Emil von Behring: Pioneer of Diphtheria Serum Therapy and First Nobel Laureate in Medicine (1901)

Nobel Information Card

• Award Year: 1901
• Field: Physiology or Medicine
• Award Rationale: For his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in medical science and placed in the hands of the physician a victorious weapon against illness and death.
• Born: 15 March 1854, Hansdorf, Prussia (present-day Poland)
• Died: 31 March 1917, Marburg, Germany
• Nationality: German
• Institution: University of Marburg

Life and Education

Emil Adolf von Behring was born on 15 March 1854 in the Prussian town of Hansdorf (today Lawice, within the borders of Poland). The second son of a family of thirteen children, Behring came from a modest farming background. His father, Georg August Behring, was a schoolmaster, and the family's finances were sharply limited. Even so, young Emil's extraordinary academic ability was recognized at an early age.

Behring received his early education at a gymnasium in Hohenstein. Although his family did not have the means to pay for a university education, an opportunity opened up for the gifted young student. In 1874 he was admitted to the Kaiser Wilhelm Academie (the Military Medical Academy) in Berlin. This institution offered its students a free medical education, but in return required ten years of military service after graduation. Behring accepted these terms and completed his medical training in 1878.

During his years as a military physician, Behring carried out intensive research on infectious diseases and antiseptic agents. After serving in Posen (today Poznań) and Bonn, in 1888 he drew attention with his work on iodoform. While investigating the disinfectant properties of iodoform in this period, he arrived at the idea that chemical substances could neutralize toxins; this thought planted the seeds of the revolutionary discovery that lay ahead.

When he joined Robert Koch's Hygiene Institute in Berlin in 1889, Behring stepped into one of the most productive scientific environments of the era. Working in Koch's laboratory was a turning point in Behring's career. There he had the opportunity to work with Kitasato Shibasaburo and to carry out his first important experiments on serum therapy.

Scientific Work

Behring's scientific career was built on the effort to understand the body's defense mechanisms against infectious diseases. Even before joining Koch's laboratory, he had carried out extensive work on antiseptic agents and their effects on living organisms. His observations on iodoform's ability to neutralize tetanus toxin, in particular, led him toward the concept of the antitoxin.

In 1890, Behring and Kitasato published one of the most important papers in the history of science. In it they showed that the blood serum of animals immunized against tetanus toxin could protect other animals subsequently exposed to the toxin. This finding announced the birth of serum therapy. The same year, in a second paper published under his name alone, Behring applied the same principle to diphtheria and proved the existence of the diphtheria antitoxin.

The practical significance of these discoveries was immense. In the late nineteenth century, diphtheria was one of the most feared diseases, especially among children. Characterized by false membranes in the throat, it killed thousands of children by asphyxiation. In Germany alone, about 50,000 children died of diphtheria each year. Behring's discovery offered the first real weapon against this terrible picture.

Behring expended great effort to optimize antitoxin production. His first experiments had been carried out on small animals, but producing enough serum to treat human patients required larger animals. Horse serum was identified as an ideal source for diphtheria antitoxin. By exposing horses to progressively larger doses of diphtheria toxin, Behring obtained sera containing high concentrations of antitoxin.

Christmas Eve 1891 became a turning point in history. In Berlin, the diphtheria antitoxin was administered for the first time to a young girl who was about to die of diphtheria. The child recovered, and this success became the first dramatic proof of the clinical efficacy of serum therapy. For the treatment to be applied widely, however, the antitoxin had to be standardized and produced on a large scale.

The Discovery That Led to the Nobel Prize

Behring's discovery of the diphtheria antitoxin rested on the understanding of several fundamental scientific principles. The first was that the symptoms of diphtheria are produced not directly by the diphtheria bacillus (Corynebacterium diphtheriae) but through the toxin it produces — an understanding that built on Friedrich Loeffler's work of 1884. The second was that the organism produces a specific antitoxin against this toxin. The third was that this antitoxin can be transferred from one animal to another to provide passive immunity.

Behring's experimental approach was systematic and meticulous. He worked first with guinea pigs and rabbits, injecting the animals with sub-lethal doses of diphtheria toxin and observing that they gradually became resistant to the toxin. He then took the blood serum of these immune animals and gave it to other animals infected with the toxin. The results were striking: the animals that received the serum survived, while those in the control group died.

To understand the mechanism of action of the antitoxin, Behring also carried out extensive in-vitro experiments. When he mixed antitoxin serum with toxin in a test tube, he showed that the toxin was neutralized. This proved that the antitoxin acted directly on the toxin to render it harmless. In the language of modern immunology, Behring had described one of the earliest examples of an antibody–antigen interaction.

