by King-Thom Chung, Department of Biology, The University of Memphis

In 1901, the first Nobel Prize for Physiology and Medicine was awarded to Emil von Behring for "his work on serum therapy against diphtheria". Diphtheria is a rare disease now because diphtheria vaccination is available to almost every child born today. But over a century ago, thousands of children died of diphtheria. Von Behring and his associates were responsible for the cease of this disease. Furthermore Dr. Lloyd G. Stevenson has well stated: "for his work on serum therapy, especially its application against diphtheria, ---he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and death." The life of von Behring is one for us to know.

Emil Adolf von Behring was born on March 15, 1854 in Hansdorf, East Prussia (Deutsch-Eylau) as one of thirteen children in a poor family. His father was a school master, and wanted him to study theology, so he prepared himself for the priesthood. But this was not realized because a military doctor, a friend of his family intervened in this decision. Instead, Adolph entered the Army Medical Academy in Berlin (the Pepiniere). He received his medical degree in 1878. Even at this early time, his effective, diligent and hard working attitude toward life could be seen. He was also very methodological. His lecture notes on subject-matter were not only systematically arranged but also enriched by his own ideas. In 1888, he became a lecturer at the Army Medical College. He also took time to participate enthusiastically in the amusement of his fellow students and was known for his incisive speech and even caustic remarks. The military style of training had already been stamped on Behring's life and remained right to the end. He got up at four o'clock every morning, and ate a juicy steak for breakfast. When other colleagues arrived in the laboratory, he had already finished half of the day's work. He maintained a very high working efficiency for a whole life. By this means was laid down the foundation for his success later in life.

To begin with, he worked as army doctor with various military units in Poznan, Eastern Germany, next at the Pharmacological Institute in Bonn, and finally (at the age of 35) he became an assistant to Robert Koch, the well known physician, in 1889, at the University of Berlin. Two years later he accompanied Koch to the Institute for Infectious Diseases where he was made professor at the age of thirty-nine. In 1894, he resigned this appointment to become Professor of Hygiene at Halle and later director at the Martburg University Institute of Hygiene.

From 1889 to 1994, Behring's main effort was to fight against diphtheria. In the beginning, he thought of how the body could be sterilized against the infection of bacteria. He used techniques from army experiences by employing iodoform, acetylene and mercury compounds as antiseptic wound dressings to kill infective bacteria. But all these attempts were failures. During his experiments, he noticed that rats were never attacked by anthrax. He discovered that rat serum was able to destroy the anthrax bacillus. This became the basis of his further experiments.

He treated cultures of diphtheria bacillus with iodine trichloride, with which he then inoculated a number of guinea-pigs. He found that some survived and they became immune to diphtheria. What had happened? Was this due to the chemical agents or some reaction of their own body? Von Behring made a series of experiments. He was able to show that minute amounts of diphtheria toxin were able to immunize the animals. By taking blood serum from an immunized guinea-pig and injecting it into another animal, he found that he was able to transfer the protection to the second guinea-pig. An animal already suffering from diphtheria toxin could sometimes be cured. He discovered that the serum did not affect diphtheria bacilli, but it neutralized the toxin they produced . He used the word antitoxin, (we now know that this is antiserum) which was directed against this the poison produced by bacteria not against the bacteria themselves. Then he treated animals with serum of an animal which had survived the disease. The results were that the serum of an animal that had been cured could cure other animals. This was called serum therapy.

It should be mentioned that the discovery by von Behring was not by accident nor made by von Behring alone. It was led by some previous experiment which von Behring and Shibasaburo Kitasato (1856-1931) worked together. Kitasato came from Japan; only the year before they had met in Koch's laboratory, Kitasato had identified the microbe which caused tetanus and shown that its danger to man lay in the toxin it produced. Together, von Behring and Kitasato were able to demonstrate that the rabbit could be immunized against tetanus in the same way as it could against diphtheria. On Dec 4, 1890, von Behring and Kitasato published their results on tetanus together. A week later, von Behring published a second paper but this one carried his name alone. The second paper described his own experiments with diphtheria. The name "antitoxin" was used. "Antitoxin" was used by him probably because it meant "to use toxin to against toxin", a concept common to the Orientals. This term was ridiculed by the scientific communities at that time because to them it explained nothing. But von Behring had certainly made his mark in this antitoxin work. Kitasato, without whom the serum might never have come into being, deserved just as much credit as von Behring for the work, but apparently was neglected by the Nobel Prize Commitee. As we have learned, racial equality at that time was not so well recognized as today.

