The Gene: An Intimate History

In recent years there have been many excellent popular science books in the fields of biology and medicine. Some are short, often interweaving personal histories, such as ‘Do No Harm’ by the brain surgeon Henry Marsh; others attempt to cover much wider fields, such as the author’s previous blockbuster, ‘The Emperor of all Maladies’, a biography of cancer. ‘The Gene – an intimate history’ is definitely of the latter variety, weighing in at close to 600 pages. The approach is historical, starting with the modern origins of the subject in the pioneering work of Darwin and Mendel and proceeding through the rise of eugenics and its advocate Galton, the solution to the structure of DNA, gene splicing and the many discoveries thereafter. The work of Galton and his many followers is the darker side of the history of genetics. They thought they could fundamentally change nature by pseudo-scientific programmes, such as the attempts in America to eradicate ‘defective strains’ by forced sterilization and other means, which continued in some countries well into the 1970s. The most perverted and horrific use of genetics took place in Nazi Germany. There the misguided views of eugenics were closely link to race and led directly to the mass murder of ‘racially undesirables’, as well as the physically and mentally handicapped, in the mistaken belief that this would lead to a superior race. Conventional eugenics is now totally discredited, and in the West genetic experiments are subject to strict controls. Neverthess, it is legal to screen embryos for serious genetic conditions before implanting them in the wombs of women undergoing IVF treatment, and in some countries with weak supervision, experiments are being done to find methods of eradicating genes which have been linked to other diseases. While this may be laudable, what is next? Perhaps eradicating the genes for unsightly large noses? At what point would these procedures be ‘enhancement’ and eugenics by another name. Are we on the verge of ‘designer babies’? These ethical questions are re-examined throughout the book and become more focussed as technical improvements in genetics research presses steadily forward. The author has a particular interest in this because he comes from a family that has a history of serious mental illness, although I found his digressions about this a little distracting and added little to the story. As research has moved forward, the realization has emerged that genes are far more complex than previously thought and it is very rare for a single gene to be the sole ‘culprit’ for a particular disease. More often multiple genes are involved, working through complex interactions that are far from being totally understood, and moreover are also influenced by external factors, so that the final outcome is very difficult to predict. The role of these external influences is embedded in the relatively recent discovery of so-called ‘epigenes’, which appear to imply that genes may be responsive to environmental factors, raising yet again the old questions of eugenics, with its far-reaching ethical and social implications. Potential readers such as myself who read ‘The Emperor of all Maladies’ are faced with a daunting prospect, because like that book this one is not only long, but also contains much technical information about genetics. Don’t let this deter you. You may not fully follow all the scientific details (I certainly did not) but the writing is so beautifully clear that at the end of ‘difficult’ sections you will still have a good overview of the problems that the field has faced, or is still facing, and the arguments for and against different positions on important topics such as gene therapy. It is a book definitely well worth the effort of reading.

