Gene Editing and the Unthinkable Power to Control Evolution

ByJennifer A. Doudna

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Readers` Reviews

★ ★ ★ ★ ☆
nancy hosman
I found the book very fascinating. The possibilities with this discovery are unlimited. I found myself not wanting to put the book down. Some of the more technical aspects needed to be explained better for the average person to understand.
★ ★ ★ ☆ ☆
muhammad abosekina
An important book about a new technology for genetic engineering, a quantum leap in scientific knowledge that every informed person ought to learn about. While written by a team promoting their own discoveries, it also does more than most 'gee whiz' science writing to explore the weaknesses and limitations of several gene editing technologies.

But several drawbacks. I found the science writing awkward and amateurish. Often found myself going on the web to find more straightforward scientific explanations for several key issues.

Like the mainstream book reviewers I also found the half the book about use and dangers of CRISPR-Cas9 to be uncritical although interesting. Some developments that this team didn't work on (gene drive) needed more detail.
★ ★ ★ ★ ★
nitica
This is a very important book which is challenging reading but well worth the effort. Gene editing is a huge breakthrough in technology but its use raises some critical decisions which society is going to have to confront!
Use Your Body's Own APO E Gene to Treat High Cholesterol :: A Journey Through African American Culinary History in the Old South :: Crown of Lies (Truth and Lies Duet Book 1) :: SAINT (Boston Underworld Book 4) :: The Lightkeepers: A Novel
★ ★ ★ ★ ☆
linsey
I’m a hard science guy and the squishier sciences make me uncomfortable but the authors very gently but thoroughly develop CRISPER to the point you will understand it.
It turns out that CRISPER has nearly the precision of engineering with its rules and results.
It’s definitely the biological equivalent of atomic energy, so you have to get it.
★ ★ ☆ ☆ ☆
lexi
As a expert biologist, Doudna explains the complex technology well for audiences that are scientifically inclined. Her conversation on the ethics of her technology are severely limited, which was rather disappointing for a book that brought claims of serious Oppenheimen reflection.
★ ★ ★ ★ ★
patricia
Review of A Crack in Creation: gene editing and the unthinkable power to control evolution by Jennifer Doudna and Samuel Sternberg
reviewed by Jerry Woolpy
Suppose we had an inexpensive technique to modify our genes that was within the grasp of a high school lab experiment and yet powerful enough to change, enhance, delete, or suppress the expression of individual genes. We do. It’s called CRISPR. This is what this book is about. It traces the international competitive effort that led to the technique. It explains how CRISPR works and its deficiencies. It analyzes the ethical debate over its use and recommends what should be done with it. The authors are expert scientists responsible in part for the successful development of the technique and fully aware of its capabilities and limitations. The book is mostly readable by scientists and lay people alike. Although some lay people may skip some of the technical discussion without missing the point, experts will thrill in the elaboration. The science is triumphant and inevitable. We ignore it at our peril. Whether you are scared by the potential of controlling evolution or intrigued by it, read this book!
★ ★ ★ ☆ ☆
lynda howe
Pretty elementary, but that is OK for non science readers. I bought the book for the ideas it might put forward about how this technology will effect future evolution. There was only a mention of these topics.
★ ★ ★ ★ ★
gepay
This is an exceptional book about gene editing. It is very much up-to-date in a field that seems to be changing faster than any other field out there (let's face it - an iPhone from 2017 is 80% the same as a 2008 model, but the field of gene editing has completely evolved in the last decade).

The first half is dedicated to how gene editing works, and how the CRISPR gene editing came about. Honestly for me there were some sections that became a bit difficult to follow, but I am not at all versed in the field. Also, there are a number of helpful illustrations that really help explain things (think of the "dino DNA" cartoon from Jurassic Park). But I think it is written at a level that people in the industry will gobble up, and people that are not in the industry can at least appreciate and get a general understanding of the technologies involved.

The second half is where it really gets interesting to me. The implications of this technology seem truly straight out of a science fiction book. Sure, we are all familiar with how genetic modifications have helped grow better crops and so on. But suddenly the human race has more or less been given the magic wand to play god. Where do we draw the line? Sure, we have all known these questions were coming and would face society someday, but this book makes it clear that the day has indeed arrived. The technology is not slowing down; other nations (China for example) WILL (and already are in some cases) be using the technology on humans. It is a fantastic and terrifying concept.

