Dobrin N. Paskalev, MD, PhD
`
`Georg Haas (1886–1971):
`The Forgotten
`Hemodialysis Pioneer
`
`“From the initial idea to the actual realization of the
`dialysis method, it was a very long way. I would
`have to say, it was the way of the Cross....”
`—Georg Haas, 1928
`
`The first human hemodialysis in the history of medicine was performed by Georg Haas in
`1924 in the town of Giessen, Germany. The procedure lasted only 15 minutes, and hirudin
`served as the anticoagulant. Haas was able to develop a dialyzer consisting of U-shaped
`collodion tubes immersed in a dialysate bath placed in a glass cylinder. He performed sev-
`eral hemodialysis procedures in uremics between 1924 and 1928, and reported for the first
`time the clinical results obtained. In 1928, Haas introduced heparin into the dialysis proce-
`dure. Because of lack of support by the medical community, Haas was forced to discontin-
`ue his promising work. His research is a real classic in the field of blood purification.
`
`T
`
`hirty years ago, on December 6, 1971,
`Georg Haas died—a German internist
`and an undeservedly forgotten pioneer
`in the field of dialysis science. He was the
`physician who performed the first human he-
`modialysis in the world, in October 1924.
`Prof. Georg Haas was born on April 4,
`1886, in the old Bavarian town of Nürnberg,
`Germany, and studied medicine from 1904
`to 1909 at the Universities of München and
`Freiburg. He wrote his doctoral thesis while
`attending the institute of the famous pathol-
`ogist Ludwig Aschoff (1866–1942).
`In 1911, Haas went to Strassburg in Al-
`sace for further postgraduate education in
`the laboratories of Franz Hofmeister, one of
`the leading figures in the science of bio-
`chemistry and physiology at that time. There
`he started working on amino acid metabo-
`lism in vivo, and experimented with the re-
`moval of some intermediate products from
`animal blood by means of dialysis.1-3
`
`The term “dialysis” had been introduced
`into the scientific literature in 1854 by the
`S c o t t i s h c h e m i s t T h o m a s G r a h a m
`(1805–1869) to describe the phenomenon of
`movement of various types of solutes
`through a semipermeable membrane due to
`osmotic pressure.3-5
`During his experiments, Haas circulated
`the animal blood through the tubular mem-
`branes that comprise reed stalks, prepared
`according to the method described by
`Philippson in 1902. The “reed dialyzer” of
`Philippson took the form of a cylinder, 15
`cm in length, with a volume of 8–10 ml and
`a membrane wall thickness of 0.08 mm.
`Philippson demonstrated the permeability of
`the reed membrane with regard to the nu-
`merous crystalloids, but all proteins, as well
`as glycogen, trypsin, and hirudin, were un-
`able to move through it.6
`Because of World War I, Georg Haas went
`to the town of Giessen, where he lived until his
`
`Dr. Paskalev is with the
`Clinic of Nephrology and
`Hemodialysis, University
`Hospital “St. Marina,”
`Medical University – Varna,
`Varna, Bulgaria.
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`GEORG HAAS
`
`death in 1971. In 1916, he attained an
`academic degree with his research work
`entitled: “Der Indikangehalt des men-
`schlichen Blutes unter normalen und
`pathologischen Zustanden” (“Blood in-
`dican level in humans under normal and
`pathological conditions”). In this paper,
`among others, he pointed out the role of
`indican—a by-product of tryptophan
`metabolism—as a useful marker for the
`evaluation of the severity of renal im-
`pairment.2 From 1921 to his retirement
`in 1950, Prof. Georg Haas served as
`medical director of “Medizinische Po-
`liklinik” (outpatient clinic) of the Med-
`ical University in Giessen.1,2
`
`Vividiffusion
`During the war years, Haas was con-
`fronted, as he own noted, with many
`cases of so-called “Kriegsnephritis”
`(trench nephritis), a clinical condition
`that often progressed to fatal uremia.7,8
`He critically analyzed the customary
`therapeutic maneuvers against ure-
`mia, such as bloodletting, forced
`sweating procedures, and dietary pro-
`tein restriction. Haas stressed that all
`of them were without any significant
`effect,8,9 and that, in part, “the blood-
`letting is even contraindicated, be-
`cause of manifested anemia and
`depressed erythropoiesis.”8
`Logically, Haas returned to the old
`idea for dialysis of blood: “Consider-
`ing the assumption that uremia is
`caused by retention of products ex-
`creted by the urine and themselves
`can be removed by dialysis, I recon-
`sidered my dialysis experiments from
`my previous metabolic studies....”8
`He noted also the advantages of the
`proposed dialysis method of treat-
`ment: “In this manner the red blood
`cells, which are very important for the
`respiration, and all blood proteins
`could be preserved, by simultaneous
`removal of excessive amounts of re-
`tained uremic toxins.”8
`Having no access to the latest sci-
`entific publications due to communi-
`cation problems during the war, Haas
`remained unaware of the work of John
`
`Abel, Leonard Rowntree, and B. Turn-
`er from the pharmacological laborato-
`ry of the Johns Hopkins University in
`Baltimore, MD. In fact, the Americans
`were the first scientists who actually
`realized the principle of dialysis to re-
`move substances from the blood of liv-
`ing animals: “...we have devised a
`method by which the blood of a living
`animal may be submitted to dialysis
`outside the body, and again returned
`to the natural circulation without ex-
`posure to air, infection by microorgan-
`isms, or any alteration which would
`necessarily be prejudicial to life”.10
`
`“I have tried a series
`of different dialyzers from
`a variety of materials,
`animal and vegetable
`membranes and paper
`dialyzers. The best
`implementation was
`obtained from collodion.”
