THE WAR AGAINST INFECTION

by Suneet Sood

The two most important events in the history of medicine must be the control of infection and the discovery of anesthesia. This article is about the control of infection.

Till the eighteenth century dying of infection was commonplace, and it was always a good idea for parents to produce spare children, much as we keep a stepney in a car. Richard Gordon gives a dramatic account of Robert Liston, who amputated a man’s leg so fast that his knife also cut his assistant’s fingers, the patient’s testes, and a bystander’s clothes. The patient and the assistant died of infection.1 Physicians believed that infection came from bad air from evil spirits who should be appeased by shrieking and dancing. Surgeons also believed that pus represented the disease expelling itself, and called it “laudable pus”. They would stand before their patients, watch pus pour out, applaud the foul discharge, giggle hysterically, and try not to breathe.

1847. The first blow against infection was struck by Ignaz Semmelweis. Semmelweiss, as a house officer in obstetrics, was posted into “Ward 1” at an Austrian hospital. The mortality from puerperal sepsis was nearly ten times higher in Ward 1 than in Ward 2. Pregnant women would plead with doctors and nurses,2 requesting to be delivered from Ward 2. Semmelweiss believed that there was a contaminant on the hands of the senior doctors who would perform serial vaginal examinations, starting in Ward 2. Of course nobody washed hands, so that by the time they reached Ward 1 their hands had collected infective souvenirs from assorted vaginas much as a traveler’s suitcase collects airline labels. Semmelweiss insisted that the doctors wash their hands before entering his ward. The result was among the most dramatic events in the history of medicine. The infection rate in Ward 1 fell with a thud. Antisepsis had begun! Unfortunately the scientific world was reluctant to accept Semmelweiss’s ideas. His boss actually fired him, defiantly maintained dirty hands, and raised his incidence of lethal puerperal sepsis to 33%, setting a lasting benchmark for scientific idiocy.

1859. Ironically, one of the biggest contributors to medicine was not a physician. Louis Pasteur, a French chemist, proved that micro-organisms grew from other micro-organisms, and did not appear by spontaneous generation. The spontaneous generation debate had been on for generations, yet Pasteur’s proof came from an experiment that was remarkable in its simplicity (see box). Pasteur also worked with the cholera bacillus. Once his culture spoiled, and would not infect chickens. He found that these chickens now could not be infected even by a fresh cholera culture. This led to the discovery of vaccination, and Pasteur later saved a boy from rabies using a vaccine.3

1867. Joseph Lister was a tall, athletic, and handsome British surgeon, but was unhappy nevertheless, because infections raised the mortality from surgery to almost 50%. He tested carbolic acid4 on patients’ wounds, believing that it would provide a barrier between air-borne infection and the wound. The mortality became 66% lower. Over time he began applying the techniques of washing and carbolic acid cleaning of hands, wounds, and instruments, and saw unbelievable success. Physicians, suspicious as ever about something new, made half-hearted objections, but Lister was more fortunate, possibly because he was better looking, than Semmelweiss, who was no Adonis. Cashing in on his results, signboards appeared in medical clinics like mushrooms after rain, declaring that they used “Lister’s methods” for surgery. Lister  finished his surgical career considerably happier than when he had started it.

Text Box: SPONTANEOUS GENERATION
 
200 years before Pasteur, people believed that sweaty underwear could change wheat to mice in three weeks, and that maggots developed spontaneously in meat. An Italian named Redi showed that maggots developed in meat in open but not in sealed flasks, indicating that maggots came from flies’ eggs. Leewenhoek produced a good microscope, and saw micro-organims (which he called animalcules), so people happily concluded that at least animalcules could generate spontaneously, if not maggots and whole mice. In 1745, Needham boiled broth in a flask, sealed it, and waited. Microbes grew in the broth. Needham thought nobody needed further proof of spontaneous generation, but Spallanzani alleged that microorganisms had entered the broth from the air after boiling, but before sealing. He repeated Needham’s experiment after sucking out the air: no growth! However, this only proved that spontaneous generation could not occur without air. Finally, Pasteur created the famous flasks that allowed air but not bacteria to enter, and killed the spontaneous generation theory. He boiled the broth in a bottle with a long, thin, tortuous neck that would allow air, but not dust, to pass in and out. Microbes never grew. Conclusion: microbes are present in dust particles, and will contaminate broth if they have access to it. This small experiment had far-reaching conclusions, and perhaps the highest cost-benefit ratio of all time.

1928. Semmelweiss, Pasteur, and Lister had established prevention by proper antisepsis, but what about the treatment of established infection? Everybody was waiting for antibiotics to be discovered. The breakthrough came with the discovery of penicillin by the Scottish bacteriologist, Alexander Fleming. Fleming served in the army during the First World War. British soldiers were always dying of septicemia, and Fleming was pretty upset about this, as, indeed, most men were (but not all men).5 He worked hard to discover an antibiotic, but without success till Fate, tired of waiting, decided to push her nose in and lend a hand.6 Once, when Fleming had been messing around with staphylococcal colonies as usual, some of his plates picked up a fungus, so he threw these plates into the trash on his way to a vacation. On this vacation he met a friend, and insisted on showing his laboratory to his friend. Fleming returned to his laboratory and picked up the discarded plates to show to his friend. The conversation probably was as follows:

Fleming: “Look at this lovely staphylococcus.”

Friend: “Yes, it’s so good it even has a halo!”

Fleming: “Hello?”

Friend: “Halo”

Fleming: “That’s what I am asking. What halo?”

Friend: “There it is. I thought you put it there on purpose.”

Sure enough, there was a clear zone around the mold-contaminated staphylococcal colony where no clear zone ought to be. The mold was producing a chemical that inhibited the growth of the staphylococci. Fleming isolated it and named it penicillin, and tests confirmed that it could save many patients with septicemia. Fleming was unable to mass-produce it, however. Later Florey and Chain, who shared the Nobel with Fleming, found a way to produce large, commercially viable quantities of penicillin. Undoubtedly Fleming’s discovery had the element of chance, but as they always say, luck favors the prepared mind. In time several other antibiotics would come along, but Fleming’s fame would never be extinguished. 7

Notes

1 And the bystander died of fright, producing the only recorded procedure in history with a 300% mortality.

2 And even ward boys.

3 Pasteur also made serious contributions to the wine industry. The world actually loves him for this, but won’t admit it.

4 Phenol.

5 Germans were not particularly upset that British soldiers were dying of septicemia.

6 This is not a mixed metaphor. Fates can do this peculiar nose-hand routine.

7 Terrible pun.