Paul Ehrlich (1854–1915), Sacachiro Hata (1873–1938)
Paul Ehrlich was one of the outstanding biomedical scientists of the twentieth century, distinguishing himself through significant discoveries in pharmacology, the chemistry of drugs, bacteriology, pathology, and immunology, including his “side-chain theory” of antibody formation, for which he received the 1908 Nobel Prize. His discoveries of Atoxyl for sleeping sickness and, more important, Salvarsan for syphilis, established his reputation as the Father of Chemotherapy.
German-born and medically trained, Ehrlich spent the first twenty years of his scientific career investigating the selective staining of cells and tissues by dye substances. He noted that some cells were stained, while others remained colorless, and he was the first to stain the tuberculosis-causing microbe, permitting its visualization for diagnostic purposes. He postulated that drugs interact with selective chemical groupings on cells, which he termed receptors.
IN SEARCH OF THE MAGIC BULLET. These studies led Ehrlich to theorize that drugs could be selectively toxic to infectious-disease-causing microbes and harmless to the patient. Seeking such a “magic bullet” and working with his Japanese colleague Sacachiro Hata at the Georg-Speyer-Haus Institute in Frankfurt, he tested hundreds of organic arsenic-containing compounds to discover a cure for syphilis. A major public health scourge that had afflicted Europe for at least four centuries, syphilis was previously treated with highly toxic mercury for the duration of a patient’s lifetime.
The 606th of these chemicals, arsphenamine or Compound 606, proved to be highly effective against the syphilis-causing microbe. It required multiple injections and often caused serious adverse effects; thus, it was not quite the “magic bullet” Ehrlich had envisioned. The drug, marketed as Salvarsan, appeared 1910, and two years later his improved compound Neosalvarsan was released, remaining the primary treatment for syphilis until penicillin became available at the end of World War II.
Ehrlich’s discovery of Salvarsan and the initial opposition he encountered before its medical acceptance (incited, in part, by anti-Semitism) are depicted in the classic 1941 film Dr. Ehrlich’s Magic Bullet, with Edward G. Robinson in the title role.
SEE ALSO Atoxyl (1905), Drug Receptors (1905), Penicillin (1928).
Congenital syphilis can become a severe and chronic disease that affects the cardiovascular and neurological systems and causes abnormalities in the lower leg, as depicted in this late 1930s poster. Salvarsan and related drugs continued to be used for the treatment of syphilis until 1944.