Starting a Revolution Isn’t Enough
Two years ago, I was working on my laptop in an airport lounge in Newark, New Jersey, when I glanced up and saw a couple walking with their two boys. The younger boy slowly made his way on crutches, displaying the telltale signs of a hereditary disease called muscular dystrophy. Generally manifesting in childhood, the disease steadily robs those who have it of their ability to walk. Eventually, I knew, the crutches would no longer be enough.
My heart skipped a beat. Most types of muscular dystrophy originate with genetic mutations that weaken key muscle proteins, and I had just come from a meeting where a cure appeared possible, using CRISPR technology to rewrite the DNA of kids just like him.
Imagining how the technology I’d helped create could change this boy’s life, I was overwhelmed with emotion. Beyond hope and wonder, I was filled with a sense of fierce urgency to expand CRISPR’s impact to the people around the world who need it most.
Biotechnology as we know it today came of age in the 1970s, when the advent of technologies to copy individual genes and mass-produce the proteins they encode spurred a molecular revolution. Companies such as Genentech leveraged this new knowledge to create novel medicines and to better control diabetes, cancer, and other debilitating conditions. But before my colleagues and I developed the technology for CRISPR genome editing, we weren’t fully aware of just how far the world was from fulfilling biotech’s promise to create a universe of accessible tools for improving human health and our environment.
In the mid-2000s, I was leading a research lab at UC Berkeley with a project investigating how microbes are able to protect themselves from viral infection. These defenses rely on repeated sequences of DNA, called CRISPR, which are contained in a microbe’s genome and are essentially a genetic record of a viral attack, derived from a snippet of a virus’s own genome. Based on these records, the bacteria use RNA, DNA’s chemical cousin, to provide proteins (called “cas,” for “CRISPR-associated proteins”) with the information needed to find and destroy future invading viruses.
In a life-changing collaboration with the French scientist Emmanuelle Charpentier, we figured out how the chemistry of this process could be harnessed not to destroy viral DNA, but to cut the genome with unprecedented ease and accuracy in virtually any cell. This niche discovery has spurred an entire biotech revolution of its own. In animal and plant cells, cutting DNA with CRISPR-Cas9 allows us to turn some genes off and to turn others on. A simple CRISPR edit can suppress the genetic defect responsible for sickle-cell disease, providing an apparent cure to this serious blood disorder. CRISPR has also been used to enable T cells to find and destroy cancer cells, and to disrupt production of a disease-causing protein in patients with hereditary transthyretin amyloidosis, a genetic disease that irreversibly damages the nerves and heart. An FDA-approved edit to cattle genes re-creates a slick coat, occasionally found in nature, that allows cows to tolerate increasing temperatures; using CRISPR to breed a tomato variety, approved for sale in Japan, has enhanced its nutritional qualities. For other crops, CRISPR is being used to increase yield, reduce pesticide and water use, and protect against disease.
These advances—and more like them to come in preventive medicine, diagnostics, agriculture, biomanufacturing, and synthetic biology—promise to improve the lives of millions of people. They’ve also launched companies and helped existing ones break new ground. This growing CRISPR economy was estimated at $5.2 billion in 2020; venture investors poured more than $1 billion into the growing ecosystem of genome-editing companies in 2021 alone.
Sometimes, when I think about my part in all this, I am overcome. Few scientists get to experience what I have. And while I’m immeasurably pleased by the progress that’s happened since the publication of our first CRISPR-Cas9 paper a decade ago, I also feel a continual sense of urgency: Are we dreaming big enough? Moving quickly enough? I think back to the advent of the cellphone—another groundbreaking technology in our shared memory. For those of us lucky enough to have experienced it, the untethering of communication from a landline was a seminal moment. But who could have predicted that this once niche and luxury technology would become so ubiquitous as to outnumber the human population, creating new economies and changing the way we live?
CRISPR may well be on a similar precipice. But for this technology to be widely adopted, it needs a push, just like mobile phones did. Fueling the proliferation of those devices was a host of other technologies and infrastructure systems—voicemail, cell towers, and processing power far exceeding the system that guided the Apollo to the moon. Ensuring that CRISPR reaches its full potential for clinical applications and beyond will require an even higher level of intentional building with diverse and dedicated collaborators. Governments, universities, and investors will need to make significant and sustained investment in cutting-edge science at labs and at biotechnology companies, as well as investments in infrastructure and manufacturing to ensure that this work is scalable. With this kind of concerted and collective effort, the applications and benefits of CRISPR could become as accessible, commonplace, and useful as the phones in our pockets.
These ambitious goals must be tempered by the knowledge that the implications of using CRISPR to change the code of life are profound. For the first time, humans have the ability to alter the foundation of who we are as a species and as individuals. This power could wash through our society to even greater human benefit, becoming a standard-of-care treatment in doctors’ offices or a widely adopted technique for producing crops and animals better adapted to our warming world. When facing progress of this magnitude, the first step toward adoption must be societal buy-in. At the core of most fear is misunderstanding and misinformation; few understand this better than scientists. The more we help people understand the science of CRISPR, the more we can open minds to what is possible when we implement it.
Powerful technology, of course, comes with the potential for misuse, and CRISPR’s powers raise important questions. How do we ensure that genome editing is deployed only when medically necessary? Who determines what medically necessary means? How do we ensure that those in need have access when people or companies with money and power cut in line? The clinical applications I’ve described so far concern individuals, where genome editing affects only the treated patient. But genome editing could also alter germ lines—eggs, sperm, or embryos—to create heritable changes that can be passed to future generations. Some environmental applications of CRISPR, too, can rapidly change the genetics of large populations. These strategies could help fight the spread of invasive species and devastating diseases such as malaria, but without careful assessment and governance, they could also pose a risk to whole ecosystems.
In 2018, three years after I first called for a voluntary stop to heritable germline editing in humans, twin girls whose genomes had been altered in order to eliminate a gene linked to HIV infection susceptibility were born in China. The “CRISPR babies” debacle demonstrated why scientists must work closely with regulators to ensure the safe and ethical use of such a powerful tool. Without these guardrails, we may not only harm humans and our environment, but also risk societal backlash against the very technologies that could preserve and improve our health and make our planet more livable.
These days, much of my own energy is focused on making sure that the people and patients who will benefit most have access to the climate strategies and medicines made possible by these early efforts and investments. But realizing CRISPR’s full potential will require many more of us to come together. We will need people to research novel clinical applications, plan environmental initiatives, and enforce safety and efficacy for every tool and therapeutic that comes to market. We will also need continual technical advances, including improved methods for delivering these molecules into cells and ensuring editing precision. Academic scientists, industry researchers, investors, policy makers, and members of the public each have a role to play.
Knowing that all of this came from humble bacteria only underscores the need for curiosity-driven research that will uncover the next breakthrough. Basic research can continually revolutionize science as we know it, but only if we find ways to keep that research going. If we do, our society will be strongly positioned to generate and harness new discoveries that can improve the human condition.
After my colleagues and I first realized what we had discovered with CRISPR, we often had late-night phone calls to discuss data and imagine where this research was headed. Right away, we started to think of the many ways that the world could use this genome editing technology. It was quickly quite a long list, but looking back now, we didn’t come close to understanding the countless different directions researchers around the world would take—or the new vision of the world this technology would inspire. Looking to the next decade and beyond, I feel both as optimistic and as impatient as I did in that airport lounge, anticipating the future that I know CRISPR will help us build.