"To Antonio van Leeuwenhoek, of Delft, belongs the high merit of having been the first to use the microscope systematically and of having brought the construction of the simple microscope in his own hands to a high degree of perfection . . . Self-taught and never having attended a university, ignorant of Latin and Greek and of the classical texts, he became one of the greatest and most expert microscopists, thanks to the sagacity of his observations and the perfection of his technique"

(Arturo Castiglioni, A history of medicine).

With skill, diligence, an endless curiosity, and an open mind free of the scientific dogmas of the day, Leeuwenhoek succeeded in making some of the most important discoveries in the history of biology. He was the first to observe bacteria and protozoa. His research on lower animals refuted the doctrine of spontaneous generation, and his observations helped lay the foundations for the sciences of bacteriology and protozoology.

Antonie van Leeuwenhoek was the son of Philips Thoniszoon, a basket-maker, and Margriet Jacobsdochter van den Berch, who came from a family of brewers. He took his surname - «Lion’s Corner» - from the corner house near the Leeuwenpoort - «Lion’s Gate» - at Delft, which was owned by his father. The family belonged to the prosperous middle class of artisans, brewers, and lesser public officials, which was typical of the Golden Age of the Dutch Republic.

Little is known of Leeuwenhoek's early life, but it is certain that he did not have an extensive scientific education. When his father died at an early age, in 1638, the fourteen year old Antonie Leeuwenhoek was sent to the grammar school of Warmond, a village near Leiden. For some time afterwards he lived in Benthuizen with an uncle who provided him with a foundation in mathematics and basic physics. When his uncle died in 1648, Leeuwenhoek, now sixteen years old, left for Amsterdam to learn a trade, opting for an apprenticeship in the Cloth Worker’s Guild. He became apprenticed in a linen-draper’s shop.

Returning to Delft when he was 20, he established himself as a draper and haberdasher. At the age of 22 he was a successful textile merchant, purchased a house and an adjoining shop in Delft, where he was to spend the rest of his life.

On July 29, 1654, he married Barbara de Mey, daughter of Elias de May, a serge merchant from Norwich, England. Of their five children only one, their daughter Maria, survived her father.

His reputation rose so that in 1660 he was able to take up a new career as a civil servant with an appointment to usher to the aldermen of the municipality of Delft.

In 1666 Leeuwenhoek was named Chamberlain of the Council Chamber of the Worshipful Sherriffs of Delft. That was the year his wife died, and two years later Leeuwenhoek made one of the only two foreign trips that he took in his lifetime, visiting the chalk hills of Gravesend and Rochester in Kent. His other occasion for travel abroad was a journey that he made to Antwerp in 1698 to see the Jesuit scholar Daniel Papenbroek. Upon his return to delft in 1699 he was appointed surveyor to the court of Holland.

In the meantime Leeuwenhoek continued to advance in the service of the city of Delft, being made chief warden of the city in 1677 and, because of his mathematical skills, “wine and liquor gauger” (or inspector of weights and measures) in 1679. The income and emoluments from these offices made him financially secure, especially in his old age, when the municipality, in gratitude for his scientific achievements, granted him a pension.

Leeuwenhoek remarried on January 25, 1671. His second wife was Cornelia Swalmius, the daughter of Johannes Swalmius, a Calvinist minister at Valkenburg, near Leiden. She died in 1694; the one child of this marriage did not survive infancy. It probably that his second wife, who was an educated women, gave Leeuwenhoek the impetus to his scientific activity. The income from his public offices as well as a family inheritance gave him sufficient resources to launch his exploration of the microscopic worlds.

In 1676 he served as the trustee of the estate of the deceased and bankrupt Jan Vermeer, the famous painter, who had been born in the same year as Leeuwenhoek and is thought to have been a friend of his.

At the time of his appointment in 1666 he had already begun to broaden his scientific horizons, studying navigation, astronomy, mathematics and natural sciences.

Into science

Leeuwenhoek’s scientific life may be said to have begun in about 1671, when he was thirty-nine years old. At that time, developing the idea of the glasses used by drapers to inspect the quality of cloth, he constructed his first simple microscope or magnifying glasses, consisting of a minute lens, ground by hand from a globule of glass, clamped between two small perforated metal plates.

He seems to have been inspired to take up microscopy by having seen a copy of Robert Hooke’s illustrated book Micrographia, which depicted Hooke’s own observations with the microscope and was very popular.

