A Kingdom of Little Animals

One night in 1677, a grizzled man in a wrinkled linen nightshirt rushed from his bemused wife’s bed with a candle in hand to examine the “remains of conjugal coitus, immediately after ejaculation before six beats of the pulse.” Using the candle to cast a pool of light in his dark study, he put a drop of the liquid into a tiny glass vial he had blown himself, attaching it to the back of a strange-looking device he had also constructed. Two rectangular brass plates, about three inches tall and one inch wide, had been riveted together and held a tiny glass orb between them. He lifted this object up into the light of the candle, closed one eye, and watched, for hours, until finally: a shiver of movement at the edge of his vision. Was it merely a mirage? Were his eyes too tired? He blinked, looked away from the light to rest them, and then resumed his careful observation. He was soon rewarded with the sight of a swarm of tiny eel-like creatures wriggling into view. Antoni van Leeuwenhoek—who died 300 years ago, on August 26, 1723—had just discovered spermatozoa.

It was not the first time that he had made the invisible visible, nor would it be the last. Leeuwenhoek was a pioneer, discovering a whole realm of living creatures that included bacteria and other “germs”—“little animals,” he affectionately called them. By doing so, he made us aware that the world contains more than meets the eye, and his crucial contributions to the field of microbiology remain as relevant as ever.

During these past three years of the Covid-19 pandemic, which has caused at least seven million deaths worldwide (more than one million in the United States alone) and which, according to the U.S. Centers for Disease Control and Prevention, has left one in 13 adults, or 19 million people in our country, with the disabling conditions caused by long Covid, my thoughts have returned often to Leeuwenhoek’s discoveries and what came after. As we carry on through these interminable Covid days (and ready ourselves for epidemics and pandemics to come), we should understand and celebrate the person who made it possible to discover the invisible causes of—and possible cures for—so many of the illnesses that plague us.

Baptized as Thonis—but always called Antonij or Antoni—he was born in Delft, Holland, in 1632, the same week as his neighbor Johannes Vermeer. His family took the surname “Leeuwenhoek” for the location of its home, “The Lion’s Corner.” Only after he had achieved worldwide fame in the 1680s did he add the aristocratic-sounding “van” to his name.

Leeuwenhoek was not an obvious candidate for upending the received view of the universe. The son of a basket weaver, he had no schooling beyond reading, writing, and some arithmetic, and he was expected to follow in his father’s profession—an important one in Delft, where a thriving export business required well-made baskets for overseas transport. But when his widowed mother remarried, he was sent to Amsterdam and eventually became apprenticed to a cloth merchant. In those days, a clever haberdasher, needing to determine the fineness of the fabric being offered to him, would use a magnifying glass to count the number of threads used in the weaving—the thread count, as we say today. This period was Leeuwenhoek’s apprenticeship in lenses as well as cloth.

When he returned to Delft after his six-year apprenticeship, Leeuwenhoek married Barbara de Meij, the daughter of a weaver, and in the front room of their house opened a successful shop that sold fabrics, buttons, lace, and other sewing supplies. Since the population of Delft numbered only about 20,000 people at the time—more than half of them women and children—a prosperous businessman was bound to become acquainted with other local grandees. His conversations with one of these, the physician Reinier de Graaf, generated his interest in science. De Graaf showed him that advances in how lenses were produced had created optical instruments with far stronger visual powers than the magnifying lens that Leeuwenhoek used for examining cloth.

Sometime around 1600, a Dutchman (not Galileo Galilei, as many believe) had made the first telescope by putting together two kinds of lenses on the opposite ends of a tube: a convex lens, fatter in the middle like a lentil (from which the word lens derives), and a concave lens, narrower in the center. This telescope was able to double the vision of the naked eye. Galileo quickly improved the device, producing a telescope that was 20 times stronger than natural vision. Turning it to the heavens, he grasped that the blotches we see on the moon’s surface are shadows made by mountains and craters, like those that exist on Earth. He later used his telescope to see that the planet Jupiter had its own moons. These observations supported Copernicus’s radical view that Earth is merely a planet like all the others, revolving around the sun. Because Galileo continued to write books asserting the truth of Copernicus’s theory after the Inquisition authorities in Italy had forbidden him from doing so, he was sentenced to spend the remainder of his life under house arrest—in a comfortable villa staffed with servants.

