The Gene: An Intimate History Kindle Edition

Genetics is humanity and life writ large, and this book on the gene by physician and writer Siddhartha Mukherjee paints on a canvas as large as life itself. It deals with both the history of genetics and its applications in health and disease. It shows us that studying the gene not only holds the potential to transform the treatment of human disease and to feed the world’s burgeoning population, but promises to provide a window into life’s deepest secrets and into our very identity as human beings.The volume benefits from Mukherjee’s elegant literary style, novelist’s eye for character sketches and expansive feel for human history. While there is ample explanation of the science, the focus is really on the brilliant human beings who made it all possible. The author’s own troubling family history of mental illness serves as a backdrop and keeps on rearing its head like a looming, unresolved question. The story begins with a trip to an asylum to see his troubled cousin; two of his uncles have also suffered from various "unravelings of the mind". This burden of personal inheritance sets the stage for many of the questions about nature, nurture and destiny asked in the pages that follow.The book can roughly be divided into two parts. The first part is a sweeping and vivid history of genetics. The second half is a meditation on what studying the gene means for human biology and medicine.The account is more or less chronological and this approach naturally serves the historical portion well. Mukherjee does a commendable job shedding light on the signal historical achievements of the men and women who deciphered the secret of life. Kicking off from the Greeks’ nebulous but intriguing ideas on heredity, the book settles on the genetics pioneer Gregor Mendel. Mendel was an abbot in a little known town in Central Europe whose pioneering experiments on pea plants provided the first window into the gene and evolution. He discovered that discrete traits could be transmitted in statistically predictable ways from one generation to next. Darwin came tantalizingly close to discovering Mendel’s ideas (the two were contemporaries), but inheritance was one of the few things he got wrong. Instead, a triumvirate of scientists rediscovered Mendel’s work almost thirty years after his death and spread the word far and wide. Mendel’s work shows us that genius can emerge from the most unlikely quarters; one wonders how rapidly his work might have been disseminated had the Internet been around.The baton of the gene was next picked up by Francis Galton, Darwin’s cousin. Galton was the father of eugenics. Eugenics has now acquired a bad reputation, but Galton was a polymath who made important contributions to science by introducing statistics and measurements in the study of genetic differences. Many of the early eugenicists subscribed to the racial theories that were common in those days; many of them were well intended if patronizing, seeking to ‘improve the weak’, but they did not see the ominous slippery slope which they were on. Sadly their ideas fed into the unfortunate history of eugenics in America and Europe. Eugenics was enthusiastically supported in the United States; Mukherjee discusses the infamous Supreme Court case in which Oliver Wendell Holmes sanctioned the forced sterilization of an unfortunate woman named Carrie Buck by proclaiming, “Three generations of imbeciles are enough”. Another misuse of genetics was by Trofim Lysenko who tried to use Lamarck’s theories of acquired characteristics in doomed agricultural campaigns in Stalinist Russia; as an absurd example, he tried to “re educate” wheat using “shock therapy”. The horrific racial depredations of the Nazis which the narrative documents in some detail of course “put the ultimate mark of shame” on eugenics.The book then moves on to Thomas Hunt Morgan’s very important experiments on fruit flies. Morgan and his colleagues found a potent tool to study gene propagation in naturally occurring mutations. Mutations in specific genes (for instance ones causing changes in eye color) allowed them to track the flow of genetic material through several generations. Not only did they make the crucial discovery that genes lie on chromosomes, but they also discovered that genes could be inherited (and also segregated) in groups rather than by themselves. Mukherjee also has an eye for historical detail; for example, right at the time that Morgan was experimenting on flies, Russia was experimenting with a bloody revolution. This coincidence gives Mukherjee an opening to discuss hemophilia in the Russian royal family – a genetically inherited disease. A parallel discussion talks about the fusion of Darwin's and Mendel’s ideas by Ronald Fisher, Theodosius Dobzhansky and others into a modern theory of genetics supported by statistical reasoning in the 40s – what’s called the Modern Synthesis.Morgan and others’ work paved the way to recognizing that the gene is not just some abstract, ether-like ghost which transmits itself into the next generation but a material entity. That material entity was called DNA. The scientists most important for recognizing this fact were Frederick Griffiths and Oswald Avery and Mukherjee tells their story well; however I would have appreciated a fuller account of Friedrich Miescher who discovered DNA in pus bandages from soldiers. Griffiths showed that DNA can be responsible for converting non-virulent bacteria to virulent ones; Avery showed that it is a distinct molecule separate from protein (a lot of people believed that proteins with their functional significance were the hereditary material).All these events set the stage for the golden age of molecular biology, the deciphering of the structure of DNA by James Watson (to whom the quote in the title is attributed), Francis Crick, Rosalind Franklin and others. Many of these pioneers were inspired by a little book by physicist Erwin Schrodinger which argued that the gene could be understood using precise principles of physics and chemistry; his arguments turned biology into a reductionist science. Mukherjee’s account of this seminal discovery is crisp and vivid. He documents Franklin’s struggles and unfair treatment as well as Watson and Crick’s do-what-it-takes attitude to use all possible information to crack the DNA puzzle. As a woman in a man’s establishment Franklin was in turn patronized and sidelined, but unlike Watson and Crick she was averse to building models and applying the principles of chemistry to the problem, two traits that were key to the duo’s success.The structure of DNA of course inaugurated one of the most sparkling periods in the history of intellectual thought since it immediately suggested an exact mechanism for copying the hereditary material as well as a link between DNA and proteins which are the workhorses of life. The major thread following from DNA to protein was the cracking of the genetic code which specifies a correspondence between nucleotides on a gene and the amino acids of a protein: the guiding philosophers in this effort were Francis Crick and Sydney Brenner. A parallel thread follows the crucial work of the French biologists Francois Jacob and Jacques Monod - both of whom had fought in the French resistance during World War 2 - in establishing the mechanism of gene regulation. All these developments laid the foundation for our modern era of genetic engineering.The book devotes a great deal of space to this foundation and does so with verve and authority. It talks about early efforts to sequence the gene at Harvard and Cambridge and describes the founding of Genentech, the first company to exploit the new technology which pioneered many uses of genes for producing drugs and hormones: much of this important work was done with phages, viruses which infect