Understanding and Treating Gonorrhea from the Eighteenth Century to the Twenty-First Century

Gonorrhea is a sexually transmitted disease, or STD, caused by the bacterium Neisseria gonorrhoeae. Common symptoms of the disease include painful urination and genital discharge. There are records of historical discussions of gonorrhea in ancient civilizations and during the Middle Ages, but scientists did not begin investigating the scientific causes and treatments of the STD until the sixteenth century. In the 1700s, physicians attributed gonorrhea to the same cause as another STD, syphilis. Later, in the 1800s, researchers discovered the two diseases were not the same and identified the bacteria N. gonorrhoeae that causes gonorrhea. By the 1900s, researchers began using antibiotics to target the bacteria, but many drugs eventually developed antibiotic resistance. In 2020, the World Health Organization, or WHO, estimated that 82.4 million individuals contracted gonorrhea globally, and as of 2024, researchers continue to experiment with various antibiotic drugs to provide adequate treatment for the disease.

1. Background and Context
2. Early History
3. Gonorrhea in the Eighteenth Century
4. Gonorrhea in the Nineteenth Century
5. Gonorrhea in the Twentieth Century
6. Twenty-First Century Developments

Background and Context

Gonorrhea is a common STD that can affect both males and females. Individuals primarily transmit gonorrhea through sexual contact, though it can also be passed from mother to fetus during pregnancy. Pregnant women with gonorrhea can transmit the disease to their baby, and that can lead to miscarriages, premature birth, or low birth weight. When sexually transmitted, gonorrhea affects the body parts involved in its transmission, which can include the throat, rectum, and genitals. Individuals infected with gonorrhea in the rectum and throat often experience anal itching or bleeding and sore or swollen lymph nodes, respectively. Men infected with gonorrhea in their genital tracts typically experience pain with urination, pus-like discharge from the urethra, which is the tube inside of the penis from which urine leaves the body, and pain or swelling in one of the testes, which are the organs which produces sperm. Untreated gonorrhea can lead to infertility in men. Common symptoms for women with gonorrhea infection include increased vaginal discharge, pain with urination, random vaginal bleeding, and abdominal or pelvic pain. Without treatment, women are at risk for pelvic inflammatory disease, or PID. PID is a bacterial infection resulting in inflammation of the organs of the female reproductive system, and it can cause scarring of the fallopian tubes, leading to infertility. As of 2024, physicians treat and cure gonorrhea with antibiotics, such as ceftriaxone, though antibiotic-resistant gonorrhea is becoming more prevalent.

Early History

Many of the first recorded historical discussions of gonorrhea began with early ancient civilizations and continued in the Middle Ages. In the second century, the physician Galen of Pergamon, Turkey, noted the disease and coined the term gonorrhea. The word gonorrhea derives from the Greek words gonos (semen or seed) and rhoia (to flow). He incorrectly attributed the disease as an involuntary ejaculation of semen. One of the first written probable evidence of gonorrhea as a recognized disease stems from the Middle Ages, a 1000-year time period from the years 476 to 1400. Scholars of the Middle Ages recorded descriptions of patient symptoms that describe no disease other than gonorrhea, including burning pain, painful urination, and difficulty passing urine. By the 1500s, gonorrhea became colloquially known as the clap. At that time, people associated gonorrhea with sex work, and as a result, the term the clap originated from the French word for a type of brothel, les clapiers (rabbit huts).

During the period following the Middle Ages, scholars began forming theories about gonorrhea, though they often confused the presentation of gonorrhea with other STDs, such as syphilis. This confusion began in the 1500s and persisted through the 1800s. Paracelsus, a physician and philosopher in Switzerland, was one of the first to associate gonorrhea with other STDs. In the early 1500s, he referred to syphilis, another STD, as French gonorrhea, which began scientific confusion between the two diseases. As later scholars and researchers studied gonorrhea, they had to consider and identify its differences with syphilis. Syphilis is a progressive disease caused by a bacterium, and its symptoms are commonly mistaken for other diseases, such as gonorrhea. The first hallmark symptom of syphilis is typically a chancre, a round painless sore that erupts on the genitals. Symptoms of later stages of syphilis include skin rashes and flu-like symptoms, such as fever, sore throat, or fatigue. By the eighteenth century, many scholars and physicians suggested that gonorrhea and syphilis had the same causal agent. However, few of them had performed experiments to test that theory using human subjects, nor had their work been adopted by the scientific community at large.

