When was syphilis cured?

The Cure For Syphilis Was Developed As Part Of The US Effort To Win World War II

The organism treponema palladium, which causes syphilis, is seen through an electron microscope, May 23, 1944. AP World War II is the deadliest conflict in history.

But the human race still emerged from the war with a few potential advances in hand, among them a cure for syphilis.

The bacteria responsible for the disease was discovered in 1905, and its eventual cure, penicillin, in the late ’20s.

But it wasn’t until 1943, in the midst of World War II, that doctors at a US Marine Hospital on Staten Island in New York applied the antibiotic to effectively cure four patients suffering from the early stages of the disease.

That October, TIME ran an article about the experiments with the headline “New Magic Bullet,” and the next year the doctors published a study on the effectiveness of penicillin injections administered every few hours for eight days.

The development was especially important given the measurable impact that syphilis and other diseases had on the manpower needed to fuel the war effort.

Nearly five percent of draftees in 1942 had syphilis, according to a medical paper published in the journal Military Medicine and entitled “History of US Military Contributions to the Study of Sexually Transmitted Diseases.”

When left untreated, the disease causes genital sores before attacking other parts of the body, including the nervous system, to cause a slew of debilitating symptoms and even eventual death. The military’s syphilis problem during a major US combat mobilization prompted the War Department “to embark on a massive educational and prophylactic campaign.”

Contemporary posters warned that “You can’t beat the Axis if you get VD,” and that venereal disease makes “a sorry ending to a furlough.”

Manpower suffered during World War I from exactly this problem. American soldiers weren’t supplied with condoms (something which would change in the next world war), and sexually transmitted diseases as a whole “were the second most common reason for disability and absence from duty, being responsible for nearly 7 million lost person-days and the discharge of more than 10,000 men,” according to an article in the Journal of Military and Veterans’ Health.

Shortly before that war, syphilis — which first got its name in an Italian poem from the year 1530 — was treated with a medical form of an arsenic compound. Its creator, a German chemist named Paul Ehrlich, won the Nobel Prize in 1908 for his discovery and the drug’s effectiveness in the Great War was noted by a medical officer in the United Kingdom’s Royal Army Medical Corps.

Still, arsenic was a toxic substance that produced adverse side effects — and it was sometimes used in combination with mercury, which is also poisonous. Penicillin was much easier for the human body to take and the discovery of its effectiveness against syphilis had positive effects that outlasted the second World War.

The disease was “the fourth leading cause of death in the United States before World War II, behind only tuberculosis, pneumonia, and cancer,” according to the article in the Journal of Military and Veterans’ Health.

In 1939, 64,000 Americans died from the disease, almost as many as died from diabetes in a recent year. Today, the rate of annual infection is round 13,000 cases for which a cure is available.

The disease has also faded in the American military. In the early years of the Vietnam War, for instance, syphilis represented only one percent of servicemen’s cases of sexual infections (though the total rate of these, mostly due to gonorrhea, was actually greater than during World War II).

In 1999, prevalence in the US military was down to 3 cases per 100,000 individuals, close to the civilian rate of 2.5.

The urgency of the US war effort 70 years ago, alongside decades of advances in publish health, reduced the sting of a once-devastating disease in the military and in American society more generally.

“Arsenobenzol, designated “606,”
whatever the future may bring to justify the present enthusiasm, is now actually a more or less incredible advance in the treatment of syphilis and in many ways is superior to the old mercury – as valuable as this will continue to be – because of its eminently powerful and eminently rapid spirochaeticidal property.”

LW Harrison, a medical officer in the Royal Army Medical Corps during World War I, described the effectiveness of Salvarsan and Neosalvarsan on soldiers who contracted syphilis during the war. Arsenic however, while being able to cure syphilis whereas mercury wasn’t, had many drawbacks – administration of treatment was complex requiring many injections over a long period of time, and it also produced toxic side effects. In 1916, A. Robert and Benjamin Sauton discovered the trypanocidal properties of bismuth, and in 1921, Robert Sazerac, Constantin Levaditi and Louis Fournier successfully treated syphilis with bismuth. It then became apparent that for arsenic to be effective, it had to be combined with small doses of either bismuth or mercury. Arsenic, mainly arsphenamine, neoarsphenamine, acetarsone and mapharside, in combination with bismuth or mercury, then became the mainstay of treatment for syphilis until the advent of penicillin in 1943.