`
`Abel and colleagues described their
`method, called “vividiffusion”: “The
`principle of the method consists in con-
`necting an artery of the animal by a
`cannula to an apparatus made from
`celloidin...in the form of tubes, im-
`mersed in a saline solution or serum
`and providing for the return of the
`blood to the animal’s body by another
`cannula attached to a vein.... The blood
`leaving the artery flows through a per-
`fectly closed system and returns to the
`body within a minute or two without
`having been exposed to contact with
`the air or any chance of microbial in-
`fection, while the diffusible substances
`which it contains can pass out, more or
`less rapidly through the walls of the
`tubes. Coagulation of the blood is pre-
`vented by injection of hirudin.”10
`The newly constructed device for
`blood purification had been named
`the “artificial kidney” in the sense
`
`that “it allows the escape of the dif-
`fusible constituents of the blood, but it
`differs from the natural organ in that it
`makes no distinction between these
`constituents, the rate of their elimina-
`tion being presumably proportional to
`the coefficient of diffusion.”10
`Working mostly with dogs, Abel
`and colleagues never applied the arti-
`ficial kidney on humans, despite their
`hope to use the vividiffusion method
`in cases of poisoning or other causes
`of acute renal impairment. The com-
`mencement of World War I limited the
`import of leeches as a source of
`hirudin from Europe, and the Ameri-
`can investigators were forced to inter-
`rupt their intriguing research in the
`field of blood purification.
`
`The First Human Dialysis
`The credit for performing the first hu-
`man dialysis belongs to Georg Haas.
`Returning in 1919 to civil medical
`work in Giessen, he became familiar
`with the papers of the Baltimore trio
`(1924), as well as with the work of the
`A u s t r i a n c h e m i s t Fr i t z P r eg l
`(1869–1930), a Nobel Prize winner in
`1923, who developed a method for
`preparation of collodion membranes.11
`Experimenting with various types of
`membranes, Haas, finally, was able to
`conclude: “I have tried a series of dif-
`ferent dialyzers from a variety of mate-
`rials, animal and vegetable membranes
`and paper dialyzers. The best imple-
`mentation was obtained with dialyzers
`manufactured from collodion with re-
`spect to fabrication, dialysis effects,
`safe sterilization and because they can
`be obtained in any geometric shape.”8
`Chemically, collodion (celloidin)
`represents a cellulose-trinitrate, the
`cellulose ester of nitric acid. H. Bran-
`connot, a French chemist, had ob-
`tained the substance for the first time
`in 1833. Collodion has explosive prop-
`erties due to its high content of nitrate
`groups, and is also known as guncot-
`ton.5 It is noteworthy that soon after its
`discovery, guncotton was selected as
`the fuel of the space rocket described
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`GEORG HAAS
`
`a blood transfusion pump between the
`artery and the dialyzer in order to over-
`come the resistance opposing the blood
`flow back to the vein. Thus, Haas used,
`for the first time, a prototype of the
`modern blood pump.1,2
`
`In January 1925, in a
`short report, Haas
`described some details of
`this first-ever dialysis of
`a human being in the
`history of medicine.
`As noted in the article,
`because the attempt was
`directed only to
`demonstrate the safety
`and reliability of the new
`technology, the procedure
`lasted only 15 minutes.
`
`In 1928, Haas reported the results of
`three blood cleansings (“Blutwaschun-
`gen”) in two patients with ESRD.8 The
`first of them, a 55-kg man in very poor
`condition despite a protein-restricted
`diet, was dialyzed on January 13, 1928.
`The newly available anticoagulant sub-
`stance heparin was used in this appli-
`cation for the first time.
`Haas performed so-called fraction-
`ated dialysis: 400 ml of blood was
`withdrawn from the patient, he-
`parinized (0.125 g of heparin in 20 ml
`of a saline solution), and circulated for
`30 min through the dialyzer. The arti-
`ficial kidney consisted of 3 glass
`cylinders, each with U-shaped collodi-
`on tubes with a total length of 756 cm
`and a surface area of 1,512 cm2. The
`blood was reinfused into the cubital
`vein. The procedure was repeated 9
`times, and Haas calculated that the to-
`tal removal of non-protein nitrogen
`was about 2,772 g. He was also able to
`demonstrate some uremic substances
`
`(indican, creatinine, phenol) in the
`dialysate bath.8
`Haas pointed out for the first time
`the impressive clinical effect achieved,
`which lasted for 6 days after the dialy-
`sis: The patient was of high spirits, free
`of vomiting and headache, and the ap-
`petite improved manifestly.8
`The second patient was dialyzed on
`March 29, 1928, and the procedure
`was repeated on May 4. Being an as-
`tute clinical observer, Haas noted a
`decrease of blood pressure and an im-
`provement in the heart rhythm at the
`end of the dialysis. He was able to
`note a temporary reduction of diure-
`sis, from 1,000–1,200 ml/24 h before
`dialysis to 507 ml on the day after the
`procedure,8 and proposed several ex-
`planations for this event.