After the invention of the telescope, natural philosophers (as scientists were then called) took note. If stronger lenses could be used to extend sight into the far reaches of the universe, could they not be used to enlarge the very small parts of it? The idea of microscopes was born. Though Galileo was not the inventor of the telescope, he may have constructed the first microscope: a small inverted telescope (with the objective lens on top, the eyepiece below) placed on a stand. He called it an occhialino, “little eye.”

British instrument makers promptly went to work creating and improving double-lens microscopes of this kind, not so different from the one I recall using in my high school biology class, bending over the eyepiece lens while moving the objective lens up and down to focus it on a specimen fixed on a glass slide or in a petri dish. In the Dutch Republic, however, natural philosophers preferred single-lens microscopes. These instruments could not only attain higher magnification, they also minimized the major optical problem with the double-lens microscopes of the day: chromatic aberration, an effect in which the viewed image is distorted by multicolored “fringes.” Not until 1672 did Isaac Newton explain why this happened, by showing that the surface of a lens, like a prism, disperses white light into its constituent colors. With two lenses, the problem was compounded, making it especially difficult to discern the smallest and most complex parts of a subject.

Unlike the double-lens microscope, the single-lens generally required you to look upward, with the specimen behind the lens, “as though you had a telescope and were trying to look at the stars in the sky,” Leeuwenhoek wrote. His method was to point his microscope at a beam of light streaming through a single hole in his closed shutters during the day, or at the light of a candle at night.

The tiny lens of this type of microscope could be made in several ways. Leeuwenhoek began with the simplest method. Since a candle’s flame is hot enough to melt glass, he would place a thin glass rod over the flame and allow glass droplets to fall onto a sheet of smooth metal. When cooled, some of these minuscule beads—those not scorched and blackened from the flame—could be slightly ground, polished, and placed between the brass or silver plates of his microscopes.

Another method Leeuwenhoek used was to grind and polish glass shards in a cup-shaped mold using a succession of finer abrasives to shape the glass, often finishing with a piece of soft leather or felt to polish the lens—a time-consuming and delicate process, especially for lenses only one to two millimeters in diameter. To speed up the process, Leeuwenhoek began to employ a pedal-powered lathe, similar to those used by jewelers. He may have learned this method from the Dutch philosopher Baruch Spinoza, who was earning his living as a lens grinder after receiving a writ of herem, a kind of excommunication from his Jewish community for espousing “heretical” beliefs. In the summer of 1665, the two men were living only four miles apart and had mutual friends.

But though the single-lens microscope reduced chromatic aberration and was relatively easy to make, it was exceedingly difficult to use. Imagine holding up a small device the size, weight, and top-heaviness of a coffee spoon and staring into a tiny lens in its center through an aperture barely larger than the head of a pin, for hours at a time. Whether your specimen was a tiny vial of liquid or a solid object attached to a pin behind the lens, any motion—even from the quivering of your pulse—could move the subject out of view.

At first, microscopes were used like magnifying lenses, to enlarge parts of nature that were small but visible to the naked eye. Insects made obvious subjects because they were everywhere: bees, aphids, and slugs in gardens; fleas, lice, and bedbugs indoors. The first published study using a microscope was Francesco Stelluti’s meticulous 1625 examination of the different parts of a bee.

The early microscope users were fascinated by the eyes of creatures, in the belief that using this new “artificial eye” would yield special insight into sight itself. In 1644, Gioanbatista Hodierna published an elegantly precise study, L’Occhio della Mosca (The Eye of the Fly). Twenty-one years later, Robert Hooke brought out a thrillingly detailed illustration of the “Eyes and Head of a Grey drone-Fly” in his magisterial 1665 book, Micrographia.

Leeuwenhoek began to make and use microscopes sometime in the early 1660s, and he, too, was fascinated by sight. He studied the eyes of flies, lice, and dragonflies. He methodically examined the optic nerves of cows, obtaining the eyes from the local butcher at the Vleesmarkt, “not more than 100 feet” from his house. When he was 81 years old, he persuaded the captain of a Greenland whaling ship to bring back a giant whale’s eye pickled in brandy. As a bonus, he received the whale’s enormous penis—between eight and 10 feet long—so that he could study its sperm.

