Author: Armand Marie Leroi
From common variants and polymorphisms which embellish, to rare traits and mutations which deform, this book is a brilliant exposition of the disparate physical anomalies that accompany human development. Arguing a perspective of mutations as qualities which are ‘just part of the spectrum of human form‘, the book paints a portrait of the human body as one that is ‘replete with variety and error‘, a source of ‘delight‘ and repulsion in equal measure. The book also portrays mutations as the rule rather than the exception when one generation replaces another, illustrating this with the astounding fact that ‘every embryo has about a hundred mutations that its parents did not have’. In discussing the distinctive mutations that constitute the book, the author provided detailed explanations of the disordered mechanisms that ‘reverse-engineer‘ the body, transforming them into mutants (pages 12-19).
Teratology, congenital abnormalities of the developing foetus, was expectedly a major topic in the book which the author explored after setting out a comprehensive description of embryonic development. The curious phenomenon of conjoined twins is at the heart of this subject, and the book furnished many intriguing observations about how this oddity develops, noting for example that conjoined twins are almost always monozygotic, and there is an ‘overwhelming’ female predominance of about 77%. The author also described the seminal experiments, especially those of Hilda Proscholdt and Hans Spemann, which revealed the mechanism by which conjoined twins arise – a process that involves such signalling genes as noggin, cerberus, and dickkopf. Of the other unusual teratologies the book discussed, the ciliary disorder Kartagener’s syndrome stood out for its astonishing inversion of internal organs, and for the ominous infertility, chronic bronchitis, sinusitis, and impaired sense of smell that accompany it (pages 34-45 and 56-59).
Some of the mutations the book depicted are so exceptional that they have achieved mythical status. A classical example of this, which the book elaborated on at length, was the case of one-eyed infants; unlike the mythical cyclops which has its single eye above the nose, the author noted that ‘the single eye of a cyclopic infant invariably lies beneath the nose – or what is left of it’. Also in contrast with the mythical cyclops, one-eyed infants often have associated brain anomalies – especially a fused forebrain – and this is so frequent as to be the ‘the most common brain deformity in humans’. The author further noted that cyclopic children occur more frequently in children of diabetic and alcoholic mothers, and the causative mutations often affect the genes that code for sonic hedgehog – the signalling protein which controls the splitting of the early embryonic forebrain and formation of the face. Another related deformity with mythical correlates in the book is sirenomelia or mermaid syndrome; this is a condition in which there is a single fused lower appendage, and which may result from a mutation of the CYP26A1 gene which codes for an enzyme that breaks down retinoic acid (pages 67-75 and 78-83).
The variation of human body size and height was a major theme of the book. A disorder at the ‘smaller’ end of the spectrum which the author discussed was pygmies, a condition which he pointed out arises from the absence of a pubertal growth spurt, itself a result of deficient insulin-like growth factor 1. Cretinism is also at the lower rung of body size, and the author emphasised its high prevalence across the world’s great mountain ranges because ‘what these areas have in common is a lack of iodine‘. Achondroplasia is another conspicuous disorder of short stature, and the book highlighted its cause being a mutation of the fibroblast growth factor receptor. Endocrine disorders dominated the books exploration of abnormally tall body forms, illustrative examples including male pseudohermaphroditism, a situation in which affected males appear as ‘exceptionally feminine‘ and ‘strikingly attractive‘ girls who ‘tend to be rather tall‘ and have ambiguous genitalia. On the other hand, the author depicted the rarer female pseudohermaphrodites as possessing very hairy skins and masculinised genitalia; this is because they have mutations in aromatase – the enzyme which converts testosterone to estrogens (pages 189, 196, 154-155, 234-239).
The extraordinary range of recognised mutations is a salient theme of the book, ranging from the exceedingly mundane to the extremely rare. Among the more commonplace mutations are disorders of the skin such as albinism, piebaldism, red-headedness, balding, and hypertrichosis or excessive hair. The skin is also remarkable for mutations simultaneously affecting its ‘intimately connected’ appendages – hair, teeth, sweat glands, and breasts. Unlike the common mutations which are frequently unremarkable, the rarer mutations tend to be striking. The author illustrated this graphically with several distinctive disorders, for example ectrodactyly, or lobster claw syndrome, in which the hands and foot are split; acheiropody or the absence of hands and feet; phocomelia or seal-limb in which there is absence of the long bones – as seen in thalidomide babies; and fibrodysplasia ossificans progressive, a disorder of excessive bone formation. On the contrary, the author noted how little genetic diversity there is between populations, an observation that raises doubts about the reality of race as a scientific concept altogether (chapter 8 and pages 337, 286-287, 108, 114-125, 118-120 and 140-141).
Greatly enhancing the book is the author’s abundant use of historical anecdotes and mythological examples as backdrops to the mutations he discussed. Indeed the author introduced his book by referring to the Vrolik teratology collection in Amsterdam which he said uniquely demonstrates ‘the limits of human form‘. Of the mythical mutants he described, the crook-foot Hephaestus, the Greek mythical god of craftsmen and smiths, was notable; he had club foot or talipes equinovarus, and he was the only Olympian to have a deformity. Of the real historical mutants in the book, the ‘two headed girl’, conjoined twins Ritta-Christina, featured prominently partly because of the scramble by Parisian anatomists to dissect their body following their death in 1829. Anatomy also played a central role in the deforming experiments carried out on Jewish prisoners at Auschwitz by Josef Mengele. Other factual anecdotes the author chronicled included the 4th century Athenian eunuchs, and the 18th century Italian castrati, who lacked testosterone and appeared unusually tall and ‘somewhat oddly shaped‘. The book was also replete with interesting trivia such as the tallest people in the world are the Dutch; polydactyly, or extra fingers, usually involves the little finger in Africans but the thumbs in Europeans; Ernest Hemingway had polydactylous cats; the French painter Achille Empéraire suffered from osteogenesis imperfecta or glass bone disease; the French painter Henri de Toulouse-Lautrec suffered from pycnodysostosis; and researchers are hunting for the scaramanga gene that causes accessory nipples (pages 23-27, 67, 109, 121-122, 147-153, 158-165, 199-209 and 290).
The is a most interesting book which exhaustively and engagingly discusses a topic that affects everyone to a lesser or greater degree. With passionate prose and striking stories, the book not only highlights some of the most compelling disorders afflicting human beings, but it also demystifies them by explaining the mechanisms driving them. Some of the historical contexts the author used to illustrate his themes seemed excessive at times, but this did not detract from the key messages he set out to portray. Almost all the themes are relevant for healthcare, and some, such as race, have wider significance to society as a whole.
This is an interesting perspective, predominantly of genetic disorders which the author presented using historical and literary backdrops to good effect. The book shines a scientific light on what are often otherwise misunderstood disorders, shrouded in mystery and mythology. The author addressed an impressive diversity of disorders and concepts which go far to emphasise the importance and impact of the subject on individuals and healthcare. Almost all the disorders the book explored are directly relevant to medical practice, and I recommend it to all doctors.
Publisher, Place, Year: Harper Perennial, London, 2003
Number of chapters: 10
Number of pages: 431
Star rating: 5