The Artificial Kidney, the Journals and the Legacy of John Jacob Abel

Most people who have heard of John Jacob Abel (1857–1938) know him for two things: the long hunt for the adrenal hormone epinephrine and the first crystals of insulin. Yet some of his most lasting work lay elsewhere. In 1913, with two young colleagues at Johns Hopkins, he ran the blood of living dogs through tubes of a thin membrane bathed in salt solution and drew substances out of it — a method he called “vividiffusion” and a London newspaper called an “artificial kidney.” It never treated a patient in his hands, but it was the first time anyone had cleaned the blood of a living animal by dialysis, and every dialysis machine since descends from the same principle.

This page follows what came after and what endured: the vividiffusion apparatus and the amino acid it found in blood; plasmapheresis; how Georg Haas in Germany and Willem Kolff in the Netherlands carried dialysis to patients; the dye test of kidney function that came out of Abel’s laboratory; the journals and scientific societies he started; the students who carried pharmacology across America; his seventeen Nobel Prize nominations; and his final experiments on tetanus toxin. The story of epinephrine and insulin themselves, and the leeches, toads and glands Abel drew on, each have their own page in this wing, linked below.

Table of Contents

  1. Vividiffusion, 1913: Blood Through Celloidin Tubes
  2. The Artificial Kidney: London and Groningen
  3. Amino Acids in the Blood and Plasmapheresis
  4. From Abel to Haas and Kolff: Dialysis Reaches Patients
  5. The Phthalein Test and Kidney Function
  6. Journals for a New Science: 1896, 1905, 1909
  7. 28 December 1908: Eighteen Pharmacologists in Baltimore
  8. Abel’s Students and the Spread of Pharmacology
  9. Seventeen Nobel Nominations
  10. Tetanus, the Last Experiments and Epinephrine Today
  11. Key Research Papers
  12. Connections

1. Vividiffusion, 1913: Blood Through Celloidin Tubes

The idea behind dialysis was old by Abel’s day. Chemists had long known that small dissolved molecules pass through certain thin membranes while large ones, such as proteins, are held back. What nobody had done was apply that principle to the blood of a living animal while its heart kept beating. Abel set out to do it with two colleagues at Johns Hopkins, the physician Leonard G. Rowntree and the chemist B. B. Turner.

The apparatus

Their device, described by Abel’s biographer William deB. MacNider and by the nephrologist-historian Garabed Eknoyan, was built from a short list of materials: celloidin (collodion) tubes, glass, and hirudin. The celloidin tubes — a membrane made from a solution of nitrocellulose — were arranged inside a glass container and surrounded by dialysing fluid. Arterial blood from a dog entered the apparatus at one connection, flowed through the tubes, and returned to the animal through a venous connection. As it passed, small molecules in the blood crossed the membrane into the surrounding fluid, where they could be collected and analysed.

Why hirudin

Blood that leaves the body clots within minutes when it touches glass or tubing. To keep it flowing the team used hirudin, the anticoagulant found in the saliva of the medicinal leech, added to the blood before it entered the apparatus. Heparin, the anticoagulant used in dialysis today, was not yet available in a usable form. The leech substance made the experiment possible, and its limitations would later help to stop it (section 4). The leech itself and the history of hirudin are told on the Glands, Toads, Leeches and Mushrooms page.

A tool for chemistry first

Abel’s first purpose was not to treat kidney failure. He wanted a way to sample the small molecules circulating in the blood of a living animal without killing it — a window into the chemistry of the body that was, in his long career, always his central interest. The name he chose, “vividiffusion,” meant diffusion out of living blood. The first report appeared in the Transactions of the Association of American Physicians in 1913, and the full papers in the Journal of Pharmacology and Experimental Therapeutics in 1914.

