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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 “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.
"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
About the Author
- ASIN : B08G1XNG7J
- Publisher : Simon & Schuster (March 9, 2021)
- Publication date : March 9, 2021
- Language : English
- File size : 55222 KB
- Text-to-Speech : Enabled
- Screen Reader : Supported
- Enhanced typesetting : Enabled
- X-Ray : Enabled
- Word Wise : Enabled
- Print length : 552 pages
- Lending : Not Enabled
- Best Sellers Rank: #4,607 in Kindle Store (See Top 100 in Kindle Store)
- Customer Reviews:
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Walter Isaacson includes mini bios for many of the scientists included in Doudna’s story and there are quite a few. At first, I was frustrated by all the incremental information - get on with it, already! As his worked progressed, peeling the onion of her life’s story, I see the value of understanding the motivation for these scientists; not all are created equally. Many of the details of Doudna’s life are glossed over so don’t expect a Hollywood style biography. Details are given as they relate to people and events of science, her personal life is not.
Doudna is an interesting woman due to the fact that she is really quite “normal” in her brilliance for bio chemistry. I was struck by her genuine affection for her co-workers that’s evidenced in the included photos as well as some of the lengths she went to helping her competition. She states that money is not her motivation but “publish or perish” is ingrained in most academics and even that seems to be under developed in Jennifer. THAT will become an issue...
Parts of this formidable volume read like a thriller. There’s intrigue, court battles, and friends with misunderstandings. Part Seven consists of 5 chapters that discuss the issues of ethics as relates to DNA and changing the structure of life, ordering the structure of life. Who has the right? Who controls the rights? Is it right at all? These are supremely serious questions that should be considered be every adult.
It would be helpful to have some science background when reading this book, but it’s not impossible without it. There are excellent footnotes to assist and if you get the Kindle version, they are interactive, which makes look ups SO much easier! Otherwise, this is definitely a worthy read. It’s very well written, challenging and up to the minute with information on the science of biochemistry and gene editing. The ethical issues should have people talking for a good, long time. The medical manifestations should have people living a healthy, long time. God Bless Us, Everyone📚
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.
It’s not that Isaacson makes grievous errors. In fact, everything in the Code Breaker is right. The explanation of the science behind Crispr is right, the biographical sketch of Jennifer Doudna seemed right, the culture of academia is captured right, he even broaches the ethical questions raised by Doudna’s work right. And yet, none of this goes beyond what you can gain from a typical extended article in National Geographic.
If Walter Isaacson were not the author, if this was simply a much needed biography of a very important scientist, it would be correctly regarded as a success. But given that Walter Isaacson is one of America’s premier biographers and Dr. Doudna one of America’s leading scientists, I was disappointed that Isaacson wrote for such a low common denominator of readership. On the other hand, if you’re looking for an easy to read book on this subject, you’ll be pleasantly surprised.
Not a bad book but Isaacson’s devoted readers, of whom I count myself one, are going to be disappointed.
The author does his best to present the story in another light but he tries too hard, and the effort comes across as a public relations project commissioned by Ms. Doudna.
I am at the same time both glad and sorry that I read the book. I am still in awe of the science, but the backstabbing among the scientists is sickening.
Top reviews from other countries
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?
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
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.