The Building Block of Life, Brick by Brick

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By the time this book is finished, I would not be surprised if the first successful targeted genome modification of a human embryo has been achieved…. The first ‘post-genome’ human might be born.

—Siddhartha Mukherjee, MD

Title: The Gene: An Intimate History
Author: Siddhartha Mukherjee, MD
Publisher: Scribner
Publication date: May 2016
Price: $32.00; hardcover, 608 pages

On February 28, 1953, James Watson and Francis Crick entered The Eagle, a favorite watering hole for researchers working at the University of Cambridge’s old Cavendish laboratory, and bragged, “We have discovered the secret of life.” That very morning, they had worked out the double-helix structure of DNA. Now, some 63 years hence, Siddhartha Mukherjee, MD, the acclaimed author of the Pulitzer Prize–winning book The Emperor of All Maladies: A Biography of Cancer has penned a tome about a segment of Watson and Crick’s discovery, The Gene: An Intimate History.

The prologue begins with an arresting story of the author’s childhood in Bengal, India, and three of his close relatives who suffered from different forms of severe mental illness that shared a strong genetic link. He uses this tragic example to frame many of the ethical questions now arising in the age of genomic mapping and manipulation of individual genes. Throughout the book, as he explores and explicates the past, present, and future of the gene, Dr. Mukherjee writes with an allegorical style that imbues his subject with deep philosophical undertones.

Historical Arc

Dr. Mukherjee is a big thinker, and this is a big book. It is organized in six parts, both chronologically and thematically. The overall arc is historical. He begins in Mendel’s pea-flower garden in a monastery in 1864, where the “gene” is discovered and quickly forgotten. His story then intersects with Darwin’s theory of evolution and its entrance into the English and American reformist movements, which hope to manipulate human genetics to accelerate human evolution. That idea, as he eloquently discusses, morphed into the perversion of social eugenics, which was designed to hasten the selection process of the “well-fitted” over the “ill-fitted” and the healthy over the sick.

In one of our darker periods, the United States embraced eugenics, which led to sterilization programs of prison inmates and those considered mentally inferior. Adolf Hitler would later use this program as a template and recreate his own form of eugenics, which was used to purge Germany of “undesirables.”

For more than 300 pages, Dr. Mukherjee covers the history of the gene and the scientists who clarified its molecular description and the mechanisms of the transmission of heredity. This section is both edifying and dense reading, and it will take dedication by many readers to move from the laboratories and minds of scientists as they move, inch by inch, over multiple chemical bonds stretching out along the length of the “chromosome fiber” and pursue “a chemical that would capture the divergent, contradictory qualities of heredity—a molecule to satisfy Aristotle. In their mind’s eye, it was almost as if they’d seen DNA.”

But that crystal ball vision befuddled as much as clarified their quest to decipher the master code of instructions that makes and defines humans; that governs our form, function, and fate; and that determines the future of our children. The book’s pace picks up as the gene transforms postwar biology and invades the discourse concerning race and identity, providing some of the most important questions and answers of our cultural and political realms.

Clash of Two Unchained Minds

One of the most illuminating and fun-to-read sections of the book is the lead-up to The Human Genome Project. Here, using two titans in gene study, the author delves deep into the heart and soul of the competitive scientific community. The Human Genome Project was, and still is, the world’s largest collaborative project. By the late 1980s, it was beginning to look like nobody would ever draw the human genome map. However, DNA co-discoverer James Watson emerged and stood before Congress in 1987 and proposed the idea. He was given a starting budget of $30 million to launch The Human Genome Project, a new division of the National Institutes of Health (NIH). He predicted a complete DNA map by 2005.

But it wasn’t long before Dr. Watson’s prickly nature caused a clash with another superego working in the project, Greg Venter, PhD. The personality clash came to a head when Dr. Venter saw the opportunity for patenting genes, which he and the NIH both saw as a huge commercial opportunity. Dr. Watson, a purest at heart, was appalled by the specter of genetic patents. Dr. Venter and the NIH pushed back, contending that patents were the future of biotechnology. The author captures the battle that history will remember as the clash of two unchained minds. The allure of commercial patents won out, and Dr. Watson was asked to resign. The rest, as they say, is history.

Hopes and Perils of Genetics

The last part of the book is called “Post-Genome,” and it offers a dizzyingly vivid picture of the hopes and perils of genetics, reading that provides valuable insight into the fate and future of our rapidly expanding genetic knowledge. Dr. Mukherjee takes the reader on a fascinating trip back into the recent past, when biologists stumbled onto a critical discovery: embryonic stem cells. With these cells, scientists learned to make genetic changes, not randomly, but in targeted positions in the genome, including within the genes themselves. This meant that scientists could intentionally manipulate virtually any chosen gene and incorporate that genetic change permanently into the genome of an animal.

This was the birth of transgenic modification, and the author leaves no stones unturned as he describes the science and its ethical implications. And the advent of gene therapy was the rebirth of positive eugenics. “The second, more radical form of gene therapy is to modify a human genome so that the change affects reproductive cells…. The change is transmitted from one generation to the next,” writes the author. This is heady and controversial content, and to his credit, he remains objective, never preachy about a subject that has caused many a heated debate.

While writing his book, he notes that several groups in China are working on introducing permanent mutations in human embryos. “By the time this book is finished, I would not be surprised if the first successful targeted genome modification of a human embryo has been achieved…. The first ‘post-genome’ human might be born.” To the eerily dystopian possibilities of that prediction, Dr. Mukherjee added, “We need a manifesto—or at least a hitchhiker’s guide—for a post-genomic world.”

The Gene is a beautifully conceived avalanche of information, at times a bit overwhelming in its approach, but it is a valuable addition to popular scientific literature. This book is highly recommended for readers of The ASCO Post. ■