At almost exactly the same time, the American researcher John Jacob Abel and the Japanese researcher Jokichi Takamine independently isolated adrenaline, or epinephrine, the main hormone of the adrenal medulla, which controls blood pressure and the “fight or flee” mechanism in higher organisms.
Adrenaline, or epinephrine, is a member of the very important group of biological messengers called hormones. These messengers control many biochemical processes necessary for the life and well-being of the whole body. They are produced in tiny amounts by organs called endocrine glands. Endocrinology, the study of the hormones, is named after these glands, which secrete hormones into the blood. The blood then takes hormones to other “target” organs, where their effects occur. The messages embodied in hormones integrate body functions, allowing them to occur with great flexibility.
Some hormones cause their effects by a mechanism that involves direct stimulation of the expression of genes in target organs. Adrenaline exemplifies another group of hormones that cause their effects by a process called a second messenger mechanism. Here, a hormone causes the production of a second chemical, the second messenger, that actually produces the effect.
Adrenaline is made by the central portion (medulla) of the adrenal glands, twin endocrine glands located atop the kidneys. It is produced from the amino acids phenylalanine and tyrosine. Adrenaline secretion triggers a series of body processes often called the “fight or flee” responses. These responses include accelerated heart rate and output, accompanied by increased energy and strength. They may explain, for example, the unexpected strength that sometimes enables a 150-pound person to lift a telephone pole off a loved one in an emergency situation.
A prominent biochemical event related to fight or flee responses is the greatly increased breakdown of the main energy reserve, glycogen (a complex carbohydrate), in muscle and liver. This prepares the body to use the energy reserve and leads to the physical responses required to fight or flee. The understanding of this process was elucidated in the 1970’s. Yet, it might not have occurred if John Jacob Abel and Jokichi Takamine had not isolated adrenaline between 1897 and 1901.
Abel’s contribution is a consequence of his lifelong effort to carry the use of the precepts and methodology of chemistry
Abel steadfastly worked on many aspects of drug and hormone research throughout his life and trained numerous biomedical scientists in the intelligent use of chemistry
The work with epinephrine that Abel carried out, from 1895 to 1905, was only one of his major efforts. It is one for which he became well known. In 1897, Abel published on the isolation of this substance from adrenal glands. Then, in 1899, he named it epinephrine (the preferred name for the hormone today). The chemical Abel actually isolated was not the free hormone, but rather a modified substance, called monobenzyl adrenaline. It was not until 1901 that Takamine isolated the pure, “free” hormone from the adrenal glands of beef cattle. The chemical structure of the hormone was not proven, however, until it was chemically synthesized by a third researcher in 1904.
Takamine received undergraduate and graduate degrees at the Universities of Tokyo and Glasgow. In 1894, he moved to the United States and founded a private research laboratory, where he isolated bovine adrenaline. In 1901, Takamine described his endeavor at a medical convention at Johns Hopkins University and patented his method for production of the hormone.
Takamine and Abel each recognized the other’s contribution to the discovery and isolation of adrenaline, which was the first hormone ever isolated in a pure and stable form. Both became prominent for their efforts, and the most immediate benefit of their dual discovery was the fact that medical practitioners found out quickly that adrenaline could be utilized to stop bleeding during surgery.
The pioneering efforts of Abel and Takamine to isolate adrenaline are viewed as being among the most important fundamental discoveries in life science; they produced pure samples of the first hormone ever isolated. Study of the pure adrenaline—in their laboratories and by numerous other researchers—laid many ground rules for the methodology utilized in study of other types of hormones. Furthermore, it led to many important discoveries, including the identification of several hormones related structurally to epinephrine (the catecholamines); explanation of the endocrine actions of the catecholamines; and development of modern explanations for aspects of nervous transmission in mental health and disease.
