WASSERMANN, AUGUST PAUL VON

(b. Bamberg, Germany, 21 February 1866; d. Berlin, Germany, 16 March 1925)

immunology, serology, bacteriology, cancer therapy.

Wassermann was the second son of Angelo Wassermann, a Bavarian court banker who was elevated to the hereditary nobility in 1910, and Dora Bauer. He attended the Gymnasium in Bamberg and studied medicine at the universities of Erlangen, Vienna, and Munich, receiving the M.D. at Strasbourg in 1888 for a work on the effect of Sulfonal. In 1895 he married Alice von Taussig of Vienna; they had two sons. Attracted by the presence of Robert Koch, Wassermann went to Berlin in 1891 and began work at Koch’s hygiene institute as assistant to Bernhard Proskauer. On 1 September 1891 he entered the newly established Institute for Infectious Diseases, headed by Koch, as an unpaid assistant in both the scientific and clinical divisions. In February 1893 he became a temporary assistant assigned to problems related to cholera, and from February 1895 to June 1896 he was inspecting physician at the institute’s antitoxin control station for diphtheria, which was transferred in 1896 to the Institute for Serum Research and Testing in the Berlin suburb of Steglitz. Wassermann then returned to the institute itself as an unpaid assistant. During this time he was senior physician in the clinical division, of which he became director on 1 April 1902.

In 1901 Wassermann became Privatdozent in internal medicine at the Friedrich Wilhelm University in Berlin, having obtained the title of professor in 1898. He was named extraordinary professor in 1902 and in 1911, honorary professor. In 1906 he, became director of the division of experimental therapy and serum research at the Institute for Infectious Diseases, and the following year he was awarded the title of Geheimer Medizinalrat. Wassermann left the institute in 1913 to become director of the Institute for Experimental Therapy at the Kaiser Wilhelm Society for the Advancement of Science in Berlin.

During World War I, Wassermann’s research was considerably curtailed and was finally suspended completely. As a hygienist and bacteriologist with the rank of brigadier general in the medical corps, he supervised epidemic control on the Eastern Front. He was subsequently appointed director of the Office of Hygiene and Bacteriology of the Prussian Ministry of War.

In the early 1920’s Wassermann’s institute was expanded and renamed the Kaiser Wilhelm Institute for Experimental Therapy and Biochemistry. Although Wassermann began to suffer in 1924 from Bright’s disease, which took his life the following year, he went to the institute whenever possible, remaining director until his death.

Wassermann’s first papers, written with Ludwig Brieger, Shibasaburo Kitasato (1892), and R. F. J. Pfeiffer (1893), dealt with cholera immunity; they were followed by his own studies of cholera immunity and diphtheria antitoxin (1894, 1895). In independent investigations Wassermann showed that many people possess diphtheria antitoxin, in varying degrees, in their serum; and he related this finding to differences in the ability to resist diphtheria infection.

Using pyocyaneous bacteria, Wassermann conducted experiments in 1896 on breaking the toxin antitoxin bonds; this research lent support to Ehrlich’s side-chain theory, of which Wassermann became a proponent. His investigations made in 1898 with T. Takaki aroused considerable interest in the theory by furnishing important support for it, for their results indicated that matter from the brain of healthy animals can bond tetanus toxin selectively and thereby detoxify it. Having observed and described the variable rate at which influenza can progress. Wassermann in 1900 attributed its periodic recurrence to a decrease in the immunity that had been acquired in the previous pandemic. He also drew attention in several works to the difference between antibacterial and antitoxic immunity.

Wassermann was the first to point out that a reagent existed in precipitins and that it was far superior in sensitivity to that usually employed in chemistry. On the basis of studies paralleling those of Paul Uhlenhuth, who preceded him in publication but used a different method, Wassermann reported the possibility of differentiating albumen by a serologic procedure, and in 1901 he pointed out its potential practical applications in a joint paper with A. Schütze. Three years earlier he had suggested to Koch that human and animal blood might be differentiated by means of specific antibodies for erythrocytes. Drawing upon his work with Schütze, he also proposed a method for the evaluation of precipitating serums.

Experiments on immunity to swine plague bacteria undertaken with R. Ostertag (1902, 1904) led Wassermann to recognize the necessity of producing polyvalent vaccines and serums, since the antigen pattern of various strains of the same type of bacterium exhibits differences. In work with J. Citron (1905) Wassermann attributed residual post typhus immunity not to antibodies in the blood but to a specific alteration of the intestinal mucosa and thus to local immunity.

After 1900 Wassermann became increasingly occupied with problems relating to complement, which had not been thoroughly investigated. Considering this omission responsible in certain instances for the failure of serum therapy (1900), he called for the determination of complement in serum (1901), expecting it to yield important clinical benefits. In 1901 Jules Bordet and O. Gengou reported on complement-fixing substances in the serum of patients recovering from cholera and in other serums obtained by specific immunization, for instance, against red blood cells. They noted that the presence of these substances could be demonstrated, in the case of red blood cells, by hemolysis, if these substances could not also react with the complement being in fresh serums.