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2. The Artificial Kidney: London and Groningen

A machine able to draw substances out of the blood could, in principle, do part of the work of the kidneys, and the press was quick to say so. According to Eknoyan’s history of the apparatus, Abel demonstrated it at University College in London, and on 11 August 1913 The Times of London reported the demonstration under the name that stuck: an “artificial kidney.”

MacNider and the Spanish medical historian José Luis Fresquet Febrer also record a demonstration of the apparatus at the Physiological Congress in Groningen, in the Netherlands, which they date to 1914. The London demonstration and The Times’s phrase belong, in Eknoyan’s account, to 1913.

A name ahead of the machine

“Artificial kidney” was a hopeful name. The device could remove some dissolved substances from a dog’s blood for a period of time, but it was small, fragile and dependent on an anticoagulant that was hard to obtain and imperfectly purified. It was a proof of principle rather than a treatment. Eknoyan’s title — “the wonderful apparatus of John Jacob Abel called the ‘artificial kidney’” — captures both the achievement and the distance still to travel.

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3. Amino Acids in the Blood and Plasmapheresis

As a chemical tool, vividiffusion worked. From the dialysing fluid that had bathed the tubes carrying dog blood, MacNider records, Abel and his colleagues recovered urea, lactic acid, beta-oxybutyric acid and other substances. One finding stood out. In MacNider’s words, “of the greatest importance was the first isolation … of an amino acid from blood.”

That mattered because it settled a real question of the time. Protein from food is broken down in the gut into its building blocks, the amino acids, but it was not yet certain in what form those building blocks travelled in the bloodstream to the tissues. Finding a free amino acid in circulating blood was direct evidence that they did travel as amino acids. The site’s Amino Acids section covers the individual amino acids and what they do.

Plasmapheresis, 1914

The same group published a second idea in the Journal of Pharmacology and Experimental Therapeutics in July 1914: “plasma removal with return of corpuscles,” which they called plasmaphaeresis. Blood was withdrawn, the liquid plasma separated off, and the red and white cells returned to the animal. The paper was reprinted in 1990, alongside the 1913 vividiffusion report, in the journal Transfusion Science, as a classic of the field. Plasma exchange and plasma donation by apheresis — in which a machine returns the donor’s cells and keeps the plasma — rest on the same principle.

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4. From Abel to Haas and Kolff: Dialysis Reaches Patients

Why the experiments stopped

The medical historian Connor, writing on the artificial kidney in North America, records that Abel’s celloidin vividiffusion experiments were abandoned in 1914. The sources point to practical limits rather than a failure of the idea. Celloidin tubes were delicate; hirudin was scarce and, in the preparations of the day, impure. Eknoyan notes that human attempts made in the following decade with Abel’s materials failed, and that practical dialysis had to wait for three later materials: cellophane membranes, the anticoagulant heparin, and Teflon for connections and tubing.

Georg Haas in Giessen, 1924

The next step was taken in Germany. According to C. W. Gottschalk and S. K. Fellner’s history of dialysis, the physician Georg Haas, at first unaware of Abel’s work, performed the first dialysis of a human patient at Giessen in 1924. Johannes Benedum’s history of the artificial kidney (published in German, with an English abstract) adds that it was Abel who told Haas that purified hirudin had become available — so the two men were in contact at some point, even if Haas began independently. Benedum’s summary of the division of credit is simple: Abel performed the first haemodialysis in animals, Haas the first in humans. Benedum also describes the toxicity of hirudin as one of the problems Haas faced.

Willem Kolff, 1945

Gottschalk and Fellner credit the Dutch physician Willem Kolff with the first clinically successful haemodialysis, in 1945, using cellophane membranes and heparin. Kolff described his apparatus in an English-language paper, “The artificial kidney,” in 1947 — the same words The Times had used for Abel’s device thirty-four years earlier. Connor’s paper adds a North American thread: the Canadian surgeon George Murray built his own artificial kidney in 1946.

