bejel, and yaws vary considerably in mortality rates and the level of human disgust they elicit, it is important to know which one is under discussion in any given case, but it remains difficult for paleopathologists to distinguish among them. (the fourth of the treponemal diseases is pinta, a skin disease and therefore unrecoverable through paleopathology.) ancient dna (adna) holds the answer, because just as only adna suffices to distinguish between syphilis and other diseases that produce similar symptoms in the body, it alone can differentiate spirochetes that are 99.8 percent identical with absolute accuracy. progress on uncovering the historical extent of syndromes through adna remains slow, however, because the spirochete responsible for treponematosis is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyze. precise dating to the medieval period is not yet possible, but work by kettu majander et al. uncovering the presence of several different kinds of treponematosis at the beginning of the early modern period argues against its recent introduction from elsewhere. therefore, they argue, treponematosis- possibly including syphilis—almost certainly existed in medieval europe. despite significant progress in tracing the presence of syphilis in past historic periods, definitive findings from paleopathology and adna studies are still lacking for the medieval period. evidence from art is therefore helpful in settling the issue. research by marylynn salmon has demonstrated that deformities in medieval subjects can be identified by comparing them to those of modern victims of syphilis in medical drawings and photographs. one of the most typical deformities, for example, is a collapsed nasal bridge called saddle nose. salmon discovered that it appeared often in medieval illuminations, especially among the men tormenting christ in scenes of the crucifixion. the association of saddle nose with men perceived to be so evil they would kill the son of god indicates the artists were thinking of syphilis, which is typically transmitted through sexual intercourse with promiscuous partners, a mortal sin in medieval times. one illuminator goes so far as to show a flagellant with an exposed penis, red at the tip as though infected with a syphilitic sore. others show the deformed teeth associated with congenital syphilis—hutchinson's incisors—or the eye deformity ptosis that often appears in victims of the disease. it remains mysterious why the authors of medieval medical treatises so uniformly refrained from describing syphilis or commenting on its existence in the population. many may have confused it with other diseases such as leprosy (hansen's disease) or elephantiasis. the great variety of symptoms of treponematosis, the different ages at which the various diseases appears, and its widely divergent outcomes depending on climate and culture, would have added greatly to the confusion of medical practitioners, as indeed they did right down to the middle of the twentieth century. in addition, evidence indicates that some writers on disease feared the political implications of discussing a condition more fatal to elites than to commoners. historian jon arrizabalaga has investigated this question for castile with startling results revealing an effort to hide its association with elites. the first written records of an outbreak of syphilis in europe occurred in 1495 in naples, italy, during a french invasion (italian war of 1494–98). since it was claimed to have been spread by french troops, it was initially called the "french disease" by the people of naples. the disease reached london in 1497 and was recorded at st batholomew's hospital as infected 10 out of the 20 patients. in 1530, the pastoral name "syphilis" (the name of a character) was first used by the italian physician and poet girolamo fracastoro as the title of his latin poem in dactylic hexameter syphilis sive morbus gallicus (syphilis or the french disease) describing the ravages of the disease in italy. in great britain it was also called the "great pox". in the 16th through 19th centuries, syphilis was one of the largest public health burdens in prevalence, symptoms, and disability,: 208–209 although records of its true prevalence were generally not kept because of the fearsome and sordid status of sexually transmitted infections in those centuries.: 208–209 according to a 2020 study, more than 20% of individuals in the age range 15–34 years in late 18th century london were treated for syphilis. at the time the causative agent was unknown but it was well known that it was spread sexually and also often from mother to child. its association with sex, especially sexual promiscuity and prostitution, made it an object of fear and revulsion and a taboo. the magnitude of its morbidity and mortality in those centuries reflected that, unlike today, there was no adequate understanding of its pathogenesis and no truly effective treatments. its damage was caused not so much by great sickness or death early in the course of the disease but rather by its gruesome effects decades after infection as it progressed to neurosyphilis with tabes dorsalis. mercury compounds and isolation were commonly used, with treatments often worse than the disease. the causative organism, treponema pallidum, was first identified by fritz schaudinn and erich hoffmann, in 1905. the first effective treatment for syphilis was arsphenamine, discovered by sahachiro hata in 1909, during a survey of hundreds of newly synthesized organic arsenical compounds led by paul ehrlich. it was manufactured and marketed from 1910 under the trade name salvarsan by hoechst ag. this organoarsenic compound was the first modern chemotherapeutic agent. during the 20th century, as both microbiology and pharmacology advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least in developed countries among those people who could afford to pay for timely diagnosis and treatment. penicillin was discovered in 1928, and effectiveness of treatment with penicillin was confirmed in trials in 1943, at which time it became the main treatment. many famous historical figures, including franz schubert, arthur schopenhauer, édouard manet, charles baudelaire, and guy de maupassant are believed to have had the disease. friedrich nietzsche was long believed to have gone mad as a result of tertiary syphilis, but that diagnosis has recently come into question. arts and literature