Anyway, this is truly a fascinating book that should be a must-read for anyone living in an advanced society; just amazing stuff!
★ ★ ★ ★ ☆
paul alexander
Dr. Doudna has written an excellent book about the gene-editing tool CRISPR, developed in her biochemistry lab in 2012. In a few short chapters, she writes an interesting and accessible synopsis of the history of gene manipulation as it developed through the latter half of the 20th century, leading up to the discovery of CRISPR, a bacterial defense against viral phages that can be re-engineered to give humans pinpoint control of their own genetic code. You may find some of her discussion harder than watching TV, but you owe it to yourself to read it carefully. This book is critically important to all 7.5 billion of us, and to our children forever.
Yes, we can now rewrite the genetic defect that predestines a person to suffer and die from Huntington's disease. In fact, we are terrifyingly close to being able to pack a virus with whatever genetic modification we would like to spread around and turn it loose. That will happen, it cannot be stopped, and Dr. Doudna, eminent, brilliant, naive Dr. Doudna, has ended our species. Homo GMO will be many different subspecies, no doubt, but none of them will be homo sapiens.
If you are a student of history, you will find Dr. Doudna's pollyanna singalong science lab views as trying as they are understandable. She is convinced that CRISPR can be contained by regulation and legislation, even though it is cheap, available, and pathetically simple to use. Imagine being able to live into your late middle age and not instantly understand that a tool like CRISPR will certainly be used (for instance) as coercion and enticement to surrender your rights to your own genetic code. Employers will be offering somatic enhancements as job perks within twenty years. Demanding to rewrite your genes for security reasons within thirty. Crafting their own engineered servitors to suit their employee requirements before the century is out. If we survive the virus hackers that long: doubtful.
Dr. Doudna lives a very long, long way from the barren urban enclaves where our enlightened, just, egalitarian society breeds its underclass prior to incarcerating them for profit, and it certainly shows in her analysis. She is right to be horrified of the genie her beautiful gene-editing tool has unleashed. She is bedazzled and foolish to think we can control it if only we ask it just the right questions. The blinding glare of powder white privilege thus renders the second half of the book much less interesting than the first, but you must read it. Try to forgive as you go. None of this is really one person's fault.
If it can be controlled, the primary function of CRISPR gene-editing will be to cement the class differences now maintained through coercion and fear into heritable biological class distinctions with real permanence. And won't our predator-owners be tall, pretty, healthy, and smart? If it cannot be controlled, some madman will surely demonstrate to our elite hyena class how much horror hubris can buy.
★ ★ ★ ☆ ☆
mary horne
Doudna and Sternberg did an excellent job of presenting from their point of view how the CRISPR-cas9 gene editing tool was developed. However, it was all so clearly written in a manner to give themselves sole credit for the discovery, mostly ignoring the contribution of other scientists in the field. I look forward to a more objective written account, which speaks to the competitive nature of the discovery and the patent law suits that ensued after the discoveries were made.
★ ★ ★ ★ ★
deangela webb
A CRACK IN CREATION: GENE EDITING AND THE UNTHINKABLE POWER TO CONTROL CREATION is a scary book, written by a biochemist whose life sciences research aided development of the new genetic-engineering tool, CRISPR. With CRISPR, scientists “can now manipulate and rationally modify the genetic code that defines every species on the planet, including our own. And … the genome … has become almost as editable as a simple piece of text.” With CRISPR, the whole process of evolution has been brought “fully under human control”.

This readable book explains in lay terms (with hand-drawn diagrams) how DNA, RNA, and CRISPR work; and how CRISPR was developed (chapters 1-4). It then discusses the mind-boggling applications of CRISPR gene-editing that already exist, such as farmed salmon that reaches market weight in half the time, and “gene drives” that harness “selfish” genes to ensure that offspring will have a 100% chance of inheriting a genetically modified DNA segment (chapter 5).

Next, it talks about advanced research into using CRISPR to fight human disease (chapter 6), and into using it to create perfect CRISPR babies via in vitro fertilization, or to create dangerous antibiotic-resistant bacterial strains (chapter 7). The final chapter explores the frightening future possibilities, if CRISPR research is allowed to continue unregulated (chapter 8).

Unfortunately, the genie is already out of the bottle. It’s doubtful--in this cynical reader’s opinion, though not necessarily in the author’s opinion--that regulatory efforts to control CRISPR will meet with more than limited success. However, this book does an excellent job of explaining to non-scientists why CRISPR opens species-changing possibilities that should be of concern to everyone. The possible unintended consequences of genetic engineering projects go far beyond whether genetically altered foods (GMOs) are safe to eat.
★ ★ ★ ★ ★
al raines
What a book! Very difficult science for someone who hasn't formally studied science for over half a century. But it was worth it to me to make the extra effort to understand. When author Doudna's explanations didn't work for me, I googled the relevant terms and found many online resources with illustrations that helped make the concepts clearer; then returned to reading the book.

