69 Homer to Vrolik. Pliny the Elder Natural history: a selection, (trans. J.F. Healy. 1991. Penguin, Harmondsworth, UK). For an early and important outline of the origin of the Plinian races and their fate in medieval literatures see Wittkower (1942). For much further detail see the very readable Friedman (1981) as well as Kappler (1980), Williams (1996) and Daston and Park (1998).
71 The first illustration of a cyclopic child. Liceti (1634) also identifies an additional two eyes on the back of the Firme child’s head, but these must be fictitious (he never saw the child himself, but worked from a sketch). The original sketch of the Janus-headed twins with cyclopia is now lost. Some, but not all, features of the presentation and subject in Liceti’s engraving are consistent with it having been derived from an original by Leonardo. No other sketches of teratologies by him are known (Martin Kemp, pers. comm.). The report of a Janus-headed twin with cyclopia is given in Abbott and Kaufmann (1916).
72 Looking at his bottled babies. For a historical account of causal theories of cyclopia in the nineteenth and twentieth centuries see Adelmann (1936). For the modern definition of holoprosencephaly see Cohen (2001); for the incidence of the disorder see Muenke and Beachy, (2000); for a review of the teratology, Cohen and Shiota (2002); and for the role of veratrum in lamb cyclopia, Incardona et al. (1998).
74 Most cases of cyclopia. Holoprosencephaly (HPE) consists of at least seven distinct inherited syndromes (HPE1 to HPE7). HPE3 (142945) is due to heterozygosity for mutations or deletions in sonic hedgehog (600725) (Roessler et al. 1996). For the spectrum of Shh mutations see Nanni et al. (1999, 2001). For the Shh knockout mouse see Chiang et al. (1996); for a general revew of the other HPE genes see Muenke and Beachy (2000).
76 An embryo’s face. See Hu and Helms (1999) for an elegant study of the role of Shh in craniofacial formation and Ditto the pig. GH3 (165240) mutations cause Greig’s cephalopolysyndactyly (175700) which is characterised by hypertelorism among other things. Hypertelorism with nasal bifurcations is characteristic of craniofrontonasal syndrome (CFNS) (304110). The causal gene underlying has not yet been identified.
78 Among the disorders that appear. For a history of sirenomelia and siren-like iconography see Gruber (1955); for a more recent review see Valenzano et al. 1999). For the CYP26A1 (602239) deletion mice see Sakai et al. (2001) and Abu-Abed et al. (2001). For pigs without eyeballs see Hale (1933); for isotretinoin in humans see Lammer et al. (1985); and for a review of retinoic acid function and gradients in the embryo see Maden (1999).
83 The consequences of cells. The claim that the lumps on the necks of Pans are supernumerary auricles is made by Sutton (1890); Cockayne (1933) discusses goats. See Boardman (1997a) pp.36–7 for the Hellenistic Pans bearing supernumerary auricles. See Boardman (1997a; b) for a technical synopsis of the history of Pan in Greek and Roman art and a charming essay on his iconography by the famous scholar of Greek art. The girl with four auricles is discussed by Birkett (1858); a more general discussion of supernumerary auricles is given by Bateson (1894) pp.177–80 and Cockayne (1933) pp.339–41.
86 Homeosis was first identified. Bateson’s (1894) purpose was not, as now, to use homeotic variation as a means for studying development. He was instead struggling towards a theory of inheritance; that is, attempting to fill the gap left by Darwin’s account of evolution. He failed, but he was among the first to retrieve Gregor Mendel’s experiments on peas from the fathomless obscurity of the Verhandlungen des naturforschenden Vereines in Brünn. As such, he is recognised today as one of the fathers of modern genetics.
87 Over the last eighty-odd years. See Lawrence (1992) for an account of the homeotic genes in Drosophila. Strictly speaking these genes specify parasegments, divisions in the embryo that contribute to, but are out of register with, the segments visible in the larva. The seminal paper on the homeotic genes is Lewis (1978). In 1995, Ed Lewis shared the Nobel Prize with two other Drosophilists, Christiane Nüsslein-Volhard and Eric Wieschaus.
91 Extra ribs have always caused trouble. See Sir Thomas Browne’s Pseudodoxia epidemica, or, enquiries into very many recieved tenents and commonly presumed truths (1646) in Works (1904) volume III chapter II pp.5–8. Estimates on the variation in rib number come from Bornstein and Peterson’s 1966 study of 1239 skeletons. They found that 9 per cent of their skeletons had thirteen pairs of ribs. Of this fraction, just under 1 per cent were due to the seventh cervical vertebra gaining ribs, about 5 per cent were due to the first lumbar vertebra gaining ribs and 3 per cent were due to a simple increase in the total number of vertebrae, that is, were not due to a homeotic transformation of vertebral type. Other studies, reviewed in Galis (1999), put the incidence of seventh cervical vertebrae ribs somewhat lower, at around 0.2 per cent. Cervical ribs can cause ‘thoracic outlet syndrome’, a compression of the nerves and blood vessels of the neck. Galis (1999) also addresses the fascinating question of why all mammals have just seven cervical vertebrae where the numbers of other vertebrae vary greatly among species. She argues that mutations that cause cervical ribs may be far more pathological than is generally appreciated and so under strong stabilising selection.
92 It is no surprise, then, that the identity of each vertebra. This account of C7 specification is based on the results of deletions for particular Hox genes in mice. It is probably incomplete and some of the AND statements should be OR (since partial transformations are common, suggesting that other Hox genes can compensate) or else couched in more quantitative terms – but it is a reasonable start. Deletions in the following genes cause C7->T1 transformations: Hoxa4 (Horan et al. 1994); Hoxa5 (Jeanotte et al. 1993); H0XD5 (Rancourt et al. 1995); Hoxa6 (Kostic and Capecchi, 1994); Hoxb6 (Rancourt et al. 1995). Other genes, such as HoXC4, may be affect this vertebra as well, but results disagree (Boulet and Capecchi 1996; Saegusa et al. 1996; Horan et al. 1995a; b)
93 Distinguishing one vertebra from another. These disorders are caused by deletions in the following genes: anteriorised limbs: Hox5b (Rancourt et al. 1995); partly missing hindbrains: Hoxai (Lufkin et al. 1991; Mark et al. 1993; Carpenter et al. 1993); hernias: Hoxd4 (Ramirez-Solis et al. 1993); no thymus: Hoxa3 (Chisaka and Capecchi 1991); unable to walk: Hoxc8 (Le Mouellic et al. 1992).
94 The Hox gene calculator. For Hox gene expression in human embryos see Vielle-Grosjean et al. (1997). The embryos used in this study were ‘collected with full ethical permission’. For a discussion of what this means and legislation of such studies in various countries see Burn and Strachan (1995).
95 Writing of the ‘calculator of fate’. For supernumerary eyelashes or distichiasis (126300) see Cockayne (1933) P-330 who notes, incidentally, that hedgehogs normally have two rows of eyelashes. For the seven-hearted chicken see Taussig (1988) following a 1904 report by the pathologist Verocay who happened to be staying at the inn and who managed to secure the viscera, but not the rest of the chicken, for study. Isidore Geoffroy Saint-Hilaire (1832–37) volume 1 pp.723–9 discusses various putative cases of heart duplications in humans but can come up with only one possibly authentic example, an early-eighteenth-century case of a grossly deformed infant. See Lickert et al. (2002) for extra hearts in ?-catenin-conditional null mutant mice.