Title page of De Fabrica

The title page of De Humani Corporis Fabrica itself is a work of art, demonstrating Vesalius as the ultimate Renaissance man, strewn with symbolism alluding to Aristotle's philosophy, royal destiny, Christian saints and Roman Emperors (Figure 2). In the centre, we have the great teacher, showman and visionary Vesalius: with a fresh perspective, he is championing meticulous observation and independent analysis over Galen's edicts, which are relegated to guidance. Vesalius's left hand pointing heavenward reminds students they are examining God's greatest creation.^{Reference Cunningham2} It is evident how he has his right hand on the cadaver – he is advocating a much more hands-on approach to anatomy.

Fig. 2. Title page of De Humani Corporis Fabrica.^{Reference Vesalius3}

Rather than looking at Galen and ‘seeing’ his texts in the body, he is inviting us to learn through our own observations. Vesalius had realised Galen did not actually have access to many bodies and performed a lot of vivisection; therefore, much of his work had been presenting animal anatomy as human. Vesalius builds on this to show human anatomy only. Two characters are visible at the front in togas and sandals; these are Aristotle and Galen. Vesalius is putting himself on a par with these greats; he is the next chapter in the advancement of medical knowledge – not just following the classics, but building on them.^{Reference Siraisi6} He is not disrespecting Galen; the skeleton in the middle of the page represents the fact that Galen always used the bones as the starting point in anatomy, a practice replicated by Vesalius.

Further evidence of Vesalius’ ambition is in his dedication of the book to the Holy Roman Emperor. This is evident from the inscription at the top of the page, but also the cadaver. This is a female cadaver, with an incision in her abdomen, bringing to mind a Caesarean section – the method of Julius Caesar's birth.^{Reference Park7} As mentioned earlier, the classics were seen as the absolute pinnacle of civilisation at this time, and the royal family in particular liked to align themselves with the Roman Emperors. Hence, Vesalius is paying tribute to them and presenting himself as the obvious choice for court physician. In the Renaissance, the majority of funding for the arts and sciences came from rich, influential dynasties, and if Vesalius wanted to be thought of as one of the greats of medicine, he had to ingratiate himself accordingly.

Thus, this title page sets out Vesalius’ intention to revolutionise the field of anatomy, which is borne out in the rest of the text, as we will examine in the case of otolaryngology.

The skull pertinent to ENT in De Fabrica

Figures 3 and 4 show two pictures of the skull base, from above and below. Here we see the first depiction on the eponymous foramen of Vesalius indicated in the image – marked with an arrow in Figure 4 – transporting the emissary veins posteriorly from the face, through which infection can cause cavernous sinus thrombosis.^{Reference Saunders and O'Malley8}

Fig. 3. Skull base, inferior view, page 28 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Fig. 4. Skull base, superior view, page 29 of De Humani Corporis Fabrica,^{Reference Vesalius3} with arrow indicating foramen of Vesalius.

Figure 5 depicts Vesalius’ description of the maxilla, which is very different to Galen's description, hence he has included a picture of a canine skull as well to remind us that Galen was not likely to have been using human maxilla for his description.^{Reference Saunders and O'Malley8}

Fig. 5. Comparing the human and canine maxilla, page 46 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Otology in De Fabrica

Vesalius describes the ear as having two membranes: the first is the tympanic membrane and the second is the lining of the labyrinth. The auditory nerve then fans out over this membrane, as seen in Figure 6. The disconnect between this illustration and contemporary anatomy shows that Vesalius was unsure of otological structures. Although the first two ossicles had previously been recognised, we have the first naming of them as incus and malleus, to the right of the middle ear; however, the stapes is not featured yet at this point.^{Reference Saunders and O'Malley8,Reference Simpson9}

Fig. 6. Middle and inner ear, with ossicles to the right, page 43 of De Humani Corporis Fabrica.^{Reference Vesalius3}

This work paved the way for Vesalius’ follower Gabriele Fallopio/Fallopius, who studied under him in Padua, and went on to greatly further our understanding of the ear in Observations Anatomicae, including distinguishing between the facial nerve and the auditory nerve.^{Reference Mortazavi, Adeeb, Latif, Watanabe, Deep and Griessenauer10} Together with Vesalius, he mentored Giovanni Filippo Ingrassia, who has been credited with the first description of the lesser wings of the sphenoid and, by some, the stapes.^{Reference Cappello, Gerbino and Zummo11} However, others attribute the stapes to Vesalius’ Rome-based rival Bartholomew Eustachi/Eustachius, along with the tensor tympani and the cervical sympathetic chain.^{Reference Simpson9}

Rhinology in De Fabrica

Firstly, we see the sphenoid in Figure 7. Without access to fixative, it was very difficult to dissect out the various neural structures at the skull base, but Vesalius attempted to give as complete a picture of this as possible.

Fig. 7. Sphenoid, page 31 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Figure 8 is an illustration of the pituitary. Vesalius thought that the pituitary collected the phlegm from the brain and then siphoned it into the nose.^{Reference Saunders and O'Malley8} He writes here about the ‘organ of smell’, which is very similar to Galen's treatise of the same name.

