What Keeps a CRISPR Creator Up at Night
Gene-editing pioneer Jennifer Doudna’s new book reveals her dreams and nightmares about what she has unleashed.
Adolf Hitler came to her in a dream, wearing a pig’s face and asking excitedly about what she had just invented.
That nightmare — and her willingness to share the story — reveals a lot about Jennifer Doudna, a biochemist at the University of California, Berkeley, and her new book, A Crack in Creation. It’s the story of how she co-developed CRISPR-Cas9, a method for editing DNA that is almost as cheap and easy for biologists as cutting and pasting letters on a word processor.
Doudna and French microbiologist Emmanuelle Charpentier startled the bio-world in 2012 when they published their first CRISPR paper in Science. Almost overnight they had ushered in a long-anticipated moment when humans could more easily bioengineer themselves.
In the five years since, Doudna’s quiet life as a researcher has been upended by magazine cover stories and marquee appearances at TED and the World Economic Forum in Davos, plus talk of her and Charpentier as shoo-ins for a Nobel Prize. Investors and entrepreneurs have raced to start companies based on the technology, raising hundreds of millions of dollars, even while legal battles rage over the patents for technologies that others have refined after Doudna and Charpentier’s initial paper.
The CRISPR technique hijacks a mechanism used by bacteria to remember the identity of invading viruses: they cut and paste sequences of the interloper’s DNA. Doudna and Charpentier’s insight was that this process could be made to happen with DNA in any organism, including humans.
Advocates expect CRISPR to soon allow physicians to edit glitches in some people’s DNA, correcting mutations for the likes of cystic fibrosis and sickle cell disease; some forms of blindness; and possibly HIV. Scientists have already had success in altering human cells to edit out some of the mutations responsible for these diseases. Researchers in China last year were the first to try CRISPR in humans, injecting edited cells into a patient with lung cancer. Other trials in China, the U.S., and the U.K. are planned for this year.
Researchers have used CRISPR to tweak tomatoes to be less squishy and to bioengineer super-muscular dogs, micro-pigs the size of house cats, and hornless cows. Doudna also describes a CRISPR future that could bring us woolly mammoths, winged lizards, and unicorns.
CRISPR remains in early days, however. General safety issues in humans still to be worked out, including, as Doudna writes, the possibility of “off-target” edits that occasionally occur in stretches of DNA beyond the intended location. This could be devastating if it happened in a human, although Doudna and other scientists believe that fine-tuning CRISPR should eliminate this problem. We’ll see.
In A Crack in Creation, Doudna and co-author Samuel Sternberg, a former PhD student in her lab, clearly describe CRISPR science and the compelling story of how Doudna and Charpentier accidently discovered it while investigating immune mechanisms in bacteria.
This is just a prelude, however, to the real reason that Doudna and Sternberg wrote this book, and wrote it now rather than waiting for years or decades to tell their story like most scientists and inventors. This emerges in the second half of the book as Doudna describes her apprehensions that CRISPR might be used for evil, and her efforts to make sure the world is aware of the potential downsides even as we revel in its possibilities.
As Doudna notes, most scientists and inventors prefer to stay in their labs and let others discuss the societal impacts of their discoveries. As a quiet person by nature, Doudna readily admits that this is her preference, too. Except that her conscience won’t let her stay out of the fray as visions of possible misuses literally haunt her — as with the Hitler dream.
She fears that CRISPR will be used to create designer people, and that scientists will use the technique to edit the so-called germline cells in human sperm, eggs, and embryos. These alterations would be passed down to children and subsequent generations, with unpredictable consequences.
It is heartening to see her weigh in early and forcefully to help steer us in the right direction.
In early 2015, Doudna acted on her qualms and gathered a group of 17 prominent scientists and ethicists in Napa Valley, California. The one-day meeting resulted in a letter calling for a moratorium on germline editing until ethical issues and safety could be further discussed.
In taking this step Doudna followed the lead of one of the scientists she invited, Stanford molecular biologist Paul Berg, now 91 years old. In the 1970s Berg had a similar crisis of conscience as a scientist on the brink of a major discovery in genetics. That technique, recombinant DNA, made it possible to splice DNA from other organisms into bacteria. His response — also unusual for a scientist — was to convene a conference in Northern California that sought to sort out the promise and the dangers of that technology. The rules that eventually came out of this process alleviated public fears enough that Berg and others could carry on experiments that launched a wave of new industries — and won Berg a Nobel Prize.
After the small Napa gathering in 2015, Doudna helped spearhead a global summit attended by 500 scientists, ethicists, and others from 20 countries in Washington, D.C. It ended with Doudna and other organizers issuing a statement that endorsed the eventual use of germline editing, but only in a very narrow set of cases where CRISPR could be used to edit out horrific diseases. And only after a host of ethical and safety issues are resolved.
One senses that A Crack in Creation isn’t Jennifer Doudna’s last word on the potential perils of CRISPR, although she has offered up an exceptional primer for why this technology needs to be openly discussed in all its facets. We may not be able to prevent a mad scientist or a just plain madman from abusing this discovery. But it is heartening to see one of its creators feeling the moral responsibility to weigh in early and forcefully to help steer us in the right direction.