bacteria. There is also an important foray into using genetics to understand embryology and human development, a topic with ponderous implications for our future. With the new technology also came new moral issues, as exemplified by the 1975 Asilomar conference which tried to hammer out agreements for the responsible use of genetic engineering. I am glad Mukherjee emphasizes these events, since their importance is only going to grow as genetic technology becomes more widespread and accessible.These early efforts exploded on to the stage when the Human Genome Project (HGP) was announced, and that’s where the first part of the book roughly ends. Beginning with the HGP, the second part mainly focuses on the medical history and implications of the gene. Mukherjee’s discussion of the HGP focuses mainly on the rivalries between the scientists and the competing efforts led by Francis Collins of the NIH and Craig Venter, the maverick scientist who broke off and started his own company. This discussion is somewhat brief but it culminates in the announcement of the map of the human genome at the White House in 2000. It is clear now that this “map” was no more than a listing of components; we still have to understand what the components mean. Part of that lake of ignorance was revealed by the discovery of so-called ‘epigenetic’ elements that modify not the basic sequence of DNA but the way it’s expressed. Epigenetics is an as yet ill-understood mix of gene and environment which the book describes in some detail. It’s worth noting that Mukherjee’s discussion of epigenetics has faced some criticism lately, especially based on his article on the topic in the New Yorker.The book then talks about early successes in correlating genes with illness that came with the advent of the human genome and epigenome; genetics has been very useful in finding determinants and drugs for diseases like sickle cell anemia, childhood leukemia, breast cancer and cystic fibrosis. Mukherjee especially has an excellent account of Nancy Wexler, the discoverer of the gene causing Huntington’s disease, whose search for its origins led her to families stricken with the malady in remote parts of Venezuela. While such diseases have clear genetic determinants, as Mukherjee expounds upon at length, genetic causes for diseases like cancer, diabetes and especially the mental illness which plagues members of the author’s family are woefully ill-understood, largely because they are multifactorial and suffer from weakly correlated markers. We have a long way to go before the majority of human diseases can be treated using gene-based treatment. In its latter half the book also describes attempts to link genes to homosexuality, race, IQ, temperament and gender identity. The basic verdict is that while there is undoubtedly a genetic component to all these factors, the complex interplay between genes and environment means that it’s very difficult currently to tease apart influences from the two. More research is clearly needed.The last part of the book focuses on some cutting edge research on genetics that’s uncovering both potent tools for precise gene engineering as well as deep insights into human evolution. A notable section of the book is devoted to the recent discovery that Neanderthals and humans most likely interbred. Transgenic organisms, stem cells and gene therapy also get a healthy review, and the author talks about successes and failures in these areas (an account of a gene therapy trial gone wrong is poignant and rattling) as well as ethical and political questions which they raise. Finally, a new technology called CRISPR which has taken the world of science by storm gets an honorary mention: by promising to edit and propagate genes with unprecedented precision - even in the germ line - CRISPR has resurrected all the angels and demons from the history of genetics. What we decide about technologies like CRISPR today will impact what our children do tomorrow. The clock is ticking.In a project as ambitious as this there are bound to be a few gaps. Some of the gaps left me a bit befuddled though. There are a few minor scientific infelicities: for instance Linus Pauling’s structure of DNA was not really flawed because of a lack of magnesium ions but mainly because it sported a form of the phosphate groups that wouldn’t exist at the marginally alkaline pH of the human body. The book’s treatment of the genetic code leaves out some key exciting moments, such as when a scientific bombshell from biochemist Marshall Nirenberg disrupted a major meeting in the former Soviet Union. I also kept wondering how any discussion of DNA’s history could omit the famous Meselson-Stahl experiment; this experiment which very elegantly illuminated the central feature of DNA replication has been called “the most beautiful experiment in biology”. Similarly I could see no mention of Barbara McClintock whose experiments on ‘jumping genes’ were critical in understanding how genes can be turned on and off. I was also surprised to find few details on a technique called PCR without which modern genetic research would be virtually impossible: both PCR and its inventor Kary Mullis have a colorful history that would have been worth including. Similarly, details of cutting-edge sequencing techniques which have outpaced Moore’s Law are also largely omitted. I understand that a 600 page history cannot include every single scientific detail, but some of these omissions seem to me to be too important to be left out.More broadly, there is no discussion of the pros and cons of using DNA to convict criminals: that would have made for a compelling human interest story. Nor is there much exploration of using gene sequences to illuminate the ‘tree of life’ which Darwin tantalizingly pulled the veil back on: in general I would have appreciated a bigger discussion of how DNA connects us to all living creatures. There are likewise no accounts of some of the fascinating applications of DNA in archaeological investigations. Finally, and this is not his fault, the author suffers from the natural disadvantage of not being able to interview many of the pioneers of molecular biology since they aren’t around any more (fortunately, Horace Freeland Judson’s superb “The Eighth Day of Creation” fills this gap: Judson got to interview almost every one of them for his book). This makes his account of science sound a bit more linear than the messy, human process that it is.The volume ends by contemplating some philosophical questions: What are the moral and societal implications of being able to engineer genomes even in the fetal stage? How do we control the evils to which genetic technology can be put? What is natural and what isn’t in the age of the artificial gene? How do we balance the relentless, almost inevitable pace of science with the human quest for responsible conduct, dignity and equality? Mukherjee leaves us with a picture of these questions as well as one of his family and their shared burden of mental illness: a mirage searching for realization, a sea of questions looking for a tiny boat filled with answers.Overall I found “The Gene: An Intimate History” to be beautifully written with a literary flair, and in spite of the omissions, the parts of genetic history and medicine which it does discuss are important and instructive. Its human stories are poignant, its lessons for the future pregnant with pitfalls and possibilities. Its sweeping profile of life’s innermost secrets could not help but remind me of a Japanese proverb quoted by physicist Richard Feynman: “To every man is given the key to the gates of heaven. The same key opens the gates of hell.” The gene is the ultimate key of this kind, and Mukherjee’s book explores its fine contours in all their glory and tragedy. We have a choice in deciding which of these contours we want to follow.

