Founding the Antibiotic Era

The antibiotic era as we know it today started with syphilis. Yes, the face-ravaging, sanity-altering sexually transmitted infection. At the turn of the 19th century, syphilis was endemic and almost incurable. Caused by the spirochete Treponema pallidium, syphilis was usually treated with inorganic mercury salts. But mercury salts treatment had extremely severe and unpleasant side effects and did not usually work very well. Paul Erlich thought there might be a better way. His idea of a “magic bullet” that selectively targets only disease-causing microbes, and not the human housing those microbes, was based on scientists noticing that aniline and other synthetic dyes, which first were produced in the late 1800s, could stain some specific microbes but not others. Paul Ehrlich argued that special chemical compounds could be created which would “be able to exert their full action exclusively on the parasite harbored within the organism.“  This idea of Erlich’s led him to begin a large-scale and systematic screening program (as we would call it today) in 1904 to find a drug against syphilis.

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Fever is an increase in core body temperature and a common symptom of infectious disease. It’s thought to be a defense mechanism against infection, because some pathogens are delicate enough to be disrupted by even a slight deviation from their ideal temperature. Indirectly, increased body temperature can hinder the effects of bacterial toxins while enhancing some immunological functions like mobility and proliferation of white blood cells.

Raising the core body temperature also uses a tremendous amount of energy; it’s not something that it makes sense for an organism to do frivolously. In addition to simply burning more calories from fat storage, energy used to run a fever is diverted from from other systems of the body. Aside from some immunological functions, most cellular processes are hindered by fever. Enzymes typically have narrow ranges of optimal function and high fevers toe the line for both host and pathogen. Too high of a fever can cause permanent brain damage.

Treponema pallidum, the bacterium that causes syphilis, is an example of a delicate heat-sensitive pathogen. Plasmodium vivax is one of many parasites in the genus Plasmodium, known for malaria, an infection that causes (among other things) severely high fevers. Before Alexander Fleming discovered penicillin in 1942, there was no reliable chemical treatment for syphilis. However, malaria could be reliably treated with quinine!

You see where this is going, right? Julius Wagner-Jauregg won the Nobel Prize in 1927 for treating syphilis with malaria. It was successful! His patients who didn’t die were cured of syphilis. But even I wouldn’t recommend getting malaria on purpose if you have syphilis. It’s easier to treat syphilis nowadays anyway.


Here’s the speculation part of this post.

The human body is capable of producing fevers high enough to cure syphilis, but it doesn’t. Syphilitic fevers are mild and don’t show up in all cases. I’d be interested to see if patients who come down with fevers in early stage syphilis have better outcomes, but I can’t find any information on that.

Dangerously high fever is one of the fatal symptoms of malaria, but Plasmodium is not heat-sensitive in the same way Treponema is. If high fever isn’t effective at killing malaria parasites, why is it a response to malaria infection?

Since the host must get bitten by a mosquito in order for a malaria parasite to complete its life cycle, lethargy in the host is helpful to the parasite. That isn’t the case for other infections–for communicable or sexually transmitted diseases, anything that reduces contact with other people reduces the chance of transmission. For vector-borne diseases, the opposite is true. It’s easier for a mosquito to bite when the host is too tired to move around or even swat.

A high fever in the host works in Plasmodium’s favor, but it’s bad news for Treponema.

Real Facts From Episode 203

While The Knick is a work of fiction, it is based on exhaustive historical research. Below, the show’s writers share some of the true facts of the era that are depicted in this episode.

Rockefeller, Carnegie, and Harriman all put money toward eugenics research. At the turn of the Century, Eugenics was viewed as an “emerging science,” an offshoot of Darwin’s theories on evolution, and a new way to understand human beings. (Image courtesy of the Burns Archive.)

Syphilis spirochete is called Treponema Pallidum. It is fairly unmistakable in appearance (it looks a lot like a ramen noodle). Thackery’s understanding of a fever’s impact on syphilis is mostly due to the work of Austrian psychiatrist, Julius Wagner Jauregg (1857-1940).

Jauregg saw a woman with severe psychosis recover after a bout of Erysipelas, a bacterial skin disease that causes high fevers. He began experimenting with tuberculin-induced fevers. After several patients died under such treatment, he stopped his experiment, only to start up again after 1900. Then in the post-WWI era, Jaurgegg switched to using Malaria to try and cure patients with Neurosyphilis. He went on to win a Nobel Prize in 1927 for his work. (Image courtesy of the Burns Archive.)

In 1900 Mount Sinai Hospital purchased an X-Ray Machine and set it up in their synagogue. )

Huber’s Palace was an establishment that housed stages for performances, exotic animals, and “freak acts” like “The Dog-Faced Boy.” Huber’s motto was “A dollar show for ten cents.”