Near the end of the 19th century, diphtheria was a terrifying disease that killed many infants and small children. The first symptom of the disease was a sore throat, often followed by the development of a gray membrane in the throat that made breathing impossible. Death occurred rapidly, even in the absence of a membrane. Frederick Loeffler, working in Robert Koch’s laboratory in Berlin, found club-shaped bacteria growing in the throat of people with the disease but not elsewhere in their bodies. He guessed that the organisms were making a poison that spread through the bloodstream. In Paris, at the Pasteur Institute, Emile Roux and Alexandre Yersin followed up by growing the bacteria in quantity and extracting the poison, or toxin, from strained culture fluids. When injected into guinea pigs, the toxin killed the animals.

Back in Berlin, Emil von Behring injected the diphtheria toxin into guinea pigs that had been previously inoculated with the bacteria and had recovered from diphtheria. These guinea pigs did not become ill from the toxin, suggesting to von Behring that something in their blood, which he called antitoxin, protected against the toxin. To test this theory, he mixed toxin with serum from a guinea pig that had recovered from diphtheria and injected this mixture into an animal that had not had the disease. The guinea pig remained well. In further experiments, he cured animals with diphtheria by giving them antitoxin.

The results of these experiments in animals were put to the test in people in late 1891, when an epidemic of diphtheria occurred in Berlin. On Christmas night in 1891, antitoxin was first given to an infected child who then recovered from the dreaded diphtheria. The substances in blood with antitoxin properties soon were given the more general name of antibodies, and materials that could generate antibodies were called antigens.

Emil von Behring received the first Nobel Prize in medicine in 1901 for this work on antibody therapy. It took many more decades of investigation before the biochemical nature of antibodies was elucidated. In 1972, Rodney Porter and Gerald Edelman were awarded the Nobel Prize for their part in determining the chemical structure of antibodies.

In the previous chapter, mechanisms of nonspecific immunity were discussed. Nonspecific immunity is innate, is present in all normal people, and is ready to act whenever the body is infected or injured. Mechanisms of innate immunity are nonspecific with respect to any offending agent. They are equally effective on the first encounter or in any subsequent encounter with an invading organism. They provide an immediate response as a first line of defense, ever ready to protect. While this early defense is at work, another even more effective response is being brought into play. This is the specific acquired immune response.