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The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race by [Walter Isaacson]

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Walter Isaacson

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race Kindle Edition

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The bestselling author of Leonardo da Vinci and Steve Jobs returns with a gripping account of how the pioneering scientist Jennifer Doudna, along with her colleagues and rivals, launched a revolution that will allow us to cure diseases, fend off viruses, and enhance our children.

In the spring of 2012, the Berkeley biochemist Jennifer Doudna and her collaborators turned a curiosity of nature into an invention that will transform the future of the human race: an easy-to-use tool that can edit DNA. Known as CRISPR, it opened a brave new world of medical miracles and moral questions. It has already been deployed to cure deadly diseases, fight the coronavirus pandemic of 2020, and make inheritable changes in the genes of babies.

The development of CRISPR and the war against coronavirus will hasten our transition to the next great innovation revolution. The past half-century has been an information-technology era, based on the microchip, the computer, and the internet. Now we are entering an even more momentous era, a life-science revolution. Children who study digital coding will be surpassed by those who study the code of life.

Should we use our new evolution-hacking powers to make us less susceptible to viruses and eliminate dreaded disorders? What a wonderful boon that would be! Right? And what about preventing congenital deafness or blindness? Or being very short? Or being depressed? Hmmm…How should we think about that? Should we allow parents, if they can afford it, to enhance the IQ or height or memory or muscles of their kids?

After helping to discover CRISPR, Doudna became a leader in wrestling with these moral and policy issues. Her life story illustrates that the key to innovation is connecting basic science to our everyday lives—moving discoveries from our labs to our bedsides—in ways that respect our moral values. It’s a thrilling detective tale that involves the most profound wonders of nature, from the origins of life to the future of our species.

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Editorial Reviews

About the Author

Walter Isaacson, a professor of history at Tulane, has been CEO of the Aspen Institute, chair of CNN, and editor of Time. He is the author of Leonardo da Vinci; The Innovators; Steve Jobs; Einstein: His Life and Universe; Benjamin Franklin: An American Life; and Kissinger: A Biography, and the coauthor of The Wise Men: Six Friends and the World They Made. Visit him at Isaacson.Tulane.edu.

Amazon.com Review

An Amazon Best Book of March 2021: Isaacson is famous for writing Steve Jobs and Leonardo da Vinci, so a title like The Code Breaker might imply a lesser book about a lesser character. But 2020 Nobel winner Jennifer Doudna, who developed the gene editing technology CRISPR, is a giant in her own right. CRISPR could open some of the greatest opportunities, and most troubling quandaries, of this century—and this book delivers. —Chris Schluep, Amazon Book Review --This text refers to an alternate kindle_edition edition.

Review

“This year’s prize is about rewriting the code of life. These genetic scissors have taken the life sciences into a new epoch.” – Announcement of the 2020 Nobel Prize in Chemistry

"Isaacson’s vivid account is a page-turning detective story and an indelible portrait of a revolutionary thinker who, as an adolescent in Hawai’i, was told that girls don’t do science. Nevertheless, she persisted." — Oprah Magazine.com

"The Code Breaker marks the confluence of perfect writer, perfect subject and perfect timing. The result is almost certainly the most important book of the year.” – Minneapolis Star Tribune

“Isaacson captures the scientific process well, including the role of chance. The hard graft at the bench, the flashes of inspiration, the importance of conferences as cauldrons of creativity, the rivalry, sometimes friendly, sometimes less so, and the sense of common purpose are all conveyed in his narrative. The Code Breaker describes a dance to the music of time with these things as its steps, which began with Charles Darwin and Gregor Mendel and shows no sign of ending.” – The Economist

“Isaacson lays everything out with his usual lucid prose; it’s brisk and compelling and even funny throughout. You’ll walk away with a deeper understanding of both the science itself and how science gets done — including plenty of mischief.” – The Washington Post

"This story was always guaranteed to be a page-turner in [Isaacson's] hands." – The Guardian

"The Code Breaker unfolds as an enthralling detective story, crackling with ambition and feuds, laboratories and conferences, Nobel laureates and self-taught mavericks. The book probes our common humanity without ever dumbing down the science, a testament to Isaacson’s own genius on the page." — O Magazine

“Deftly written, conveying the history of CRISPR and also probing larger themes: the nature of discovery, the development of biotech, and the fine balance between competition and collaboration that drives many scientists.”— New York Review of Books

“The Code Breaker is in some respects a journal of our 2020 plague year.”— The New York Times

"Walter Isaacson is our Renaissance biographer, a writer of unusual range and depth who has plumbed lives of genius to illuminate fundamental truths about human nature. From Leonardo to Steve Jobs, from Benjamin Franklin to Albert Einstein, Isaacson has given us an unparalleled canon of work that chronicles how we have come to live the way we do. Now, in a magnificent, compelling, and wholly original book, he turns his attention to the next frontier: that of gene editing and the role science may play in reshaping the nature of life itself. This is an urgent, sober, accessible, and altogether brilliant achievement." —Jon Meacham