The line from Abel to modern dialysis is therefore not a straight one. It ran through a pause of a decade, a German physician who started on his own, and a set of new materials that Abel never had. But the principle — blood flowing past a semi-permeable membrane, with small molecules drawn across into a bath — is the one his group demonstrated in 1913. The site’s Dialysis and Kidney Transplant page describes dialysis as it is practised today, and Kidney Disease: History and Discovery places Abel in the wider story.

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5. The Phthalein Test and Kidney Function

Abel’s partnership with Leonard Rowntree began before the artificial kidney. From 1909, MacNider records, the two studied the phthaleins, a family of synthetic dyes. Out of that work came the Rowntree–Geraghty kidney-function test, based on the dye phenolsulphonphthalein, and later a test of liver function.

How a dye test works

The principle of a dye-excretion test is simple. A measured amount of a dye that the kidneys clear from the blood is given, and the amount that appears in the urine over a set time is measured. Healthy kidneys put out more of it, damaged kidneys less. In an era before the blood creatinine and estimated filtration-rate measurements described on the site’s Kidney Function Tests page, a test of this kind gave physicians one of their first numbers for how well a patient’s kidneys were working.

Drugs against parasites

The same years saw Abel and Rowntree working on compounds of antimony and arsenic in experimental trypanosomiasis, the parasitic infection that causes sleeping sickness. It was the era of Paul Ehrlich’s arsenical drugs and of the search for chemicals that would strike a parasite harder than its host — a story told on the site’s Paul Ehrlich page. Abel’s laboratory thus worked across the full range of early pharmacology: pure hormones from animal glands, poisons from mushrooms and toads, synthetic dyes, and heavy-metal drugs.

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6. Journals for a New Science: 1896, 1905, 1909

A science needs places to publish. When Abel came home from Germany in 1891, American laboratory medicine had few journals of its own, and serious experimental papers often went to German periodicals. Over the next eighteen years Abel had a hand in founding three of the most important American journals of biomedical research.

The Journal of Experimental Medicine, 1896

In 1895, according to MacNider and to the American Society for Pharmacology and Experimental Therapeutics’ own history, Abel suggested to Daniel Coit Gilman, the president of Johns Hopkins, that the university start a journal of experimental medicine. The Journal of Experimental Medicine began publication in 1896, with the pathologist William H. Welch as its editor. It is still published today.

The Journal of Biological Chemistry, 1905

Abel’s interest in the chemistry of the body led to a second journal. With the New York physician Christian A. Herter, who funded the venture, he founded the Journal of Biological Chemistry; its first number appeared in October 1905. The following year, on 26 December 1906, Abel called the meeting at the Hotel Belmont in New York that formed the American Society of Biological Chemists.

The Journal of Pharmacology and Experimental Therapeutics, 1909

The third journal grew out of the society described in the next section. Its first issue appeared in June 1909. Abel edited it from 1909 until July 1932, the month he retired from his chair — twenty-three years in which it carried, among much else, his own vividiffusion and plasmapheresis papers. He then gave the journal to the society; ASPET’s history dates the gift to 1933, while MacNider gives 1934.

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7. 28 December 1908: Eighteen Pharmacologists in Baltimore

By 1908 there were enough pharmacologists in North America — many of them trained by Abel or by his German teachers — to form a society of their own. On 28 December 1908, at Abel’s invitation, eighteen of them met in his laboratory in Baltimore and organised the American Society for Pharmacology and Experimental Therapeutics (ASPET). One of the founders, V. E. Henderson, came from Toronto, so the society was North American from its first day.

Abel was elected the first president and Reid Hunt the secretary. The society’s stated purpose, as its own history records it, was “to further the growth of pharmacology and experimental therapeutics in this country and to facilitate personal intercourse among investigators.” Before the meeting adjourned, Abel announced the new Journal of Pharmacology and Experimental Therapeutics (section 6).

