slider top

When we unlock the secrets of our genes, what do we do with that knowledge?

The Gene, by Siddhartha Mukherjee (Scribner, 2016)

Review of “The Gene: An Intimate History,” by Siddhartha Mukherjee (Scribner. 592 pp. $32)

The many applications of scientific progress — computers, advanced medical procedures, rapid means of transportation, nuclear missiles — sometimes distract us from the abstract nature of most scientific insight. That is to say that the advancement of societies is often separate from the accumulation of knowledge. Genetics is among the areas of inquiry in which the ambition to know has been often in distressing proximity to the ambition to deploy that knowledge. Indeed, genetics has two histories: the history of what we have found out, and the history of the uses and abuses of those discoveries.

In his latest book, The Gene, Siddhartha Mukherjee explores the nature of this double narrative in considerable detail. He never loses sight of the tension between those who wish to understand genetics and those who wish to apply such emerging knowledge, but neither does he fall into the obvious trap of seeing the first category as the good guys and the second as the bad ones. Mukherjee contends that while genetic theories have provided crucial medical insights, they have also fueled the depraved thinking that reached its nadir in eugenics.

In one of the book’s sharpest observations, he draws parallels between the Nazi genocide and Soviet collectivization: “The two theories of heredity may have been spectacularly opposite — the Nazis were as obsessed with the fixity of identity as the Soviets were with its complete pliability — but the language of genes and inheritance was central to statehood and progress: it is as difficult to imagine Nazism without a belief in the indelibility of inheritance as it is to conceive of a Soviet state without a belief in its perfect erasure.” In these instances, the gene “had become one of the most dangerous ideas in history.” What we believe about genes is much of what we believe about ourselves and our fellow men and women, and those beliefs can amplify our humanity or demean it; they can be the basis for liberatory identity politics or for the Holocaust.

Although the translation of a theory from a scientist’s mind to a patient’s body can be fraught, it is equally fraught to hold back what looks like progress, to insist that theory remain theoretical, instead of sprinting to apply it when it seems possible that it would save lives. Mukherjee catalogues medical triumphs but acknowledges ambitious physicians who overrated their own abilities, and eulogizes their dying patients. He describes with heartbreaking clarity his conversation with the father of a boy who died unnecessarily in a poorly designed trial of a novel genetic therapy: “There was an infinite horizon of grief in his voice. ‘They didn’t have a handle on it yet,’ he said. ‘They tried it too quickly. They tried it without doing it right. They rushed this thing. They really rushed it.’?”

Genetic research, like research in physics, can materialize into a bomb. Researchers swept up in their own ideas sometimes lose sight of the very real problems those ideas are intended to address.

Mukherjee recounts the momentousness of each shade of progress. He cites the gene therapist William French Anderson, who began human genetic manipulation with the caution: “Nobody knows what may happen when new genes enter the body of a human being. It’s a total black box, despite what anyone tells you. .?.?. Eventually, you have to try it in a person.” He reviews the complex questions involved in rearranging the genes of plant and animal species with a fitting mix of wonderment and alarm. The medical geneticist Eric Topol said: “Genetic tests are also moral tests. When you decide to test for ‘future risk’ you are also, inevitably, asking yourself, what kind of future am I willing to risk?” That risk may once have manifested in eugenics, but now it resides in the craze for tampering with nature — from genetically modified foods to genetically screened embryos — that seems pitched to unlock both thrilling and alarming new powers.

What are the risks we take, and how wisely do we take them? Mukherjee draws a distinction between heritable and inheritable risks, strengths, capacities and vulnerabilities. That is to say that what is determined by genes is not necessarily shared across generations. Cases of incomplete penetrance — of genes that raise the chances of a clinical syndrome rather than determine it absolutely — lead to moral quandaries. Someone with the BRCA1 gene mutation has a 70 percent chance of developing breast cancer over her lifespan. What is the appropriate way forward, given that she has no idea when or how severely it will manifest, if at all? Mukherjee writes with zeal but champions the cautious use of genetic information, which is so often confusing and ambiguous. Not everyone with the BRCA1 gene needs to rush out to have a double mastectomy.

Mukherjee structures The Gene as a whodunit about a field groping its way toward coherence. He catalogues ancient errors that are echoed in recent prejudices. His description of how Christianity stood in the way of insight for centuries feels especially poignant in an America where religious efforts at suppression continue to roil state legislatures on topics such as evolution. The church resisted the very idea of genes. New genetic science is often intended to “improve on God’s work,” an idea that feels threatening to established orthodoxies.

We are introduced to a cavalcade of geniuses, including Charles Darwin, Gregor Mendel, Hugo de Vries, Thomas Morgan, Theodosius Dobzhansky, Fred Griffith, Linus Pauling, Rosalind Franklin, James Watson and Francis Crick. Their stories are written with the rollicking enthusiasm of sports journalism; you half-expect to hear cheers break out in the stands each time a new revelation arrives. Mukherjee has an ear for his subjects’ rhetorical brilliance. He quotes Crick’s description of most experimental methods to determine the structure of DNA as being “like trying to determine the structure of a piano by listening to the sound it made while being dropped down a flight of stairs.” More imagination and less calculation were needed to figure out what was going on.

Genetic research, like research in physics, can materialize into a bomb. Researchers swept up in their own ideas sometimes lose sight of the very real problems those ideas are intended to address.