"When a great biographer combines his own fascination with science and a superb narrative style, the result is magic. This important and powerful work, written in the tradition of The Double Helix, allows us not only to follow the story of a brilliant and inspired scientist as she engages in a fierce competitive race, but to experience for ourselves the wonders of nature and the joys of discovery." —Doris Kearns Goodwin

“He’s done it again. The Code Breaker is another Walter Isaacson must-read. This time he has a heroine who will be for the ages; a worldwide cast of remarkable, fiercely competitive scientists; and a string of discoveries that will change our lives far more than the iPhone did. The tale is gripping. The implications mind-blowing.” – Atul Gawande

"An extraordinary book that delves into one of the most path-breaking biological technologies of our times and the creators who helped birth it. This brilliant book is absolutely necessary reading for our era." — Siddhartha Mukherjee

“Now more than ever we should appreciate the beauty of nature and the importance of scientific research; This book and Jennifer Doudna’s career show how thrilling it can be to understand how life works.” —Sue Desmond-Hellmann

“An extraordinarily detailed and revealing account of scientific progress and competition that grants readers behind-the-scenes access to the scientific process, which the COVID-19 pandemic has taught us remains opaque to the wider public. It also provides lessons in science communication that go beyond the story itself.” – Science Magazine

“An indispensable guide to the brave… new world we have entered." – Pittsburgh Post-Gazette

"A vital book about the next big thing in science—and yet another top-notch biography from Isaacson." — Kirkus Reviews (starred review)

"In Isaacson's splendid saga of how big science really operates, curiosity and creativity, discovery and innovation, obsession and strong personalities, competitiveness and collaboration, and the beauty of nature all stand out." — Booklist (starred review)

"Isaacson depicts science at its most exhilarating in this lively biography of Jennifer Doudna, the winner of the 2020 Nobel Prize in medicine for her work on the CRISPR system of gene editing...The result is a gripping account of a great scientific advancement and of the dedicated scientists who realized it." — Publisher's Weekly (starred review)

"Isaacson, the Pulitzer Prize-winning author of best sellers Leonardo da Vinci and Steve Jobs, offers a startling, insightful look at this lifesaving, hugely significant scientific advancement and the brilliant Doudna, who wrestles with the serious moral questions that accompany her creation. Should this technology be offered to parents to tailor-make their babies into athletes or Einsteins? Who gets altered and saved and why?” — AARP

"A brilliant and engaging book. There are many quotable gems but I have chosen one sentence from the epilogue that epitomizes not only Doudna but also Isaacson himself, whose book title ends with a hortatory claim that CRISPR affects the future of the human race: 'To guide us, we will need not only scientists, but humanists. And most important, we will need people who feel comfortable in both words, like Jennifer Doudna.'" — Policy Magazine --This text refers to an alternate kindle_edition edition.

Excerpt. © Reprinted by permission. All rights reserved.

Introduction
Into the Breach

Jennifer Doudna couldn’t sleep. Berkeley, the university where she was a superstar for her role in inventing the gene-editing technology known as CRISPR, had just shut down its campus because of the fast-spreading coronavirus pandemic. Against her better judgment, she had driven her son, Andy, a high school senior, to the train station so he could go to Fresno for a robot-building competition. Now, at 2 a.m., she roused her husband and insisted that they retrieve him before the start of the match, when more than twelve hundred kids would be gathering in an indoor convention center. They pulled on
their clothes, got in the car, found an open gas station, and made the three-hour drive. Andy, an only child, was not happy to see them, but they convinced him to pack up and come home. As they pulled out of the parking lot, Andy got a text from the team: “Robotics match cancelled! All kids to leave immediately!”

This was the moment, Doudna recalls, that she realized her world, and the world of science, had changed. The government was fumbling its response to COVID, so it was time for professors and graduate students, clutching their test tubes and raising their pipettes high, to rush into the breach. The next day—Friday, March 13, 2020—she led a meeting of her Berkeley colleagues and other scientists in the Bay Area to discuss what roles they might play.

A dozen of them made their way across the abandoned Berkeley campus and converged on the sleek stone-and-glass building that housed her lab. The chairs in the ground-floor conference room were clustered together, so the first thing they did was move them six feet apart. Then they turned on a video system so that fifty other researchers from nearby universities could join by Zoom. As she stood in front of the room to rally them, Doudna displayed an intensity that she usually kept masked by a calm façade. “This is not something that academics typically do,” she told them. “We need to step up.”2

It was fitting that a virus-fighting team would be led by a CRISPR pioneer. The gene-editing tool that Doudna and others developed in 2012 is based on a virus-fighting trick used by bacteria, which have been battling viruses for more than a billion years. In their DNA, bacteria develop clustered repeated sequences, known as CRISPRs, that can remember and then destroy viruses that attack them. In other words, it’s an immune system that can adapt itself to fight each new wave of viruses—just what we humans need in an era that has been plagued, as if we were still in the Middle Ages, by repeated viral epidemics.

