From “WIRED“: “The Secret Microscope That Sparked a Scientific Revolution”

From “WIRED“

9.27.22
Cody Cassidy

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Illustration: Ariel Davis.

How a Dutch fabric seller made the most powerful magnifying lens of his time—and of the next 150 years—and became the first person ever to see a microorganism.

“On September 7, 1674, Antonie Van Leeuwenhoek, a fabric seller living just south of The Hague, Netherlands, burst forth from scientific obscurity with a letter to London’s Royal Society detailing an astonishing discovery. While he was examining algae from a nearby lake through his homemade microscope, a creature “with green and very glittering little scales,” which he estimated to be a thousand times smaller than a mite, had darted across his vision.

Two years later, on October 9, 1676, he followed up with another report so extraordinary that microbiologists today refer to it simply as “Letter 18”: Van Leeuwenhoek (lay-u-when-hoke) had looked everywhere and found what he called animalcules (Latin for “little animals”) in everything.

He found them in the bellies of other animals, his food, his own mouth, and other people’s mouths. When he noticed a set of remarkably rancid teeth, he asked the owner for a sample of his plaque, put it beneath his lens, and witnessed “an inconceivably great number of little animalcules” moving “so nimbly among one another, that the whole stuff seemed alive.” After a particularly uncomfortable evening, which he blamed on a fatty meal of hot smoked beef, he examined his own stool beneath his lens and saw animalcules that were “somewhat longer than broad, and their belly, which was flat-like, furnished with sundry little paws”—a clear description of what we now know as the parasite giardia.

With his observations of these fast, fat, and sundry-pawed creatures, Van Leeuwenhoek became the first person to ever see a microorganism—a discovery of almost incalculable significance to human health and our understanding of life on this planet.

Microorganisms are the second most abundant life-forms on Earth. Two of the types that Van Leeuwenhoek identified—protozoa and bacteria—are by some estimates responsible for more than half the deaths of every human who has ever lived, and yet until he observed them their existence had hardly been seriously postulated, much less proven. Of course, he had no idea about the pivotal role his little animals played, but his revelation provided the foundation for germ theory—the greatest leap forward in the history of medicine. Even more surprising, this monumental discovery was not made by one of the 17th century’s great scientific minds such as Galileo or Isaac Newton. Instead, a secretive, obsessive, self-taught Dutchman of little renown did it by handcrafting a lens 10 times more powerful than anything built before it. His design wouldn’t be bested for another 150 years.

Yet even as scientists steadily unlocked the secrets of Van Leeuwenhoek’s microworld over the past 350 years, one great mystery eluded them: How the hell did he do it? How did a shopkeeper working during his off hours build a microscopic lens that surpassed the world’s greatest by an order of magnitude?

While Leeuwenhoek shared nearly everything he saw through his microscope in exactingly detailed letters, he zealously guarded how he made his revolutionary lens. When asked, he declined or obfuscated. Even as his discoveries made him so famous that the King of England requested to see his animalcules and Peter the Great stopped in Delft to see his lenses, the Dutchman never revealed his secrets.

Van Leeuwenhoek crafted more than 500 microscopes but only 11 of his instruments survive today—and only one that produces the 270X magnification he used to make his greatest discovery. Because that lens remains sandwiched between brass plates, determining its mode of manufacture would require disassembling the microscope—an affront tantamount to scraping paint off the Mona Lisa to determine the sequence of Leonardo’s brush strokes.

Most of Van Leeuwenhoek’s contemporaries believed he had invented a new glassblowing technique. Clifford Dobell, who wrote the brilliant 1960 biography Antony Van Leeuwenhoek and His Little Animals, postulated that he created his best lenses by simply grinding and polishing them better than anyone else. But in three centuries of speculation, no one could say for sure.

Tiemen Cocquyt’s interest in Van Leeuwenhoek’s secrets began in the late 2000s, soon after first seeing one of his microscopes, which was then locked away in the basement of the University Museum Utrecht. “How could this toy open up the microworld?” Cocquyt remembers thinking.

Cocquyt is a curator in the National Museum Boerhaave in Leiden, Netherlands, which houses an array of early optical instruments, including several of the microscopes. He has spent much of his career investigating the origins of Europe’s 17th-century optical revolution, when visual instruments suddenly leaped from simple magnifiers to the great telescopes of Galileo and Christiaan Huygens. (That revolution was inadvertently sparked, Cocquyt says, by Italian advances in making ultra-clear glass.)

