Nicolaas Hartsoeker, depicted here looking rather self-satisfied in a lavish red robe, discovered the sperm. Although it is difficult to comprehend an age in which crude descriptions of the contents of mysterious bodily fluids could conjure paradigm shifts in thought, Hartsoeker and his mentor, Antonie van Leeuwenhoek, were venerable pioneers in optics and the nascent fields of Microbiology and Embryology. In the wake of his remarkable discovery of the seed of life, Hartsoeker described the homunculus – a miniscule character trapped within the head of the sperm, complete with head, heart and limbs, whose delivery to the egg was the impetus for enormous growth. While only a hypothesis for Hartsoeker, other microscopists described actually seeing these tiny homunculi down the microscope. This included van Leeuwenhoek, who went on to examine sperm from over 30 different animal species. The emerging school of preformationist thought used these descriptions as ammunition, claiming that only God could create man, not self-organising biological messes. Even the inevitable problem of infinite regress – that within the gonads of each homunculus lived numerous even more miniscule homunculi – could be stomached on the basis that all of mankind that would ever be once resided in Adam’s testes.

Drawing of a homunculus enclosed within the head of a sperm, by Nicholaas Hartsoeker (1694)

The concept of the homunculus no longer wields any scientific merit, primarily thanks to incredible advances in microscopy, following the pioneering work of van Leeuwenhoek and Hartsoeker. Nonetheless, it is an incredibly powerful image. For one, it epitomises the almost impossible task of envisaging the complex architecture of the human body in anything but its complete and polished form, at least without any clues. We have very strong preconceptions of what we and our peers look like, such that we can rapidly seek out human forms in our surroundings with only minimal information. This astuteness comes back to bite us when we spot faces in clouds, crisps and shrubbery. Acknowledging this tendency, it’s perhaps not surprising that those first examining animal sperm were inclined to project onto the images shapes that they expected to find, resembling those of the adult anatomy. Nonetheless, the homunculus is far from the truth. Preformationism has been surpassed by epigenesis – a framework in which anatomical structures are said to emerge progressively, by gradually adding layers of detail and complexity to a naïve set of parts. Instead of a capsule for transporting miniature humans, the sperm is a vehicle for the delivery of paternal genetic information to the egg. Upon arrival, fusion of the paternal and maternal genomes generates a unique genetic code, which contains the information required to convert a single cell – the fertilised egg – into a human being. To labour the enormity of this task, the human body contains some 37 trillion (37 million-billion) cells, each with an identity in terms of gene expression and behaviour, and knowledge of its spatial position. What’s more, the ordered biological patterns of the body – the arrangements of digits on the hands, the symmetrical distribution of organs on the face or the repetitive distribution of vertebrae along the body axis – emerge with precision in a system that is oblivious to its destination. It is an incredible feat of self-organisation.

So, how does order emerge from disorder? Essentially, this question equates to asking how cells come to know that they are different to their neighbours – how they know to occupy a different position, exhibit different behaviours or adopt a different shape. In the limbs, some cells will secrete a collagen matrix that will become mineralised to form bone, while others will fuse, elongate and cluster to form muscle, and others will generate tubes for transmission of blood. A more graspable context to think about making differences is much earlier in development, when a mass of cells generated through division of the fertilised egg divides into the three primary tissue lineages – the ectoderm will form skin and nervous tissue, the mesoderm muscle, bone and blood, and the endoderm most of the digestive system and viscera. Surprisingly, in many cases, this decision is made quite arbitrarily. For example, in frogs, the orientation of these tissues depends on the position at which the sperm contacts the egg. Meanwhile, in the sea urchin, the boundary between ectoderm and mesoderm/endoderm is placed randomly, through amplification of transient differences in cellular gene expression. In chickens, it involves the orientation of the egg as it is laid. In each case, the initial symmetry breaking event offers spatial information for successive developmental events. Thanks to such decisions, the cells of each embryo know which end is up and which is down, which is back and which is front, and so development can proceed in the right directions. The decision is paramount, but the details are surprisingly of little importance – if the same frog sperm met the same frog egg at a slightly different orientation, the cells that formed the brain might instead have formed the gut. But it doesn’t matter, the product is the same and the frog is none the wiser.

Images of mouse embryos at successive developmental stages, showing progressive formation and refinement of anatomical traits. Taken from: http://www.hhmi.org/research/mechanism-and-function-epigenetic-modifications

More pertinent for Hartsoeker, I imagine, is when a human embryo starts to look human, and what unimaginable shape it has beforehand. The three tissue lineages mentioned before become appropriately placed in the embryo in the process of gastrulation. The endoderm is internalised and forms the primitive gut, which is wrapped in mesoderm and finally a layer of ectoderm. Remarkably, at this point all vertebrate embryos look very similar. Line up a human, cow, salmon, and dolphin and they will all have a similar structure. What this shows is that processes occurring at this stage are difficult to tinker with in evolution, possibly because of their importance for laying out the basic vertebrate body plan. The genes expressed at this point are actually some of the evolutionarily oldest in the genome. From this point on, vertebrates diverge in their structure as species-specific modifications to the common body plan are imposed. While both the human and cow will form similar limb protrusions, the digits will be shaped differently into hands or hooves, and the primitive gut will swell into one or four stomachs. Because detail is added progressively, human embryos will gradually look less like their animal peers and become more aligned with our preconceptions of human form. The image of the homunculus stresses a purity of the human form, and an isolation from the rest of the animal kingdom. In contrast, comparative embryology has reinforced that humans share a developmental and evolutionary heritage with other animals. We are one variant on a theme in a diverse, but united, animal group.