The Seeds of Life

by Edward Dolnick

  These were daring arguments, even with Harvey as a shield. De Graaf knew that his critics were poised to burst into laughter at the mere mention of women and eggs, but he warned that they would look “frivolous and stupid” if they did not heed him.

  He turned his wrath toward those writers who viewed women as incomplete, inferior men or as ornaments whose role was to beautify the world “like the peacock’s tail.” This was “ridiculous” and insulting both to women and to God. “Nature had her mind on the job when generating the female as well as when generating the male,” de Graaf thundered.

  Such fervor in defense of women was unusual.* Typically, in the early modern age, women were condemned for their lustful, fickle natures. Men were supposedly higher-minded. Certainly this was the view of Robert Boyle, one of the founders of the Royal Society and the most important English scientist in the generation before Isaac Newton. Celibate through his long life, Boyle feared the wanton, scheming ways of women, all of them temptresses like Eve: “I am confident that thousands would be whores could they but be so without being thought so.” Men’s highest calling was to study God’s works, but women would lure the weak and unwary from that sacred mission. Who would peer through a microscope, Boyle asked, when he might be staring down a lady’s cleavage?

  De Graaf had little use for such attacks. Focused on his work, he called on anatomists to amend their language, as a first step: “The common function of the female ‘testicles’ is to generate the eggs, foster them, and bring them to maturity. Thus, in women, they perform the same task as do the ovaries of birds. Hence they should be called women’s ‘ovaries’ rather than ‘testicles,’ especially as they bear no similarity either in shape or content to the male testicles.”

  De Graaf paused for breath, then sped across the finish line: “On account of this lack of similarity, they have been regarded by many as bodies without function; quite wrongly, because they are absolutely essential for generation.”

  DE GRAAF HAD SEEN THE BIG PICTURE: WITHIN THE OVARIES were eggs, and those eggs, in some mysterious conjunction with semen, formed embryos. And yet de Graaf had not seen eggs. Not quite. He believed sincerely that he had. What he had actually seen were the follicles that contain the eggs. Today those small, bumpy structures embedded inside the ovary are called Graafian follicles. A follicle ruptures and releases the egg within, which travels through the Fallopian tubes. (Vesalius, anatomy’s founding father, had observed these follicles a hundred years earlier but had dismissed them as signs of infection rather than anything to do with conception. We will run into many similar examples in the course of our story, where a brilliant investigator notices a smoking gun, picks it up, mulls it over, and then tosses it aside as irrelevant.)

  With a series of elegant and bold experiments, de Graaf came within inches of piecing together the whole egg story. He began with experiments akin to Harvey’s dissections of deer, though he used rabbits instead. But unlike Harvey, who had failed to see any changes in the ovaries, and therefore discounted them, de Graaf saw changes galore.

  In the first few days after mating, the follicles in the ovary had reddened and swelled and then burst. Staring intently, de Graaf grew to suspect that something within the follicles “had been disrupted or expelled.” (In theory, de Graaf might have managed to spot an egg with his naked eye, but it would take his successors, armed with microscopes, another 150 years to do so. We think of eggs as easy to find, but that is because we picture bird’s eggs. Those eggs are enormous, since they have to provide all the nourishment that the developing chick will ever get.)

  Though he had missed the release of the egg itself, de Graaf continued his surveillance. Now he kept careful watch on the uterus, too. His tools were little more than sharp eyes and the ability to count. Instead of dissecting his rabbits only a few hours or even a few days after they had mated, he waited several days. Now he found ruptured follicles in the ovary and tiny embryos in the uterus. De Graaf asked the crucial question: How many of each?

  To his delight, the number of ruptured follicles matched the number of embryos! Detectives on the track of a killer could hardly have put together a more promising case. It was as if the police had been trailing a murderer who liked to poison his victims. On a night when their suspect had been caught with two empty vials in his overcoat pocket, detectives had found two victims. On another night, three vials, three victims.