Pharmacology as its own discipline

The meeting marked a separation. Until then pharmacology in America had sat inside older subjects — materia medica, therapeutics, physiology. The same year, 1908, Johns Hopkins split Abel’s own department in two: biological chemistry went to Walter Jones, and Abel kept pharmacology alone. A society, a journal and a dedicated university department, all within about a year, gave the subject an identity of its own. ASPET still exists and still publishes the journal Abel founded.

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8. Abel’s Students and the Spread of Pharmacology

Abel’s influence travelled through people as much as through papers. MacNider names among his students and associates Crawford, Aldrich, Hunt, Voegtlin, Loevenhart, Rowntree, Turner, Macht, Geiling, Marshall, du Vigneaud and Chen. Several are met elsewhere in this wing: Albert C. Crawford, his partner on the first epinephrine paper; Rowntree and Turner, his partners on vividiffusion; David Macht, with whom he studied the toad Bufo agua; and E. M. K. Geiling, his partner on crystalline insulin.

Where the line led

Others went on to their own landmarks. Reid Hunt became the first secretary of ASPET. E. K. Marshall Jr. succeeded Abel in the Hopkins chair of pharmacology in 1932. Vincent du Vigneaud later received the 1955 Nobel Prize in Chemistry for work on the pituitary hormones — the same gland whose puzzling extracts Abel had studied. And K. K. Chen, a Chinese-born pharmacologist who worked with Abel, is remembered for the pharmacology of ephedrine, the active principle of the traditional Chinese herb ma huang — one of the clearest cases in modern pharmacology of a medicine taken straight from an old plant remedy.

Teaching without ceremony

Abel built this school in an unusual way. MacNider records that he was opposed to specialised doctorates in pharmacology and held no formal seminar. The teaching happened at informal lunches with his staff, where the day’s experiments were argued over. His own lineage ran back through Oswald Schmiedeberg in Strassburg, the founder of experimental pharmacology as a laboratory science, and forward through these students to the pharmacology departments of America. The chain from Buchheim and Schmiedeberg to Abel is told on the Buchheim and Schmiedeberg page, and Abel’s own life on Life and Career.

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9. Seventeen Nobel Nominations

Abel never received a Nobel Prize, though he was nominated many times. The medical historians Pohar and Hansson, drawing on the Nobel nomination archives, count seventeen nominations: five in Chemistry, from 1925 to 1927, and twelve in Physiology or Medicine, the whole run spanning 1925 to the late 1930s. The nominations followed the crystallisation of insulin and his long hormone work.

Hammarsten’s verdict

Nominations are assessed by committee reviewers. For the Chemistry committee, Pohar and Hansson report, the Swedish biochemist Einar Hammarsten reviewed Abel’s work and judged the hormone research not worthy of the prize — in part because, in his assessment, other scientists had made more important discoveries in the same fields. Epinephrine was the obvious example: Jokichi Takamine and Thomas Aldrich had obtained the crystalline hormone and its formula in 1901, while Abel’s own isolation had stopped at a benzoyl derivative (that story is told on the Epinephrine and Crystalline Insulin page).

“Between two stools”

Pohar and Hansson titled their study “Between two stools?” Pharmacology sat between chemistry and medicine, and a pharmacologist could fall into the gap: too medical for one committee, too chemical for the other. Abel’s case is their main example. The same paper notes that he is repeatedly referred to as the “Founder of American Pharmacology” — a title that, unlike the prize, nobody has disputed.

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10. Tetanus, the Last Experiments and Epinephrine Today

Tetanus toxin, 1932–1938

Abel retired from his chair in July 1932, at seventy-five, and became director of the Laboratory for Endocrine Research at Johns Hopkins. He did not slow down. From 1932 until his death he worked on tetanus toxin — the poison made by the soil bacterium Clostridium tetani (then called Bacillus tetani) that causes the rigid muscle spasms of lockjaw — and in particular on how the toxin travels to the central nervous system. In 1934 he published a two-part lecture in Science, “On poisons and disease and some experiments with the toxin of the Bacillus tetani.” His final paper appeared in 1938. The disease itself is described on the site’s Tetanus page.