In 1917 Julius Wagner-Jauregg, an Austrian physician, introduced the treatment of neurosyphilis with fever therapy by infecting the patient with malaria, then treating the malaria with quinine. The observation had been made that after a febrile illness the symptoms of neurosyphilis diminished, and the rationale was that it was easier to treat malaria with quinine than the syphilis with mercury or arsenic. Fred A. Kislig and Walter M. Simpson, two American physicians, introduced in 1936 the treatment of electropyrexia, using a short-wave apparatus to induce pyrexia in a patient to treat syphilis and gonorrhoea.

In 1943 penicillin was introduced as a treatment for syphilis by John Mahoney, Richard Arnold and AD Harris. Mahoney and his colleagues at the US Marine Hospital, Staten Island, treated four patients with primary syphilis chancres with intramuscular injections of penicillin four-hourly for eight days for a total of 1,200,000 units by which time the syphilis had been cured. This became a turning point in the treatment for syphilis as penicillin was shown to be highly effective when administered during either its primary or secondary stages, and it had few side effects of any significance when compared to mercury or arsenic. Arnold wrote in 1986 of his early work with penicillin and syphilis:

“Syphilis was once a dreaded and dreadful disease involving millions of US citizens. Before the introduction of penicillin, the heavy-metal cure often caused thousands of deaths each year. The morbidity and mortality of the disease itself was horrendous, involving all ages from the fetus to the elderly.”

Was syphilis introduced from the New World into the Old World by Christopher Columbus in 1493 ?

Over the past five centuries, and particularly in the last century, the origins of syphilis have caused great controversy amongst historians, physicians, anthropologists and palaeontologists. Up until the early 20th century the most popular theory on the origin of syphilis was that it was a new disease, contracted by Columbus’ men in the New World and introduced to the Old World after their return to Spain on 15th March of 1493. An alternative theory was put forward in 1934 by Richmond Cranston Holcomb that syphilis had already existed in the Old World before Columbus’ time, and in the latter part of last century palaeopathologists found possible evidence that this may have been so. A recent analysis of the evidence however by Kristin N. Harper, George J. Armelagos and other US anthropologists in 2011 has swung back to the “Columbian hypothesis” of the origin of syphilis.

There have been three main hypotheses on the origin of syphilis – the Columbian hypothesis that Columbus brought syphilis from the New World, the pre-Columbian theory that syphilis had already existed in the Old World and had evolved into a more virulent form around the time of Columbus, and the Unitarian theory that all treponematoses are a single disease with syphilis being an environmentally determined variant where social and environmental conditions in the late 15th century favoured its transmission by sexual intercourse.

Because the Naples syphilis epidemic appeared two years after Columbus returned in 1493 from Hispaniola, the belief that Columbus’ crew had contacted the disease in the New World arose in the scholarly and medical literature by the early 16th century. When Charles VIII invaded and seized Naples in 1495, Naples was populated by Spanish immigrants and was defended largely by Spanish mercenaries who had probably already contracted the disease in Spain and who then passed the disease onto Charles’ soldiers and followers when they invaded Naples. Schreiber and Mathys (1987) describe that the disease had first appeared in Barcelona in 1493 and had spread throughout Spain that year.

Castiglioni (1946) , Wills (1996) and Harper et al (2011) state that the Columbian hypothesis is supported by descriptions by several 15th and 16th century scholars such as Fernandez de Oviedo y Valdes in 1526, Bartolome de las Casas in 1530, Ruy Diaz de Isla in 1539, the latter a Barcelona physician who claimed to have treated Columbus’ men for the disease, and Gabriele Fallopius (1523-1562), all of whom stated that Columbus’ crew had a new disease and that a similar disease had been present on the island of Hispaniola for many centuries before Columbus.

The Columbian hypothesis that syphilis was brought to Europe from America in 1492 was reaffirmed in the 1950s and 1960s by a number of historians and physicians such as Harrison (1959), Dennie (1962), Goff (1967), and Crosby (1969). Crosby (1969) and Harrison (1959) state that the two most important historians of the time, Fernandez de Oviedo y Valdes and Bartolome de las Casas, were eyewitness to conditions in Hispaniola when Columbus was there and both considered that Columbus brought the disease back from the New World to Europe. Crosby states that both Ulrich von Hutton and Ruy Diaz de Isla identified 1493 as the year the disease first appeared in Europe. Crosby quotes Ulrich von Hutton as saying, “In the yere of Chryst 1493 or there aboute this most foule and most grievous disease beganne to sprede amonge the people.” Crosby”s view was that treponematosis was originally a single disease which evolved into several related but distinct diseases and that venereal syphilis is the variant that developed in America, from which it probably was introduced to Europe with the return of Columbus.

