Abel, John Jacob

(b. near Cleveland, Ohio, 19 May 1857; d. Baltimore, Maryland, 26 May 1938)

pharmacology, biochemistry.

Abel, the son of George M. and Mary Becker Abel, was born on a farm. His parents were moderately prosperous, and their Rhenish origin may have helped in shaping his receptivity to German academic values. Abel attended high school in Cleveland and entered the University of Michigan in 1876, graduating with a Ph.B. in 1883. He overcame the obstacle of a financially dictated three-year interruption, during which he served first as principal in and then as superintendent of the La Porte, Indiana, public schools. During that period he met Mary Hinman, who was also teaching in La Porte and whom he married in 1883. After graduation Abel went to the Johns Hopkins University, and spent part of a year in Newell Martins’s laboratory.

In 1884 Abel sailed for Germany, where he remained until late 1890—the longest German apprenticeship served by any prominent American scientist of his generation. The first two years were spent in Leipzig, studying the basic medical sciences—physiology, histology, pharmacology, and chemistry; like many other Americans he worked with Carl Ludwig. Not surprisingly, Abel undertook and electrophysiological problem. Finally titled “Wie verhalt sich die negative Schwankung des Nervenstroms bei Reizung der sensiblen und motorischen Spinal-surzeln des Frosches?”, it was presented as a doctoral thesis at Strasbourg in 1888.

The next two years were spent in Strasbourg, with short periods of clinical study at WÜrzburg and Heidelberg. Abel received his M.D. from Strasbourg in 1888, then spent the winter semester of 1888–1889 in Vienna, taking postgraduate clinical courses. His interests had already turned to biochemistry and experimental pharmacology; in 1889–1890 he worked in M. von Nencki’s laboratory in Berne and in the fall of 1890 returned to Leipzig to work with Drechsel, the physiological chemist at Ludwig’s institute. he completed his first essentially biochemical studies in Berne, one on the composition of melanin and another on the determination of the molecular weights of cholic acid, cholesterol, and hydrobilirubin.

While studying in Europe, Abel was aware that when he returned to the United States, he would in all probability have to depend upon clinical work for a livelihood, although he hoped to find a position in which he would have the opportunity to conduct research. He was fortunate to be offered a full-time teaching position at the University of Michigan school of medicine just as his funds were running low. This offer came through the good offices of Victor Vaughan, who had taught Abel as an undergraduate and shared his conviction that chemistry was to play an increasingly central role in the future of medical research.

Abel was appointed lecturer in materia medica and therapeutics in January 1891. Classroom teaching, of course, and not research or laboratory instruction, at first made up the bulk of Abel’s duties. By his third year, however, he was able to offer a graduate course on “the influence of certain drugs in the metabolism of tissue” and another on “the methods of modern pharmacology.” In 1893 the Johns Hopkins University offered Abel its first professorship of pharmacology, a position that he accepted and occupied continuously until his retirement in 1932. Until 1908 he was also nominally in charge of instruction in physiological chemistry. Abel’s research was his life: in his mature years he evinced little concern for the formal routine of teaching. From his retirement until his death, Abel remained steadfastly and constructively at work in his laboratory.

Through this ascetic dedication to research, Abel made one of his most significant contributions to the development of biochemistry and pharmacology in the United States. It was his way of life, his students and colleagues agreed, that influenced them—not his teaching of particular techniques. Almost all his memorialists, for example, mention the intellectual stimulation they received at the austere lunch the laboratory staff shared each day at a plain table, the legs of which were immersed in cans of kerosene to discourage Baltimore’s predatory cockroaches. Photographs show Abel’s never-changing laboratory attire—white operating-room cap, gray laboratory coat, and long white apron. In values and style of life, Abel seemed to embody the idealized figure of the German professor.

The character of Abel’s work played a significant and distinct influence in the reshaping of his discipline. The key to this influence lay in his complete and farsighted commitment to the importance of chemistry in medicine and physiology. Few other biological scientists of his generation had had the prescience to undertake the high-level chemical training necessary in a world of medical and biological research that was increasingly dependent upon chemical and physical sophistication. In the analysis of vital phenomena, Abel warned in 1915, “the investigator must associate himself with those who have labored in fields where molecules and atoms rather than multi-cellular tissues or even unicellular organisms are the units of study,” In his own work, Abel was consistently motivated by the chemist’s concern with determining the composition and structure of the substances with which he worked; such concerns were, of course, highly atypical in the medical world of the 1890’s. At Johns Hopkins, Abel sought, for example, to introduce microanalytic techniques and even the formal teaching of biophysics. His correspondence and programmatic statements indicate his assumption of what might, if formally articulated, be called a biochemical and biophysical reductionism.