Always prepared and methodical, Doudna (pronounced DOWDnuh) presented slides that suggested ways they might take on the coronavirus. She led by listening. Although she had become a science celebrity, people felt comfortable engaging with her. She had mastered the art of being tightly scheduled while still finding the time to connect with people emotionally.

The first team that Doudna assembled was given the job of creating a coronavirus testing lab. One of the leaders she tapped was a postdoc named Jennifer Hamilton who, a few months earlier, had spent a day teaching me to use CRISPR to edit human genes. I was pleased, but also a bit unnerved, to see how easy it was. Even I could do it!

Another team was given the mission of developing new types of coronavirus tests based on CRISPR. It helped that Doudna liked commercial enterprises. Three years earlier, she and two of her graduate students had started a company to use CRISPR as a tool for detecting viral diseases.

In launching an effort to find new tests to detect the coronavirus, Doudna was opening another front in her fierce but fruitful struggle with a cross-country competitor. Feng Zhang, a charming young China-born and Iowa-raised researcher at the Broad Institute of MIT and Harvard, had been her rival in the 2012 race to turn CRISPR into a gene-editing tool, and ever since then they had been locked in an intense competition to make scientific discoveries and form CRISPRbased companies. Now, with the outbreak of the pandemic, they would engage in another race, this one spurred not by the pursuit of patents but by a desire to do good.

Doudna settled on ten projects. She suggested leaders for each and told the others to sort themselves into the teams. They should pair up with someone who would perform the same functions, so that there could be a battlefield promotion system: if any of them were struck by the virus, there would be someone to step in and continue their work. It was the last time they would meet in person. From then on the teams would collaborate by Zoom and Slack.

“I’d like everyone to get started soon,” she said. “Really soon.”

“Don’t worry,” one of the participants assured her. “Nobody’s got any travel plans.”

What none of the participants discussed was a longer-range prospect: using CRISPR to engineer inheritable edits in humans that would make our children, and all of our descendants, less vulnerable to virus infections. These genetic improvements could permanently alter the human race.

“That’s in the realm of science fiction,” Doudna said dismissively when I raised the topic after the meeting. Yes, I agreed, it’s a bit like Brave New World or Gattaca. But as with any good science fiction, elements have already come true. In November 2018, a young Chinese scientist who had been to some of Doudna’s gene-editing conferences used CRISPR to edit embryos and remove a gene that produces a receptor for HIV, the virus that causes AIDS. It led to the birth of twin girls, the world’s first “designer babies.”

There was an immediate outburst of awe and then shock. Arms flailed, committees convened. After more than three billion years of evolution of life on this planet, one species (us) had developed the talent and temerity to grab control of its own genetic future. There was a sense that we had crossed the threshold into a whole new age, perhaps a brave new world, like when Adam and Eve bit into the apple or Prometheus snatched fire from the gods.

Our newfound ability to make edits to our genes raises some fascinating questions. Should we edit our species to make us less susceptible to deadly viruses? What a wonderful boon that would be! Right? Should we use gene editing to eliminate dreaded disorders, such as Huntington’s, sickle-cell anemia, and cystic fibrosis? That sounds good, too. And what about deafness or blindness? Or being short? Or depressed? Hmmm . . . How should we think about that? A few decades from now, if it becomes possible and safe, should we allow parents to enhance the IQ and muscles of their kids? Should we let
them decide eye color? Skin color? Height?

Whoa! Let’s pause for a moment before we slide all of the way down this slippery slope. What might that do to the diversity of our societies? If we are no longer subject to a random natural lottery when it comes to our endowments, will it weaken our feelings of empathy and acceptance? If these offerings at the genetic supermarket aren’t free (and they won’t be), will that greatly increase inequality—and indeed encode it permanently in the human race? Given these issues, should such decisions be left solely to individuals, or should society as a whole have some say? Perhaps we should develop some rules.

By “we” I mean we. All of us, including you and me. Figuring out if and when to edit our genes will be one of the most consequential questions of the twenty-first century, so I thought it would be useful to understand how it’s done. Likewise, recurring waves of virus epidemics make it important to understand the life sciences. There’s a joy that springs from fathoming how something works, especially when that something is ourselves. Doudna relished that joy, and so can we. That’s what this book is about.

The invention of CRISPR and the plague of COVID will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery, beginning just over a century ago, of the three fundamental kernels of our existence: the atom, the bit, and the gene.

The first half of the twentieth century, beginning with Albert Einstein’s 1905 papers on relativity and quantum theory, featured a revolution driven by physics. In the five decades following his miracle year, his theories led to atom bombs and nuclear power, transistors and spaceships, lasers and radar.

