History of syphilis

Portrait of Gerard de Lairesse by Rembrandt van Rijn, ca. 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.^[1]

The history of syphilis has been well studied, but the exact origin of syphilis is unknown.^[2] There are two primary hypotheses: one proposes that syphilis was carried to Europe from the Americas by the crew of Christopher Columbus, the other proposes that syphilis previously existed in Europe but went unrecognized.^[3] These are referred to as the "Columbian" and "pre-Columbian" hypotheses.^[3]

In late 2011, newly published evidence suggested that the Columbian hypothesis is the valid one.^[4]

Skeletal evidence that reputedly showed signs of syphilis in Europe and other parts of the Old World before Christopher Columbus made his voyage in 1492 does not hold up when subjected to standardized analyses for diagnosis and dating, according to an appraisal in the current Yearbook of Physical Anthropology. This is the first time that all 54 previously published cases have been evaluated systematically, and bolsters the case that syphilis came from the New World.

The first written records of an outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion.^[3][5] Because it was spread by returning French troops, 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.^[5] The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905.^[5] The first effective treatment (Salvarsan) was developed in 1910 by Sahachirō Hata in the laboratory of Paul Ehrlich which was followed by the introduction of penicillin in 1943.^[5] Many famous historical figures including Franz Schubert, Arthur Schopenhauer, and Édouard Manet are believed to have had the disease.^[5]

Origin

The exact origin of syphilis is unknown.^[2] Two primary theories have been proposed. It is widely agreed upon by historians and anthropologists that syphilis was present among the indigenous peoples of the Americas before Europeans traveled to and from the New World.^[3] However, whether strains of syphilis were present in the entire world for millennia, or if the disease was confined to the Americas in the pre-Columbian era, has been debated.^[3]

• The Columbian theory holds that syphilis was a New World disease brought back by Columbus and Martín Alonso Pinzón. Columbus's voyages to the Americas occurred three years before the Naples syphilis outbreak of 1494.^[3] This theory is supported by genetic studies of venereal syphilis and related bacteria, which found a disease intermediate between yaws and syphilis in Guyana, South America.^[6][7]
• The pre-Columbian theory holds that syphilis was present in Europe before the arrival of Europeans in the Americas. Some scholars during the 18th and 19th centuries believed that the symptoms of syphilis in its tertiary form were described by Hippocrates in Classical Greece.^[8] Skeletons in pre-Columbus Pompeii and Metaponto in Italy with damage somewhat similar to that caused by congenital syphilis have also been found.^[9][10][11] However, these claims have not been submitted for peer review, and the evidence that has been made available to other scientists is weak.^[12] Nevertheless Douglas W. Owsley, a physical anthropologist at the Smithsonian Institution, and other supporters of this idea, say that many medieval European cases of leprosy, colloquially called lepra, were actually cases of syphilis. Although folklore claimed that syphilis was unknown in Europe until the return of the diseased sailors of the Columbian voyages, Owsley says that "syphilis probably cannot be "blamed"—as it often is—on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres from prehistoric times. It is only coincidental with the Columbus expeditions that the syphilis previously thought of as "lepra" flared into virulence at the end of the 15th century."^[13] Lobdell and Owsley wrote that a European writer who recorded an outbreak of "lepra" in 1303 was "clearly describing syphilis."^[13]

Historian Alfred Crosby suggests both theories are partly correct in a "combination theory". Crosby says that the bacterium that causes syphilis belongs to the same phylogenetic family as the bacteria that cause yaws and several other diseases. Despite the tradition of assigning the homeland of yaws to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease having been present in pre-Columbian Europe, Africa, or Asia. Crosby writes, "It is not impossible that the organisms causing treponematosis arrived from America in the 1490s...and evolved into both venereal and non-venereal syphilis and yaws."^[14] However, Crosby considers it more likely that a highly contagious ancestral species of the bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of treponematosis and, in time, closely related but different diseases."^[14]

However, in late 2011 the Yearbook of Physical Anthropology published an appraisal by George Armelagos of Emory University, Molly Zuckerman, and Kristin Harper of previous studies that the "skeletal data bolsters the case that syphilis did not exist in Europe before Columbus set sail."^[15] The scientific evidence as determined by a systematic review of all published, peer-reviewed instances, best supports the theory that syphilis was unknown in Europe until Columbus returned from the Americas.

The historical origin of syphilis has modern social effects.^[16] The arrival of Europeans in the New World resulted in the damaging effects of colonialism and the spread of deadly diseases like smallpox that European explorers unintentionally brought to the Americas. According to biologist Marlene Zuk, "The origin of syphilis has always held an implied accusation: if Europeans brought it to the New World, the disease is one more symbol of Western imperialism run amok, one more grudge to hold against colonialism."^[16]

European outbreak

A medical illustration attributed to Albrecht Dürer (1496) depicting a person with syphilis. Here, the disease is believed to have astrological causes.

