Julius Axelrod was an American biochemist who received a share of the Nobel Prize in Physiology or Medicine in 1970 for his work on neurotransmitters. His discoveries were foundational to pharmacology and neuroscience, leading to the development of many modern medications. Axelrod’s research changed the scientific understanding of how the nervous system functions and opened new avenues for treating a wide range of conditions.
From Lab Technician to Scientist
Julius Axelrod was born in New York City in 1912 to Polish Jewish immigrants. His father was a basket weaver, and Axelrod grew up in a poor neighborhood on the Lower East Side of Manhattan. Despite his modest background, he developed an early interest in science and pursued a bachelor’s degree in biology from the College of the City of New York, graduating in 1933. He initially aspired to become a physician but was rejected by every medical school he applied to.
A significant setback occurred when a laboratory accident, an exploding bottle of ammonia, cost him the sight in his left eye. This injury further complicated his career aspirations. For years, Axelrod worked as a laboratory technician, including a position at the New York City Department of Health testing vitamin supplements in food. He continued his education through night school, earning a master’s degree from New York University in 1941.
To advance his research career, Axelrod took a leave of absence from his work at the National Institutes of Health (NIH) in 1954 to pursue a doctorate. He enrolled at George Washington University Medical School and, by submitting some of his previous research, was able to complete his Ph.D. in just one year at the age of 43. This path from a long-term lab technician to a credentialed scientist was a testament to his perseverance.
Unraveling the Nervous System
When Axelrod began his research, scientists understood that nerve cells communicate by releasing chemical messengers called neurotransmitters, such as norepinephrine. Ulf von Euler had already identified norepinephrine as a primary transmitter. However, a major question remained: what happens to these neurotransmitters after they deliver their message? It was unclear how their signals were terminated to prevent constant nerve stimulation.
Axelrod’s research provided the answer. He discovered that the action of norepinephrine was primarily ended through a process called “reuptake.” His experiments showed that the same nerve endings that release the neurotransmitter also reabsorb it from the synapse, the small gap between nerve cells. This mechanism allows the neurotransmitter to be stored for later reuse.
This discovery identified a previously unknown process that regulates nerve signaling. Before Axelrod’s work, it was believed that enzymes primarily broke down neurotransmitters to inactivate them. While he also identified a key enzyme involved in this degradation, catechol-O-methyltransferase (COMT), the reuptake process proved to be the main “off switch.”
This finding revealed a new target for drug development. Understanding that nerve communication could be modulated by blocking this reuptake pump allowed researchers to design medications to alter brain chemistry. This work laid the groundwork for modern psychopharmacology.
Other Key Scientific Contributions
Long before his Nobel-winning research, Axelrod made a significant contribution to pain relief. While working with his mentor, Bernard Brodie, at Goldwater Memorial Hospital in the late 1940s, he investigated why a drug called acetanilide was effective but also toxic. Their research revealed that the body metabolizes acetanilide into a different, active compound that was responsible for the pain-relieving effects. This active metabolite was paracetamol, now widely known as acetaminophen.
This discovery was important because it isolated the beneficial component from its more harmful parent drug. The finding helped pave the way for the development of acetaminophen (sold as Tylenol) as a safe and effective non-aspirin pain reliever. It became one of the most widely used over-the-counter analgesics in the world.
Later in his career at the National Institute of Mental Health (NIMH), Axelrod turned his attention to the pineal gland, a then poorly understood organ. He and his team characterized the function of melatonin, a hormone produced by the pineal gland, and uncovered its role in regulating the body’s sleep-wake cycle, or circadian rhythms. This work provided the first real understanding of the pineal gland’s biological function.
The Axelrod Legacy
The most lasting impact of Axelrod’s work was its application to mental health treatment. His discovery of the neurotransmitter reuptake mechanism provided the scientific foundation for a new class of antidepressant medications. These drugs, known as selective serotonin reuptake inhibitors (SSRIs), include medications like Prozac and function by blocking serotonin reuptake, thereby increasing its availability in the brain. This approach revolutionized the treatment of depression and anxiety disorders.
Beyond his scientific discoveries, Axelrod cultivated a legacy as a mentor at the NIMH. He joined the institute in 1955 and became chief of the pharmacology section. For nearly three decades until his retirement in 1984, he trained and influenced a generation of young scientists, and several of his trainees went on to become leading researchers and Nobel laureates.
His influence extended beyond his own laboratory. He served on the editorial boards of multiple scientific journals and published articles in accessible publications like Scientific American to broaden public understanding of his field. Through his research and dedication to mentoring, Julius Axelrod’s work continues to underpin modern pharmacology and neuroscience.