A third important scholar of the time who believed in the Columbian origin of syphilis was Ruiz Diaz de Isla, a Barcelona physician, who published in a book in 1539 that Columbus’ men contracted the disease in Hispaniola in 1492 and that he had observed its rapid spread through Barcelona after Columbus’ return. De Isla wrote that he had treated the men for the disease but hadn’t realised it was the same disease that had been ravaging Europe until many years later. He called it Morbo serpentine, ‘the hideous, dangerous, terrible disease’.

The pre-Columbian theory arose in the early 20th century. Garrison refers to a 1912 publication by Karl Sudhoff , a German medical historian from the University of Leipzig, who stated that the Naples epidemic was typhoid or paratyphoid fever. That syphilis was present in Europe before Columbus’ return from Hispaniola was supported by the facts that many literary works and religious edicts referred to syphilis before the Naples siege of 1495, and also that mercury treatment had been used since the 12th century for a diversity of infectious disorders that were probably syphilis. Garrison himself says “That sporadic syphilis existed in antiquity and even in prehistoric times is quite within the range of probability.”

An editorial article in JAMA in 1935 cited Capper (1926) as stating that many historical descriptions of leprosy were in fact syphilis, and that syphilis among the Romans was described by Celsus, Aretaeus and Aetius. The article also cited Butler (1933) as stating that historical evidence of aortic aneurysm being treated by Antyllus, a contemporary of Galen in Romans times, was evidence of the existence at that time of syphilis, and that Celsus accurately described a genital syphilitic chancre. Richard Holcomb’s argument in 1935 that syphilis was of pre-Columbian origin was based on a description by Michael Angelus Blondus, a 16th century Italian surgeon, who identified it with a disease described by Aurelius Cornelius Celsus, a 2nd century Greek philosopher, and Paul of Aegina, a 7th century Greek physician. In 1974, two anthropologists, John Lobdell and Douglas Owsley, stated “syphilis can probably not be “blamed”, as it often is, on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres of the world from prehistoric times. It is probably only coincidental with the Columbus expeditions that the syphilis previously thought of as “lepra” in Europe flared into virulence at the end of the fifteenth century.”

Several medical historians over the last century have postulated other reasons for syphilis being a pre-Columbian Old World disease – a greater lay and medical recognition of syphilis developed in recent eras, and that syphilis had evolved from other treponeal diseases into a more virulent form due to a combination of social, cultural and environmental changes around the time of Columbus. In the last several decades development of palaeopathology has enabled close evaluation of Old World skeletons and many studies have published their findings of evidence for syphilitic bone disease.

The Unitarian hypothesis, proposed by EH Hudson in 1928 , that treponematoses are environmentally determined expressions of the same disease of which syphilis is one variant, with syphilis being hindered from skin to skin transmission because of development of hygiene and changing to become a sexually transmitted disease, has been refuted by genetic studies which show the different treponeum subspecies are genetically distinct and evolved along different paths.

Critics of recent palaeopathological studies have pointed out the difficulties in distinguishing syphilis from other diseases that had similar symptoms and left similar bone scars such as leprosy, osteomyelitis, hypertrophic osteoarthropathy, and histiocytosis In 2005 Bruce M. Rothschild published a review of the historical and palaeopathological record of syphilis. Rothschild found that the pathological osseotype features of syphilis were absent in human specimens from re-Columbian Europe, Africa and Asia. However specimens with evidence of treponeal disease were identified from North America dating back some 8,000 years. Bruce Rothschild as co-author with Christine Rothschild in their review study in 2000 found that somewhere between 2000 and 1800 years ago the first identified osseotype evidence of syphilis occurred in North America and it appeared that syphilis had transmutated from yaws. Rothschild (2005) states that it is clear syphilis was present in the New World at the time of Columbus’ arrival, perhaps in a milder or a non-venereal form, and there is evidence it existed in the same area of the Dominican Republic at which he landed. Rothschild also states that all evidence for treponeal disease existing in re-Columbian Europe represents isolated cases for which alternative diagnoses are more likely.

A review of palaeopathogical studies of treponeal disease in the New and Old World by Baker and Armelagos in 1988 documented an abundance of pre-Columbian New World finds, but an absence of Old World finds, a finding that was reaffirmed by Powell and Cook and by Rothschild in 2005. Baker and Armelagos (1988) concluded that pre-Columbian American skeletal analyses reflect a treponematosis that spread to the Old World through non-venereal contact, and that European social and environmental conditions at the time favoured the development of venereal transmission. They also stated that the rapid spread of syphilis throughout Europe around 1500 reflected the introduction of a virulent disease into a population that had not been previously exposed and had no immunity to it. In 2008 Harper et al published a comprehensive phylogenetic analysis of 26 geographically disparate strains of pathogenic Treponema, which found that the venereal syphilis strains originated recently and were more closely related to yaws strains from South America than to other non-venereal strains, further supporting the hypothesis that syphilis, or a progenitor of the bacteria, came from the New World.

