The identity of the first person to see sperm through a microscope has been a matter of dispute. A strong claim lies with that pioneer of the microscope, the Dutch scientist Antony van Leeuwenhoek (1632–1723), although it was fiercely contested at the time by another microscopist, Nicolas Hartsoeker (1656–1725). Either way, it seems certain that sperm were first seen through a microscope in the early or mid-1670s. Leeuwenhoek did not help his case by announcing his many findings in letters to his friends, who would broadcast the news without necessarily acknowledging their source. This seems to have been the case with sperm. It appears that Leeuwenhoek described sperm in a letter to a friend, the distinguished poet and polymath Constantijn Huygens (1596–1687), who passed the letter on to his equally distinguished but more technologically minded son, Christiaan (1629–95), who would have had more of an idea of what to make of new discoveries made with the aid of the microscope.
Seventeenth-century Holland was synonymous with fine optics in the same way that modern Switzerland is associated with expensive watches. The first telescopes were probably made in Holland, and Galileo used a Dutch telescope – or at least one of Dutch design – to discern the moons of Jupiter in 1610. Less well known is that Galileo may have had a simple microscope at about the same period. The word ‘microscope’ was coined in 1625, and microscopy became the fashion that no well-connected Dutchman could afford not to follow. Christiaan Huygens was as well acquainted with microscopes as were Malpighi or Highmore, although his fame lay in the discoveries he made with his telescope. By the time he received Leeuwenhoek’s letter from his father, Christiaan could claim several important astronomical discoveries, including that of Titan, the largest moon of the planet Saturn.
Christiaan announced the discovery of sperm in 1678, without any attribution to Leeuwenhoek, in a discussion of animals said to arise spontaneously, from putrefaction. In his report, Christiaan describes animals found in semen that are
formed of a transparent substance, their movements are very brisk, and their shape is similar to that of frogs before their limbs are formed. This discovery, which was made in Holland for the first time, seems very important, and should give employment to those interested in the generation of animals.1
The closer you read this important-sounding announcement, the less it seems to say. On the one hand, it suggests that sperm are complete yet very small animals, no different from the other small animals that microscopists were discovering, in pond water, for example. At the same time, the announcement suggests that sperm might be of interest to those studying generation – or, then again, they might not. The role of sperm in generation was still not as clear cut as the role of the egg.
Many of the early microscopists were physicians or anatomists. For a doctor, at a time when infestations and infectious diseases were common and the importance of sanitation was unsuspected, it would have been quite natural to look at sperm and think they were no more than another case of worms. That flies, worms, and so on were spontaneously generated from diseased or putrefying matter was a seemingly obvious deduction in a world in which the stench of decomposition was familiar to everyone, and was assumed to be true by such authorities as Christiaan Huygens. No wonder then, that when sperm were first discovered, they were almost automatically assumed to have been interlopers – parasites – with, perhaps, no direct relevance to generation.
This is why the first impulse of many of sperm’s earliest observers was to classify them in their own right, as something quite other than the animals they appeared to inhabit. In 1700, the French physician Nicolas Andry de Bois-Regard published a large work entitled De la génération des vers dans le corps de I’homme (‘An Account of the Breeding of Worms in Human Bodies’), which became a standard work on medical parasitology. One kind of worm had a special place in Andry’s affection – the so-called spermatic worm. Andry’s views exemplify a general ambiguity about the role of sperm which persisted for more than a century: he was quite prepared to believe that sperm played a dual role, as free-living parasites and as carriers of the preformed embryos of organisms. In The Ovary of Eve: Egg and Sperm and Preformation (1997), her sparkling reassessment of preformation, biologist and historian Clara Pinto-Correia suggests that the close association drawn by Andry between infestation and generation would have damaged the prevailing concept of sperm as agents for the spark of human life, and this association would have acted as a strong disincentive to scientists who might have sought in sperm the answers to the great questions of generation.
However, it was clear to Andry and to other observers that sperm were found only in male animals of reproductive capacity and in good health, and that each species had its own variety of sperm. Given this coincidence, some did begin to wonder whether sperm might not be parasites after all, but particles directly concerned with generation. But it was not a simple matter to rule out other possibilities. As early as 1679, Robert Hooke reported the presence of sperm in the testes of a horse, and had failed to find them in immature males; yet he could not discount the idea that sperm were parasites specifically found in the testes of mature males. Because of the ambiguity about the role and nature of sperm – as parasites, as agents of generation, or both – the idea that sperm were organisms in their own right proved an enduring one. As late as 1835, zoologist Richard Owen (1804-92) classified spermatozoa as a distinct order of animal life; the term ‘spermatozoa’ was coined as late as 1827, by the zoologist Karl Ernst von Baer (1792–1876).