  Then came trouble. De Graaf cut open a rabbit that had mated six days before. He counted ten ruptured follicles but only six embryos! This was not a problem, de Graaf insisted. The key was that he never saw more embryos than ruptured follicles. Most likely, de Graaf proposed, things simply went wrong sometimes—by random misfortune, the missing embryos had “come to a sinister end.” That argument carried weight. Everyone knew that human pregnancies often end in miscarriage. Crisis averted.

  De Graaf had moved well beyond Harvey. His biggest advance was conceptual. When Harvey talked about an egg, he had in mind a living organism in its earliest stages and not the female’s contribution to a new, living creature. That confusion of “embryo” and “egg” had muddied the picture. De Graaf cleared things up and convinced the world to shift focus. In his picture, the egg emerged from the female’s ovary and combined somehow with semen from the male to form a new organism.

  This was an especially bold claim, since de Graaf had never quite managed to see the egg directly. He came to his insight partly by virtue of intellectual daring and partly by good fortune. Harvey’s choice of deer made trouble for him, as we have seen. De Graaf’s choice of rabbits made matters clear, and at times misleadingly clear. It so happens that in rabbits the act of mating stimulates the female to release eggs.* Watching his rabbits, de Graaf witnessed a straightforward series of events: a female mated, follicles within her ovary changed, the follicles ruptured, embryos developed, and the number of embryos matched (usually) the number of ruptured follicles.

  But for most mammals, mating does not induce ovulation. If de Graaf had happened to choose a different animal to study—if, for instance, he had somehow managed to look at human beings—he would have seen that whether an egg is released has nothing to do with mating. The pattern with women is not so tidy as with rabbits—virgins release one egg a month, and so do women with sexual partners—and de Graaf might have joined the throng of befuddled scientists unsure just what eggs had to do with conception.

  As it was, he made errors aplenty. The biggest was following Harvey when it came to thinking about semen’s role. For both these scientists, semen retained its mystery because they could not find it anywhere within the bodies of the female animals they dissected, even knowing it had to be there. Instead, they talked of “seminal vapor” and “irradiation,” and pictured semen somehow manipulating the process of conception like a magician waving his fingers and making a silken handkerchief across the room dance and flutter.

  DE GRAAF’S BOOK ON WOMEN’S ANATOMY APPEARED IN MARCH 1672, a hectic, charged time in his own life and in the life of his country. He knew he had produced a masterpiece. Three months later, in June, he married. His wife became pregnant almost at once. Also in June 1672, war broke out, and France invaded Holland. Deeply troubled by news of battles and riots, de Graaf wrote a letter to the Royal Society in July 1672, lamenting “the disaster falling upon the whole of my country.” (One month later, a Dutch mob would kill the prime minister and his brother, hang the bodies upside down, and mutilate the corpses.)

  In the meantime, de Graaf’s onetime friend Swammerdam shoved his way into the picture. First, he wrote an angry letter attacking de Graaf’s book and charging him with intellectual theft. Credit for discovering the egg belonged to Swammerdam himself, he insisted, as well as to several others. Swammerdam followed up his letter with a full-length book of his own, The Miracle of Nature, or the Structure of the Female Uterus. This work, which appeared only weeks after de Graaf’s, spelled out Swammerdam’s views on conception and made his attack on de Graaf public and impossi
ble to miss.

  In March 1673, Maria de Graaf gave birth to a son. The parents named the boy Frederick. He died at the age of one month. In August of the same year, de Graaf himself died, perhaps of plague. He was thirty-two.

  In the last year or two of his brief life, de Graaf had written a momentous book. Just four months before his death, in the spring of 1673, he had written a momentous letter. De Graaf informed the secretary of the Royal Society that he wanted to introduce a fellow resident of Delft. “I am writing to tell you that a certain most ingenious person here, named Leeuwenhoek, has devised microscopes which far surpass those we have hitherto seen.”

  De Graaf himself had peeked through one of those microscopes, and he believed he knew what they would reveal.

  He did not.

