Scientists now have a relatively easy and inexpensive way to read, write, and edit the building blocks of life—the genome-editing technique known as CRISPR-Cas9. And while the technology was developed only five years ago, CRISPR’s ability to target—and modify—specific sections of DNA is already supercharging the pace of scientific breakthroughs in medicine and agriculture. It’s even being used to try to bring the woolly mammoth back to life. Investors (including Bill Gates and Sean Parker) and pharmaceutical companies have plowed millions of dollars into CRISPR-driven research; philanthropies have granted millions more to support scientists working on cures for genetic diseases; and in China, at least seven human clinical trials are moving forward. But it all started when a small group of scientists, working in collaboration, stumbled on an organic biological process that had existed for millennia. Among the leaders was molecular biologist Jennifer Doudna, who heads the Doudna Lab at the University of California, Berkeley. She’s the coauthor of a new book tracing CRISPR’s evolution, A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. “[CRISPR] is a great illustration of how technologies are born,” says Doudna. “They often come about in unexpected ways.” And the outcomes can be just as unpredictable, and dangerous—a fact that has prompted her to become a global advocate for the responsible use of CRISPR. In this excerpt, Doudna talks about its transformative power. —Noah Robischon
Tomatoes that can sit in the pantry slowly ripening for months without rotting. Plants that can better weather climate change. Mosquitoes that are unable to transmit malaria. Ultra-muscular dogs that make fearsome partners for police and soldiers. Cows that no longer grow horns.
These organisms might sound far-fetched, but in fact, they already exist, thanks to gene editing. And they’re only the beginning. As I write this, the world around us is being revolutionized by CRISPR, whether we’re ready for it or not. Within the next few years, this new biotechnology will give us higher-yielding crops, healthier livestock, and more nutritious foods. Within a few decades, we might well have genetically engineered pigs that can serve as human organ donors—but we could also have woolly mammoths, winged lizards, and unicorns. No, I am not kidding.
It amazes me to realize that we are on the cusp of a new era in the history of life on earth—an age in which humans exercise an unprecedented level of control over the genetic composition of the species that coinhabit our planet. It won’t be long before CRISPR allows us to bend nature to our will in the way that humans have dreamed of since prehistory. When that will is directed toward something constructive, the results could be fantastic—but they might also have unintentional or even calamitous consequences.
The impact of gene-edited plants and animals is already being felt in the scientific community. For example, researchers have harnessed CRISPR to generate animal models of human disease with far greater precision and flexibility than before—not just in mice, but in whatever animals best exhibit the disease of interest, whether it be monkeys for autism, pigs for Parkinson’s, or ferrets for influenza. One of the most interesting aspects of the CRISPR technology is the way it enables the study of features unique to certain organisms, such as limb regeneration in Mexican salamanders, aging in killifish, and skeletal development in crustaceans. I love the notes and pictures colleagues send me describing their CRISPR experiments—the beautiful butterfly-wing patterns whose genetic underpinnings they’ve uncovered, or the infectious yeast whose ability to invade human tissues they’ve dissected at the level of individual genes. These kinds of experiments reveal new truths about the natural world and about the genetic similarities that bind all organisms together. They’re enormously exciting to me.
Related: The Ethics Of CRISPR
At the other end of the spectrum are gene-editing applications that read more like science fiction than the contents of a scientific journal.
For example, I was amazed to learn that several research teams are using CRISPR to “humanize” various genes in pigs in the hope that life-threatening organ-donor shortages might one day be solved by xenotransplantation—the transfer of organs grown in pigs (or other animals) into human recipients. In a sign of the kinds of aesthetic changes to animals that are now possible, companies have used gene-editing technologies to create new designer pets, such as gene-edited micropigs that never grow larger than small dogs. And in a page taken straight out of a famous book-to-film sci-fi franchise, some laboratories are pursuing a venture known as de-extinction, which is nothing less than the resurrection of extinct species through cloning or genetic engineering. My friend Beth Shapiro, a professor at the University of California, Santa Cruz, is excited to use this strategy to re-create extinct species of birds for the purpose of studying their relationships to modern species. Along the same lines, efforts are already under way to convert the elephant genome into the woolly mammoth genome, bit by bit, using CRISPR.
Ironically, CRISPR might also enable the opposite: forcible extinction of unwanted animals or pathogens. Yes, someday soon, CRISPR might be employed to destroy entire species—an application I never could have imagined when my lab first entered the fledgling field of bacterial adaptive immune systems just 10 years ago.
Some of the efforts in these and other areas of the natural world have tremendous potential for improving human health and well-being. Others are frivolous, whimsical, or even downright dangerous. And I have become increasingly aware of the need to understand the risks of gene editing, especially in light of its accelerating use.
CRISPR gives us the power to radically and irreversibly alter the biosphere that we inhabit by providing a way to rewrite the very molecules of life any way we wish. At the moment, I don’t think there is nearly enough discussion of the possibilities it presents—for good, but also for ill. It’s a thrilling moment in the life sciences, but we can’t let ourselves get carried away. It’s important to remember that, while CRISPR has enormous and undeniable potential to improve our world, tinkering with the genetic underpinnings of our ecosystem could also have unintended consequences. We have a responsibility to consider the ramifications in advance and to engage in a global, public, and inclusive conversation about how to best harness gene editing in the natural world, before it’s too late.
From A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, by Jennifer Doudna and Samuel H. Sternberg. Reprinted with permission of Houghton Mifflin Harcourt.