Book review: a fascinating and sobering history of our knowledge of genes

The Gene: An Intimate History by Siddhartha Mukherjee Scribner 4/5 stars “Like Pythagoras’ triangle, like the cave paintings at Lascaux, like the Pyramids in Giza, like the image of a fragile blue planet seen from outer space, the double helix of DNA is an iconic image, etched permanently into human history and memory,” Siddhartha Mukherjee writes in The Gene: An Intimate History, a fascinating and often sobering history of how humans came to understand the roles of genes in making us who we are – and what our manipulation of those genes might mean for our future. Mukherjee, an oncologist, won the Pulitzer Prize for an earlier non-fiction book, The Emperor of all Maladies, a history of cancer and its treatment that also delved into the lobbying, fundraising and awareness effort known as the War on Cancer. Mukherjee interspersed some stories from his medical practice in the narrative history of Maladies; in The Gene, he gets even more personal, writing about several family members with inherited mental illness. Getting to know an ancient foe He goes back to ancient Greece for early theories about how human characteristics are passed through generations, including Aristotle’s surprisingly prescient thought that the transmission of heredity was primarily the transmission of information. Nineteenth-century pioneers Gregor Mendel (a monk whose abbot, Mukherjee jokes, “didn’t mind giving peas a chance”) and Charles Darwin are given their due in crisp, detailed accounts of their work. “The essence of Darwin’s disruptive genius was his ability to think about nature not as fact – but as process, as progression, as history,” Mukherjee writes. Unfortunately, their advances indirectly led to the first, but hardly last, wave of eugenicists, and such horrors as the court-sanctioned sterilisation of Carrie Buck to prevent her “feebleminded” line from continuing, and the Nazi eugenics programme, including Josef Mengele’s notorious twin studies. “Mengele’s experiments putrefied twin research so effectively, pickling the entire field in such hatred, that it would take decades for the world to take it seriously,” Mukherjee writes. The Gene captures the scientific method – questioning, researching, hypothesising, experimenting, analysing – in all its messy, fumbling glory, corkscrewing its way to deeper understand and new questions. Scientists had a fuzzy notion of what genes were long before they could explain how they worked. One of this book’s surprising heroes is Erwin Schrödinger, the physicist who also gave the world a thought experiment about a cat in a box to illuminate a problem in quantum mechanics. In a 1944 lecture published as What is Life?, Schrödinger imagined what a gene is and how it must work as if he saw DNA in his mind, including “a chemical with multiple chemical bonds stretching out along the length of the ‘chromosome fibre’.” Mukherjee’s thrilling account of how James Watson and Francis Crick developed the double-helix model also describes Rosalind Franklin’s overlapping research – and the contributions of other scientists to the nutrient dish of the times. Approaching our own times, the pace of discovery quickens as researchers refine both their questions and their tools, leading to the Human Genome Project and gene therapy – and to difficult ethical questions. Mukherjee reminds us of Richard Dawkins’ remark that most genes are recipes, not blueprints. A few illnesses, such as Huntington’s or sickle-cell disease, are caused by single-gene mutations. But often, as in the mutant BRCA1 gene that increases the risk for breast cancer, not all women carrying that mutation develop the disease. “Such trigger-dependent or chance-dependent genes are described as having partial or incomplete ‘penetrance’ – i.e., even if the gene is inherited, its capacity to penetrate into an actual attribute is not absolute. Or a gene may have variable ‘expressivity’ – i.e., even if the gene is inherited, its capacity to become expressed as an actual attribute varies from one individual to another.” Hard to put down - a hectic but rewarding year in books One woman with the BRCA1 mutation may develop aggressive cancer, another may develop a slower-growing cancer, and a third no cancer at all. “You cannot use just the genotype – BRCA1 mutation – to predict the final outcome with certainty,” Mukherjee writes. His discussions of expressivity and penetrance are among the most helpful parts of his book. Scientists now have the ability to manipulate almost any gene and to incorporate that genetic change permanently in an animal. But should they do so in humans? Leading researchers in this field, such as Jennifer Doudna of the University of California, Berkeley, one of the inventors of genome-editing technique, have called for a moratorium on using that technique in human germ line engineering — i.e., making gene changes that would be passed on to offspring. Tribune News Service