PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Obituary for Dr. Julius Axelrod May 30, 1912 - December 29, 2004 by Tahira Farooqui, Ph.D. Dr. Julius Axelrod 92, died Wednesday, December 29th, 2004 in Rockville, MD. Dr. Axelrod was one of the outstanding leaders in neuroscience. He published many important papers on several topics including catecholamines (I have listed only few references below). His absence will make scientists realize that they have lost “a great neuroscientist, a pharmacologist and a biologist” who devoted his career to academic excellence. Dr. Julius Axelrod was born May 30th, 1912 in New York City in the East side of Manhatton. He received his Masters degree in Chemistry in 1941 and Ph.D. in Pharmacology in 1955. He became chief of the National Institute of Mental Health's pharmacology section and worked there for almost 30 years. He was awarded a noble prize in Medicine or Physiology, along with Bernard Katz and Ulf von Euler in 1970 on the work involving storage, release and inactivation of catecholamine neurotransmitters. He continued directing research even after his retirement in 1984. His work with Bernard B. Brodie on chemistry of analgesics in 1948 resulted in an important publication (The Fate of Acetanilide in Man, published in the Journal of Pharmacology and Experimental Therapeutics, 1948). They reported that acetanilide, which falls in the same class as acetaminophen (later developed as Tylenol by Johnson and Johnson) was an active ingredient in aspirin, phenacetin and caffeine. Axelrod noted that there were individual and genetic differences in animals and humans which are responsible for different drug metabolism. His work on monamine oxidase inhibitor in 1957 showed that after release of neurotransmitters in the synapse, they can be taken up by pre-synaptic end terminals via a reuptake mechanism. An antidepressant drug, Fluoxetine hydrochloride (brand name Prozac), a selective serotonin reuptake inhibitor was synthesized based on Dr. Axelrod’s neurotransmitter reuptake work (Whitby et al., 1960). Drs. Axelrod and Snyder (1964) were the first to report that antidepressant drugs (depending on the type) work by different mechanisms. Drs. Wurtman and Axelrod (1963) demonstrated a sensitive and specific assay for the estimation of monamine oxidase, enzyme responsible for removal of amine group from variety of substrates including norepinephine, epinephrine, dopamine, tyramine and 5-hydroxytryptamine. He discovered and characterized catechol-o-methyltransferase, a specific enzyme that accepts only catechols as substrates and thus inactivates catecholamines by O-methylation of the meta hydroxyl group. He and his colleagues were responsible for the discovery of pineal gland, and melatonin hypothesis (detailed study published by Wurtman and Axelrod, 1965). His research contribution in transduction pathways associated with G-protein coupled receptors, involvement of signaling enzymes (such as phospholipase A2, phospholipase C, adenylate cyclase) and release of second messengers is quite significant. His curiosity and broad interest in pharmacological science made him work on different research projects. In mammals, trace amines (such as octopamine, tyramine, tryptamine and phenylethylamine) are present in low levels. Therefore, these amines often have been referred as “false transmitters”. Levels of trace amines have been shown to be altered in human disorders. In mammals, octopamine is formed from tyramine through beta-hydroxylation by dopamine beta-hydroxylase in the sympathetic nerves, and it is partially stored in nerve endings with a subcellular distribution similar to that of norepinephrine (Saavedra and Axelrod, 1976). Since octopamine occurs in unusually high concentrations in certain neurological and hepatic diseases therefore it may have a pathophysiological role (Saavedra and Axelrod, 1976). Because levels of trace amines have been known to alter in brain disorders therefore it will be important to examine the roles of these amines, their signaling pathways, metabolites and degradative products in future studies. This information will be useful when developing new targets for novel therapeutic drugs. Dr. Axelrod also made a tremendous contribution in invertebrate field. In invertebrates, norepinephrine and epinephrine (major neurotransmitters in vertebrates) have no physiological relevance and are replaced by tyramine and octopamine. Axelrod and Saavedra (1977) provided a compelling evidence that octopamine serves as a major neurotransmitter with neuromodulator and neurohormone functions that allow to mediate diverse roles in the peripheral and central nervous systems of invertebrates. Twenty-eight years after this discovery, quite a bit is known about octopamine in invertebrates. It is known that octopamine is formed from hydroxylation of tyramine by tyramine beta-hydroxylase. Furthermore, it is also synthesized by a salvage pathway in which dopamine is first dehydroxylated to tyramine by dopamine dehydroxylase. Then