This is an exceptional book in so many ways. Siddharta Mukherjee is a medical expert, an oncologist with many years experience of treating cancer patients, whose first book "The Emperor of all Maladies" (also highly recommended) describes what happens when genes malfunction. In this book he describes the human genome in its normal, fully functional state, covering many diverse aspects of genetics. Mukherjee is also a gifted writer, able to explain complex ideas clearly, he is both lyrical & incisive in his insights and syntheses. Running throughout the book are personal stories that transform this from a purely scientific account to a very human story. He describes the scientists who made the key discoveries, as well as the people affected by genetic diseases or treatments. Most personally he describes how genetics has touched the lives of his own family. Part 1 (1865-1935) covers the early history of genetics, its landmark discoveries, & key personalities, from the early Greek ideas of heredity, Mendel's discovery of heritable factors & laws of heredity, Darwin's theory of Evolution by Natural Selection, to the Eugenics proposed by Galton and put into practice in the early 20th century in the US & Europe. Part 2 (1930-1970) describes the search for the physical particle of heredity, finally determined to be DNA, the discovery of its helical structure by Watson & Crick and the attempts to decipher the universal genetic code spelt out within DNA, to an understanding of how genes regulate the expression of proteins and control the devlopment of multi cellular organisms from a single fertilised egg. Armed with this knowledge, Part 3 (1970-2001) describes attempts to manipulate the genome via techniques such as gene cloning, the creation of synthetic proteins like insulin and the rise of biotechnology in the 80's & 90's. In Part 4 (1970-2005) he describes the growing understanding of how genes affect human health, for example, the discovery by Nancy Wexler of the gene for Huntington's disease, its exact location on chromosome 4, to an understanding of its DNA sequence, which in turn explained its effect on sufferers. It also describes polygenic diseases such as schizophrenia and cancer & attempts to map the location of these genes via genetic markers. This, in turn, lead to the idea of mapping the entire human genome - rather than searching for disease-causing genes one by one, this would provide a template against which polygenic diseases could be compared. The Human Genome Project was a massive international scientific collaboration, spiced up by the competition between the publicly funded NIH Consortium and commercially minded Craig Venter's Celera. Part 5 (2001-2015) describes how the new genetics can be used to illuminate complex concepts such as human evolutionary history, language, memory, culture, sexuality, identity & race. This is complex and must consider the twin effect of nature & nurture, genes & environment. Part 6 (2015-....) looks into the future and describes the new technologies that are currently being explored, such as pluripotent stem cells, transgenic organisms, whole genome screening to predict future health, personalised genetic therapies, to the spectre human genomic engineering. I can highly recommend this book to anyone with an interest in the origin, functioning & nature of that incredibly complex and ingenious entity that is the human body.

It’s a in-depth read You need an understanding of human anatomy and mental health

The book begins as an intimate history of genetics but develops into the intimate future of one of the most powerful and dangerous ideas in the history of science: the gene, the fundamental unit of hereditary and the basic unit of all biological information. The power of the idea can be seen today in the way personal genomics is revolutionising drug development, therapy and precision oncology – preventing and treating diseases taking into account individual variability in genes , environment and lifestyle. Genomics is being combined with Artificial Intelligence to mine vast amounts of genetic information for new clues about disease, diagnosis or treatment and combining the amazing potential in AI and genetics for opening new horizons in healthcare. Why is the idea dangerous? Because like the other two profoundly destabilising scientific ideas of the atom and the byte that richochet through the 20th century, the gene has transformed culture, society, politics and language. Mukhergee goes right back to the first steps in understanding the mechanism and influence of genes with Mendel and Darwin and roller coasters through the 20th century. The scientific progress falls into 4 stages ; the establishment of the cellular basis of heredity: the chromosomes; the molecular basis of hereditary :the double helix; the informational basis : the genetic code and sequencing of the human genome; and finally the era of genomics: the deciphering, reading and understanding the human genome and developing medical applications. He tells history is told in an extremely personal and readable way describing how scientists built on each others’ contribution with accelerating progress. The book is full of detective stories – for example how it had taken Morgan and his team three decades to collect fifty fly mutants in New England. Then one night in 1926 Muller discovered the effects of radiation and mutated half that number in a single night. Or for example, the detective work of Watson and Crick in discovering the double helix structure of DNA following the groundbreaking work of Linus Pauling, Robert Corey, Maurice Wilkins and Rosalind Franklin. There is a feeling of balance in Mukhergee’s account of the race for sequencing the human genome, once Muller had discovered the way to copy a human gene in a test tube. The US National Institute of Health (NIH) was chosen as the lead agency to sequence the entire human genome with the US’s DOE and the UK’s Medical Research Council and Wellcome Trust joining the effort. However a little known, pugnacious, single minded neurobiologist at the NIH, Craig Venter, proposed a shortcut to genome sequencing. James Watson and the NIH were appalled at not only at Venter’s technique but at his proposal to patent genes. Scientists at Stanford had patented methods to recombine pieces of DNA to create genetic chimeras, Genetech had patented processes to express proteins such as insulin, Amgen had filed a patent for isolation of erythropoietin using recombinant DNA but nobody had patented a gene or piece of genetic information for its own sake. The race between the US and UK’s public agencies and Craig Venter’s privately funded company Celera was on. The Wellcome Trust doubled its funding and congress threw open the slices of federal funding. But a kind of truce was struck and in 2001 the Human Genome Project and Celera both published their results of the sequencing of the human genome marking the start of the era of genomics. But the history of the gene is told not just from the angle of scientific discoveries. The social effects of the development of the genetics are explored. The history of eugenics and its misuse widely in the USA for sterilising imbeciles to improve human intelligence is shown to be based on a totally fallacious theory of hereditary. The Nazi eugenic experiments and the holocaust gruesomely exposed the danger of false science. The Asilomar meeting in 1973 of leading virologists, genetiscists, biochemists and microbiologists addressed the growing concerns about gene – manipulation techniques. Asilomar II in 1975 got unanimous support for ranking the biohazard risks of genetic recombination. This has resulted until recently in three unspoken principles which guide the arena of genetic diagnosis and intervention. Firstly diagnostic tests have been restricted to gene variants that are singularly powerful determinants of illness – for examplehighly penetrant mutations like Downs syndrome and cystic fibrosis. Secondly, the diseases caused by these mutations have generally involved extraordinary suffering. Thirdly justifiable interventions have been defined by social and medical consensus, and all interventions have been governed by complete freedom of choice. But these boundaries could be loosening from these originals - of high penetrance genes, extraordinary suffering and justifiable interventions - to genotype-driven social engineering. Mukherjee provides examples of genetic diagnosis being transformed into clinical and personal realities. Individuals are inspired to get our personal human genome mapped which could lead to determining genetic fitness. Individuals are not so easily governed by guiding principles. Evidence of the influence this book has had on me is that I have now set out to get my personal genome sequenced!