  TEN

  A WORLD IN A DROP OF WATER

  ANTONY VAN LEEUWENHOEK MADE AN UNLIKELY EXPLORER. Proud and prickly, he was a forty-year-old merchant who sold fabric, buttons, and ribbons to the prosperous citizens of Delft. Leeuwenhoek had no scientific training and only a middling education, but he had infinite patience and far-ranging, unpredictable curiosity. And he had stumbled on a world that no one else had ever seen. More than that, he found himself alone and astonished in a world that no one had ever even imagined.

  In September 1674, a year after de Graaf’s letter of introduction, Leeuwenhoek sent a long letter to the Royal Society. He had written before, reporting on familiar objects like a bee’s stinger seen in close-up. (These were the peeks he had offered de Graaf.) This was different. About two hours from his home, Leeuwenhoek explained, was a large, murky lake. For no particular reason, he had collected a vial of greenish, goopy water from near the shore. The next day he examined a drop of water with his microscope. To his astonishment, “very many little animalcules” swam into view.

  Leeuwenhoek had seen fleas and mites and other tiny bugs. So had everyone else. But what a dog was to a flea, in size, a flea was to one of Leeuwenhoek’s “animalcules.” (Leeuwenhoek wrote in Dutch, and “animalcules” represented one early translator’s best try at describing his discovery in English. Other translators preferred the term “little animals.”) No one had ever suspected that the scale of life continued downward beyond what the eye could see. Why would it, if the world was made for the benefit of humans?

  Leeuwenhoek stared in giddy astonishment. “The motion of most of the animalcules in the water was so swift and so various, upwards, downwards, and round about, that ’twas wonderful to see. And I judge that some of these little creatures were above a thousand times smaller than the smallest ones I have ever yet seen upon the rind of cheese in wheat flour, mold, and the like.”

  Leeuwenhoek was not the first man to peer through a microscope. Half a century before, Galileo had thrilled at the sight of “flies which looked as big as a lamb” and nonchalantly walked upside down. A decade before Leeuwenhoek, Robert Hooke, one of the most talented men at the Royal Society, had examined fleas and slices of cork and dots of ink printed on a page. Hooke marveled at the surprises that his lenses revealed. The perfect, polished tip of a needle turned out to be jagged and irregular, “like an Iron bar [worn] by Rust and Length of Time.” The humble flea was outfitted with a perfect “suit of sable Armour, neatly jointed.”

  But those ventures were only a warm-up act for Leeuwenhoek. Pioneers such as Hooke had taken the known world and, essentially, held a magnifying glass up to familiar scenes. With lenses far more powerful than any that had come before, Leeuwenhoek spied the coastline of a new, undreamed-of continent and then plunged ashore and into the forest, where every leaf on every tree bustled with bizarre forms of life.

  Leeuwenhoek confirmed almost at once that the creatures he had found were not unique to the lake where he had gathered them. In a sample of rainwater, he found “little animals more than a thousand times less than the eye of a full-grown louse.” These were not mere dots fixed in place but darting, hovering creatures overflowing with energy. Some of the tiny animals “twirled themselves round with a swiftness such as you see in a top a-spinning before your eyes.”

  In a frenzy—his fascination would endure for fifty years—Leeuwenhoek set out to put the whole world under his lens. Every observation was brand-new, and the Dutch cloth merchant found himself struggling to pin names to countless unfamiliar sights, like Adam in Eden. His approach was utterly unsystematic, zigzagging from project to project as curiosity and happenstance led him.

  He did not turn at once to the mysteries of conception, but it was almost certain that he would arrive there before long. Soon after his letter about the bee’s stinger, the secretary of the Royal Society had written to him with a request: Would Leeuwenhoek please use his microscope to examine “saliva, chyle, sweat, etc.”?

  Leeuwenhoek cringed. Saliva and sweat were not problems, nor was chyle, which was food that had been transformed in the digestion process. The problem was the “etc.,” which Leeuwenhoek took to be a euphemism for semen. “I felt averse from making further inquiries,” he wrote later, “and still more so from writing about them. I did nothing more at that time.”

