Even earlier, in 1929, Alexander Fleming had noticed that a soluble product of a Penicillin mold which he called penicillin had valuable "antiseptic" properties and seemed entirely harmless to man. This fact did not bear fruit until 1940 1941, when, partly under the stress of war, Chain, Florey, and their associates in England were able to show how to produce penicillin in usable quantities. Within a short time penicillin had been tried and shown to be effective against a wide range of diseases, conspicuous among them both gonorrhea and syphilis. At first the method of treatment followed one that had just been worked out for the arsphenamines, based on findings with the sulfonamides. A series of injections was given every few hours over a period of days, so as to maintain an effective concentration of the drug in the blood. (This is the kind of treatment Burns describes in The Gallery. But as early as 1945, while distrust of penicillin for syphilis was still present, so that it was often used in combination with arsenoxide and bismuth, a method permitting a single dose of penicillin had been suggested. Several such drugs have been made "repository" penicillins, from which the active material is released slowly after they are injected into a muscle (usually of the buttock). The first contained beeswax and oil. The two in widest use today are benzathine penicillin, called "Bicillin" and by other names, which is especially suited to the single dose method, and a compound including penicillin in an insoluble soap, aluminum monostearate, known as PAM. While multiple injections have continued to be used, field conditions often dictate a single injection treatment (or several injections made together), not only for syphilis but on a world wide scale for the non-venereal treponematoses, for which penicillin is equally effective.

Success with penicillin followed not only for early infectious syphilis but also for late syphilis, which had been refractory to the arsphenamine drugs. In 1923 a somewhat heroic method of treating neurosyphilis had been introduced: The patient was deliberately inoculated with malaria so that the resulting fever would kill the spirochetes. Later, noninfectious and more easily controlled means of raising body temperature came into use and were credited with helping to bring the syphilis rate in the United States down after Surgeon General Parran's control program was instituted in 1938, and before penicillin became available. But by 1954, ten years after the first wide scale use of penicillin, all authorities in the United States agreed that penicillin alone was more effective than anything ever tried before, and that it worked in late as well as in early syphilis. (see PENICILLIN TREATMENT OF SYPHILIS PART II)