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The Gene: An Intimate History
Author: Siddhartha Mukherjee

Publisher: Penguin Books
ISBN: 978-0670087143
Pages: 592
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Spanning the globe and several centuries, The Gene is the story of the quest to decipher the master-code that makes and defines humans, that governs our form and function.

The story of the gene begins in an obscure Augustinian abbey in Moravia in 1856, where a monk stumbles on the idea of a ‘unit of heredity’. It intersects with Darwin’s theory of evolution, and collides with the horrors of Nazi eugenics in the 1940s. The gene transforms post-war biology. It reorganizes our understanding of sexuality, temperament, choice and free will. Above all, this is a story driven by human ingenuity and obsessive minds–from Charles Darwin and Gregor Mendel to Francis Crick, James Watson and Rosalind Franklin, and the thousands of scientists still working to understand the code of codes.

This is an epic, moving history of a scientific idea being brought to life, by the author of The Emperor of All Maladies. But woven through The Gene, like a red line, is also an intimate history–the story of Mukherjee’s own family and its recurring pattern of mental illness, reminding us that genetics is vitally relevant to everyday lives. These concerns reverberate even more urgently today as we learn to ‘read’ and ‘write’ the human genome–unleashing the potential to change the fates and identities of our children. Majestic in its ambition, and unflinching in its honesty, The Gene gives us a definitive account of the fundamental unit of heredity–and a vision of both humanity’s past and future.

Most Helpful Customer Reviews :

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.
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