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Nobel Laureate Axelrod, Neuroscience Pioneer

Press Release

Nobel Laureate Julius Axelrod, Ph.D., an NIMH researcher since 1955, died in his sleep early Wednesday morning, December 29, 2004. Axelrod is probably best known for his work on brain chemistry in the early 1960's that led to our modern-day treatments for depression and anxiety disorders. He inspired generations of neuroscientists during his long career at the National Institutes of Health (NIH). In 1996, NIH awarded him the title Scientist Emeritus.

"Dr. Axelrod was one of the giants upon whose shoulders today's neuroscientists stand. His contribution to the fields of mental health and neuroscience make possible current breakthroughs on mood and anxiety disorders, and myriad other areas," said Thomas R. Insel, M.D., NIMH director. "His legacy lives on in the work of others. He will be greatly missed."

In 1970, Axelrod, known to his colleagues as "Julie," was awarded the Nobel Prize in Physiology or Medicine for his discoveries about how brain cells communicate with each other. He explained how neurotransmitters operate in the brain, forever altering the way modern antidepressant drugs are designed. Axelrod laid the groundwork for the treatment of anxiety and depression. He coined the phrase 're-uptake' inhibitors, referring to the 're-uptake' mechanism in brain cells that regulates the level of neurotransmitters available, influencing how neurons communicate. This revolutionary understanding of the brain's chemistry led to the modern generation of antidepressant medications—Selective Serotonin Reuptake Inhibitors (SSRIs).

Colleagues say Axelrod had a remarkable approach to discovery, not only because of the breadth and depth of subject matter, but also his attitude in the lab. He mentored and trained more than 70 scientists, many of whom went on to become leaders in brain research. One of his most distinguished protégés, Solomon H. Snyder, M.D., at Johns Hopkins Medical School, Baltimore, and co-discoverer of the brain's opiate receptor, called Axelrod, "a humble giant of neuroscience and pharmacology. Most will agree that his contributions to our understanding of how drugs act in the brain was greater than any other scientist of the last half of the 20th century. Julie never tooted his own horn, preferring the lab to the lecture circuit. Indeed, at a banquet honoring Julie following his receipt of the Nobel Prize, he quipped, 'it seems these honors are a conspiracy to keep me out of the lab.'"

Axelrod's studies of brain chemicals were far from his only laudable success in science. He also helped to discover the pain-relieving properties of acetaminophen, better known by its brand name, Tylenol.

Axelrod took a circuitous route through science, initially hoping to be a physician but he was rejected from all the medical schools to which he applied. Refusing to accept defeat, Axelrod began his career by using his degree in biology and chemistry to test vitamin supplements for the New York City Department of Health's Laboratory of Industrial Hygiene. While at that lab, he took night courses towards his Master of Science degree in chemistry. He wrote his master's thesis on the chemical breakdown of enzymes in cancerous tumor tissues.

In 1949, Axelrod joined the NIH at the then National Heart Institute (now the National Heart, Lung, and Blood Institute), where he studied the tissue distribution and metabolism of caffeine, amphetamines, ephedrine, and narcotic drugs. In 1953, he delved into diabetes research, where he described a new class of enzymes in liver microsomes that metabolized drugs by a variety of pathways—all before receiving his Ph.D.

Axelrod returned to school in 1954 and one year later received his Ph.D. from George Washington University. He promptly began a new career in neuroscience research at NIMH. His early work at NIMH focused on the metabolism of lysergic acid diethylamide (LSD) and other psychoactive drugs. He went on to revolutionize the field of pineal gland research, discovering melatonin as the gland's key hormone. He also made key discoveries about the regulation and interaction of stress hormones.

Until his retirement in 1984, Axelrod worked on research projects that sought to elucidate the relationship between drugs and behavior. His research suggested that mental states were the result of complicated physiology and brain chemistry, rather than the sole result of psychological or environmental factors. For at least 10 years after his official retirement he continued to come to the lab about three times a week as an unpaid guest to conduct research on transduction of neurotransmitter signals in cells. More recently, he had been involved in studies on the natural ligand of the cannabinoid receptor anandamide. His many contributions are still felt among his colleagues.

Reflecting about his mentor and friend, long-time NIMH co-worker, Michael J. Brownstein, M.D., says Axelrod was special: "It wasn't only that he had a capacity to enjoy other people's novel findings, he had a special appreciation for data and biology. He showed me that science could and should be fun. There was nobody who was more genuinely buoyant about the scientific enterprise than Julie. He loved to read and think about science, and talk about data. His magic was not in doing experiments that required lots of technical finesse; it was in doing work that anyone could have done—if they'd had the ideas. What separates the giants from the rest is the capacity to ask great questions."

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About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website .