`Haas also pointed out the decrease
`of blood volume during the extracor-
`poreal circulation and noted the loss
`of 100 ml of water from 400–500 ml
`of blood during the 30-min hemodial-
`ysis session. This event was caused by
`ultrafiltration brought on by positive
`pressure in the blood compartment,
`not by osmotic fluid removal, because
`an isotonic Ringer’s solution served as
`the dialysate. As such, Haas recom-
`mended a hemodialysis treatment in
`hyperhydrated patients due to
`nephrotic edema.8
`The author ended his article with op-
`timism: “...despite the limited number of
`observations, I have already gotten the
`distinct impression that it is worth the ef-
`fort to continue along the way taken”.8
`
`A True Pioneering Effort
`Because of lack of support by the
`medical community, Haas was forced
`to discontinue his promising work in
`the field of dialysis.1,2,4,5 Writing for
`the last time in 1952, Haas reminded
`the community that it was he, working
`in his laboratory in Giessen, Germany,
`who introduced hemodialysis as a
`therapeutic method.14
`Fifteen years after the last human
`dialysis in Giessen, in the small town
`of Kampen, The Netherlands, Willem
`
`Kolff (physician) and Hendrik Berk
`(engineer) constructed their rotating
`drum artificial kidney with its “large
`surface area.”15 Their paper, published
`about 20 years after the first article of
`Haas, makes reference to him.15 Thus,
`the way was continued....
`
`I am deeply grateful to my colleagues
`Mrs. L. Stefanova, RN, and Mrs. I.
`Tatcheva, dipl.eng., for their friendly
`help and encouragement during the
`writing of this article.
`
`References
`1. Seyffart C. Die erste Hamodialyse am Men-
`schen (Georg Haas, 1886-1971). Aktuelle
`Nephrologie (Fresenius) 1988; 21:337- 341.
`2. Wizemann V, Benedum J. Nephrology Dialysis
`Transplantation 70th Anniversary of Haemodialy-
`sis: The pioneering contribution of Georg Haas
`(1886-1971). Nephrol Dial Transplant 1994;
`9(12):1829-1831.
`3. Drukker W. Haemodialysis: A Historical Re-
`view. In: Replacement of Renal Function by Dialy-
`sis (2nd Ed.), Drukker W, Parson F, Maher J (eds.).
`Boston: Martinus Nijhoff Publishers, 1983, pp 3-52.
`4. Gottschalk CW, Fellner SK. History of the science
`of dialysis. Am J Nephrol 1997; 17(3-4):289-298.
`5. Vienken J, Diamantoglou M, Henne W, Ned-
`erlof B. Artificial dialysis membranes: From con-
`cept to large-scale production. Am J Nephrol
`1999; 19:355-362.
`6. Philippson P. Uber die Verwendbarkeit der
`Schilfschlauche zur Dialyse. Beitr Chem Phisiol
`Pathol 1902; 1:80-82.
`7. Haas G. Versuche der Blutauswaschung am
`Lebenden mit Hilfe der Dialyse. Klin Wochenschr
`1925; 4(1):13-14.
`8. Haas G. Uber Blutauswaschung. Klin Wochen-
`schr 1928; 7(29):1356-1362.
`9. Haas G. Uber Versuche der Blutauswaschung
`am Lebenden mit Hilfe der Dialyse. Arch Exp
`Pathol Pharmakol 1926; 116:158-172.
`10. Abel JJ, Rowntree LG, Turner BB. On the re-
`moval of diffusible substances from the circula-
`tion blood of living animals by dialysis. J
`Pharmacol Exp Ther 1914; 5:275-316.
`11. Pregl F. Beitrage zur Methodik des
`Dialysierverfahrens von E. Abderhalden. Fer-
`mentforschung 1914; 1:7-12.
`12. Verne J. De la terre a la lune. Sofia, Narodna
`mladez [in Bulgarian] 1973; 56-62.
`13. Haas G. Die Methoden der Blutauswaschen.
`Abderhalden’s Handbuch der biologischen Ar-
`beitsmethoden 1935; 8:717-755.
`14. Haas G. Uber die kunstliche Niere. Dtsch Med
`Wochenschr 1952; 77(52):1640-1641.
`15. Kolff W, Berk H. The artificial kidney: A dia-
`lyser with a great area. Acta Med Scand 1944;
`117:121-134. D&T
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