Pox, pustules and pestilence – A history of syphilis treatment

By Robert MacLean on September 7, 2015 • ( 3 )

Syphilitic pustules on the nose of a patient. From the title page in Richard Carmichael’s Observations on the symptoms and specific distinctions of venereal diseases. Sp Coll DK.13.24

Syphilitic pustules on a patient’s nose. From Carmichael’s “Observations on the symptoms and specific distinctions of venereal diseases”. Sp Coll DK.13.24

Post by Caitlin Jukes, a current University of Glasgow PhD student researching in Microbiology. She is currently undertaking a three month BBSRC-funded placement in Special Collections working with the Glasgow Syphilis Collection. The Glasgow Syphilis Collection comprises circa 250 early printed works on the disease, recently described in a Wellcome-funded project.

In Special Collections we have one of the best collections of books relating to syphilis in the UK, ranging from 15th century printed accounts, contemporary with the first appearance of the disease, to much later publications concerning its classification and treatment. As a microbiologist I find this fascinating as there are probably few other pathogens for which there is such a strong historical record. Using the collection I will explore various aspects of the disease including treatments and the origins of the illness.

Treatments for syphilis were horrific. In some cases it may be argued that they were as damaging as the illness itself. However people were willing to try anything to be cured. There was a reason for their desperation. During the first few years of the outbreak syphilis was terrible: stinking pustules covering the body, incredible pains in the joints and the destruction of flesh and bone were all common. The pustules were described by Ulrich Von Hutten, who himself suffered from syphilis, as,

‘Boils that stood out like acorns, from whence issued such filthy stinking matter that, whosoever came within the scent believed himself infected’ (1)

The Virgin Mary with Jesus is her arms who is punishing the people with syphilis. Grünpeck’s “Tractatus de pestilentiali scorra siue mala de Franzos”. Sp Coll Hunterian Bx.3.38. (Ausburg, 1496)

The outbreak began suddenly in 1495 among French troops in Naples. The spread was rapid and unstoppable and before long most of Europe and Asia was affected. We now know that syphilis is a sexually transmitted bacterial infection but at the time, it was widely believed that the new sickness was punishment from God and was caused by an unusual astrological phenomenon. It was punishment for sins and was seen as a moral disease inflicted upon the people who most deserved it.

The first treatments to emerge were based on remedies for skin conditions. Mercury, not yet identified as a toxic heavy metal, was widely used. It proved to be a popular treatment for a staggering 400 years until the late 19th century – remarkable as it is a painful and ineffective treatment. It was given as an ointment, in tablets and in the form of a mercury bath, where patients were placed in a hot room and left to inhale vaporised mercury every day for up to a month. Most treatments were designed to cause sweating, salivating, diarrhoea and vomiting to purge the ‘poison’ from the body. All of these side effects are strong indicators of mercury poisoning and I can only imagine what it would be like to endure a ‘cure’ of this nature. Some doctors even went as far as suggest how much saliva the patient should be expected to produce each day, in some cases as much as 3 or 4 pints! The side effects were terrible, with patients losing their teeth and hair, suffering from neurological problems and often dying from mercury poisoning. It resulted in the saying,

‘A night with Venus, and a lifetime with mercury’

Another popular treatment used the bark from the Guaiacum tree, boiled into an ointment and given as a drink. It was believed that God would provide a cure for the disease in the place from which it originated: in this case the Americas were suspected as the source of syphilis, hence bark from the tropical Guaiacum tree was a logical, if once again ineffective, choice. Guaiacum was championed by many people including Ulrich Von Hutten, although it’s worth noting he eventually succumbed to the disease so it can’t have worked that well!

Mercury won the popularity contest though, and was considered the most effective cure. Championing it as a ‘cure’ wasn’t completely far-fetched since we now know that it is highly effective at combatting the bacterium that causes syphilis. The problem is that the level required to kill the bacteria and the level that is toxic to humans is quite similar making it a terrible treatment (2).

A man having mercury ointment applied to his legs. This was done with a spatula to avoid the doctor coming into contact with the sores and the mercury. From Paracelus’ “Erster Theil [-der dritte] der grossen Wundartzney die Frantzosen genannt”. Sp Coll Ferguson Ap-d.51 (Frankfurt, 1562).

