As early as 1731, R. Nesbitt,[222] in two lectures delivered to the Royal College of Surgeons, demonstrated that in the human foetus some bones were formed not in cartilage but directly in fibrous tissue, and this observation was confirmed by other human anatomists, particularly by Sharpey at a considerably later date. In 1822 Arendt[223] focussed attention upon the remarkable structure of the skull of the Pike, with its cartilaginous brain-box studded all over with bony plaques, an arrangement which had already attracted the interest of Cuvier and Meckel. K. E. von Baer[224] in 1826 discussed at some length the relation between the bony and the cartilaginous skull in fishes, with particular reference to the sturgeon, coming to the following just conclusion:--"If we consider the fibrous skeleton of _Ammocoetes_ as the first foundation of the skeleton of Vertebrates, we can form a series among the cartilaginous fishes, according as a cartilaginous skeleton penetrates more and more into this fibrous foundation. In the same way the process of ossification supplants the cartilaginous skeleton. So long as the ossifications lie in the skin, as in the sturgeon, they form corneous bones (_Hornknochen_), but when they lie under the skin, they form true bones, _e.g._, the bones of the skull in the pike" (p. 374). Embryologists soon become aware that a similar distinction between a primitive cartilaginous foundation and a secondary overlying ossification of the skull showed itself in the development of all Vertebrates. Duges, in his _Recherches sur l'osteologie et la myologie des Batraciens_ (1834), distinguished between such bones as are formed by direct ossification of the cartilaginous groundwork of the skull, and such as are developed in the periosteal fibrous tissue.