My daughter wrote summary of this book.The “Missing Science of Heredity” is a chapter covering the oldest history of the gene - the discovery (and re-discovery) of genes. It may be split into two parts. The first part covers the theories that existed for heredity in the past (preformation), and the observations of the leading scientists at the time (Pythagoras, Aristotle, Mendel, Darwin, and others, progressively moving forward in time). It covers the issues with initial theories, and shows consequent theories, proved from correlation and evidence (pangenesis) and terms created at the time (composites, alleles, dominant, recessive, gemmules), and the eventual discovery of evolution. The second part of the chapter covers the more - well - unnatural - and human - history of the gene. After discovering natural selection, the idea was created that unnatural selection could be induced, eliminating more undesirable traits. Eugenics. It covers how the word gene was christened from pangene, and genotypes. The beginning of eugenics is covered in this part of the chapter, as well as racial purity and ‘cleansing’, of which two types are detailed.“In the Sum of the Parts, There Are Only the Parts” is a chapter covering how scientists connected environments and physical body parts to the abstract concept of the gene. Protein, form, function, genotypes, and phenotypes are slowly linked together by brilliant minds. From Dobzhansky to Watson and Crick, this chapter also elaborates on how these scientists, though brilliant, may not have been the best people. This chapter also shows how discrepancies, or ‘mistakes’ in the genome can cause dangerous diseases. To sum it up, it covers inheritance. It also covers eugenics, and the danger of falling onto the path of thinking you can fix the genome by editing it. It elaborates on the horrific experiences of concentration camps. It also covers how DNA and genes were discovered separately and only linked together later as two parts of the same whole.“The Dreams of Geneticists'' is a chapter covering the sequencing and cloning of genes. Genetic hybrids are covered in this chapter along with terms such as recombination, splicing, exons, and introns, while also including key scientists. Composition, decomposition, and cloning of genes are covered. In this chapter there’s also a captioned selection of pictures that are relevant to genes.“The Proper Study of Mankind Is Man” is a chapter covering deeper gene editing, and delving deeper into connections between diseases and genes from Parkinson’s disease to cystic fibrosis. It also gives information on how the human genome was finally sequenced, and the trouble in fragmented overlapping of the human genome. It shows the exact ways gene-caused diseases are caused hereditarily, and/or the mutations which cause them. After a brief skimming of neo-eugenics, the chapter also goes into how scientists and doctors have tried to cure these gene-caused diseases, both by preventing them before they happen and gene editing after they have happened. The chapter is completed with a subchapter: The Book of Man (in Twenty-Three Volumes).Through the Looking Glass is a chapter covering how genes affect identity - the effect of genes on sexuality and gender identity, and how environments also may or may not contribute to these. It also covers the issue of “race based intelligence”, and how stereotypes and standards are enforced leading to more issues, not because of genes. It covers how sex and gender identity may be tied to genes, or of course, may not be, ending with the a diagram of the phenotype-genotype cycle.Post-Genome is a chapter covering the future of genes and genomics. It covers current gene therapy and gene editing procedures and why it’s flawed, and that may be improved in the future. It covers crossovers between different species, and choosing ideal genes from each species. It also covers diseases caused by a single, relatively common mutation (breast cancer), multiple, untreatable mutations (schizophrenia, bipolar disorder), or a few extremely rare mutations and different and irreversible effects on people afflicted with them (previvors). When should these diseases be fixed? Positive eugenics is also discussed. Then the book discusses the differences between genetic emancipation - and genetic enhancement, and the questions which come about these two. It discusses the difference between editing a gene and editing the genome. The chapter shows the difference between phenotype and genotype, and how the two are inevitably linked, and it is impossible to have one without the other. It ends with a list of thirteen things to learn from the book in sum.