At that time, the Royal Society of London, founded in 1660, was the main scientific society in the world, and natural philosophers from all over wrote in to have their discoveries officially recognized. The Society’s secretary, Henry Oldenburg, was so besieged by letters that he requested some of his correspondents to address them to “Mr. Grubendol” to keep the authorities from noticing his contact with such a large number of foreigners. England, Spain, and the Dutch Republic had been at war with one another intermittently for decades, and spies abounded. Oldenburg later shuddered at the memory of the time in 1667 when, with Dutch ships thundering up the Thames, he was briefly imprisoned in the Tower of London under suspicion of “carrying on political correspondence with parties abroad.”

By the early 1670s, Leeuwenhoek was no longer a merchant but a civic leader and a licensed surveyor, spending much of his time making discoveries with his microscope. But he was ashamed that he knew no Latin, the lingua franca of the scientific world, and hesitated to write to the esteemed Royal Society. In the spring of 1673, Reinier de Graaf sent Oldenburg a sheaf of papers scribbled by Leeuwenhoek, along with a cover letter vouching for him. Oldenburg was a polyglot, fluent not only in his native German but also in English, Latin, French, Italian, and Dutch. As he casually leafed through these papers, not expecting to find much of interest, he quickly grasped that this unknown and untrained Dutchman had seen things that even Robert Hooke had not. Oldenburg had an inkling that the scientific world was about to change.

In the summer and early fall of 2012, I spent nearly every day in the shadow of the Empire State Building at what used to be the Science, Industry, and Business branch of the New York Public Library, located in the former B. Altman and Company department store. The branch closed in 2016, its materials moved to the newly renovated Mid-Manhattan Library or to offsite storage, but in 2012, the 15 published bilingual volumes of Leeuwenhoek’s letters—an immense project begun in 1939 and not yet completed—were accessible to anyone with a library card.

On my first day there, none of the helpful staff members could find this set of books. No one even remembered seeing them, but a persistent search through the closed stacks turned up the first two hefty volumes: each 12 inches high, nine and a half inches deep, and at least 500 pages long. The books had been so hard to find because they had never been entered into the computer system; cards were still attached to the inside back covers where the date of use was stamped. The stamps indicated that no one had requested the books for decades.

It amazed me that these dusty tomes—in this case not merely a cliché but an accurate description, as my blackened clothing and worsened asthma attested at the end of each day—had been ignored for so long, given that the letters constitute the foundation of modern microbiology and medicine. Leeuwenhoek never wrote a scientific treatise. All he left us was his correspondence: more than 350 letters written over a period of 50 years, some 20 to 30 pages long, most of them addressed to the Royal Society, and nearly all of them translated and published in the Society’s journal, The Philosophical Transactions of the Royal Society. More than just detailing his scientific work, they are a window into the mind of a brilliant and obsessive man. I was entranced.

Reading all of them, I felt I got to know him and his daily habits. By the time he began to write to the Royal Society, Leeuwenhoek, then a widower, had married his second wife, Cornelia Swalmius, who came from an educated and distinguished family. She was eager for her husband to gain the respect of the Royal Society and gladly took part in his studies, not only by indulging his semen observations but also by carrying a small box filled with silkworm eggs “in her Bosom night and day,” as he reported, so that he could scrutinize the larvae the moment they emerged. His growing confidence was exemplified by the change in the way he addressed members of the Royal Society—first as a humble supplicant and later as a man who expected, and deserved, respect. I saw how he delighted in showing off what could be seen with his microscopes to all who knocked on his door, until he was so hounded by visitors that he could not work. He had to ask his only child, Maria, to turn away anyone without a letter of introduction. He did, however, make exceptions, consenting to see a tutor who turned up one day with an excited young charge. Perhaps the enthusiastic boy reminded Leeuwenhoek of his younger self and the glee he felt on seeing the invisible for the first time. And of course, being a vain man who would crow about the plaudits he received, he also made exceptions for royalty. Peter the Great chatted with Leeuwenhoek for hours (the Russian czar could speak Dutch) and inspected the circulation of blood in the tail of an eel. Leeuwenhoek also boasted of showing James the Duke of York (the future King James II) the sperm of a dog. If only Leeuwenhoek had been home when Queen Mary II (on her way to England with her husband, William III, to depose her father, James II) stopped by to see his wonders.