Working with Carl Bruck, Wassermann conducted experiments on complement fixation, one of which was designed to find antibodies against tuberculin in the vicinity of tubercular foci (1906). A new feature of this research was that the reaction was carried out not only with unchanged bacteria but also with extracts derived by agitation. Employing the latter to effect fixation of the complement, Wassermann determined the strength of the meningococcal antiserum; and with Wilhelm Kolle at the Institute for Infectious Diseases he produced it for practical application. In 1906, with Albert Neisser and C. Brück. Wassermann published” Eine serodiagnostische Reaktion bei Syphilis, “in which the authors examined experimentally induced syphilis in apes and then investigated human patients infected with the disease. Wassermann described the principle guiding their research:

The so-called fixation of the complement… depends upon this principle: that when an antigen is mixed with its homologous immune body a union occurs between the two. If complement—a constituent of every fresh serum —is added at the same time, it becomes anchored through the union of the antigen and antibody. It follows, accordingly, that if the complement is anchored, the conclusion may be drawn that either the homologous antigen or the homologous immune body is present in such a mixture. The determination whether in such an experiment the complement is bound can be made easily and convincingly. For this purpose one needs simply to add simultaneously, or somewhat later, the serum of an animal which has been previously treated with red blood corpuscles, the so-called amboceptor, together with its homologous erythrocytes. If the complement has already become bound as a result of the union between the antigen and immune bodies, then it is no longer available for the haemolytic amboceptor and the red blood corpuscles. Consequently the latter remain undissolved… [and] from the appearance or non-appearance of haemolysis, one can draw the conclusion as to whether the sought-for antigen or immune body is present.

Beyond facilitating diagnosis in acute cases of syphilis, the reaction illuminated certain unproved relationships between diseases. In 1906 Wassermann demonstrated with Felix Plaut that in creeping paralysis the Wassermann reaction shows positive when carried out on spinal fluid. The findings of Wassermann and his co-workers not only made it possible to detect syphilis but also established a new basis of therapy.

After a short time, Wassermann had to abandon the theory with which he had begun his research, namely that his experiments demonstrated the presence of specific antibodies against the agent of syphilis or its extracted portions; for the reaction showed positive in persons infected with the illness even when extracts from normal organs were used. In research at his own institute, Wassermann later sought to find a theoretical explanation of the reaction, which was rapidly proving its worth in clinical practice. With this end in view he attempted in 1922 to culture Spirochaeta pallida.

Around 1910 Wassermann began to devote his major efforts to discovering a way of treating cancer via the bloodstream. Unfortunately, in treating human patients, he was unable to repeat his success at Koch’s institute in 1911, when he had arrested the growth of tumors in mice by administering selenides and tellurium salts. During his last years Wassermann focused his research primarily on obtaining a complement-fixation reaction in tuberculosis (1923).

Although small in stature, Wassermann was not —contrary to assertions —stooped, and he had bright blue (not dark) eyes. He was an impulsive man whose rich intellectual endowment soon became evident in conversation. Gifted with exceptional oratorical ability, he had an outstanding capacity to render complicated theoretical problems comprehensible to the uninitiated. He often lectured at weekly sessions of the Berlin Medical Society and eagerly accepted invitations to speak before local groups and international congresses. He was fond of similes and continually devised new ones in his lectures —comparing specificality, for example, to a light source that has a maximum but also a cone of dispersion. Similarly, he sought to find “railroad tracks” in an organism that might provide a clue for cancer therapy; the particular “car” that circulates on them was of only secondary importance.

With Rudolf Kraus, Wassermann was a cofound-er of the Free Association for Microbiology, and he served as president of the Academy for Knowledge of Judaism. Although occasionally sarcastic, he was always helpful and kind, even under difficult conditions. He once characterized himself as a “laboratory worker.” His many honors included orders and decorations from Prussia, Belgium, Japan, Romania, Spain, and Turkey. In 1921 Wassermann was the first recipient of the Aronson Foundation Prize.

BIBLIOGRAPHY

I. Original Works. There is no collected edition of Wassermann’s more than 150 scientific publications, most of which are listed by K.-E. Gillert and K. Gerber (see below). Wassermann’s separately published monographs include Hämolysine, Cytotoxine unci Präzipitine, Sammlung Klinischer Vorträge, no. 331 (Leipzig, 1902), 2nd ed., rev by J. Leuchs and M. Wassermann (Leipzig, 1910). His important collaborative effort with W. Kolle resulted in Handbuch der patheogenen Mikroorganismen,, 6 vols. (Jena, 1903-1909), 2nd ed., enl. (1912-1913), to which he contributed many articles: and he was author of “Allgemeine Lehre der Infektionskrankheiten,” in W.Ebstein and J. Schwalbe, eds., Handbuch der praktischen Medizin, 2nd ed., 4 vols. (Stuttgart, 1906); and “Schweineseucheserum,” in R. Kraus and C. Levaditi, eds., Handbuch der Technik und Methodik der Immurtitätsforschung, II (Jena, 1909).