This book itself is interesting because it brings so many aspects of CRISPR together in one place: a bit of history of earlier developments in this area, research in this century, Doudna's and her colleagues' efforts, and finally the ethical issues implicated by CRISPR & Cas9's power. Things are changing much more rapidly than I realized.

I was prompted to take a look at my own DNA via 23andme and will later get reports through Promethease and others. And I'm looking again at the GMO issue, which is unfortunately so clouded with misinformation (as is so much these days). But back to this book: I recommend it to everyone. I think we will be confronted with many ethical and personal issues regarding DNA and its manipulation and this work will help prepare us to make educated decisions. Highly recommended.
★ ★ ★ ★ ☆
nilanjona
I enjoyed the technical parts of the book; the ethical discussion, not so much. The book is mildly schizophrenic: the first part is written for venture capitalists, who want to hear about profit opportunities, not problems or limitations with the technology. In the second part, the author tries to assuage her guilty conscience as she and others potentially place the biosphere at risk while pursuing CRISPR-related entrepreneurial ventures. The book devotes only 3 pages to limitations and problems with the technology. If the author would like to make an additional substantial contribution to the ethical discussion, she should write an encyclopedic book describing everything we don't know about cell and molecular biology (while keeping in mind that the 'unknown unknowns' may be the most dangerous).
★ ★ ★ ★ ★
milja
Humans have reshaped the physical world for millennia, but the effects have never been as dramatic as they are today. Industrialization has caused climate change that threatens life around the globe. The biological world is also undergoing profound, human induced change. For billions of years, life progressed according to Darwin's theory of evolution - random genetic variations conferring advantages in survival, competition, and reproduction. Humans have managed to influence and speed the process through selective breeding of plants and animals - but changes produced are still slow and uncertain.

Now, within the last few years, scientists have succeeded in bringing this process more fully under human control. The tool utilized, CRISPR, offers the promise of major genetic changes in a wide range of organisms in the near future. Already scientists have created dogs with super-muscular physiques, micro-pigs, disease-resistant rice, more slowly ripening tomatoes, and soybeans with healthier polyunsaturated fat. Near-term hopes include 'humanizing' pig DNA - allowing them to serve as organ donors for humans, eradicating mosquito-borne illnesses - if not the mosquitoes as well, correcting mutations responsible for cystic fibrosis, sickle cell disease, etc. Most of these feats have been or are hoped to be accomplished by finding and fixing single incorrect DNA letters out of the 3.2 billion that make up the human genome. Theoretically, every disease for which we know the underlying mutation(s) is a potentially treatable target. Even some cancers are now experimentally treated with edited genes that hunt down and cancerous cells. Doudna even believes it could modify human germlines connecting one generation to the next - preventing diseases in future humans.

Another possibility - upgrade norm genes to supposedly superior versions - eg. lowering the lifetime risk of heart disease, Alzheimer's diabetes, cancer, etc., or providing greater strength and increased cognitive abilities. Someday we may consider it unethical not to use this new tool to alleviate human suffering.

Each specific sequence of DNA letters provides instructions to produce a particular protein inside the cell, The proteins go on to carry out most of the critical functions in the body - eg. breaking down food, recognizing and destroying pathogens, and sensing light. To transform the instructions contained in DNA into proteins, cells use a closely related molecule called RNA - produced from the DNA template. RNA ferries information from the nucleus, where the DNA is stored, to the cell's outer regions where individual protein molecules are produced.

Most bacterial genomes exist inside the cell as a single continuous piece of DNA. The human genome is composed of 23 pieces (chromosome) ranging from 50 to 250 million letters. Like almost all mammal, human cells normally contain two copies of each chromosome - one from the father, one from the mother. Each parent contributes 23 chromosomes, giving the offspring a total of 46. The human genome also includes a separate mini-chromosome - 16,000 letters of DNA located in the energy-producing batteries of the cell (mitochondria). (Mitochondrial DNA is inherited exclusively from the mother.) Mutations in one of the 23 nuclear chromosome pairs or the mitochondrial chromosome can cause genetic disease. The full set of nuclear chromosomes can be found in almost every cell in the body (red blood cells lack a nucleus.

