The first recorded outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion. Because it was spread geographically by French troops returning from that campaign, the disease was known as "French disease", and it was not until 1530 that the term "syphilis" was first applied by the Italian physician and poet Girolamo Fracastoro. The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905 at the Charité Clinic in Berlin. The first effective treatment, Salvarsan, was developed in 1910 by Sahachiro Hata in the laboratory of Paul Ehrlich. It was followed by the introduction of penicillin in 1943.
Many well-known figures, including Scott Joplin, Franz Schubert, Al Capone, and Édouard Manet are believed to have contracted the disease.
Origin The history of syphilis has been well studied, but the exact origin of the disease was the source of debate until archaeological and genetic evidence showed conclusively it originated in the Americas. There were two primary hypotheses: one, first proposed in the 1880s, was that syphilis was carried to Europe from the Americas by the crew(s) of Christopher Columbus as a byproduct of the Columbian exchange. The other hypothesis, first proposed in the 1930s, was that syphilis previously existed in Europe but went unrecognized. In 2020, there was a skeletal discovery in the Yucatán Peninsula dating over 9,900 years ago of a 30-year-old woman who had Treponema periostitis, an inflammation of the periosteum (the membrane surrounding the bones) that can be caused by the bacteria that causes syphilis. Phylogenetic analyses in 2008 and 2024 showed syphilis originated in the Americas around 9,000 years ago, adding to a preponderance of archaeological evidence showing the disease existed in the Americas prior to the arrival of Europeans, and the historical evidence documenting the arrival of syphilis in Europe coinciding directly with the arrival of the crew(s) of Columbus.
Historical debate over European origins The deadliest of the four diseases that constitute treponematosis is syphilis, a sexually transmitted disease of adults. The others are bejel, yaws, and pinta, endemic childhood diseases that are usually not fatal, if still unpleasant and disfiguring. Throughout human history, confusion has reigned about the presence of syphilis in various populations around the world. It was often confused not only with the other treponematoses, but also with completely different diseases that produced similar symptoms. These included leprosy (Hansen's disease), elephantiasis, and scabies, among many others. For this reason syphilis came to be called "the great imitator", and in many places for long stretches of time it did not even have its own name.Osler, W. (1910) Aequanimitas: With Other Addresses to Medical Students, Nurses, and Practitioners of Medicine, 2nd ed. (Philadelphia: Blakiston's), 140. As a result of the difficulty of identifying syphilis in any given population, historians and paleopathologists have engaged in a long debate over its origins in Europe, where it famously ravaged the population in the late fifteenth and early sixteenth centuries. Two primary hypotheses emerged. One proposed that syphilis was carried to Europe from the Americas by the men who sailed with Christopher Columbus as a byproduct of the Columbian exchange. The other held that it previously existed in Europe but went unrecognized. These are referred to as the "Columbian" and "pre-Columbian" hypotheses.
There is no doubt that treponematosis existed in the Americas long before contact with Europe and Afro-Eurasia. For decades scholars of North and South American prehistory have agreed that the evidence from bones and teeth is clear. Genomic evidence places the time of origin for syphilis in the New World at about 9,000 years ago. The situation in the Old World had been murkier, with fewer specimens clearly pointing to treponematosis rather than some other disease. Added to this conundrum, there was no documentary record on syphilis, a particularly horrible disease that should have elicited commentary from priests, scholars, and/or kings in medieval Europe.
A lack of written evidence for the existence of syphilis in Europe, combined with an explosion of sources attesting to the appearance of a virulent new disease following exploration of the Caribbean islands, led some historians to accept the opinions of contemporary medical writers that Columbus and his men had brought the disease to Spain from America. From there it spread rapidly. In particular, the reliance of King Charles VIII of France on mercenary troops (some of them Spanish) at the time of his attack on Naples in the winter of 1495 had led, most historians believed, to the dissemination of the highly contagious "French pox" throughout Europe when those troops returned home to their own countries. This epidemic, perhaps the result of a more transmissible or deadlier variant of treponematosis, although that is not yet known, led to significant confusion beginning in the eighteenth century and exemplified most recently in the work of Kristin N. Harper and colleagues. Yet all this time some scholars believed that evidence from skeletal remains and documentary accounts did point to the existence of syphilis in Afro-Eurasia beginning in ancient times, even if it were rare. Foremost among them was Ellis Herndon Hudson, a clinician who published extensively about the prevalence of treponematosis, including syphilis, in times past.