tyramine is converted to octopamine by tyramine beta-hydroxylase. Octopamine has been reported to play an important role in modulating various processes related to peripheral and central nervous systems in insects. Therefore, full characterization of octopamine receptors in insects will also have an industrial relevance. It will help scientists in developing highly specific and potent receptor agonists and antagonists leading to be potential insecticides. Because of his major contribution in neuroscience, Dr. Axelrod always was and will remain with us. His findings will lead the way for many future scientists having interest in hormones, neurotransmitters and neuromodulators. Based on findings of his research, future scientists will be able to design new drugs to block reuptake with higher specificity, affinity and potency resulting in few adverse effects when taken for relieving mental illnesses (such as mood and anxiety disorders). Dr. Axelrod wanted to be a physician but did not get the admission in the medical school. Therefore, he started his career in a laboratory testing vitamin supplements, but ended up being a well-known successful scientist. Therefore, I would like to conclude this commentary with a quote by Ralph Waldo Emerson, US essayist & poet (1803 - 1882): “Do not go where the path may lead, go instead where there is no path and leave a trail .“ We should remember above quote during struggle in our lives. We should have a fighting spirit to further try and leave a trail by using Dr. Axelrod as our idol! Time Line 1912 :– Born in New York City 1933 :– B.S. in Biology, City College of New York 1933-35 :– Laboratory assistant, Department of Bacteriology, New York University Medical School 1941 :– M.S. in Chemistry, New York University 1946-49 :– Research Associate with Bernard B. Brodie at Goldwater Memorial Hospital, New York 1955 :– Ph.D. in Pharmacology, Thesis entitled "The Fate of Phenylisopropylamines", George Washington University (Advisor: George Mandel) 1955-84 :– Chief, Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health 1960 :– Whitby, L.G., Hertting, G., Axelrod, G. Effect of cocaine on the disposition of noradrenaline labelled with tritium. Nature 187: 604-5. 1958-61 :– Discovery of reuptake mechanism of norepinephrine 1963 :– Wurtman, R.J., Axelrod, J. A sensitive and specific assay for the estimation of monamine oxidase. Biochem Pharmacol 12: 1439-1441. 1960-65 :– Melatonin hypothesis from pineal gland 1964 :– Proved that serotonin was necessary for maintaining the sleep cycles of rats 1967 :– Recipient of Gairdner Foundation International Award 1970 :– Nobel Prize co-recipient in Physiology or Medicine with two other scientists (Sir Bernard Katz, London and Ulf von Euler, Sweden) 1970 :– Psychopharmacology Study Section, National Institute of Mental Health 1972 :– Axelrod, J., Weinshilboum, R. Catecholamines. N Engl J Med 287: 237-242. 1972 :– Axelrod, J. Biogenic amines and their impact in psychiatry. Semin Psychiatry 4: 199-210. 1974 : – Saavedra, J.M., Brownstein, M.J., Carpenter, D.O., Axelrod, J. Octopamine: presence in single neurons of Aplysia suggests neurotransmitter function. Science 185: 364-365. 1976 :– Grobecker, H., Saavedra, J.M., Roizen, M.F., Weise, V., Kopin, I.J., Axelrod, J. Peripheral and central catecholaminergic neurons in genetic and experimental hypertension in rats. Clin Sci Mol Med Suppl 3: 377s-380s. 1976 :– Saavedra, J.M., Axelrod, J. Octopamine as a putative neurotransmitter. Adv Biochem Psychopharmacol 5: 95-110 1977 :– Axelrod, J., Saavedra, J.M. Octopamine. Nature (London) 265: 501-504 1977 :– Axelrod, J. Catecholamines: effects of ACTH and adrenal corticoids. Ann N Y Acad Sci 297: 275-83. 1977 :– Axelrod, J. Catecholaminergic systems in the brain. Acta Neurol Scand Suppl 64: 85-89. 1977 :– Axelrod, J. Nonstriatal dopaminergic neurons: Section I. Mesocortical dopaminergic neurons: Introduction: mesocortical dopaminergic neurons. Adv Biochem Psychopharmacol 16: 1-3. 1977 :– Schaeffer, J.M., Brownstein, M.J., Axelrod, J. Thyrotropin-releasing hormone-like material in the rat retina: changes due to environmental lighting. Proc Natl Acad Sci U S A. 74(8): 3579-81. 1984 :– Retired formally from National Institute of Mental Health 1987 :– Establishment of Julius Axelrod Distinguished Lecture in Neuroscience by Raymond and Beverly Sackler Foundation at City College of New York 1992 :– One day scientific symposium held in honor of Julius Axelrod 1996 :– Scientist Emeritus of the National Institutes of Health 2004 :– Deceased in Rockville, MD (Summarized from http://profiles.nlm.nih.gov/HH/Views/Exhibit/narrative/biographical.html) ### Tahira Farooqui, Ph.D. Research Scientist The Ohio State University Department of Entomology Dr. Farooqui has been a member of The Science Advisory Board since November 2004. Sources: http://www.washingtonpost.com/wp-dyn/articles/A35661-2004Dec29.html ### << Previous Next >> [ View All Perspectives ] |
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