4.5/5 But what is ”natural”? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other, constancy, permanence, indivisibility, fidelity. Bhed. Abhed. It should hardly surprise us that DNA, the molecule of contradictions, encodes an organism of contradictions. . . . Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of
4.5/5 But what is ”natural”? I wonder. On one hand: variation, mutation, change, inconstancy, divisibility, flux. And on the other, constancy, permanence, indivisibility, fidelity. Bhed. Abhed. It should hardly surprise us that DNA, the molecule of contradictions, encodes an organism of contradictions. . . . Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess Its stewardship may be the ultimate test of knowledge and discernment for our species.

Sura-na Bheda Pramaana Sunaavo;Bheda, Abheda, Pratham kara Jaano.Show me that you can divide the notes of a song;But first, show me that you can discernBetween what can be divided

And what cannot.

— An anonymous musical composition inspired by a classical Sanskrit poemThis wondrous journey through the history of genetics and genomics left me surprisingly hopeful and somehow less fearful of the future despite the potential risks of genomic technologies and the enormous changes Mukherjee foresees on the horizon, where “what can be divided and what cannot” is yet unknown. With a gentle, compassionate voice, an open mind, and a sense of humor (he’s unable to resist a groan-worthy literary pun) you would definitely want this man as your personal physician. Looking soberly at the risks and atrocities past, present, and (potential) future, he nevertheless exudes a calm and infectious sense of wonder, acceptance of life’s infinitely creative diversity, and careful hope for benefit to humankind.

Aesthetic appreciation was no small part of my delight, not only in the writing but in the thrill of learning about the gene and the genome, the literal stuff of life. One semester in college I took a course in Ancient Greek Philosophy together with one in Modern Physics (relativity, quantum theory, etc.) delighting in the juxtaposition of the ancient and modern minds, each seeking the secrets of the universe in their own time. This time around, unplanned, I experienced similar juxtapositions of ancient and modern “seekers” by reading in parallel an imaginative analysis of the biblical origin story: The Beginning of Desire: Reflections on Genesis by Avivah Gottlieb Zornberg. To my surprise and delight, both authors crammed their books with literary references. Shakespeare, Kafka, and especially Wallace Stevens were quoted in both tomes. And what a treat for my poetic imagination. Genesis. Gene-sis. DNA, the “script” of every living being on earth, begins to look to me like an unfurling scroll. On it are written the instructions for our creation in combinations of four letters: A, C, G and T. They could just as well be four musical notes playing the unique song of each individual being. (Surely some composers have taken inspiration from this?) Or the four letters in the traditional Hebrew Divine Name, creating infinite marvelous variations in its own image and likeness. And today I read in the news that some poet is genetically altering a bacteria to encode his own poetry into its genome. (“Translated” somehow into the four-letter code, I guess.)

I found the storytelling in The Gene: An Intimate History compelling for the most part. With a delicate touch Mukherjee interwove his own family’s troubled medical history with tales of the scientists and their discoveries, from the unlikely father of genetics, the gentle monk Gregor Mendel and his almost unimaginably rigorous analyses and documentation of tens of thousands of meticulously cross-bred pea plants grown in his monastery garden (after his superior had nixed his similar attempts to cross-breed mice in his monastic cell) — to the recent discoveries by Jennifer Doudma and Emmanuelle Charpentier of CRISPR/Cas9 technologies that allow precise gene editing based on what bacteria naturally do to combat viruses. (This gave me a deeper understanding of current news stories.) A medical doctor, Mukherjee focused on the human medicine perspective — he doesn’t say much about genetically modified organisms in other contexts such as agriculture.

As in my recent journey through the history of geological science with John McPhee’s Annals of the Former World series, there was no shortage of scientists behaving badly. For example, Mendel’s unique, groundbreaking work was suppressed (and plagiarized in part) by an envious scientist to whom Mendel had sent his paper — setting back science for 35 years until Mendel’s research was “discovered” after his death and widely published. And then there were the atrocities committed in the name of human improvement (sometimes) — from forced sterilizations of people on the basis of poverty or race in the United States, to the “final solution” of the Nazis and the “medical” experiments of Josef Mengele at Auschwitz. Could things like this be repeated? Maybe. Terrible things are happening now, Mukherjee contends: in his birth country of India and in China, tens of millions of girls are selectively aborted or removed from the human race by infanticide or exposure. As a caution to the world, Siddhartha Mukherjee dedicated this book to Carrie Buck, the first woman to be forcibly sterilized.

Getting further into controversial territory, I was, perhaps naively, surprised and dismayed to learn that the current state of genetic medicine is as primitive as it is, consisting primarily of identifying genetic abnormalities in utero and offering the option of terminating the pregnancy. Ostensibly this is done only by choice, and only for only the most extreme medical conditions that would cause great suffering, but as Mukherjee pointed out, reality is a different story. He also points out the slippery quality of the concept of "great suffering": -- what is it, and who decides? Another major current application of genetic medicine is through in-vitro fertilization, when embryos can be genetically tested and selected or not selected for implantation. Mukherjee discusses some of the ethical concerns with these approaches. What about actually curing genetic diseases? So far, the dangers and technical difficulties of making targeted genetic changes, including fatal screw-ups by overeager experimenters, have held back progress, but Mukherjee believes we are on the cusp of seeing this change, although he cautions that this approach may only apply to conditions that are traceable to a single gene or a simple combination of a few genes -- and we do not know whether changing those genes will also change other, desirable characteristics. We do not know what can be divided and what cannot.Mukherjee tries to speak evenhandedly and sensitively about the dilemmas of genetic “abnormalities” — or, more neutrally, genetic "variations" — which can sometimes also be gifts. For instance the common co-occurrence of genius and mental illness (as occurred in his family) can be traced to genetics and isn’t just the stuff of legends and movies. And most of the time, genes only indicate a potential that may or may not be realized. One special case that is more genetically clear-cut than most, but ethically less so, is Down syndrome. Even this seemingly straightforward chromosomal variation can result in a wide range of outcomes for people born with this condition -- some people born with Down syndrome can have relatively healthy, relatively independent lives. Mukherjee also points out (at least twice) the sweet, almost angelic disposition of people with Down’s syndrome, implying how much would be lost if they were all eliminated from the human race as "undesirable". (Having worked and lived for two summers with Down syndrome youth, I agree.) On the other hand, Mukherjee is sensitive to women who may have reason to make another choice. He mentions the case of a woman who, after having a child with Down syndrome who suffered greatly from medical conditions, underwent many painful surgeries, and died young, decides to abort a subsequent Down fetus. (I couldn’t help but contrast Mukherjee’s sensitive perspective to Richard Dawkins who has said that a woman would be immoral not to abort a fetus with Down syndrome. I find that horrible, and so much for women’s autonomy, some men can’t resist telling us what to do even without a religion to blame it on.)

In short, I recommend this book to those interested in a human-focused book on the science of genetics and genomics in pretty close to its current state. I will definitely read Mukherjee’s cancer book now, and I’m also looking forward to reading a new (2018) book with an epigenetic focus: She Has Her Mother’s Laugh: The Powers, Perversions and Potentialities of Heredity by Carl Zimmer (also new to me). Since finishing this book I've also listened to several extended interviews of Dr. Mukherjee on YouTube about this book and his early book on cancer; my overall impression is of a humble, thoughtful man who cares deeply for us humans.

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