelerated Roche’s diagnostic franchise. Using the morphine antibody as a tool, Syd also showed for the first time the presence and potential importance of endogenous morphine in the human body. He also significantly advanced our understanding of benzodiazepines and peripheral benzodiazepine receptors using a multiple technologies and pharmacologic studies.

Syd also excelled in his dedication to nurturing and developing scientific talent, launching the careers of a legion of scientists, a number of whom became drug discovery and research leaders in their own right. As excited as Syd was about the science and his innovative new discoveries and tools, the success of his colleagues and students was even more thrilling and sustaining to him. Syd said the following in an interview with Fridolin Sulser in 1998 for the ACNP. “I am reminded of a Chinese maxim that if you plan for a year you plant rice, if you plan for decade you plant trees and if you plan for a millennium you teach.” Once Syd introduced a new approach to those in his lab, he freely shared his ideas and advice, reaping enormous satisfaction in the new discoveries and collaborations of the next generation of scientists that he trained.  "I" was not a big word in Syd’s vocabulary. He was humble to the very core. There is a Yiddish word for a kind and decent person that comes to mind that many of us would agree applies to Syd — he was a reference standard “Mensch,” a trait as admirable as his scientific brilliance.

Syd’s sense of humor permeated his life and interactions with colleagues, his family and friends. “Humor is a rubber sword — it allows you to make a point without drawing blood (Mary Hirsch).” He was the master of the one liner, which seemed a talent that he fine-tuned with age. While Syd could be appropriately critical, this was always accomplished with a spirit of helpfulness and kindness.

Syd published more than 200 scientific papers and received multiple awards and honors (including the ASPET Award in Experimental Therapeutics, and the Julius Axelrod Award) and was elected President of ASPET in 1979. After retiring from the Roche Institute, Syd moved to Nashville, Tennessee in the early 1990’s where he enjoyed an appointment in the Pharmacology Department at Vanderbilt University. Here, he continued to be actively engaged in scientific thought, nurturing students and reconnecting with his athletic and artistic interests via daily gym workouts and painting.

Anyone who worked with Syd was welcomed into the Spector family by Syd and Bettie. There, we could all see and feel their love and friendship — what a great team Syd and Bettie, his wife for 64 years, were. They were devoted to each other, and enjoyed travelling the world together usually related to some scientific undertaking or meeting; and they much enjoyed the interactions and friendship of their colleagues and their children.

Syd and Bettie were caring and supportive parents to Neil and Faye, both of whom became physicians. They in turn took great care of Syd and were so enormously proud of him. After relocating to Chapel Hill, North Carolina, Syd was energized in his later years through his ongoing scientific association with Neil. He continued to have innovative ideas and tested them. At age 76, Syd and Neil (an outstanding scientist and oncologist) published an excellent paper and obtained a patent on a new anticancer compound as a prototype for an entirely novel approach to cancer therapy and to aurora kinase regulation, based on Syd’s ideas. As late as 2011, Syd continued to work in the lab with Neil, testing new hypotheses and maintaining a full and active life, priding himself on a rigorous daily exercise routine that was the envy of those half his age. Throughout his life, Syd’s style, innovative actionable ideas and enthusiasm for science and drug discovery are qualities that defined him as a very special person, unique scientist, and leader.

Syd Spector was indeed a multi-tool person, excelling in matters of family, teaching and outstanding scientific accomplishment. Syd’s loss as a scientist and friend is enormous, yet his legacy continues in his wonderful family and his enormous contributions to pharmacology. His colleagues and students will always be so very grateful and better that we knew and learned from Sydney Spector.

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Barry A. Berkowitz, Ph.D (Bessor Pharma, LLC Framingham, MA, 01701)

Marlene L. Cohen, Ph.D (Distinguished Research Fellow (retired), Eli Lilly and Company; Creative Pharmacology Solutions LLC, Carmel, IN, 46032)

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