A Deep and Intimate Inquiry of Genes SiddharthaMukherjeeThe Gene: An Intimate History2016Scribner608 pp. $32.00

If you were to write your first book and get a Pulitzer Prize, you might think about resting on your laurels, to quit while you’re ahead. But not Siddhartha Mukherjee, who felt compelled, after his Emperor of All Maladies definitive biography of cancer, to take on the big, highly ambitious project of telling the story of the gene—a story that had been previously told in many pieces but not from Pythagoras (530 BC) to the present, no less the ‘‘future of the future.’’ Mukherjee frames the discovery of the gene—the particulate unit of heredity— as a puzzle that took many decades to solve, getting off to a serious start with Darwin and Mendel in the mid-1800s. He connects the two: ‘‘both clergymen, both gardeners, both obsessive observers of the natural world’’ and that their work complemented one another—‘‘heredity was the yin to evolution’s yang.’’ Their classic work with finches and peas, respectively, was not appreciated when presented. Darwin’s was described that it had ‘‘not yielded any particularly noteworthy discoveries’’ and Mendel’s 44-page paper was cited only 4 times between 1866–1900. Talk about sleeping beauty scientific publications. The problem was that the gene was conceptual and only abstract, a ‘‘ghost lurking in the biological machine,’’ even when the term genetics was coined by Bateson in 1905 and gene in 1909 by Johannsen. A break occurred in 1911, when Sturtevant, an undergraduate student in the Morgan lab studying Drosophila genetics, produced the first linear genetic map. Yet the value of such a linkage framework to map the human genome took almost seven more decades before Botstein, Davis, and Skolnick published their paper in 1980 that ultimately led to the Human Genome Project (Am. J. Hum. Genet. 32, 314–331). That paper is described in typical Mukherjee style: ‘‘festooned with statistical data and mathematical equations, reminiscent of Mendel’s classic paper.’’ It took the concrete discovery of DNA’s structure by Watson, Crick, and Franklin and the ability to sequence the genome by pioneering efforts of Sanger, Gilbert, and others to eventually realize that mapping the human genome could indeed be accomplished. Mukherjee is one the most talented doctor-authors of our era, who has a remarkable way with words, exemplified by many passages throughout the book, as he takes on the role of master explainer. For epigenetic marks, he turns to margin notes written in a book that change the context without changing the words. He likens the CRISPR/Cas9 genome editing system of ‘‘seeker’’ and ‘‘hitman’’ to Bonnie and Clyde. The Y chromosome is a ‘‘victim of planned obsolescence, destined to a male-only convalescence home where it can vanish, puffing its last cigar, into oblivion.’’ Human embryogenesis is described: ‘‘A dormant spaceship comes to life.genes that coordinate metabolism, motility, cell fate, and identity fire ‘on.’ The boiler room warms up. The lights flicker on in the corridors. The intercom crackles alive.’’ Besides the frequent use of metaphors, he bends our minds by quoting an eclectic group of people ranging from Snoop Dogg to Shakespeare. The dark side of genetics occupies a significant portion of the book. Ironically, Darwin’s cousin, Francis Galton, a pioneer of the eugenics movement in the late 1800s, initially takes us there. The horrific story of Carrie Buck, born in 1906, sterilized and institutionalized despite being normal, is an exemplar; the book is co-dedicated to her for experiencing the perils of eugenics. For Mukherjee acknowledges that the ‘‘gene,’’ ‘‘the fundamental unit of heredity, and the basic unit of all biological information’’ is ‘‘one of the most powerful and dangerous ideas in the history of science.’’ The deep dive into eugenics characterizes Nazism’s ‘‘applied biology’’ and ‘‘racial hygiene,’’ the Sterilization Law that led to about 400,000 sterilizations between 1933 and 1943, and ultimately the systematic genocidal extermination of millions of people. The depiction of how eugenics scorched the earth includes the Soviet collectivization and later in the book the ‘‘ghastly distinction falls on India and China, where more than 10 million female children are missing from adulthood because of infanticide, abortion, and neglect of female children.’’ Mukherjee doesn’t shy away from other ominous directions in genetics, including several chapters that debunk gender, race, sexual orientation, intelligence, and the politics of identity. He exudes compassion when describing children with Down’s syndrome having ‘‘an extraordinary sweetness of temperament, as if in inheriting an extra chromosome they had acquired a concomitant loss of cruelty and malice.’’ Regarding a teenager with profound neurologic impairment but intact cognitive ability, he points out: ‘‘To fail to acknowledge the depth of Erika’s anguish is to reveal a flaw in our empathy. But to refuse to acknowledge the price to be paid in this trade-off is to reveal, conversely, a flaw in our humanity.’’ But it is clear that there is something that really haunts him, perhaps the real motivation for taking on this formidable book project—his family history with two