In 2011 Harper et al evaluated all published reports of pre-Columbian Old World treponeal disease, using a systematic approach involving diagnostic criteria, certainty of diagnosis, and the accuracy and reliability of palaeopathological dating and radiocarbon dating. The authors concluded that among the 54 reports they evaluated using their criteria they did not find a single case of Old World treponeal disease that had both a certain diagnosis and a secure pre-Columbian date. They came to the overall conclusion that evidence for an Old World origin for syphilis remains absent, and that this further supported the hypothesis that syphilis, or its progenitor, came from the New World.

Syphilis was a terrible disease because of its propensity to mimic many medical disorders, and its importance to medicine was emphasised by Sir William Osler who in an address given to the New York Academy of Medicine in 1897 titled Internal Medicine as a Vocation said :

“I often tell my students that it is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”

From its beginning, syphilis was greatly feared by society – because of the repulsiveness of its symptoms, the pain and disfigurement that was endured, the severe after effects of the mercury treatment, but most of all, because it was transmitted and spread by an inescapable facet of human behaviour, sexual intercourse. The origin of syphilis is still a topic of debate and research, believed by physicians and scholars up until early last century to have been brought to the Old World from America by Christopher Columbus. In recent times, archaeologists and palaeontologists had found possible evidence it existed in the Old World before Columbus . This has been disputed by other researchers however and it seems that it is still possible that Columbus did bring syphilis, or its progenitor, to the New World.

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Syphilis: The Painful History of an Odd Bug

Syphilis was a major threat to the health of soldiers in both the First and Second World Wars. Getty Images (2)

Looking for Others to Blame

Squillaci called syphilis the “French disease” in his letter. By doing so, the Italian doctor fell in line with an often-seen tendency in early discussions of the illness. That is, people from one area have repeatedly blamed people from another area for the illness.

Like Squillaci, residents of parts of Europe we now call Germany and the United Kingdom also used to call syphilis “the French disease.” Meanwhile, French people referred to syphilis as “the Neapolitan disease,” meaning it came from Naples, Italy.

Russians have called it “the Polish disease,” while Poles have called it “the German disease.” Turks used to call syphilis “the Christian disease,” while Muslims blamed syphilis on the Hindus. In fact, few groups have not been blamed for syphilis at one time or another.

Source of the Name ‘Syphilis’

An Italian poet named Giralamo Fracastoro was the first person to call the illness “syphilis.” In a long poem of that title published in 1530, Syphilis is a character, possibly based on one in Ovid’s Metamorphoses, who is a shepherd to a king. This shepherd angers the sun god Apollo by blaming the god for a drought. In response, Apollo curses Syphilis with a dreadful disease that spreads wildly throughout the area where Syphilis lives. It even infects the king whose flock Syphilis tends.

The fact that this story describes syphilis infecting a king would have rung true to the poem’s audience. Many leaders, writers, and artists throughout history appear likely to have had syphilis. Although the facts are not always clear, records of the illnesses of many famous people strongly suggest that their troubles were caused by syphilis.

Among those greats who may have had syphilis are the composers Ludwig van Beethoven and Franz Schubert, the writers Oscar Wilde and James Joyce, and political figures such as Napoleon Bonaparte. Many other renowned people probably had the illness too, writes Deborah Hayden in her book Pox: Genius, Madness and the Mysteries of Syphilis.

Spreading Worldwide

Syphilis swept across Europe in short order. By the end of 1495, it had reached France, Switzerland, and Germany. By 1497, it took hold in England and Scotland. By 1500, the epidemic had Scandinavia, Hungary, Greece, Poland, and Russia in its grip.

During the 1400s and 1500s, European explorers sailed the globe. These explorers brought syphilis with them to India, Africa, the Near East, China, Japan, and the Pacific islands.

In the 16th and 17th centuries, some people thought of syphilis as a punishment for sin and believed that people with the disease didn’t deserve treatment. Some people believed that people with syphilis should be subjected to harsh, painful remedies.

Taking a more enlightened view in 1673, a British physician named Thomas Sydenham wrote that any moral aspects of the disease should be of no concern to doctors. He believed that all people deserved to be treated for their ills and not be judged by physicians.

By the early 18th century, syphilis was no longer the highly virulent epidemic it had been in previous years. It then came to resemble more closely the version of the disease we find today.

Scientific Inquiry and a Cure

In 1905, Fritz Richard Schaudinn, a German zoologist, and Erich Hoffman, a dermatologist, discovered the cause of syphilis: the bacterium called Treponema pallidum.