The problems of defining the place of sperm in nature dogged the wider acceptance of what came to be called spermism –the sperm-based idea of preformation – that, whatever else they did, sperm acted as the vehicles for the transmission of inheritance, and that all human generations would have been present in the testes of Adam, and not in the ovaries of Eve. These problems were deepened by several issues that had more to do with the image of spermism than its substance.
The idea that sperm, not eggs, might contain the germs of all future generations was taken up by Nicolas Hartsoeker. In a throwaway remark in a 1694 book mostly about optics, he suggested that were we to have microscopes powerful enough, we might find embryos rolled up inside the heads of sperm. Pictures made subsequently of little foetuses rolled up inside sperm heads were only cartoons lampooning this idea – and yet gave rise to the seemingly unshakeable conclusion that Hartsoeker and others had actually made and reported such observations, a legend that has since been perpetuated down the ages – by its own memetic regeneration – as an example of how daft and deluded our ancestors must have been to subscribe to preformationism of any kind, whether based on sperm or eggs. To make matters worse, Hartsoeker’s apocryphal rolled-up foetus was referred to as a homunculus. This word may seem innocuous enough (after all, it only means ‘little man’ in Latin), but it had already been appropriated in the literature of medieval alchemy for a person created artificially, by occult recipes or magic. For example, the famous Swiss alchemist Theophrastus von Hohenheim (1493–1541), usually known as Paracelsus, reported a recipe for making homunculi that required a mixture of human semen, human blood and horse dung to be left to putrefy for more than a month, after which the blind stirrings of the homunculi might be observed. No true science of the Enlightenment could retain any shred of credibility if forced to bear the embarrassment of such medieval stenches.
The final knell for spermism was based more on ethics than on science, in particular the propriety of working with human semen as a biological material. Given that masturbation was proscribed by scripture, early microscopists were sometimes less than clear about whose semen they had used for their observations. This reticence became near-total silence after 1715, when an anonymous pamphlet entitled Onania, detailing the evils of masturbation and its fearful consequences, achieved wide currency in Europe. After that, no serious discussion of spermism was possible. In 1722, even such a leading exponent of spermism as Hartsoeker publicly renounced this view.
The fading of sperm-based preformationism after 1715 left the field clear for a resurgence of the older idea that preformed embryos were to be found in eggs. This ovism – which ran counter to spermism and in parallel with it – was to become the predominant theory of generation for the rest of the eighteenth century, thanks to three colossal yet complementary talents: a dour Protestant physician named Albrecht von Haller (1708–77); the precocious French entomologist Charles Bonnet (1720–93), discoverer of the phenomenon of parthenogenesis, who went on to become the leading theorist of preformationism; and Lazzaro Spallanzani (1729–99), an urbane Italian priest, arguably one of the finest experimental scientists who ever lived. They were a band disparate in background, temperament and talent, yet their work turned preformationism into a mature discipline, grounded in well-honed theory, supported by rigorous experiment, and unassailable except by developments in experimental science as opposed to changes in theological dogma or ethical outlook.
Haller, the eldest of the three, was widely admired as a physician, although he wasted much energy in fruitless worry – about money, social status, and trying to reconcile his findings with his strict Swiss Protestant outlook. Haller had been a student of the Dutch physician Hermann Boerhaave (1668–1738), who favoured spermism but was sufficiently broadminded to consider all views. This generous spirit made Boerhaave both popular and respected, and his mildly spermist views were initially adopted by his adoring student, Haller, who might have persisted in this view but for the biological bombshell of the 1740s – the discovery of the phenomenon of regeneration.
In the early 1740s, a relation of Bonnet’s named Abraham Trembley (1710–84) published his experiments on the freshwater polyp, a microscopic creature with a small stem and tentacles, yet curiously mobile. Opinion was divided on whether the polyp was an animal or a plant. As part of a programme to investigate this, Trembley sliced the creatures into pieces and found that entire, new polyps formed from the fragments. The power of regeneration in such a modest corner of creation earned this organism a powerful name: Hydra, after the horrific many-headed monster of Greek myth which startled Hercules by replacing each severed head with two new ones. Trembley’s work caused a sensation, and before long other zoologists were busily testing the regenerative properties of various creatures. Regeneration poses an obvious difficulty for preformation. If many complete creatures can be regenerated from a single individual that has been fragmented, the role of the preformed germ is called into question. Questions were indeed raised in Haller’s mind, and he started thinking along epigenetic lines. Even though there was no mechanism to explain the origin of form from formless matter, the bare facts of regeneration showed that preformationism was in trouble.