Gonorrhea in the Eighteenth Century

In 1786, John Hunter, a surgeon from London, England, published his book A Treatise on the Venereal Disease, which considered the theory that gonorrhea and syphilis were manifestations of the same disease. Venereal disease is another term for sexually transmitted diseases. In his book, Hunter concluded that gonorrhea and syphilis were different physical phenomena of the same infectious agent, which he referred to as the poison. In his book, Hunter defined gonorrhea as the first stage of disease and syphilis as the second stage. He explains that gonorrhea and syphilis do not always occur at the same time because the presence of either gonorrhea or syphilis acts as a deterrent to prevent the other condition from arising in the body simultaneously. Hunter drew those conclusions from his 1767 experiment, where he collected the discharge from an individual with gonorrhea, then inoculated another person with the discharge. After ten days, the inoculation recipient formed a chancre and other physical symptoms of syphilis, which Hunter interpreted to mean that he had successfully induced syphilis in a person using gonorrheal discharge. Hunter argued that the results of that experiment confirmed that the same infectious agent or poison causes both gonorrhea and syphilis. In his 1994 text The Scars of Venus, John David Oriel, a physician and disease historian, argues that the person in Hunter’s experiment likely developed symptoms of syphilis because they had been infected with both diseases already. As of 2024, it is scientifically accepted that the two are distinct, separate diseases. However, at the time of his book’s publication, Hunter’s book received support from other scholars, philosophers, and physicians.  

In 1793, Benjamin Bell, a surgeon from Scotland, was one of the first scholars recorded to propose that gonorrhea and syphilis were not the same disease in his book Treatise on Gonorrhoea Virulenta and Lues Venerea. His theory contradicted the widely accepted beliefs of Hunter’s proposal. In his book, Bell provides case descriptions of patients with gonorrhea, which he used to form several guidelines on the nature of gonorrhea. Bell states that on occasion, individuals suffer from both gonorrhea and syphilis at the same time, which Bell argues contributed to other physicians’ beliefs that they rise from the same origin. He agrees with the well-established thought that gonorrhea is a localized disease, primarily affecting the urethra, while syphilis is a constitutional disease, one that disseminates throughout the body over time. Subsequently, he asserts that because the diseases have different symptoms, they likely have different causal agents too. Elaborating upon that statement, Bell explains it is well known and accepted that the first symptom of syphilis is almost always a chancre on the penis. He argues that if gonorrhea comes from the same origin as syphilis, then gonorrhea should also manifest in the form of a chancre as syphilis does. Also in his treatise, Bell explains that inflammation of the urethra due to gonorrhea frequently causes swelling of the testes but the same is not true of syphilis, which he presents as further evidence of the two diseases having different causal agents.

Gonorrhea in the Nineteenth Century

In the nineteenth century, Phillipe Ricord, a surgeon who studied sexually transmitted diseases in France, argued that gonorrhea and syphilis were distinct, separate diseases and published the results of the experiments in his 1838 book Traité Practique des Maladies Vénériennes (A Practical Treatise on Venereal Diseases). Ricord disagreed with many of Hunter’s conclusions about the origin of gonorrhea and criticized his and other researchers’ inoculation research. In the 1830s, Ricord performed over 2,500 inoculation experiments by inserting discharge from the urethra or genital sore of a person infected with gonorrhea into the thighs of his patients. Then, he covered the injection site with a piece of glass and monitored the inoculation site for symptoms related to syphilis or gonorrhea. Based on those experiments, many of which he discussed in his 1838 book, Ricord concluded that inoculation with gonorrheal discharge did not give rise to syphilis. He also found that when he injected gonorrheal discharge into a person’s thigh, it did not cause a chancre to develop. However, when he injected syphilitic discharge from a chancre into a person’s thigh, it did result in another chancre. Thus, he determined that gonorrhea and syphilis are not caused by the same infectious agent. Despite Ricord’s accurate conclusion that syphilis and gonorrhea are two separate diseases, as of 2024, scientists argue that his inoculation technique and experiment were incorrect and flawed.