I could distinctly hear the voice of a man in a hurry, who couldn’t wait to put down his quill and pick up the microscope again. Leeuwenhoek often admitted that he had not ordered his thoughts but conveyed his results as he saw them, “unarranged promiscuously as put down during my observations.” It was as if Leeuwenhoek were excitedly describing his discoveries to a friend, and as I read on, I became that friend.

His first letter described the spores of mold, suggesting—before anyone else—that they contained seeds. He agreed with Hooke’s description of the “lowse” as having “a short tapering nose, with a hole in it, out of which … it thrusts its sting” to feed. Leeuwenhoek’s next letter described how he proved this: by “several times” putting a “hungry lowse upon my hand, to observe her drawing blood from thence.” As the louse sucked on his blood, he watched it with the microscope in his other hand, noticing how the blood first moved to the head of the louse and then was propelled to a sac at its back. I shivered to think of the kind of attention and scientific devotion it would take to sit still while observing a louse sate itself on my blood.

It was not long before Leeuwenhoek broke through to the invisible realm. In April 1674, he wrote to his friend Constantijn Huygens (the elder)—a diplomat, poet, art collector, and science enthusiast who always carried a microscope with him and took a great interest in Leeuwenhoek’s work. He told Huygens that he had pricked his thumb and drawn some of his blood into a tiny glass pipette. Observing it carefully, he found numerous “red globules” floating in what appeared to be a clear and crystalline fluid. He had discovered red blood cells. Although others had seen something in the blood, Leeuwenhoek was the first to observe that these cells were round, red, and gave blood its color. Soon he even measured them, finding that 100 red blood cells were the size of a coarse grain of sand measuring about 1/30th of an inch. That means he estimated each red blood cell to be 1/3000th of an inch, or 8.5 microns, in diameter, which is impressively close to the modern measurement of 7 to 8 microns. His most extraordinary discovery, though, was yet to come.

It happened at the Berkelse Lake, about a two-day’s journey from Delft. Passing by in the summer of 1674, Leeuwenhoek noticed that the water looked particularly murky. He took a clean vial from his pocket, knelt down, filled it with a sample of the liquid, and stoppered it tightly. Back home in his study, he closed all the shutters except part of one, through which the light of the sun beamed. He put a drop of the cloudy water into the glass tube affixed to the back of his microscope. Raising it to the light, he turned the specimen pin attached to the tube this way and that, to focus the view. When the initially blurry image became clear, what he saw startled him so much that he may have cried out, perhaps even spilled the water and had to try again.

Taking a deep breath and steadying his hand, Leeuwenhoek looked once more. Yes, it was true: the drop of water contained a multitude of tiny particles of different shapes, sizes, and colors. They were moving themselves by the use of minuscule legs and fins and hairs. Moving themselves! These particles were living beings!

Some have argued that when Copernicus’s theory flung Earth from the center of the universe and took away its special status, making it just one of a number of planets, it resulted in the most radical transformation in our view of the world. I disagree. Leeuwenhoek’s discovery showed not merely that the universe had a different structure than had been thought before, but that it contained within it a hidden universe of diverse living creatures, a world within a world.

Leeuwenhoek verified his observations many times over the next three months. Finally, he was ready to make his world-altering announcement. He sharpened his quill, took a deep breath, and began to write to Oldenburg in September 1674.

Perhaps he was nervous: he did not come right out and announce his incredible discovery. Instead, Leeuwenhoek wrote, and wrote, and wrote: more than 20 pages about all sorts of experiments, ending with a bizarre passage on the difference between the chalk in English soil and the dark clay of Delft, and how Delft’s clay had to be mixed with Flemish dirt to make Delftware porcelain. Only then did he finally describe his visit to the lake and the “little animals” he had found in its water:

Some of [them] were roundish; those that were somewhat bigger than others, were of an Oval figure: On these latter I saw two legs near the head, and two little fins on the other end of their body. Others were somewhat larger than an Oval, and these were very slow in their motion, and few in number. These little animals had diverse colors, some being whitish, others pellucid; others had green and very shining little scales: others again were green in the Middle, and before and behind very white …

According to modern microbiologists, Leeuwenhoek had seen rotifers (strange parasites with body cavities filled with fluid), ciliates (including Paramecium species), and a type of protozoan called Euglena viridis.

