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JULIUS AXELROD

By Irwin J. Kopin

Julius Axelrod (30 May 1912 – 29 December 2004) shared the 1970 Nobel Prize with Ulf von Euler and Bernard Katz for his discoveries related to catecholamine metabolism and termination of the actions of norepinephrine by reuptake into the nerve terminals from which it was released. In his Nobel lecture (Axelrod 1972), Julie cited over 50 of his papers that elucidated the regulation of norepinephrine biosynthesis, storage, release, metabolism, and inactivation, in brain, as well as at peripheral sympathetic nerve terminals. Equally important, he showed that drugs, such as amphetamine, cocaine and antidepressants affect norepinephrine reuptake.This means of terminating actions of neurotransmitters has been verified for other neurotransmitters; serotonin, dopamine, glutamate and  gamma-aminobutyric acid (GABA), providing an important target for drug development, particularly “serotonin-selective reuptake inhibitors” (SSRIs), e.g. fluoxetine (Prozac).

A short profile cannot adequately describe all of Julie’s many important other discoveries that help shape the development of Psychopharmacology and Neuroscience, fields that that did not exist until the middle of the 20th century. Nor can it adequately reflect an appreciation of his mentorship of a host of young physician-scientists that have progressed to leadership roles in academia and the pharmaceutical industry. With regard to the Prize, those of us who were privileged to have worked with Julie concluded that “Nice guys do win ball games.” Sol Snyder, in a bibliographic memoir of Julie’s “most improbable” scientific success story (Snyder 1987) and Julie’s own chronicle of “Journey of a Late Blooming Biochemical Neuroscientist” (Axelrod 2003) relate the evolution of his earliest employment in a laboratory measuring vitamins in foods, the beginning of a research career in 1945, when Bernard Brodie invited him to work in his laboratory at Goldwater Memorial Hospital on the metabolism of analgesics, which led to their discovery of acetaminophen, the move to the National Institutes of Health (NIH) and the work for which he obtained his PhD from George Washington University, and his recruitment to the National Institute of Mental Health (NIMH), where he spent to rest of his career. At NIMH, he began studies on metabolism of psychoactive drugs, but in 1957, with the discovery of vanillylmandelic acid (VMA) as the major urinary excretion product of epinephrine, he embarked on a second major field, the series of studies on catecholamines, for which he was awarded the Nobel Prize. His ability to distinguish important from trivial questions, his elegantly simple design of experiments to provide clear results, his style of mentorship to bring out the best in his postdoctoral students, Julie’s contributions to chronobiology via melatonin and pineal function, his studies of methylation of phospholipids and a host of other accomplishments followed in the more than three decades after he received the Prize. After his death, a number of lengthy tributes to him by former postdoctoral fellows were published, e.g. Sol Snyder (2005), Leslie Iversen (2006), as well as his featured inclusion in 'Robert Kanigel’s “Apprentice to Genius: The Making of a Scientific Dynasty” (Kanigel 1986). There is also brief summary about Julie and his research in Wikipedia.

Axelrod J. Noradrenalin: Fate and Control of its Biosynthesis, Nobel Lectures, Physiology or Medicine 1963-1970.  Amsterdam: Elsevier Publishing Company; 1972.

Axelrod J. Journey of a late blooming biochemical neuroscientist. J. Biol. Chem. 2003; 278:1-13.

Iversen L. Julius Axelrod 2006  Biogr. Mems Fell. R. Soc. 87 (December)

Kanigel R. Apprentice to Genius: The Making of a Scientific Dynasty. Baltimore: The Johns Hopkins University Press; 1986.

Snyder SH. A Biographical Memoir of Julius Axelrod. 2005 Biographical Memoirs of the National Academy of Science; Volume 87

 

Irwin J. Kopin
November 6, 2014