The Gene 

The Gene
Author: Siddhartha Mukherjee

Synopsis

This exceptionally detailed and well-written account of heredity covers a subject the author depicted as ‘one of the most powerful and dangerous ideas in the history of science’. In his brilliant retelling of the ‘birth, growth, and future‘ of genetics, the author used his distinctively eloquent prose to weave history, culture, and medicine into the grand mosaic that defines us as individuals and peoples. Besides an exciting chronological narration of the discoveries which unlocked the riddle of heredity, the author also provided detailed biographical sketches of the pioneers who established and expanded the field, and the torchbearers who continue to reveal the apparently endless secrets that reside in the gene. The book’s exhaustive approach to the subject is reflected in its references to such diverse concepts as race, intelligence, gender and sex, and such disparate genetic disorders as Huntington’s disease, cystic fibrosis, and ornithine transcarbamylase deficiency. The book is also semi-autobiographical, the author revealing his own family heritage of schizophrenia, a disorder that has bedevilled his ancestry and that made topics such as normalcy and identity ‘recurrent themes of conversation’ in his family. Just as this reality made the author remark that ‘the weight of heredity is not an abstraction for me’, the book makes it clear that heredity should not be an abstraction for anyone else (pages 7, 9, 14, 342-345, 355-369, 281-290, 422-423 and 429). 

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A central feature of the book is its historical account of genetics which the author recounted with a rich, flowing prose. The book traced the earliest understanding of genetics to Gregor Mendel whose experiments with peas enabled him to tap into heredity’s ‘inner logic‘, and to introduce the concepts of dominant and recessive traits. In a rather tragic turn of events however, the author related why, for decades, Mendel’s insights were overlooked until his work was rediscovered and accorded its rightful place by William Bateson, the English biologist who coined the term ‘genetics’, and who ‘made it his personal mission to ensure that Mendel… would never again be ignored’ (pages 50-62). The history of genetics after this was dominated by the cell biologist Thomas Hunt Morgan who pried open ‘the black box of genetics’ and ‘unlocked the secret of the chromosome’. Working on the fruit fly Drosophila, and building on earlier works by Theodor Boveri on sea urchins, Walter Sutton on grasshoppers, and Nettie Stevens on worms, the author demonstrated how the research carried out in Morgan’s laboratory would set off a ‘chain reaction of discoveries‘ which ensured that ‘Morgan, his students, his students students, and even their students’ would all win Nobel Prizes (pages 92-97). The conflicts and competition that characterise many scientific fields were unfortunately also evident in this history of genetics, the author noting that Morgan’s students, Alfred Sturtevant, Calvin Bridges, and Hermann Muller, would eventually ‘quarrel fiercely, unleashing a cycle of envy and destructiveness that would blaze through the discipline of genetics’ (page 94). 

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The subsequent history of genetics the book related was notable for the awe-inspiring breakthroughs that enabled scientists to manipulate the gene itself. Charting breakthrough after breakthrough in what is a truly astonishing saga, the author chronicled a scientific drama dominated by the sterling contributions of several key actors such as Matthew Meselson, Frank Stahl, and Arthur Kornberg who discovered the role of the enzyme DNA polymerase in the process of DNA replication; Sydney Brenner who mapped the complete cellular lineage of the worm C. Elegans; double Nobel prize winner Frederick Sanger who invented an ingenious genetic sequencing technique; and Kary Mullis who devised polymerase chain reaction or PCR (pages 179-180, 191, 218, 261 and 302). The history also covered such fascinating innovations as the seminal discovery, by Jennifer Doudna and Emmanuelle Charpentier, of the CRISPR/cas9 gene editing tool which ‘allows us to add information to the genome’, and recombinant protein technology which generated therapeutic products such as insulin, factor VIII, and growth hormone (pages 470-477 and 245-252). Other notable discoveries the author highlighted are those which introduced novel concepts such as genetic variation by Ronald Fisher and Theodosius Dobzhansky; genetic transformation by Frederick Griffith; and random X chromosome inactivation by Mary Lyon (pages 28-40, 102-110, 112-114 and 399-400). 

