DNA
Author: James Watson

Synopsis

Written by a scientist who played a crucial role in unlocking its mysteries, this book about DNA recounts the intrigues and ingenuity that have characterised the arduous journey to reveal ‘the secret of life‘. Metaphorically referring to DNA as the conductor orchestrating ‘the incredibly complex world of the cell’, the author chronicled the ingenious experiments, and the serendipitous discoveries, that unravelled its double helical structure, and its intricately complex function. Rather voluminous, the size of the book is nevertheless justified by the diversity of topics the author covered, from race, intelligence, behaviour, eugenics, euthansia, and genetically modified foods, to the human genome project, genetic therapy, palaeogenetics and DNA fingerprinting. The book is also an inspiring homage to the innovative scientists who deciphered the enigma that is DNA, from Sidney Brenner, Francis Crick, Marshall Nirenberg, Heinrich Matthaei and Gobind Khorana who determined the complete triplet-based genetic code, to Stanley Cohen, Herbert Boyer and Paul Berg who pioneered recombinant DNA technology and genetic engineering (pages xiii, 75-78, 90-92, 121, 196, 108-109, 94-98 and 524).

Like most historical accounts of genetics, the author traced the first meaningful insights into the nature of heredity to Gregor Mendel, the monk whose perceptive work on peas ‘would have been unintelligible to most scientists of the era’, and perhaps inevitably got ‘buried in an obscure journal‘ (pages 7-9). Subsequent developments were however anything but opaque or shrouded; rather, the author went through an avalanche of pivotal breakthroughs ranging from the determination of chromosomal inheritance by Walter Sutton and Theodor Boveri, to the recognition of DNA as the agent of genetic transmission by Friedrich Miescher, Frederick Griffith, and Oswald Avery. The author narrated such exciting landmarks as the elucidation of the chemical nature of nucleotides by Alexander Todd and Erwin Chargaff, and the discovery of sex-linkage, gene recombination, and chromosome mapping by Thomas Hunt Morgan and his ‘boys’ who studied the fruit fly Drosophila melanogaster. Equally gripping is the author’s portrayal of the discovery of DNA polymerase by Arthur Kornberg; the recognition by Paul Zamecnik that protein synthesis takes place on the ribosome; and the discovery by Linus Pauling, while working on sickle cell anaemia, that genes code for proteins. But perhaps the pinnacle of this early phase of genetic discoveries is what the author called ‘the most elegant experiment in biology‘: the study by Matthew Meselson and Frank Stahl which used two types of nitrogen to prove that DNA duplication required the unzipping of DNA (pages 11-15, 37-41, 60, 67, 73 and 59).

A most revealing feature of the book’s narrative is the author’s autobiographical account of the central role he played in solving the structure of DNA. It was interesting to learn, for example, that the source of his inspiration was the physicist Erwin Schrodinger, who stated in his book, What is Life, that ‘life could be thought of in terms of storing and passing on biological information’. In portraying his research odyssey, the author described how he started off by studying bacteriophage reproduction with Salvador Luria, Max Delbruck, and Alfred Hershey, and how he changed his focus after listening to a talk by the physicist Maurice Wilkins on the utility of X-Ray diffraction in revealing the structure of DNA. Illustrating the impact of this on his career, he referred to how it motivated him to move to the Cavendish laboratory in Cambridge where he worked with leading scientists such as Lawrence Bragg, John Kendrew, and Max Perutz, and where he found himself ‘sharing space in the biochemistry room’ with Francis Crick, with whom he will forge a famous and groundbreaking scientific relationship. In acknowledging the various influences that enabled the pair to accomplish their historic feat, the author referred to learning from the ‘model building approach‘ of Linus Pauling, the X-Ray diffraction photographs of Rosalind Franklin, and the discovery of the equal ratios of DNA pairs by Erwin Chargaff. Also critical to their construction of the simple and elegant double helix was the fortuitous visit to their laboratory by the theoretical physicist Jerry Donohue who corrected their mistaken concept of the nature of nucleic acid bonding (pages 35 and 42-54).

