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To most scientific researchers, it comes unannounced: an ordinary moment that jolts a career in a new and unexpected direction. For University of California, Berkeley, molecular and cell biology professor Jennifer A. Doudna, it was a phone call in 2006, nearly ten years into her tenure there.
The caller was Jillian Banfield, a fellow Berkeley professor whom she knew only by reputation. Banfield was looking for a collaborator in studying something that sounded like "crisper," a newly discovered mechanism that enabled bacteria to fight off infectious viruses, also called bacteriophages.
Doudna's work on the molecular structure and potential cell-repair function of the ribosome--a complex molecular machine that builds essential proteins from amino acids in living cells--made her well positioned to make sense of a region of bacterial DNA known by the acronym CRISPR (clustered regularly interspersed short palindromic repeats).
As she describes in A Crack in Creation, seamlessly co-written in her voice with her former Ph.D. student Samuel H. Sternberg, CRISPR led her in unexpected research directions. The results were discoveries that both hold the promise to cure numerous genetic diseases and carry the potential to change the course of human evolution.
See our earlier review of The Gene: An Intimate History by Siddhartha Mukherjee, which puts CRISPR in a historical perspective.
Doudna and Sternberg note that combining CRISPR with CRISPR-associated (cas) genes and proteins, most notably the protein known as Cas9, has led research in a remarkable new direction. "[S]cientists can now manipulate and rationally modify the genetic code that defines every species on the planet, including our own. And with the newest and arguably most effective genetic engineering tool, CRISPR-Cas9 (CRISPR for short), the genome--an organism's entire DNA content, including all its genes--has become almost as editable as a simple piece of text."
Applied in clinical medicine, that tool will allow the repair of defective genes that lead to many human diseases, such as the sickle-cell trait, hemophilia, Duchenne's muscular dystrophy, Huntington's disease, and numerous other fatal or debilitating conditions. It could even transform immune cells into cancer killers or to become impenetrable to HIV/AIDS.
Unfortunately, as the authors note, CRISPR-Cas9 has a dark side as well, "in which the power to edit genes of other species could prove to be more dangerous than any changes humans have made to the planet so far. I'm referring to a revolutionary technology known as a gene drive,... a way to drive new genes--along with their associated traits--into wild populations at unprecedented speeds, a kind of unstoppable, cascading chain reaction."
Add to that the potential to edit human embryos, and you have the ability to make changes that will be inherited in future generations. In chapters entitled, "The Reckoning" and "What Lies Ahead," the authors do not shy away from that possibility and the ethical issues it presents, including echoes of the now discredited eugenics movement of the late 19th and early 20th centuries.
As is often the case of new technologies, the potential benefits make them impossible to stop. But it is not too late to establish political and cultural norms. Those are not questions for scientists and practitioners alone to answer.
Still, it is important for those experts to explain their work and its implications to society at large. Although the authors do not state it explicitly, that seems to be one of their major motivations in setting their work aside long enough to write this book. They deserve both our thanks and the investment of our own time to read it.