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Epidemic remembered

In 1735, a diphtheria epidemic swept through Connecticut and the rest of New England. It started in Princeton, N.J., and raged up the coast for several years, killing children throughout New England, including Connecticut. In one family it killed all eight children, swelling their throats until they suffocated. Except for a monograph written in 1939 that was based on the memoir of a Puritan minister, the epidemic would probably not be remembered. For an additional 200 years, parents lived in fear of diphtheria and other epidemics. Now we have a vaccine, but the bacteria are not gone and we should not stop vaccinating. Haiti is currently threatened with a disastrous epidemic. Type “Sean Penn and diphtheria” into your search engine and you will see what I mean. Diphtheria was one of the first infectious diseases to have a scientific remedy, and the way that happened is an interesting story. Until 1857, when Louis Pasteur revealed that bacteria or other microorganisms were responsible for fermentation and putrefaction, no one thought that bacteria could cause disease. In 1865, the English surgeon Joseph Lister, applying Pasteur’s ideas, showed that bacteria were responsible for wound infection and that antiseptic surgical techniques could keep patients from dying of infection, which many did in those days. The scientific and medical world was skeptical of the new germ theory of disease because they could not conceive that something as small as a bacterium, which could barely be seen under the microscopes of the day, could kill a human. Fortunately, Lister was quietly persuasive (it helped that he was Queen Victoria’s physician). Pasteur, who was not a physician, was downright combative. The germ theory slowly won adherents and by the 1880s, Robert Koch and his students had discovered the bacteria that cause tuberculosis, cholera and other diseases. The bacterium that causes diphtheria was cultured from the throats of its victims in 1884 and made to grow in a test tube with a soup of nutrients. It is called Corynebacterium diphtheriae.This microbe releases a toxin that poisons the tissues of the patient, often with fatal results. Although the bacteria usually stay in the throat, where they produce a fearsome coating, the toxin travels in the circulation and affects the heart and other organs. The critical observation was that guinea pigs that survived the disease had something in their blood that would protect them from reinfection. If the serum of an immune guinea pig was inoculated into another guinea pig, it too became immune to diphtheria infection. These blood factors turned out to be antibodies. But how were physicians to find enough serum to treat the tens of thousands of children who die every year from diphtheria? Emile Roux, protégé of Pasteur and one of the creators of anthrax and rabies vaccines, realized that small amounts of diphtheria toxin injected into a horse would not kill it, and with boosters of toxin, the horse became an antibody factory. Roux recovered the antibody by bleeding, without harming the horse, which if well cared for, can spare a couple of liters of blood. In 1894, he conducted a trial in the Paris hospitals and showed that if administered early enough, half of the children who were expected to die were saved by the serum. He announced the results at a conference in Budapest and there was such excitement that the participants rushed to cable offices to alert the people back home to buy horses and inject them with the toxin. The effect on the public imagination is shown in a cartoon from the time. The face is that of Emile Roux. The antitoxin from horses is still essential and there is a critical shortage in Haiti. Diphtheria remained a fearsome disease — ambulances delivered gasping children and terrified parents to dedicated wards in hospitals where nurses and doctors tried to keep the children breathing. The author’s father, now a cogent 99, remembers having diphtheria and getting the injection in 1923. He was sick enough to miss a year of school but was probably saved by Roux’s serum. An effective vaccine was developed in the 1930s from inactivated toxin, and the disease disappeared from the United States and Europe. Vaccines have put diphtheria and other diseases in abeyance, but if we stop vaccinating they will come back, as diphtheria has in Haiti. Now that we have the means of prevention, why are these solutions not universally applied? It is a question to which we will return. Richard Kessin, Ph.D, is professor of pathology and cell biology at the College of Physicians and Surgeons of Columbia University. He lives in Norfolk and can be contacted at rhk2@columbia.edu.

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