Twenty-three years later, in 1928, Alexander Fleming, a London scientist, discovered penicillin.

Finally, 15 years after that, in 1943, three doctors working at the U.S. Marine Hospital on Staten Island, in New York, first treated and cured four patients with syphilis by giving them penicillin. To this day, penicillin remains the cure for syphilis.

An Odd Bug

Syphilis belongs to a group of four diseases known to be caused by bacteria that are members of the Treponema family. The others are yaws, bejel, and pinta, all of which are spread through skin contact, primarily among children living in areas with poor hygiene.

As mentioned above, in the case of syphilis, the culprit is a spiral-shaped organism known as Treponema pallidum.

“This is an odd bug. It can’t make its own proteins or lipids , which other bacteria typically do. It cuts off parts of itself so it can bind closely to the cells of the host ,” says Sheila A. Lukehart, PhD, a professor of medicine and global health at the University of Washington in Seattle and an expert on Treponema pallidum. “It has only the characteristics it needs to survive.”

Prospects for Control of Syphilis

Some of its traits make this bacterium extra tricky to address with a vaccine, says Dr. Lukehart. Nonetheless, researchers are trying to find a vaccine that will work against syphilis.

One of Lukehart’s graduate students is working on a vaccine that would first block the development of any chancre, or sore, in an infected person. By blocking the development of sores, the vaccine could block transmission of the illness from one person to another, since contact with the chancre is how a person without syphilis catches it from an infected person.

Lukehart is optimistic, with some reservations. “I don’t think we are ever going to treat syphilis out of existence, but I do hope that we can treat congenital syphilis out of existence. By screening you should be able to do that.”

PMC

An important aspect to consider is also that syphilis was, at the very beginning, a disease of great severity, a more rapid spreading and atypical in its evolution as compared to nowadays syphilis, the fatal cases were not rare. The supporters of the Columbian hypothesis advocate that the extreme severity if the condition was mainly due to its novelty, as the population had no time to gain any immunity against the ailment as the venereal syphilis became endemic in Europe, certain strains of T. pallidum have selected, and the disease gained a milder course .

The spread of the syphilis across Europe was frequently associated with the invasion of Naples by the French army. However, ever since fewer popular theories have been developed. In 1492 Ferdinand de Aragon and Isabel of Castilla issued the Edict of Expulsion of the Jews, stating that all the individuals of Hebrew origins refusing to convert to Catholicism were to be expulsed from Spain and the rest of its territories. On this occasion, approximately 200.000 Jews have left the country for Northern Africa and Southern Europe. On their way, a part of them temporarily settled at the gates of Rome; they were not allowed in Rome, and in the new Diaspora an outbreak occurred, killing 30000 individuals. Despite all efforts, the disease later identified as syphilis entered the city of Rome. Therefore, some of the chroniclers of the time blamed the Jews for the spread of syphilis in Europe; according to them, the disease was already present on Italian territory before Naples invasion by the French in 1495 .

Syphilis in artistic representations

The oldest artistic representation of syphilis is considered one on a Peruvian jug dating back to VIth century, depicting a mother suffering from syphilis holding a child in her arms; the mother shows a saddle nose and superior incisive teeth with notches on their free margins. The piece belongs to a collection of jugs also encompassing two jugs illustrating leprosy and leishmaniasis .

Albrecht Dürer, a German artist, depicts in woodcuts, for the first time in Europe, in 1496, the image of a mercenary whose skin bears sores of multiple chancres (Fig. 1). Next to the image lays written a text by physician Theodorus Ulsenius warning on the new disease, also describing its signs and symptoms, mentioning that the illness is not curable and establishing a direct link between the epidemic and the grand astrological conjuction in 1484 .

A mercenary whose skin presents multiple chancres, woodcut by Albrecht Dürer, 1496 –published in a Romanian book in 1933

A work of Sebastian Brandt depicting Saint Mary with the Child dates from the same year, 1496 (Fig. 2); the Holy Child throws light spears to punish or cure the sufferers of syphilis, represented as individuals with multiples ulcers and sores. In another part of the woodcut depiction, King Maximilian I and his Knights are ready to receive the crown as reward for the edict he issued in 1495, stating that the disease was a consequence of blasphemy and sins, punishing the suffers of syphilis for their immoral behavior .

Saint Mary and the Holy Child punishing the sufferers of syphilis, woodcut, 1496

Another significant painting belongs to Jacques Laniet, in the XVIIth century, an illustration of a man in a fumigation stove, a fashionable method of treatment at that time (Fig. 3). On the barrel lays written “pur un plaisir, mil douleur” (fr. correspondent of the phrase “For a pleasure, a thousand pains”), a proverb very used in those years. Another verbatim translation of this proverb is “for a night with Venus, a life with Mercury” .

