An Amazing 10 Years: The Discovery of Egg and Sperm in the 17th Century
Author’s address (for correspondence): M Cobb, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. E-mail: email@example.com
The scientific identification of the key components of sexual reproduction – eggs and sperm – took place during an amazing decade of discovery in the 1660s and 1670s. The names of many of the people involved are now forgotten, and yet their work, and the difficulties they faced and the conflicts they endured, resonate strongly to the present day. Despite this period of innovation, the respective roles of egg and sperm remained unclear for another 170 years. Why did this take so long? And what did people think before these discoveries? By tracing the contours of this major milestone in human knowledge, we can also gain insight into our current knowledge, and the boundaries we may be unwittingly trapped by.
The 17th century discovery of the role of egg and sperm in reproduction can be traced to two letters, written 7 years apart, each by a remarkable man who is largely forgotten today. Those letters heralded an amazing decade of discovery that eventually shaped the way we now understand life.
In April 1665, Melchisedec Thévenot (c.1620–92), a French patron of the sciences, wrote to his friend Christiaan Huygens (1629–95), a Dutch mathematician and astronomer: ‘We took the opportunity provided by the cold of recent months and applied ourselves to dissections and to investigating the Generation of animals’ (Thévenot 1665). The ‘we’ referred to two of Thévenot’s protégés, the Dutchman Jan Swammerdam (1637–1680) and the Dane Niels Stenson (‘Steno’) (1638–86). This was the start of a process of discussion, dissection and experimentation that would soon lead Swammerdam and Steno to the conclusion that all animals – including humans – come from eggs.
The second letter was sent 9 years later, in April 1674. It was written by Henry Oldenburg (c.1615–77), the German secretary of the Royal Society (Hall 2002) and was sent to a Delft draper, Leeuwenhoek (1632–1723). In the letter, Oldenburg asked Leeuwenhoek to use his microscope to study semen, saliva, chyle, sweat and other bodily fluids. With this inspiration, in 1677, Leeuwenhoek would make one of the most stupendous discoveries in the history of science: the observation of spermatozoa.
To understand why these two letters were so important, we need to unlearn all that we know about reproduction, beginning with that word. The term ‘reproduction’ was first introduced by Buffon in 1749 (Roger 1997). Up until then, people spoke about ‘generation’, and this was taken to include both how organisms grow apparently from nothing, and how male and female contributed to new life (Cole 1930).
Although the simple answer to the question ‘where do babies come from?’ is fairly obvious – they come out of the female vagina – arriving at an explanation of how the baby got there in the first place proved quite difficult (Cobb 2006a). It seems very likely that early human populations did not know that intercourse led to babies. There are number of reasons for thinking this. Firstly, how could they know? The link between intercourse and pregnancy is not at all clear or immediate – people can easily have intercourse without the woman getting pregnant and the first signs of pregnancy may not be seen for weeks after the act. This surprising supposition is supported by the widespread existence of matrilineal communities in hunter-gatherer societies, which suggests that men’s role in generation was uncertain.
It is possible that the domestication of animals provided the key. In all domesticated animals, mating takes place only during oestrus (Potts and Short 1999). Placing the animals together to allow mating would have been an important step in domestication and in ensuring the survival of the animals and of the human group that owned them. According to an un-testable hypothesis, this could have had two inter-linked consequences: it may have revealed the role of male animals (and, by extension, of men) in generation, and also created an economic surplus. And once wealth became widespread, the question of paternity became fundamental for society.
Aristotle, Hippocrates and Harvey
Probably the most influential thinking on generation came from the Greeks. Aristotle divided all animals into two kinds – the ‘bloodless’ animals (insects and so on), which generated spontaneously, and the remainder, in which mating played a decisive role. For Aristotle, the woman (or the female animal) provided the ‘matter’ for the baby, through her menstrual blood, while the male’s semen gave that ‘matter’ form, like a seal stamping hot wax. Another analogy, which echoes down to the present day, was that semen was like a seed (‘semen’ means ‘seed’), which was sowed on fertile ground. Although the Roman physician Galen adopted Hippocrates’ view that there were two ‘semens’– one male, the other female – acceptance of this theory was hampered by the fact that it was not possible to identify the female semen, and Aristotle’s view predominated. It was also echoed in the major monotheistic religions of the west (Judaism, Christianity and Islam), which all stated that the male semen was the primary component. On the other side of the planet, Chinese thinking about generation focused on the ‘generative vitality’ of each sex, defined in terms of the energy flows of organ networks, rather than on particular structures (Furth 1999). On a world scale, therefore, there was little agreement about how generation took place or about how each sex contributed.