Use of mercury was widely criticised by many doctors such as Andrew Mathias, who recognised that mercury treatment could be more dangerous than the disease itself,

“Effects so deplorable have preceded [from the use of mercury], as to leave no doubt that in these instances it has been infinitely more destructive to health than the disease for the removal of which it was originally employed”(3)

However there was resistance to the use of other treatments and it seemed that people were almost obsessed with the idea of using mercury, as John Hennen alludes to in his book,

“It is a very remarkable fact, that, in a variety of instances, whenever a rival medicine has started up in opposition to mercury, while the blind supporters of that mineral seemed to be confirmed in their conviction of its exclusive power the rival is often allowed to have “some powers” or “under certain circumstances to be useful”…. The roguery of the quacks in putting corrosive sublimate into their boasted syrups to be composed of vegetable alone, cannot be adduced to controvert the fact; It only proves that the ignorant quack and the learned physician were equally bigoted mercurialists.”(4)

Doctors were unsure about the cause of the disease until the corkscrew shaped spirochete (ie. bacterium) now known as Treponema pallidum was isolated from a syphilitic sore in 1905. This was quickly followed in 1906 by an immunoglobulin test for infection called the Wasserman test which allowed for easy detection and helped to prevent misdiagnosis. However there was still no clear treatment. In 1909 Paul Ehrlich and Sahachiro Hata finally found a compound that could clear infection from rabbits, compound 606 or Salvarsan. Arsenic based and hurriedly put through clinical trials, it was approved for sale and widely used from 1910. It was effective but very difficult to administer with many side effects and problems reported from patients.

The discovery of penicillin in 1928 by Alexander Fleming was the real game changer when it came to the treatment of this disease. Penicillin was used from 1943 with supply often failing to meet demand. After its introduction the number of reported cases of syphilis decreased dramatically and the associated morbidity and mortality dropped by a dramatic 90% between 1945 and 1975 (5). After more than 400 years of searching, a cure for syphilis was found.

Clostridium difficile on an agar plate

Antibiotics like penicillin have revolutionised medicine. However, increasingly bacteria are evolving to develop resistance to the current antibiotics we use to treat them. Without research into new antibiotics and alternative treatments we could return to a world where a horrific outbreak like this could be a reality. In my PhD I work on a bacterium called Clostridium difficile, itself caused by use of antibiotics. It is the leading cause of antibiotic associated diarrhoea worldwide and can be fatal as it is incredibly difficult to treat since further antibiotics are often ineffective. Patients can relapse and are left in a cycle of temporary cure and relapse, sometimes for years. It is now known that the 2kg of bacteria that reside in the gut, your microbiota, are extremely important for helping to resist infections (among lots of other amazing things!) When you take a course of antibiotics, be it for an infection in a completely different site, the bacteria in your gut are affected and protective species can be wiped out leaving you vulnerable to C. difficile. New therapies focus on replacing these protective species using faecal transplants. Although a bit disgusting these are incredibly effective at supressing C. difficile infection (90% cure with one treatment vs 30% with antibiotics) but for obvious reasons are not an ideal therapy. My PhD is focused on determining which bacteria in your gut are able to protect against C. difficile with the hope of making a synthetic version of the current treatment. Research like this, as well as research into new antibiotics, is all important in the fight against antibiotic resistance.

References

Ulrich Von Hutten De Morbo Gallico. Sp Coll Hunterian Ab.8.36 (London 1533)
J G O’Shea ‘Two minutes with venus, two years with mercury’ – mercury as an antisyphilitic chemotherapeutic agent. Journal of the Royal Society of Medicine Volume 83 June 1990
Andrew Mathias. The mercurial disease. An inquiry into the history and nature of the disease produced in the human constitution by the use of mercury, with observations on its connexion with the lues venerea. Sp Coll e.3.20 (London 1816)
John Hennen. Principles of military surgery, comprising observations … history, treatment, and anomalies of variola and syphilis Sp Coll NN.5.14 (Edinburgh 1820)
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2006. Atlanta, GA: US Dept of Health and Human Services; November 2007