The Royal Society’s reaction was as strange as the letter itself: there was no response at all. Apparently, that was fine with Leeuwenhoek. For the next two years, he continued to write, keeping the Society apprised of his work: further investigations into salt crystals, tiny vinegar eels (a type of nematode), the leg of a louse, the roe of a cod, blood serum, the veins of connective tissue between muscles, and more. He cut thin slices of a cow’s optic nerve with his shaving razor (his own red blood cells can be seen on them with a microscope even today), dried them, and sent them with one of his letters. These specimens remain at the Royal Society, among a set of frail little packets labeled by Leeuwenhoek more than 350 years ago. Under the careful eye of the Society’s librarian, I was allowed to examine the one on which Leeuwenhoek had written (in Dutch), “Pieces of the optic nerve of a cow and cut into transverse slices.” With trembling hands, afraid of damaging the treasures inside, I unfolded the packet to find 12 to 14 fawn-colored, hand-cut sections, slightly curled with age. They reminded me of desiccated slices of parmesan cheese.

Leeuwenhoek continued his observations of his little animals, sending his precise notes to the Royal Society. He found the animals everywhere: in rainwater, in his own well water, in saltwater, in melted snow, in water from Delft’s famously clean canals. He infused the water from these different sources with pepper, cloves, ginger, and nutmeg, labeling each concoction with the type of water, the spice, and the date when he combined them. He put these infusions in china teacups and stored them on shelves and tables all around his study, leaving little space for his dissections and observations.  He checked the teacups periodically to see what little animals might appear, taking extensive notes each time.

I’ve always wondered why Leeuwenhoek used teacups rather than flasks or beakers. Did he occasionally sip from the cups to see whether certain tastes corresponded to the number of little animals he found in them?

In December 1675, now growing impatient, Leeuwenhoek reminded the Royal Society of his world-changing discovery. Still no answer. He shrugged and left for vacation in August. Leeuwenhoek had continued recording his observations of the little animals in the teacups right up until the moment of departure. He must have been thinking of them the entire time he was away, because one of the first things he did when he returned after eight days was rush to the teacups and observe how the little animals had fared in his absence. Now that he was back, he wrote, “it was pretty to behold the motion, quivering and trembling all the time.” These little animals had apparently taken the place of his beloved “little dog, which was much admired by everybody for its long and purely white hair.” His dog had died in 1674, right around the time Leeuwenhoek found his new pets.

He wrote again to the Royal Society, and again received no response. It was time to compose a letter that he knew would grab its members’ attention. In October 1676, Leeuwenhoek informed the Society that he had measured the little animals by comparing them to a grain of sand. The ones he found in the pepper-infused water were so astonishingly small, he estimated one million of them would not equal the dimension of a grain of sand. He had now seen bacteria.

Oldenburg and the members of the Royal Society could no longer ignore Leeuwenhoek’s claims. When they printed his letter in the Transactions, they prefaced it with a disclaimer that they could not give their approval to his findings without being informed of how he had made his observations. The Society demanded that Leeuwenhoek reveal his method of making microscopes, of observing with them, and of calculating size so that his results could be replicated by their own members.

Scientific conventions were starting to change. It had not previously been expected that a discovery be replicated in another laboratory for it to be accepted by the scientific community. But suddenly the Royal Society demanded that Leeuwenhoek do just that. And like many scientific innovators even now, Leeuwenhoek wanted to keep his trade secrets—he needed to earn a living selling his microscopes without other instrument makers copying them. Inevitably this led to conflict. Leeuwenhoek tried to appease the members by inviting them to Delft; after all, as the Royal Society’s own motto instructed: nullius in verba, “take nobody’s word for it.” It is unclear why they did not come to see the little animals for themselves, since England and the the Dutch Republic were not at war, and it was only 272 nautical miles (503 kilometers) from the port of London to Rotterdam and a further 15 kilometers to Delft. To verify such a world-changing discovery, surely several members could have spared a week or so.

After his invitation was refused, Leeuwenhoek sent to Oldenburg affidavits by such witnesses as the pastor of the English congregation in Delft, two Lutheran pastors, and a doctor of medicine at the University of Montpellier. Each attested that he had observed the little animals, that they moved on their own, and that, as one Englishman noted, when Leeuwenhoek added vinegar to the water, the animals stopped moving, “being killed by the vinegar.”