MacNider records that only hours before his death Abel was planning, with an associate, the continuation of their tetanus work. He died at the Johns Hopkins Hospital on 26 May 1938, a week after his eighty-first birthday, four months after the death of his wife Mary.

Epinephrine today

The hormone Abel spent ten years trying to isolate has outlived every argument about who isolated it first. Epinephrine is the drug that anaphylaxis guidelines name as the first-line treatment for a severe allergic reaction, given by injection into the muscle, and it is the medicine inside the auto-injector pens carried by people with serious allergies. It is also used in cardiac arrest and, in small amounts, alongside local anaesthetics to narrow blood vessels. The site’s Anaphylaxis page and the interactive anaphylaxis and epinephrine animation show what the hormone does in the body during that emergency.

What endures

Abel’s papers, kept at Johns Hopkins, remain a primary source for the history of American pharmacology, and the centenary of his birth in 1957 was marked at Johns Hopkins by tributes from former students and colleagues and by an exhibit described by his successor, E. K. Marshall Jr. The things that outlived him are of three kinds: substances (epinephrine named, insulin crystallised); methods (dialysis of living blood, plasmapheresis, a dye test of the kidneys); and institutions (three journals, two scientific societies, and a generation of pharmacologists trained at his lunch table).

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Key Research Papers

  1. Eknoyan G. The wonderful apparatus of John Jacob Abel called the “artificial kidney”. Semin Dial. 2009;22(3):287-96. PubMed PMID: 19573009
  2. Abel JJ, Rowntree LG, Turner BB. On the removal of diffusable substances from the circulating blood by means of dialysis. Transactions of the Association of American Physicians, 1913. Transfus Sci. 1990;11(2):164-5. (Reprint of the 1913 first report.) PubMed PMID: 10160880
  3. Abel JJ, Rowntree LG, Turner BB. Plasma removal with return of corpuscles (plasmaphaeresis). The Journal of Pharmacology and experimental therapeutics Vol. V. No. 6, July, 1914. Transfus Sci. 1990;11(2):166-77. (Reprint of the 1914 paper.) PubMed PMID: 10160881
  4. Gottschalk CW, Fellner SK. History of the science of dialysis. Am J Nephrol. 1997;17(3-4):289-98. PubMed PMID: 9189249
  5. Benedum J. [The early history of the artificial kidney]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003;38(11):681-8. (In German.) PubMed PMID: 14600857
  6. Connor JT. The artificial kidney in North America: George Murray and the Canadian connection. Biomed Instrum Technol. 1989;23(5):384-7. PubMed PMID: 2679944
  7. Kolff WJ. The artificial kidney. J Mt Sinai Hosp N Y. 1947;14(2):71-9. PubMed PMID: 20255749
  8. 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
  9. Abel JJ. On poisons and disease and some experiments with the toxin of the Bacillus tetani. Science. 1934;79(2039):63-70. PubMed PMID: 17798140
  10. 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
  11. Becker RA. The John Jacob Abel papers--primary sources for the history of American pharmacology. Pharm Hist. 1982;24(3):115-6. PubMed PMID: 11615884
  12. Marshall EK Jr. An exhibit at the centennial celebration of John Jacob Abel’s birth. Bull Hist Med. 1958;32(4):356-65. PubMed PMID: 13573011
  13. Arthur G. Epinephrine: a short history. Lancet Respir Med. 2015;3(5):350-1. PubMed PMID: 25969360

PubMed Topic Searches

  1. PubMed: vividiffusion
  2. PubMed: “John Jacob Abel”
  3. PubMed: history of hemodialysis, Haas and Kolff
  4. PubMed: history of the American Society for Pharmacology and Experimental Therapeutics

Further Reading

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Connections