Recessive genetic diseases require both copies of an individuals HBB gene to carry the mutation for that person to be affected - if only one copy has the alteration, the non-mutated gene can produce enough normal hemoglobin to overcome the negative effects of the mutated hemoglobin. People with only one mutated copy of the HBB gene still carry the sickle cell trait, are usually unaffected, but can pass the mutated gene on to their offspring. Other genetic diseases exhibit dominant inheritance, meaning that just a single copy of the mutated gene is enough to cause the disease.

Genetic diseases can result from insertions or deletions in DNA. In Huntington's disease, a mutation of the HTT gene has the same three letters of DNA repeated too many times. Deletions are the culprit in the most common type of cystic fibrosis. Other diseases occur when segments of a gene are inverted.

The size of a genome and number of genes is contains varies widely across different kingdoms of life. Most viruses have just a few thousand letters of DNA (or RNA - some viral genomes contain no DNA) and a small handful of genes. Bacterial genomes are millions of letters long and contain about 4,000 genes. The human genome comprises about 3.2 billion letters of DNA, with around 21,000 protein-coding genes.

Beginning in 1990, scientists teamed up to sequence the entire human genome, facilitated by new technology and complex computational algorithms. In 2001, at a cost of over $3 billion dollars, the first draft of the genome was published. It now costs far less.

'Recombinant DNA' - genetic code produced in a lab.

'Retroviruses' - a large class of viruses that include HIV. They splice their genetic material into the genome of cells it is infecting. About 8% of the human genome (over 250 million DNA letters) are remnants of ancient retroviruses. In the late 1980s, retooled retroviruses were used to insert lab-produced genes into mice.

One of the hidden problems with gene splicing is that unplanned results can occur - eg. the new material can be inserted in locations it was not intended for.
★ ★ ★ ★ ☆
margarida monsanto
A must read book with a remarkably short shelf-life!

CRISPR-Cas9 could prove to be the biggest innovation of our time, which is full of astonishing developments in the fields of AI, robotics, solar, autonomous vehicles, block chain, VR and many others.

And, this is about the first popular book written on this monumental and yet esoteric discovery (also by one of the field's pioneers). The pace at which the field is changing is bound to make the book outdated in months. Far better explanations are going to flood the market too as others have a crack at explaining what this technology is. Even the long-winded moral/ethical discussions that fill the book towards the end will evolve fairly quickly.

Yet, the authors' audacious explanatory work should be read to understand where it all began. That there are naturally occurring viral DNA strands that could be used to precisely locate a region of DNA, which could then be altered at will (none of these precisely true yet) is actually true is lesser of the marvels. That we have science and scientists who actually uncover all this and are able to manipulate deserves the bigger gasp. It would be one of those mother of all understatements to state that the implications of what is being achieved in this field are far-reaching. Effectively, unless this entire gene editing technic is proven to be a Y2K-like hoax for whatever reason, life is never going to be the same. Literally.

So for all the faults, here is a must read book until the next ones begin to emerge!
★ ★ ☆ ☆ ☆
patrick
Update:
Since originally writing this review, I have discoversed that Dr. Doudna, one of its authors, has engaged in several very dubious practices.

Namely, in 2014, she lambasted Eric Lander, head of MIT, over a history of CRISPR he wrote, claiming serious misconduct with regard to failing to report conflicts of interest.

The accusation wasn't completely without merit, as Dr. Lander was the head of an institution embroiled in an intense patent debate with Berkeley (Doudna's) institution. But, Dr. Lander announced those conflicts, and the publishing company decided to ignore it.

Doudna, meanwhile, makes it almost halfway through her book before she bothers to tell us that she has ownership interest in SEVERAL companies that are attempting to license CRISPR.

So, that's pretty egregiously hypocritical.

Lately, she's been trashing research articles that question the proclaimed accuracy of CRISPR, again without any apparent declaration of her conflicts.

At this juncture, the idea of Doudna leading the bioethical debate about CRISPR is....questionable, at best. As mentioned below, her ability to do it is suspect, but her willingness to do it is now suspect as well.

TL; DR: This book is a wonderful introduction to CRISPR, for all audiences. But it is a piteous, woefully incomplete statement of bioethics, with little or no understanding of how to get from where we are to where we need to be.

Slightly longer:

Every once in a while, something comes along and you feed obligated to review it, not so much for yourself, but for everyone else. Most of the people who get this and review it will probably be the same as "The Immortal Life of Henrietta Lacks" crowd. (I.e., well-meaning people who are generally sort of amateurs at molecular biology. I am a professional. So.

