May 15, 2016

NY Times Books of The Times

Review: Siddhartha Mukherjee’s ‘The Gene,’ a Molecular Pursuit of the Self

by Jennifer Senior

 

Dr. Siddhartha Mukherjee

Thank heavens Gregor Mendel was a lousy priest. Had he shown even the faintest aptitude for oratory or ministering to the poor, he might never have determined the basic laws of heredity. But bumbling he was, and he made a rotten university student to boot; his failures drove him straight to his room, where he bred mice in secret. The experiment scandalized his superiors.

“A monk coaxing mice to mate to understand heredity was a little too risqué, even for the Augustinians,” writes Siddhartha Mukherjee in “The Gene: An Intimate History.” So Mendel switched — auspiciously, historically — to pea plants. The abbot in charge, writes the author, acquiesced this time, “giving peas a chance.”

Love Dr. Mukherjee, love his puns. They’re everywhere. I warn you now.It is Dr. Mukherjee’s curse — or blessing, assuming he’s a glass-half-full sort of fellow — to have to follow in his own mammoth footsteps. “The Emperor of All Maladies: A Biography of Cancer,” his dazzling 2010 debut, won the Pulitzer and almost every other species of literary award; it became a three-part series on PBS; Time magazine deemed it one of the 100 most influential books written in the English language since 1923.

In his acknowledgments to “The Gene,” Dr. Mukherjee, a researcher and cancer specialist, confesses that he once feared his first book would also be his last — that “‘Emperor’ had sapped all my stories, confiscated my passports and placed a lien on my future as a writer.” The solution, he eventually realized, was to tell the story of the gene. It is his debut’s natural prequel, a tale of “normalcy before it tips into malignancy.”

By the time “The Gene” is over, Dr. Mukherjee has covered Mendel and his peas, Darwin and his finches. He’s taken us on the quest of Watson, Crick and their many unsung compatriots to determine the stuff and structure of DNA. We learn about how genes were sequenced, cloned and variously altered, and about the race to map our complete set of DNA, or genome, which turns out to contain a stunning amount of filler material with no determined function.

Many of the same qualities that made “The Emperor of All Maladies” so pleasurable are in full bloom in “The Gene.” The book is compassionate, tautly synthesized, packed with unfamiliar details about familiar people. (Francis Galton, the father of eugenics, used to rank the beauty of women on the street by “using pinpricks on a card hidden in his pocket.” Ick.)

But there are also crucial differences. Cancer is the troll that scratches and thumps beneath the floorboards of our consciousness, if it hasn’t already beaten its way into the room. The subject immediately commands our attention; it’s almost impossible to deny, and not to hear, the emotional clang of its appeal. In Dr. Mukherjee’s skilled hands, the story of this frightening disease became a page-turner. He explained its history, politics and cunning biological underpinnings; he traced the evolving and often gruesome logic underlying cancer treatment.

And in the middle of it all, agonizing over treatment protocols and watching his patients struggle with tremendous existential and physical pain, was the author himself.

There are far fewer psychological stakes in reading about the history of genetics. “The Gene” is more pedagogical than dramatic; as often as not, the stars of this story are molecules, not humans. Dr. Mukherjee still has a poignant personal connection to the material — mental illness has wrapped itself around his family tree like a stubborn vine, claiming two uncles and a cousin on his father’s side — but this book does not aim for the gut. It aims for the mind.

So what does this mean? That there are many excursions deep into the marshes of biochemistry and cellular biology. Bring your waders. It gets dense in there. Dr. Mukherjee can write with great clarity about difficult genetic concepts — he’s especially handy with metaphors — but the science gets increasingly complex, and it lasts for many pages. Even when the going is easy, readers should be prepared for parentheticals like this: “i.e., ACT CCT GGG –>ACU CCU GGG.”

Dr. Mukherjee’s explanations are sometimes so thorough they invite as many questions as they answer — from the most elementary (why is something that contains so many bases called deoxyribonucleic acid?) to the more esoteric (if, as he says in a Homeric footnote on Page 360, the Y chromosome is so unstable it might eventually disappear, will we still reproduce?)

I do not mean to suggest that Dr. Mukherjee has neglected to attend to big questions or ideas in this work; they just get lesser billing than I’d have liked. But any book about the history of something as elemental and miraculous as the gene is bound, at least indirectly, to tell the story of innovation itself. “The Gene” is filled with scientists who dreamed in breathtakingly lateral leaps.

Erwin Schrödinger in particular was one visionary cat: In 1944, he hazarded a guess about the molecular nature of the gene and decided it had to be a strand of code scribbled along the chromosome — which pretty much sums up the essence of DNA.

With each and every genetic discovery, a host of questions arose, both ethical and philosophical. What are the implications of cloning, of creating genetic hybrids, of gene editing? Is there any value in knowing about the existence of a slumbering, potentially lethal genetic mutation in your cells if nothing can be done about it? (Personally, I wish he’d dedicated 50 pages to this question — it’d have offered a potentially moving story line and a form of emotional engagement I badly craved.)

