It was once characterized as “The Strangling Angel of Children.” Diphtheria is a bacterial infection transmitted via respiratory secretions spread through the air. The bacteria produce a toxin that causes a thick film to develop in the throat, making breathing difficult, and in the worst case, strangling the patient. The name of the disease derives from the Greek for “leather,” an apt description of the distinctive coating seen in the victim’s throat.

In 1878, Britain was shocked by the diphtheria deaths of Alice, Queen Victoria’s thirty-five-year-old daughter, and Alice’s youngest child. Apparently, the disease could be spread by the innocent kiss between a mother and child, the “kiss of death.” The tragic case invigorated research and within a few years, the bacterium responsible for diphtheria was isolated, and the toxin it produced identified as a specific protein. Although the concept of immunization had been introduced in 1796 by Edward Jenner’s prevention of smallpox through inoculation with cowpox extract, a similar regimen was not possible for diphtheria. Attempts at immunization with small doses of the bacterium ended up causing disease. Another approach was needed and was found by German researchers who injected the toxin into a horse. This did not harm the animal but provoked the production of white blood cells from which an “antitoxin” was isolated. That “antitoxin” turned out to be the first “antibody” ever identified. While it saved the lives of many diphtheria victims, it did not prevent the disease, nor did it stop it from spreading.

Then in 1923, Gaston Ramon made a landmark discovery at the Pasteur Institute in Paris. Exposing diphtheria toxin to minute amounts of formaldehyde resulted in the loss of its toxicity but the ability to stimulate antibody production was retained. This opened the door to the possibility of formulating a vaccine with the altered diphtheria toxin, now renamed as a “toxoid.” Indeed, by the end of the 1920s, carefully controlled trials in some 36,000 Canadian children had shown that toxoid injections reduced diphtheria incidence by at least 90%. The first modern vaccine was born!

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