The second half of the twentieth century was an information-technology era, based on the idea that all information could be encoded by binary digits—known as bits—and all logical processes could be performed by circuits with on-off switches. In the 1950s, this led to the development of the microchip, the computer, and the internet. When these three innovations were combined, the digital revolution was born.

Now we have entered a third and even more momentous era, a life-science revolution. Children who study digital coding will be joined by those who study genetic code.

When Doudna was a graduate student in the 1990s, other biologists were racing to map the genes that are coded by our DNA. But she became more interested in DNA’s less-celebrated sibling, RNA. It’s the molecule that actually does the work in a cell by copying some of the instructions coded by the DNA and using them to build proteins. Her quest to understand RNA led her to that most fundamental question: How did life begin? She studied RNA molecules that could replicate themselves, which raised the possibility that in the stew of chemicals on this planet four billion years ago they started to reproduce
even before DNA came into being.

As a biochemist at Berkeley studying the molecules of life, she focused on figuring out their structure. If you’re a detective, the most basic clues in a biological whodunit come from discovering how a molecule’s twists and folds determine the way it interacts with other molecules. In Doudna’s case, that meant studying the structure of RNA. It was an echo of the work Rosalind Franklin had done with DNA, which was used by James Watson and Francis Crick to discover the double-helix structure of DNA in 1953. As it happens, Watson, a complex figure, would weave in and out of Doudna’s life.

Doudna’s expertise in RNA led to a call from a biologist at Berkeley who was studying the CRISPR system that bacteria developed in their battle against viruses. Like a lot of basic science discoveries, it turned out to have practical applications. Some were rather ordinary, such as protecting the bacteria in yogurt cultures. But in 2012 Doudna and others figured out a more earth-shattering use: how to turn CRISPR into a tool to edit genes.

CRISPR is now being used to treat sickle-cell anemia, cancers, and blindness. And in 2020, Doudna and her teams began exploring how CRISPR could detect and destroy the coronavirus. “CRISPR evolved in bacteria because of their long-running war against viruses,” Doudna says. “We humans don’t have time to wait for our own cells to evolve natural resistance to this virus, so we have to use our ingenuity to do that. Isn’t it fitting that one of the tools is this ancient bacterial immune system called CRISPR? Nature is beautiful that way.” Ah, yes. Remember that phrase: Nature is beautiful. That’s another theme of this book.

There are other star players in the field of gene editing. Most of them deserve to be the focus of biographies or perhaps even movies. (The elevator pitch: A Beautiful Mind meets Jurassic Park.) They play important roles in this book, because I want to show that science is a team sport. But I also want to show the impact that a persistent, sharply inquisitive, stubborn, and edgily competitive player can have. With a smile that sometimes (but not always) masks the wariness in her eyes, Jennifer Doudna turned out to be a great central character. She has the instincts to be collaborative, as any scientist must, but ingrained in her character is a competitive streak, which most great innovators have. With her emotions usually carefully controlled, she wears her star status lightly.

Her life story—as a researcher, Nobel Prize winner, and public policy thinker—connects the CRISPR tale to some larger historical threads, including the role of women in science. Her work also illustrates, as Leonardo da Vinci’s did, that the key to innovation is connecting a curiosity about basic science to the practical work of devising tools that can be applied to our lives—moving discoveries from lab bench to bedside.

By telling her story, I hope to give an up-close look at how science works. What actually happens in a lab? To what extent do discoveries depend on individual genius, and to what extent has teamwork become more critical? Has the competition for prizes and patents undermined collaboration?

Most of all, I want to convey the importance of basic science, meaning quests that are curiosity-driven rather than application-oriented. Curiosity-driven research into the wonders of nature plants the seeds, sometimes in unpredictable ways, for later innovations.3 Research about surface-state physics eventually led to the transistor and microchip. Likewise, studies of an astonishing method that bacteria use to fight off viruses eventually led to a gene-editing tool and techniques that humans can use in their own struggle against viruses.

It is a story filled with the biggest of questions, from the origins of life to the future of the human race. And it begins with a sixth-grade girl who loved searching for “sleeping grass” and other fascinating phenomena amid the lava rocks of Hawaii, coming home from school one day and finding on her bed a detective tale about the people who discovered what they proclaimed to be, with only a little exaggeration, “the secret of life.”
--This text refers to an alternate kindle_edition edition.

