Author: Matt Ridley
This whirlwind tour of the human genome, what the book described as ‘a dynamic, changing scene’, is an exciting exploration of the implications of genetics to health and society (page 146). The author aimed to present a comprehensive but concise account of the human genome, and he did this by exploring an extensive range of themes such as life, species, intelligence, fate, death, and immortality. He weaved a seamlessly rich tapestry of history and culture, an approach that greatly enriched the scientific text and helped to simplify the complex genetic concepts at the heart of the book. The book’s impressively detailed content belies the fact that the author is not a scientist but a journalist who, by a brilliant combination of scholarly work and illustrative anecdotes, provided a panoramic view of a subject which has overarching contemporary relevance.
The inspiring feature of the book is the uplifting history the author narrates of the emergence of the science of genetics: this highlighted the achievements of the scientists who pioneered the field, and the discoveries which enhanced our understanding of the human genome. In a chronological presentation, the book referred, for example, to how Gregor Mendel determined the inheritance of genetic characteristics whilst studying peas; how Archibald Garrod recognised the genetic nature of in-born errors of metabolism when studying subjects with alkaptonuria; how Thomas Hunt Morgan, ‘the father of American genetics’, and his illustrious proteges such as Hermann Muller, initiated the study of mutations in fruit flies; how Francis Crick and James Watson demonstrated the structure of DNA; and how Marshall Nirenberg and Johann Matthaei cracked the genetic code. The book also celebrated many latter scientists, all Nobel Prize winners, who have made groundbreaking genetic breakthroughs; these include Barbara McClintock who discovered transposons or jumping genes in maize; Elizabeth Blackburn who discovered telomerase; Eric Kandel who discovered the genetic changes that give rise to learning and memory; and Stanley Prusiner who established the genetics of prions (pages 128-129, 197, 225 and 276-277).
The chromosome, the structure which hosts the genome, was a central subject matter of the book, and in exploring this theme, some of the most striking concepts the author discussed related to the sex chromosomes. For example, in depicting the Y chromosome as largely non-active, the author noted that ‘the great bulk of its length consists of non-coding DNA‘. He however also observed that there are some critical regions in the Y chromosome, one of which is the ‘peculiar’ SRY gene which determines male sex, and which is well-preserved and almost mutation-free (pages 111-122). Similarly, the book’s discussion of the X chromosome revealed several compelling phenomena; one of these describes how the paternal X chromosome plays a more dominant role than the maternal X chromosome in the development of the female social brain, with the result that males, who only inherit their mother’s X chromosome, have less developed verbal and executive function skills than females. The phenomenon also explains why autism develops more frequently in males than in females (pages 216-217). A distinguishing feature of the larger X chromosome, unlike the Y chromosome, is its influence in regulating far more diverse human traits, and one example the author cited is the monoamine oxidase A gene which mediates mood and aggression, and which may predispose to criminality (page 172).
One of the most revealing themes in the book is the genetics of human reproduction, a topic which the author tackled with particular emphasis on the paternal imprinting of placental genes. In discussing this most unusual phenomenon, the author observed that, unlike the development of the foetus which is mainly guided by maternal genes, the formation of the placenta is determined predominantly by genes that are derived from the father. It is interesting that the opposing roles of the parental genes arise from a ‘conflict of interest‘ that exists between them, the author quipping that the paternal genes ‘do not trust the mother’s genes to make a sufficiently invasive placenta to nourish the foetus’, because this will be at the expense of the mother’s health (pages 209 and 215). The competing actions of the paternal genes, the author asserted, also go a long way to support the concept of sexual antagonism – the notion that placentation is ‘a parasitic takeover‘ of the mother’s body by the paternal genes (page 114). Another similarly exciting theme, relevant to reproduction, is the role of the homeotic or Hox genes, one of which is named hedgehog. These genes, the book argued, have been well-conserved across all species because of their critical function in guiding the segmental sequence by which all embryos develop (pages 175-177 and 182-183).
Fundamental to the book’s discourse on the human genome are the genetic diseases which arise when the genome becomes dysfunctional, and the author approached this theme by reviewing the science and personalities behind some prominent genetic disorders. Symbolic of this approach is the book’s analysis of Huntington’s disease in which the author narrated the role of Nancy Wexler in pioneering the research that culminated in identifying the causative CAG polyglutamine mutation on chromosome 4. Haunted and driven by her own family history of Huntington’s disease, Wexler succeeded by going out to Venezuela to study a community which was ravaged by the disorder. Further discussing Huntington’s disease, the book noted that the total deletion of the causative gene gives rise to a completely different disorder called Wolf-Hirschhorn disease (pages 55-59). Other genetic disorders the book featured include Werner’s syndrome, a disease which confers short telomeres and manifests with premature ageing; Prader Willi and Angelman syndromes, genetic opposites that arise from the same mutation but on the respective paternally or maternally inherited chromosome 15; and Williams syndrome, which presents with impaired linguistic skills (pages 203, 207 and 97).
Many of the topics the book discussed stood out for the surprising and puzzling facts they threw up. Amongst these is the observation that 97% of the human genome is made up of so-called junk DNA which ‘does not consist of true genes at all’ but is ‘a menagerie of… pseudogenes, retropseudogenes, satellites, microsattelites, transposons, and retrotransposons‘. First discovered by the geneticist Alec Jeffreys, junk DNA serves as a genetic fingerprint because it is made up of repeating sequences that are sufficiently different between individuals; this unique characteristic, the author said, makes junk DNA useful in forensics; in the identification of human remains; and in the determination of paternity (pages 123-124 and 132-134). Other intriguing genetic details the book reviewed include the facts that 1.3% of the human genome is derived from viral genomes called human endogenous retroviruses; the observation that apes have 2 pairs of chromosomes more than humans in whom ‘two ape chromosomes have fused‘ as chromosome 2; the knowledge that people with the AB blood group are ‘virtually immune to cholera‘; and the phenomenon of the immunocompetence handicap – how the immune suppressing effect of testosterone contributes to the higher mortality of males compared to females (pages 125, 24, 140 and 157).
This book addresses an array of fascinating facts about the genome, with riveting details about the mechanisms behind genetic disorders. The concepts the book covers demonstrate the level of complex organisation that takes place in the genome. The lucid explanation and careful simplification of complex areas enhanced the book although in some places the author made long-winded commentaries to explain his themes. The discussion of some topics, such as eugenics and freewill, particularly seemed disproportionally excessive and perhaps even superfluous. These shortcomings however are overshadowed by the lucid prose and the illuminating content.
This is a revealing book, written by a non-scientist who however shows an excellent grasp of the subject. It provides a wide perspective of the topic, from the genetic underpinnings of medical disorders, to the implications of genetics in society. It is a useful primer for a broad understanding of the genome, and I recommend it to all doctors.
Publisher, Place, Year: Harper Perennial, London, 1999
Number of chapters: 22
Number of pages: 344
Star rating: 4