John Jacob Abel: Epinephrine, Crystalline Insulin and the Founding of American Pharmacology

Table of Contents

1. Deep-Dive Articles
2. 1. Who John Jacob Abel Was
3. 2. The Discovery on One Page: Pure Hormones from Glands
4. 3. The Natural Sources: Glands, a Toad, a Leech and a Mushroom
5. 4. The Artificial Kidney and the Journals
6. 5. Timeline at a Glance
7. 6. Later Significance
8. Key Research Papers
9. Connections
10. Featured Videos

Deep-Dive Articles

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1. Who John Jacob Abel Was

Abel was born on 19 May 1857 near Cleveland, Ohio, into a family of German immigrants whose roots lay in the Rhine Valley of the Palatinate in Germany. He took his Ph.B. at the University of Michigan in 1883, interrupting his studies for three years to work as a high-school principal and then superintendent of schools in La Porte, Indiana, where he taught mathematics, Latin, chemistry and physics. There he met Mary Hinman, a fellow teacher; they married in July 1883, and according to his National Academy of Sciences biographer their combined savings paid for the years of study that followed.

After a year of physiology under H. Newell Martin at Johns Hopkins, Abel spent about seven years in Europe: Leipzig under Carl Ludwig and others, Strassburg, Heidelberg, Würzburg, Vienna, Berne and Berlin. He took his medical degree at Strassburg in 1888, and his biographer writes that it was Oswald Schmiedeberg who “first aroused Abel’s interest in pharmacological research, particularly in its chemical aspects.” On Schmiedeberg’s recommendation Michigan offered him its chair, and in 1893, answering a letter from William Osler, he moved to Johns Hopkins. He held the pharmacology chair there until he retired in 1932, then directed a Laboratory for Endocrine Research until his death in Baltimore on 26 May 1938. The full story is told in Life and Career of the Father of American Pharmacology.

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2. The Discovery on One Page: Pure Hormones from Glands

In 1894–95 the English physician George Oliver and the physiologist Edward Schäfer showed that an extract of the adrenal (suprarenal) glands sharply raised blood pressure in animals. Abel set out to isolate the substance responsible. In 1897, with Albert C. Crawford, he reported a benzoyl derivative of the active principle, and in 1899 he named the substance “epinephrin.” His formula, however, described a derivative rather than the free hormone. In his own 1927 Willard Gibbs Lecture he recalled that the Japanese chemist Jokichi Takamine visited his laboratory, then “simply added ammonia — the reagent that I had so long employed — to his concentrated extracts” and obtained the hormone itself as crystals. Takamine, whose assistant Keizo Uenaka did much of the bench work, reported crystalline adrenaline in 1901, and Thomas B. Aldrich worked out its formula that same year. Historians, among them John Parascandola, have written about how this priority story is told; the name “epinephrine” stayed in American usage and “adrenaline” in European.

The second hormone went the other way. In the autumn of 1924 the chemist A. A. Noyes invited Abel to the California Institute of Technology in Pasadena to study insulin, discovered in Toronto only three years before. Abel’s group first asked whether insulin was an unstable sulphur compound (1925), and in 1926 he announced crystalline insulin in the Proceedings of the National Academy of Sciences, with fuller proof with E. M. K. Geiling and colleagues in 1927 that the activity belonged to the crystals themselves. A pure crystal gave a definite standard against which the strength of insulin could be measured. Both stories are told in Epinephrine and Crystalline Insulin.

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3. The Natural Sources: Glands, a Toad, a Leech and a Mushroom

Abel worked before hormones could be made from scratch, so every project began with a natural raw material. The adrenal medulla gave epinephrine, the hormone that raises heart rate and blood pressure in the body’s response to stress. The pancreas gave insulin, and a few years after Abel’s crystals the Toronto chemist D. A. Scott found that zinc plays a part in insulin crystallisation. From 1917 Abel studied extracts of the posterior pituitary gland, reporting albumoses and histamine in them and arguing over whether its blood-pressure, uterine and kidney effects came from one hormone or several.