Over Zoom, Cocquyt shows me a replica of a Van Leeuwenhoek microscope, and it does look like a toy—a doll’s hand mirror, to be exact. It’s barely 3 inches tall, with a thin handle leading to a square brass plate. The lens sits beneath a pinhole in the plate’s center, and on the back side a pin for holding samples is connected to a set of screws for focal adjustment.

When Cocquyt first examined the exposed glass of the lens, he believed its smooth surface indicated it could only have been created by heat. Thus, like many of Van Leeuwenhoek’s contemporaries, he suspected the Dutchman had invented a new glassblowing technique. But without looking inside, he could only speculate.

The definitive answer, he hoped, might be found with the help of a nuclear reactor.

At its simplest, a magnifying lens is nothing more than a curved piece of transparent material—usually glass. As light passes through that angled glass, it decelerates, and its path is redirected, or refracted. Depending on its design, a lens can manipulate light in any number of ways, but magnifying lenses like Van Leeuwenhoek’s are spherical—technically called bi-convex—and refract light into a single focal point. “In essence, it serves as a light funnel,” says Steve Ruzin, curator of the Golub Collection of antique microscopes at The University of California-Berkeley. Place your eye at the narrow end of the funnel, and an enormous amount of light arriving from the lens’s focal point crams through your pupil.

This has two effects. First, the more light your eye receives from an object, the more detail it can perceive. Second, by funneling all the light hitting the lens through the width of your pupil, the image consumes your entire field of view. An object that once projected onto your retina as an undetectable speck now appears in Imax.

Of course, not all spherical lenses magnify equally. A big lens with a gentle curve refracts the light traveling through it only slightly, and thus barely enlarges the image. A small lens with a sharp curve refracts the light more, enlarging the image a great deal. Moderately powered spherical lenses of the 17th century were about the size of a pea. Van Leeuwenhoek’s greatest lenses were smaller than a sixth that size. At that diameter, construction becomes exceptionally difficult. Even the smallest manufacturing defect—a bubble, scuff, or scratch—could project an enormously disfiguring visual aberration. Larger, less powerful lenses are far more forgiving. They are simple enough to create that they’ve been found among remnants of the oldest civilizations. The earliest-known handcrafted lens is a piece of ground rock crystal capable of 3X magnification that archeologists discovered in a nearly 3,000-year-old Assyrian palace. But because glass occurs naturally, its magnifying power has probably been independently discovered and harnessed many times throughout history.

Nevertheless, lenses never exceeded much beyond the power of typical modern reading glasses until the early 1590s, when a Dutch lens maker named Hans Janssen built a microscope capable of 9X magnification. Janssen’s contraption inspired many copycats, one of which intrigued Galileo, who modified one of his own telescopes to produce a microscope that one witness claimed could show “flies which appear large as a lamb.”

In 1665—only a few years before Van Leeuwenhoek peered through his first lens—microscopes emerged into the public consciousness when the polymath Robert Hooke published his surprise bestseller Micrographia. The book included Hooke’s observations, interpretations, illustrations, and even simple instructions on how anyone could make their own lenses: Hold a thin hair of glass over a flame until a bead forms, ‘which will hang at the end of the thread,’ writes Hooke. Snap off the bead, and the result is a spherical magnifier.

But despite the prodigious genius of Galileo and Hooke neither produced lenses with anything close to the magnifying power of Van Leeuwenhoek’s. “Leeuwenhoek took an opportunity that lay somehow undeveloped in the 1660s and pushed it into the best result that was possible,” Cocquyt says.

He did so by first eschewing Hooke’s and Galileo’s preference for using multiple lenses arranged in sequence. This design is common in modern microscopes—it’s a bit like projecting an image into another projector—but achieving that magnifying effect without producing huge distortions requires extreme precision. Until that challenge was solved in the early 19th century, single-lens microscopes like Van Leeuwenhoek’s could achieve far superior results.

Hooke was aware of this shortcoming in his design, yet he still preferred multiple lenses, thanks in part to their ease of use. High-powered lenses have such an extremely short focal point that with just one, the viewer has to place their eye incredibly close to the lens, making blinking difficult. Hooke wrote that he found single-lens microscopes “offensive to my eye.” Ruzin told me that looking through one of Van Leeuwenhoek’s surviving devices is “terribly uncomfortable.”