Does the genome have anything to tell us about race, sexual identity, gender? Do these three-billion-plus base pairs connect, in any way, to what we think of as “a self”?

Dr. Mukherjee answers these questions cautiously and compassionately, if at times too cursorily for my satisfaction. He notes, repeatedly, that for all we know about the genome, there is so very much we don’t — it is a recipe, not a blueprint, as Richard Dawkins likes to say. Yes, sometimes one gene controls one specific trait; but often, dozens of genes do, and in ways we do not understand (or cannot even fully identify), and they interact mysteriously with the environment all along the way.

But as research continues apace, we must entertain the sci-fi prospect of one day customizing ourselves and our children. For now, we’re burdened with more and more moral decisions to make as genetic tests become increasingly refined.

“If the history of the last century taught us the dangers of empowering governments to determine genetic ‘fitness,’” Dr. Mukherjee writes — referring to Nazism, eugenics, every genocidal experiment involving social engineering — “then the question that confronts our current era is what happens when the power devolves to the individual.”

But we are not apps. Dr. Mukherjee knows this, struggles with it. Is optimization really the point of life? “Illness might progressively vanish,” he writes, “but so might identity.”

A version of this review appears in print on May 9, 2016, on page C1 of the New York edition with the headline: In Molecular Pursuit of the Genetic Code. Today’s Paper.

4 thoughts on “

  1. Over to CLF, Conrad and other scientists who comment on this blog to share their view on genetics and this deadly malady. My layman’ s question is : Are we any closer to understanding cancer given the advances we have through understanding the gene? I can handle economics but on this subject, I recognise my limitations and will leave the matter in their good hands. –Din Merican

  2. Pharmacogenomics – to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup – is becoming very important. Clinical trials of gene therapy products are more and more prevalent. There is a growing trend of pharmacists who are deeply involved in emerging medical sciences research, which include pharmacogenomics, gene therapy, biosimilar drug therapy and nanomedicine, among others. Gene therapy may be among the best opportunities for managing diseases like bladder cancer, pancreatic cancer and melanoma. I truly believe that these kinds of trials will make some cancers chronic illnesses or possibly cure them.

  3. Genes and Genetics? The New God of Science izzit? That’s lame..

    The Human Genome Project (HGP) although completed in April 2004 – in part (cuz only the euchromatic portion was fully mapped, while the heterochromatic potion was not), is still in the process of interpretation and analysis. It hasn’t really spun off the anticipated benefits as a therapeutic tool – but more as a diagnostic one. So don’t hold your breath, if you are suffering anything from prosaic Erectile Dysfunction to croaking from any of the myriads of Malignancy. Heck they haven’t even found an efficient or proper delivery system for one of the simplest form of genetic disorder – viz cystic fibrosis.

    A lot of folk misunderstand the ‘Utility’ of the HGP. That’s because our 20,500 or so genes (about the same as a rat), ain’t nothing compared to Rice (yeah, nasi/beras) which is more complicated. Doesn’t mean the more you have, the better, Ok?

    I hated Genetics, but was required to study it all those years ago. It wasn’t the ACTG nucleotides, mutational or translational processes etc. What i was disenchanted about was the fact that it looked to mechanical.. You know, like unzipping one’s pants? After graduation, the Epigenetic ‘Revolution’ began – and that re stoked my curiosity. “Ghost in the Gene” like.

    All i can say about Dr. Mukherjee’s book, is that i’ll read as i have read Stephen Hawking’s “A History of Time”. Interesting but not earth shaking. It ain’t gonna give me an epiphany, like Brian Greene’s “The Elegant Universe” – which broke my reticence to the Religion i was born in.

    Francis Collins the director of the HGP at the time of it’s publication and now the director of the National Institute of Health in Maryland – and a Christian, like me share similar experiences when it came to Purpose. Except he was much smarter, with a PhD in Physical Chemistry followed by an MD. He (along with Tsui Lap Chee) also discovered the genetic defect in the afore-mentioned Cystic Fibrosis, and many others. Some folks, just aren’t able to stop.. ya?

    I would rather understand photosynthesis – which produces the oxygen i breathe, explained by quantum tunneling – than to obsess about the minutiae of genetic aberrations that will kill me sooner rather than later. So Quantum Biology should screw up the typical hard-core Categorizing atheistic Biologist, pretty good. This then would be an excellent melding of hard and soft sciences. Meanwhile, i’ll just go on with my mushy job.

    Life after all, is NOT about a biological zipper.

  4. I admit, I am a sucker for these science types using narrative tropes to educate . So yeah, I thought Siddhartha Mukherjee’s The Emperor of All Maladies , was a pretty terrific read.

    This new book, is on my reading list and I have no doubt, it will be interesting – or at least this is what those who know my taste, say.

    I am by no means science literate, semi- maybe, but I’m in no position to answer the question you ask, in any meaningful way.

    To me Cancer is the only type of threat which could be labelled “existential” without rendering the term banal.

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