In the West (including the Arab world), the ideas of Aristotle and Hippocrates dominated thinking about generation for over 1500 years. The first systematic attempt to explore the problem was made by William Harvey (1578–1657) in his 1651 book De Generatione Animalium (On the generation of animals) (Harvey 1651). Harvey was convinced that the ‘egg’ was fundamental to generation, although what exactly he meant by ‘egg’ is unclear. In the 1630s, Harvey dissected red deer during the rut and tried to find changes in the females’‘testicles’ (as ovaries were then called). But he could find no changes, nor any sign either of semen or of an ‘egg’ in the uterus (Short 1978).
Bemused by his failure, Harvey concluded that new life was produced in the uterus following coitus in the same way that imagination and appetite are produced in the brain and that the female’s ‘testicles’ played no role at all. In the absence of any better evidence, Harvey fell back on something that looked like Aristotle’s ideas: eggs were generated like thought, while semen had some indefinable action at a distance. Even one of the greatest minds of the age, steeped in the new scientific method that used experimentation rather than logic, could not crack the problem of generation.
Women have Eggs
Nevertheless, within 25 years of the publication of Harvey’s book, thinkers throughout Europe were convinced of the ‘egg theory’ and were certain that all female animals – including women – produced eggs (Short 1977). This momentous change came about because of the inspiration and inquisitiveness of Melchisedec Thévenot, a one-time French ambassador who had his own small group of scientists and experimenters (Cobb 2006a). During a visit to Leiden University in the Dutch Republic, Thévenot had met some brilliant young medical students, including Swammerdam and Stenson (‘Steno’), whom he invited to his house outside Paris and encouraged to start thinking about generation. Thévenot wanted to show the superiority of the experimental method as against Descartes’ recently published theoretical approach to generation, which was based entirely on Aristotle’s ideas.
Although neither Swammerdam nor Steno made any decisive discoveries in their months with Thévenot, from mid-1665, they both became focused on trying to understand generation. Swammerdam returned to the Dutch Republic and initially focused on the generation of insects (he was a keen entomologist) and through careful observation and dissection, he came to the radical conclusion that ‘all animals come from an egg laid by a female of the same species’ (Swammerdam 1669). Given that nearly 2000 years of Aristotlean thought, plus a great deal of casual observation, suggested that insects appeared from nowhere, Swammerdam’s statement – complete with empirical proof – was remarkable.
Swammerdam’s work appeared the year after an experimental study by the Italian physician Francesco Redi (1626–97) which concluded that insects came from eggs, with the striking exception of gall wasps which he thought were spontaneously generated (Redi 1668). It seems probable that Redi was indirectly inspired by Thévenot, too, as in 1666 Steno had travelled to Florence, where Redi was the physician to the Tuscan court, and the two men became close friends. While in Florence, Steno published what turned out to be his most influential scientific work, Elementorum Myologiae Specimen (A model of elements of myology), in which he accurately described the function of the muscles, using both dissection and mathematical models (Steno 1668). In an additional part of this work, Steno incidentally founded the science of geology, suggesting that the ‘vipers’ tongues’ that were found in rocks and which looked like sharks’ teeth were in fact the teeth of sharks that had been stranded on hilltops after the Flood. Most decisively, Steno included a brief nine-page description of a dissection of a viviparous dogfish. Primed by his anatomical dissections in Leiden, and by discussions with Thévenot, Steno drew a comparison between the anatomy of the viviparous dogfish and of egg-laying rays: ‘having seen that the testicles of animals contain eggs, and having noticed that their uterus opened into the abdomen like an oviduct, I have no doubt that the testicles of women are analogous to the ovary’ (Steno 1668).
The Race to Find Proof
This simple but revolutionary statement – which had no proof to back it up – soon caused consternation back in Leiden, where Swammerdam and Professor Van Horne (1668) had already set out about trying to identify eggs in the ovaries of dead women. Van Horne, like his former pupil, Steno, had come to the conclusion that the vesicles in the woman’s ‘testicles’ were, or contained, eggs. Together with Swammerdam, van Horne even showed that the vesicles in the ovaries of a cow turned white when boiled, just like a chicken’s egg. But it now appeared that their friend Steno had published the discovery first. Their only hope was to provide what Steno’s brief account lacked: proof. A few months later, van Horne published a brief summary of his discoveries (Van Horne 1668), but the major work that he promised himself and Swammerdam never appeared. In January 1670, van Horne died of a plague that swept through Leiden, killing five of the University’s 15 professors (Luyendijk-Elshout 1965).