Haller’s dalliance with epigenesis did not last. In the 1750s his own studies on chickens and eggs, in the style of Malpighi or Fabricius, led him firmly and finally to preformationism. Close study of the membranes within the egg as it developed convinced him that the yolk was continuous with the skin and gut of the foetus, and that since the yolk could be found in unfertilized eggs, then so too must the embryo.
During Haller’s reconversion to preformationism he received a fan letter from Charles Bonnet, who was making a name for himself as a talented scientist with sympathies for preformationism. Haller – flattered, naturally – wrote back immediately, starting a lifelong correspondence and friendship. Bonnet’s career had begun in earnest just a few years earlier, after he had written to the distinguished entomologist René-Antoine Ferchault de Réaumur (1683–1757), a polymath in the occasional employ of King Louis XIV. Bonnet had read Réaumur’s book Mémoires sur les insectes, tried a few of the suggested experiments, found them wanting, and sought to communicate with the author. Réaumur, like Haller, was warmed and charmed by the enthusiasm of this bright young man, and under Réaumur’s influence Bonnet made a careful study of aphids. In so doing he discovered what looked to be sure and certain evidence for preformation. The discovery catapulted Bonnet, just twenty years old, to scientific stardom.
As long ago as 1677, Leeuwenhoek had reported to the Royal Society in London that female plant lice, or aphids, could reproduce without males. We now know that aphids, as well as many other animals, can dispense with sexual reproduction and reproduce clonally – that is, they can make genetic copies of themselves. The offspring of this process are always female, and the process itself is called parthenogenesis. The advantage of parthenogenesis is that it allows a species to reproduce with great speed to take advantage of an ephemeral or temporary resource; aphids are very good at this (all the better to consume your roses). What Bonnet found – and his findings remain valid today – was that aphids are so rushed, it seems, that entire generations are telescoped together: the body of a single female may contain the bodies not only of the next generation, but the germs of her grandchildren, even before her own children have been born. Female aphids are living Russian dolls, and offered graphic proof of preformation.
Aphids are tiny, and the strain of trying to discern generations of progeny concealed within their minute bodies undoubtedly contributed to Bonnet’s early blindness. This, and his increasing deafness, confined Bonnet to a life of the mind – an enforced concentration which led to his writing a book, Considérations sur les corps organisés. Published in 1762, it marked the high-water mark of preformationism.
Bonnet based preformationism on, essentially, two hypotheses. The first stemmed from his observations of aphids, from which he generalized that the bodies of organic beings had stored within them the germs of all beings to come. These germs were not exact miniatures of adult creatures, but a formulation of what Bonnet called their ‘essential parts’, which would enlarge and become more organized through the process of development. The second hypothesis was rather more fanciful. Bonnet called it dissemination. He supposed that it might not be possible to encase the multitude of future generations in a single organism, and instead that the invisible germs of species might be disseminated throughout air and water, waiting to meet fully formed bodies of their cognate species in which they might lodge and grow.
Bonnet’s justification of preformation rested on the seeming impossibility of understanding the initial formation of organisms epigenetically, that is, as if from nothing. Therefore, he reasoned, organisms must have existed for all time (or at least since the divine Creation), either as organized bodies or as germs. In hindsight, Bonnet’s notion of essential parts is an exact operational description of the genome, for, in bald terms, the genome can be thought of as the representation of the essential parts of an organism, whose full expression becomes manifest only through development. Crucially, the genome itself is passed down from generation to generation, and in some sense all future generations might be predicated on the genome of our ultimate ancestor, even if the precise form of each generation is conditioned by chance and circumstances rather than divine decree at the moment of Creation. Bonnet’s idea of essential parts expresses a continuity of inheritance we now appreciate in the genome. His complementary idea of dissemination, although less justifiable in modern terms, resonates at least emotionally with the concerns of modern environmentalists about how genes might float about in the air, waiting for an appropriate organism to settle in.
