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Book review: ‘A Crack in Creation.’ Jennifer Doudna’s journey of discovery

Famed CRISPR researcher Jennifer Doudna, along with a past student Samuel Sternberg (starting his own lab in at Columbia University), wrote an account of her CRISPR discoveries and the possibilities the technology unleashes. The book, “A Crack In Creation: Gene Editing and the Unthinkable Power to Control Evolution“,  is written from Prof. Doudna’s perspective (so I’ll refer to her throughout this review, sorry Sam). The excitement of explaining this powerful new technology comes with a weight of responsibility over what CRISPR might do for good or ill. She walks us through the discovery, development, and potential of CRISPR to manipulate biology and re-ignite ethical debates over gene editing.

There are some personal anecdotes from Prof. Doudna, but she largely maintains a more academic voice than a tell-all about the dramas surrounding CRISPR.  While Jennifer Doudna has been involved in a publicized patent battle that pits UC Berkeley, where her lab is based, with the Broad Institute of MIT and Harvard, you won’t find any gossipy details of that dispute in this book. You will find her side of how the discovery of CRISPR as a gene editing tool unfolded and much more on where she thinks it can go.



Doudna describes her journey as a scientist and the field’s journey to putting all of the pieces together that allow gene editing with CRISPR tools. As she describes the science, there are helpful pen and ink illustrations (done by Jeffery Mathison) of the concept being discussed.

Early on she alludes to the eventual impact of genome editing while describing the early days, but it’s really incredible to think about all of the applications mentioned later given how obscure some of the work to discover CRISPR sounds. A good portion of the early research on how CRISPR is used to for bacteria to defend against viruses came from scientists working on yogurt production. Viruses that attack bacteria, called phages, can kill yogurt bacteria and cause losses in the yogurt industry. This is how scientists discovered that CRISPR was involved in the bacterial defense system against phages.

Upon looking at how prevalent the CRISPR repeats were Doudna writes, “These bits of information sent a little shiver of intrigue down my spine; if CRISPR was present in so many different species, there was a good chance that nature was using it to do something important.”

From there, researchers still needed to find how CRISPR works and how it can be modified for our use as a technology. The book nicely lays out  the discovery process for us in hindsight, and shows that finding a powerful tool like the CRISPR technology was never guaranteed in the context of studying how a bacteria defends itself from viruses.


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Impacts of CRISPR on human health

Currently CRISPR-Cas9 is already being used in research labs around the world as a tool for biomedical research. This research can lead to more discoveries for drug targets and mechanisms of diseases. But CRISPR also holds the potential to target genes in the clinic where it can directly act as a treatment.

In the clinic, there are clinical trials ramping up for treatments based on somatic cells. That means editing the cells of an adult person that would not be passed on to their offspring. In many cases this is done by removing the cells from a patient, editing the cells, and then putting the edited cells back into the patient. However, using techniques like viral or nanoparticle delivery could lead to editing cells directly in the human body. Safe and efficient use of CRISPR technologies could lead to curing many genetic diseases like sickle cell anemia or Duchenne muscular dystrophy would be huge wins for medicine.

Another use that has enormous potential benefit for human health is gene drives. Gene drives use CRISPR-Cas9 to spread a gene through a population faster than typical genetic would expect. If an organisms inherits a gene drive from one parent and a normal set of gene from the other parent, the gene drive copies itself over to create two copies. Then that organisms has two copies of the gene drive and will pas it on to any of its offspring only to be copied again. This type of technology could rapidly reshape evolution of a species and be used for health applications like eliminating or altering mosquitoes so they can’t spread diseases like Malaria. As mosquito-borne diseases are major global health problems – like Malaria, West Nile, Zika, or yellow fever – a tool that could stop or alter their spread would be incredibly powerful

Overall, CRISPR technologies have opened up many research avenues and spurred research and development of potential new treatments. Doudna estimates new studies at rate of “more than five per day” and “well over a billion dollars” into startups trying to get CRISPR tools into the clinic.

Ethical debates

Jennifer Doudna admits that she hadn’t engaged much with how research leaves the lab until CRISPR started rapidly opening new possibilities in the world.

Early in these discussions she says, “The idea of taking a public stand on a scientific issue, no matter how important, felt foreign to me, almost transgressive.”

But after realizing the power of CRISPR enabled genome editing, she’s continued to be at the forefront of talking about CRISPR’s implications for humans control over so much of biology potentially including our evolution.

Doudna recounts a dream where she comes faces to face with Adolf Hitler, who says to her “I want to understand the uses and implications of this amazing technology you’ve developed.” Obviously this reflects a profound concern over how CRISPR as a technology could be used for good or bad purposes. What’s difficult is keeping up with a fast moving technology enough to understand the good or bad implications of any given use.

“Few technologies are inherently bad or good; what matters is how we use them. And when it comes to CRISPR. the possibilities of this new technology – good and bad – are limited only by our imaginations.” A Crack in Creation

Jennifer Doudna speaks about wanting a broad societal consensus around these thorny issues. She seems still not ready to let loose on germline and wants us to grapple with how we would pick and choose as a society. How well we can have those conversations and make difficult policy on a case-by-case basis remains to be seen.


Still many open questions

The book ends with discussions and open questions on gene editing and how we want to deal with it as a society. As a researcher who knew a lot of the CRISPR research I found this the most interesting third of the book, but the ethical questions of how we should allow manipulation of human DNA should be interesting to anyone.

Much like the larger conversation being had over CRISPR, this book tries to span that gamut to engage technical audiences and people who knew little of CRISPR before picking it up. It has very basic explanations of central dogma in the beginning but names the actual molecular biology involved when talking about disorders in later chapters. Depending on your background you may find yourself skipping small sections here or there but that’s part of trying to have a book that allows for conversation among different levels or areas of scientific background. Books like A Crack in Creation are a necessary step to engaging everyone in a conversation that we need to be having.

Gene editing and CRISPR are sure to dramatically affect how we control our health and the world around us. A Crack in Creation is worth a read to catch up on the fast-moving field, especially if you want to take an informed look at the ethical questions surrounding CRISPR. Ultimately Doudna and Sternberg  do not try to give you the answers but set you up to think about them for yourself.




Conflicts of Interest:

I work at MIT and have a Broad Institute affiliation (Broad Institute is involved in various legal patent disputes with Jennifer Doudna and UC Berkeley), and I have collaborated with members of Feng Zhang’s lab at the Broad Institute. While I have institutional conflicts of interest because of the Broad’s financial stakes in the patent dispute, I have no personal financial stakes in any CRISPR related companies or intellectual property.

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