The first well-recorded European outbreak of what is now known as syphilis occurred in 1495 among French troops besieging Naples, Italy.^[3] It may have been transmitted to the French via Spanish mercenaries serving King Charles of France in that siege.^[13] From this centre, the disease swept across Europe. As Jared Diamond describes it, "[W]hen syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." The disease then was much more lethal than it is today. Diamond concludes,"[B]y 1546, the disease had evolved into the disease with the symptoms so well known to us today."^[17] The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.

Researchers concluded that syphilis was carried from the New World to Europe after Columbus' voyages. Many of the crew members who served on this voyage later joined the army of King Charles VIII in his invasion of Italy in 1495, resulting in the spreading of the disease across Europe and as many as five million deaths.^[7] The findings suggested Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions and low immunity of the population of Europe.^[18] Syphilis was a major killer in Europe during the Renaissance.^[19] In his Serpentine Malady (Seville, 1539) Ruy Diaz de Isla estimated that over a million people were infected in Europe.^[20]

Historical terms

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his pastoral noted poem, written in Latin, titled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530.^[5] The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him.^[5] From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases").^[21]

Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy, Poland and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank (Western European) disease" (frengi) and the Tahitians called it the "British disease". These "national" names were generally reflective of contemporary political spite between nations and frequently served as a sort of propaganda; the Dutch, for example, had a colonial rivalry with the Spanish, so referring to Syphilis as the 'Spanish' disease reinforced a politically useful perception that the Spanish were immoral or unworthy. The inherent xenophobia of the terms also stemmed from the disease's particular epidemiology, often being spread by foreign sailors and soldiers during their frequent sexual contact with local prostitutes.

During the 16th century, it was called "great pox" in order to distinguish it from smallpox. In its early stages, the great pox produced a rash similar to smallpox (also known as variola). However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues"^[22] (or Lues venerea, Latin for "venereal plague") and "Cupid's disease"^[23] have also been used to refer to syphilis. In Scotland, syphilis was referred to as the Grandgore. The ulcers suffered by British soldiers in Portugal were termed "The Black Lion".^[24]

Historical treatments

An artificial nose from the 17-18th century. Such cosmetic replacements were sometimes used due to effects of the disease.

An early technique for grafting tissue to surgically correct a nose defect.

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), a herb with antimicrobial activities.^[25] 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".^[26] It was administered in various fashions, including by mouth, by rubbing it on the skin, and by injection.^[27] One of the more curious methods was fumigation, in which patients were placed in closed boxes with their heads sticking outward. 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),^[28] 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.

Before effective treatments were available, syphilis could sometimes be disfiguring in the long term, leading to defects of the face and nose ("nasal collapse"). Syphilis was a stigmatized disease due to its sexually transmissible nature. Such defects marked the person as a social pariah, and a symbol of sexual deviancy. Artificial noses were sometimes used to improve this appearance. The pioneering work of the facial surgeon Gasparo Tagliacozzi in the 16th century marked one of the earliest attempts to surgically reconstruct nose defects. Before the invention of the free flap, only local tissue adjacent to the defect could be harvested for use, as the blood supply was a vital determining factor in the survival of the flap. Tagliacozzi's technique was to harvest tissue from the arm without removing its pedicle from the blood supply on the arm. The patient would have to stay with their arm strapped to their face until new blood vessels grew at the recipient site, and the flap could finally be separated from the arm during a second procedure.

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,^[29] 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.^[30] 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.^[31]

History of diagnosis

In 1905, Schaudinn and Hoffmann discovered Treponema pallidum in tissue of patients with syphilis.^[5] One year later, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the detection and prevention of syphilis. By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected. In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positive reactions than the Wassermann test. Both of these early tests have been superseded by newer analytical methods.

While working at the Rockefeller University (then called the Rockefeller Institute for Medical Research) in 1913, Hideyo Noguchi, a Japanese scientist, demonstrated the presence of the spirochete Treponema pallidum in the brain of a progressive paralysis patient, associating Treponema pallidum with neurosyphilis.^[32] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands. Without its cause being understood, it was sometimes misdiagnosed and often misattributed to damage by political enemies. It is called "the great pretender" for its variety of symptoms. Felix Milgrom developed a test for syphilis. The Hideyo Noguchi Africa Prize, was named to honor the man who identified the agent in association with the late form of the infectious disease.^[33]

See also

• Columbian Exchange, the spread of animals, plants, people, and diseases between the Old World and the New World

References