Bonnet also had a way of accommodating a recurrent criticism of preformation, that of ‘sports’, or creatures born with obvious defects such as withered limbs or cleft palates. Surely, detractors asked, no beneficent Creator would have wished disability on a hapless and innocent infant at the very moment of Creation? Bonnet countered that if all generations had been encapsulated in the same moment by the Creator, then there is no reason why all individual variations, including monstrosities, could not have been so accommodated.
Among Bonnet’s correspondents was the priest Lazzaro Spallanzani. Spallanzani’s father had wanted him to study law. For a while Spallanzani complied, but he was forever distracted by the more exciting prospects offered by the natural world. Eventually he became a priest, and used his ecclesiastical income to fund his passion for nature. Whereas most naturalist clerics were content to observe and make notes, Spallanzani went further: he manipulated nature, created hypotheses and designed experiments to test them.
In his most famous experiments, Spallanzani sought to discover whether semen needed to come into direct contact with eggs in order to fecundate them – that is, to stir them into life. Following the work of Fabricius and others, it was thought that semen had no direct role in fecundation but acted as a source of energy or ‘spirit’ – Swammerdam’s aura seminalis – to jolt the egg into development.2 As an experimentalist, Spallanzani saw that the existence of this elusive fluid might be investigated. At Bonnet’s suggestion, Spallanzani chose to do his experiments with frogs, for the simple reason that in the wild male frogs shed semen on the eggs immediately after they are laid by the female. This means that both eggs and semen are accessible just before fertilization takes place, and the effects of the proximity of semen on the properties of eggs can be examined directly. Spallanzani showed unequivocally that semen and eggs had to come into direct contact for the process to work. He proved this in the breach, and in the breeches, by showing that fertilization was impeded if the male frogs were engaged in courtship while wearing little taffeta trousers of Spallanzani’s own design.
In another experiment, Spallanzani showed that eggs could be fertilized by frog semen diluted in water to various degrees. But when a mixture of semen and water was progressively filtered to remove any particulate matter, the filtered fluid became less and less potent. If, however, the sediment, deposited on the filter, were immediately redissolved in water, the mixture was as potent as ever.
To modern eyes, the conclusion is obvious: the sediment removed by the filter contains agents necessary for fertilization, and it is at least possible that these agents are sperm, given that sperm are found in the filter and not in the strained and impotent fluid. However, Spallanzani was convinced that the germ of the tadpole was present in the unfertilized egg of the frog; that semen was merely a substance which activated the egg; and that any sperm to be found in the semen were irrelevant and parasitic contaminants. Spallanzani supposed that sperm, as parasitic worms, could infect a new host at a very early stage of development, and might even infect unfertilized eggs. ‘It is rather alarming’, comments Elizabeth Gasking, ‘to think that had Spallanzani really seen the penetration of the eggs by the spermatozoa he would have regarded it as a confirmation of this hypothesis.’3
Spallanzani outlived both Haller and Bonnet, and his death in 1799 was soon followed by that of preformation itself. In the first few years of the nineteenth century, the Quaker meteorologist and chemist John Dalton (1766-1844) developed his atomic theory of matter. Derived from a wealth of data on the behaviour of gases and chemicals in general, Dalton’s theory showed that matter was not infinitely divisible, and that there was a lower limit on size. Although Dalton was not a biologist, the implication of his ideas on preformation was clear: microcosmos could not forever give way to microcosmos, allowing for multitudes of generations to be telescoped together down to some arbitrary degree of smallness.
Of perhaps more direct relevance to biology – and the fall of preformationism – was the development of cell theory, which came into flower in the early nineteenth century after a long dormancy. Nowadays we are accustomed to the idea that all living things large enough to see with the naked eye are made of a large number of tiny bodies called cells. Human beings consist of trillions of them, most highly specialized to perform certain functions such as nervous transmission or muscular contraction.
Leeuwenhoek saw cells perhaps as long ago as the 1770s. Indeed, sperm are individual cells in the sense that we now understand the term. In the simplest microscopes, cells are seen as featureless blobs, and this is undoubtedly how Leeuwenhoek would have observed them. Rapid advances in microscopy revealed that many cells each contain a smaller, concentrated body now known as the nucleus. The nuclei of plant cells may have been observed in the 1780s, although it was 1833 before the presence of nuclei was documented as a consistent feature of cells. More modern techniques have revealed great complexity within the nucleus, in the other matter, or cytoplasm, that surrounds it, and in the membrane that forms the boundary of the cell.
