Julius Axelrod Biography
Julius Axelrod
May 30, 1912 – December 29, 2004
Julius Axelrod was one of the twentieth century’s greatest biochemical pharmacologists, a respected mentor and colleague to many. He shared the Nobel Prize in Physiology and Medicine in 1970 for his discovery that catecholamine (epinephrine and norepinephrine) neurotransmitters of the sympathetic nervous system are inactivated through their reuptake by presynaptic nerve terminals, an unprecedented concept at the time for how neurotransmitters work.
Axelrod’s story is one of a man whose keen interest in science despite not having elaborate academic credentials. He grew up the son of a poor basket-maker in New York City. After graduation from the City College of New York in 1933, he applied to numerous medical schools, only to be rejected. This was the time of the Great Depression, and Julius Axelrod was fortunate to find work at the Harriman Research Laboratory at New York University, where he assisted Dr. K. G. Falk with his research on enzymes in malignant tumors. In 1935, laboratory funds ran out, and Axelrod obtained a position as a chemist in the Laboratory of Industrial Hygiene, New York City Department of Health, where he was tasked with monitoring the vitamin content of foods. In 1942, he received a M.S. degree in Chemistry at New York University after taking night courses for several years. He was deferred from the World War II draft due to the loss of one eye in a laboratory accident.
In early 1946, there was an unexpected change in the career of Julius Axelrod. As he later described it, “At that time, analgesic drugs such as acetanilide and phenacetin were widely used. Some people who used excessive amounts of these drugs became habituated and developed methemoglobinemia. An independent organization, the Institute for the Study of Analgesic and Sedative Drugs, approached Dr. George B. Wallace, then president of the Laboratory of Industrial Hygiene and retired Chairman of the Department of Pharmacology at New York University, for advice. Dr. Wallace asked me if I would like to work on this problem and he suggested that I consult Dr. Bernard B. Brodie.” During this assignment, Axelrod identified the metabolite, N-acetyl-p-aminophenol, more commonly known as acetaminophen, as being responsible for the analgesic effects of the most popular headache remedy (aspirin-phenacetin-caffeine) at that time. This analgesic metabolite to which Axelrod brought attention is now widely known as Tylenol. Thus began an interest and scientific career in understanding how drugs act.
In 1950, Axelrod accepted a position at the newly formed National Institutes of Health (NIH). He retained his interest in drug metabolism and is credited with the discovery of the cytochrome P450 family of drug-metabolizing enzymes, a classic advance in pharmacology
Each of these research discoveries was made without Julius Axelrod having a doctoral degree. With pressure from friends, however, Axelrod finally obtained his Ph.D. from George Washington University in 1955 at the age of 42. He was promptly made head of pharmacology in the Laboratory of Clinical Science at the National Institute of Mental Health, NIH. It was in this capacity that he made two more significant discoveries. First, in continuing with his interest in metabolizing enzymes, Dr. Axelrod discovered an enzyme that uses S-adenosylmethionine to methylate catechols, which he termed catechol-O- methyltransferase (COMT). This led to the identification of several additional methyltransferases. Second, although it was thought at the time that neurotransmitter inactivation occurred primarily via enzymatic degradation, Axelrod discovered that rather than being metabolized, adrenaline or noradrenaline inactivation occurred via their re-uptake into neurons. Further, his research identified compounds that could inhibit the re-uptake of neurotransmitters, thereby contributing to the eventual discovery of antidepressants, including fluoxetine (Prozac).
Dr. Axelrod chose to work in a small laboratory of three or four scientists. He had the gift as a mentor, carefully structuring research projects for new students, encouraging independent thinking, and exhibiting a positive demeanor towards his students’ efforts no matter how interesting the experimental results. Axelrod thoroughly enjoyed scientific discovery. This showed in both his research and mentoring activities.
For additional perspectives on the life and career of Dr. Julius Axelrod, see the following:
Axelrod, J (2003) Journey of a Late Blooming Biochemical Neuroscientist, J. Biol Chem 278: 1 –13.
Snyder, SH (2005) Julius Axelrod (1912 – 2004), Nature 10: 593.
Snyder, SH (2006) Turning off Neurotransmitters, Cell 125: 13 – 15.
Snyder, SH (2007) Biographical Memoirs: Julius Axelrod, Proc Amer. Philosophical Soc. 151: 82 – 90.
About the Julius Axelrod Prize
The Julius Axelrod Prize was established to honor a scientist with distinguished achievements in the broad field of neuropharmacology or a related area and exemplary efforts in mentoring young scientists. The prize, which includes $25,000, is presented each year at the Society's annual meeting. The recipient is invited to speak at a symposium organized by three institutes of the National Institutes of Health - the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. Nominees do not have to be SfN members.