Genes, Chance And Destiny: Siddhartha Mukherjee Chronicles The Human Genome’s Turbulent Future

Genes, Chance And Destiny: Siddhartha Mukherjee Chronicles The Human Genome’s Turbulent Future
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Dr. Mukherjee in his lab
Dr. Mukherjee in his lab
Lloyd Sederer

At 46, Siddhartha Mukherjee, is a man driven by questions, by puzzles in science and society. In 2011, his first book, a 600-page book on the history of cancer, The Emperor of All Maladies, won a Pulitzer Prize, among other accolades. Time magazine lists the book among the one hundred most influential books written since 1923.

His new and third book, The Gene, an Intimate History, published in 2016, sets out to tackle another crucial question that sits at the edge of science and society. This book is a finalist for the UK’s top award for nonfiction writing, the Baillie Gifford Prize, putting him in competition with a Nobel Laureate. More about both books below.

As technologies accelerate, so does what we know about the human genome – the complete code of DNA in our cells and bodies that orchestrates our destiny. Mukherjee knows that the prospect of understanding aspects of our genetic code is no longer ‘if’ but when and how. As that happens, he asks us to wonder, as he does himself, what will we do with these new-found powers? What does the future hold for the human genome – now that we are learning to “read” and “write” our own codes of instruction?

The easy answers are their application in preventing disabling and deadly genetic diseases and mitigating the progression of many illnesses, especially cancers. But science is agnostic, it does not set social or moral boundaries. Mukherjee comments that we are creating questions for our children as we master the capacity to not only decode but also to recode the genetic building blocks of our lives. We may be cutting, splicing, and inserting different genetic sequences that make us, and our progeny, truly different, where the consequences are deeply uncertain as to whether good or bad ― or both ― will result.

I met with him at his lab and office at Columbia’s Irving Cancer Center, in Washington Heights in Northern Manhattan, on a bright September morning that itself radiated hope. He was quick to let me know that he is a cell biologist, that his work and his insistent queries, scientific and societal, are meant to answer “how and why do cells go wrong {that is, mutate and become cancer}...and conversely how do they not go wrong?”, and all the variation that exists in between.

Dr. Mukherjee spends a half a day each week seeing patients in a Columbia oncology clinic. That is time where he confronts the human faces and anxieties that patients and their families endure when nature goes awry and cancer takes its toll. He also has a lab that studies stem cells, the originating, undifferentiated cells that become every other type of cell in our body, from blood and bone marrow cells (his focus), to our heart, neurons and nerves, skin, nose and toes, to name a few. Stem cells undergo radical transformations and may supply clues to understanding cellular aberration and reveal how disorders can be prevented or treated. He is a husband who spoke proudly of his wife’s accomplished artistry and a dad who wonders about the future and fate of his two daughters.

After Mukherjee won the Pulitzer Prize in 2011 for The Emperor of All Maladies, a masterpiece on the history and science of cancer, the storied documentary producer, Ken Burns, then gave us a 3 part, 6 hour PBS video rendition. True to the book, the documentary is gripping in its tales of patients and 1000 years of science.

I asked him where did this book (Emperor) come from? “It began as a diary. Every night after rounds, as an oncology fellow, I would write down notes... “ ― observations, questions, comprehensible and incomprehensible experiences drawn from clinical practice, I surmise, until after a year he had a “sheaf” of paper that sat on the passenger seat of his car, like a fellow traveler on his medical and personal journey. Then one night, in 2006, sitting in his car with his notes at his elbow, reflecting on an urgent question from a patient about “what am I fighting?” he realized he had a question he needed to answer, namely “how did we get here?” The answers lay in a millennium of history and in the lives of patients and families, doctors, and scientists ― and the intersection of the two. He spent the next years painting that picture on a canvas of paper that took the world by very illuminating surprise. After he had written the 600 pages he said, “Only my mother would read it.” I guess he was wrong there.