Depiction of a man in a fumigation stove, engraving by Jacques Laniet, Paris, 1659, as published in a Romanian book in 1933

“The allegory of syphilis”, a work of Luca Giordano depicting Venus and a young man with alopecia and crusted papules on the scalp, as well as collapsed nose bone, and “Warning against syphilis” painted by Johan Sadeler presenting Venus giving birth to a contaminated milk spring from her breasts and a shepherd -allusion to Francasto’s poem on the origins of syphilis .

The autoportraits of Gerard de Lairesse (1641-1711), as well as his portrait painted by Rembrandt in the XVIIth century highlight in a clear manner the congenital syphilis sequelae of the Dutch painter, amongst which, frontal bossing and saddle nose .

Eduard Munch (1863-1944), an expressionist Norwegian painter presents in “The inheritance” the image of a young mother in tears holding a child with syphilis stigmata in her arms. The painting was initially named “the syphilitic child. According to some critics, Munch was ridiculing in his painting the iconic image of Madonna and the child. Pablo Picasso (1881-1973) was also impressed by this disease. His work “The Wages of Sin” is an allegory of venereal diseases and presents a sailor among prostitutes and a medical student holding a skull, as the symbol of death. This work represents actually a sketch of Les Demoiselles d’Avignon (1907), in which the artist gives up the male characters of the painting and illustrates solely the women who are no longer feminine and beautiful, but unattractive. Some critics believe that this painting points out the artist’s fear of venereal disease .

Famous historical figures diagnosed with or strongly suspected of syphilis

The transmittance of sexual diseases has always been associated with promiscuity and vulnerable population groups . However, the rapid spreading proved not to avoid any geographical, racial or social barriers, affecting also great personalities along the history.

The writers were among the most affected category which was more likely, due to the promiscuous and bohemian life, to have the disease. Alphonse Daudet, Thomas Chatterton, Keats, James Boswell, Baudelaire, Heinrich Heine, Dostoievski and Oscar Wild are only a few examples of writers suffering from syphilis. Romanian poet Mihai Eminescu was diagnosed with syphilis too. He died in a mental institution at the age of 39 years . Even the philosophers, who were usually considered superior minds, insensitive to women charms, also have suffered for syphilis. The most famous of them were Friedrich Nietzsche (1844-1900) and Arthur Schopehnauer (1788-1860). The last has contracted the disease while still a student, and in time, developed a tendency to misogyny .

Famous Casanova is widely and iconically known for his excellent techniques of seduction. However, most of his sexual partners were actually prostitutes, and this may be the reason why he had gonorrhea four times, cancroids for five times, syphilis and genital herpes .

It is also presumed that famous painters as Eduard Manet, Paul Gauguin, Vincent van Gogh and Goya, as well as composers like Ludwig van Beethoven, Robert Schumann and Franz Schubert suffered for syphilis .

Furthermore, the monarchy was not spared of the implacable disease. One example is Tsar Ivan IV Vasilievici (known in history as Ivan the Terrible), Prince of Moscow (1530-1584) who contacted syphilis after the death of his wife. Some authors blame syphilis for his brutal behavior . King Henry III and Charles V of France, Henry VIII and George IV of England, Paul I of Russia and Maximilian I of Holy Roman Empire are other examples.

Al Capone, the famous gangster who led a crime syndicate in the times of Prohibition in the United States supposedly died of neurosyphilis, as a consequence of aggravation of its manifestation after his imprisonment in Alcatraz .

The history behind the establishment of the etiology of syphilis

From the very beginning numerous theories on the origin of syphilis existed, most of which linking initially syphilis and leprosy together. According to several fables of the early XVI th century, syphilis was the result of a sexual relation between a Spanish prostitute and a leper. The prostitute also infected the soldiers of Charles VIII. Paracelsus (1493-1541) considered that syphilis was the result of a sexual intercourse between a prostitute suffering from gonorrhea and a French leper. In compliance to other theories of the time, the disease might have been the outcome of the relationship of a prostitute having a uterine abscess with a leper or the result of poisoning the wine with blood coming from a leper .

Sexual transmitted diseases were seen as a single disease for many centuries. The differentiation between gonorrhea, cancroids and syphilis as distinct maladies was achieved no earlier than XIXth century. In the beginning of XVIIIth century there were several doctors who treated syphilis and gonorrhea as separate entities. However, in 1767 John Hunter a famous physician of venereal diseases at that time (1728-1793) conducted an experiment consisting of an inoculation of the urethral secretion of a gonorrhea patient in the prepuce of a healthy patient, the last developing syphilis shortly afterwards. Consequently, his experiment proved that syphilis resulted from gonorrhea. What Hunter has missed out was that the patient from whom the urethral secretion was taken had both syphilis and gonorrhea. However his experiment, widely acknowledged in his époque, delayed the differential diagnosis of the two diseases with a few decades .