His raw materials also came from outside the slaughterhouse. In 1912, with David Macht, he obtained epinephrine from the skin-gland secretion of the tropical toad Bufo agua, together with a second crystalline substance, bufagin, which acted on the heart like the foxglove drug digitalis. In 1907 he and W. W. Ford studied the poisons of the death cap mushroom, Amanita phalloides, one of the most dangerous mushrooms known. And his artificial kidney depended on hirudin, the anticoagulant in the saliva of the medicinal leech, first noted by Haycraft in 1884 and named in 1904. The biology of each is told in Glands, Toads, Leeches and Mushrooms.

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4. The Artificial Kidney and the Journals

In 1913 Abel, Leonard G. Rowntree and B. B. Turner passed the hirudin-treated arterial blood of dogs through tubes of celloidin (collodion) membrane inside a glass vessel filled with salt solution, then returned it to a vein. Substances diffused out of the blood into the fluid. They called the method vividiffusion; The Times of London, reporting a demonstration at University College in August 1913, called it an “artificial kidney.” From dog blood they isolated urea and other substances, and Abel’s biographer singles out the first isolation of an amino acid from blood. In 1914 the same group described plasmapheresis, removing plasma and returning the blood cells. The experiments stopped in 1914, and later human attempts with the same materials failed; Georg Haas performed the first human dialysis in Giessen in 1924, and Willem Kolff the first clinically successful haemodialysis in 1945, after cellophane and heparin had replaced collodion and hirudin.

Abel was equally a builder of institutions. He suggested to Johns Hopkins president Daniel Coit Gilman the journal that became the Journal of Experimental Medicine (1896), co-founded the Journal of Biological Chemistry with C. A. Herter (1905), and called the 1906 meeting that formed the American Society of Biological Chemists. On 28 December 1908 eighteen pharmacologists met at his invitation in his Baltimore laboratory and organised the American Society for Pharmacology and Experimental Therapeutics, with Abel as president; its Journal of Pharmacology and Experimental Therapeutics first appeared in June 1909, and Abel edited it until 1932. See The Artificial Kidney, the Journals and the Legacy.

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5. Timeline at a Glance

• 1857 — Born 19 May near Cleveland, Ohio.
• 1879–1882 — High-school principal, then superintendent of schools, in La Porte, Indiana.
• 1883 — Ph.B., University of Michigan; marries Mary Hinman; a year of physiology at Johns Hopkins follows.
• 1884–1891 — About seven years of study in Europe; MD at Strassburg, 1888, where Schmiedeberg turns him toward pharmacology.
• 1891 — Begins teaching at Michigan, the first full professorship of pharmacology in the United States.
• 1893 — Professor of pharmacology at the new Johns Hopkins medical school.
• 1896 — Journal of Experimental Medicine founded on his suggestion.
• 1897–1899 — Benzoyl derivative of the adrenal principle with Crawford; names it “epinephrin.”
• 1901 — Takamine reports crystalline adrenaline; Aldrich determines its formula.
• 1905 — Journal of Biological Chemistry founded with C. A. Herter.
• 1907 — Death-cap mushroom poisons studied with W. W. Ford.
• 1908 — 28 December: the American Society for Pharmacology and Experimental Therapeutics is organised in his laboratory.
• 1909 — First issue of the Journal of Pharmacology and Experimental Therapeutics, which he edits until 1932.
• 1912 — Epinephrine and bufagin from the toad Bufo agua, with Macht.
• 1913–1914 — Vividiffusion, the first “artificial kidney,” with Rowntree and Turner; plasmapheresis.
• 1924–1926 — Insulin research at Caltech; crystalline insulin announced in 1926.
• 1925 onward — Seventeen Nobel Prize nominations in two categories; never awarded.
• 1932 — Retires from the chair; directs the Laboratory for Endocrine Research.
• 1932–1938 — Studies how tetanus toxin travels to the nervous system.
• 1938 — Dies 26 May in Baltimore, four months after Mary.

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6. Later Significance

Abel never won the Nobel Prize. Pohar and Hansson, who studied the Nobel archives, found that he was nominated seventeen times, in both chemistry and physiology or medicine, and that the chemistry committee’s reviewer judged his hormone work not prizeworthy, partly because others had made the more important discoveries in the same fields. Yet the pieces of his work run through modern medicine. Epinephrine, the adrenal hormone he spent a decade chasing, is the drug medical guidelines name as the first-line treatment for anaphylaxis. Crystalline insulin made it possible to standardise the hormone’s strength. The principle of his vividiffusion apparatus — blood flowing past a membrane, waste diffusing into fluid on the other side — is the principle of every dialysis machine since.

