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Julius Axelrod
Pages 74-91

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From page 75... ... Whenever in Washington for a morning meeting, I would try to get away early to visit either my father, who lives in nearby Rockville, Maryland, or my mentor Julie Axelrod, who lived only a few miles away from my father's home. I had decided that day to call Julie for a lunch date when my cell phone rang with a message from my secretary that Julie had died early that morning. Read the entire page →
From page 76... ... His high school, Seward Park, subsequently became well known for its show business graduates, Tony Curtis, Walter Matthau, and Zero Mostel, but not for any intellectual tradition. Julie long maintained that his "real education" came from voracious reading of volumes from nearby Hamilton Fish Park Library. Read the entire page →
From page 77... ... In 1935, when the laboratory lost its funding, he obtained a position in the Laboratory of Industrial Hygiene, a nonprofit unit set up by the New York Health Department to evaluate vitamin supplements. Julie remained employed by that laboratory from 1935 to 1946. Read the entire page →
From page 78... ... Julie remained with Brodie and participated in numerous drug metabolism studies. When James Shannon, director of the Goldwater Memorial Laboratories, was chosen in 1949 to head the recently established National Heart Institute in Read the entire page →
From page 79... ... Lacking expertise in this area, he obtained the assistance of Gordon Tompkins and in early 1953 was able to demonstrate that in liver homogenates, amphetamine could be degraded but only if cofactors such as NAD, NADP, and ATP were added. In assessing the role of various subcellular fractions, Julie noted that enzyme activity required a combination of the microsomal fraction (obtained when one centrifuges supernatant fractions of mitochondria at 100,000 times gravity) Read the entire page →
From page 80... ... Evarts offered Julie the opportunity to head the Section on Pharmacology, which initially consisted only of Julie himself. In 1956 Kety presented to the NIMH staff a highly publicized and provocative publication by the Canadian psychiatrists Abram Hoffer and Humphrey Osmond purportedly showing that epinephrine, the hormone of the adrenal medulla, was transformed in the blood of schizophrenics but not of normals to an oxidized, pink-colored substance called adrenochrome. Read the entire page →
From page 81... ... The collaborative atmosphere of the NIH provided Julie with the assistance that facilitated many of its discoveries. The distinguished organic chemist Bernhard Witkop and his associate Siro Senoh provided the chemical synthetic efforts enabling Julie to show that his enzyme did indeed methylate epinephrine and norepinephrine to form, respectively metanephrine and normetanephrine. Read the entire page →
From page 82... ... VMA measurements in the urine became the standard method for diagnosing pheochromocytomas, epinephrine-secreting adrenal tumors that cause hypertension. With the availability of SAM radiolabeled in the methyl group, Julie proceeded to identify a variety of important methylating enzymes, such as the enzyme that methylates and inactivates histamine and the enzyme that converts norepinephrine to epinephrine in the adrenal gland and elsewhere. Read the entire page →
From page 83... ... At the time that Julie began this work it was thought that neurotransmitters were inactivated by metabolic alterations as was well known for the first characterized neurotransmitter acetylcholine, which is inactivated by the enzyme acetylcholinesterase. Enzymatic degradation of norepinephrine by COMT or monoamine oxidase was assumed to serve as the inactivating mechanism, but inhibiting these enzymes did not terminate the effects of injected epinephrine or norepinephrine. Read the entire page →
From page 84... ... Julie soon explored actions of drugs and discovered that cocaine, amphetamine, and other sympathomimetic amines blocked this uptake process. Inhibition of norepinephrine uptake could explain the ability of drugs to potentiate the effects of sympathetic nerve stimulation, providing compelling evidence that reuptake is the physiologic mode for neurotransmitter inactivation. Read the entire page →
From page 85... ... When the pineal-gland hormone melatonin was discovered by Aaron Lerner to be 5-methoxyN-acetylserotonin, Julie identified the methylating enzyme that generates melatonin. With Richard Wurtman he then showed that melatonin is the active principle of the pineal gland, which mediates organismic influences of light, presaging a vast body of work establishing melatonin as a regulator of sleep and circadian rhythms. Read the entire page →
From page 86... ... He opened the talk by saying, "It seems that all these speaking invitations are a conspiracy to get me out of the lab. I find it hard to imagine that I am paid a good salary for doing things that are so much fun that I'd work in the lab for no pay." When a critical experiment was completed, he was often so excited that standing in front of the liquid scintillation counter, which records radioactivity levels, he almost jumped up and down using body English to accelerate or decelerate the accumulation of radioactive counts, depending on what result he was seeking. Read the entire page →
From page 87... ... Julie married Sally Taub in 1938. She had grown up in the same lower East Side environment as Julie and worked for many years as a second grade school teacher. Read the entire page →
From page 88... ... 88 B I O G R A P H I C A L M E M O I R S good judgment, have intelligence, imagination, determination and a little luck." Then Julie got to the heart of the matter, commenting, "One of the most important qualities in doing research, I found, was to ask the right questions at the right time. I learned that it takes the same effort to work on an important problem as on a pedestrian or trivial one. Read the entire page →
From page 89... ... 97:58 67. 1954 Studies on sympathomimetic amines. Read the entire page →
From page 90... ... Localizing tritiated norepinephrine in sympathetic axons by electron micro scopic autoradiography. Science 138:440-442. Read the entire page →
From page 91... ... Characterization and substrate specificity of a protein carboxymethylase in the pituitary gland. Read the entire page →

From page 75...

... Whenever in Washington for a morning meeting, I would try to get away early to visit either my father, who lives in nearby Rockville, Maryland, or my mentor Julie Axelrod, who lived only a few miles away from my father's home. I had decided that day to call Julie for a lunch date when my cell phone rang with a message from my secretary that Julie had died early that morning.

Julius Axelrod Pages 74-91

Julius Axelrod
Pages 74-91