Behring, Emil von

Behring, Emil von

(b. Hansdorf, Germany, 15 March 1854; d Marburg, Germany, 31 March 1917)

medicine, serology.

Behring, one of twelve children of August Georg Behring, a teacher, and his second wife, Augustine Zech, grew up in simple circumstances in Hansdorf, a small town that is now under Polish administration. His father intended him to be a teacher or a minister, both traditional family professions, and in 1866 enrolled him in the Gymnasium of Hohenstein, in East Prussia. During his school years Behring discovered his interest in medicine, but he saw no hope of pursuing it. Accordingly, he planned to enter the University of Königsberg as a theology student.

Fortunately, one of Behring’s teachers arranged for his acceptance at the Friedrich Wilhelms Institute in Berlin, where future military surgeons received a free medical education in return for promising to serve in the Prussian Army for ten years after passing their university examinations. Thus. in 1874 Behring became a cadet at the institute. In 1878 he received the M.D. and in 1880 passed his state board examinations. In the same year he was appointed intern at the Charitè, a Berlin hospital, and in 1881 was attached to a cavalry regiment in Posen (now Poznan, Poland) as assistant surgeon. In between, he served for a short time as physician to a battalion stationed in Wohlau.

Behring, who had shown remarkable dedication at the Friedrich Wilhelms Institute, began to ponder scientific questions during his service in Wohlau and Posen. He was particularly interested in the possibility of combating infectious diseases through the use of disinfectants.

In 1881 Behring wrote his first paper on sepsis and antisepsis in theory and practice. In it he raised the question whether, in addition to external disinfection, the entire living organism could not be disinfected internally. He started investigations on iodoform (discovered as early as 1822 but introduced into wound treatment only in 1880) and the disinfecting effect of its derivatives. In 1882 he published his first treatise, “Experimentelle Arbeiten über desinficierende Mittel,” which had been written in Posen. He had to admit that in many cases the disinfectant’s toxic effect upon the organism was obviously much stronger then its disinfecting effect upon the bacteria. He concluded that the favorable results observed after the application of iodoform to infected wounds were not due to its being a parasiticide, but to its antitoxic effects. On the basis of later research, however, he came to reject its general use. In 1898 he wrote:

The fact that living animal and human body cells show much more sensitivity to disinfecting agents than any hitherto known bacteria may almost be considered a law of nature. As a result, before bacteria are killed by a disinfectant or their growth in the organs can be stunted, the infected animal body itself is killed by this same agent [“Über Heilprinzipien, insbesondere über das ätiologische und das isopathische Heilprinzip,” in Deutsche medizinische Wochenschrift, 24 . no. 5 (1898), 67].

According to Behring’s own statements, these iodo form experiments were the beginning of his preoccupation with antitoxic blood-serum therapy.

In 1883, at his own request, Behring was transferred from remote West Prussia to Winzig, Silesia. There he published another paper on iodoform poisonings and their treatment. At this time he prepared for the civil service medical examinations, since he planned to enter the Prussian Public Health Service after completing his service as a military surgeon. In 1887 he was promoted to captain and sent to the Pharmacological Institute in Bonn for further training. The director of this institute, Carl Binz, was especially interested in all problems concerning disinfectants. In the same year Behring published a report on new investigations concerning iodoform and acetylene. At the institute he acquired the knowledge and working habits necessary for accurate animal experiments and research in toxicology. In 1888 Behring was sent to Berlin, and after a brief service at the Academy for Military Medicine, in 1889 he joined the Institute for Hygiene of the University of Berlin, then presided over by Robert Koch. Here, between 1889 and 1895, Behring developed his pioneering ideas on serum therapy and his theory of antitoxins. Also in 1889, Behring finished his army service and became Koch’s full-time assistant.

As early as 1887, in Bonn, Behring had ascertained that the serum of tetanus-immune white rats contained a substance that neutralized anthrax bacilli. This he saw as the cause of “resistance.” Beginning in 1889, he worked in Berlin with Shibasaburo Kitasato on the isolation and definition of this agent. One of their goals was still the discovery of suitable systemic disinfecting agents, especially against anthrax, for which iodine, gold, and zinc compounds were tested. But of greater promise were experiments aimed at inhibiting the causative agents by using certain sera similar in effect to disinfectants, since the organism showed far greater tolerance to the sera. On 4 December 1890 Behring and Kitasato jointly published their first paper on blood-serum therapy, followed on 11 December by another report, signed by Behring alone, which discussed the blood-serum therapy not only in the treatment of tetanus but also of diphtheria. In it he stressed four points:

(1) The blood of tetanus-immune rabbits possesses tetanus toxin-destroying properties.

