Germ theory of disease

• 1. Introduction

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  The germ theory of disease is the accepted scientific explanation for why infections happen, yet one of its earliest hints appears in a Roman farming manual. In 36 BC, the statesman Marcus Terentius Varro advised that "Precautions must also be taken in the neighborhood of swamps". His reason was that swamps breed "certain minute creatures which cannot be seen by the eyes". He wrote that these creatures float in the air, enter through the mouth and nose, and cause serious diseases. That is a startlingly modern idea for a book about agriculture. Yet physicians in Europe went on resisting it for many centuries. Why did they cling to a rival explanation built on foul smells? Who first pointed a lens at decay and saw living things? And what kind of evidence finally made doctors stop arguing and start washing?

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• 2. Bad Air and Seeds

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  The Greek historian Thucydides, who lived from about 460 to about 400 BC, left the first known written suggestion that illness can pass from a sick person to others. He made it in his account of the plague of Athens. Around 56 BC, the Roman poet Lucretius offered a mechanism in his poem De rerum natura, which means On the Nature of Things. He described the world as full of "seeds", called semina in Latin, and said some could sicken a person who inhaled or swallowed them.

  The Greek physician Galen, who lived from AD 129 to around 200 or 216, returned to the same imagery. Around 175 AD he speculated about "seeds of fever" and "certain seeds of plague" drifting in the air. A year or so later, in his Epidemics, he explained relapses another way. Some "seed of the disease" might lurk inside a patient, and it would bring the illness back if the person ignored a physician's regimen.

  But a competing doctrine took hold. Miasma theory takes its name from the Ancient Greek word for pollution. It blamed illnesses such as cholera and the Black Death on a poisonous mist rising from rotting organic matter, recognizable by its stench. Contaminated water and poor hygiene counted as causes too. Crucially, sick people were not thought to pass the illness along. Only those living where the vapors arose were at risk. In Europe, scientists and doctors followed Galen's miasma theory, not his seeds.

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• 3. Medieval Glimmers

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  In 1025, the Persian physician Ibn Sina, known in Europe as Avicenna, completed The Canon of Medicine. It blended the two rival ideas. He wrote that people can give each other disease through their breath, and he observed contagion in tuberculosis. He also discussed illness traveling through water and dirt.

  Earlier, around AD 613, Isidore of Seville had mentioned "plague-bearing seeds", or pestifera semina, in his On the Nature of Things. Then in 1345, Tommaso del Garbo of Bologna repeated Galen's "seeds of plague" in his commentaries on Galen's books.

  The Reformer Martin Luther seems to have grasped something of contagion, judging by a story he told about himself. He had survived three plagues, and he had touched the plague spots of two patients without harm. Then, having forgotten to wash, he put his hands on the face of his baby daughter Margaret, born in 1534. He called that act, had he done it knowingly, "tempting God".

  The most thorough early statement came in 1546. The Italian physician Girolamo Fracastoro published De Contagione et Contagiosis Morbis, three books on the nature of contagious diseases, how to sort the major pathogens, and how to prevent and treat them. He blamed "seeds of disease" that spread by direct contact, by contaminated objects called fomites, or through particles in the air. More than a century later, a simple experiment with jars of rotting meat would attack a different old belief.

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• 4. Animalcules Under Glass

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  In 1668, the Italian physician Francesco Redi laid out meat in jars and watched where the maggots appeared. They arose only on uncovered rotting meat. When he covered jars with gauze, the maggots showed up on the gauze instead. This was later understood as the smell of the meat passing through the mesh and drawing flies to lay eggs. His result cut against spontaneous generation, the belief that living creatures arise from nonliving matter.

  The 1670s brought the microscope into the story. Anton van Leeuwenhoek is called the Father of Microbiology, and he is said to have been the first to describe bacteria, in 1674. He also saw yeast cells, algae-like life in a drop of water, and blood corpuscles moving through capillaries. No word for bacteria existed, so he named them "animalcules", meaning little animals. He found them in rainwater, pond and well water, and in the human mouth and intestine.

  A German Jesuit scholar may have looked first. In 1646, Athanasius Kircher wrote about the wonderful structure of things seen through the microscope. He asked who would believe that "vinegar and milk abound with an innumerable multitude of worms." When bubonic plague struck Rome in 1656, he examined the blood of victims and reported tiny worms, which he concluded caused the disease. He published his theory in Scrutinium Physico-Medicum in Rome in 1658. What he saw was probably blood cells, not the plague agent. Even so, his conclusion was correct. He also urged isolation, quarantine, burning the clothes of the infected, and wearing facemasks.

  The 18th century produced more proposals, and they struggled. In 1700, the physician Nicolas Andry blamed "worms" for smallpox and other diseases. In 1720, Richard Bradley argued that plague and "all pestilential distempers" came from "poisonous insects" visible only through microscopes. In 1762, the Austrian physician Marcus Antonius von Plenciz published Opera medico-physica. It tied specific animalcules in soil and air to specific diseases, and it was unusual for describing germs in ulcerating wounds. The scientific community rejected it anyway.

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• 5. Silkworms and Mosquitoes

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  A collapse in silk production in the early 19th century pushed the Italian entomologist Agostino Bassi into the laboratory. Silkworms were dying of a disease that left white fungal spots on the caterpillars. French speakers called it muscardine, and Italians called it calcinaccio or mal del segno. Between 1835 and 1836, Bassi published his finding that fungal spores carried the disease from one caterpillar to the next. He advised removing sick caterpillars quickly and disinfecting their surfaces, methods that modern preventive healthcare still uses. The naturalist Giuseppe Gabriel Balsamo-Crivelli named the fungus after him, and it is now classified as Beauveria bassiana.

