In 1906, Clemens Pirquet and Béla Schick described serum sickness in children receiving large quantities of horse-derived antitoxin.Between 1910 and 1911, Béla Schick developed the Schick test to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were vaccinated. A massive, five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by the Metropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria." A vaccine was developed in the next decade, and deaths began declining significantly in 1924. In 1919, in Dallas, Texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the New York State Health Department. Mulford Company of Philadelphia (manufacturers) paid damages in every case.In the 1920s, each year an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States. Children represented a large majority of these cases and fatalities. One of the most infamous outbreaks of diphtheria occurred in 1925, in Nome, Alaska; the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the Iditarod Trail Sled Dog Race.In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria toxoid (a modified version of the toxin used for vaccination) by treating it with aluminum salts. Vaccination with toxoid was not widely used until the early 1930s.
Behring used this antitoxin (now known to consist of antibodies that neutralize the toxin produced by C. diphtheriae) for human trials in 1891, but they were unsuccessful. Successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized. Von Behring won the first Nobel Prize in medicine in 1901 for his work on diphtheria.In 1895, H. K. Mulford Company of Philadelphia started production and testing of diphtheria antitoxin in the United States. Park and Biggs described the method for producing serum from horses for use in diphtheria treatment.In 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin. This was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines.In 1901, 10 of 11 inoculated St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of tetanus. This incident, coupled with a tetanus outbreak in Camden, New Jersey, played an important part in initiating federal regulation of biologic products.On 7 January 1904, Ruth Cleveland died of diphtheria at the age of 12 years in Princeton, New Jersey. Ruth was the eldest daughter of former President Grover Cleveland and the former first lady Frances Folsom.In 1905, Franklin Royer, from Philadelphias Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin.