Béla Schick and Serum Sickness

Circulating Now welcomes guest bloggers Diane Wendt and Mallory Warner from the Division of Medicine and Science at the Smithsonian National Museum of American History. As curators of our most recent exhibition, From DNA to Beer: Harnessing Nature in Medicine and Industry, Diane and Mallory spent months researching four different microbes and the influence they’ve had on human life.

Corynebacterium diphtheria, the bacteria which causes diphtheria, is easily the nastiest microbe we researched for From DNA to Beer.  Its terrifying symptoms—from slowly poisoning the victim to forming a pseudomembrane in the throat causing slow suffocation—are the stuff of nightmares.  It should come as no surprise then, when Emil von Behring developed diphtheria antitoxin serum as a cure in the 1890s it was hailed as nothing short of a miracle.

A doctor give a small child an injection assisted by two nurses.

“Injecting Diphtheria Antitoxin,” illustration from a Parke Davis publication, 1895.
Courtesy The Historical Medical Library of The College of Physicians of Philadelphia.

Soon the antitoxin, which works to neutralize the effects of C. diphtheria’s toxin in the body, became used for more than just treating the infected.  Doctors quickly recognized its potential as a prophylactic and began controlling outbreaks by dosing residents and employees of closed-quartered institutions like hospitals and orphanages with serum after coming into contact with an infected person.  An injection conferred immunity on a patient for approximately three weeks.

As with many miracles, however, antitoxin came with a hitch:  serum sickness.  In some patients, injections of antitoxin resulted in an immune reaction characterized by fever, rash, swelling of the glands, and joint pain.  In 1905, Austrian pediatricians Clemens E. von Pirquet and Béla Schick published the results of their investigation into this phenomenon, in their treatise Serum Sickness (in the original German, Die Serumkrankheit.)

Their research demonstrated that patients who were repeatedly injected with serum suffered not only more intense bouts of sickness with each successive injection, but in some cases, antitoxin injections resulted in dangerous anaphylaxis.  What patients were experiencing was in fact an allergic reaction to horse proteins present in the antitoxin serum.  (Von Pirquet and Schick coined the word “allergy” in 1906.)

So now doctors were faced with a conundrum: how to balance the risks of serum sickness with the benefits of controlling diphtheria outbreaks through preventative antitoxin injections?  Enter the Schick test.  In the early 1910s, Schick developed a simple skin test that allowed doctors to distinguish between those with a natural immunity to diphtheria from previous exposure and those who stood to gain protective temporary immunity from an injection.

Doctors injected a very small dose of diphtheria toxin in a salt solution (1/50 of the minimal lethal dose for a guinea pig) into the arm of a patient to be tested.  As a control, the other arm was injected with the same amount of toxin in a salt solution, mixed with enough antitoxin to neutralize its effect.  Within 24-48 hours, those patients who had never been exposed to diphtheria showed a redness at the injection site of the toxin as the body mounted an immune response to the novel substance.  This “positive” Schick test identified which patients would benefit from a dose of preventative antitoxin serum.

The test proved useful not only in preventing unnecessary exposure to serum, but in developing a greater understanding of the epidemiology of diphtheria.  Schick tests on large groups of people provided data indicating that the time of greatest susceptibility to diphtheria was between the ages of one and four. This window encompassed a period when infants had lost the immunity provided to them from their mothers but before children had enough exposure to non-virulent strains to develop their own immunity.

In 1923, Schick moved to the US, after accepting a post at New York’s Mount Sinai Hospital.  Just two years prior to his arrival, his test provided the New York Public Health System with an important tool in their mass diphtheria immunization campaign for the city’s school children.  The Schick test determined which students were not yet immune and should receive a dose of a new vaccine which conferred immunity for years rather than the mere three weeks of the earlier antitoxin serum.  Students participating in the drive were given buttons reading “I am Schicked! Are you?”

In 1957, with diphtheria under control in the United States, an 80 year old, still-practicing Schick was featured in Life magazine.  Despite his lengthy pediatric career, Schick remained best known for his test, prompting him to tell the reporter documenting his day-to-day work “You see, I’m not just a scratch on the arm!”

Explore From DNA to Beer: Harnessing Nature in Medicine & Industry online for yourself at http://www.nlm.nih.gov/exhibition/fromdnatobeer/index.html. To book the traveling exhibition or see when it comes to your town, visit the traveling exhibition page at http://www.nlm.nih.gov/hmd/about/exhibition/fromdnatobeer-bookinfo.html. Read more posts in this series here.