August 10, 2006


Alexander Fleming, On the Antibacterial Action of Cultures of a Penicillium, With Special Reference to Their Use in the Isolation of B. Influenzæ, 1929

Alexander Fleming's "serendipitous" discovery was actually quite likely, given his work habits. One description of his laboratory had him "completely surrounded by plates and dishes of bacterial colonies -- growing quilts of reds, greens, and yellows. Other culture dishes were stacked up at random in corners. Test tubes and glass slides littered the counters." Fleming liked to leave his dishes of bacteria lying about for weeks at a time. One day he looked at one of his petri dishes and saw this:

He immediately used his skills in bacteriology to start answering questions. Which moulds created antibacterial compounds? (Only one of 13 strains he tested.) Which bacteria were affected? (Several groups were vulnerable, but a lot weren't.) How effective was the substance, quantitatively? What were its properties? Perhaps most importantly, he injected it into rabbits and mice, and found that it was completely non-toxic.

His discovery took over a decade to mature. A method for manufacturing a concentrated form of the active molecule was not discovered until 1938, just in time for WWII. Penicillin's success led to the discovery of new antibiotics, including streptomycin, which can cure tuberculosis and the plague, in 1943.

Many great advances are triggered by the discovery of new observational tools, which can suddenly give access to a flood of new information. The increasing skill of Dutch lens-makers in the 1600s lead to the creation of the telescope, and then, equally important, the microscope. Suddenly exposed to the eye was a whole new ecology of microorganisms: tiny multicellular plants, animals, and fungi, single-celled protozoa, and bacteria, much simpler, older, and hardier than protozoa.

By the 1920s many diseases were known to be caused by specific microorganisms, and two types of tools had been created to combat them. One was very simple: use toxic chemicals to kill the microorganisms, and hope that the patient can recover from the damage caused once the self-replicating disease has been eradicated. The other was very sophisticated: use bits and pieces of dead disease organisms to trigger the body's immune system, allowing it to build up strong defenses without opposition. Chemotherapy was crude, but had one great advantage over vaccination: it could save patients that were already infected.

Fleming discovered a new strategy, one which fell between chemotherapy and vaccination in sophistication. In the microecology, as in the ecology we can study with the naked eye, there is plenty of competition. Fleming found that we could borrow a substance being used by one microorganism to kill others without harming itself.

Chemotherapy, which once used substances such as mercury, arsenic compounds, and carbolic acid, usually kills everything in the infected area, including the patient's own immune cells. Penicillin, on the other hand, is targetted: it affects specific species of bacteria, and only those bacteria. It was discovered later that penicillin blocks the production of a key component of bacterial cell walls, causing them to dissolve.

Penicillin, and antibiotics in general, are not a magic bullet that has ended all disease. They have no effect on diseases caused by genetic defects, viruses, protozoa, or multicellular parasites. Nonetheless, Penicillin has been a major benefit to humanity. It kills bacteria which cause strep throat, meningitis, pneumonia, gonorrhea, and diphtheria, all of which have practically been eradicated in the developed world. It has also led to the development of further antibiotics, which cure many other bacterial diseases, including typhus, tuberculosis, and the plague, and to an ongoing search for targetted antimicrobial drugs which disrupt disease causing microorganisms without causing collateral damage.


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