Microbe Hunters

1. The First Glimpse: An Unseen World Teeming with Life

This janitor of Delft had stolen upon and peeped into a fantastic sub-visible world of little things, creatures that had lived, had bred, had battled, had died, completely hidden from and unknown to all men from the beginning of time.

A new universe. Antony Leeuwenhoek, a simple Dutch janitor and shopkeeper in the 17th century, became the first microbe hunter not through formal training, but through an obsessive love for grinding lenses. His self-made microscopes, superior to any others of his time, allowed him to magnify objects with unprecedented clarity.

Peering into the unknown. Driven by insatiable curiosity, Leeuwenhoek turned his lenses on everything imaginable, from whale muscle fibers to the sting of a flea. His most momentous discovery came when he examined a drop of seemingly pure rainwater, revealing a hidden world of "little animals" (microbes) swimming and playing.

An accurate observer. Despite his lack of formal education and inability to read Latin (the language of science), Leeuwenhoek was a remarkably precise observer. He meticulously documented the shapes and movements of these tiny creatures, estimating their sizes and noting their presence in various substances like water, pepper infusions, and even his own mouth, laying the groundwork for future microbe hunters.

2. Life Begets Life: Debunking Spontaneous Generation

Seal your soup flasks in a flame, and nothing can get into them from outside.

Challenging old beliefs. Lazzaro Spallanzani, an Italian priest and scientist born after Leeuwenhoek's death, took up the study of microbes amidst a raging debate: could life arise spontaneously from non-living matter? Common belief, even among scientists, held that creatures like mice and insects could simply appear from mud or decaying meat.

Experiments with soup. Inspired by Redi's experiments disproving spontaneous generation for flies, Spallanzani applied rigorous methods to the microscopic world. He prepared nutrient broths (soups from seeds or meat), boiled them for varying lengths of time, and sealed the flasks by melting the glass necks shut, preventing anything from entering.

Proof through exclusion. Spallanzani's meticulous experiments showed that if a broth was boiled long enough to kill existing life and then sealed, no microbes would appear, even after long periods. Microbes only grew in flasks that were left open or inadequately sealed, demonstrating that they came from the outside air, not spontaneously from the broth itself. This dealt a significant blow to the idea of spontaneous generation for microbes.

3. Microbes at Work: Fermentation, Spoilage, and Early Disease Links

It is living things, sub-visible living beings, that are the real cause of fermentations!

From chemistry to life. Louis Pasteur, a brilliant French chemist, stumbled into the world of microbes while investigating problems in the brewing industry. Distillers were losing money due to failed fermentations, and Pasteur, initially focused on chemical processes, began examining the vats with a microscope.

Fermentation is life. Pasteur observed that healthy alcoholic fermentation was associated with living yeast cells, while "sick" fermentations producing unwanted acids contained different types of microbes. Through ingenious experiments, he proved that specific microbes were responsible for specific types of fermentation, transforming sugar into alcohol or lactic acid.

Beyond fermentation. Pasteur's work extended beyond industry. He showed that microbes caused spoilage in wine and beer, leading to the development of pasteurization (heating to kill unwanted microbes). His studies on silkworm diseases further solidified the link between specific microbes and specific diseases, setting the stage for his later, more dramatic work on human and animal illnesses.

4. The Specific Cause: One Germ, One Disease

First of all searchers, of all men that ever lived, ahead of the prophet Pasteur who blazed the trail for him, Koch had really made sure that one certain kind of microbe causes one definite kind of disease...

A country doctor's quest. Robert Koch, a German country doctor, began hunting microbes in his spare time with a microscope given to him by his wife. Dissatisfied with the helplessness of medicine against diseases like anthrax, he sought their root causes.

Tracking anthrax. Koch observed rod-shaped bacteria (bacilli) in the blood of animals that died of anthrax but not in healthy ones. Through meticulous experiments using mice, he showed that these bacilli multiplied rapidly in sick animals and could transmit the disease. He then devised methods to grow these bacilli purely outside the body in nutrient fluids.

Pure cultures and postulates. Koch's major breakthrough was developing solid culture media (like gelatin or agar) to grow pure colonies of specific microbes, separating them from others. This allowed him to prove definitively that his cultured anthrax bacilli, when injected into healthy animals, caused anthrax. This work led to Koch's postulates, criteria for proving that a specific microbe causes a specific disease, a cornerstone of modern microbiology.

5. Deadly Poisons and Their Antidotes

It was to save babies that they killed so many guinea-pigs!

The mystery of diphtheria. While Koch established that specific microbes cause specific diseases, the mechanism of how they killed remained unclear for many. Diphtheria, a terrifying disease killing thousands of children, was linked to a bacillus found in the throat, but the microbe didn't seem to invade the rest of the body.

Discovering the toxin. Emile Roux, a student of Pasteur, and Emil Behring, a student of Koch, independently pursued this mystery. Roux, through painstaking experiments, showed that the diphtheria bacillus produced a potent poison (toxin) that spread throughout the body from the throat, causing paralysis and death, even when the bacteria themselves remained localized.

Finding the antitoxin. Behring, initially searching for chemical cures, stumbled upon the idea that the blood of animals that survived diphtheria contained something that neutralized the toxin. Through extensive, often brutal experiments on guinea-pigs, he demonstrated that serum from immune animals could protect others from the toxin and even cure them if administered early. This led to the development of diphtheria antitoxin, a life-saving treatment.