In 1879, Albert Neisser discovered the causal agent of gonorrhea, later named Neisseria gonorrhoeae. Neisser, a physician who studied sexually transmitted diseases in Poland during the late nineteenth century, used microscopy technics to examine the discharge from thirty-five people living with gonorrhea. He discovered microscopic bacterial organisms in the samples, or micrococci, which he described as round organisms almost always appearing in pairs of two, suggesting a figure-eight shape. He published his findings in his 1882 article titled “Ueber eine der Gonorrhoe eigentümliche Micrococcusform” (On a Form of Micrococcus Peculiar to Gonorrhea). He argued that the micrococci are present in all gonorrheal infections, and thus, a physician can diagnose a person with gonorrhea by examining their pus. Following the publication of his results, scientific debate regarding the causal agent of gonorrhea ceased as researchers began to accept Neisser’s findings.

Following Neisser’s experiments and discovery of the causal agent of gonorrhea, two addition scientists performed experiments that supported Neisser’s findings. In 1883, Ernst von Bumm, who studied gynecology, successfully induced gonorrhea in an individual by inoculating them with the lab-grown gonorrhea micrococci identified by Neisser. In 1891, Ernst Wertheim, who studied gynecology in Vienna, Austria, repeated the same experiment and successfully induced gonorrhea in his patient. Those experiments confirmed that the micrococci bacteria Neisser had identified indeed caused gonorrhea in people. The discovery and confirmation of N. gonorrhoeae as the cause of gonorrhea provided the foundation that physicians and researchers needed to develop targeted treatments.

Gonorrhea in the Twentieth Century

Although gonorrhea treatment began as early as the sixteenth century, physicians discovered medically effective treatment methods only in the early 1900s. Early treatments before the 1900s were ineffective at combatting infection. In the sixteenth century, physicians treated gonorrheal infection by injecting mercury into the urethra of infected individuals. In the eighteenth century, physicians determined the treatment method based on the quantity and quality of pus excretion from the urethra. Individuals with mild symptoms received bland fluid, while individuals with severe symptoms often received urethral lavage, which was a painful procedure involving the flushing of water into the urethra to eliminate infection. In the early 1900s, researchers began intravenously infusing a compound called mercurochrome into patients, but that was less effective than later treatments. During the early twentieth century, researchers created antibiotic drugs, which are capable of targeting specific bacteria and treating bacterial diseases, as treatments for a variety of bacterial diseases such as meningitis, pneumonia, and syphilis. The first antibiotic used to treat of gonorrhea emerged a few decades into the twentieth century.

In the 1930s, Gerhard Domagk, discovered the antibiotic properties of sulfanilamide, which was the first antibiotic treatment to effectively kill N. gonorrhoeae and treat gonorrhea. Domagk was a researcher who studied bacteria, infection, and antimicrobial compounds at I.G. Farbenindustrie, a pharmaceutical company in Wuppertal, Germany. In the early twentieth century, Domagk began researching chemical compounds to measure their effectiveness against various bacterial diseases. In 1935, Domagk noticed that one of the compounds, a red dye, had antibacterial properties against streptococcal bacteria, a type of bacteria that can cause disease, including strep throat. After that discovery, Domagk derived the drug sulfanilamide, the chemical compound responsible for the antimicrobial properties, from the dye. Given the drug’s efficacy in treating streptococcal bacterial infections, researchers decided to test sulfanilamide against other coccal bacteria, which is a class of sphere shaped bacteria, including N. gonorrhoeae. In 1938, researchers conducted a clinical trial of oral sulfanilamide for treating gonorrhea in 633 men and women, which revealed sulfanilamide effectively cured gonorrhea in eighty percent of the participants after three weeks of treatment. By the 1940, sulfonamide became widely available as a treatment option for gonorrhea and other infections.

In the 1930s, scientists created varying types of other sulfonamides, such as sulphapyridine and sulfathiazole, which physicians then used to treat gonorrheal infections, especially those that sulfanilamide failed to cure. Sulfonamides, or sulfa drugs, did not remain an effective treatment for gonorrhea for long. By 1944, researchers observed that over ninety percent of gonorrhea bacteria had developed resistance to sulfa drugs, the drug class including sulfanilamide and similar antimicrobials, when tested in a laboratory. The gonorrhea bacteria developed resistance through mutation, or sporadic changes to its genome that allow it to better survive in human hosts. Resistance often develops when bacteria fail to respond to the medication, making infections harder to treat. Medications can also fail to eliminate diseases when people misuse antibiotics by not taking the entire dose of medication, taking antibiotics they were not prescribed, or even by physicians prescribing antibiotics to people who do not need them.