His third book, The Gene, is yet another exegesis driven by Mukherjee’s need to answer questions about the nature of our genes, all 21,000 of them and the billions of their nucleotides (DNA), wherein live the code for all living organisms, the genesis of life, and of its human variation and disorder, physical and mental. Mukherjee is a fine teacher, who in this book has not forgotten the third leg of the didactic stool, namely ethos – to complement the logos and pathos he provides. The scientific advances in gene sequencing coupled with massive data storage and computational capability have placed us, he explains, on the frontier of totally new territory for the human species. He enables us to wonder, as he does, about uncertainty, risk and choice. We can stand with him envisioning the promise and peril, the allure and the hazards, of the future that knowledge and technological brilliance are poised to deliver for us all. I saw this as his alerting us to the daunting ethical questions ahead. The Gene tackles a mere 150 years, rather than 1000, but they were not dormant times.

I asked, too, about The Gene and when he knew he had to write it? He said, “I began The Gene as a Bengali family story, but it could be the story any family. I went with my father to visit my cousin in a Calcutta mental institution, a grim place where I saw a man disintegrated from schizophrenia and from institutionalized life.” In The Gene, he wrote that “Madness, it turns out, has been among the Mukherjees for at least two generations…”, making inheritance of a potentially disabling mental disorder a fearsome shadow in his life, and that of his family for generations to come. This book, with “intimate” in its subtitle, is about the intimacies of genes, the vagaries of science and scientists, as well as about his family.

Both books, Mukherjee adds, ask and try to answer “what is ahead?” There the material cannot singularly, nor does he confine himself, examine science. “We are an experiment in process,” he remarks. He sees the books as a pair, but not intended to be. There are four dimensions to the science he writes about: the genes themselves, their environment (in every respect), the triggers that turn on and off genetic activity in living organisms, and the most haunting of all ― chance. Answers lie in all these interacting facets of life. “As we get better at predicting, our kids will come to think differently. We are not there yet because even when we can predict, offer probabilities for groups, populations, of patients we cannot tell any one person with confidence how nature will unfold for them.”

Mukherjee likens this to the “Last Mile” problem, where the greatest distance is that last mile. The finish line may be visible but it is a long way ahead. What if, he asked rhetorically, we could “predict with 10% fidelity a future illness in an unborn fetus?” What if, as has happened in all our pasts, “a premium is placed on some people and not others?” We have no universal moral standards, and very few regulations governing the march of science, especially in rogue countries and in what he called the “genetic arms race.” We have no forum, yet, to struggle with the opportunities and perils that our new technologies will place at our feet. He is a man beset with the dilemmas of science as they penetrate our social and ethical fabric, as we face decisions not just about cancer but about identity and the “self” as more is revealed about how the brain and the mind operate.

What was his 2nd book, you may have wondered? It appeared in the fall of 2015 and was called The Laws of Medicine. A mere 65 pages, it was built out of a TED talk he had given yet reads as much as memoir as it does of science. This book seems to derive from his experiences as a practicing doctor, and emerged after a two week run, always a bear, as a medicine ward attending. He remarked, “If you scratch the surface of medicine’s conventional laws there are others perhaps more telling. These are laws about uncertainly, bias and outliers. I wrote about how a good intuition is more powerful than a weak test; that normals teach us rules, outliers laws; and for every perfect medical experiment there is a perfect human bias.” These laws of our imperfections are told by Mukherjee with patient stories and personal vignettes. The whole book is like having a long walk and talk with a highly reflective man.

Mukherjee called his thinking and writing process “ruminative.” The material keeps pouring in, clinically, scientifically and personally. And when he know the question(s) he needs to try to answer he goes at it whenever there is a free moment.

Right now, he concludes, at least at the time of this profile, he is in a “quiet phase.” He does not know when the next impetus, in the form of a disturbing question, will move him to his next book or project. He adds, “Maybe I will write fiction, science fiction... I re-read 1984 when working on The Gene. Where might science take us?” That is the great mystery ahead.

Lloyd I. Sederer, MD*


*Medical Editor for Mental Health, The Huffington Post; Adjunct Professor, Columbia/Mailman School of Public Health; Chief Medical Officer, The NYS Office of Mental Health.


My new book, Improving Mental Health: 4 Secrets in Plain Sight, (Foreword by Patrick Kennedy) will be released in November, 2016.

4 Secrets in Plain Sight by Dr. Lloyd Sederer
4 Secrets in Plain Sight by Dr. Lloyd Sederer
Am. Psychiatric Assn Publishing

The opinions expressed herein are solely my own as a psychiatrist and public health doctor.

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