Children, with their small airways, were particularly susceptible to the dangers of diphtheria (and any respiratory infection). Toward the end of the 19th century, the doctor’s option was to stand by and watch them suffocate or, as a last resort, to perform a tracheotomy, cutting a hole into the airway. It was a last resort because it was so dangerous; between the diphtheria and the surgery, survival odds were low for kids who got that sick.
There were severe diphtheria epidemics in the second half of the 19th century, with high mortality rates, but no one knew what actually was causing the infection until 1883, when the bacterium was identified by Edwin Klebs, a pathologist working in Switzerland; one year later, Friedrich Loeffler, a German bacteriologist, was able to grow what became known as the Klebs-Loeffler bacterium in culture, and then to confirm that it caused diphtheria by injecting it into guinea pigs, rabbits, horses and dogs.
Scientists were also able to show that what did the damage was a poison, rather than the organisms themselves — even if all the bacteria were removed from the culture fluid, the fluid was still dangerous and capable of causing the disease. Building on that work, in 1890, Behring and his Japanese colleague, Dr. Shibasaburo Kitasato, developed what they would ultimately call antitoxins to diphtheria and to tetanus, another dangerous organism that does its damage by producing a toxin.
Behring had been an army surgeon and then gone to work as a researcher in bacteriology. The great contribution of the work he did with Kitasato was to show that animals produce specific substances in response to the toxin, which can neutralize the effects. In so doing, they had developed a theory of how the immune system works that would change medicine and medical therapy; in 1901, Behring would win the first Nobel Prize in medicine for his work.
Understand, they had not made an antibiotic that would actually attack the bacteria, but they had gotten infected animals — in this case, guinea pigs, to make antibody, their immune systems’ biological defense against the poison. The guinea pigs were injected with diphtheria toxin that had been inactivated by heating it — so they didn’t get sick, but their immune systems still recognized the substance, reacted and made the antitoxin. When those same animals were exposed to virulent diphtheria bacteria making potent active toxin, they were resistant, and an extract of their blood could be injected into other guinea pigs, and transmitted the ability to withstand infection.