Viewed one way, this book has two equally important functions.

First, to inform readers (both specialists and lay audiences) about the way CRISPR works and the things that it can do (i.e., what types of genetic changes it makes possible). On this front, the book is a complete success. To dramatically shorten what it says, CRISPR basically rips open the genome of any organism that you want and allows you to edit it the way you would a document in a word processing program. The power? Vast. The potential? Immense. Basically limited only by our imagination and willingness to tolerate mistakes and misses. If you've seen GATTACA, this is the technology that makes that happen.

Which brings us to the second function. Which is to present the ethics of this tool. And Doudna and Sternberg completely fall short. As an example of the nuanced bioethics statements in the book: "With suitable guidelines, I view the use of farm animals for biomedical research purposes as more acceptable than the use of companion animals like primates" (pg 139). Setting aside the contentious notion of primates being companion animals, there is nothing in the surrounding region of the text (or in the book at all, really) to explain how this is intended to be grounded in any sort of normative ethic. Instead, it just "feels" correct to the author(s). So, if you come here looking for a discussion of bioethics...you won't find it. And I'm not really surprised. As the author herself points out, "...in truth, I much preferred working in the lab and trying new experiments to thinking about the theoretical, long-term implications of my research and trying to explain them to non-scientists." Which is, to say, the thing that she has failed at is the thing that she didn't want to do.

I say this as a person who has been thoroughly trained in both ethics and in molecular biology. Only one aspect of this book was even remotely good. And the other part is so bad that it frequently made me angry or disappointed.
★ ★ ★ ★ ★
deborah
The scariest book I've read since Regenesis by George Church. After reading it, I understand better his claim that 1990s were still the Stone Age of genetic engineering compared to the industrial age of when he wrote the book (published in 2012, it surely was written at least the year previous). Doudna published her paper on CRISPR applications for gene editing in Science in June of 2012. If 2011 was the industrial age of genetic engineering, 2017 is well into the Information Age. We have moved on from genetic engineering to gene editing.

One of the authors' most chilling (and telling) statements is that "what used to require years of work in a sophisticated biology laboratory can now be performed in days by a high school student." (p. 113) They state that a CRISPR lab can be set up for just $2,000. What is scary about this? CRISPR can make gene edits that are heritable. The age is upon us, exciting and chilling. Genome beware, Tinkering-man is coming for you!
★ ★ ★ ★ ☆
cavan
The subject matter is very interesting, and I learned quite a lot from the book, but it was hard to read. The language is quite awkward in places, and some colorful word choices are puzzling, but this is mostly relates to the parts that are not about science, but about people and relationships.. The science parts were much more readable and interesting.
It was very interesting for me to learn about CRISPR and powers it gives to people. Pretty scary stuff in the hands of ignorants but it also can give us so much in many ways.
★ ★ ★ ★ ★
ashu
This is a very interesting read on various aspects of what is truly a revolution in science. It covers the history that got us to CRISPR-cas9, what it might be possible to do with it, and the ongoing exploration into the ethical considerations. The book is all the more interesting because it was written by people who played a significant role in making it all happen.

It feels like the *point* of the book is the ethical discussion, and indeed there are some big questions there, especially with respect to its use in humans (as opposed to agriculture). What will we allow this to be used for? What about people who can't afford the therapies? I applaud the authors for their role in organizing discussion about the ethical considerations.

The book doesn't actually go into that much detail about the technology itself. If you are looking for more than a high-level discussion of how CRISPR works, you should look elsewhere.

There was one meta-level ethical consideration which was not raised in the book: what gives one person the right to decide for another whether or not they can use technology for a particular purpose? The discussions about "what will we allow this to be used for and what will we make illegal?" are great, but don't forget the question of "what gives me the right to make that decision for someone else?"

For example, some people feel that nobody should be able to have their child be engineered to be free of genetic diseases if others cannot afford the therapy -- it would increase inequality. Many people's hackles are raised at the thought of an advantage that can be bought; you can only buy your kids that advantage if you also buy it for ours, because we can't afford it! But really, what gives a society the *right* to prevent parents from doing something they believe to be positive for their children. If such a right exists, where does it come from?

The traditional notion of liberty, that "Your right to swing your arms ends just where the other man’s nose begins," only applies here if we consider that being "left behind" is a kind of harm. For example, if you buy a new car, and I still have to drive my old beater, have you harmed me?