The Royal Society remained dissatisfied. The English, it seemed, would not believe Leeuwenhoek’s discovery until English eyes had seen the little animals on English soil in an experiment conducted by an English natural philosopher. It is hard to avoid the conclusion that they were upset that Leeuwenhoek—a Dutchman—had beaten their own compatriot Hooke to the discovery. Exasperated, Leeuwenhoek gave Hooke a few hints, and then, finally, on November 1, 1677—a full three and a half years after the first sighting—Hooke observed Leeuwenhoek’s little animals. Even that was not enough; Hooke had to show them to the Royal Society’s gentleman members. This he did on November 15. The next issue of the Transactions announced: “The [little animals] were observed to have all manner of motions to and fro in the water and by all who saw them they were verily believed to be animals.” Hooke stressed the attendance of “Sir Christopher Wren, Sir John Hoskyns, Sir Jonas Moore … and divers others so that there was no longer any doubt of Mr. Leeuwenhoek’s discovery.”

Perhaps feeling abashed, the Royal Society named Leeuwenhoek a fellow, an honor usually reserved for British natural philosophers. He was so pleased that when his portrait was done around 1680, he made sure that the fellowship certificate with its distinctive red ribbon and the silver box in which it was sent were featured beside him in the painting. It was around this time that he added the “van” to his name.

He lived a long life, never ceasing his investigations. After his discovery of spermatozoa in his own semen, he went on to try to find the source of sperm. While dissecting a hare, he found the answer while observing sperm oozing from the vas deferens and testicles. He examined the sperm of 30 animals in all: rats, dogs, several kinds of fish, mussels, oysters, roosters, frogs, and insects of many kinds, including tiny aphids and gnats.

On his deathbed, in 1723, he dictated two letters to the Royal Society describing a histological study he had performed on cells of the diaphragms of a sheep and an ox, to disprove his doctor’s theory that he was dying of heart palpitations. He believed, rather, that he suffered from convulsions or spasms in the tendons of the diaphragm that made it difficult to breathe. He was correct, and this rare disorder is now called Van Leeuwenhoek’s Disease.

Leeuwenhoek’s discoveries did not immediately change medicine. “Germ theory”—the idea that microorganisms cause disease—did not become accepted until there was compelling evidence for it, which Leeuwenhoek lacked. One crucial step was made in the mid-1850s, when the work of Louis Pasteur provided evidence that wine and milk were being contaminated with—and spoiled by—microorganisms. In 1876, more than 150 years after Leeuwenhoek’s death, Robert Koch discovered the anthrax bacillus, proving that a particular bacterium does cause an associated disease. Neither discovery could have been made without the use of microscopes and the knowledge that microorganisms exist.

Leeuwenhoek believed that no one during his lifetime could see the invisible better than he could. Yet he suspected that even his own efforts had not penetrated to the very depths of the hidden universe. Writing to Huygens in 1679, he predicted that “all we have as yet discovered is but a trifle in comparison of what lies hidden in the great treasure of nature.”

A trifle indeed.

Viruses such as SARS-CoV-2, which causes Covid-19, are about 1/100th the size of bacteria, much too small to be seen by microscopes that use light. They are “submicroscopic” and can be seen only with electron microscopes, which use beams of electrons rather than visible light photons as a source of illumination. This and other new technologies for seeing the invisible would have delighted Leeuwenhoek.

Whereas the first microorganisms took millennia to find, the SARS-CoV-2 virus was identified in a matter of days, thanks to the work of Leeuwenhoek and those who followed him. But we should also reflect on the relevance today of Leeuwenhoek’s belief that the little animals are not dangerous to humans, that they are instead our friends. Indeed, he resisted the suggestion of Hans Sloane of the Royal Society that little animals might be found in the pustules of smallpox victims. And even when Leeuwenhoek discovered some in his own feces while suffering an intestinal disorder, he refused to blame them for his illness.

In his 50s, at an age when most men had lost at least some of their teeth, he proudly described his own full, healthy set. The reason, he insisted, was because he scrubbed his teeth and gums each day with salt. After rinsing with water, he would take a clean, sharp quill and pick between his teeth, finishing up by rubbing his teeth with a muslin cloth.