It was through his letters - more than 300 of them, written to private scientists and amateurs in both Holland and other countries - that Leeuwenhoek made his work known. He wrote exclusively in Dutch, but had a few of his letters translated for the benefit of his correspondents. It was his friend Regnier de Graaf (1641-1693) who made sure that Leeuwenhoek's achievements became known to a wider audience. De Graaf put Leeuwenhoek in contact with the Royal Society in London, to which he communicated most of his discoveries in papers in the form of a lengthy correspondence with Henry Oldenburg, the Society’s secretary. His first letter, of 1673, contained some observations on the stings of bees. His letters, written in Dutch, were translated into English or Latin and printed in the Philosophical Transactions of the Royal Society, and often reprinted separately. All together he sent 190 papers to the Royal Society, to which he also donated 26 microscopes.

“Very little animalcules”

Leeuwenhoek made his most important discovery early in his scientific career, in 1674, when he recognized the true nature of microorganisms. He began to observe bacteria and protozoa, his "very little animalcules," which he was able to isolate from different sources, such as rainwater, pond and well water, and the human mouth and intestine. Starting from the assumption that life and motility are identical, he concluded that the moving object that he saw through his microscope were little animals.

He recorded these observations in his diary, and two years later, in a letter of October 9, 1676, communicated them to the Royal Society, where they caused a sensation. Indeed, such was the disbelief of some of fellows of that body that Leeuwenhoek felt obliged to procure written attestations to the reliability of his observations from ministers, jurists, and medical men. Leeuwenhoek subsequently described, in about thirty letters to the Royal Society, many specific forms of microorganisms, including bacteria, protozoa, and rotifers, as well as his incidental discovery of ciliate reproduction.

The boys in the lab

In letters to the Royal Society of London of 1699, later 1701, he mentions male and female sperm animals: Hoc videns mihi imiginabar, alterum esse masculinum, alterum femininum. I have often observed the sperm of a healthy man without waiting for it to become corrupt or fluid/watery, five or six minutes after ejaculation. I have noticed that a large number of small animals, I think it must be more than a thousand, on an area no larger than a grain of sand."

Leeuwenhoek used the terms animalculi e semini, animalculi seminis, vermiculi minutissimi in the same way. The totality of it he called semen masculorum.

It was necessary to devise a scale by which to measure this formerly invisible new world, and Leeuwenhoek therefore developed a practical system of micrometry, utilizing as standards a grain of coarse sand (870 µ), a hair from his beard (100 µ), a human erythrocyte (7,2 µ), and bacteria in peppe-water (2-3 µ).

In 1677 Leeuwenhoek described for the first time the spermatozoa from insects, dogs, and man. He was drawn to the investigation of animal reproduction when Stephen Ham of Arnhem, a medical student, told him that he had seen animalcules in human seminal fluid. Ham presumed that these little animals had been generated by putrefaction; Leeuwenhoek, however, supposed them to be a normal component of semen throughout the animal kingdom. He described the semen as "sperm animals", sperm cells, which he considered to be the nucleus of the new individual, while the egg cell was supposed to be just nourishment for the sperm animal". In the course of forty years, he described the spermatozoa of arthropods, molluscs, fishes, amphibians, birds, and mammals.

Leeuwenhoek's research on the life histories of various low forms of animals were in opposition to the doctrine that they could be produced spontaneously or bred from corruption. Thus, in 1680 he noticed that yeast consist of minute globular particles. Thus, he showed that the weevils of granaries (in his time commonly supposed to be bred from wheat as well as in it) are really grubs hatched from eggs deposited by winged insects.

He discovered the "animalcules" in the tartar on his teeth and, even after meticulous cleansing, the remaining opaque deposits isolated between his teeth "as thick as if it were batter". These deposits, he observed, contained a mat of various forms of bacteria.

Flower power

Since he believed in all living forms to be functionally similar to one another, Leeuwenhoek also made extensive investigations of reproduction in plants. In a letter of October 12, 1685, he drew upon his studies of the seeds of angiosperms to explain his theory of plant reproduction: since motionless plants could not copulate, each individual had to provide for its own propagation. The embryonic plant was therefore the source of new life; the endosperm was the primary nutritive uterus and the earth the secondary nutritive uterus for the seed of the plant. Since he considered the flower to be beautiful but functionless ornament of the plant, Leeuwenhoek did not investigate the anthers and the ovaries.

Bloody!