Perhaps his largest legacy is the discipline itself. Through Schmiedeberg, Abel carried the German experimental tradition of Rudolf Buchheim to America; through his students and associates, among them Reid Hunt, Carl Voegtlin, Leonard Rowntree, E. K. Marshall Jr., E. M. K. Geiling, Vincent du Vigneaud and K. K. Chen, it spread to laboratories across the country. The journals and the society he founded still exist. His papers at Johns Hopkins remain a primary source for historians of American pharmacology.

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Key Research Papers

1. Pohar M, Hansson N. Between two stools? Pharmacologists nominated for Nobel prizes in "physiology or medicine" and "chemistry" 1901-1950 with a focus on John Jacob Abel (1857-1938). Naunyn Schmiedebergs Arch Pharmacol. 2021;394(3):503-513. PubMed PMID: 33057776
2. Parascandola J. John J. Abel and the early development of pharmacology at the Johns Hopkins University. Bull Hist Med. 1982;56(4):512-27. PubMed PMID: 6760940
3. Parascandola J. Abel, Takamine, and the isolation of epinephrine. J Allergy Clin Immunol. 2010;125(2):514-7. PubMed PMID: 20196206
4. Oliver G, Schäfer EA. The Physiological Effects of Extracts of the Suprarenal Capsules. J Physiol. 1895;18(3):230-76. PubMed PMID: 16992252
5. Abel JJ. Crystalline Insulin. Proc Natl Acad Sci U S A. 1926;12(2):132-6. PubMed PMID: 16587069
6. Murnaghan JH, Talalay P. John Jacob Abel and the crystallization of insulin. Perspect Biol Med. 1967;10(3):334-80. PubMed PMID: 5340582
7. Abel JJ. Chemistry in relation to biology and medicine with especial reference to insulin and other hormones. Science. 1927;66(1710):307-19. PubMed PMID: 17797869
8. Eknoyan G. The wonderful apparatus of John Jacob Abel called the "artificial kidney". Semin Dial. 2009;22(3):287-96. PubMed PMID: 19573009
9. Gottschalk CW, Fellner SK. History of the science of dialysis. Am J Nephrol. 1997;17(3-4):289-98. PubMed PMID: 9189249
10. Anderson RJ. John Jacob Abel: the fifth horseman. Mol Interv. 2009;9(2):52-60. PubMed PMID: 19401535
11. Dale HH. John Jacob Abel, 1857 - 1938. Obituary Notices of Fellows of the Royal Society. 1939;2(7):577-585. DOI: 10.1098/rsbm.1939.0019

PubMed Topic Searches

1. PubMed: “John Jacob Abel”
2. PubMed: epinephrine history and Takamine
3. PubMed: crystalline insulin history
4. PubMed: vividiffusion

Further Reading

• MacNider WdeB. Biographical Memoir of John Jacob Abel, 1857–1938. National Academy of Sciences Biographical Memoirs, vol. 24. nasonline.org
• The American Society for Pharmacology and Experimental Therapeutics: The First Sixty Years, 1908–1969. aspet.org

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Connections

• Pharmacology: Notable Doctors
• John Jacob Abel: Life and Career of the Father of American Pharmacology
• Epinephrine and Crystalline Insulin: John Jacob Abel’s Hunt for Pure Hormones
• Glands, Toads, Leeches and Mushrooms: The Natural Sources of John Jacob Abel’s Chemistry
• The Artificial Kidney, the Journals and the Legacy of John Jacob Abel
• Rudolf Buchheim and Oswald Schmiedeberg: The Founders of Experimental Pharmacology
• Earl Sutherland: Cyclic AMP, and How a Hormone Talks to a Cell
• Katz, von Euler and Axelrod: How Nerves Talk
• William Withering: Foxglove and the Birth of Digitalis
• Frederick Banting: Insulin and the First Great Cure of Modern Medicine
• Diabetes: History and Discovery
• Dialysis and Kidney Transplant
• Anaphylaxis
• Anaphylaxis and Epinephrine (Biology animation)

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