Discoveries in paleopathology In 2020, a group of leading paleopathologists concluded that enough evidence had been collected from bones and teeth to prove that treponemal disease existed in Europe prior to the voyages of Columbus. At least fifteen cases of acquired treponematosis based on evidence from bones, and six examples of congenital treponematosis based on evidence from teeth, are now widely accepted as ancient or medieval. In several of the twenty-one cases the evidence may also indicate syphilis specifically. Highlights of this important literature include: Two burials of adolescents from the Greek colony of Metaponto in southern Italy holding dental evidence of congenital syphilis, specifically incisors and molars deformed in particular ways. The children died c. 580–250 BC.Henneberg, M.; Henneberg, R.J. "Treponematosis in an ancient Greek colony of Metaponto, southern Italy, 580–250 BC." In In the Apple Down cemetery in West Sussex, UK archaeologists uncovered the skeleton of a young man with extensive damage to both his skull and long bones, a combination typical of syphilis. He died in the 6th century. In Anatolia in western Turkey the skeleton of a teenager revealed not only the same deformed incisors and molars as in Metaponto, but also damage to the entire post-cranial skeleton. Involvement of both teeth and bones in the same individual, and especially the large number of bones affected in this case, points to syphilis. The victim died in the 13th century. A young adult female buried in the cemetery of the Dominican Friary of Blackfriars in Gloucester, UK has been dated to the mid-15th century by traditional archaeological methods.Roberts, C.A. "Treponematosis in Gloucester, England: A theoretical and practical approach to the Pre-Columbian theory." In This skeleton holds widespread evidence of treponematosis ranging from caries sicca and nasopalatine destruction on the skull to numerous lesions on the long bones, ribs, clavicles, scapulae, and sternum. This combination makes it a good candidate for a diagnosis of syphilis.
While the absolute number of cases is still small, they keep turning up, most recently in 2015 in London and St. Pölten, Austria. Yet there is an outstanding issue. Damaged teeth and bones seem to hold proof of pre-Columbian syphilis, but there is a possibility that they point to an endemic form of treponematosis instead. Some researchers have expressed skepticism regarding whether the cases from Metaponto, Apple Down and Turkey even represent treponemal diseases at all.
Discoveries in ancient DNA studies As syphilis, 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. (Pinta is 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 the various treponemal diseases through their aDNA remains slow, however, because the spirochete responsible for treponematosis, Treponema pallidum, is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyze.
The genetic sequence of Treponema pallidum was deciphered by Claire M. Fraser and colleagues in 1998, and success in analyzing a 200-year-old example extracted from bones by Connie J. Kolman et al. came the next year. In 2012, Rafael Montiel and his co-authors were successful in amplifying two Treponema pallidum DNA sequences dated to the sixteenth and seventeenth centuries in southwestern Spain. In 2018 Verena J. Schuenemann and colleagues successfully recovered and reconstructed Treponema pallidum genomes from the skeletons of two infants and a neonate in Mexico City, from the late 17th to the mid-19th centuries. Two are believed to have had congenital syphilis and one congenital yaws. A breakthrough example (2020) from early modern Europe can be found in the work of Karen Giffin and her co-authors, who sequenced a genome of Treponema pallidum subspecies pertenue, the causal agent of yaws, from a Lithuanian tooth radiocarbon-dated to 1447–1616 (95 percent probability). The ability to sequence the entire genome is especially important for distinguishing among syndromes of treponematosis because of their close similarity. In this case, whole genome sequencing has resulted in two startling discoveries: that the subtropical syndrome yaws existed in northern Europe at the turn of the sixteenth century, and that yaws in its modern form is a relatively young disease that emerged only in the 12th to 14th centuries. Finally, in October 2020 Kerttu Majander and colleagues published research revealing that as early as the fifteenth to eighteenth centuries Treponema pallidum existed as syphilis and yaws in Finland, syphilis in Estonia, and a previously unknown basal strain in the Netherlands. Although precise dating to the medieval period is not yet possible, 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.
A 2024 study published in Nature analysed pre- and peri-contact ancient treponemal genomes from the Americas that represent ancient relatives of the T. pallidum pallidum (syphilis), T. pallidum pertenue (yaws) and T. pallidum endemicum (bejel) lineages. The study concluded: "Our data indicate unexplored diversity and an emergence of T. pallidum that post-dates human occupation in the Americas. Together these results support an American origin for all T. pallidum characterized at the genomic level, both modern and ancient".
Evidence from art