Bought this for use as a possible textbook for my college course DNA and Society, easy reading of what can be a difficult topic for college students.

I liked the book-The Gene: An Intimate History by Siddhartha Mukherjee. Being a former teacher of Human Anatomy including Genetics, I am aware of the vastness of the subject and its branches but this book covers all the important aspects in less than 600 pages. The book has been divided into Parts and in each Part, there are several chapters; this makes convenient reading. All the parts and chapters have been thought provokingly titled.The author has meticulously avoided technical terms as the book is intended to be for the lay readers. If you are interested in the development and evolution of the subject, this is a book for you; it makes interesting reading. The author’s background has lent authenticity to the contents. He has tried to give justice to every character who contributed significantly: Aristotle, Darwin, Mendel, Morgan, Bateson, Johannsen, Galton, Garrod, Beadle and Tatum, Jacob and Monod, Watson and Crick, Khorana, McKusick, Sanger, Berg, Venter, Gurdon and Yamanaka; it is actually ‘Who is who’ of Genetics. Some new terms like previvors have been introduced and Human Genome project has been discussed in details.The narrative is so detailed and vivid that we feel that the author was personally present when and where the history (and the future) happened! I enjoyed reading accounts pertaining to Eugenics, BRCA1, Indian counter part of Nazism, sexual identity, Gay gene etc. I tend to agree with the author’s prediction- “The discontinuity of genes-the discreteness and autonomy of each individual unit of heredity-will turn out to be an illusion: genes may yet be more interconnected than we think.” That would be the end of the prevalent reductionist view of the word-Gene. A clinician is mainly concerned with what can be applied on patients in the clinic. In spite of the tremendous strides that Genetics has taken in recent years, there is not much that can be offered to the needy patients as far as the curative treatment is concerned; this is particularly true for the mental ailments (the author with several members of his family suffering from such disorders knows about this more intimately than anyone else) and the cancers. Some of the advancements are rightly facing political, social and ethical hurdles. If researches on the stem cell and gene therapy are approved wholeheartedly in due course of time, we may see more practically beneficial genetics which not only satisfy curiosity but also cures. Human Genome project has been rightly proved to be just the beginning in this direction; we are now eagerly awaiting the outcomes of Human Epigenome project and Encode. This is a book that broadens your vision whatever your background may be.

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!

I enjoyed the 'Emperor of all maladies' book from this author, so I was keen to read this new tome as well. I was not disappointed. His prose is engaging and his reports of some of the genetics luminaries are amusing (I wish I had someone like him as my Genetics professor at Uni). Most importantly, the concepts arising from genetic research and technology are explained in a way that is understandable by the vast majority of the public. For me the last chapters are particularly stimulating and thought provoking. a must read!

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 one to give praise too freely. I'm an author and scientist (in a different field) and a critical reader by disposition and training. This book, however, deserves the highest praise. It's a masterpiece. The science is pitched perfectly for a layman. The history is enthralling. The two are woven together in a beautiful, thoughtful way. I would make this book required reading for everyone. Bravo Mr Mukherjee.