Von Behring had then to get enough blood serum containing his diphtheria antitoxin to begin trials on human beings. He started with immunized guinea-pigs. From there he progressed to rabbits and from rabbits to sheep. By Christmas of 1891, he had enough antitoxin to take a needle and inject a small child lying in a Berlin hospital. This immunization was a remarkable success. After careful testing in Berlin's Charite Hospital and later in Leipzig, the serum was made available to doctors. Finally von Behring was successful in establishing a method for the immunization of human being against diphtheria and produced the vaccine called "T.A." for diphtheria.

Another person should be mentioned in the work of diphtheria antitoxin. This was Paul Ehrlich. Ehrlich did pioneering work on the staining of bacteria and on their immunity. He also made the suggestion to use goats and horses to obtain antitoxin many times more powerful than von Behring had succeeded in preparing. He also discovered a method of measuring the amount of antitoxin in blood, and calculated how much of it was needed to effect a safe cure in human beings. Of course, the major contributions were made by von Behring and credit went to him. But Paul Ehrlich did not receive the credit on diphtheria work to the extent as he would have liked to. Nevertheless, Ehrlich was later recognized and awarded the Nobel Prize for his other work (in 1908).

Von Behring was also able to develop commercialization of the antitoxin in 1892. He was approached by the representatives of the Lucius and Bruning dye works at Hochst near Frankfurt. Von Behring agreed to have his product developed and marketed by the Hochst firm. (Von Behring obtained benefits.) The success of diphtheria gave him both fame and fortune. He won a professorship and also some ennoblement with the right to properly call himself "von Behring."* He established his own chemical factory: the "von Behring Works." And he married the daughter of the director of the Berlin Charite Hospital, who was only twenty years old .

For years von Behring worked tirelessly day and night. In the later years, he was particularly interested in the fight against tuberculosis, a terrible disease at that time. Unfortunately at the age of 50, he contracted tuberculosis himself. He then established a research institute to study tuberculosis. He donated all his properties including his Nobel Prize awards and many other awards to the institute. Many well known scientists came to work for him. Unfortunately, he did not succeed in combating tuberculosis, and died on March 31st, 1917, two weeks after his 63rd birthday.

During the period when von Behring and Ehrlich both worked in the Koch laboratory, there was much competition, both racing to be the first. Paul Enhlich did not speak to von Behring nor give him any good comments. Von Behring's style might be considered personal, acquisitive and aggressive in scientific work. But his military training made him go straight to the goal. Because of his military background, he might have cultivated a good relationship with the Ministry of Culture and other governmental officers of Germany, which might have helped von Behring to be successful more rapidly than Ehrlich. The hard, efficient working habits of von Behring, and also his generosity in spending money was a big contradiction to Ehrlich's habits. Despite the conflict and the bad comments from Paul Ehrlich during his life time, at the funeral of Paul Ehrlich in 1915, von Behring was one of the scientists who walked behind Ehrlich's coffin to his grave where he said " If we have hurt you, forgive us". Behring was not vindictive. He lived during the first World War, when the waves of national enthusiasm were running high. Von Behring never took a chauvinistic attitude. He dedicated his last book, published in 1915 to Elie Metschnikoff (a Russian scientist who lived in Paris) with the words : Travaillona! Von Behring was a great human being indeed.

The contribution made by von Behring to the signal triumph of conquerring such a terrible disease was great. His hard working, efficient dedication to science gives much for us to learn. A Russian woman in Moscow wrote a letter to von Behring and said " I do not know if many mothers have expressed their gratitude to you. But my child is saved because you thought wisely and fought for science---your name is blessed by happy mothers like me." This short statement surely described well the great contribution made by von Behring. In this spirit, we should respect and emulate such a pioneer of microbiology and medicine.

References:

1. Hermon, Armin. and Kolbe Jurgeo. 1968. German Nobel Prize Winners. Heinz Moos Verlagsgesellsachaft, Munich, Germany. Pp. 43-44.

2. Reid, Microbes and Men. Chapter 8. Pp. 109-123.