After van Horne’s death, Swammerdam continued their work, but soon became aware that someone else was studying the same problem: his one-time student friend, de Graaf (1641–73). In May 1671, following a brief meeting at which it became apparent that they were both approaching completion, de Graaf hastily published a brief outline of his work, in which he summarized his view of how ‘eggs’ in the ‘testicle’ became ‘fertile’ through the action of the ‘seminal vapour’ rising up from the uterus via the Fallopian tubes (De Graaf 1671). In December 1671, Swammerdam riposted by publishing a single sheet drawing of his dissection of the human ovary and the uterus, which he sent to the Royal Society in London (Swammerdam n.d.). Although neither man had yet provided any clear evidence that human ovaries contained eggs, they were now on a collision course.
De Graaf apparently won the race when, in March 1672, he published his brilliant De Mulierum Organis Generationi Inservientibus Tractatus Novus (New treatise concerning the generative organs of women) (De Graaf 1672; Jocelyn and Setchell 1972). Although the book contained dissections of humans, rabbits, hares, dogs, pigs, sheep and cows, its decisive part was a section on rabbit mating and pregnancy. Here, de Graaf referred to the follicles or their contents as eggs, and gracefully gave his former teacher, van Horne, the credit for this discovery, pointing out that Steno had merely said that ovaries contained eggs without identifying them. Above all, de Graaf used careful experimental dissection to show that in rabbits the follicles reddened and ruptured following mating and that 3 days after copulation, small spherical structures could be found in the Fallopian tubes. De Graaf emphasized that the number of these spheres was generally identical to the number of ruptured follicles and that it never exceeded them. Because mating induces follicular rupture in the rabbit, de Graaf mistakenly suggested that the same thing must happen in women, which would imply that virgins would show no ruptured follicles. Finally, like Harvey, de Graaf looked for signs of semen in the uterus and Fallopian tubes, but could find none. He concluded that only a ‘seminal vapour’ reached the eggs and fertilized them. Through his experimental work, de Graaf showed the power of the scientific method, and also demonstrated that mammals – including women – have eggs.
In response, in May 1672, Swammerdam published his own account of human generation, Miraculum Naturae, sive Uteri Muliebris Fabrica (The miracle of nature, or the structure of the female uterus) (Swammerdam 1672a,b). This contained no experimental studies, merely a great deal of dissection, some of which was highly pertinent, as it showed that virgin women also have ruptured follicles. Swammerdam also explored the very real problem of how the fluid in the follicle – which he felt was the egg – could move from the ovary across into the Fallopian tube. But the central theme was Swammerdam’s claim that van Horne had been the first person to accurately describe the female reproductive organs and that he, Swammerdam, had first suggested that the egg was in the follicle. The book closed with a polemical appendix, in which Swammerdam sneered at the quality of de Graaf’s drawings and even at the fact he had studied ‘rabbits and brute animals’ rather than humans, thereby inadvertently showing that he had entirely missed the point of de Graaf’s work. Swammerdam dedicated his book to the Royal Society, and sent it off to London, followed by a beautifully preserved human uterus, along with twelve other items of genital anatomy, both male and female. Above all, Swammerdam asked the Royal Society to adjudicate on who had the priority in stating that women have eggs.
Less than a year later, as the Dutch Republic was wracked by a murderous invasion by the French in the opening battle of a war that lasted 6 years, de Graaf produced a blistering response to Swammerdam, Partium Genitalium Defensio (Defence of the genital parts) (De Graaf 1673a,b). This savage polemic – written in the immediate aftermath of the death of de Graaf’s month-old baby son, Frederick – reproduced letters between de Graaf and Swammerdam, quoted conversations and made accusations that far exceeded anything seen in a modern row on the internet. De Graaf flatly denied that he knew that Steno had ever published about eggs (the two men had in fact corresponded on the question several times), and accused Swammerdam of plagiarism and of piling ‘lie upon lie’. De Graaf then sent what he admitted was a ‘not very polite’ book to the Royal Society and, like Swammerdam, asked them to judge who had priority.