Most living things live their lives entirely within the frame of a single cell. Pond organisms such as paramecia and amoebae are unicellular, and creatures such as these would have been among the first organisms seen by the earliest microscopists. Leeuwenhoek and his colleagues, on first observing cells, would have had no reason to think that living matter is normally subdivided into legions of tiny compartments – and why should they? To them, paramecia and amoebae were tiny animals, very much alive despite their smallness. According to Aristotle (and to common sense), the status of bodies as living things implied the presence of fully functional systems of organs: a heart, a liver, and so on. When they were discovered, spermatozoa were also supposed to have complete internal organs – even if the head of each sperm did not contain a tiny homunculus. It could not possibly have occurred to a seventeenth-century anatomist, armed with a simple microscope, that the organs of higher animals are composed of cells, each one a discrete living entity, and that it was possible for animals to lead busy, active lives even in the unicellular state, without what we would think of as distinct tissues and organs.
The idea of cells as units of life that were fundamental rather than incidental started with studies of the microscopic anatomy of plants. Hooke, on first noticing regular spaces in slices of cork, named them ‘cells’ because they reminded him of the discrete, austere rooms of monks. The cells of plants are in general very much larger than those of animals, and have more definite boundaries: stiff curtain-walls of cellulose, rather than the soap-bubble membranes that serve in the cells of animals. This makes plant cells much easier than those of animals to see in a simple microscope. Cells were initially regarded as curiosities of plants, of no relevance to the animal world, and there was then no reason to suspect that cells were any more than structural components, or had anything to do with the creation of life.
With time, more powerful microscopes, and chemical techniques for staining cells and nuclei to make them easier to see, it became evident that all living things – animals as well as plants – were very largely composed of cells, and that these cells were not simply structural elements, like bricks. In 1839 two German biologists, Theodore Schwann (1810–82) and Matthias Schleiden (1804-81), declared that cells were the fundamental particles of organisms, in the same way that atoms were the elementary particles of matter. All creatures were made out of cells. Either they consisted of a single cell, as with paramecia and amoebae, or they were made of many cells stuck together, as in humans.
Schwann and Schleiden’s idea came to be known as the cell theory. It did not change the world overnight, because it threw up a number of other issues in its wake. What were cells made of, and what was their origin? The answer to the first question led to the development of the idea of protoplasm (the jelly-like substance from which cells are made) as the fundamental state of living matter, and yet it was unclear how protoplasm originated from the inanimate world – if, indeed, it did. The answer to the question of where cells came from proved both frustrating and inedifying: cells came from other cells. Organisms do not grow by accumulating cells from some external source, but by making more cells from within. Cells were found to be capable of dividing into two, and dividing again, each daughter cell growing until it was the size of the original, and then dividing further – or specializing to become a component of brain, or liver, or muscle, or bone. This division – or fission – was what passed for reproduction in single-celled creatures such as amoebae.
The theory of cells as fundamental units of life put paid to the stupefying infinities of preformation by establishing a lower bound on organic smallness, but it did not in itself solve the problem of the origin of form. Cell theory still left unbridged a great divide between the simplest cell and the most complex non-living matter, to the extent that protoplasm was thought to be a distinct and special substance, containing a vital spark unseen in the world of the inanimate. Nevertheless, cell theory advanced biology by finally opening the way to a theory of generation which did not sidestep the issue by booting it back to the Creation, as Bonnet and Spallanzani had done. If plants and animals are made of collections of cells, each kind more or less specialized for a certain function, could there not be cells that were specialized for generation? Once this realization dawned, spermatozoa were seen in an entirely new light, as cells of the host body, specialized for the task of generation.
As the single-celled representative of a multicellular male, it made sense that the sperm should have a unicellular, female counterpart. In one sense, Harvey, Swammerdam and Malpighi had been right all along in their insistence on ova as the primary seat of generation. But the absence of cell theory, and of microscopes consistently powerful enough to resolve animal cells with clarity, left them without the tools necessary to draw a distinction between unicellular eggs on one side, and multicellular embryos on the other, and without which both were regarded as indefinite ‘primordia’.
The decisive result came in 1828, when von Baer, a year after he coined the term ‘spermatozoa’, described the human ovum as a single cell, an austere room in which no space could be found for preformed germs – neither physically nor conceptually. It became clear that all ova are single, indivisible cells, whether they are very small, like the ova of human beings or of the deer studied by Harvey; or very large, like the eggs of hens studied by practically everyone since antiquity. Once that was realized, the search for nested generations of preformed embryos was finally exposed as futile. Harvey was right – form emerges from nothing, and everything comes from the egg.