(2) These properties are also present in extravascular blood and in the cell-free serum obtained from the letter.

(3) These properties are so lasting that they remain effective when injected into other animals, thus making it possible to achieve excellent therapeutic effects with blood or serum transfusions.

(4) Tetanus toxin-destroying properties are not present in the blood of animals not immune to tetanus.

Behring immediately recognized that evidently a new principle of defense by the organism against infection had been discovered, one that clearly clashed with the then-prevalent cellular pathology of Virchow. Subsequently, Behring clashed with Virchow over the importance of his discoveries. One day before the publication of Behring’s discovery, Ludwig Brieger and Carl Fränkel published a paper in the Berliner klinische Wochenschrift on the isolation of a protein substance—in their opinion a toxic substance—from bacteria; they called it “toxalbumine” and ascribed to it the severity of various infectious diseases. In the following years, however, Behring was able to show that the therapeutic principle in the serum, which he called “antitoxin” was ineffective against “toxalbumine” but acted against a specific toxin secreted by the bacteria. Incidentally, he succeeded in obtaining his new antitoxin-containing blood serum from guinea pigs treated not only with live diphtheria bacilli but also with diphtheria toxin alone in increasing dosages. Thus, in contrast with the hitherto prevailing phagocytosis theory of Élie Metchnikoff, he demonstrated the humoral defense capacities of the organism. Accordingly, he terminated his first work with the famous passage from Goethe’s Faust :“Blood is a very special liquid.”

When Paul Ehrlich demonstrated in 1891 that even vegetable poisons led to the formation of antitoxins in the organism, Behring’s theory was confirmed and a lifelong friendship was formed. Both Behring and Ehrlich were then serving as assistants at the Koch Institute in Berlin. Behring immediately recognized the unusual importance of his discovery, and wrote:

For hundreds and thousands of years the wisest physicians and scientists have studied the properties of blood and its relation to health and illness, without ever suspecting the specific antibodies appearing in the blood as a result of an infectious disease, which are capable of rendering infectious toxins harmless [Kleinschmidt, p. 347].

In 1891, at the Seventh International hygiene Congress in London, Behring apperared for the first time before the public and delivered a lecture entitled “Desinfektion am lebenden Organismus.” He stressed that his method resulted above all in a natural increase of natural healing powers, leading in turn to increased resistance to nerve and cell toxins produced by pathogens. In 1892 he published his investigations in Die praktischen Ziele der Blutserumtherapie and der Immunisierungsmethoden zum Zwecke der Gewinnung von Heilserum and Das Tetanusheilserum and seine Anwendung auf tetanuskranke Menschen. Behring had to defend himself incessantly against all kinds of attacks. Failures due to the low antitoxin content or his first sera made his enthusiastic statements lesscredible. Furthermore, Behring—who at times used sharp language in his polemics—was forced to take issue with priorty claims by other authors.

The legendary account of the first use of diphtheria serum on a patient on Christmas Eve 1891 has not been fully verified. A crital case of diphtheria is said to have been successfully treated with the serum by Behring’s colleagues Geissler and Wernicke, in the infectious-disease ward of the surgical clinic of Berlin University. It is doubtful that sufficient serum was available at that time, since it was obtained exclusively from guinea pigs and then from sheep. When, in 1894, Roux and André Martin introduced the immunization of horses, Behring immediately adopted and extended this procedure. From 1892 on, he was backed by Farbwerke Meister, Lucius and Brüning, a dye works in Höchst, a suburb of Frankfurt. Until then Behring had put his own money in his research.

From 1893 on, serum therapy experimentation was conducted on a more extensive scale. In that year Behring became professor. Soon afterward there appeared the first publications by Hermann Kossel and Otto Heubner on results obtained with the new serum therapy, which reduced the mortality rate from 52 percent to 25 percent. In 1894 the first serum therapy experiments were carried out in France, England, and the United States. In the meantime, in 1893 Behring had written two important works on problems of great interest to him, Die ätiologische Behandlung der Infektionskrankheiten and Geschichte der Diphtherie, to which he added two books on the treatment of infectious diseases (1894, 1898).