Many people think OK, you can use CRISPR to prevent genetic diseases, but you can't use it for cosmetic purposes. But again, what gives you the right to dictate that? A short man, who almost surely has an even shorter wife if he has one at all, is very likely to have a short child. I know such a man who decided not to have kids in part because he knows that his children would likely be short. He knows what that means, statistically, in the real world: short men are much less likely to be leaders, are paid less, are rejected by most women as partners, often get picked on as kids, etc. Being short as a child may contribute to self-esteem problems, which compound the other problems. So if it were possible for this couple to pay, say, $20,000 to ensure that their child would be 5' 10" instead of 5' 4" or 5' 5", what gives anyone else the right to say that they cannot do so? It may actually be more important to that child's overall well being than resistance to cancer, if the child's psychology is considered.

What gives one person the right to play God with regard to what another person can do with available technology?

If it is wrong, on the basis of a pursuit of equality, for parents to buy their children height, then ask yourself this. The technology could presumably also be used to ensure that a child is 5' 10" instead of 6' 8". Should we, as an equality-seeking society, forcibly perform that edit? If not, then isn't the argument against buying height based on something else besides inequality? Perhaps a fallacious Appeal to Nature?

They didn't get into any of that, but there is plenty of food for thought in the book. Definitely timely and worth a read!
★ ★ ★ ★ ☆
aran suddi
The first half of the book reads like an unfolding of a scientific mystery and provides uncommon insight into the workings of a biomedical research lab. The second half of the book focuses on the ethical questions in future modification of animal and human germline cells, which could lead to a world where wealthy parents can "order up" designer babies.The only reason I'm giving it a 4 is that the illustrations were a good idea but so basic that they didn't add much except decoration. No matter, Dr. Doudna is a lock for a future Nobel Prize recipient and reading her account of one of the greatest biomedical discoveries of all time is well worth it.
★ ★ ★ ★ ★
dan haugen
Not since "Microbe Hunters" by Paul de Kruif Microbe Hunters and "The Double Helix" by Watson and Crick The Double Helix: A Personal Account of the Discovery of the Structure of DNA has the excitement of discovery in the biological sciences been expressed and made vivid for lay readers in the way that Douda and Sternberg's account of their research into Bacterial Immunological Systems and application of CRISPR/CAS9 for Gene Editing displays. This easily understood scientific autobiography documents much of the research that led to one of the most important discoveries in molecular biology and genetic engineering in recent decades. The clear prose and simple diagrams which document CRISPR and its mechanisms make clear and make exciting this journey of scientific discovery,

Highly Recommended
★ ★ ★ ★ ★
brad o
“A Crack in Creation” by Jennifer A. Doudna and Samuel H. Sternberg is simply a must-read popular science book. Professor Doudna led the research team responsible for the breakthrough gene editing technology, CRSIPR. This important book promises to stimulate informed conversation about the new, unprecedented powers of creation that have recently been placed in human hands.

The book is divided into two sections. Part I: The Tool documents the discovery process that led to CRISPR. No doubt, the author’s painstaking reconstruction of events will prove immensely valuable to students and scientists. The authors have a knack for explaining complex concepts in an accessible manner. Still, for generalists like myself, I found myself skimming through sections because the science (for my taste) trends towards the arcane.

Part II: The Task talks about the potential uses and abuses of CRISPR. The authors envision useful systemic applications including immunotherapy to fight disease, the purposeful engineering of more productive crops and livestock, and so on. Human germline applications, of course, are more problematic. The authors are sympathetic to the cause of eradicating genetic conditions but are concerned about unwise experimentation (e.g., designer babies). After reading the author’s reasoned thoughts and perspectives, I feel much better informed and engaged. There is no doubt that gene editing will be widely discussed and debated for many years to come.

I highly recommend this excellent book to everyone.
★ ★ ★ ★ ☆
scott cunningham
Very clear and interesting text and illustrations make it easy to learn about the CRISPR technology, its antecedents, and its uses. The first part of the book focuses on the core science and technology, and the second on its ethical, social and economic implications. The book ends with a call for scientists to engage with other professionals and with government officials to facilitate a public, global discussion on CRISPR usage and regulation.
★ ★ ★ ☆ ☆
letizia
I'll approach this book from a slightly different angle from other reviews to date: focusing on the narrative.

This book suffers from following an inappropriate formula, which I suspect was urged on the authors by their agents and editors. (I'll refer to the authors collectively as JD, because poor SS has entirely effaced his own individuality from this story.) It's as if JD mentioned during a meeting that in her youth she'd read "The Double Helix" -- James Watson's notoriously gossipy recounting of the discovery of DNA's molecular structure -- and the suits said, "Exactly, make it like that -- show us the *personal* side of how you made this tremendous discovery. Love it!"