One day, a beggar with rotting and missing teeth told Leeuwenhoek that he had never washed his teeth in his life. Going boldly where other investigators might have quailed, Leeuwenhoek scraped the man’s putrid teeth. He found so many little animals that they were in a tangle and could hardly move. He suggested that they were responsible for the man’s “stanching breath.” He even implied that they were responsible for the man’s decaying teeth.

And yet, when he found some plaque on the quill after picking his own healthy teeth, he mixed it with rainwater and some spittle and also found many little animals moving; some had “a strong and swift motion, and shot through the water like a pike,” while others “spun around like a top.” He realized with glee that “there are more living animals in the unclean matter in the teeth in one’s mouth than there are men in a whole Kingdom!” If the little animals were everywhere—in our drinking water, inside our bodies, even on healthy, clean teeth—how could they be dangerous?

He was, it turns out, partly correct. Scientists now recognize the importance of “the microbiome”: the bacteria, viruses, and fungi that reside on our skin and inside our gut. Studies have shown that the microbiome plays a critical role in our well-being. A healthy gut microbiome helps us digest our food and produce vitamins crucial to our health: B12, thiamine, riboflavin, and vitamin K (which helps clot the blood). Some studies have concluded that the specific microbiome with which we are born also helps shape our future life by making us more or less likely to develop autoimmune illnesses such as Crohn’s disease, diabetes, rheumatoid arthritis, and multiple sclerosis. Researchers are working on how we can manipulate the microbiome to prevent—and possibly even cure—these chronic and often debilitating diseases by introducing certain “good” bacteria to counteract the “bad.”

Using good bacteria to cure disease caused by bad bacteria is not merely a dream but a reality. Clostridioides difficile (C. diff  ) is a bacterium in the intestines that can cause life-threatening diarrheal infections. It is harmlessly present in many peoples’ microbiomes but can become virulent when antibiotics prescribed for another ailment kill off the bacteria that were keeping C. diff in check. When other antibiotics are then used to control C. diff,  they often cause only temporary remission. The overuse of antibiotics has led to the emergence of antibiotic-resistant strains. In 2005, the CDC warned of an emerging strain of C. diff with epidemic potential. But another treatment was found that did not rely on antibiotics.

This treatment, a fecal microbiota transplant (FMT), filters the stool of a healthy person and transfers its good microbes, including fecal bacteria, into the patient’s lower intestine. FMT restores the bacteria that prevent C. diff from causing illness. This treatment has a high success rate with almost no relapses. Although it was already being used by doctors under what the FDA calls “discretionary enforcement” or as part of clinical trials (both of which limited its use), the FDA placed FMT under a “special guidance” rule in 2013, allowing all patients with C. diff who were unresponsive to antibiotics to receive it. In 2022 and earlier this year, the FDA approved two pharmaceutical products for the treatment. FMT is also being tested as a treatment for other gastrointestinal diseases such as irritable bowel syndrome and colitis. Research suggests that it may help patients with Parkinson’s disease, multiple sclerosis, and additional neurological conditions. Leeuwenhoek’s “little friends” are already succeeding in curing serious, even deadly, illnesses, and in the future may cure more—perhaps even Covid-19.

Recent research at the National Institutes of Health, using both animal models and human subjects, has suggested that the SARS-CoV-2 virus disrupts the microbiome in such a way that bacterial infections can take over the gut and alter the gut lining—allowing pathogenic (or bad) bacteria to spread to the bloodstream and leading to the serious secondary infections that are often fatal to Covid-19 patients. And scientists at the University of Chicago found that an analysis of personal gut microbiomes can predict the outcomes of patients with severe Covid-19. Such discoveries raise the hope that someday we will be able to create personalized probiotics that can introduce good bacteria into a patient’s microbiome to limit the damage of the virus, perhaps even destroy it, and prevent the disabling sequelae that cause untold suffering even after an initial “recovery.” Research on how to use good bacteria to help Covid-19 patients continues.

Microorganisms make up about half of our total cell count. One of Leeuwenhoek’s contemporaries, the natural philosopher Margaret Cavendish, wrote a poem called “Of Many Worlds in This World,” a paean to the new discovery of an invisible realm of  “creatures.” It ends: “And if thus small, then ladies may well wear / A world of worlds, as pendants in each ear.” It turns out that this world of worlds exists not merely on our earlobes but inside of us—acting as friends as well as foes.