The widespread impact of the discovery of adrenaline on medical science arose from understandings of its actions in preparing living organisms to flee from danger or to fight—the so-called fight or flee responses. This was caused by the biological effects of the hormone, including increased alertness, elevated heart rate and blood pressure, and increased blood levels of glucose (the source of most of the body’s energy). For example, it was examination of the basis for adrenaline effects on glucose levels that led Eugene Sutherland to identify the second messenger mechanism for adrenaline action. Once the second messenger process in adrenaline action was understood, other researchers showed that the mechanism could be applied to explanation of the action of many other hormones.
The observation that adrenaline caused increased mental alertness led to the development of many stimulants, once its chemical structure had been identified as 3,4-dihydroxyphenyl-2-methyl-aminoethanol. The first such chemicals were the structurally related drugs known as the amphetamines (for example, Benzedrine and methedrine). The earliest amphetamines were made by German organic chemists
Eventually, abuse of catecholamine-related drugs (such as the amphetamines) was useful also; understanding of such abuse helped other scientists identify the catecholamine involvement in nervous transmission. In fact, the current explanations of mania, depression, and their effective treatment began with the catecholamine hypothesis of affective disorders, which was proposed in 1965. This hypothesis supposed that depression arises from suboptimum catecholamine production or utilization, while mania is caused by its excess. Spinoffs of successful application of the hypothesis include the choice of new drugs for therapeutic use on the basis of their effect on catecholamine levels and the implication of other “biogenic amines” (for example, serotonin), related structurally to catecholamines, in nerve transmission and its diseases.
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Geiling, E. M. “John Jacob Abel.” In Dictionary of Scientific Biography, edited by Charles Coulston Gillispie. Vol. 1. New York: Charles Scribner’s Sons, 1971. This brief biographical sketch provides insight into Abel’s personality and wide impact on biochemistry and pharmacology. -
Harrow, Benjamin. Textbook of Biochemistry. 10th ed. Philadelphia: W. B. Saunders, 1971. This textbook, first published in 1938, describes briefly the original methodology for isolation and for chemical synthesis of adrenaline. Also provides several important early references on the hormone. -
Lamson, Paul D. “John Jacob Abel—A Portrait.” Bulletin of The Johns Hopkins Hospital 68 (1941): 119-157. This very pleasant and entertaining article is a detailed personal account of Abel’s life and career. It provides very interesting and engaging reading and describes Abel both as an individual and as a scientist. -
Lehninger, Albert L., David L. Nelson, and Michael M. Cox. Principles of Biochemistry. 4th ed. New York: Freeman, 2005. Chapter 25 of this excellent college textbook concisely describes the chemistry, biochemistry, and mechanism of epinephrine. It is especially valuable as a relatively simple, technical explanation of the hormone and its actions and the second messenger mechanisms of hormone action with adrenaline and other hormones. -
Murnaghan, Jane H., and Paul Talalay. “John Jacob Abel and the Crystallization of Insulin.” Perspectives in Biology and Medicine 10 (1967): 334-380. This review of Abel’s work on insulin emphasizes its importance and describes the skepticism with which his contemporaries met the concept of a protein hormone. It also places the impact of Abel’s research in the broad context of biochemistry of the first half of the twentieth century and cites references on Abel’s life and endeavors. -
Sutherland, E. W. “Studies on the Mechanism of Hormone Action.” Science 177 (1972): 401-408. This article explains the important aspects of the Sutherland group’s developing understanding of cyclic AMP function in epinephrine action. The evolution of the second messenger concept is well developed by its originator. -
Voegtlin, Carl. “John Jacob Abel, 1857-1938.” Journal of Pharmacology and Experimental Therapeutics 67 (1939): 373-406. This article describes Abel’s scientific work, providing details about the discovery and study of adrenaline. Makes clear Abel’s excellent scientific ability and aspects of his personality. -
White, James T. “Jokichi Takamine.” In The National Cyclopedia of American Biography. Vol. 40. New York: James T. White, 1955. This brief biographical sketch is one of the only readily available references on Takamine’s life and work. It discusses some aspects of his early life as well as his education, career, and accomplishments. Takamine is portrayed as a very solid scientist and a successful entrepreneur.
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