Watson's book paints a vivid contrast between himself, a footloose biologist in his mid-20s, and his collaborator Francis Crick, a brilliant physicist in his late 30s and already into his second marriage. The portraits of the various other scientists with whom they worked or competed in the race to find the structure of DNA are at times catty, misogynistic or worse, and the narrative suspenseful -- e.g., Watson & Crick might not have "won" if the brilliant chemist Linus Pauling hadn't wasted time following up a wrong hunch. The book became a scandal, a bestseller and a classic. CRISPR technology rests on Watson & Crick's discovery, but its practical impact might come close to being as great. So it doesn't take much imagination to see why the publishers might have been hoping for another firecracker of a bestseller. But they seem not to have known the authors very well.

At center stage here isn't a duet but a solo act with a large supporting cast. To help us feel the personal angle, JD dutifully tells us about Hawai'i, where she grew up. She reminisces about going for runs along the Charles River by Harvard. She recalls particular days when she drank coffee before going into a conference session, etc. There's just one problem -- or several. There's absolutely no suspense. There's absolutely no drama. There's absolutely no gossip. And there's absolutely no revelation of JD's personality. James Watson had plenty of his own mishugas, and didn't hide it (see his sequel memoir, "Genes, Girls and Gamow" for way too much evidence of same). But here we learn nothing about JD's personality other than that she was a dutiful high-achiever who loves her work. She's "thrilled" when a famous Stanford scientist agrees to attend an ethics conference (@206-207). JD may be a role model to young women in science, but if she ever encountered any obstacles in her career due to her gender (which, given her generation, seems likely), they aren't mentioned here. And far from dishing about her competitors, JD is never anything but gracious about them. More specifically: she's gracious about mentioning their names. A striking aspect of the narrative portion of this book is that there aren't any characters at all -- only names and accomplishments, and the occasional shared cup of coffee.

This isn't at all to say that it's wrong to acknowledge colleagues; nor do I mean to suggest that JD lacks a personality. But it does mean it was a conventional and even silly idea to apply this "Double Helix" narrative formula to such a square, straightforward story, particularly when the narrator doesn't want to share much about who she is. Ironically, there really is some drama in the CRISPR case: JD's home institution of UC Berkeley is currently fighting an epic patent battle with the Broad Institute/MIT. Plus, the scientific board of Editas Medicine, which initially contained a "supergroup" of researchers from Berkeley, MIT and France, including JD, broke up just months after JD finished this manuscript (with the East Coast fraction remaining on the board). Such rivalry and the race to get credit for discovery were a lot of what made "The Double Helix" work. But whether on lawyers' advice or just due to JD's temperament, instead of interpersonal tensions, angst and quirkiness we get the Travel Channel. I entirely respect JD's choice, but her editors should have realized at some point how futile it would be to inflate this into a personal drama.

My own purpose in reading this book was to learn about how CRISPR works, period. I had no interest, neither before nor after reading the book, in whom JD interviewed for her lab, or with whom she went sight-seeing in Old San Juan. If CRISPR had been discussed in a new edition of some college-level genetic engineering textbook like Old & Primrose, I'd have gone for that. But at this writing there isn't any such introductory science pedagogy about CRISPR, only lab manuals for practicing scientists or else popularizations. The book helped me towards achieving my goal, but only after wasting a lot of time on personal backstory. To be fair, the science backstory -- the history of other discoveries leading up to the CRISPR-cas9 system -- I did find helpful. Still, many things are unexplained, such as the nature of the "tracrRNA" sequence that's essential for the CRISPR-Cas9 system to work, and the difference, if any, between the Doudna/UCBerkeley group approach and the Zhang/MIT/Broad approach. There are also some oversimplifications that even I could spot, such as the description @102 that makes it sound as if DNA is transcribed directly into messenger RNA that's used for producing proteins, when actually the direct RNA transcript is usually heavily edited first.

The book might have provided an even clearer understanding of CRISPR, but for another editorial misjudgment: editors of popularized science have a misplaced faith in the power of their scientist-authors to explain stuff clearly in *words* while keeping the reader awake. A book like this should have MANY more illustrations -- roughly one for each paragraph of technical exposition. I've been reading the "easy" pages at the front of Science and Nature for years, so I've had some exposure to some of the basic ideas discussed; yet even I would have appreciated more graphics. So I'm sure that readers who are new to the science would benefit as well. The few ink drawings that are included aren't always clear. Some are even downright puzzling, if not miraculous: such as one that appears to show a human embryo being incubated in a man's armpit and then emerging from his navel (@159).