Despite an occasional disdain for mere matters of administration, Abel also played a significant role in the institutional development of American science. He was instrumental in the founding of the Journal of Experimental Medicine in 1896 and, in conjunction with Christian Herter. the Journal of Biological Chemistry in 1905. Abel was one of the principal organizers of the American Society of Biological Chemists in 1906 and the American Society for Pharmacology and Experimental Therapeutics in 1908. A year later he led in establishing the Journal of Pharmacology and Experimental Therapeutics, a publication that he edited until his retirement. Abel’s statements and actions indicate a rare mixture of insight and practicality in his understanding of the conditions favoring institutional growth. He of course also figured prominently in shaping the evolution of the traditionally didactic and empirical field of materia medica into modern, laboratory-oriented pharmacology.

After his physiological interlude with Ludwig, Abel’s work was, for the half century of his active scientific life, essentially biochemical. His first significant work related to the metabolism of sulfur, a problem he had begun in Leipzig with Drechsel and had continued in Ann Arbor. Abel succeeded in demonstrating the presence of ethyl sulfide in dog urine and, in a related protect, in explaining the presence of ammonia in the urine of children who had been given large quantities of limewater. He suggested that it was a product of the breakdown of carbamic acid, a substance Abel had previously studied in alkaline horse urine.

Soon after coming to Johns Hopkins, Abel turned to work with the physiologically active substance found in extracts form the adrenal medulla; this became his all-consuming interest form 1895 to 1905, He published his first article on the substance he had isolated in 1897(with A.C. Crawford), and in 1899 he christened this blood-pressure-raising hormone “epinephrine,” The substance he described, however, was not the free hormone, but a monobenzoyl derivative. This work was the first to give Abel international prominence, although in 1900 Jokichi Takamine was able to isolate the hormone without the benzoyl radical. Both assumed, of course, that they were dealing with a unitary substance. In the years after 1905, Abel completed less elaborate studies of the physiological effects of alcoholic beverages, isolated epinephrine from the parotid secretions of the South American roat Bufo agua, studied the poisons of the mushroom Amanita phalloides—and even published on the pharmacology of several new cherno-action of phthalein derivatives led to the elaboration of a test for kidney function.

In 1912 and the years immediately following, Abel became deeply interested in work with the protein constituents of the blood. He suggested in 1912 that an “artificial kidney” might be utilized in the removal and study of diffusible substances of the blood. An apparatus of coiled collodion tubes surrounded by a saline solution was soon devised and used for this purpose; arterial blood was shunted through these tubes and then returned to the experimental animal’s vein. Using this technique, Abel succeeded in demonstrating the existence of free amino acids in the blood. Even at this time(1913), Abel seems to have been aware of the clinical potential of what he called his “vividiffusion” apparatus; it might, he suggested, prove useful in managing renal failure. A second and related aspect was Abel’s demonstration that large quantities of blood could be removed from the circulation if the washed and centrifuged corpuscles were returned. Abel also showed remarkable foresight in his suggestion that “plasmaphaeresis”—his term for this procedure—might ultimately be used to create “blood banks” for use in traumatic and surgical emergencies.

A natural extension of this work led Abel’s laboratory to a concern with amino acids and protein degradation products in the blood. A related study of histamines, however, soon revived his earlier interest in hormones. (A resemblance between histamine and the active principle of the posterior pituitary seemed at first to exist.) From the publication of his first paper on the pituitary in 1917 until 1924, when he turned abruptly to work with insulin, Abel labored single-mindedly, although fruitlessly, to isolate a unitary hormone with the protean physiological characteristics associated with pituitary extracts.

Abel’s interest in insulin resulted from the explicit invitation of his personal friend A. A. Noyes of the California Institute of Technology. Noyes had acquired funds to subsidize an attempt to isolate pure insulin from the expensive, although readily available, commercial preparation. Abel accepted Noyes’ invitation, arrived in Pasadena in October 1924, and was soon able to report encouraging findings. A key step forward lay in his insight that amounts of labile sulfur in his fractions of commercial insulin were directly correlated with physiological activity. Not only did this have ultimate structural implications but—more immediately—it allowed Abel to save a great deal of time; he could now separate out the more active fractions by the use of this criterion without resorting to as yet unstandardized bioassay procedures, in which his laboratory had never excelled and which were far more time-consuming.