In response to the pleas from the excitable Dutchmen, the Royal Society set up a three-man committee to deal with the fractious dispute. When the committee eventually reported, in October 1673, they decided that neither de Graaf, nor Swammerdam, nor van Horne had been first to discover that women have eggs. That honour, they stated, went to Steno. This verdict turned out to be completely pointless. A week before the committee completed its work, de Graaf died, aged only 32. Swammerdam wrote an immediate reply, of which no trace remains, and then never referred to the matter again. Steno, meanwhile, was on the verge of abandoning science to become a Catholic bishop, and there is no evidence he ever heard of his ‘victory’. Even the Royal Society seems to have lost heart, for the report was not published for more than 80 years (Birch 1756–7). Ironically, history has adopted a very different view: the follicles are now known as Graafian follicles and the part played by Steno, Swammerdam and van Horne is forgotten to all but a handful of historians.
Whatever the ins and outs of the priority dispute, the key issue was that by the mid-1670s, the ‘egg theory’ came to dominate. In 1679, the French scientific publication Journal des Sçavans wrote: ‘The view that man, as well as all other animals, are formed from eggs is something that is now so widespread that there are hardly any new philosophers who do not now accept it’ (Anonymous 1679). However, even as the ink was drying on the page, an amazing new discovery was challenging that view, and would once again throw the scientific community into turmoil.
Enter the Sperm
When Reinier de Graaf sent his polemical book to the Royal Society in April 1673, he included a report which a friend of his, ‘a certain very ingenious person named Leeuwenhoek, has achieved by means of microscopes’ (De Graaf 1673a,b). Leeuwenhoek’s brief letter included descriptions of a bee sting, a louse and a moss. This was the beginning of a long relationship between Leeuwenhoek and the Royal Society, which spanned the next 50 years and consisted of nearly 200 letters from the Dutchman (Dobell 1932).
Unlike de Graaf, Steno and Swammerdam, Leeuwenhoek (he later adopted the prefix ‘van’ as an affectation) was not academically trained. He was a draper, who had begun making his own single-lens microscopes for reasons that remain obscure (Ford 1985). Although the microscope had been invented at the beginning of the 17th century, they were generally little better than magnifying glasses (Ruestow 1995; Wilson 1995). The power of this instrument was brought to public attention in 1665 when Robert Hooke (1635–1703) published his magnificent book Micrographia, complete with stunning illustrations (the full text of this amazing work can be found on the internet). But Hooke used a compound microscope, which was very difficult to focus, as Samuel Pepys (a member of the Royal Society) discovered when he bought one of these new-fangled devices having been impressed by Hooke’s book (‘the most ingenious book that I ever read in my life’). To his disappointment, Pepys found it very difficult to see anything like the images printed by Hooke, and he felt that the princely sum of £5 10s he had spent on the microscope was wasted (Tomalin 2002).
The single-lens microscope was far easier to construct – it simply involved polishing a tiny glass ball approximately 1 mm across – and it was widely adopted in the Dutch Republic, with some of its main practitioners including Swammerdam, who saw red blood cells and drew the first cell divisions in a fertilized frog egg, and the great philosopher Benedict Spinoza (Ruestow 1995). Leeuwenhoek’s long career as a pioneer microscopist was encouraged by Henry Oldenburg, who published Leeuwenhoek’s first letter in the Philosophical Transactions and then, in 1674, wrote that letter to Leeuwenhoek, inviting him to turn his attention to the composition of various bodily fluids, including semen (Cole 1930). Over the next few years, Leeuwenhoek sent a number of letters to London, amazing his readers with descriptions of tiny ‘animalcules’ in water (these were protists and large bacteria) (Leewenhoecks (sic) (1677). Then, in autumn 1677, a young medical student from Leiden, Johann Ham, brought Leeuwenhoek some pus mixed with semen to examine. Ham claimed that this had been produced by a ‘friend’ who had ‘lain with an unclean woman’. When Ham had looked at the sample under his microscope, he had noticed many ‘animalcules’ in it; alarmed or enthused (it is not clear which), Ham brought the sample to Leeuwenhoek, who confirmed the observation and did the obvious thing: he looked at his own semen. To his amazement, Leeuwenhoek saw there were millions of tiny animalcules thrashing about in the sample. These things were eventually given the name by which they are still known today, and which completely misclassifies them: ‘spermatozoa’– semen animals.