Some reviewers fault JD for her approach to ethical issues in the book's Part II. I don't have sufficient expertise to judge that sensitively. But JD doesn't hide her involvement in some CRISPR-related startups, and in fact mentions what an interesting new perspective that gave her. Nor does she hold herself out as an expert on ethics. As one of the "parents" of a new technology, she seems to me to be entitled to express her hopes and fears about its future despite her not being a professional ethicist, just as the parent of a child can express concerns about the child's emotional health without first having to get a degree in developmental psychology. Whether the parent's, or JD's, views should be regarded as definitive and authoritative is a different matter. One curious thing, though, -- or maybe "obvious" is a better adjective -- is that the ethics of private ownership of intellectual property in these various biochemical techniques and genetically-modified organisms is never up for debate in books like this.

In the 1997 film "Fierce Creatures," a small-animal zoo is taken over by a Rupert Murdoch-type global conglomerate. The new owner promptly decrees that all cute animals must be removed in favor of violent ones, on the theory that this will increase ticket sales. The staff can't bring themselves to do this, and instead replace the signs on the exhibits with new graphics, such as of snarling, teeth-baring chipmunks. Despite the apparent hopes of corporate publishers and agents to turn this book into another juicy "Double Helix," the result came out as more of a literary equivalent to the chipmunks, without even the snarls. A more straightforward approach to the science in Part I of the book would have saved readers' time, and perhaps better reflected the writers' personalities as well. The public's need to understand CRISPR technology and its implications is too great for the details to be buried in formulaic stylistic fluff.
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carter youmans
I applaud the authors for bringing better awareness to the public the astonishingly fast advances being made in biomolecular technologies. CRISPR has in many ways already revolutionized the field of biology and shortened the turn-around for research results and has great therapeutic potential in addressing diseases. It also has the potential to "enhance" our natural biology. For instance, some "brave" (in my mind foolish) have used the technology to essentially "turn-off" a gene that down-regulates muscle production via injectable delivery. In particular, such an approach was used to increase muscularity and strength to a muscle of the forearm. Potentially for muscle wasting diseases, this might be a promising future therapeutic or a horrible nightmare still awaiting discovery. For one thing, biology is mind-boggling complicated and astoundingly non-linear. Even seemingly knowing all the variables involved in a biological phenomena is no guarantee there will be an understanding of the how the phenomena functions. Slow down let along shut down one proverbial clog in a massively inter-dependent system, it is far more likely that very unintended consequences will emerge. On the other hand, there are so many redundant genetic "backups" that compensate for a loss of gene functions that even if you delete a gene, no apparent effect is evident. In short, despite our advances in knowledge and technology, we still have a long way to fully understanding gene regulation. Therefore the claim that we are poised to direct our "evolution" is at best a great overstatement; at worst a foolhardy belief. Still the ethics of CRISPR and other developing technologies need to be addressed and this is a good read in general but really meant as a layman's book and more geared toward entertainment than a more seriously involved discussion. For that, I would recommend Bioethics: An Anthology by Helga Kuhse.
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jonnie estes
In other words, usurping the power of God. Has that old idea been used in a title before? Now we live on FORBIDDEN PLANET and are The Krell? Does indeed Mother Nature have a sleeve for frightening things to be up inside ? Or is it Pandora's Box? That title exists too. I guess people who ignorantly do not believe in Evolution will not buy this book. Ignorance is Strength. Close the EPA. Who needs an Environment anyway? Turn up the air conditioner and stay indoors. I just wish I could genetically modify the U. S. Government Heads, without having to use a Guillotine ( for Stopping Abuse of Power Since 1814 ). Send House and Senate back to Kindergarten. Ask Kathy G. about Freedom of Speech. Dictators cannot stand cartoons. They can fire whole Science Departments, but a cartoon magazine has to be decimated by a couple of religious terrorists. Bad taste is worse than total scientific ignorance?
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angelique du plessis
Mind boggling wonderful and at the same time frightening what advances are becoming possible with gene editing - not only the future of medical treatment interventions - but potentially the god-like alteration of human beings. Fascinating and easily readable - this book was written by the researcher who created the breakthrough tool which makes these gene altering changes possible.
Please RateGene Editing and the Unthinkable Power to Control Evolution
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