In response to the spread of sulfonamide-resistant gonorrhea, physicians began to use penicillin, another antibiotic created in the early 1900s, to effectively treat gonorrhea. In 1943, a team of physicians at the Mayo Clinic in Rochester, Minnesota, conducted a study with three men who had sulfonamide-resistant gonorrhea. The researchers administered penicillin treatment to the men, and subsequently, the treatment successfully eliminated the infection. Later, in 1944, researchers from the US Army and US Public Health Service examined the effects of penicillin treatment again. They treated 1,686 patients with sulfonamide-resistant gonorrhea with penicillin, and the penicillin effectively cured gonorrhea in ninety-nine percent of the participants. Other studies throughout the 1940s continued to verify the effectiveness of penicillin for treating gonorrhea. For a few decades, penicillin remained effective at treating gonorrhea and medical providers continued to use it to treat gonorrheal infections. However, N. gonorrhoeae continued to develop resistance over time and disseminate globally during those decades until medical providers stopped using penicillin to treat gonorrhea in the late 1980s.

Researchers used numerous different antibiotics to treat gonorrhea throughout the twentieth century, but the bacteria continued to evolve resistance to the drugs over time, which led to the use of new antibiotics, including spectinomycin, tetracyclines, and fluoroquinolone. After resistance to sulfonamides and penicillin developed, researchers developed spectinomycin, an antibiotic made in the 1960s specifically to treat gonorrhea, and it became a widespread treatment for the condition. However, scientific reports by scientists in the Netherlands and Philippines in 1967 and 1981, respectively, noted evidence of spectinomycin-resistant gonorrhea among individual patients. In 1983, experts observed twenty-two strains of spectinomycin-resistant gonorrhea in patients at a hospital in London, England, which led physicians globally to stop using spectinomycin for gonorrheal treatment. In 1986, physicians globally had to abandon an entire drug class, tetracyclines, because gonorrhea had developed resistance to several tetracycline drugs. Following the tetracyclines, fluoroquinolone antibiotics, first synthesized in the 1960s, effectively treated gonorrhea but the gonococcus also developed resistance with cases of treatment failure occurring in the 1990s. By the early 2000s, the Centers for Disease Control and Prevention, or CDC, stopped advising the use of fluoroquinolones for the treatment of gonorrhea due to widespread incidence of resistance.

Twenty-First Century Developments

After abandoning fluoroquinolones to treat gonorrhea in the early 2000s, physicians began using a class of antibiotics called cephalosporins to treat gonorrhea, including the drugs cefixime and ceftriaxone. However, N. gonorrhoeae evolved resistance to cephalosporins as well by the start of the twenty-first century. One hospital in Japan saw four cases of cefixime-resistant gonorrhea necessitating treatment with ceftriaxone between November 2002 to May 2003. Researchers continued to record multiple instances of cefixime-resistant gonorrhea in subsequent years. Eventually, cefixime resistance spread widely, and experts in Japan stopped using cefixime to treat gonorrhea. Following that, cefixime-resistant gonorrhea spread to multiple countries in Europe, South America, and Canada. In 2012, the CDC stopped recommending the use of cefixime for gonorrheal infections, leaving ceftriaxone as one of the last effective treatments against gonorrhea. However, in 2011, researchers in Japan observed a case of highly ceftriaxone-resistant gonorrhea, with several other instances of ceftriaxone-resistant gonorrhea appearing in other countries in the years following.

As of 2024, experts at the CDC continue to recommend treating gonorrhea with a single dose of 500 mg of intramuscular ceftriaxone. While ceftriaxone is still largely effective at treating gonorrhea, researchers have expressed concern over the cases of ceftriaxone-resistant gonorrhea. For example, researchers in Japan from the 2011 case of ceftriaxone resistance expressed concern that N. gonorrhoeae threatens effective disease control. If ceftriaxone resistance rises, researchers have stated that newly developed antibiotics will soon be necessary to effectively treat gonorrhea. Other researchers have proposed gonorrhea surveillance programs and combination antimicrobial therapy as potential measures to address impending ceftriaxone resistance.

As of 2024, gonorrhea is one of the most common sexually transmitted disorders that affects both male and female reproductive health. Understanding the history of gonorrhea is important for individuals to understand the differences between gonorrhea and other STDs. It also helps individuals experiencing symptoms to understand that symptoms may return due to antibiotic resistance, because of failure to eliminate infection. Because untreated gonorrhea infection can lead to scarring, pain, or irreversible infertility, it is important for individuals presenting with gonorrhea-related symptoms to seek out health care assistance after exposure to the disease or following the onset of symptoms.