  Nothing more to investigate semen, he meant. But nearly everything else in the world came in for Leeuwenhoek’s obsessive scrutiny. One of his house servants had the task of collecting fleas for her master to study. He nagged her for blood samples, too, and then he compared her blood with his own and with that from every other creature that darted or crawled into view. He pestered shopkeepers for spoiled bits of food that might harbor tiny pests, and he asked his neighbors to bring him stubble from their beards after they had visited the barber.

  Soon after his rainwater experiment, Leeuwenhoek found himself wondering what gives pepper its sharp flavor. Could it be that pepper grains have miniature thorns that stab the tongue? He soaked some pepper in a bowl of water, to soften it. Then, for some reason, he examined the water. He saw four sorts of “little animals,” and the smallest were “so small that I judged that even if 100 of these very wee animals lay stretched out one against another, they could not reach to the length of a grain of coarse sand; and if this be true, then ten hundred thousand of these living creatures could scarce equal the bulk of a coarse sand grain.”

  The pepper mystery lay neglected. Leeuwenhoek grappled with a revelation—there was nothing special about a lake or a cup of rainwater. Tiny, hidden life seemed to turn up everywhere, not only in one or two rare locales. Leeuwenhoek had not only discovered a handful of new creatures living in an unsuspected world; he had found microworlds all around, all teeming with swimming, tumbling, too-tiny-to-notice forms of life. What were they for? Why had God made them?

  STARTLED BY LEEUWENHOEK’S REPORTS BUT UNSURE WHETHER to trust them, the Royal Society set out to look for itself. (“We had such stories written us from Holland,” recalled the philosopher John Locke, a Royal Society member, “and laughed at them.”) The job fell to Robert Hooke. History has neglected Hooke a bit—he had the misfortune to live in the shadow of Isaac Newton, and no man could have had a more talented or bad-tempered rival—but Hooke was brilliant. His skills spanned so many fields that one biographer dubbed him “England’s Leonardo.”

  An architect and astronomer and engineer, for starters, Hooke could design anything from a cathedral to a mousetrap. More than that, he knew all about lenses. He had written (and illustrated himself) a best-selling book called Micrographia, which showed gorgeous drawings of such wonders of nature as a fly’s eye, enormously magnified. No man could have been better suited to check Leeuwenhoek’s astounding claims.

  Lenses themselves were nothing new. Magnifying glasses had been known in the ancient world, and eyeglasses since around 1300. For generations, the inability to see fine detail had been a problem that troubled only a handful of people—seamstresses, goldsmiths, monks copying manuscripts or scholars studying them.* But the invention of the printing press, in 1453, brought an explosion in the number of books. For the first time vast numbers of people realized that their vision was i
nadequate. That led to a flurry of experimentation with different lenses, which led first to eyeglasses and then, as an almost inevitable spinoff, to telescopes and microscopes. In hindsight the path from reading small print to exploring the heavens and the microworld was almost a straight line.

  FIGURE 10.1. Hooke marveled at the intricate design of a fly’s eye. His drawing showed “near 14,000” eye parts arranged “in very lovely rows.”

  Leeuwenhoek’s first encounter with lenses most likely involved examining fabric samples through a magnifying glass. But that ancient invention, and even spectacles, paled next to the seventeenth century’s technological marvels. Spectacles and magnifying glasses enhanced a view that you could begin to make out with the unaided eye; the telescope and microscope brought into focus sights whose existence had never been suspected. The difference was akin to that between a pencil and a magic wand.

  On November 1, 1677, Hooke made his first try at seeing Leeuwenhoek’s “animalcules.” Leeuwenhoek, always secretive about his techniques, had not offered much help. Rather than reveal how he had fashioned his microscopes, he had mailed along testimonials praising his lenses. Eight prominent citizens, including two ministers, explained that Leeuwenhoek had let them peek through his microscopes; they, too, had seen the miracles he described.

  That would never do. Hooke set to work, presenting an array of contrivances fashioned from glass and brass. He had taken particular trouble with a set of glass tubes that ranged in size from ten times bigger than a human hair to ten times smaller. Hooke had a theory that a drop of water inside a glass tube might reveal more when examined under a microscope than a drop of water sitting in the open. Hooke labored, the Society members stared, but… nothing. “No discovery made.”