More complex combinations of genes that might cause tendencies toward disease are also identified by genome sequencing. When children with such predicted tendencies are born, they are offered selective interventions throughout childhood.
It is a world inhabited by “previvors” and “post-humans”: men and women who have been screened for genetic vulnerabilities or created with altered genetic propensities.
It begins with madness. And, it is difficult to resist. Siddhartha Mukherjee took the literary world by storm with The Emperor of All Maladies: A Biography of Cancer. It wasn’t just the research; it was the writing—lucid, lyrical and lush with details. The Gene is no different. It is a book that will stay on bookshelves, not just because of its sheer size but because it is the kind that will be savoured slowly again, and again.
Epic in its scope as well as the writing, the book begins with a personal journey that becomes an exploration for a greater public cause. Mukherjee's family—his father’s two brothers, Rajesh and Jagu, and his nephew Moni—have had mental illness. They “played an outsize role” in the imagination of his family in his childhood and in his adult life, and when he meets his future partner, Sarah, he tells her about the “splintered minds” of his uncles.
There is a period in time when as a teenager he stopped talking to his parents and burnt his books and when his father “dragged” him “glumly” to the same doctor who diagnosed Jagu. Inheritance of loss is at the heart of this mammoth book. Mukherjee travels through centuries and leapfrogs across continents to trace the beginnings of the ‘unit of heredity’ to today, where genes determine identity and certainly can point towards disease.
The book is about vulnerability. It is about ambition. It is about progress. It is about limits and surpassing them. It is also about mortality as well as morality. Mukherjee, known for making complex ideas accessible, is a natural storyteller. He blends history, puffing life into dry academic, medical jargon. There are the early explorers—the plain speaking, ambitious Rosalind Franklin, Charles Darwin, Gregor Johann Mendel, an Augustine monk who can’t master biology, yet discovers the unit of heredity by breeding mice in his room and when frowned upon by the abbot he “switched to plants”—and the dark experiments under Hitler.
Making science interesting might require a skill, and there are plenty of writers who do that and well, but The Gene goes from being just a book about the discovery of this breakthrough unit in science and the history behind it because Mukherjee makes it about a more philosophical point.
At the heart of this book, which talks about the aspect of inheritance and the future where it may be possible to eliminate the sequencing of certain genes totally, is an ethical question and even a moral one: “Under what circumstances can we or should we intervene?” He uses three cases to illustrate his dilemma—Jane Sterling, 37, a nurse who is diagnosed with the breast cancer gene, his uncle Rajesh’s bipolar disease and Erika, a 15-year-old girl with a progressive, degenerative genetic disease. The elimination of his uncle’s madness would also rob him of his genius. (He solved a mathematical puzzle, staying up at night scribbling furiously.) And, then it leads to the logical question: Would it mean the possibility of flawless human beings? The “refusal to acknowledge the price of this tradeoff,” as he says, is “a flaw in our humanity”.
Imagine, then, a world in which these technologies can be routinely deployed. When a child is conceived, every parent is given the choice of testing the fetus using comprehensive genome sequencing in utero. Mutations that cause the most severe impairments are identified, and parents are given the option of aborting such fetuses at the earliest stages of pregnancy, or selectively implanting only the “normal” fetuses after comprehensive genetic screening (we might call this comprehensive preimplantation genetic diagnosis, or c-PGD).*
More complex combinations of genes that might cause tendencies toward disease are also identified by genome sequencing. When children with such predicted tendencies are born, they are offered selective interventions throughout childhood. A child with a predilection toward a genetic form of obesity, for instance, might be monitored for changes in body mass, treated with an alternative diet, or metabolically “reprogrammed” using hormones, drugs, or genetic therapies in childhood. A child with a tendency for an attention-deficit or hyperactivity syndrome might undergo behavioral therapy or be placed in an enriched classroom.
If and when the illnesses do emerge or advance, gene-based therapies are deployed to treat or cure them. Corrected genes are delivered directly into the affected tissues: the functioning cystic fibrosis gene, for instance, is aerosolized and injected into the lungs of patients, where it partially restores the normal function of the lung. A girl born with ADA deficiency is transplanted with bone marrow stem cells carrying the correct gene. For more complex genetic diseases, genetic diagnostics are combined with genetic therapies, with drugs and with “environment therapies.” Cancers are comprehensively analyzed by documenting the mutations responsible for driving malignant growth of one particular cancer. These mutations are used to identify culprit pathways that fuel the growth of cells and to devise exquisitely targeted therapies to kill malignant cells and spare normal cells.
“Imagine you are a soldier returning from war with PTSD,” the psychiatrist Richard Friedman wrote in the New York Times in 2015. “With a simple blood test looking at gene variants, we could discover whether you were biologically adept at fear extinction.... If you had a mutation that reduced your ability to extinguish fear, your therapist would know you might just need more exposure—more treatment sessions—to recover. Or, perhaps a different therapy altogether that doesn't rely on exposure, like interpersonal therapy, or medication.” Perhaps drugs that can erase epigenetic marks are prescribed in combination with talk therapy. Perhaps the erasure of cellular memories can ease the erasure of historical memories.
Genetic diagnoses and genetic interventions are also used to screen and correct mutations in human embryos. When “intervenable” mutations in certain genes are identified in the germ line, parents are given the choice of genetic surgery to alter their sperm and eggs before conception, or prenatal screening of embryos to avoid implanting mutant embryos in the first place. Genes that cause the most detrimental variants of illness are thus excised from the human genome up front by positive or negative selection, or by genome modification.
If you read that scenario carefully, it inspires both wonder and a certain moral queasiness. The individual interventions may not push the boundaries of transgression—indeed some, such as the targeted treatment of cancer, schizophrenia, and cystic fibrosis, represent landmark goals for medicine—but aspects of this world seem distinctly and even repulsively alien. It is a world inhabited by “previvors” and “post-humans”: men and women who have been screened for genetic vulnerabilities or created with altered genetic propensities. Illness might progressively vanish, but so might identity. Grief might be diminished, but so might tenderness. Traumas might be erased but so might history. Mutants would be eliminated but so would human variation. Infirmities might disappear, but so might vulnerability. Chance would become mitigated, but so, inevitably, would choice.*
In 1990, writing about the Human Genome Project, the worm geneticist John Sulston wondered about the philosophical quandary raised by an intelligent organism that has “learned to read its own instructions.” But an infinitely deeper quandary is raised when an intelligent organism learns to write its own instructions. If genes determine the nature and fate of an organism, and if organisms now begin to determine the nature and fate of their genes, then a circle of logic closes on itself. Once we start thinking of genes as destiny, manifest, then it is inevitable to begin imagining the human genome as manifest destiny.
The Gene: An Intimate History
By Siddhartha Mukherjee
Published by Penguin Books India
Price Rs 699; pages 592