  The Sussex doctor Gideon Mantell is better known for finding dinosaur fossils. In his 1850 book Thoughts on Animalcules, he wondered whether "many of the most serious maladies which afflict humanity, are produced by peculiar states of invisible animalcular life".

  A far bolder claim came from the French tropical medicine specialist Louis-Daniel Beauperthuy. In 1838 he pioneered the use of microscopy on disease and independently concluded that all infectious diseases stemmed from parasitic animalcules. With help from his friend M. Adele de Rosseville, he presented the theory to the French Academy of Sciences in Paris. By 1853 he was convinced that mosquitoes spread malaria and yellow fever. He even singled out the "domestic species" of "striped-legged mosquito" for yellow fever, which can be recognized as Aedes aegypti, the true vector. He published this in 1854 in the Gaceta Oficial de Cumana. An official commission assessed his reports and discarded the mosquito theory.

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• 6. Hands and Water

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  At the Vienna General Hospital in 1847, the Hungarian obstetrician Ignaz Semmelweis noticed a grim pattern. Mothers died of puerperal fever far more often after births assisted by doctors and medical students than after births attended by midwives. Semmelweis traced the difference to examinations by physicians who had often come straight from autopsies. He concluded that the fever was contagious and that matter from autopsies helped spread it. So he made doctors wash their hands in chlorinated lime water before examining pregnant women. Over the following year, he recorded the mortality rate falling from 18% to 2.2%. Most of the medical establishment rejected him and his theories regardless.

  Across the Channel, the British physician John Snow is credited as a founder of modern epidemiology for his study of the 1854 Broad Street cholera outbreak. Years earlier, in his 1849 pamphlet On the Mode of Communication of Cholera, he had proposed that the disease spreads by the fecal-oral route and multiplies in the lower intestines. He disputed the early 18th century anatomist Giovanni Maria Lancisi, who blamed swamp miasma for malaria, by noting that bad air from decomposing organisms was not present in every case.

  In the second edition, published in 1855, Snow theorized that cholera was caused by cells smaller than human epithelial cells. Robert Koch confirmed the bacterium Vibrio cholerae as the cause in 1884. Snow recommended boiling and filtering water, an ancestor of modern boil-water advisories.

  His statistics were just as persuasive. Areas supplied by the Southwark and Vauxhall Waterworks Company, which drew sewage-polluted water from the River Thames, suffered fourteen times as many deaths as areas served by the Lambeth Waterworks Company. Lambeth drew its water upriver at the cleaner Seething Wells. Snow persuaded the Board of Guardians of St James's Parish to remove the handles of contaminated pumps and won praise for it. He himself noted that cases were already falling because frightened residents had fled the area.

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• 7. Pasteur and Lister

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  A transitional period began in the late 1850s with the French microbiologist Louis Pasteur. In the mid-19th century he showed that boric acid applied to the female genital tract killed the microorganisms behind postpartum infections without harming mucous membranes.

  His best-known experiment used flasks with long curved necks, shaped like a swan's, filled with nutrient broth. The broth fermented only when the curved tubing was removed and outside air reached it directly. Building on Redi's earlier work, this disproved spontaneous generation. It also showed that bacteria travel between places to colonize new environments.

  Like Bassi before him, Pasteur turned to silkworms. His subject was pébrine, which leaves brown spots on the insects. The Swiss botanist Carl Nägeli had discovered the fungal species Nosema bombycis in 1857. Pasteur applied that finding to recommend better ventilation and the screening of silkworm eggs, an early form of disease surveillance.

  Pasteur's papers on bacterial fermentation reached the British surgeon Joseph Lister. Lister realized that compound fractures, where bone breaks through the skin, were especially prone to infection because the wound was exposed to microorganisms in the environment. His remedy was carbolic acid, which he found could be applied to the site of injury as an effective antiseptic.

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• 8. Koch's Four Rules

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  In 1884, the German bacteriologist Robert Koch published four criteria for proving that a specific microorganism causes a specific disease. These became known as Koch's postulates. First, the microbe must be abundant in every sick organism and absent from healthy ones. Second, it must be isolated and grown in pure culture. Third, that culture should cause disease when given to a healthy host. Fourth, the same microbe must be recovered from the newly sick host and match the original.

  Koch himself saw that the rules did not always fit. Asymptomatic carriers of cholera break the first postulate. The third says "should" rather than "must" because not every exposed host falls ill, perhaps owing to differences in earlier exposure. Later work exposed more cracks. Viruses are obligate intracellular parasites and cannot be grown in pure culture, so the second postulate is impossible for them. Prions are misfolded proteins that spread by passing their shape to other proteins instead of copying themselves.

  Still, the postulates endure as a reminder that correlation does not imply causation, and many pathogens are accepted as causes without meeting every criterion. By the end of the 1880s, miasma theory was struggling against germ theory. Viruses were first discovered in the 1890s. A golden era of bacteriology followed, in which germ theory quickly pointed to the organisms behind many diseases.

  Today "germ" covers far more than bacteria. It includes protists, fungi, parasites, viruses, prions and viroids, and these agents can infect animals, plants and even bacteria. A pathogen is rarely the whole story, since environmental and hereditary factors often shape how severe an illness becomes and whether an exposed person is infected at all. In 1988, the American microbiologist Stanley Falkow published a molecular version of Koch's postulates, linking microbial genes to virulence factors.

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