Behring was quick to see that in order to obtain results in man, methods for standardizing the serum must be found. These methods were developed in 1897 by Ehrlich. Since 1895, however, standardization of the serum had been under state control. In 1896 the control authority became the Institute for Serum Research and Testing; today it is known as the Paul Ehrilich Institute and performs the same tasks on a more extensive scale.

In the fall of 1894 Behring, whose relationship with Koch had perceptibly cooled, was appointed associate professor of hygiene in Halle. He taught there for only a short time and with moderate success. The following year he was appointed professor of hygiene in Marburg—against the wishes of the Medical Faculty and thanks to determined efforts on his behalf by Friedrich Althoff, a powerful figure in the Prussian Ministry for Education. In Marburg, Behring carried on intensive research and organized what is now known as the Behring Institute. In the meantime, he had acquired great renown, especially in France, where Roux and Metchnikoff had become his close friends. He was made an officer of the Legion of Honor in 1895 and with Roux shared the 50,000-franc prize of the Académie de Médecine as well as the 50,000-franc prize of the Académie des Sciences. Also in 1895 he received the Prussian title of Geheimrat (privy councillor), and in 1901 his lifework was crowned with the first Nobel Prize in physiology and medicine, followed by his elevation to the hereditary nobility.

Beginning in 1889, Behring dedicated himself to a new task, the fight against tuberculosis. In competition with Koch he also attempted to find a substance suitable for tuberculosis vaccination. Finally, he felt he had succeeded with “tulase,” an extract from tuberculosis bacilli treated with chloral hydrate, but his vaccination attempts failed. Nevertheless, we are indebted to Behring for his important findings on the spread of tuberculosis, which he ascribed mainly to the consumption by infants with Koch, he was convinced bovine and human tuberculosis were identical a belief based on an understandable error. Nevertheless, his suggestions for combating bovine tuberculosis were of extreme importance and brought about vital changes in public health policy. In 1900, however, he realized that he was not achieving his objective and concluded one of his papers as follows: “Here I should like to say simply that I have definitely abandoned my hope for obtaining antitoxin for humans from cured and immunized tubercular cattle. Consequently, I have stopped searching for an antitoxin against tuberculosis.”

Nevertheless, Behring’s preoccupation with tuberculosis continued, and in 1903 and 1904 he devoted two monographs to this subject. Finally, in 1905 he suggested disinfection of milk for infants by adding Formalin and hydrogen peroxide, a process that proved impractical.

In 1913, in dogged pursuit of his theory of the origin of antitoxins as a result of insufficient toxin in the organism, Behring introduced active preventive vaccination against diphtheria, Its basis was a balanced toxin-antitoxin mixture, rendered stable by formaldehyde.

World War I, which separated Behring from his friends outside Germany, helped to substantiate his theories. The preventive, although still passive, tetanus vaccination saved the lives of millions of German soldiers. For his contributions Behring was a warded the Iron Cross, an unusual decoration for a non-combatant.

In 1896 Behring and married Else Spinola, daughter of one of the directors of the Charité Hospital in Berlin, who bore him six sons. The Villa Behring in Marburg, still standing today, was the gathering place of society. Behring also owned a house on Capri, where he was fond of vacationing. He liked to seclude himself in Switzerland, especially when suffering from the serious depressions that occasionally required sanatorium treatment. A fractured thigh, which initially seemed harmless, led to a pseudarthrosis that resulted in increasingly limited mobility,. When Behring contracted pneumonia, his already weakened constitution was unable to with stand the multiple strain, and he died in Marburg on 31 March 1917.

For the discovery of antitoxins and the development of passive and active preventive vaccinations against diphtheria and tetanus, Behring was honored with the epithet “Children’s Savior.” By the same token, he could be called the “Soldier’s Savior.” His modern concepts raised humoral pathology to renewed importance, and he was certainly the equal of the other two pioneers in bacteriology, Pasteur and Koch. In his antitoxin theory Behring discovered a new principle in the fight against infections. He was able to realize his plan for an important and worthwhile lifework only by single-mindedly pursuing his original ideas. He thereby became involved in disputes with certain experts. Also, since he embraced the principle of “authority, not majority,” he was not particularly adept at making friends or founding a school. He remained one of the great solitary figures in the history of medicine.

