There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicado wrote El modo de adoperare el legno de India (Rome, 1525) about the use of Guaiacum in the treatment of syphilis. He himself suffered from syphilis. Nicholas Culpeper recommended the use of heartsease (wild pansy), an herb with antimicrobial activities. Another common remedy was mercury: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury". It was administered in various fashions, including by mouth, by rubbing it on the skin,and by injection. One of the more curious methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed inside the box and a fire started under the box, causing the mercury to vaporize. It was a grueling process for the patient and the least effective for delivering mercury to the body. The use of mercury was the earliest known suggested treatment for syphilis. This has been suggested to date back to The Canon of Medicine (1025) by the Persian physician Ibn Sina (Avicenna), although this is only possible if syphilis existed in the Old World prior to Columbus (see Origins section). Giorgio Sommariva of Verona is recorded to have used it for this purpose in 1496.
As the disease became better understood, more effective treatments were found. An antimicrobial used for treating disease was the organo-arsenical drug Salvarsan, developed in 1908 by Sahachiro Hata in the laboratory of Nobel prize winner Paul Ehrlich. This group later discovered the related arsenical, Neosalvarsan, which is less toxic. Unfortunately, these drugs were not 100% effective, especially in late disease, and were sometimes unpredictably toxic to patients. It was observed that sometimes patients who developed high fevers were cured of syphilis. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers (a form of pyrotherapy). This was considered an acceptable risk because the malaria could later be treated with quinine, which was available at that time. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. This discovery was championed by Julius Wagner-Jauregg, who won the 1927 Nobel Prize for Medicine for his discovery of the therapeutic value of malaria inoculation in the treatment of neurosyphilis. Later, hyperthermal cabinets (sweat-boxes) were used for the same purpose. These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured.