Emil von Behring: Father of Serum Therapy and the First Nobel Prize in Medicine

Nobel Information Card

• Award Year: 1901
• Award Category: Physiology or Medicine
• Laureate: Emil Adolf von Behring
• Award Rationale: His work on serum therapy, especially its application against diphtheria
• Birth: 15 March 1854, Hansdorf, Prussia
• Death: 31 March 1917, Marburg, Germany
• Nationality: German
• Institution: University of Marburg
• Significance: First recipient of the Nobel Prize in Physiology or Medicine in history

Life and Education

Emil Adolf von Behring was born on March 15, 1854, in Hansdorf, Prussia (now within Poland's borders). His father was an elementary school teacher and had to support a large family of 13 children. Growing up in an environment where financial conditions were extremely limited, Behring showed great interest in education at an early age. The young man who drew attention with his intelligence and perseverance was accepted into the Kaiser Wilhelm Academy in Berlin (Military Medical Academy) in 1874 because his family could not afford university expenses. This institution required students to serve in the military after graduation as a condition for providing free medical training.

Behring began his medical education in 1878 and started working as a military doctor in the Prussian army upon completion. In his early years, he served in Posen (now Poznań) and Bonn. During this period, his interest in treating infectious diseases deepened. In the early 1880s, he conducted research on the disinfectant properties of iodine and other antiseptic substances. His observation that iodine could neutralize diphtheria toxins later led to the development of the concept of serum therapy.

In 1888, a pivotal moment arrived in Behring's scientific career: he was appointed as a researcher to Robert Koch's Hygiene Institute in Berlin. Koch's laboratory was one of the most prestigious microbiology centers of its time, and here Behring had the opportunity to learn the most advanced techniques in bacteriology. Working alongside Koch expanded Behring's scientific vision and directed him towards systematic experimental research. His collaboration with Japanese scientist Kitasato Shibasaburo, whom he met while working in Koch's laboratory, laid the groundwork for a discovery that would change the course of medical history.

Scientific Work

The focus of Behring's scientific career was combating diphtheria, a terrifying cause of death among children in the late 19th century. Diphtheria was a deadly infection caused by Corynebacterium diphtheriae bacteria that produced a powerful exotoxin, forming a thick membrane in the throat and blocking airways, causing damage to the heart and nervous system. In the final quarter of the 19th century, thousands of children lost their lives to diphtheria every year in Europe; Germany's annual diphtheria mortality rate exceeded 50,000.

While working in Koch's laboratory, Behring was trying to understand the body's natural defense mechanisms against infectious diseases. In the early 1890s, together with Japanese researcher Shibasaburo Kitasato, he made a series of pioneering experiments. By administering small amounts of diphtheria and tetanus toxins to animals, Behring and Kitasato observed that the animals developed resistance to these toxins. Crucially, when they transferred serum from these immunized animals to other animals, the recipient animals also became resistant. This finding showed that immunity was carried by a transferable substance in the blood — a substance Behring called antitoxin.

In December 1890, Behring and Kitasato published one of the most important articles in medical history: their discovery of diphtheria and tetanus antitoxins was reported in the Deutsche Medizinische Wochenschrift journal. In their study, they experimentally demonstrated that serum from animals immunized against diphtheria toxin could either cure or protect other infected animals when injected into them. This marked the first systematic demonstration of passive immunity in medical history.

Paul Ehrlich's contributions to Behring's work also played a significant role in its practical application. Ehrlich was crucial in standardizing antitoxin serums and optimizing production processes. With collaboration from Hoechst pharmaceutical company, large-scale production of diphtheria antiserum began.

The Discovery That Led to the Nobel Prize

Behring's discovery of the diphtheria antitoxin was put into clinical practice on Christmas Eve 1891. In a Berlin hospital a child on the verge of death from severe diphtheria was treated with diphtheria antiserum for the first time, and survived. This dramatic clinical success made antiserum therapy a sensation throughout Europe. By the end of 1893 antitoxin serum was being mass-produced and distributed to hospitals across Europe; it brought about a striking reduction in mortality from diphtheria, which had until then been a major cause of death among children.

Large-scale clinical trials conducted between 1893 and 1894 definitively confirmed the efficacy of diphtheria antiserum. The mortality rate among patients treated with antiserum plummeted dramatically compared to those who did not receive treatment. While the death rate from diphtheria approached 50% before serum therapy, it dropped below 25% with treatment. This success sparked widespread excitement across Europe and led to rapid expansion of antiserum production.