10% absolutely fascinating 90% above my head. Well worth the effort.

The Gene: An Intimate History is an epic story of how we have come to understand some of the fundamental building blocks of life on earth. From Mendel growing his peas via Darwin and the origin of species, eugenics and the Nazis, Crick and Watson discovering the double helix structure of DNA to the tantalising prospects of genome enhancement, Siddhartha Mukherjee takes us comprehensively through the whole history. It's a complex subject, but the writing is just the right level for someone (like me) with no biology or chemistry background at all to understand. He also covers the moral and ethical aspects of some of the research as well as the science. There's a lot to it, and it does take a while to read, but it's such a fascinating tale that it's well worth the effort. Awe-inspiring and downright mind-boggling in places, if popular science is your thing then you won't want to miss this one.

I'm not a scientist – who am I to review a heavy (2½lbs) book on a great scientific issue ? Well, why not ? - I drive a car and use computers without much clue about how they work. And, it's a great story, told, (like good war history) by mixing anecdotes and theory. It begins in the 1850s with Gregor Mendel breeding sweet peas and exploring how their characteristics (tall, short, flower colour and so on) were transmitted, while Charles Darwin was studying wildlife and exploring why species developed and changed. Both men had ideas about what was happening, but didn't know how it was done. Something was being passed from one generation to the next, and adapting to change - but what was it ? And then, Mendel's work was forgotten for 40 years. By the 1920s, American scientists were using the still barely understood process to eliminate inferior humans by sterilising women with mental or physical problems, and to run "Better Babies" events ~ an early version of Eugenics before that concept was debased by Nazi Germany in the very years when the presence of genetic information was discovered in DNA. In the 1950s, British scientists pioneered techniques to identify the structure of the DNA in chromosomes. By now it will be clear that the science is above my head, but even a complete layman can see the beauty of the “double helix” and enjoy the ferocious rivalries, cheating and squabbling between the scientific teams. From then on, the story becomes more and more bewildering. The role of the gene in illnesses like haemophilia, AIDS and cystic fibrosis was gradually uncovered: on its own that's enlightening enough, but gene combinations were identified at the root of more complex medical conditions and even perhaps of differing human temperaments. Gene modification entered the scene, with the possibility of Eugenics returning in one form or another. Lawyers joined the scientists in their debates, albeit to advise on how to counter legal action when experiments go wrong, rather than to tease out ethical issues, When you read that modifying the gene sequence in an embryo stem cell before it is implanted in an IVF candidate's womb could end the risk of hereditary disease in all future generations of that family …. well, you can see why the author talks of “ethical vertigo”. I'll have to read the book again to be sure I've grasped as much as a layman can, but it will stand a second reading. When I said it was heavy, I meant the weight of the book, not its content.

Love this book and all the past gossips about genes!