The molecular me, tracing the history of the gene
Siddhartha Mukherjee, an oncologist and researcher at Columbia University, grew up under the shadow of madness: A cousin and two uncles experienced psychotic breakdowns and schizophrenia, a fate that his parents worried might eventually befall him when he began acting out as a teenager. By adulthood, he writes, “heredity, illness, normalcy, family, and identity had become recurrent themes of conversation in my family.’’
In his new book, “The Gene: An Intimate History,” Mukherjee ponders the thorny problems of inheritance, nurture, fate, and chance. His father is diagnosed with a neurological condition that runs in families but only emerges in him through aging and after the happenstance of a fall. His mother and aunt are identical twins whose lives and appearance diverge over the years, yet they still share a temperament — what he calls “the first derivative of identity.”
All families have experiences like these. Traits surface in different ways as if distorted by a funhouse mirror. Familial illnesses cast shadows over younger generations. We marvel at how similar we are to our siblings — and how different.
Mukherjee’s previous book, “The Emperor of All Maladies,” winner of the 2011 Pulitzer Prize, was a “biography of cancer” told by a clinician and researcher seeking to understand his nemesis. “The Gene” offers up a similar blend of personal story, vivid scientific and social history, and, in this case, meaty explanation of genetics instead of oncology. Its breadth can at times be exhausting, but Mukherjee has a knack for transforming seemingly dry subjects into elegant and urgent narratives.
His topic is compelling. The pull of inheritance has fascinated and troubled writers for centuries. But now that science is allowing us to glean information and make decisions based on genetics, Mukherjee argues, we need to reckon with our genes.
The book traces the concept of “the gene” as a fundamental unit of heredity, from its historical roots to scientific discovery starting in the mid-19th century. Mukherjee calls it “one of the most powerful and dangerous ideas in the history of science.” It’s powerful because — like the atom and the byte — it allows us to understand a larger system through its constituent parts. And it also lets us begin to manipulate those parts to change the system.
“The Gene” details the work of scientists in laboratories, as well as how their discoveries have ricocheted into the wider world. And it couldn’t have come at a better time.
“We can now ‘read’ human genomes, and we can ‘write’ human genomes in a manner inconceivable just three or four years ago,” Mukherjee writes. Scientists can sift through the genetic codes of thousands of people to find patterns underlying any sort of disease, characteristic, or behavior. Last month, for instance, a study in Nature Genetics found 38 genetic variants related to the age when people first have sex.
Meanwhile, the newly developed genome-editing technology CRISPR-Cas 9 makes it more feasible than ever to create gene therapies or someday even to re-engineer human genomes.
With a spit sample, any of us can obtain stories of our ancestry and our future risk of disease. We can screen fetuses for certain genetic conditions before birth. Genetics has gone finally gone mainstream.
“The Gene“ explains the research that made these feats possible. It retells some familiar stories: Charles Darwin’s voyage on the Beagle, the monk Gregor Mendel observing patterns of inheritance in pea plants, James Watson and Francis Crick deducing the structure of DNA from an x-ray crystallography image by Rosalind Franklin. But Mukherjee also dives into more arcane research on genetic regulation, cell biology, and embryology (it’s a testament to the complexity of this stuff that Mukherjee’s recent attempt to publish a slice of his material on epigenetics in The New Yorker ignited criticism from prominent researchers for misrepresenting the science). He captures the heady days of molecular biology research in the late 20th century, as scientists began to unravel how genes are switched on and off, create genetically modified organisms, and link specific genetic mutations to disease. He takes us into the race to sequence the human genome, the discovery of embryonic stem cells, and the harnessing of CRISPR.
Scattered among these achievements is a messier social history. In the early 20th century, eugenicists in the United States led an effort to confine and sterilize thousands of people deemed “genetically unfit.” These ideas fell out of public favor only when taken to brutal extremes by the Nazis. Arguments about the genetic basis of intelligence were used to justify racial bigotry. Society has struggled to make sense of research linking genes to sexual orientation, gender identity, and personality. Too often, we take sides for “nature” or “nurture” without considering the interplay between genes and experience.
Genetic advancements have brought mixed blessings. With DNA testing, Mukherjee says, we have created a population of “previvors,” people who must make major decisions based on uncertain genetic risks. “The genome will thus be read not in absolutes,” he writes, “but in likelihoods — like a report card that does not contain grades but probabilities, or a résumé that does not list past experiences but future propensities.”
Looking to the future, Mukherjee suggests that our greatest challenge will be deciding how much to intervene in our own genomes. History shows an even greater danger: that we continue to underestimate the complexity of biology. Genes shape the development of mental disorders, behaviors, and even quirks of personality. But this influence is one factor in a larger system. Our ability to manipulate the genome may outpace our understanding of it.
Mukherjee imagines a world, for instance, in which a child is screened for “predicted tendencies” and offered interventions accordingly (an alternative diet, behavioral therapies). We might correct detrimental mutations in human embryos with “genetic surgery.” Such a scenario “inspires both wonder and a certain moral queasiness,” he writes. Any intervention requires a value judgment about what’s better, healthy, or normal. And it’s in making these kinds of judgments where humanity often fails.
An Intimate History
By Siddhartha Mukherjee
Scribner, 592 pp, illustrated, $32
Courtney Humphries is a freelance science writer in Boston.