Book Review

The Chronicles of CRISPR

In A Crack in Creation, trailblazing biologist Jennifer Doudna explores the revolutionary new technology that is poised to rewrite the code of life.

By Kevin Davies featured image

According to Change Agent, a much-anticipated new book, in the not-too-distant future geneticists will use a revolutionary gene-editing technology called CRISPR to engineer pinpoint corrections into the human genetic blueprint. This brave new world will result in cures for a host of devastating hereditary conditions, the eradication of infectious diseases such as malaria and Zika, and a new age of genetically modified crops to feed the planet. Of course, there’s a catch: This same tool can (and probably will) be used for controversial or unethical purposes, including by parents looking to enhance the memory, intelligence, and physique of their precious newborns. In short, CRISPR affords scientists the ability to direct evolution itself.

A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution By Jennifer A. Doudna and Samuel H. Sternberg Houghton Mifflin Harcourt 307 pp.

A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution
By Jennifer A. Doudna and Samuel H. Sternberg
Houghton Mifflin Harcourt
307 pp.

Such is the juicy premise of the latest science fiction novel by Daniel Suarez, writing in full Michael Crichton mold. His novel has even been optioned to Netflix. But these same themes are very much entwined in A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. While it may sound like a futuristic thriller, this is a grounded, accessible, and very personal account of the ongoing revolution in gene editing by one of the giants of the field, Berkeley’s Jennifer Doudna, and her colleague Samuel Sternberg.

The acronym CRISPR stands for “Clustered Regularly Interspersed Short Palindromic Repeats,” a peculiar repetitive motif in bacterial DNA first observed in 1987. For the next 15 years, researchers puzzled over these strange patterns with no known purpose, like genomic crop circles. Then in the early 2000s, Spanish researcher Francisco Mojica ran a computer search on some of the DNA segments and discovered matches with sequences from viruses.

Researchers began to put the pieces of the puzzle together: CRISPR was a microbial immune system, a means by which bacteria cleverly archive fragments of invading viral DNA into their genomic DNA, forming a sort of mugshot gallery. These sequences are then used as cues to identify and target future viral invaders, guiding a DNA-cleaving enzyme (Cas, or CRISPR-associated sequence) to carve up the viral DNA.

All well and good, but the showstopper came in 2012, courtesy of Doudna and her French collaborator, Emmanuelle Charpentier. They adapted the CRISPR/Cas system to create a simple, customizable tool to target and cleave essentially any piece of DNA. The system can cut up DNA, and it can also be used to cut and paste any desired replacement sequence, paving the way to correct many disease mutations. Barely six months later, Boston-based researchers Feng Zhang and George Church independently demonstrated that CRISPR could edit DNA in human cells. In the blink of an eye, CRISPR has fueled a research bonanza, a billion-dollar patent saga, a cameo on The X-Files, a swirling bioethical debate, and short odds that the CRISPR creators will be summoned to Stockholm for a date with the king of Sweden and the Nobel Prize. They’ve already won just about everything else.

Agent of Change

Caught in the center of this scientific tsunami, Doudna has somehow found the time to co-write a book about the origins, applications, and ethical minefield unleashed by CRISPR. A Crack in Creation is a most timely and vital read. Written in Doudna’s voice, the book offers a near-perfect primer into the science and development of CRISPR as the agent of custom gene editing. There is also an excellent discussion of the myriad applications of CRISPR, including “gene drives” to engineer infectious disease pathogens out of the mosquitoes that carry them and the many ways CRISPR can be used to make more nutritious crops.

Doudna drives home the importance of the unfashionable basic research that many of her colleagues conducted into microbial genomics and immunity over decades that culminated in her eureka moment. Surprisingly perhaps, the man many view as Doudna’s chief rival, MIT’s Feng Zhang, is hardly mentioned at all. She also resists the temptation to “tell all” regarding her disappointment at losing the initial U.S. patent decision to Zhang and the Broad Institute. (Given the very high stakes at play as courts in the U.S. and Europe try to settle who “invented” CRISPR — the patent can’t be awarded to bacteria, presumably — I think Doudna made a rational, if less titillating, decision.)

Being hailed as the creator of CRISPR — at least in the American media — has brought Doudna fame, celebrity, and wealth (the internet mogul-sponsored Breakthrough Prize alone was worth $3 million). But after wrestling with nightmares about where this technology could go, she has commendably taken it upon herself to be one of the consciences of the CRISPR field, bringing researchers and scholars from many fields together to highlight and discuss the ethical complications of CRISPR technology. This, it seems, is what really compelled her to write the book.

Doudna lays out the potential misuses of CRISPR — from the ethics of tampering with or enhancing human embryos to the unthinkable appropriation of CRISPR for bioterrorism. These issues aren’t going to go away: In April 2015, Chinese scientists reported using CRISPR to correct disease genes in human embryos. More recently, in July 2017, scientists in Oregon announced the successful editing of viable human embryos harboring disease-causing mutations.

Do we have the moral right to edit human embryo DNA, which could permanently eradicate or alter the passage of particular gene variants in human populations? Her own views are still evolving, Doudna writes, but she comes down on the pro-choice side: “We must respect people’s freedom to choose their own genetic destiny and strive for healthier, happier lives.” She quotes former NBC correspondent Charles Sabine, who has Huntington’s disease: “Anyone who has to actually face the reality of one of these diseases is not going to have a remote compunction about thinking that there is any moral issue at all.”

There is no escaping CRISPR, which is bursting into the popular consciousness: Consider that another Jennifer (Lopez) is reportedly developing a new TV drama to be called C.R.I.S.P.R. With the debate just beginning, we can expect many more books and potentially binge-worthy TV shows in the years ahead detailing real and fictional twists and turns in the CRISPR saga. A Crack in Creation isn’t the whole story, but it marks the genesis of an extraordinary new era for science and medicine — and possibly for humanity itself.