A leading authority on the relationship between brain chemistry and behavior and on the neurotoxicity of various prescription and illicit drugs, Lewis S. Seiden, PhD, professor emeritus of pharmacological and physiological sciences and of psychiatry at the University of Chicago, died Thursday, July 26, in the Vitas Hospice unit at Mercy Hospital in Chicago after a 50-year struggle with dystonia.
Seiden, 72, was one of the world’s experts on how drugs, especially the amphetamines, could selectively damage certain neurons, particularly those that produced the neurotransmitters dopamine and serotonin — chemical signals that relay messages within the brain. He methodically demonstrated that this damage occurred in rats, guinea pigs, cats, and nonhuman primates. In rats, he reported, “one high dose of methamphetamine is enough to cause damage. Prolonged dosage seems to make it worse.”
These studies “opened up a whole research field,” recalled former colleague Charles R. Schuster, PhD, who went on to become Director of the National Institute on Drug Abuse. “Students who were around at that time … made a lifetime profession out of studying the mechanisms of neurobehavioral toxicity of amphetamine and amphetamine analogues.”
Data collected by Seiden and Schuster played a key role in persuading the federal Drug Enforcement Agency to declare the popular mood-altering drug Ecstasy (MDMA, chemically similar to the stimulant methamphetamine) a Schedule 1 controlled substance in 1985.
Seiden also testified before the Food and Drug Administration in 1996 about potential serotonin neurotoxic effects of another stimulant, dexfenfluramine. Although dexphenfluramine, sold as Redux, was approved for treatment of weight loss in 1996, both dexfenfluramine and fenfluramine (often taken with phentermine — a combination popularly known as fen-phen) were withdrawn from the market in 1997 because of potentially lethal cardiovascular side effects, now thought to be related to serotonin.
“Lew Seiden was not only a brilliant scientist but also a warm human being, curious about the whole world and a joy to work with,” said former graduate student George Ricaurte, MD, PhD ’79, now a professor of neurology at Johns Hopkins University. “He had a unique ability to talk to anyone, a genuine interest in what they had to say, and the capacity, when necessary, to disagree without being disagreeable.”
“He was, in many ways, typical of what the University is all about,” Ricaurte added, “a solid, extremely bright, scholarly individual going about the advancement of knowledge, but doing so with a marvelous sense of humor and a complete lack of pretentiousness.”
Born August 1, 1934, in Chicago, Lewis Stanford Seiden grew up in Chicago’s South Shore neighborhood. When his family moved to newly created suburb of Park Forest, he attended a nearby rural high school for two years before he was granted early admission and a full-tuition scholarship to the University of Chicago.
At age 20, shortly before his expected graduation, Seiden was stricken with dystonia musculorum deformans, a disease characterized by uncontrollable muscle contractions. He spent a year convalescing. Dr. John Mullan, then head of neurosurgery at the University, made it possible for Seiden to return to his studies, with creative peripheral neurosurgical procedures. “I want to make it possible for you to sit in a chair and drive a car,” Seiden often quoted Mullan as saying. Despite considerable residual disability, Seiden did return, earning his AB in liberal arts from the University in 1956, and his SB in biology in 1958.
He had originally planned to go on to medical school but his dystonia made him reconsider. Instead, according to his son Samuel, the illness tilted his interests toward neurobiology. Although it left him with balance, movement and speech impairments, his dystonia did not keep him out of the laboratory, interfere with his teaching or prevent him from continuing his life-long hobby of sailing on Lake Michigan.
In 1962, Seiden completed his PhD in biopsychology at the University of Chicago. He did post-doctoral research with Arvid Carlsson at the University of Goteborg, Sweden, where he introduced behavioral pharmacology to their research. Carlsson, who received the Nobel Prize for medicine in 2000, later commented, “The remarkable thing about Lew’s stay with us, was that he was able to teach us just as much as we could teach him.”
“As a scientist he could see aspects of a problem that other people just didn't notice,” said his wife Anne, a physician, whom he met when they were both graduate students in psychology at the University of Chicago in 1956 and married in 1962. “He was interested not just in how a drug influenced a patient’s behavior but also in how individual differences in patients could alter the effects of a drug.”
Seiden returned to the University of Chicago as a research associate in pharmacology in 1963. He then did a second post-doctoral fellowship with Keith Killam at Stanford, in 1964-65, and returned to Chicago an instructor in the Departments of Pharmacology and Physiology and of Psychiatry in 1965. He never left. He rose steadily through the academic ranks, becoming an assistant professor in 1967, associate professor in 1972 and full professor in 1977. He also taught in the College and was a member of the Committee on Neurobiology and the Brain Research Institute.
Seiden quickly established himself as one of the pioneers in the emerging field of psychopharmacology, the study of the behavioral effects of drugs and how they work in the brain. A prolific author, he published more than 220 scientific papers, 40 book chapters on neurochemistry, the brain and behavior, drug effects, and neurotoxicity. He co-authored a 1977 textbook with Linda Dykstra, then one of his students, titled Psychopharmacology: A Behavioral and Biochemical Approach. He served on the editorial board for several specialty journals, including Biological Psychiatry and the Journal of Pharmacology and Experimental Therapeutics, where he also served as a field editor.
Seiden was selected to serve on various national committees, including the President’s Advisory Committee on Mental Health in 1978, the board of scientific counselors for the National Institute of Environmental Health Services, and the Life Sciences Working Group for the National Aeronautics and Space Administration, as well as consistent participation in National Institutes of Health research review committees.
He won many awards for his research. He was elected a Fellow of the American Association for the Advancement of Science and of the American Psychological Association. In 1999 the University of Goteborg awarded him an honorary doctorate in medicine. In 2002 he received the University of Chicago’s Gold Key Award, which recognizes outstanding and loyal service to the Biological Sciences Division and to the University.
He was also known as a teacher. Seiden trained more than 30 doctoral students, including many scholars who went on to leading roles in the field. “Lew was someone who really taught by example,” Ricaurte said. “He allowed his students a great deal of independence, yet his door was always open, and he was always excited to look at their data.”
Seiden is survived by his wife, Anne Seiden, MD ’64, of Chicago; their three children: Alex (Larraine) Seiden, Evelyn (Toby) Ivey, DVM; and Samuel C. Seiden, MD ’06; and one grandson, Lewis George Seiden, all of whom reside in the San Francisco Bay area.
The memorial service will be held on Sunday, August 19th, at 5 pm in the University of Chicago’s Bond Chapel, 1050 E. 59th St. A reception will follow at the Quadrangle Club, 1155 E. 57th Street. In lieu of flowers, donations may be made to the Dystonia Medical Research Foundation, http://www.dystonia-foundation.org, One East Wacker Drive, Suite 2430, Chicago, Illinois 60601-1905.