Late in 1925, Abel succeeded in forming crystals that, according to the chemical criteria he instinctively employed—crystallization, optical rotation, melting point, and elementary analysis—seemed to be the pure hormone. Despite early scientific enthusiasm at the announcement of this finding in 1926, Abel spent much of the next four years in defending his discovery. The reasons for skepticism were several. One was an initial difficulty in reproducing his crystals. Perhaps more important were certain theoretical implications. It seemed apparent that the substance isolated was a protein, and it was difficult for Abel’s contemporaries to believe that the immense protein molecule, of which the regularity of structure was still very much in doubt, could be capable of performing the precise physiological functions of a hormone. The protein, many biochemists believed, must necessarily be an inert carrier, the active principle an adsorbent on its surface. (Similar objections greeted the parallel findings of J.B. Sumner and of J.H. Northrop and M. Kunitz when they announced the protein nature of enzymes they had crystallized.)

By the mid-1930’s, however, it was becoming generally assumed that proteins could act as enzymes. The isolation of insulin and its attendant publicity had, of course, helped to sharpen the debate. Abel’s insulin work and that of his students played an important part in the line of research culminating in Frederick Sanger’s identification in 1955 of the complete primary structure of insulin, the first protein structure to be thus elucidated. After his crystallization of insulin, Abel turned back to his earlier work on the pituitary. When he retired in 1932, he was placed at the head of a laboratory of endocrinology created especially for him at Johns Hopkins. With a touch of characteristic individuality, he then abandoned his hormone work and devoted the remaining years of his life to a study of tetanus toxin and the pathological mechanism through which it acts.

BIBLIOGRAPHY

1. Original Works. A complete bibliography of Abel’s work is available in William deB. MacNider, “Biographical Memoir of John Jacob Abel 1857–1938,” in National Academy of Sciences, U.S.A., Biographical Memoirs, 24 (1946), 231–257. Several of Abel’s own papers provide Valuable synthetic and expository accounts of his work. See Experimental and Chemical Studies of the Blood With an Appeal for More Extended Chemical Training for the Biological and Medical Investigator, the first Mellon lecture, given at the University of Pittsburgh under the auspices of the Society for Biological Research (Pittsburgh, 1915), also in Science, 42 (1915), 135–147, 165–178; “Some Recent Advances in Our Knowledge of the Ductless Glands,” in Bulletin of the Johns Hopkins Hospital, 38 (January 1926), 1–32; and “Chemistry in Relation to Biology and Medicine With Especial Reference to Insulin and Other Hormones,” in Science, 66 (1927), 307–319, 337–346.

The most important source for Abel’s life and scientific career is his papers, deposited at the Welch Medical Library, the Johns Hopkins University. This extensive collection, including correspondence, notebooks, and other memoranda, constitutes an important source of information on the development of American biochemistry and pharmacology as well as for the history of the specific research areas that concerned Abel.

II. Secondary Literature. There is no full-length biography of Abel available, but among the most useful of numerous biographical sketches are Carl Voegtlin, “John Jacob Abel. 1857–1938,” in Journal of Pharmacology and Experimental Therapeutics, 67 (1939), 373–406, a detailed account of Abel’s scientific work; H. H. Swain, E. M. K. Geiling, and A. Heingartner, “John Jacob Abel at Michigan. The Introduction of Pharmacology Into the Medical Curriculum,” in University of Michigan Medical Bulletin, 29 (1963). 1–14; E. K. Marshall, Jr., “Abel the Prophet,” in The Johns Hopkins Magazine, 1 (1950), 11–14; Paul D. Lamson, “John Jacob Abel—A Portrait,” in Bulletin of the Johns Hopkins Hospital, 68 (1941), 119–157, an engagingly detailed personal portrait; McNider’s “Biographical Memoir.’ cited above; H. H. Dale, “John Jacob Abel. 1857–1938,” in Obituary Notices of Fellows of the Royal Society, 2 (1939), 577–581; and E. M. K. Geiling, “John Jacob Abel.” in Dictionary of American Biography, XXII, Supp. 2 (New York, 1958), 4–5. John Jacob Abel, M.D., Investigator, Teacher, Prophet. 1857–1938 (Baltimore, 1957) is a useful commemorative volume that includes the Lamson and Marshall sketches cited above, as well as a number of Abel’s most important papers. In 1957 the Johns Hopkins University celebrated the centenary of Abel’s birth with a syposium to which contributions were made by Torald Sollman, Samuel Amberg, Carl Voegtlin, L. G. Rowntree. E. K. Marshall, Jr., E. M. K. Geiling, and Warfield M. Firor; the proceedings appeared in the Bulletin of the Johns Hopkins Hospital, 101 (1957), 297–328. An excellent recent study of Abel’s insulin work by Jane Murnaghan and Paul Talalay that succeeds in placing this research in the broader context of twentieth-century biochemistry is “John Jacob Abel and the Crystallization of Insulin,” in Perspectives in Biology and Medicine, 10 (1967), 334–380.

Charles E. Rosenberg