In 1831 Ricord has designed a larger study on syphilis and gonorrhoea and succeeded to show that the last occurs only after contact with gonorrohea patients, whilst the former –only after contact with syphilis patients .

It was not earlier than 1905 that Schaudinn (1871-1906) and Hoffman (1868 – 1959) have discovered the etiologic agent of syphilis, whom they have named Spirochaeta pallida, on various syhilis lesions, proving its existence in both fresh and Giemsa coloured specimens. It was them who changed the name of the bacterium subsequently to Treponema pallidum .

In 1906 Landsteiner introduced the use of the dark-field microscopy method for the detection of the spirochete of syphilis. In 1910 the German bacteriologist August Wasserman (1866-1925) came with the first serologic test for syphilis and in 1949 Nelson and Mayer have conceived Treponema pallidum immobilization test (TPI), the first specific test for T. pallidum . Their discoveries had a very important role in detecting the disease in patients who were suspected of syphilis, as well as in other healthy individuals, and in monitoring syphilis response to treatment.

Syphilis treatments along the history

Initially, the treatment of syphilis included less efficient methods that were accompanied by pain and multiple adverse reactions . Taking into consideration that the disease was associated with the discovery of the American continent, numerous treatments included plants brought from the New World, such as the guaiac tree (lat. Guaiacum Officinale), known also as sasafras or willow (Salix), which led to the widest recognition at the time (Fig. 4). These plants acted as purgative agents, lead to sudoration, diarrhea and the increase in urinary debt and were believed to be “blood cleansers” . One of the main supporters of the guaiac tree utilisation in the treatment of syphilis, and in the same time an ardupus opponent of mercury treatment, was Ulrich von Hutten (1488-1523), a former priest who described in a detail the manifestations of the disease as well the simptoms of mercury intoxication, based on his own experience as a sufferrer from the disease . From the guaiac tree a decoction was made, the resulted potion was boiled and the patient was assumed to consume the mixture daily for 30 days. Before drinking the potion, the patient was covered in blankets in order to induce perspiration, and a mild purgative was also administered .

Guaiacum officinale (guaiac tree), used widely for the treatment of syphilis

Paracelus (1493-1541) was one of the first supporters of the mercury treatment. Mercury was used in Arabic medicine in the treatment of several dermatomes as well as leprosy, and succeeded to gain rapidly an important place in medical field at that time. Mercury is a potent diuretic that also leads to excessive salivation when administered in toxic doses. At the time, is was considered that the “virus” was eliminated from the body through sweat, salivation and diuresis . There were several methods of administering mercury. Thus, in a mixture with grease, mercury was administered topically, leading to ulcerations. Barbarossa pill, named after the Turk admiral who gave the pill to his soldiers and was affected by the malady, contained a mixture of mercury and perfume essence and fruit flavours . Mercurous chloride (calomel, Hg2Cl2) was a white salt able to be administered orally, topically or by injections. The metallic form of mercury was administered also under the form of therapeutic fumigation. Patients seemed to find the adverse reactions of the treatment acceptable, however, the treatment lead to systemic intoxication (hidrargirism) and pneumonia .

Bismuth salts were introduced in syphilis treatments in 1884. These compounds were less toxic than mercury, in the same time bearing a stronger bactericidal effect that the former, consequently, becoming the cardinal heavy metal employed in syphilis treatment .

German scientist Paul Ehrlich (1854-1915) received Nobel Prize in Physiology and Medicine in 1908 for his discovery of arsphenamine (Salvarsan). The scientist discovered the compound that acted like an antibiotic by accident, while working on finding a cure for Trypanosoma brucei. Ehrlich’s desire was to discover a “magical bullet”- a drug able to specifically bind to a bacterium and kill it, without affecting human cells. Salvarsan was also denominated as “Compound 606”, as it was discovered after 606 failed experiments (Fig. 5) . The safer novel drug that superseded the more toxic and less water-soluble salvarsan as a treatment for syphilis was Neosalvarsan, also an arsenic compound. Both Salvarsand and Neosalvarsan were replaced in the treatment of syphilis by Penicillin, after 1940.

