The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race - book cover
Community & Culture
  • Publisher : Simon & Schuster; First Edition
  • Published : 09 Mar 2021
  • Pages : 560
  • ISBN-10 : 1982115858
  • ISBN-13 : 9781982115852
  • Language : English

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

A Best Book of 2021 by Bloomberg BusinessWeek, Time, and The Washington Post

The bestselling author of Leonardo da Vinci and Steve Jobs returns with a "compelling" (The Washington Post) account of how Nobel Prize winner Jennifer Doudna and her colleagues launched a revolution that will allow us to cure diseases, fend off viruses, and have healthier babies.

When Jennifer Doudna was in sixth grade, she came home one day to find that her dad had left a paperback titled The Double Helix on her bed. She put it aside, thinking it was one of those detective tales she loved. When she read it on a rainy Saturday, she discovered she was right, in a way. As she sped through the pages, she became enthralled by the intense drama behind the competition to discover the code of life. Even though her high school counselor told her girls didn't become scientists, she decided she would.

Driven by a passion to understand how nature works and to turn discoveries into inventions, she would help to make what the book's author, James Watson, told her was the most important biological advance since his codiscovery of the structure of DNA. She and her collaborators turned a curiosity of nature into an invention that will transform 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.

The development of CRISPR and the race to create vaccines for coronavirus will hasten our transition to the next great innovation revolution. The past half-century has been a digital age, based on the microchip, computer, and internet. Now we are entering a life-science revolution. Children who study digital coding will be joined by those who study genetic code.

Should we use our new evolution-hacking powers to make us less susceptible to viruses? What a wonderful boon that would be! And what about preventing depression? Hmmm…Should we allow parents, if they can afford it, to enhance the height or muscles or IQ of their kids?

After helping to discover CRISPR, Doudna became a leader in wrestling with these moral issues and, with her collaborator Emmanuelle Charpentier, won the Nobel Prize in 2020. Her story is an "enthralling detective story" (Oprah Daily) that involves the most profound wonders of nature, from the origins of life to the future of our species.

Editorial Reviews

Named one of the Best Books of the Year by Time Magazine, The Washington Post, Smithsonian Magazine, Amazon, BookPage, Science News

"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

"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...

Readers Top Reviews

I throughly enjoyed reading this book, the narrative carries u along the discovery of CRISPER and its massive impact on science and society. There r loads of names n lots of scientific terms yet the major figures and terminology r constantly referenced so we can still follow the threads of the narrative. At times the time spent on the ethical arguments seem a bit too protracted and repetitive, but that is merely nitpicking to find fault. An excellent book for readers who lack a science background.
Serghiou Const
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. ...
Dr Mike
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.
Anantha Narayan
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
Wei ZhaoAran Joseph
This book makes the same mistake as many others by implying that CRISPR-Cas9 is all that is needed for gene-editing. In reality, CRISPR-Cas9 by itself can only accomplish half of the task, which is finding the exact location in the genome very specifically and efficiently. To be clear, this is indeed a huge discovery, and Jennifer and Emmanuel's groudbreaking work is well deserved to win the Noble Prize. However, once finding the correct location for editing, all Cas9 can do by itself is cutting the DNA double helix at this location. Nevertheless, cutting alone usually disrupts the target gene by a mechanism called nonhomologous end joining. Human does possess another DNA repair pathway called HDR, which can fix the gene if a DNA template is nearby. Unfortunately, the latter one only works in the dividing cells and its editing efficiency is often miserably low, especially when editing in vivo. For all the above reasons, CRISPR-Cas9 needs to pair with other editing modules to complete the other half of the job, the actual editing, to fully unlock its potential. This is where the base editor or prime editor comes into the scene. Invented by Harvard Chemist David Liu and his postdocs, both base editor and prime editor can offer much higher "editing" efficiency than HDR. And both editors are widely adopted and hailed by the gene-editing labs across the globe since their debut in 2016 and 2019 respectively. As such, it is a major disappointment for this book that Walter Isaacson failed to dedicate at least one complete chapter to highlight base/prime editor and have an interview with David Liu to discuss his transformational work.

Short Excerpt Teaser

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.<...