Mukherjee’s first book, The Emperor of All Maladies, published in 2010, was subtitled A Biography of Cancer; the subtitle of The Gene is An Intimate History. This rhetorical use of humanist designations for scientific books reflects his inclination to soften the edges of medicine. He is all doctor, but he is also all bedside manner (and hence his books are bedside-table manner). He nourishes dry topics into engaging reading, expresses abstract intellectual ideas through emotional stories and repackages intimidating hypotheses in language that is almost cozy. Don’t worry if you can’t make heads or tails out of biology, these titles seem to say. You’ll like these books anyway. Mukherjee swaddles his medical rigor with rhapsodic tenderness, surprising vulnerability and occasional flashes of pure poetry. His books succeed both as narratives and as arguments about our organic selves, holding steady between the Scylla of abstruseness and the Charybdis of reductiveness.

Mukherjee interweaves the history of science with that of his own family, within which schizophrenia and bipolar disorder have surfaced across generations. The purpose, it would seem, is to explain why genetics is so urgent to him. This is hardly necessary; if someone knows anyone in whose family no genetic disease has surfaced, I’d like to meet that avatar of health. “Memories sharpen the past,” he writes in describing a return to his father’s childhood home. “It is reality that decays.” The chronicle’s patina of nostalgia owes not only to that personal history but also to a field of research barreling along so fast that insights achieved a year ago already feel quaint.

Despite touching anecdotes and some generous-hearted language, Mukherjee understands the pathos of sickness better than the politics of identity. He devotes considerable space to issues of gender, race, sexual orientation and disability, but his book would have benefitted from a clearer exposition of the women’s movement, with its disruption of power structures long presumed to be based in biology; of the civil rights movement, which disentangled equality from equivalence; of the gay rights movement, which has questioned the tyranny of the majority in defining difference as abjection; and of the disability rights movement’s contention that variances from a mapped genetic ideal are often pathologized inappropriately. Mukherjee does not reckon adequately with the burgeoning discourse about human variation.

He also can get a bit strained with his metaphors: “Griffith’s experiment may have stuffed genetics into a one-way taxicab and sent it scuttling toward a strange future — but Avery was reluctant to climb on that bandwagon.” Watson and Crick’s model of DNA “looks like a latticework corkscrew invented by a madman, or an impossibly fragile spiral staircase that might connect the human past to its future.” And as he watched a woman with a genetic disorder, “I saw her crossing the parking lot in her wheelchair, her scarf billowing in the wind behind her, like an epilogue.” That must have been quite some scarf. He also occasionally succumbs to overstatement for the sake of theatricality, as when he describes Pauling revealing his findings about DNA “with the dramatic flair of a sorcerer pulling a molecular bunny out of a hat.”

Genetic medicine requires that we use our knowledge not for narrowing humanity but for expanding our collective imagination.

But he has a commensurate knack for the similes that make complex ideas accessible and even lively: “A viral gene drops into the genome like a candy wrapper thrown from an airplane into the Atlantic: there is no way to predict where it might land.” He is also eloquent on the hermeneutics of scientific language, limning its oblique relationship to other modes of description. “The word diagnosis arises from the Greek ‘to know apart,’ but ‘knowing apart’ has moral and philosophical consequences that lie far beyond medicine and science. Throughout our history, technologies of knowing apart have enabled us to identify, treat, and heal the sick. .?.?. The history of human genetics has reminded us, again and again, that ‘knowing apart’ often begins with an emphasis on ‘knowing’ but often ends with an emphasis on ‘parting.’?” In other words, genetic medicine requires that we use our knowledge not for narrowing humanity but for expanding our collective imagination. This is a chronicle of dreamers and dreams, but it is told with remarkable clarity, even as it encompasses some of the most intricate and convoluted processes in chemistry. It bridges the split narrative of genetics.

Mukherjee quotes the famous University of Minnesota twin study that located identical twins who had been separated in infancy yet still had everything in common; one pair had given their dogs the same name. He ruminates about the interplay between genetic predestination and the free will of lived experience. “Genes must carry out programmed responses to environments — otherwise, there would be no conserved form,” he writes. “But they must also leave exactly enough room for the vagaries of chance to stick. We call this intersection ‘fate.’ We call our responses to it ‘choice.’ An upright organism with opposable thumbs is thus built from a script, but built to go off script. We call one such unique variant of one such organism a ‘self.’?” In general, genes give us likelihoods and no more. They factor into our destiny, Mukherjee argues, but our nurturing of our children and our inclination toward self-determination should not be discounted: We are programmed for bolts from the blue.

The Gene has its own elegant, twisting structure, in which evidence is suspended between the spines of history and science. It never pretends to ingenuousness; indeed, one is often tempted to give the author an A for visible effort. But with a marriage of architectural precision and luscious narrative, an eye for both the paradoxical detail and the unsettling irony, and a genius for locating the emotional truths buried in chemical abstractions, Mukherjee leaves you feeling as though you’ve just aced a college course for which you’d been afraid to register — and enjoyed every minute of it. You may, however, need to repeat the class pretty soon, since part of the message of The Gene is its own looming obsolescence.

Our knowledge remains elementary, Mukherjee observes, but “with enough subjects, and enough computational power, nearly all of the predictive capacity of the genome can, in principle, be determined and computed.” The history of the gene proceeds at a geometric rate, and everything we know now will shortly be outdated — some of it proving false and the rest coming to seem primitive. “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.” Both passivity and grandiosity inhere in the concept of manifest destiny. Vibrantly disseminating the knowledge of how we got here and what mistakes were made along the way strengthens the defense against repeating errors of science, philosophy or government.

There is an ethical divide here that warrants infinite restatement. Acquiring knowledge almost always serves the public good. Deploying that knowledge is a 50-50 enterprise at best. Recognizing the discreteness of these two elements of science is the surest way to reconcile them. And nowhere has the tension been more explicit than it is in genetics.