The laboratory in which famous 606 compound was invented

Observing that fever lead to symptomatic improvement of neurosyphilis, various methods of fever induction have been experimented with turpentine, tuberculine, mercury and even Salmonella typhi. In 1917, the Austrian physician Julis Wagner-Jauregg (1857-1940) includes malaria in the treatment of syphilis. Malaria induced fever paroxysms able to be controlled, as quinine had already been discovered. Jauregg injected patients suffering from malaria with blood presenting Plasmodium vivax. The patients exhibited fever paroxysms lasting for approximately 6 hours and core temperature returning to normal values; quinine was injected after 3-4 cycles on a 2 day period, in order to treat malaria. In 1927 Jauregg received Nobel Prize for Physiology and Medicine for his discovery .

In 1928, Alexander Fleming (1881-1955) discovered penicilin and from 1943, it became the main treatment of syphilis . Nowadays, worldwide, prevention and treatment programs control syphilis spreading.

The first magic bullet was fired at syphilis on this day in 1909.

Although specific diseases responded better to some drugs than to others, before the early 1900s development of Salvarsan, an arsenic-based drug to treat syphilis, drugs weren’t developed to target a specific disease. A German biochemist named Paul Ehrlich changed all that when he targeted syphilis, a disease that had plagued Europe for 500 years.

“In 1906 Ehrlich prophesied the role of modern-day pharmaceutical research, predicting that chemists in their laboratories would soon be able to produce substances that would seek out specific disease-causing agents,” writes the Chemical Heritage Foundation. “He called these substances ‘magic bullets.’”

These magic bullets would destroy infectious microbes without hurting the people who harbored them. Ehrlich had been looking for them since the 1870s, writes Hadley Leggett for Wired, but it took him a long time to find one that worked for any illness.

Ehrlich was innovative in seeing the body’s immune response as a matter that could be studied by chemists. “ He saw toxins and antitoxins as chemical substances at a time when little was known about their exact nature,” writes the Chemical Heritage Foundation. This perception, which earned him the 1908 Nobel Prize in Medicine, led him to see that chemicals introduced into the body could help it in fighting disease–if they were the right chemicals for the right disease.

When his collaborator Sahachiro Hata finally tested Ehrlich’s syphilis drug on a rabbit on this day in 1909, it seemed they’d truly found one. “Hata injected chemical No. 606 into a rabbit with syphilitic ulcers,” writes Leggett. “The next day, no live could be found on the animal’s ulcers, and within three weeks, the ulcers were completely gone.”

A Salvarsan treatment kit. Salvarsan treatment was extremely painful and didn’t work right away, but compared to previous types of treatment, it was a wonder. (Wikimedia Commons)

Syphilis was a big problem in Europe at this time. “Historians mining the archives of prisons, hospitals and asylums now estimate that a fifth of the population might have been infected at any one time,” writes Sarah Dunant for The Guardian. By the 1920s, writes Stefan H. E. Kaufmann in Nature Reviews Drug Discovery, Ehrlich’s innovations had dramatically improved the situation.

Previous treatments for “the French disease” were horrifying and ineffective. “The old adage ‘a night with Venus; a lifetime with Mercury’ reveals all manner of horrors, from men suffocating in overheated steam baths to quacks who peddled chocolate drinks laced with mercury so that infected husbands could treat their wives and families without them knowing,” Dunant writes. “Even court fashion is part of the story, with pancake makeup and beauty spots as much a response to recurrent attacks of syphilis as survivors of smallpox.”

Syphilis was known to be a sexually transmitted infection, but the microbe that caused it—the bacteria Treponema pallidum, which attacks the nervous system and the organs–wasn’t identified until 1905. The next year, Ehrlich and his colleagues started looking for its magic bullet, according to Chemical Heritage.

Salvarsan, an arsenic-based drug, proved to be just that. It was the result of three years of testing of different arsenical compounds–300 of them, according to the Chemical Heritage Foundation. Salvarsan was on the market by 1910, writes Amanda Yarnell for Chemical and Engineering News, and quickly became the most widely prescribed drug in the world.

“It was the world’s first blockbuster drug and remained the most effective drug for syphilis until penicillin became available in the 1940s,” Yarnell writes. But it didn’t work well with patients in the later stages of syphilitic infection, as well as being hard to administer. In fact, some of the side effects that it was said to cause were actually caused by physicians being unable to properly administer the drug, writes Yarnell. Ehrlich observed that “the step from the laboratory to the patient’s bedside… is extraordinarily arduous and fraught with danger.” In response to these issues, Ehrlich synthesized a refined compound, Neosalvarsan, by 1914.

Salvarsan was a big deal for syphilis sufferers, but the work of Ehrlich and his collaborators also changed how disease was thought of and how drugs were developed. The fact that his drug was on the market within a year of being developed shows how new his approach to medicine was.

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