One of the book’s key objectives was to demonstrate the widespread and important applications of genetics to society, and one such area the book highlighted was the study of human origins – what the author symbolised as the interrogation of humanity’s history. In discussing this topic, the author referred to the deployment of mitochondrial genetics and Y chromosome analysis to map the human genetic family tree into two major branches; pioneered by Allan Wilson, Rebecca Cann, and Luigi Luca Cavalli-Sforza respectively, these techniques have been used to confirm that modern humans most probably originated from the San people of Southern Africa about 150,000 years ago (pages 317-322). It was also enlightening that genetic studies of human population migration have enabled the creation of a global genetic map on which all humans are ‘99% alike’, any differences being accounted for by minor mechanisms such as copy number variation (pages 330-333). In a similar fashion, the author referred to the genetic studies that have dispelled any race-specific genetic differences, specifically pointing out that differences in skin colour ‘are probably products of natural selection’ which have relevance only to health, such as in cancer prevention and Vitamin D metabolism (pages 333-345). To illustrate his discussion on the related subject of ancestry, the author recounted anecdotes which demonstrated how genetics identified the remains of the murdered Russian Romanov royal family of Tsar Nicholas II; confirmed the identity of the remains of the Plantagenet King Richard; and established Thomas Jefferson‘s possible paternity of a child he had with his slave, Sally Hemings (pages 365-378).

The human genome was expectedly a prominent theme in the book, and the author discussed this in the context of its fascinating, and frequently counterintuitive, qualities. Perhaps the most surprising feature of the genome the book highlighted was its relatively small size, graphically contrasting it to the genomes of the mustard plant and of the nematode worm, C. elegans; noting that both of these contain thousands of genes more than the human genome, he attributed this to the paradoxical hypothesis that ‘there is a correlation between intelligence and low gene count‘ (pages 256-266). Amongst the several other interesting observations the author made regarding the human genome are that 50% of it is made of junk-like sequences, and 60% consists of ‘genetic fossil pseudogenes‘.  (page 265-286). The book’s exploration of the human genome also threw up many compelling trivia, such as the observation that the chimpanzee has a pair of chromosomes more than the 23 pairs in humans because the human chromosome 2 is a fusion of two chimpanzee chromosomes; chromosome 1, the largest human chromosome, contains 8% of the total human DNA material; and the source of DNA polymerase used in polymerase chain reaction is Thermus Aquaticus, ‘a bacterium that lives in the hot springs of Yellowstone National Park. Despite the advances made in understanding the human genome however, the author made the humbling admission that we ‘know remarkably little about what the vast majority of human genes do’ (pages 340, 89, 112, 198 and 226).

Arguably, the most practical aspects of the book are those which relate to the implications of genetic research on health. In this regard, the author narrated a fascinating account of the pioneering work of Archibald Garrod who first recognised that alkaptonuria was an inherited inborn error of metabolism, and how this was later confirmed to arise from a mutation in the phenylalanine hydroxylase gene (pages 63-64 and 409). The author also narrated subsequent research in genetic diseases in which he recognised such trailblazers as geneticist Nancy Wexler whose work contributed to locating the gene mutation responsible for Huntington’s disease on chromosome 4. Born to a family which was afflicted with the disease, the author depicted how Wexler made her breakthrough by studying a Venezuelan community which had a high incidence of the disease, and how the gene mutation was mapped using the technique of linkage analysis (pages 385-340). Similarly uplifting were the stories of the isolation of the Duchenne muscular dystrophy gene, the largest gene mutation at the time, by Lou Kunkel and Tony Monaco  (pages 392-393). The author also explored genetic therapeutic products such as the HER2 receptor blocker Herceptin for breast cancer, the protein kinase inhibitor Gleevec for chronic myeloid leukaemia, the checkpoint inhibitor Keytruda for malignant melanoma, and the genetic therapy Eteplirsen for Duchenne muscular dystrophy (pages 134-139,491-494, 508 and 394).

Opinion

This book is a broad sweep of genetics, with a very helpful perspective of its history, its current status, and its future direction. The author highlighted all the major genetic breakthroughs in a narrative that provided interesting insights into the science, and the scientists behind them. He also reviewed the applications of genetics to several fields, from healthcare and genealogy to forensics and agriculture. A major player in genetic research for most of his lifetime, the author also expressed his strong personal opinions about science policy, patents and the human genome project. The writing is excellent, the history revealing, and the lessons educational. Some of the topics, such as the discussion of the nature-nurture debate, were not very illuminating, whilst other important topics, such as telomeres and CRISPR-guided gene editing, were only mentioned in passing. These minor omissions aside, the overall content is relevant and appropriate, and very elegantly presented.

Overall assessment

The impact of genetics to society and human health can not be overestimated, and this book explores this in detail. The author eminently succeeded in portraying how the gene works, and how it can now be manipulated to great benefit in diverse aspects of life. With revealing coverage of the history and clinical implications of our understanding of DNA, the book is an inspiring take on what is clearly fundamental to human progress. The lessons of the book have profound relevance to healthcare, and I recommend it to all doctors

Book details

Publisher, Place, Year: Arrow Books, London, 2017
Number of chapters: 14
Number of pages: 595
ISBN: 978-1-784-75804-2
Star rating: 4
Price: £10.49