John Jacob Abel’s pursuit of a technique that would remove metabolic end products and poisons from the blood enabled the development of the artificial kidney.
The origins of the artificial kidney are found in the biochemical research of John Jacob Abel, the first professor of pharmacology at The Johns Hopkins University School of Medicine, and the clinical investigations of Willem Johan Kolff, a Dutch physician. Abel, often praised as the “father of American pharmacology,” is the prototype of the first generation of professional American scientists. To pursue a career in physiological chemistry, Abel went to Europe, where he worked in the laboratories of several notable biochemists. Under their tutelage, he learned both the theory and the laboratory technique necessary to conduct independent biochemical research. He received his medical degree in Strasbourg in 1888.
Soon after Abel returned to the United States in 1891, Victor Vaughan, his former chemistry professor at the University of Michigan, offered him a full-time instructorship in materia medica at that university. When Abel moved to Johns Hopkins in 1893, he not only had begun to earn a reputation for excellent research but also had incorporated German pedagogical models into Michigan’s medical education. His courses in pharmacology at Michigan and Johns Hopkins were the first such courses offered in the United States.
Around 1912, Abel began to investigate the metabolic by-products carried in the blood. He noted that this work was difficult, for it was nearly impossible to detect, let alone study, the trace amounts of the many substances found. The theoretical foundation in physical chemistry needed to solve this problem was readily available, but no suitable technique or apparatus had been devised that could remove these substances from blood. Abel recognized that a semipermeable membrane and a slightly saline solution removed these substances from the blood by dialysis. Constructing a dialysis machine occupied Abel and two of his colleagues, Leonard Rowntree
The first tests were performed on rabbits and dogs. Abel studied the isolated substances and discovered that in addition to urea, free amino acids were passed out. Abel termed this process “vividiffusion.” Although he experimented on rabbits and dogs only, Abel quickly realized the clinical implications of his discovery. He wrote that “in the hope of providing a substitute in such emergencies, which might tide over a dangerous crisis, as well as for the important information which it might be expected to provide, concerning the substances normally present in the blood, . . . a method has been devised by which the blood of a living animal may be submitted to dialysis outside the body, and again returned to the natural circulation.” The removal of large quantities of urea and other poisonous substances occurred in a relatively short time, therefore indicating that vividiffusion could serve as an artificial kidney during cases of renal failure. Abel’s physiological research necessitated removing, studying, and replacing without hemolysis (breaking of red blood cells) large amounts of blood from living animals. He noted that this process, which he termed “plasmaphaeresis,” could create blood banks for the storage of blood.
In 1914, Abel published reports of these two discoveries in a series of three articles in the Journal of Pharmacology and Applied Therapeutics and demonstrated the techniques in London and in Groningen, the Netherlands. Although he suggested clinical applications for the techniques, his interest remained primarily biochemical. Abel turned to other pharmacological pursuits, such as the crystallization of insulin, and never returned to the research possibilities that inhered in vividiffusion.
Georg Haas,
In 1937, Kolff was a young physician at Groningen. In his account of the manufacture of the artificial kidney, he recounted his pain at seeing patients die from renal failure and added that the emotion stimulated him to search for some cure or relief. After hearing physicians discuss the possibility of dialysis on human patients, he decided to build such a machine. Kolff knew that cellophane was an excellent dialyzing membrane and that heparin was a good anticoagulant, but he recognized that Abel’s and Haas’s machines had insufficient capacity to be clinically useful. There was no theoretical barrier to constructing such a machine, which he did, but he never used it clinically.
John Jacob Abel.
During World War II, aided by the director of the local enamel factory, Kolff constructed an artificial kidney that received its first clinical trial on March 17, 1943. Between March, 1943, and July 21, 1944, Kolff used his secretly constructed dialysis machines on fifteen patients—of whom only one survived—and then published his results in the journal Acta Medica Scandinavica. By the time the war ended, he had collected enough data and had sufficiently refined the technique that he was confident that renal dialysis was a viable therapeutic measure. He brought machines to Amsterdam and The Hague and encouraged other physicians to employ them. He continued to study hemodialysis and improve his machines. This work was successful, and in 1947 he brought improved machines to London and the United States. By the time he reached Boston, however, he had given away all of his machines. Empty-handed, therefore, he explained the technique to John P. Merrill,
Nils Alwall
Abel’s work not only divulged the existence of previously unknown substances in the blood and inspired the development of the artificial kidney, but it also spurred interest in the possibility of organ transplantation, created new questions in immunology, and raised ethical issues about the allocation of scarce resources. The development of kidney transplantation
After World War II, surgeons attempted to transplant kidneys from one animal to another, but after a few days the recipients’ bodies began to reject the new kidneys, and the animals died. Despite several discouraging failures, researchers in Europe and America transplanted kidneys in several patients to devise methods to combat the physiological and clinical difficulties encountered in such operations. These surgeons used artificial kidneys to sustain patients who were waiting for transplants or to maintain them until their transplanted kidneys began to function. In 1954, John P. Merrill of Boston’s Peter Bent Brigham Hospital—to whom Kolff had demonstrated an artificial kidney—successfully transplanted kidneys in identical twins. The development in 1962 of immunosuppressant drugs made transplantation surgery more feasible and widened the range of possible donors.
