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

Eye-opening, well written and thought provoking book

Muy buen libro, explica de forma sencilla pero concisa conceptos importantes sobre genética y biotecnología, además que la forma de llevar la historia lo hace de acuerdo a los eventos más relevantes y en orden cronológico sobre dichas áreas.

De schrijver, van oorsprong oncoloog, beschrijft zijn zoektocht naar de genetische informatie die van de chromosomen vanaf de moestuin in het klooster dat Mendel kan worden afgelezen. Met verbazing kijkt hij achterom en ziet de ongelooflijk secure wijze waarop de wetenschappers grip krijgen op de "zwarte materie"die zich in de celkern bevindt. Maar ook beschrijft hij de pseudowetenschappelijke eugenetica van het Duitse Rijk onder Hitler, die een voortzetting van de gedachtenexperimenten van o.a. Galton, de neef van Darwin bleken te zijn. Van de chromosomen en de genen dalen we af in de getordeerde wereld van het DNA en RNA met als bouwteen voor de informatie de vier welbekende aminozuren. Erfelijkheid is echter afhankelijk van de dubbel aanwezige genen en de genexpressie. De zoektocht naar de locatie van het gen voor homoseksualiteit (Mukherjee noemt alleen de mannelijke variant) is een schoolvoorbeeld van inductie vanuit de wereld van tweelingen. Harde conclusies zijn er niet. Fraai uitgewerkt is het epigenetische geheugen met het intron als essentieel onderdeel. De zoektocht naar gentherapie is aanvankelijk een onthutsende beschrijving van gedroomde resultaten op basis van onvoldoende geverifieerde inzichten. Het zal anders worden, wanneer het enzymmechanisme van het HIV-virus wordt gebruikt om de echte gentherapie te ontwikkelen. Dit alles is geschreven in prachtig Engels. Lezen, zou ik zeggen..

A very interesting introduction to the science behind genetics and genomics that reads like a thriller. Not a dry and uninteresting text book, but the sort of book you can't put down until the last page. Comprehensive and well written, with plenty of references to the original research documents quoted if you want to go deeper into the subject.

I finished reading ‘The Gene’ by Siddhartha Mukherjee last month. It has been a fascinating voyage in the world of biology- genetics to be precise. As I wrote before too, it has been written with great erudition and is richly laced with metaphor and similes to make it comprehensible even for a non-biologist. It staggers my mind to think how must an ocean of research material have been mined for it, grasped, and then put to masterly use by the doctor-writer. Only a man of SM’s calibre who gave us a wonderful book on cancer ‘The emperor of all maladies’ before, could have done it. The gene book tells us in gripping detail the whole story of the gene right from early meanderings before the Christian era by the Greek Philosophers like Pythagoras (530 BC), Anaxagoras (400 BC), Aristotle (350 BC) and many others to unravel the mystery of inheritance. (Incidentally, Anaxagoras thought that the essence of heredity was carried by the male sperm, while the female only “shaped’ male semen in the womb to produce the foetus! And Aristotle argued that hereditary information is transmitted in the form of messages.) Nothing is in fact left out by the author in this long journey of man’s search for answers to the intriguing gene puzzle: Mendel’s experiments on pea to unravel the mystery of inheritance of characters, Darwin’s great voyage, how Watson and Crick cracked the DNA code, the human genome, how the new findings have helped mankind in understanding and curing genetic disorders by gene therapy, gene edting and gene surgery and the future scenario in regard to genomics and humankind. A lot has been done but a lot more still needs to be discovered. So many tricky genetic ailments such as Haemophilia, sickle cell anaemia etc which have afflicted mankind causing huge suffering, are now being cured thanks to new insights into the subtle working of the gene. Many more are on the threshold of being tamed and treated through gene therapy. The quest is on. Needless to say, the coming decades will see man (or a geneticist) playing God with gene editing and cloning technologies in his kitty. It will be for the humankind though to see and decide where to draw the line. What makes the book so outstanding is the interesting manner and the arresting narrative with which the whole story of the gene is laid bare before the mesmerized reader with fascinating details about the personal lives of Mendel, Darwin and all other luminaries who have been involved in their scientific endeavours in unravelling the mystery of the gene right from the beginning till date, their obsessions, devotion, dedication, foibles, failures, jealousies, the politics and so on. Having been a zoologist myself – though not a great one! – I could strike an instant chord with the book and had it fill many gaping voids in my understanding of the gene. Subhash Sharma, Palampur, Kangra HP