Nothing illustrated the significant implications of genetics to society as the role it played in the history of eugenics, the abhorrent practice whose goal was ‘to accelerate the selection of the well-fitted over the ill-fitted, and the healthy over the sick’. The author narrated several tragic stories to demonstrate the dreadful human and social ramifications of the idea that was first advocated by Francis Galton and propagated by prominent eugenists such as Alfred Ploetz and Charles Davenport. One if such sad stories was of Carrie Buck, the subject of the infamous Buck v Priddy legal case which eugenists used to promote their misguided policies; even though her ‘practical knowledge and skills were found to be normal’, the eugenists labelled Buck a moron and subjected her to ‘eugenic sterilization‘. This case, the author argued, was the point at which the gene ‘transformed from an abstract concept in a botanical experiment to a powerful instrument of social control‘ (page 73-84). Documenting even more sinister applications of eugenics, the book charted its gradual evolution to ‘outright murder‘ when the Nazis sought to apply a ‘genetic final solution‘ to eliminate all those they considered unworthy of life – ‘the deaf, blind, mute, lame, disabled, and feebleminded‘, and this culminated in the horrific holocaust (pages 122-124). Other equally false and destructive scientific and social theories of heredity the book explored included spermism, preformation, Lamarkism and Lysenkoism (pages 21-26 and 126-127).

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Throughout the book the author expressed his wonder and reverence for the astonishing structure and function of the gene. He cited numerous illuminating facts to illustrate this, for example when he pointed out that the human genome, with about 20,000 genes, is ‘only 1,796 more than worms, 12,000 fewer than corn, and 25,000 fewer genes than rice or wheat’. Even more surprising is that ‘a bewildering 98 percent‘ of the chromosome ‘is not dedicated to genes’ at all (pages 322-325). Some of the most interesting features of the gene the book noted relate to its complex role in human reproduction; for example, describing the sperm as ‘no more than a glorified delivery vehicle for male DNA‘ he pointed out that the mitochondrial genome of a child, and ‘all the cellular material of the embryo‘, come from the mother (page 337). He author further noted that ‘each one of us can trace our mitochondrial lineage to a single human female who existed in Africa about two hundred thousand years ago’, and this is the so-called genetic Mitochondrial Eve (page 338). Also interesting is the observation that the Y chromosome, ‘the smallest of all chromosomes’, is also ‘the most vulnerable spot in the human genome’; the author portrayed it as ‘pockmarked with the potshots and scars of history’ because, being unpaired, ‘it cannot be fixed, repaired, or recopied’ (page 359).

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The book’s content is greatly enhanced by stories which depict how genetics has influenced human history. One of such accounts is of Alexei, heir to Czar Nicholas II, Emperor of the collapsing Russian Empire. Alexei, who inherited haemophilia from his mother Alexandra. suffered from the devastating impact of this bleeding disorder. In a memorable phrase that merges the medical with the historical, the author referred to ‘the metaphorical potency of Alexei’s illness’ as being ‘symptomatic of an empire gone sick, depending on bandages and prayers, hemorrhaging at its core’ (pages 98-99). A similarly striking anecdote was of the Dutch Hongerwinter during World War II, when the Germans banned food exports to Northern Holland; this resulted not only in starvation in the residents, but in higher rates of obesity and heart disease in their progeny spanning several generations. Using this story to illustrate the impact of epigenetics – the effect of the environment on genes – the author said ‘the acute period of starvation had somehow altered genes not just in those directly exposed to the event; the message had been transmitted to their grandchildren‘ (pages 393-394 and 405-406). 

Opinion

This ‘intimate history’ of the gene made compelling reading not only because it charts the detailed chronology of our understanding of the gene, but it also reveals the author’s own genetic history. With strikingly uplifting prose, the author infused the fundamentally academic narrative with a touching and appropriate personal touch which brought the subject to life. Highlighting great human achievements, and emphasising the huge importance of the bench-to-bedside method of medical progress, the whole book a wholly inspiring work. It is a comprehensive account of historical breakthroughs, illustrative anecdotes, and the current state of the field that makes for essential reading.

Overall assessment

This book, voluminous but informative, chronicles the gene literally from its conception. The content is relevant for healthcare because it illustrates the causes and the consequences of genetic disorders quite graphically. Extremely well-written and enlightening, the themes it discusses play central roles in a diverse range of medical specialties, and I highly recommend it to all doctors.

Book details

Publisher, Place, Year: Vintage , London, 2016
Number of parts: 6
Number of pages: 593
ISBN: 978-0-099-78457-5
Star rating: 5
Price: £9.39

3 thoughts on “The Gene 

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