Product details

ASIN ‏ : ‎ B08MFT5J95
Publisher ‏ : ‎ Simon & Schuster Australia (March 9, 2021)
Publication date ‏ : ‎ March 9, 2021
Language ‏ : ‎ English
File size ‏ : ‎ 55202 KB
Text-to-Speech ‏ : ‎ Enabled
Screen Reader ‏ : ‎ Supported
Enhanced typesetting ‏ : ‎ Enabled
X-Ray ‏ : ‎ Enabled
Word Wise ‏ : ‎ Enabled
Sticky notes ‏ : ‎ On Kindle Scribe
Print length ‏ : ‎ 560 pages

Best Sellers Rank: #309,920 in Kindle Store (See Top 100 in Kindle Store)
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Walter Isaacson

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Walter Isaacson, University Professor of History at Tulane, has been CEO of the Aspen Institute, chairman of CNN, and editor of Time magazine. He is the author of Leonardo da Vinci; Steve Jobs; Einstein: His Life and Universe; Benjamin Franklin: An American Life; and Kissinger: A Biography. He is also the coauthor of The Wise Men: Six Friends and the World They Made.

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LA in Dallas

I am not the target market for this book

Reviewed in the United States 🇺🇸 on February 13, 2022

Verified Purchase

The first thing that struck me as I began reading The Code Breaker was "I know these people!" Note 6 in chapter 4 ("The education of a biochemist") especially brought this home to me:

"6. Sharon Panasenko, “Methylation of Macromolecules during Development in Myxococcus xanthus,” Journal of Bacteriology, Nov. 1985"

I knew Sharon Panasenko. She and I overlapped in the close-knit Stanford Biochemistry Department, and after she left we were both members of the small community of myxobacteria researchers. It is even possible that I met Jennifer Doudna around this time, when I was a Stanford grad student and she a Pomona College chemistry undergrad in Sharon's lab. The book is full of names familiar to me, known to me by reputation or in a few cases personally. The only major player in the CRISPR story I know personally is Eric Lander. (By "know personally" I mean we worked in the same lab and had multiple conversations.) But I also know several of the minor players and have met and spoken with many of the older participants.

Doudna (whom I have never met) seems a quite familiar type of scientist to me. Although she is clearly an extraordinary biologist, there are hundreds of extraordinary biologists, and Doudna is extraordinary in an ordinary way -- that is, she is extraordinary in the same way that most extraordinary biologists are extraordinary. The best short description of her comes from her PhD mentor Jack Szostak, “Jennifer was fantastically good at the bench, because she was fast and sharp and could seemingly get anything to work,” Szostak says. “But we talked quite a bit about why the really big questions are the important questions.”

Let's dispose of the "big questions" cliche. Isaacson recounts the following:

"Szostak’s excitement about discovering how life began taught Doudna a second big lesson, in addition to taking risks by moving into new fields: Ask big questions."

"Ask big questions" is a cliche among scientists. I have heard versions of it hundreds of times. It is like a Disney Princess saying "True Love conquers all" or a coach in a Hollywood sports movie saying "You can do anything if you put your mind to it." It is not evidence of deep thought, but rather the opposite.

What's more, it is, like the Hollywood examples, problematic. The injunction to "ask big questions" mistakes the goal for the path. Clearly you want to ANSWER big questions. (And, to give credit where it's due, Szostak is one who has done that.) It is natural to think that the way to answer big questions is to ask big questions. Natural but wrong. The way to answer big questions is to ask little questions. Isaacson gives several examples, from Darwin asking "What birds live on the Galapagos Islands?" to Mendel's pea-breeding hobby. And the CRISPR story is a prime example of asking little questions. Who could forget the yogurt microbiologists? I could easily give dozens of examples from the history of science and mathematics, but you're already bored.

What Doudna is is "fantastically good at the bench, ... fast and sharp and [able] seemingly [to] get anything to work". She's a top-notch bench scientist. That is the ordinary way for an extraordinary biologist to be extraordinary.

It seems obvious to me that Isaacson chose to present Doudna this way. As he tells us early in the book, he wants to reveal some truths about how science is really done. Among these truths is that the myth of the hero-scientist is wrong and pernicious. (He doesn't say that in so many words -- this is my surmise.) Could Isaacson have written Doudna as a hero scientist? Well, what do you think? Isaacson is an accomplished biographer, who has written biographies of Einstein, Da Vinci, and Franklin. Could he have written a hero story for Doudna?

Of course he could. Hero-scientist stories persist not because they are true, but because they are entertaining. Isaacson wants us to know that biological research is a collective endeavor, and that you grossly misunderstand it if you make the players solitary heroes. In fact, as he writes later of a conversation at a CRISPR conference.

'“Is there any field that is more cutthroat and competitive than biological research?” one of the participants asks me after Zhang and Sternberg give their dueling talks. Well, yes, I think, almost every field can be, from business to journalism. What distinguishes biological research is the collaboration that is woven in. The camaraderie of being rival warriors in a common quest suffuses the Quebec conference.'

He is right!

The first quarter of the book describes how Charpentier and Doudna figured out CRISPR, culminating in the June 2012 paper. This is the best part of the book. After that we get into tedious wrangling when competitors leapt onto the discovery to develop methods for gene editing in humans. (For what it's worth, I personally am convinced that the Nobel Committee was right in giving credit to Doudna and Charpentier. After their work the applications were obvious and required no extraordinary tricks.) Doudna has a problem with private-sector work -- as recounted in the book, she twice had to give up participation in commercial research because it literally made her sick.