6. The Body's Defenders: Phagocytes on the Front Line

Phagocytes! Phagocyte is Greek for devouring cell—phagocytes is what you must call them!

An eccentric naturalist's insight. Elie Metchnikoff, a Russian zoologist with a flair for the dramatic and a deep interest in evolution, turned his attention to immunity not through studying human disease, but by observing starfish larvae. He noticed mobile cells within the larvae that would engulf foreign particles like carmine granules.

The devouring cells. In a flash of intuition, Metchnikoff hypothesized that these wandering cells, which he named "phagocytes," were the body's primary defense against invading microbes. He proposed that immunity was not solely due to substances in the blood, but to these cells actively engulfing and destroying pathogens.

A fierce debate. Metchnikoff's theory sparked a major scientific battle with scientists like Behring, who championed the role of blood serum (containing antibodies) in immunity. Metchnikoff defended his "phagocyte theory" with passionate arguments and often unconventional experiments, showing phagocytes engulfing microbes in various animals, from water fleas to monkeys, laying the foundation for the study of cellular immunity.

7. The Insect Connection: Ticks and Texas Fever

It was Theobald Smith who made mankind turn a corner.

A puzzling cattle plague. Texas fever, a devastating disease killing northern cattle moved to the South, baffled farmers and scientists alike. Southern cattle were unaffected but seemed to carry the disease, which only appeared in northern herds weeks after exposure to southern pastures.

Listening to farmers. Theobald Smith, an American government scientist, was assigned to investigate. Dismissing prevailing scientific theories, he paid attention to a folk belief among cattlemen: that ticks were somehow involved. He designed experiments not in a lab, but in fenced fields.

The tick's secret. Smith and his colleague Kilborne conducted meticulous field trials. They showed that northern cattle exposed to southern cattle with ticks died, while those exposed to southern cattle without ticks remained healthy. Crucially, they discovered that the disease was transmitted not by the adult tick, but by its offspring, which picked up the pathogen from infected cattle and transmitted it when they bit new hosts. This groundbreaking work was the first proof that an insect could transmit a microbial disease.

8. The Mosquito's Secret: Unraveling Malaria

Malaria must be wiped from the earth.

An ancient scourge. Malaria, a disease causing debilitating fevers and chills, plagued millions worldwide. While the parasite causing malaria had been identified in the blood, how it spread remained a mystery, despite various theories involving bad air or contaminated water.

Two hunters, one goal. Ronald Ross, a British army doctor in India, and Battista Grassi, an Italian zoologist, independently pursued the idea that mosquitoes might be the vector. Ross, guided by Patrick Manson's hypothesis, conducted painstaking experiments with birds and mosquitoes, eventually demonstrating that the malaria parasite developed in the mosquito's stomach and migrated to its salivary glands, ready to be injected into a new host.

Identifying the culprit. Grassi, working in Italy, used his extensive knowledge of insects to identify the specific type of mosquito responsible for human malaria: the Anopheles. Through rigorous field observations and human transmission experiments, he confirmed that only the bite of an infected female Anopheles mosquito could transmit the disease, providing the crucial link needed for control efforts.

9. Human Trials and Yellow Fever's Carrier

In the Interest of Science—and for Humanity!

A terrifying epidemic. Yellow fever, a deadly disease causing jaundice, black vomit, and high mortality, devastated populations in tropical and subtropical regions, including American soldiers in Cuba after the Spanish-American War. Traditional methods of control, like fumigation and quarantine, proved ineffective.

Finlay's hypothesis. For years, Cuban doctor Carlos Finlay had argued that yellow fever was transmitted by a specific type of mosquito, but his experiments were unconvincing, and his theory was widely dismissed as the idea of a "theorizing old fool."

The Reed Commission. Major Walter Reed led a U.S. Army commission to Cuba to investigate. After failing to find a bacterial cause, Reed, influenced by Finlay and the recent discoveries about insect transmission, decided to test the mosquito theory using human volunteers. In a series of daring and ethically complex experiments at Camp Lazear, volunteers were exposed to infected mosquitoes or contaminated bedding. The results were clear: only mosquito bites transmitted the disease, while contact with contaminated objects did not. This proved Finlay right and paved the way for eliminating yellow fever by controlling the Aedes aegypti mosquito.

10. Hunting Sleeping Sickness with Bruce and the Tsetse Fly

Africa swarmed with mysterious viruses that made the continent a hell to live in; in the olive-green mimosa thickets and the jungle hummed and sizzled a hundred kinds of flies and ticks and gnats. . . . What a place for discoveries...

A new African plague. Sleeping sickness, a fatal disease causing lethargy and coma, swept through parts of Africa, decimating native populations and hindering colonial expansion. Its cause and mode of transmission were unknown.

Bruce's African hunts. David Bruce, a British army doctor with a taste for adventure and a proven track record in identifying insect-borne diseases (like nagana in horses, also carried by a tsetse fly), was sent to investigate. Working in challenging conditions in Uganda, Bruce and his team identified the trypanosome parasite as the cause of sleeping sickness.

The tsetse fly link. Through meticulous field work and experiments involving human volunteers and monkeys, Bruce demonstrated that the disease was transmitted by the bite of the tsetse fly, specifically species found near water. His work led to strategies for controlling the disease by clearing tsetse habitats and relocating populations away from fly-infested areas, significantly reducing the spread of sleeping sickness.

Last updated: May 9, 2025