Julius Axelrod Biography (1912-)

biochemist, pharmacologist

Julius Axelrod is a biochemist and pharmacologist whose discoveries relatingto the role of neurotransmitters in the sympathetic nervous system earned himthe Nobel Prize in physiology or medicine in 1970, together with Ulf Euler of Sweden and Sir Bernard Katz of Great Britain. As Axelrod himself has said, he was a late starter as a distinguished scientist, due to boththe humble circumstances of his birth and his coming of age in the Great Depression of the l930s. He only began real scientific research in 1946, and earned his Ph.D. in 1955. From then on he compensated for lost time and became the first chief of the pharmacology section of the National Institute of Mental Health, a branch of the prestigious National Institutes of Health.

Axelrod was born on May 30, 1912, in a tenement house in New York City, the son of Isadore Axelrod, a maker of flower baskets for merchants and grocers, and Molly Leichtling Axelrod. His parents had immigrated to the United Statesfrom Polish Galicia in the early years of the century, met and married in NewYork, and settled in the heavily Jewish area of the Lower East Side of Manhattan. Julius Axelrod attended public elementary and high schools near his home but later recalled that he got his real education in the neighborhood public library, reading voraciously through several books a week, everything frompulp novels to Upton Sinclair and Leo Tolstoy. He studied for a year at New York University, but when his money ran out he transferred to the tuition-freeCity College of New York, from which he graduated in 1933 with majors in biology and chemistry. He later claimed that he did most of his studying on thelong subway rides between his home and the uptown Manhattan campus of City College.

Axelrod applied to several medical schools but was not admitted to any. It has been widely reported, in the New York Times, for example, that hefailed to get into medical school because of quotas for Jewish applicants. Itwas difficult to find any work in New York in the depths of the Depression,and Axelrod was fortunate to find employment in 1933 as a laboratory assistant at the New York University Medical School at $25 per month. In 1935 he tooka position as chemist at the Laboratory of Industrial Hygiene, a nonprofit organization set up by the New York City Department of Public Health to test vitamin supplements added to foods. He married Sally Taub on August 30, 1938,and they eventually had two sons, Paul Mark and Alfred Nathan. Axelrod took night courses and received an M.A. in chemistry from New York University in 1941. In the early 1940s he lost the sight of one eye in a laboratory accident.

Axelrod later speculated that he might have remained at the Laboratory of Industrial Hygiene for the rest of his working life. The work, he said, was moderately interesting, and the pay adequate. However, in 1946, quite by chance,he received the opportunity to do some real scientific research and found itexciting. The laboratory received a small grant to study the problem of why some persons taking large quantities of acetanilide, a non-aspirin pain-relieving drug, developed methemoglobinemia , the failure of hemoglobin to bind oxygen for delivery throughout the body. Axelrod, who had little experience in such work, consulted Dr. Bernard B. Brodie of Goldwater Memorial Hospital of New York. Brodie was intrigued with the problem and worked closely with Axelrod in finding its solution. He also found Axelrod a place among the research staff at New York University. The two men soon discovered that the body metabolizes acetanilide into a substance with an analgesic effect, and another substance that causes methemoglobinemia. They recommended that the beneficial metabolic product be administered directly, without the use of acetanilide. Related analgesics were investigated in the same manner.

In 1949, Axelrod, Brodie, and several other researchers at Goldwater Hospitalwere invited to join the National Heart Institute of the National Institutesof Health in Bethesda, Maryland. There Axelrod studied the physiology of caffeine absorption and then turned to the sympathomimetic amines , drugs whichmimic the actions of the body's sympathetic nervous system in stimulating thebody to prepare for strenuous activity. He studied such compounds as amphetamine, mescaline, and ephedrine and discovered a new group of enzymes which allowed these drugs to metabolize in the body. By the mid 1950s, Axelrod decided that he needed a doctorate to advance in his career at the National Institutes of Health. He took a year off to prepare for comprehensive examinations at George Washington University in the District of Columbia, submitted research work he had already done to satisfy the thesis requirements, and received aPh.D. in pharmacology in 1955, at the age of forty-three. He was then offered the opportunity to create a section in pharmacology within the Laboratory of Clinical Sciences at the National Institute of Mental Health, another branch of the National Institutes of Health. He became chief of the section in pharmacology and held that position until his retirement in 1984.

In 1957 Axelrod began the research which eventually led to the Nobel Prize. He and his colleagues and students studied the manner in which neurotransmitters, the chemicals which transmit signals from one nerve ending to another across the very small spaces between them, operate in the human body. In the 1940s the Swedish scientist Ulf von Euler had discovered that noradrenaline, ornorepinephrine, was the neurotransmitter of the sympathetic nervous system. Axelrod was concerned with the way in which noradrenaline was rapidly deactivated in order to make way for the transmission of later nerve signals. He discovered that this was accomplished in two basic ways. First, he found a new enzyme, which he named catechol-O-methyltransferase (COMT), which was essentialto the metabolism, and hence the deactivation, of noradrenaline. Second, through a series of experiments on cats, he determined that noradrenaline was reabsorbed by the nerves and stored to be reused later. These seemingly esoteric discoveries in fact had enormous implications for medical science. Axelroddemonstrated that psychoactive drugs such as antidepressants, amphetamines, and cocaine achieved their effects by inhibiting the normal deactivation or reabsorption of noradrenaline and other neurotransmitters, thus prolonging their impact upon the nervous system or the brain. His experiments also pointed the way to many new discoveries in the rapidly growing field of neurobiological research and the chemical treatment of mental and neurological diseases. The 1978 Nobel Prize in physiology or medicine, shared with Ulf von Euler and Bernard Katz, crowned his achievements in this area.

In his later years, Axelrod has worked in many areas of biochemical and pharmacological research, notably in the study of hormones. Especially important to the advancement of medical science was his development of many new experimental techniques which could be widely applied in the work of other researchers. He also had a great impact through his training of and assistance to a long line of visiting researchers and postdoctoral students at the National Institutes of Health. He continued his own research at the National Institute ofMental Health following his formal retirement in 1984. Early in 1993 Axelrodhad the unusual experience of having his own life saved through a scientificdiscovery he had made many years before. At the age of eighty, he suffered amassive heart attack. The cardiologists at Georgetown University Medical Center soon determined that several of his coronary arteries were almost completely blocked by blood clots and that he must have immediate triple coronary-artery bypass surgery. The complication was that his blood pressure had fallen so dangerously low that he might not survive the operation. The solution to this crisis was to inject a synthetic form of noradrenaline to stimulate the contractions of his heart and thus raise his blood pressure to a more acceptable level. Axelrod survived the operation and within two months was back at work and attending conferences in foreign countries.

Recent Updates

December 29, 2004: Axelrod died on December 29, 2004, at his home in Rockville, Maryland. He was 92. Source: Washington Post, www.washingtonpost.com, December 30, 2004.

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