Leeuwenhoek was particularly attentive to the blood vessels and the blood. Harvey had described the circulation of the blood in 1628, while Malpighi discovered the capillaries in 1661 and, in 1665, observed the corpuscles for the first time (although he wrongly identified them as fat globules). Malpighi in 1684 gave the first accurate description of red blood cells. Leeuwenhoek, unaware of Malpighi’s work, effectively rediscovered the blood corpuscles, in 1674, and the blood capillaries in 1683.

Beginning in 1679, the French Journal Recueil d’expériences et observations sur le combat qui procède du mélange des corps published Leeuwenhoek's letters, translating them from the Philosophical Transactions. Leeuwenhoek himself did not publish his work until 1684, when he brought out some of his letters in Dutch. From 1687 he adopted a more systematic course of publication, however, and in 1718 he brought out a collected edition of his letters in Dutch, followed in 1722 by a Latin edition.

In his observation on rotifers in 1702, Leeuwenhoek remarked that, "In all falling rain, carried from gutters into water-butts, animalcules are to be found; and that in all kinds of water, standing in the open air, animalcules can turn up. For these animalcules can be carried over by the wind, along with the dust floating in the air."

Of major importance were his description of the optic lens in many species of animals. Leeuwenhoek studied the structure of the optic lens, and he demonstrated the striation in skeletal musculature. In 1719 he introduced histological staining, using saphron for investigating muscle fibres.

The fly

His letter on the flea, in which he not only described its structure but traced out the whole history of its metamorphosis, beginning with its first emergence from the egg, is of great interest, not so much for the exactness of his observations as for illustration of his opposition to the spontaneous generation of many lower organisms, such as "this minute and despised creature." Some asserted that the flea was produced from sand, others form dust, etc. but Leeuwenhoek showed it to be "endowed with as great perfection in its kind as any large animal" and proved that it bred in the regular way of winged insects.

Ants and mussels

Leeuwenhoek also carefully studied the history of the ant and was the first to show that what had been reputed to be ants' eggs, were really their pupae, containing the perfect insect nearly ready for emergence, and that the true eggs were much smaller and gave origin to maggots, or larvae. He argued that the sea mussel and other shellfish were not out of sand found at the seashore or mud in the beds of rivers at low water but from spawn, by the regular course of generation. He maintained the same to be true of the freshwater mussel, whose embryos he examined so carefully that he was able to observe how they were consumed by "animalcules," many of which, according to his description, must have included ciliates in conjunction, flagellates, and the Vorticella. Similarly he investigated the generation of eels, which were at that time supposed to be produced from dew without the ordinary process of generation.

A man unto himself

Despite his achievements and the respect he enjoyed in the Royal Society of London, Leeuwenhoek remained in relative scientific isolation. One consequence of this was that he was not always fully acquainted with the researches and theories of his fellow scientists, and so could not incorporate their sometimes valuable suggestions into his own work. But he was thus able to work with full independence and to make sharp distinction between the empiricism and speculation that marked the sometimes chaotic world of seventeenth-century science.

To his work in lens-grinding Leeuwenhoek brought a good pair of eyes, mathematical exactitude, great patience, and even greater manual dexterity. These same qualities, together with a keen, practical intellect, served him in the exploration of the whole field of natural science that occupied him in fifty years of continuous work. Strictly speaking, his scientific training was incomplete - he never attended a university - and he was limited by his lack of skill in classical and foreign languages. He was, however, able to rely upon such friends as Regnier de Graaf and Constantijn Huygens (1596-1687) as well as upon professional translators to aid him. He derived much of his scientific knowledge from Dutch authors - for example, Cornelis Bontekoe (1640-1685) on medicine and Jan Swammerdam (1637-1680) on insects - and from Dutch translations of standard works, or, indeed, from illustrations of books that he was not otherwise able to read - Robert Hooke (1635-1703) on microscopy, Nehemiah Grew (1641-1712) on plant anatomy, and Francesco Redi (1626-1697) on insects). He gained new information, too, from his correspondence with the Royal Society and from conversations with visiting scholars.



Leeuwenhoek’s work and microscopes

About 1671, when he was thirty-nine years old, Leeuwenhoek began developing the idea of the glasses used by drapers to inspect the quality of cloth. He constructed his first simple microscope or magnifying glasses, consisting of a minute lens, ground by hand from a globule of glass, clamped between two small perforated metal plates. To this apparatus he fixed a specimen holder that revolved in three planes. From these beginnings Leeuwenhoek went on to grind more than 400, maybe as many as about 550 lenses in his lifetime.