The transition to clinical practice was difficult. The first serum preparations were not standardized and their potency varied. Behring worked together with Paul Ehrlich to make important advances in the standardization of antitoxin units. The toxin–antitoxin titration method developed by Ehrlich made it possible to dose serum preparations reliably. Although this collaboration would later give rise to serious disputes between the two men, it was scientifically extraordinarily productive.

In 1893 Behring proposed that toxin–antitoxin mixtures could be used to prevent diphtheria. This approach was a forerunner of the concept of active immunization and would later form the basis for vaccine development. From 1894 onward, diphtheria antitoxin serum began to be produced and used widely throughout Europe. Through his collaboration with the Hoechst company, large-scale commercial production was achieved.

The clinical results of serum therapy were striking. Before antitoxin treatment, the mortality of diphtheria was over 50 percent. With serum therapy, that rate fell below 25 percent, and in cases treated early it dropped much further. This dramatic improvement deservedly earned Behring great renown, and the public bestowed on him the title of 'savior of children'.

The Prize and Its Aftermath

At the first Nobel Prize ceremony held in Stockholm on 10 December 1901, the first Nobel Prize in Physiology or Medicine was presented to Emil von Behring. Receiving the award from the hand of King Oscar II of Sweden, Behring noted that the honor belonged not only to himself but to the entire field of serology. The Nobel Committee's citation emphasized that Behring had opened a new road in medical science and placed in the hands of the physician a victorious weapon against illness and death.

After the Nobel Prize, Behring continued his work at the University of Marburg. In 1901 the Prussian government raised him to the nobility with the title 'von'. He used a substantial portion of the prize money to finance his research and to set up a serum-production facility near Marburg. This facility operated under the name Behringwerke and later became one of Germany's most important producers of biological products.

In the last years of his career, Behring concentrated on work on tuberculosis. He had been struck by the failure of Robert Koch's tuberculin therapy and tried to develop alternative approaches. He developed a vaccine against bovine tuberculosis (Bovovaccin), but it did not bring the hoped-for success. During the First World War, his work on tetanus serum therapy made important contributions to military medicine.

Emil von Behring died of pneumonia in Marburg on 31 March 1917. The scientist, who passed away at the age of sixty-three, left behind a vast scientific legacy that laid the foundations of modern immunology. After his death, his name continued to live on through Behringwerke and its production of sera and vaccines.

Legacy and Impact Today

Emil von Behring's scientific legacy continues to be felt in many areas of modern medicine. The concept of serum therapy today underpins passive immunotherapy. The principle of antitoxin treatment has led to the development of life-saving therapies in many conditions besides diphtheria — among them tetanus, botulism, and snake bites.

Behring's work played a critical role in the understanding of the humoral (fluid-based) arm of the immune system. The discovery of antitoxins was the first and most important step on the road to the identification of antibodies. Paul Ehrlich's side-chain theory was developed to account for Behring's experimental findings and laid down the conceptual framework of modern antibody biology.

Today, thanks to effective vaccination programs, diphtheria has been almost eliminated in developed countries. The DTaP (diphtheria–tetanus–acellular pertussis) vaccine is one of the core components of childhood immunization programs worldwide. The first link in this chain of success is Behring's discovery of the antitoxin in 1890.

The emergence of convalescent plasma therapy during the COVID-19 pandemic showed that the principle of serum therapy laid down by Behring 130 years ago remains valid. The therapeutic use of plasma from recovered patients is essentially a modern application of Behring's antitoxin approach. Monoclonal antibody therapies represent the most advanced point of this tradition.

Behring's name lives on today in many institutions across Germany. The Emil von Behring Library at Philipps University in Marburg preserves his memory. The German Postal Service has issued stamps in his honor over the years. Behringwerke, after various mergers and acquisitions, continues operations today under the name CSL Behring and remains one of the world's leading producers of plasma-derived therapies.

Lesser-Known Facts

• Behring was not able to attend the ceremony when he received the Nobel Prize; he received the award through the German embassy in Sweden. Ill health prevented him from traveling.
• Despite Paul Ehrlich's critical contributions to the standardization of the antitoxin, Behring did not share the Nobel Prize with him. This caused a long-standing tension between the two men.
• Behring, who had begun his career as a military physician, had to complete his ten-year mandatory service and was only able to move into civilian research at the age of 35.
• The story of the first child treated with the diphtheria antitoxin caused a great stir in Germany because it coincided with Christmas Eve, and gave Behring the status of a popular hero.
• Behring made a substantial fortune from the antitoxin-production agreement he had with the Hoechst company and used it to buy a large estate near Marburg.
• In his personal life he was rather reserved and prone to depression. He frequently quarreled with colleagues and was especially sensitive about questions of scientific priority.
• In addition to being the first recipient of the Nobel Prize in Medicine, Behring received many other international honors and medals, including the Legion of Honor.