Fig. 8. Pituitary gland, showing drainage channels of phlegm, page 64 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Although Vesalius did not carry out much more dissection after the second edition of De Humani Corporis Fabrica, because of his duties at the royal court, his own copy of the book has been found with his annotations in the margins, where he was planning a third edition, which has been examined by Vivian Nutton.^{Reference Nutton12} In it, he changes the term ‘organ of smell’ to ‘the instrument which distinguishes smells’, a very subtle shift that nonetheless implies that he is moving away from Galen to a more complex pathway. He also starts to expand more on the foramina of the skull and their contents.

His notes here also describe people occasionally being able to taste in their mouth what is put into their ears, showing that he is expanding his understanding of the Eustachian tubes (although Eustachius is mentioned above as a contemporary of Vesalius, the Eustachian tubes were actually described much earlier than this time period, possibly around 500 BC, by the Greeks^{Reference Simpson9}).

Laryngology and the neck in De Fabrica

We now turn our attention to the trachea and laryngeal cartilages pictured in Figures 9 and 10. The epiglottis is depicted as very small – possibly because of the way the specimens were prepared by boiling them in water, which may have distorted the cartilages.

Fig. 9. Trachea and laryngeal cartilages, page 184 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Fig. 10. The larynx and its musculature, page 304 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Figure 11 shows the cricoid – it is not yet known as the cricoid (coming from the Greek for ‘ring’: ‘kricoid’). However, although Vesalius names it with the widely used, contemporary term ‘innominate’, he is the first to point out that it looks like a ring, likening it in the accompanying text to the rings the Turks use for archery.^{Reference Lydiatt and Bucher13} Later on, William Harvey (another University of Padua alumnus) adopted the term ‘ring’ also.

Fig. 11. The cricoid, with an inscription describing it as being shaped like the Turks’ archery rings, page 187 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Vesalius’ other work on the upper airway is similarly precise. He determines that ‘larynx’ cannot be simply interchanged with ‘pharynx’ or ‘throat’. Likewise, the glottis makes up but a small part of the airway, rather than its whole. The thyroid cartilage is shield-like (scutiform), rather than the commonly used (at the time) shield-shaped (scutalis). In addition, the ‘arytenoids' (derived from the Greek ‘arytaina’, or ladle or vessel) refer specifically to the spout shape, rather than the whole vessel as implied by other anatomists.^{Reference Lydiatt and Bucher13,Reference Garrison and Hast14}

There is also arguably the first mention of the thyroid gland in modern anatomy – it can be seen in Vesalius' drawing, just inferior to the lateral thyroid cartilage in Figure 12. It is visible within Figure 9 too, if one looks closely at the same location. In the text, Vesalius describes the two fleshy glandulae laryngis at the second laryngeal cartilage.^{Reference Lamberg and Solin15} However, Galen had previously alluded to a set of glands in the pharynx and near the larynx in animal studies. In addition, Mondino de’ Luizzi (also known as Mundius Liucius) at the University of Bologna, a follower of Galen's teachings, published Anothomia Mundini in 1316, in which the thyroid does convincingly appear to be mentioned as almond-shaped glands beneath what we now call the strap muscles. Furthermore, Leonardo da Vinci's human anatomy drawings, known to be influenced by Mondino, do feature thyroid glands. Confusingly, though, Mondino calls them amigdalae, which was the contemporary term for tonsils, and Galen only writes about these glands in connection to those in the pharynx also, which is perhaps why his successors seemed to prefer to gloss over this portion of his work, making Vesalius’ description appear novel.

Fig. 12. Trachea and vessels, demonstrating the position of the thyroid, page 523 of De Humani Corporis Fabrica.^{Reference Vesalius3}

Vesalius would have been familiar with the works of Mondino and his amygdalae. Furthermore, he had often been accused of minimising the influence of recent and contemporary anatomists, something highlighted by Nutton in his examination of Vesalius’ editing of the first and second versions of De Humani Corporis Fabrica, where he appears to be phasing out others’ contributions in this area of the neck.^{Reference Nutton12} He postulates that this may in part be because of his increasing rivalries with Eustachius, mentioned earlier, and Realdo Colombo, whom Vesalius had considered an assistant at Padua but who had probably been on a more equal standing,^{Reference Lydiatt and Bucher13} referred to in the first edition of De Humani Corporis Fabrica but subsequently erased after a conflict over the composition of the laryngeal structures (ultimately, Vesalius’ conviction that they were made of cartilage and not bone prevailed). He was known to later acknowledge Fallopius’ and Ingrassius’ ‘discoveries’ of levator palpebrae superioris and the stapes respectively, and corroborate these with his own dissections, but this was perhaps after the editing of the text had occurred.^{Reference Nutton12}

In summary, Vesalius likely knew that these glands in the neck he was highlighting were not his ‘discovery’, and a different author might possibly have credited Mondino at this point. Nevertheless, Vesalius certainly brought more attention to the thyroid, and a more accurate depiction, than those before him.