Three months later, Leeuwenhoek dispatched a carefully worded letter to London, written in Latin, insisting that should the society consider it ‘either disgusting, or likely to seem offensive to the learned, I earnestly beg that [it] be regarded private and either published or suppressed as your Lordship’s judgement dictates’ (Leeuwenhoek 1678). In a process that will be familiar to modern readers, the Royal Society then sat on Leeuwenhoek’s earth-shattering discovery. Oldenburg had died a few months earlier, and there was a hiatus in the offices of the Philosophical Transactions. The new editor, Nehemiah Grew, had his doubts about Leeuwenhoek’s findings and eventually wrote back in January 1678 asking him to look at the semen of dogs, horses and other animals. Two further letters from Delft followed with the requested observations, but they merely added to Leeuwenhoek’s previous findings. The lack of urgency suggests that no one at the Royal Society understood why Leeuwenhoek’s discovery was so important (they do not appear to have considered it ‘disgusting’). Leeuwenhoek’s letter was finally published in January 1679, nearly 18 months after his initial discovery (Leeuwenhoek 1678).
Leeuwenhoek’s letter makes clear that he thought that the spermatozoa were merely another example of the ‘animalcules’ he could see everywhere he pointed his microscope. He was much more interested in a tangled mass of tiny vessels which he saw in ‘the denser substance of the semen’. This structure led Leeuwenhoek to claim without the slightest evidence that ‘it is exclusively the male semen that forms the foetus and that all the woman may contribute only serves to receive the semen and feed it’. In other words, Aristotle had been right all along. The exact nature of the mass of vessels remains obscure – Leeuwenhoek later admitted that it was ‘merely accidental’ (Leeuwenhoek 1683). Whatever the case, Leeuwenhoek did not immediately grasp the significance of his discovery of animalcules in semen.
Other people were far more astute than either Leeuwenhoek or the Royal Society, and realized that the animalcules themselves were highly significant. Prior to publication, news got out about what Leeuwenhoek had seen. A few months after Leeuwenhoek’s original observation, in January 1678, Swammerdam wrote a letter to Thévenot stating that he had observed ‘innumerable small worms’ in mouse and dog semen (Lindeboom 1975). Even more importantly, in the summer of 1678 – over 6 months before the Royal Society published Leeuwenhoek’s letter – Huygens printed a brief account of the study in the Journal des Sçavans, which concluded: ‘This latest discovery, which has been made in Holland for the first time, seems to me to be extremely important and will provide material for those who seriously study the generation of animals’ (Huygens 1678).
150 Years of Confusion
A naive modern reader could reasonably assume that this was the end of the matter and that everyone soon realized that egg and sperm were complementary, each containing half of what was necessary to produce new life. Not at all. Firstly, there were technical issues: no one had yet seen a human egg, and would not do so until 1827 (Von Baer 1956). But above all, it was not clear what the discoveries meant. For nearly 150 years, thinking about generation was dominated by either ‘ovist’ or ‘spermist’ views (Pinto-Correia 1997; Roger 1997). Each approach considered that only one of the two parental components provided the stuff of which new life was made, with the other component was either food (as the spermists saw the egg), or an immaterial force that merely ‘awoke’ the egg (as the ovists saw the spermatozoa).
There were many reasons underlying this apparent scientific dead end. For example, in chickens the two elements did not seem to be equivalent at all: there was a single, enormous egg which was apparently passive, while the ‘spermatic animals’ were microscopic, incredibly active and present in mind-boggling numbers. Ultimately, however, the reason why late 17th-century thinkers did not realize what to us seems blindingly obvious – that both egg and sperm make equal contributions to the future offspring – was that there was no compelling evidence to make them appreciate this.
It was not until the 19th century that the requisite combination of evidence and theory came together. To understand the complementary nature of egg and sperm, scientists needed to have a theory that could explain that complementarity. This came in two forms in the early decades of the 19th century (Cobb 2006b). The development of ‘cell theory’ by Schleiden and Schwann gave an explanation for why egg and sperm were equivalent, despite their manifold differences – they were both reproductive cells. The other factor was that realization that heredity had a biological content and that something was inherited, which was contained in egg and sperm, respectively. This development came about through the conjunction of three areas: the work of agro-industrialists such as Robert Bakewell, who carried out massive selective breeding programmes on domesticated animals; the studies by thinkers such as Maupertuis and Réaumur, who explored large and complex family trees in the light of particular characters; and by French physicians who studied the inheritance of diseases (Cobb 2006b). This was finally given form in a monastery in Brno, where Gregor Mendel was just one of many people thinking about the nature of heredity. Oddly enough, by the time that the fusion of egg and sperm was observed for the first time, by Hertwig and Fol in the late 1870s, it was almost an anti-climax. People thought it was obvious. Which in a way, it was, but getting to such a point had been anything but straightforward, and would not have occurred without that exciting spasm of discovery in the 17th century.
Conflicts of interest
None of the authors have any conflicts of interest to declare.