In basic design, probably all of Leeuwenhoek’s instruments were simply powerful magnifying glasses, not compound microscopes of the type used today. Compared to modern microscopes, it is an extremely simple device, using only one lens, mounted in a tiny hole in the brass plate that makes up the body of the instrument. The specimen was mounted on a sharp point that sticks up in front of the lens, and its position and focus could be adjusted by turning two screws. The entire instrument was only 8-10 cm long, and had to be held close to the eye; it required good lighting and great patience to use.

Compound microscopes (that is, microscopes using more than one lens) had been invented around 1595, nearly forty years before Leeuwenhoek was born. Several of Leeuwenhoek's predecessors and contemporaries, notably Robert Hooke in England and Jan Swammerdam in the Netherlands, had built compound microscopes and were making important discoveries with them. These were much more similar to the microscopes in use today. Thus, although Leeuwenhoek is sometimes called "the inventor of the microscope," he was no such thing.

However, because of various technical difficulties in building them, early compound microscopes increased the problem of chromatic aberration and were not practical for magnifying objects more than about twenty or thirty times natural size. A master lens grinder, Leeuwenhoek made microscopes consisting of a single, high-quality lens of very short focal length. Together with his naturally acute eyesight and great care in adjusting the lighting where he worked, enabled him to build microscopes that magnified over 200 times, with clearer and brighter images than any of his colleagues could achieve. What further distinguished him was his curiosity to observe almost anything that could be placed under his lenses, and his care in describing what he saw. Although he himself could not draw well, he hired an illustrator to prepare drawings of the things he saw, to accompany his written descriptions. Most of his descriptions of microorganisms are instantly recognizable.

Leeuwenhoek kept his microscopy techniques a secret, and they are still much of a mystery. In his life he grinded more than 400 lenses, of which most were very small, some of them not larger than a needle’s head. They were mounted between two thin brass plates riveted together. A large collection of his lenses was bequeathed to the Royal Society of London, and they have been found to have magnifying degrees of 50 upwards. The best that survives of his lenses, in the University Museum of Utrecht, has a linear magnifying power of 270 times and a resolving power of 1,4 µ.

From his recorded observations it may be surmised that he must have actually made lenses of 500 power, with a resolution of 1,0 µ. In order to observe phenomena as small as bacteria, Leeuwenhoek must have employed some form of oblique illumination, or other technique, for enhancing the effectiveness of the lens, but this method he would not reveal. We know, however, that he used a reflector of polished copper. Whatever his methods, Leeuwenhoek’s instrument were not surpassed until the nineteenth century.

Leeuwenhoek has been condemned for failing to link microorganisms to transmissible diseases. It is argued that, in his appreciation of the wonder of microbes in the firmament of living organisms, Leeuwenhoek was closer to a true appreciation of their role in the conduct of a global ecology than much contemporary science. He described Giardia lamblia i his own faeces.

Honours

Leeuwenhoek’s scientific achievements were recognised during his lifetime by both his colleagues and the public. In 1680 he was elected a fellow of the Royal Society of London; in 1699 he was appointed a correspondent of the Paris Académie des sciences; and in 1716 the Louvain College of Professors awarded him a silver medal. In addition to the pension that it gave him, the municipality of Delft made him special awards upon the publication of several of his books.

The dramatic nature of his discoveries made him world famous, and he was visited by many notables in his former dry-goods shop. The increasing number of learned and eminent visitors from several countries eventually caused Leeuwenhoek to demand introductory letters; his guests included kings and princes, among them James II of England, Frederick the Great of Prussia, Elector August II of Saxony, and the Grand Duke Cosimo of Tuscany. Peter the Great of Russia in 1798 visited him during his great European journey. On that occasion Leeuwenhoek demonstrated circulation in the capillaries of an eel to the tsar.

In his old age, Leeuwenhoek became a legend; to his displeasure, his fellow townsmen reverently referred to his as a magician.

He dictated two final letters to the Royal Society 36 hours before his death at age 90. The first ever presentation of a bacteria can be seen on a drawing by Leeuwenhoek in the Philosophical Transactions of the Royal Society for 1683.

In 1932, in commemoration of the tercentenary of his Leeuwenhoek’s birth, the Royal Academy of Sciences of Amsterdam and the Nederlands Tijdschrift voor Geneeskunde undertook a complete critical edition of all his letters.