After the silly wrangling about credit for applications, we have two major sections of the book left: ethics and Covid. The ethics of gene editing is not a new question. I appreciated that Isaacson made an effort to present the question thoughtfully, without the performative appeal to rhetorical hysteria that contaminates so much of this discourse. On the other hand, if you have been following the question over the years there is nothing new in his discussion.

Covid doesn't really make sense as a part of the story Isaacson set out to tell. I have the feeling that when the pandemic struck Isaacson's journalistic instincts kicked in. Finding himself with extraordinary access (because of his work on the biography) to two labs that were mounting responses to Covid, he couldn't resist the temptation to report on it. But I have followed the technical side of the Covid story very closely since January 2020 and I'm bored with it.

So, that explains my headline. There were large parts of the book I didn't much appreciate because of who I am and what I already know. Others might enjoy it more.

I will say one thing for Isaacson: he gets stuff right. Although he necessarily simplifies the science at times, I never caught him doing it in a way that would cause serious misunderstanding. That is a rare thing in science popularization.

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Anthony Conty

What Can RNA Do for You

Reviewed in the United States 🇺🇸 on October 2, 2022

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“The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race” by Walter Isaacson takes its science seriously and dumbs down absolutely nothing. I am neither the smartest nor dumbest guy in the room, but I had never heard the term CRISPR before cracking this open. The gentleman at Starbucks asked me what I was reading. When I told him, he said, “Ooh! Fun with CRISPR!”. Who says the schools have failed?

The first part of the book is about competition. Many people, including our hero Jennifer Doudna, knew the potential of gene editing and manipulation, but few could agree on who deserved the credit or made the most important discovery. Next, we meander into a portion about the ethics of gene manipulation in what seems to be a different, but still successful novel. In another’s hands, this could have been, as one reviewer put it, “too ambitious.” This book, however, is not Isaacson’s first rodeo, so he knows what to do here.

Most will seek out this type of story in order to hear the ethical arguments that came up over the span of the last few decades. Isaacson, a veteran author of history, seems less concerned with establishing a narrative and more focused on demonstrating how the national argument meandered. The scientists involved constantly battled with their desire for credit and responsibility to societal ethics. Most could see both the power of technology and the need for limits. Most agreed that only life-threatening reasons required such a boost.

We all draw the line differently. What qualifies as an “enhancement” instead of a “requirement” for life? The most emotionally resonant sections interview deaf and autistic adults who do not, under any uncertain terms, recognize their conditions as disabilities. Some wanted children that reflected their culture. These arguments show how differently we think as Americans. A specific population believes that it is immoral to genetically engineer, while a nearly equal amount feel that it is terrible not to if you prevent debilitating conditions.

I wish that I did not have anxiety but the coping mechanisms have proven to me that I have more resilience than anticipated. The same goes for my eldest child but seeing them tackle their fears shows that they will persevere. Our opinions do not condemn those of others.

Isaacson acknowledges a blurry line and slippery slope but does not condone those who think differently than he does. He brings together some of the most brilliant minds in science and shows that they all had different goals and visions for the potential of their discoveries. You will want to know more about them. Once we end at the Coronavirus mission, we know how we need to protect these minds.

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M. Marchand

Highly recommended

Reviewed in the United States 🇺🇸 on January 2, 2023

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Once again Isaacson delves into a complicated story of an important person in history, and presents a story that allows us to better understand his/her life. This time it's Jennifer Doudna, the primary scientist behind the discovery and ongoing development of the CRISPR gene-editing process. Don't get bogged down by the description of the legal battles between competing scientific camps here. I almost did. It was a tough slog and probably could have been shortened. Still, I was rewarded by my decision to stick with it. I would love to see Jennifer's story come to life in a video documentary or movie. She's an amazing human being. Like Isaacson's other biographies this is well worth investing the time to read.

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Hande Z

All cut up

Reviewed in the United Kingdom 🇬🇧 on May 24, 2021

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There are several books on CRISPR and genetic engineering published in 2020 and 2021. It is almost as if the writers were racing against each other the way the scientists from Berkeley (Doudna & Co) and Zhang (MIT/Harvard) raced against each other, first in determining how to use CRISPR to edit the human gene, and later, in the race to file the patent for the procedure.

This book is 481 pages long but is an easy and exhilarating book written by an experienced hand. Issacson, however, openly declares that he tells the story primarily from Jennifer Doudna’s point of view. He has done his best to be an impartial reporter and recorder of the story, yet it is obvious, and perhaps unavoidable, that some characters are cast in poorer light against Doudna, who Issacson shines the light of sainthood upon.

