Cells and Serum
The idea of cells defending the body against invaders was proposed by the Russian zoologist I. I. Mechnikov. He saw that a yeast infecting a transparent water flea was surrounded by white blood cells that stuck to the yeast and killed it.
Mechnikov called the cells phagocytes (Mechnikov 1884; Besredka 1921). As Arthur Silverstein has pointed out, phagocytosis at this time was associated with the pathology of inflammation rather than immunity. The first experimental work on immunity, Pasteur’s early experiments on chicken cholera, was only four years old in 1884 when Mechnikov’s work appeared, and the germ theory of disease itself was hardly any older (Silverstein 1979). Mechnikov’s idea attracted Pasteur’s interest, and Mechnikov was invited to Paris in 1888.In Germany, especially among the Berlin bacteriologists around Robert Koch, the chief role in defense appeared more and more clearly to belong to the blood serum rather than the cells. This group of workers had earlier mounted an all-out attack on Pasteur and the French workers, including Mechnikov. This was a transposition into scientific terms of the old nationalistic hatred between France and Germany that had resulted in the Franco-Prussian War of 1870 (Foster 1970). In this case, the Germans had some very telling ammunition. In 1890, Emil von Behring and his Japanese colleague Shibasaburo Kitasato, working at Koch’s institute, diverted attention from cellular to so-called humoral immunity when they showed that animals could be made immune to the effects of the toxins produced by both the tetanus and diphtheria bacilli. Immunity could be transferred by an injection of immune serum, a finding that was quickly applied outside the laboratory. Within a year, on Christmas Eve of 1891, the serum was tried out on a child acutely ill with diphtheria. The results were sensational (Behring 1895).
The production of sheep and goat serum began in 1892, and in 1894 it was introduced into the Berlin hospitals. There was an immediate fall in diphtheria mortality (Behring 1895). Meanwhile in Paris, Emile Roux and Alexandre Yersin made the large-scale production of the serum possible by using horses as a source of antitoxin. In their first 300 cases, mortality fell from 50 to 25 percent. In 1894 the Pasteur serum was taken to England by Joseph Lister, and it was equally successful there (Parish 1965).In England, cells and serum came together in the work of the clinical bacteriologist Almroth Wright. Wright demonstrated that phagocytes could not engulf their victims without the help of a serum factor that he called an opsonin. The level of opsonic activity showed the state of his patients’ defenses against bacterial infection and their response to the vaccines he prepared for them. Local infections, such as boils, acne, appendicitis, and tuberculosis, were treated with autovaccines made from the patient’s own organisms and calculated, in Bernard Shaw’s phrase, to stimulate the phagocytes. At the Department for Therapeutic Immunization at St. Mary’s Hospital in London, he and a devoted group worked night and day at stimulating the phagocytes and determining opsonic indices. Autovaccination and injections were the treatment of the moment, especially, it seems, in the English-speaking world. From about 1945 onward, however, autovaccines were superseded by antibiotics. Among the young bacteriologists who were Wright’s colleagues was Alexander Fleming, who later discovered penicillin. The department Wright founded is now the Wright-Fleming Institute.