BIBLIOGRAPHY

I. Original Works. Most of Behring’s scientific papers may be found in two editions of collected works, the first covering the period 1882–1893 and the second the later period up to 1915: Gesammelte Abhandlugen zur ätiologischen Therpaie von ansteckenden Krankheiten (Leipzing, 1893); and Gesammelte Abhandlungen. Neue Folge (Bonn, 1915). The most important papers and monogrpahs are “Über lodoform und lodoformwirkung” in Deutsche medizinische Wochenschrift, 8 (1882), 146–148; “Die Bedeutung des lodoforms in der antiseptrischen Wundbehandlung,” ibid., 323–329; “Über das Zustandekommen der Diphtherie–lmmunität and der Tetanus-lmmunitat bei Thieren,” ibid., 16 (1890), 113–114, written with S. Kitasato; “Untersuchungen über das Zustandekommen der Diphtherie–lmmunitat bei Thieren,” 1145–1148; “Über Immunisierung und Heilung von versuchsthieren bei der Diphtherie,” in Zeitschrift für Hygiene und Infektionskrankheiten, 12 (1892), 10–44, written with E. Wernicke; Die praktischen Ziele der Blusterumtherapie und die Immunisierungsmethoden zum Zwecke der Gewinnung von Heilserum (Leipzig, 1892); “Die Behandlung der Diphtherie mit Diphtherieheilserum,” in Deutsche medizinische Wocheschrift, 19 (1893), 543–547, and 20 (1894), 645–646; Die Geschichte der Diphtherie (Leipzig,1893); Die Bekämpfung der infektionskrankheiten (Lepzig, 1894; Allgemeine Therapie der Infektionskrankheiten (Berlin-Vienna,1898); Diehthereie, Begriffsbestimmung, Zustandekommen, Erkennung und Verhutüng (Berlin,1901); Tuberkulosebekämpfung (Marburg, 1903); “Tuberkuloseentstheung, Tuberkulosebekämpfung und Säuglingsernährung,” in Beiträge zur experimentellen Therapie, 8 (1904); Einführung in die Lehre von der Bekämpfung der infektionskrankhetitn (Berlin, 1912); and “Über cinncues Diphtherieschutzmittel,” in Deutsche medizinische Wochenschrift, 39 (1913), 873–876, and 40 (1914), 1139.

II. Secondary Literature. The best biography, with many illustrations and references, is H. Zeiss and R. Bieling, Behring. Gestalt and Werk (Berlin, 1940). An exhaustive bibliography may be found in H. Dold, In memoriam Paul Ehrlich and Emil von Behring zur 70. Wiederkehr ihrer Geburtstage (Berlin, 1924). A biographical novel is H. Unger, Emil von Behring (Hamburg, 1948). Additional biographical articles are E. Bauereisen, “Emil von Behring,” in Neue deutsche Biographie, li ((Berlin, 1955), 14–15; H. von Behring, “Emil v. Behring,” in Lebensbilder aus Kurhessen and Waldeck, 1 (1935), 10-14; and “Emil v. Behring zum 100. Geburtstag,” in Deutsches medizinisches Journal, 5 (1954), 172–173; A. Beyer, “Zum 100. Geburtstag von Paul Ehrlich and Emil v. Behring,” in Deutsches Gesundheitswesen, 9 (1954), 293-296; C. H. Browning, “Emil von Behring and Paul Ehrlich; Their Contributions to Science,” in Nature, 175 (1955), 616-619; K. W. Clauberg, “Das immunologische Vermächtinis Emil von Behrings and Paul Ehrlichs,” in Deutsches medizinisches Journal, 5 (1954), 138–146; C. Hallauer, “Emil von Behring and sein Werk,” in Schweizerische Zeitschrift für allgemeine Pathologie and Bakteriologie, 17 (1954), 392–399: M. Jantsch, “Gemeinsames im wissenschaftlichen Werk Ehrlichs and Behrings,” in Wiener klinische Wochenschrift, 66 (1954), 181–182; H. Klein-schmidt, “Zuni 100. Geburtstag von Emil v. Behring,” in Medizinische (1954), 347-348; A. S. Macnalty, “Emil von Behring,” in British Medical Journal (1954), 1 668–670; and P. Schaaf, Emil von Behring zurn Gedächtnis. Herausgegeben von der Universität Marburg (Marburg, 1944); Robbert Koch and Emil von Behring. Ursprung and Geist einer Forschung (Berlin, 1944); and obituary notices in British Medical Journal(1917), 1, 498; and Lancer(1917), 1, 890.

H. Schadewaldtz