After kidney transplantation gained widespread acceptance, the artificial kidney came to be considered a stopgap measure, ideally used only until a permanent solution—that is, a donated kidney—could be obtained. The machinery is cumbersome, and the need to use it can significantly alter the patient’s quality of life. The problem, however, is that the demand for organs for transplant is greater than its supply. Hospital administrators, physicians, and medical ethicists grapple with the difficult moral dilemma of how to allocate the scarce resources among individuals who need them so desperately.
The work of immunologists and transplant surgeons is marked by mutual stimulation and exchange. Modern transplantation became possible only after Peter Medawar’s discovery in the 1940’s of the mechanics of immune rejection. Thomas Starzl, who worked at the University of Colorado in the 1960’s, could not have begun his extensive series of transplantations without the presence of several immunosuppressant drugs. Surgeons’ clinical application of these drugs, in turn, provides information that immunologists apply to a wide variety of problems, including the struggle against acquired immune deficiency syndrome (AIDS).
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Abel, John J., L. G. Rowntree, and B. B. Turner. “On the Removal of Diffusable Substances from the Circulating Blood of Living Animals by Dialysis.” Journal of Pharmacology and Applied Therapeutics 5 (1914): 275-316. This article, in which Abel announced his discovery, is an excellent example of clear scientific writing. The researcher’s elegance of experimental technique is mirrored in his prose. -
Cameron, J. S. History of the Treatment of Renal Failure by Dialysis. Oxford, England: Oxford University Press, 2002. Covers the history of the development of the artificial kidney, including Abel’s role in that work, as well as the medical and ethical dilemmas attached to the use of dialysis. Features illustrations and index. -
Harvey, A. McGehee, Gert Brieger, Susan L. Abrams, and Victor McKusick. A Centennial History of Medicine at Johns Hopkins. 2 vols. Baltimore: The Johns Hopkins University Press, 1989. A general history of The Johns Hopkins University School of Medicine that places Abel in his institutional context. Volume 2, a pictorial companion to volume 1, contains illustrations of Abel’s vividiffusion apparatus. -
Kolff, Willem J. Artificial Organs. New York: John Wiley & Sons, 1976. An account of the medical and technical issues in the development and use of artificial kidneys and hearts. -
_______. “First Clinical Experience with the Artificial Kidney.” Annals of Internal Medicine 62 (1965): 608-619. Kolff’s account of how he overcame various difficulties to develop the artificial kidney. -
Parascandola, John. “John J. Abel and the Early Development of Pharmacology at The Johns Hopkins University.” Bulletin of the History of Medicine 56 (1982): 512-527. An examination of Abel’s role in the separation of pharmacology from pharmacy and the establishment of professional pharmacology in the United States in the first two decades of the twentieth century. -
Tilney, Nicholas L. Transplant: From Myth to Reality. New Haven, Conn.: Yale University Press, 2003. This book, suitable for both professionals and laypersons, traces the evolution of organ transplantation from its beginnings in the imaginations of human beings to its current status as accepted treatment. Describes early transplantation attempts, the evolution of surgical technique, the first successful kidney transplant (in 1954 between identical twins), the introduction of the concept of host tolerance, and scientific advances for suppressing the immune system. -
Wilson, Leonard. “The Development of Organ Transplantation at Minnesota.” In Medical Revolution in Minnesota: A History of the University of Minnesota Medical School. St. Paul, Minn.: Midewiwin Press, 1989. Surgeons at the University of Minnesota Medical School pioneered heart transplantation surgery. Wilson provides the background to such surgery, notably the development of kidney transplantations.
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