The modern era of so called chemotherapy dates from the announcement of Salvarsan Ehrlich's No. 606 as a specific for syphilis. Ehrlich had won a Nobel Prize (with Metchnikoff) two years before for his studies of immunity. In 1909 his young Japanese assistant, Sahachiro Hata, who had learned how to work with syphilis in rabbits, retested two of Ehrlich's organic arsenical compounds ("arsphenamines"), numbered 418 and 606; earlier tests by another assistant had shown promise for the first but not for the second. In Hata's competent hands the reverse proved true, and 606, Salvarsan or arsphenamine, was announced as the first specific remedy for syphilis. But arsphenamine was soon found to have unpleasant side effects, which were modified but never entirely eliminated in successive years by synthesis of variants with improved properties. Among these, arsenoxides (such as Mapharsen) came to supplant the earlier compounds; but toxic effects and the need for prolonged treatment continued until penicillin displaced the arsenical drugs entirely.

In the meantime compounds of bismuth were introduced (first in 1921), and although they are again somewhat dangerous, their use as adjuncts in the treatment of late syphilis has not entirely disappeared today.

The status of the treatment of syphilis in the heyday of the secinal drugs (1936) is suggested in these comments by a syphilologist, J.E. Klein:

“For proof of the eradication of the spirochete it is necessary to present a convincing series of careful necropsy [autopsy] studies on patients known to have had syphilis which was thoroughly treated. Thus far there has been no such proof. It is illogical to set a time limit, such as from three to five years, after which a patient may marry presumably with assurance of safety. From an ideal eugenic standpoint the syphilitic person is undesirable marriage material. Modem syphilographers recommend continuous treatment until the disease is clinically and serologically "cured," and then a lifetime of medical supervision. At best there may be offered a prospect of a reasonable span of life with a minimum of complications and assurance of arresting the infection if it is properly treated in time.”

In those days the treatment of syphilis was largely in the hands ( of dermatologists, who took Klein's "lifetime of medical supervision" seriously. There was a standing joke: "The syphilologist may be dying, but syphilis is not." Klein's viewpoint, however extreme, was medical rather than moral. In itself it suggests that little progress had been made since the time of Brieux's doctor a generation earlier. At most it seems that arsphenamines helped individual patients but hardly touched the problem of syphilis.

At the very time that Dr. Klein was making his gloomy pronouncement, the new age of chemotherapy was being born, first in the laboratories of the German dye trust where Gerhard Domagk found as early as 1932 that a sulfur containing dye called prontosil could prevent otherwise fatal streptococcal infections in mice. Even before publication of this work in 1935, clinical trials were confirming the effects in man. By 1936 it became clear as a result of studies in France and England that the active component Of prontosil was a rather simple benzene (or benzoic acid) derivative, sulfanilamide, and in succeeding years this and similar compounds called, as a class, sulfonamides (or sulfa drugs), proved dramatically effective in a range of bacterial diseases including gonorrhea.

But within a few years the gonococcus developed resistance to the sulfonamides to the point where they became useless against it. The advent of penicillin saved the day and held it longer; but the same problem has since come up again.