Before the race to discover how CRISPR might be used on human genes, they first have to discover CRISPR – the acronym for Clustered Regularly Interspaced Short Palindromic Repeats. As it appears, scientific discoveries are made a step at a time, almost always by different scientists. The Japanese Yoshizumi Ishino was the first to discover the repeat structures in a bacteria. It was Francisco Mojica who realised what these do, and it was he who came up with the name CRSPR. Then came Jennifer Doudna and Emmanuelle Charpentier.

In brief, they discovered how bacteria defend themselves against their old enemy, the virus. The bacteria cut up some of the DNA from the virus and then implant them on themselves so that they can identify the invading virus when they attacked again.

The story continues to the crucial race to discover how exactly the bacteria cut up the virus DNA. That was main work of Doudna and Charpentier. They discovered the process through the RNA and how the TRACR RNA helps identity then guide the bacteria’s protein enzyme to the target. All that is exciting, yet the book’s attraction lies in many other aspects.

We see how fame and money (the scientists get millions of dollars from prizes) change or perhaps reveal the dark side of even the seemingly nicest of people. We see how quiet, unassuming, dedicated scientists turn to ego-sensitive, prize-grabbing people. We may also question the way the patent system works. Reading between the lines of this book (remember, Isaacsson is a little beholden to Doudna for the backbone of his story) we might get a slightly different take.

Ethical issues involve not only the big question as to whether we should allow genetic editing in humans, but also the subsidiary question, of when we are ready for it. Thus enters the Chinese scientist He Jiankui who used CRISPR to edit the genes of a pair of twins so that they are genetically resistant to the HIV virus. Yet He Jiankui created an uproar in the West, and the worldwide outrage led to him being found guilty of conducting experiments without official approval and was sentenced to three years jail. He rushed ahead before the all-clear signal.

But now, with the COVID pandemic, scientists are open to using gene editing as an answer. Furthermore, even Doudna is working on other diseases that can be cured. They include the sickle cell disease, Alzheimer’s, and also cancer. There are also problems that the present system has not yet addressed – gene-editing as a medical magic wand seems destined to be available only for the rich.

We also learn from this book that the US military, DARPA (Defense Advanced Research Projects Agency) was so very much interested in gene technology in the last six years or so that it invested US$65m into research involving CRISPR and genetic engineering specifically for military purposes. Doudna is in one of the seven teams involved with DARPA funded research.

The moral and ethical issues are enough to keep one thinking long after the last page is turned. One big question is how different are the modern-day eugenics different from the eugenics of the early 20th century?

37 people found this helpful

Anantha Narayan

Helps understand biogenetics but drags in parts

Reviewed in India 🇮🇳 on April 11, 2021

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The Code Breaker traces the history of gene editing while simultaneously tracking Jennifer Doudna’s life — she has received a Nobel prize for being a pioneer of the CRISPR technology (an immune system that bacteria adapt whenever they get attacked by a new virus).

There is a key difference between this book and Isaacson’s biography of Steve Jobs. I did not learn anything new from the latter as I was aware of most of the key events in the life of Jobs and in the history of Apple; however the insights that he provided into Jobs’ personality and the behind-the-scenes happenings at Apple made it an extremely interesting read. The Code Breaker, on the other hand, was extremely informative given my limited knowledge of gene editing; however, in its quest for being informative, the book ends up being somewhat tedious.

Doudna has led an extremely laudable professional life. However, her personal life has been largely commonplace, and while Isaacson tries his hardest to create a sense of excitement around it, he fails to do so. He focuses all his efforts on this front in the third part of the book — Gene Editing — where he chronicles the intense rivalry between Feng Zhang and Doudna, tracing their race to get credit, important prizes and patents. But this attempt falls short.

The most interesting part of the book for me was the section where Isaacson explores the moral or ethical issues around gene-editing. This is best exemplified by the question, “would it be wrong to do so or would it be wrong not to do so”. Isaacson discusses where boundary lines should be drawn — somatic editing versus germline editing (the latter is hereditary), the use for treatment of diseases versus for enhancement of human characteristics, the types of diseases that should be edited out, disadvantages that are disabling versus those that are simply so because of societal constructs (such as homosexuality) and finally whether the individual or the community should control this. From this part onwards, the book is less about Doudna and more about the science.

The book ends on an optimistic note, while discussing the Covid-19 disease and the race to find a vaccine, on how reprogrammable RNA vaccines could pave a way for finding faster cures to diseases and pandemics in the future.

Pros: Helps understand the science of biogenetics, interesting debate on the ethical aspects

Cons: Drags in parts

56 people found this helpful

Dr Mike

Gripping account

Reviewed in the United Kingdom 🇬🇧 on March 17, 2021

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I'd bought the author's biography of Steve Jobs but have never managed to get through it. THIS book took me just two days to read and held my attention through every page; falls into convenient quarters if the reader needs to break the reading up. Excellent account of what drives a Nobel winner. Excellent account of a development that may become important in what is left of my lifetime.

