Siddhartha Mukherjee didn’t want to write a provocative book, but that’s what he ended up doing. For, like many scientists before him, however empirically he sets out to answer the question, ‘What makes us who we are?’, he ends up challenging dogmas and beliefs that have persisted and mutated, much like the human gene, across cultures, religions and continents over centuries.
You probably know Mukherjee as the cancer physician, researcher, geneticist and Pulitzer Prize-winning author of The Emperor of All Maladies. His new book is The Gene – An Intimate History, and it’s partly a memoir and partly a history of the scientific, philosophical and moral questions and answers emerging as we continue to unravel the human genome. The book is also about the future, with Mukherjee flagging ethical issues that cannot be ignored when using technology that comes “with great promise and great peril”.
Who am I?
“The understanding of the human genome certainly changes the way you think about human beings. John Sulston [director of Sanger Institute when it was part of the global consortium that sequenced the human genome] asked the philosophical question, ‘What happens to the organism that learns to decode the instructions that make itself?’ We are nowhere near there yet,” Mukherjee says.
We have just figured out what the 3 billion letters are in the human genome alphabet, adds Mukherjee, who is in Delhi to be with his ailing father, diagnosed with hypertension of the brain, an illness with no known cause that runs in families.
“How those three billion letters combine in space and time to make you and me, to make it so we look similar and yet have profound differences, we don’t know. But we know the basics. I think that puts us in a philosophical and, ethically speaking, a very, very novel, space,” he says.
“We are now trying to figure out what piece of it governs what part of you. And that’s not like a blueprint. It’s an intersection of multiple genes, one’s environment and chance. And you can begin to decode some of that. You can also begin to intervene on some of those, and what’s going to change, I think, is our idea of who we are as humans.”
Watch | Siddhartha Mukherjee on whether post-genomic knowledge changes us as human beings
Close to home
The book is intimate not just because it flirts closely with the innermost codes of what makes us tick but also because of the history of mental illness – schizophrenia, in particular -- in the Mukherjee clan. This made “heredity, illness, normalcy, family and identity… recurrent themes of conversation in my family,” he writes, narrating that so concerned was he with this “scar of history” that he told Sarah, now his wife, about the splintered minds of his cousins and two uncles on their fourth or fifth meeting. “It was only fair to a future partner that I should come with a letter of warning,” he writes.
With a sudden flood of information on the genetics of familial schizophrenia -- like most forms of complex human disease, there is no one single gene for schizophrenia -- Mukherjee considered sequencing his own genome.
“I thought about it quite deeply and I decided that I would not... partly because I would not know what to do with the information,” he says. “It would only kind of give a set of probabilities. So in the end I decided that we weren’t ready, and the world is not ready for that kind of information yet,” he says.
Watch| Why Mukherjee opted out of sequencing his own genome
Recipe, not blueprint
In addition to exploring why we are the way we are, genes force us to ask ourselves what we are likely to pass on to the next generation. There are no simple answers.
On the one hand, the capacity to treat terrifying disease like cancers is advancing rapidly. “Gene therapy has been used re-educate a young woman’s T-cells to recognise and kill her cancer; she is in remission,” he says. “On the other hand, you can foresee tremendous moral implications that tampering with the human genome can have for the future.”
Do genes determine sexual orientation? Twin studies show that sexual preference has strong genetic determinants. “If you take identical twins, the concordance between the likelihood that both of them share the same sexual preference is much higher than random chance. In fact, it drops between identical twins and fraternal twins and that itself suggests that there is a powerful influence of genetics on sexual orientation,” says Mukherjee.
The influence is powerful, but not 100%. “Multiple genetic determinants are only responsible in part for determining sexual orientation. There is a role of environment and chance too,” Mukherjee says.
Watch | Do genes determine sexual orientation?
The hardest part
In his book, Mukherjee’s narrative changes the language of science by pulling it out of sterilised biozones and immersing it in the whirlpool of emotions that define all life. “These books sit in a weird space. They are not classical science writing; they somehow fit between memoir and future. No one knows what to call them, which shelf to stack them on. I like that idea actually, I like writing that kind of book,” he says.
The book took nearly six years, and the hardest part, Mukherjee says, was deciding what to leave out. “The hardest thing to do… is to keep it, as [evolutionary biologist Richard] Dawkins would say, a recipe rather than a blueprint,” he says. “I might write science fiction in the future just because I think the harder it is to pen down, the more interesting the book is.”
The Gene addresses reality with no trace of fantasy. And it answers a question that’s haunted most of us, in one way or another, since kindergarten: Which came first, the chicken or the egg? Mukherjee uses spontaneous mutation to answer this troubling question that has no right answer: “A chicken is merely the egg’s way of making a better egg.”
Excerpts from The Gene: An Intimate History
We need a manifesto – or at least a hitchhiker’s guide – for the post-genomic world. Historian Tony Judt once told me that Albert Camus’s novel The Plague was about the plague in the same sense as King Lear is about a king named Lear. In The Plague, a biological cataclysm becomes the testing ground for our fallibilities, desires and ambitions. You cannot read The Plague except as a thinly disguised allegory of human nature. The genome is also the testing ground of our fallibilities and desires, although reading it does not require understanding allegories and metaphors. What we read and write into our genome is our fallibilities, desires, and ambitions. It is human nature.
The task of writing that complete manifesto belongs to another generation, but perhaps we can scribe its opening salvos by recalling the scientific, philosophical, and moral lessons of this history:
1. A gene is the basic unit of hereditary information. It carries the information needed to build, maintain, and repair organisms. Genes collaborate with other genes, with input from the environment, with triggers, and with random chance to produce the ultimate form and function of an organism.
2. The genetic code is universal. A gene from a blue whale can be inserted into a microscopic bacterium and it will still be deciphered accurately and with nearly perfect fidelity. A corollary: there is nothing particularly special about human genes.
6. It is nonsense to speak about “nature” or “nurture” in absolutes or abstracts. Whether nature – i.e., the gene – or nurture – i.e., the environment – dominates in the development of a feature or a function depends, acutely, on the individual feature and the context. The SRY gene determines sexual anatomy and physiology in a strikingly autonomous manner; it is all nature. Gender identity, sexual preference, and the choice of sexual roles are determined by intersections of genes and environments – i.e., nature plus nurture. The manner in which “masculinity” versus “femininity” is enacted or perceived in a society, in contrast, is largely determined by an environment, social memory, history, and culture: this is all nurture.
7. Every generation of humans will produce variants and mutants; it is an inextricable part of our biology. A mutation is only “abnormal” in a statistical sense: it is the less common variant. The desire to homogenize and “normalize” humans must be counterbalanced against biological imperatives to maintain diversity and abnormalcy. Normalcy is the antithesis of evolution.
13. History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part, because history does. The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome. And history has, in turn, selected genomes that carry these impulses, ambitions, fantasies and desires. This self-fulfilling circle of logic is responsible for some of the most magnificent and evocative qualities of our species, but also some of the most reprehensible. It is far too much to ask ourselves to escape the orbit of this logic, and recognizing its inherent circularity, and being skeptical of its overreach, might protect the weak from the will of the strong, and the “mutant” from being annihilated by the “normal.”
Perhaps even the skepticism exists somewhere in our twenty-one thousand genes. Perhaps the compassion that such skepticism enables is also encoded indelibly in the human genome.
Perhaps it is part of what makes us human.