The Gene: An Intimate History
Read an extract from Pulitzer Prize-winning author Siddhartha Mukherjee's and Wellcome Book Prize shortlisted history of the gene, all the way from Aristotle to the Human Genome Project.
The annual Wellcome Book Prize celebrates the best new fiction and non-fiction books that engage with an aspect of medicine, health or illness, and each week until the announcement of the winner on 24 April at the Wellcome Collection we will be featuring an extract from the WBP2017 shortlist here on sciencefocus.com.
See the full shortlist at the bottom of this article, but first read the prologue of The Gene, a magnificent history of the gene by Pulitzer Prize-winning and New York Times bestseller Siddhartha Mukherjee.
Extract from ‘Prologue: Families’
As I write this, organisms endowed with genomes are learning to change the heritable features of organisms endowed with genomes. I mean the following: in just the last four years—between 2012 and 2016—we have invented technologies that allow us to change human genomes intentionally and permanently (although the safety and fidelity of these “genomic engineering” technologies still need to be carefully evaluated). At the same time, the capacity to predict the future fate of an individual from his or her genome has advanced dramatically (although the true predictive capacities of these technologies still remain unknown). We can now “read” human genomes, and we can “write” human genomes in a manner inconceivable just three or four years ago.
It hardly requires an advanced degree in molecular biology, philosophy, or history to note that the convergence of these two events is like a headlong sprint into an abyss. Once we can understand the nature of fate encoded by individual genomes (even if we can predict this in likelihoods rather than in certainties) and once we acquire the technology to intentionally change these likelihoods (even if these technologies are inefficient and cumbersome) our future is fundamentally changed. George Orwell once wrote that whenever a critic uses the word human, he usually renders it meaningless. I doubt that I am overstating the case here: our capacity to understand and manipulate human genomes alters our conception of what it means to be “human.”
The atom provides an organizing principle for modern physics—and it tantalizes us with the prospect of controlling matter and energy. The gene provides an organizing principle for modern biology—and it tantalizes us with the prospect of controlling our bodies and fates. Embedded in the history of the gene is “the quest for eternal youth, the Faustian myth of abrupt reversal of fortune, and our own century’s flirtation with the perfectibility of man.” Embedded, equally, is the desire to decipher our manual of instructions. That is what is at the center of this story.
This book is organized both chronologically and thematically. The overall arc is historical. We begin in Mendel’s pea-flower garden, in an obscure Moravian monastery in 1864, where the “gene” is discovered and then quickly forgotten (the word gene only appears decades later). The story intersects with Darwin’s theory of evolution. The gene entrances English and American reformers, who hope to manipulate human genetics to accelerate human evolution and emancipation. That idea escalates to its macabre zenith in Nazi Germany in the 1940s, where human eugenics is used to justify grotesque experiments, culminating in confinement, sterilization, euthanasia, and mass murder.
A chain of post–World War II discoveries launches a revolution in biology. DNA is identified as the source of genetic information. The “action” of a gene is described in mechanistic terms: genes encode chemical messages to build proteins that ultimately enable form and function. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin solve the three-dimensional structure of DNA, producing the iconic image of the double helix. The three-letter genetic code is deciphered.
Two technologies transform genetics in the 1970s: gene sequencing and gene cloning—the “reading” and “writing” of genes (the phrase gene cloning encompasses the gamut of techniques used to extract genes from organisms, manipulate them in test tubes, create gene hybrids, and produce millions of copies of such hybrids in living cells.) In the 1980s, human geneticists begin to use these techniques to map and identify genes linked to diseases, such as Huntington’s disease and cystic fibrosis. The identification of these disease-linked genes augurs a new era of genetic management, enabling parents to screen fetuses, and potentially abort them if they carry deleterious mutations (any person who has tested their unborn child for Down syndrome, cystic fibrosis, or Tay-Sachs disease, or has been tested herself for, say, BRCA1 or BRCA2 has already entered this era of genetic diagnosis, management, and optimization. This is not a story of our distant future; it is already embedded in our present).
Multiple genetic mutations are identified in human cancers, leading to a deeper genetic understanding of that disease. These efforts reach their crescendo in the Human Genome Project, an international project to map and sequence the entire human genome. The draft sequence of the human genome is published in 2001. The genome project, in turn, inspires attempts to understand human variation and “normal” behaviour in terms of genes.
The gene, meanwhile, invades discourses concerning race, racial discrimination, and “racial intelligence,” and provides startling answers to some of the most potent questions coursing through our political and cultural realms. It reorganizes our understanding of sexuality, identity, and choice, thus piercing the center of some of the most urgent questions coursing through our personal realms.*
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There are stories within each of these stories, but this book is also a very personal story—an intimate history. The weight of heredity is not an abstraction for me. Rajesh and Jagu are dead. Moni is confined to a mental institution in Calcutta. But their lives and deaths have had a greater impact on my thinking as a scientist, scholar, historian, physician, son, and father than I could possibly have envisioned. Scarcely a day passes in my adult life when I do not think about inheritance and family.
Most important, I owe a debt to my grandmother. She did not—she could not—outlive the grief of her inheritance, but she embraced and defended the most fragile of her children from the will of the strong. She weathered the buffets of history with resilience—but she weathered the buffets of heredity with something more than resilience: a grace that we, as her descendants, can only hope to emulate. It is to her that this book is dedicated.
* Some topics, such as genetically modified organisms (GMOs), the future of gene patents, the use of genes for drug discovery or biosynthesis, and the creation of new genetic species merit books in their own right, and lie outside the purview of this volume.
The full 2017 Wellcome Book Prize shortlist is:
- How to Survive a Plague by David France (USA) Picador, Pan Macmillan
- When Breath Becomes Air by Paul Kalanithi (USA) The Bodley Head, Penguin Random House
- Mend the Living by Maylis de Kerangal (France) trans. Jessica Moore MacLehose Press
- The Tidal Zone by Sarah Moss (UK) Granta Books
- The Gene by Siddhartha Mukherjee (USA) The Bodley Head, Penguin Random House
- I Contain Multitudes by Ed Yong (UK) The Bodley Head, Penguin Random House
The Gene: An Intimate History by Siddhartha Mukherjee is out now (Vintage Books, £8.99 Paperback, £25 Hardback)