The Birth of The Germ Theory

Posted on | April 21, 2025 | Comments Off on The Birth of The Germ Theory

Mike Magee

When Yellow Fever broke out shortly after the arrival of a trading ship from Saint-Dominque in Philadelphia among colonists with no immunity in 1793, the main response was panic, fear, and mass evacuation from the city. Five thousand citizens, roughly 10% of the population, including Alexander Hamilton and his wife, fled. Experts were at a loss to explain the cause, and were even more confused how to treat the disease.

Benjamin Rush was the primary leader of Medicine in the young nation where physicians were scarce and nearly all relied on Europe for their advanced education. In confronting the epidemic, Rush believed the problem involved a disturbance of the four humors – blood, phlegm, black bile and yellow bile. His solution was the rather liberal and barbaric use of cathartics and blood letting. For the most severe cases, Rush warehoused dying victims in the first “fever hospital” in the new nation.

But a century later, as historian Frank Snowden wrote, “Humoralism was in retreat as doctors absorbed ideas about the circulatory and nervous systems, and as the chemical revolution and the periodic table undermined Aristotelian notions of the four elements composing the cosmos…More change occurred in the decades since the French Revolution than in all the centuries between the birth of Socrates and the seizure of the Bastille combined.”

During the 20th century, but especially in the second half of the 1800’s, scientific progress was self-propagating. Much of the credit for this enlightened progress goes to the rapid evolution of “the germ theory.” No single genius was responsible. Rather, knowledge built step wise and involved a collective (if not fully cooperative) effort by multiple scientists.

One of the early insights was that late stage disease in morbid hospitalized patients literally “on their last leg” was the tail end of a process. French physiologist, Claude Bernard in his “An Introduction to the Study of Experimental Medicine,” made the point that the challenge was to uncover the “beginnings” of these “final stages.” Rather than observe dying bedridden patients, he promoted “experimentalism medicine” in outside laboratories. In doing so, Bernard was likely not fully aware that he was tipping the national scale of medical discovery toward Germany where scientific and research laboratories enjoyed popular support.

It’s important to note that leaders at the time were not intellectual elites, but rather more often skilled artisans of the natural world. A prime example was Antonie van Leeuwenhoek who opened his first store as a cloth merchant at the age of 22 in 1654. Prior to this, he had served as an apprentice to a lens grinder and metalworker. It was in pursuit of a better view of the threads of cloth he was purchasing and selling that he devised one of the first single lens microscopes which had a magnification of 275X.

His curiosity spilled over to the natural world as well. And so it was that he noted in a liquid specimen single cell organisms he labeled “animalcules” in a poorly received communication to the Royal Society of London at the age of 44 in 1676. After a year of hedging, the Royal Society finally acknowledged such creatures existed.

But another seventy years would pass before a connection was made between microscopic “animalcules” and disease. The insight came thanks to the dogged experimentation of an Hungarian gynecologist who put 2 and 2 together in 1847. Maternal mortality from “puerperal fever” was commonplace at Vienna General Hospital at the time. But Ignaz Philipp Semmelweis, the physician director of the service, noticed that mortality rates between his two service – one run by physicians and the other midwives – was strikingly different. (20% vs. 2%). Delivery practices were roughly the same. But one difference stuck out. The physicians also were in charge of mandatory autopsies, and often shuttled between the delivery suite and morgue without a change in clothing or any cleansing whatsoever. Also one of Semmelweis’s trainees who cut himself during an autopsy also died of an identical disease. So he decided to require that members of both team would wash their hands in a chlorine solution before entering the maternity area. Mortality rapidly dropped to 1.3%.

Others were making the connection as well. For example, few stories are as well known as the case of John Snow, the London public health pioneer, who in 1854, traced the death of 500 victims during a cholera epidemic to a contaminated Broad Street water pump. Removing the pump handle was curative. As important as the investigative findings were his publication the following year titled “On The Mode of Communication of Cholera” because scientific progress relies heavily on transfer of knowledge and sequential collaboration. That same year, an Italian physician, Fillippo Pacini, first visualized the organism. But 3 more decades would pass before the German physician, Robert Koch, would isolate the bacterium in pure culture.

Koch was one of “The Famous Trio,” credited by historian Frank Snowden with creating “a wholesale revolution in medical philosophy.” In addition to Koch, these included French scientist Louis Pasteur and Scottish surgeon, Joseph Lister.

I. Louis Pasteur (1822-1895) was a French chemist (not a biologist or physician) who famously stated that “Where observation is concerned, chance favors only the prepared mind.” In the 1850s, while investigating spoilage of wine and milk, he developed the theory that putrefaction and fermentation were not “spontaneous”, but the result of bacterial processes, and that these degrading actions could be altered by heat. Heat destroyed the bacteria, and prevented spoilage (ie. pasteurization). This insight launched the field of “microbiology”.

Pasteur also helped define the principles of “nonrecurrence” (later called “acquired immunity”), and “attenuation”, a technique to render microbe causing disease specimens harmless when introduced as vaccines.

II. Robert Koch (1843-1910) was a German physician 20 years younger than Pasteur. He investigated Anthrax in the mid-1870’s at the University of Gottingen. Luckily the bacterium was very large and visible with the microscopes of the day. He was able to reproduce the disease in virgin animals by injecting blood from infected sheep. But, in addition, he detected and described spores formed by the bacterium, which were left in fields where infected animals grazed. The spores, he declared were why virgin animals grazing in these fields, became infected.

Teaming up with the Carl Zeiss optical company, Koch focused on technology, improving magnification lens, developing specialized specimen stains, and developing fixed culture media to grow microbes outside of animals. Armed with new tools and stains, he discovered the Mycobacteria tuberculosis and proved its presence in infected tissues, and described his findings in “The Etiology of Tuberculosis” in 1882.

“Koch’s Postulates” became the 4 accepted steps constituting scientific proof of a theory.

1) The microorganism must be found in infected tissue.

2) The organism must be grown in fixed culture.

3) The grown organism must instigate infection in a healthy laboratory animal.

4) The infective organism must be re-isolated from the lab animal, and proven identical to the original microbes.

III. Joseph Lister (1827-1912), the third of our trio, was a professor of surgery at Edinburgh. At the time, major complications of surgery were pain, blood loss and deadly post-operative infections. In the 1840s, ether and nitrous oxide were introduced, controlling intra-operative pain. As for infection, Lister suggested scrubbing hands before surgery, sterilizing tools, and spraying carbolic acid into the air and on the patient’s wound. Koch took an alternate approach, advocating sterile operating theories and surgeons in gowns, gloves, and masks. The opposing techniques merged and became common surgical practice in the 1890s.

For New York City, Chadwick’s sanitary movement and the “famous trio’s” germ theory couldn’t arrive soon enough. The Civil War had been a wake-up call. Of the 620,000 military deaths, 2/3 were from disease. At the top of the list was dysentery and diarrheal disease, followed by malaria, cholera, typhus, smallpox, typhoid and others. Filth, disease, and disorder ruled the day. But opportunity lay in the wings. As historians described the challenge of those days: “New York City experienced a pivotal moment in its development following the historic 1898 consolidation, which united Manhattan, Brooklyn, Queens, The Bronx, and Staten Island into one comprehensive entity. By the year 1900, the city’s population had surged to 3,437,202 according to the U.S. Census.” Keeping those millions healthy would be a public health challenge of the first order.