Wassermann’s memoirs cited in the present article include “Über künstliche Schutzimpfung von Thieren gegen Cholera asiatica,” in Deutsche medizinische Wochenschrift,18 (1892), 701, written with L. Brieger; “Untersuchungen über Immunität gegen Cholera asiatica.” in Zeitschrift für Hygiene und Infektionskrankheiten, 14 (1893), 35–45; “Untersuchungen über das Wesen der Cholcraimmunität.” ibid., 46–63, written with R. F. J. Pfeiffer; “über die Gewinnung der Diphtherie-Antitoxine aus Blutserum und Milch immunisierter Thiere,” ibid., 18 (1894), 239–250, written with P.Ehrlich; “über die persönliche Disposition und die Prophylaxe gegenüber Diphtherie,” ibid., 19 (1895). 408–426; and “über tetanusantiloxische Eigenschaften des normalen Centralnervensystems,” in Berliner klinische Wochenschrift,35 (1898), 5-6, written with T. Takaki.

Works published after 1900 include “Einige Beiträge zur Pathologie der Influenza,” in Deutsche medizinische Wochenschrift, 26 (1900), 445–447; “Über eine neue forensische Methode Zur Unterscheidung von Menschen-und Thierblut,” in Berliner klinische Wochenschrift,38 (1901), 187-190, written with A. Schütze; “über die Bildungsstätten der Typhusimmunkörper. Ein Beitrag zur Frage der localen Immunität der Gewebe,” in Zeitschrift für Hygiene und Infektionskrankheiten, 50 (1905), 331–348, written with J. Citron: “Eine serodiagnostische Reaktion bei Syphilis,” in Deutsche medizinische Wochenschrift. 32 (1906), 745–746. written with A. Neisser and C. Bruck, in which the test for syphilis was announced; and “Reinkulturen der Spirochaeta pallida in festem und flüssigem Nährboden sowie Übertragung dieser Kulturen auf Tiere,” in Klinische Wochenschrift,1 (1922), 1101, written with M, Ficker.

II. Secondary literature. There is no full-length biography. Studies of individual aspects of his research and obituaries include G. Bako. “August von Wassermann (1866–1925),” in Journal of the American Medical Association,209 (1969); G. Blumenthal, “August von Wassermann zum 25. Todestage,” in Zeitschrift für Immunitätsforschung und experimentelle Therapie, 107 (1950), 380–384; T. Brugsch, Arzt seit fünf Jahrzehnten (Beriin. 1957), 148–149; “Wassermann: Nachhaltige Reaktion,” in Selecta,8 (1966), 606; E. Friedberger, “August von Wassermannt†,” in Zeitschrift für Immunitätsforschung und experimentelle Therapie,43 (1925), i-xii; K. Gerber. “Bibliographie der Arbeilen aus dem Robert Koch-Institut 1891-1965,” in Zentralblatt für Bakteriologie, Purasitenkunde. Infektionskrankheiten und Hygiene. I. Abnteilung, Referate, 203 (1966), 1-274; K.E. Gillert. “Bibliographie der Arbeiten August von Wassermann’s 1914–1925,” ibid.,254 (1977), 289–291; N. Korken, Jewish Physicians. A Biographical Index (Jerusalem. 1973), with references to fürther literature: R. Kraus, “August von Wassermann 1865–1915.” in Seuchenbekämpfung und experimentelle Therapie…. 11 (1925), 104–106; “Wassermann,” in British Medical Journal (1966),1 436-437; H. Mengel, “August von Wassermann zum 100. Geburtstag,” in Münchner medizinische Wochenschrift. 108 (1966), 1434–1436; A. Keitner, ed., Menschen und Menschenwerke, I (Vienna, 1924), 669–670; H. Mühsam, Jüdisches Lexikon, IV. pt. 2 (Berlin, 1930), cols, 1344–1346; F. Neufeld, “August von Wassermannt,† in Deutsche medizinische Wochenschrift,16 (1925) 667-668; I., Mc. I., “August von Wassermann, M.D.,” in British Medical Journal (1925), 1, 638; .J Piesch, János Ein Arzt erzählt sein Leben (Munich, 1951), 70, 74-76; H. Reiter. “August von Wassermannt†.” in Münchener medizinische Wochenschrift,72 (1925), 813–814; H. Sachs, “August von Wassermann.” in Klinische Wochenschrift,4 (1925), 902-903; G. H. Schneider. “August Paul von Wassermann zum 100. Geburtstag,” in Berliner Ärzteblatt, 79 (1966), 278–279; “Zum 100. Geburtstag von August von Wassermann,” in Deutsches Ärzteblalt, 63 (1966), 586: and “Persönliche Erinnerungen an August Paul von Wassermann….” in Deutsche Apotherkerzeitung,106 (1966), 1908-1909; and E. Witebsky and F. Milgrom, “August von Wassermann (1866-1925). Wassermann Reaction,” in Journal of the American Medical Association,204 (1968), 1000–1001.

Karl-Ernst Gillert