Van Leeuwenhoek’s design may have been torture to use, but it was also brilliant—and that brilliance extended beyond his super-powered lenses. Because his device was handheld, he could backlight his sample by holding it up against sunlight or a flame, while his contemporaries’ desk-bound microscopes could only be lit from above. Top-down lighting works well for opaque objects, such as a bee’s stinger, but not for pond water and other translucent samples, where it’s far easier to see microorganisms. To observe these liquids, Van Leeuwenhoek filled a small glass capsule, glued it to the microscope’s pin, and held the instrument up to light.

“It almost seems as if Van Leeuwenhoek knew that a new microworld was to unfold,” Cocquyt told me. One of his scientific rivals, Johannes Hudde, later said, “isn’t it surprising that we never had the creativity to use these ball lenses to observe little things against the daylight, and that an uneducated and ignorant man such as Van Leeuwenhoek had to be the one to teach this to us.”

Van Leeuwenhoek was the fifth son of a basket maker, born in the Delft—a small port city in South Holland known for its picturesque waterways, pottery, and beer. At 16 he departed for an apprenticeship as a dry goods seller in Amsterdam, but six years later he returned home, married the daughter of a well-regarded local brewer, and purchased his own fabric shop.

He spent his twenties growing a successful business but suffered immense personal tragedy. Of the five children he and his wife Barbara had in their 12 years of marriage, four died in infancy; Barbara would soon follow. Few biographical details have survived from his first decade back in Delft, but he held a number of odd jobs in addition to running his draper shop, including working as chief custodian of the local courthouse. A stint as town surveyor offers one clue to Van Leeuwenhoek’s budding scientific potential: proof he had learned geometry.

His obsession with magnifying lenses began sometime in his mid-thirties. How he came upon it isn’t known. His writings never touch on its origins. Perhaps, as many have speculated, he started using lenses to inspect the quality of his cloth. Or maybe he got caught up in the public mania for microscopes following the publication of Hooke’s Micrographia. Van Leeuwenhoek never mentions the book in any of his letters, but the timing aligns, and he clearly read it: Some of his experiments replicate Hooke’s too closely to be a coincidence. But regardless of how Van Leeuwenhoek got into microscopy, by 1668 he had begun pursuing it with an unusual tenacity. While traveling in England that year, he saw the white cliffs of Dover and felt compelled to examine their chalky slopes beneath his lens: “I observed that chalk consisteth of very small transparent particles; and these transparent particles lying one upon another, is, methinks now, the reason why chalk is white.”

By 1673, though still operating in complete obscurity, he was already making the world’s most powerful lenses. His obscurity might very well have continued, and the momentous discovery of microorganisms might well have served only to satisfy this curious individual’s psychological compulsion, were it not for a Delft physician named Renier de Graaf.

De Graaf had come to some renown through his experiments using dyes to determine organ function, and in 1673 he introduced Van Leeuwenhoek to the Royal Society with a note calling him a “most ingenious person … who has devised microscopes which far surpass those which we have hitherto seen.” Following that preamble, Van Leeuwenhoek described the body parts of a louse in his precise-yet-meandering writing style that is, as one biographer notes, “distinguished with a certain business formality, but an almost total lack of coherence.” Over the next year, he sent five more letters to the Royal Society conveying interesting but not particularly controversial observations about the globules in milk and the structure of his fingernails. Then, on September 7, 1674, he sent the letter reporting his shocking discovery: Within an otherwise unremarkable drop of pond water he had seen “glittering” creatures a thousand times smaller than any animal he had previously observed.

The Society’s secretary, Henry Oldenburg, replied to Van Leeuwenhoek with understandable restraint: “This phenomenon, and some of the following ones seeming to be very extraordinary, the author hath been desired to acquaint us with his method of observing, that others may confirm such observations as these.” Van Leeuwenhoek quickly responded, providing eyewitness accounts of a few local dignitaries who had looked through his lenses—but refused to disclose the secrets of his techniques. “My method for seeing the very smallest animalcules and minute eels, I do not impart to others; nor how to see very many animalcules at one time. That I keep for myself alone,” he wrote. Even when Hooke himself, who learned to speak Dutch just so he could communicate with Van Leeuwenhoek without translation, specifically asked how he made his observations, the stubborn scientist refused for reasons that were, as Hooke later wrote, “best known to himself.”