Emil von Behring's work extended beyond diphtheria treatment, creating a paradigm shift for all immunological treatments against infectious diseases. The concept of serum therapy was based on the idea of toxin-antitoxin interaction, which formed one of the fundamental principles of modern immunology. Therefore, in 1901, the first Nobel Prize in Physiology or Medicine was awarded to Emil von Behring upon establishment of the new Nobel Prizes.

The Nobel Committee highlighted Behring's work in the field of serum therapy, particularly its application against diphtheria, as opening up a new path in medical science and giving doctors a victorious weapon against disease and death. With this achievement, Behring became the first recipient of the Nobel Prize in Medicine. Interestingly, many scientists believed that Kitasato Shibasaburo should have also shared this award; however, the Nobel Committee awarded it solely to Behring.

The Prize and Its Aftermath

After receiving the Nobel Prize, Behring continued his work at the University of Marburg. In the years following 1901, he shifted his focus towards developing an improved diphtheria vaccine. While antiserum treatment was life-saving, its protective effects were temporary; Behring aimed to develop an active vaccine that would provide lasting immunity. In 1913, he introduced an active immunization method using toxin-antitoxin mixtures against diphtheria, which later became the precursor to the toxoid vaccine developed by Gaston Ramon.

During World War I, Behring made great efforts to increase production of tetanus antiserum. The antiserum played a vital role in protecting soldiers from tetanus infections at the front lines. He also conducted research on tuberculosis treatment, but was less successful in this area than he had been with diphtheria.

In 1901, the Prussian government bestowed nobility title upon him, adding "von" to his name. In 1903, he founded the pharmaceutical company Behringwerke, which industrialized the production of sera and vaccines. Today, this company continues its activities under the name CSL Behring and is one of the leading companies worldwide in blood products and immunological drugs.

Emil von Behring died of pneumonia in Marburg on 31 March 1917. He passed away at the age of 63, leaving behind a scientific legacy that has saved millions of lives.

Legacy and Impact Today

Behring's serum therapy discovery has directly impacted many areas of modern medicine. The principle of passive immunization remains widely used in clinical practice today. Monoclonal antibody therapies used in rabies prophylaxis, hepatitis B, neonatal Rh incompatibility, and most recently in the COVID-19 pandemic are all extensions of the fundamental principle established by Behring over 130 years ago.

Diphtheria has been brought largely under control thanks to the vaccine and antitoxin programs developed in the wake of Behring's discovery. Within the Expanded Programme on Immunization of the World Health Organization, the diphtheria-tetanus-pertussis (DTP) vaccine is administered to billions of children worldwide. Following in Behring's footsteps, scientists have carried the fight against infectious disease to new dimensions by developing toxoid vaccines, conjugate vaccines, and monoclonal antibody technologies.

Behring's work also contributed to the emergence of immunology as an independent field of science. The discovery of antitoxins paved the way for Paul Ehrlich's side chain theory, Jules Bordet's discovery of the complement system, and Karl Landsteiner's identification of blood groups. These chain discoveries have brought revolutionary progress in understanding the immune system.

In Germany, the memory of Behring is kept alive. The Emil von Behring Library exists at the University of Marburg, and the city of Marburg regularly holds scientific events in honor of Behring. The German Postal Service has issued a stamp featuring Behring's portrait. The CSL Behring company, which bears his name, continues to carry on his legacy on an industrial scale.

Lesser-Known Facts

• Behring was the eldest of 13 siblings; his family was so poor that, unable to afford university fees, he had to enroll in the military medical academy.
• The first clinical use of diphtheria antiserum took place on Christmas Eve 1891; this is why in Germany Behring was popularly nicknamed the "Saviour of the Children."
• A dispute over the priority of the antitoxin discovery between Behring and Kitasato continued for many years. Kitasato's contribution was for a long time not adequately appreciated.
• Despite his significant contributions to the standardization and production of diphtheria antiserum, Paul Ehrlich was deeply disappointed that his name was not included in the 1901 Nobel Prize.
• Behring was only 47 when he received the Nobel Prize, and although in his later years he worked on tuberculosis treatment he was never able to repeat his diphtheria success.
• During the First World War the Behringwerke factory he founded produced tetanus antiserum for the soldiers at the front, saving the lives of thousands of troops.
• In a survey carried out in Germany in 1940, Behring was ranked third among the most admired German scientists.