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Ethical Vertigo and the Human Genome: On Siddhartha Mukherjee’s ‘The Gene’

By posted at 12:00 pm on May 25, 2016 0

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“Six things you can’t live without,” the online dating site commanded to me to include in my new profile. The blank spot below the prompt begged for something more than a tepid, “addicted to my iPhone/I love my mother” answer, but I felt stumped. What to say? After a moment’s hesitation, I went full geek. I can’t live without cytosine, adenine, guanine, thymine, and uracil, I wrote. I also like cappuccino.

It’s true: like all living things, I’d be nothing without the components of my DNA. (I could not exist at all, in fact.) But the nitrogenous base pairs I’d listed were clearly unfamiliar to plenty of prospective online suitors — which is also true for a large percentage of the American public. For them — for all of us — a trip through Siddhartha Mukherjee’s The Gene: An Intimate History offers startling clarity.

coverThe Gene is a follow-up to Mukherjee’s Pulitzer Prize-winning medical history of cancer, The Emperor of All Maladies. “The archetypal genomic disease is cancer,” Mukherjee explains in The Gene, connecting that book to this one (he later calls The Gene a “prequel” to The Emperor). While it’s fair enough to say that genes influence the development of cancer — and while Mukherjee spends a fair number of words to describe how that can happen — The Gene extends far beyond that relatively niche topic. Rather, Mukherjee tackles the entire history of genetics, from its origins as a passion project of a Czech monk named Gregor Mendel to Charles Darwin’s journeys to Galapagos to the Nobel Prize-winning discovery of the structure of DNA by James Watson, Francis Crick, and their colleagues. After rehashing that relatively well-known history, he traverses more recent, obscure, and often contentious topics, including eugenics, gene therapy, and the daunting ethical challenges of the future. In short, the work serves as a kind of primer on the whole of the topic, an unsurprising repackaging of a few major sections of an undergrad biology degree.

That said, it’s more appealing than any other molecular biology text I can recall. “Excuse my big yawn, but I just came from my own lecture,” a genetics professor tells a student halfway through the book. The comment is as an apt reminder of the Spockian science-nerd stereotype (perhaps the reason I’m still single?) and it almost comes across as Mukherjee’s admonishment to himself. He needn’t have worried. The book is defined best not by a crack about boredom but rather by a remark Mukherjee co-opts from the French impressionist Paul Cézanne, who once said about his friend Claude Monet: “Monet is but an eye, but, God, what an eye.”

“DNA, by that same logic, is but a chemical,” Mukherjee writes. “But, God, what a chemical.”

Humans depend on DNA, but not only. All life makes use of the exact same unique double helix of base pairs, sugar, phosphate, and water molecules. “A gene from a blue whale can be inserted into a microscopic bacterium and it will be deciphered accurately and with near perfect fidelity,” Mukherjee notes. Elsewhere, he constructs a list of DNA’s features in evocative, quasi-anthropomorphic language: “it is fiercely inventive…encrusted with history…[and] poised to evolve.”

Of course, our genes are also tightly tied to our daily existence — although that, too, Mukherjee describes as “surprisingly beautiful:” “On a vast stretch of [human] chromosome eleven, for instance, there is a causeway dedicated entirely to the sensation of smell. Here, a cluster of 155 closely related genes,” encodes “professional smell sensors…[for] spearmint, lemon, caraway, jasmine, vanilla, ginger, pepper.” The author’s enthusiasm for his simultaneously transcendent and mundane subject can make the dense text feel light.

Some readers have found the book a little too light. This month an excerpt printed in The New Yorker prompted controversy: a group of epigenetics researchers took issue with Mukherjee’s approach, alleging it misrepresents epigenetics (the process by which environmental factors can modify the structure and function of genes). “Their main criticism was that Mukherjee’s article put too much emphasis on histone modification and DNA methylation, which they say are relatively minor contributors to gene regulation,” an article in the science magazine Nature summarized. “They and other critics argued that Mukherjee ignored [other] well-established mechanisms of gene regulation.” In a statement published on a website (but since removed), Mukherjee prefaced a point-by-point rebuttal with a frank statement that he thought he had described epigenetics accurately. He also acknowledged errors.

But to argue too much about the fine points of The Gene seems to misunderstand its purpose. The book doesn’t serve only to attempt a summary of the technical points of a field that — as Mukherjee accurately reports — often advances through contentious debates. Rather, it serves to make the generalities of the topic accessible to the 90-odd percent of Americans who do not hold degrees in genetics or molecular biology. And here — amid odes to smells, plus lyrics to a Sanskrit folk tune and a stray quote from Snoop Dogg — Mukherjee delivers.

The debate also obscures this book’s other compelling accomplishments. First, Mukherjee takes on the ethically heavy topic of willful modifications to the human genome. “The most remarkable fact about human genomic engineering today is not how far out of reach it is, but how perilously, tantalizingly near,” he writes. These alterations have been proposed as ways to cure or prevent genetic illnesses. But because the genome (the sum total of genes in a given living being) is highly complex, willfully altering it carries the potential for unintended, potentially disastrous consequences. His solution? “We need a manifesto — or at least a hitchhiker’s guide — for a post-genomic world,” he writes. He doesn’t offer it himself, acknowledging in several places that geneticists are collectively grappling with their field’s ethical issues. Instead, he adds what he calls “an opening salvo,” which functions to distill the issue for readers. He ends with an appeal to skepticism at the value of genomic engineering, and adds, “Perhaps the compassion that such skepticism enables is also encoded indelibly in the human genome.”

The author is a good example of this compassion. Mukherjee interweaves the text with the story of his own family, particularly two uncles and a cousin with serious mental illnesses. (This, too, has been partially excerpted in The New Yorker.) Another chapter, “The Miseries of My Father,” documents a genetic brain disease Mukherjee’s dad is currently experiencing.

To oversharing-prone Americans, these disclosures might seem small. But they are not. What Mukherjee calls “ethical vertigo” with genomic engineering was what prompted me to leave biology and go into public health. Partly on the strength of a recommendation from a genetics professor (who, like Mukherjee, is a Bengali raised in Delhi), I won a Fulbright in the Bengal region to conduct research on mental health.

The topic was so intensely neglected I could not find an appropriate mentor for my work. (What ad hoc assistance I got was unsafe and often plain loony: one university administrator told me to manage people in psychiatric crisis by phoning an anthropologist in Germany. “Don’t call me,” that anthropologist later said, and I agreed.) Mental health was taboo enough to prompt flat rejections — and occasionally open anger — from my colleagues in health research.

In that context, Mukherjee’s forthright discussion of his own Bengali family’s psychiatric health is rare and courageous. It’s also worthwhile. If ethical issues in genetics are to be solved (or even communicated effectively to the public), we’ll need not only skepticism and compassion, but also a clear understanding of the humans our choices affect.

If I were joining that dating site today, I might alter my answer a bit. I can’t live without cytosine, adenine, guanine, thymine, and uracil, I would write. I also enjoyed The Gene, by Siddhartha Mukherjee.





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