Three years later, after a few failed attempts by others, Hooke finally managed to re-create Van Leeuwenhoek’s experiment well enough to prove his observations at a gathering of the Royal Society. The confirmation made the Dutch draper famous, but despite repeated inquiry he took his secrets to the grave.

In 2018, Cocquyt and his team of researchers set out to reveal them without taking Van Leeuwenhoek’s 350-year-old microscope apart. That’s where the nuclear reactor comes in.

Neutron tomography is a scanning technique that is as remarkable as it is completely insane. It involves blasting neutrons generated by atomic collisions through a large-caliber barrel—which sticks out of a reactor’s nuclear chamber like the devil’s cannon—and into whatever object needs scanning. Neutrons, beyond irradiating everything they hit, pass right through metals but slam into most low-mass elements, including those in glass. Sensors behind the object detect the neutrons, producing an image that reveals their inner structure. Recent scans have led to the discovery of a dinosaur inside another dinosaur’s belly and the remnants of ice in martian meteorites.

A nuclear reactor in Van Leeuwenhoek’s hometown of Delft had recently installed a neutron tomography instrument, and Cocquyt used it to examine the Dutchman’s lenses in their birthplace. He first placed a replica microscope in front of the neutron scanner—a test to ensure he didn’t render a priceless piece of scientific history radioactive for 1,000 years. When he next scanned the inventor’s less-powerful microscopes, the images clearly showed the glass to have hard edges and a slight lentil shape. “Exactly what you would expect for a ground lens,” Cocquyt says.

But on his most powerful lens, neutron tomography revealed that Van Leeuwenhoek used another technique entirely. It was almost perfectly spherical and completely smooth, without the sharp rim inevitably created by a traditional grinding cup. Even more tellingly, the lens retained the faint remnants of a snapped stem, concealed by the brass plates since the day Van Leeuwenhoek had placed it there.

The stem is a smoking gun. It’s the unavoidable result of forming a lens by melting a thread of glass until a bead forms on its end and then snapping it off. In other words, to make his greatest lens, Van Leeuwenhoek copied Hooke’s simple recipe from the book that likely inspired him. Cocquyt believes this may explain why he was so circumspect when Hooke asked about his methods; he wanted to avoid giving credit to Hooke himself.

Published in Science Advances [below] last year, Cocquyt’s discovery that Van Leeuwenhoek used a well-known technique reveals a deeper truth about the state of microscopy in the 17th century. It suggests that for all the crafting genius required to make his tiny, super-powered lens, Van Leeuwenhoek’s greatest insight may have been that there was something new to see by making one.

Fig. 1 The two original Van Leeuwenhoek microscopes that were studied with neutron tomography.
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The lens sits mounted between the brass plates, at the position of the specimen pin. (A) A medium-powered (×118) instrument (Rijksmuseum Boerhaave, Leiden, inventory number V7017). Note that there is a redundant drill hole in the upper left corner of the instrument, not to be confused with its lens aperture, which is directly behind the pin. This microscope is numbered #1 by Van Zuylen. Photo credit: Tom Haartsen Fotografie, Ouderkerk aan de Amstel. (B) The instrument with the highest magnification among the preserved ones (×266) (Utrecht University Museum, inventory number UM-1). This microscope is numbered #3 by Van Zuylen. Photo credit: Utrecht University Museum.

Fig. 4 Orthogonal cross sections of computed tomography of the Van Leeuwenhoek microscopes from Leiden and Utrecht.
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(A) The cross sections of the lentil-shaped lens of the medium-powered microscope (V7017). (B) The circular cross section of the high-powered microscope (UM-1). The XZ projection shows that this ball-shaped lens has a tiny glass stem connected to it.

[More instructive images are available in the science paper.]

This seems intuitive and incredibly obvious to a modern reader. What kind of scientist wouldn’t want to see in greater detail? But before Van Leeuwenhoek, most microscopists used their lenses to reveal greater detail about the visible world—things they could already see to some degree with the naked eye. Their drawings of bee stingers and ant legs do not lose their resemblance to the creatures readers were familiar with. Had they used Van Leeuwenhoek’s high-powered lenses, their depictions would not have been recognizable to anyone.

Leeuwenhoek had no inkling that minuscule, alien-like creatures awaited him, but his obsession with the microworld drove him to leave the visible world behind and discover a vast new microbial one living under—and inside—our noses.”

Science paper:
Science Advances

See the full article here .

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