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Serghiou Const

Gene editing in humans

Reviewed in the United Kingdom 🇬🇧 on November 24, 2021

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For the first time in the evolution of life on this planet, a species (Homo sapiens) developed the capacity to edit its own genetic make up. It is now possible to carry out genome modifications in the germline that is in sperms, eggs and early stage embryos, thereby altering the genetic make up of every differentiated cell with the result that these changes will be passed on to the organism's progeny and all subsequent generations. It is only prudent that we now pause until the societal, ethical and philosophical implications of germline editing are properly and thoroughly discussed. I wish, however, to clarify that there has already been general acceptance of somatic editing that is changes that are made in targeted cells of a living patient and do not affect reproductive cells. If something goes wrong in these therapies, it can be disastrous for the individual but not the species.

The book covers, in chronological order, a time span of 160 years from Darwin's publication 'On the Origin of Species' in 1859 to the development of mRNA vaccines against the coronavirus in 2020.

A fascinating aspect is that the book is not written in the abstract but through the personalities of scientists involved in the race for gene editing, their cooperation, rivalries, patents, forming companies, therapies, prizes, moral issues and the corona virus.

The main rivalry was between Jennifer Doudna and her research associates at Berkeley and Feng Shang at the Broad Institute in Cambridge Massachusetts. The winner was Doudna who shared with Emmanuelle Charpentier the Nobel prize for chemistry in 2020.

A starting point leading to the discovery of the gene editing system is the year 1990 when Francisco Mojica in sequencing genome regions of archaea (a kind of bacteria), spotted fourteen identical DNA sequences which repeated at regular intervals and between them were 'spacer' segments. They seemed to be palindromes, meaning they read the same backward and forward. Searching the literature, he found that Yoshimuzi Ishino studying E. Coli, a very different bacteria, similarly spotted these repeated sequences and spacer segments. This convinced Mojica that the phenomenon must have some important biological significance. Mojica coined the acronym CRISPR, for 'clustered regularly interspersed short palindromic repeats.' In most organisms that had CRISPRs, the repeated sequences were flanked by one of several genes, which encoded directions for making an enzyme. These were named 'CRISPR - associated or Cas enzymes. What fascinated Mojica were the spacers, those regions of normal looking DNA segments that were nestled in between the repeated CRISPR segments. He took the spacer sequences of E. Coli and run them through databases. What he found was intriguing: the spacer segments matched sequences that were in viruses that attacked E. coli. He found the same thing when he looked at other bacteria with CRISPR sequences; their spacer segments matched those of viruses that attacked that bacteria. Mojica found that bacteria with CRISPR spacer sequences seemed to be immune from a virus that had the same sequence. But bacteria without the spacer were in fact infected. It was a pretty ingenious defense system, but there was something even cooler: it appeared to adapt to new threats. When new viruses came along, the bacteria that survived were able to incorporate some of that virus DNA and that create, in its progeny, an acquired immunity to that new virus.

Mojica published a paper with his findings which was the beginning of a wave of articles providing evidence that CRISPR was, indeed, an immune system that bacteria adapted whenever they got attacked by a new type of virus.

By 2009 there was consensus that the Cas 9 was the most interesting of the CRISPR - associated enzymes. Researchers had shown that if you deactivated Cas 9 in bacteria, no longer cut up the invading viruses. They had also established the essential role of another part of the complex: CRISPR RNA, known as crRNA. These are small snippets of RNA that contain some genetic coding from a virus that had attacked the bacteria in the past. This crRNA guides the Cas enzymes to attack that virus when t tries to invade again. These two elements are the core of the CRISPR system: a small snippet of RNA that acts as a guide and an enzyme that acts as scissors. But there was one additional element of the CRISPR - Cas9 system that played an essential role, in fact, two roles. It was dubbed as 'trans - activating CRISPR RNA' or tracrRNA, pronounced 'tracer - RNA.' First, it facilitates the making of crRNA sequence that carries the memory of a virus that previously attacked the bacteria. Then it serves as a handle to latch on the invading virus so that crRNA can target the right spot for the Cas9 enzyme to chop.

As I have indicated in the beginning of the review the CRISPR - Cas9 system has been adapted from bacteria to edit human genes.

The distinguished Israeli author, Yuval Noah Harari, has aptly remarked that Homo sapiens has become Homo Deus.

4 people found this helpful

Sankarasivasubramanian P

Not worth the money

Reviewed in India 🇮🇳 on June 5, 2021

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I bought the book with an expectation that this will teach about CRISPR. But this tells about the early life, school life, marital life etc. of Jennifer Doudna. Gave up after about 100 pages. Very boring and puts me to sleep. Her life story is what you want to know, then you may like this book. If you are interested in the science, there may be better books.

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