Abstract

If someone were to start a CRISPR lab today, what area should they focus on? Where could they have the most impact?
Despite the frenetic pace at which CRISPR-based genome editing is being deployed for human therapeutic applications, and the continued enthusiasm that scientists and investors are showing in pursuit of CRISPR medicines, it is worth noting the tremendous potential that exists for other applications. Indeed, while we continue to accept manuscripts for this journal's next themed installment (“CRISPR's Path to the Clinic”), most of the articles in this particular issue highlight how novel CRISPR-based tools can be used and deployed beyond humans, spanning various environmental and pathogenic bacteria, as well as tools to decipher their community composition. This issue also features novel tools and recent advances for Cas7–11, Cas12a, and Cas9 base editors, as well as various methods to deliver and deploy them. Of course, we also discuss plant genome editing and CRISPR applications in less fashionable organisms: our cover highlights a stunning example of how editing can be used to manipulate visually compelling insect phenotypes (see page 739 and the accompanying First Cut by Michael Smanski on page 628).
An in-depth look at the CRISPR-fueled genome editing literature reminds us that the vast majority of the research underway remains focused on medical applications. This is, of course, critical to address a host of genetic diseases and patient needs. Yet, it is also important to ponder how we can—and perhaps should—allocate more resources to address other crucial issues such as climate change and a sustainable agriculture. The impossible task of comparing and contrasting impact across disparate fields seems foolish at times: how should we balance saving lives with advanced therapeutics versus breeding a more sustainable agriculture to feed the world or design a more efficient forest to address global warming and climate change?
It is probably futile to ponder how many individuals would be impacted by these various options if we could fully exploit CRISPR-based technologies in the next decade. By 2030, how many patient lives could we save and improve? How many mouths could we feed? How many individuals would benefit from a healthier forest if we had to prioritize our efforts strategically? How should individuals, funding agencies, and investors, allocate resources to these various challenges? At a time when CRISPR can tackle colossal problems—literally, in the case of George Church, launching a company called Colossal to address species extinction by hopefully restoring the woolly mammoth to the Siberian frozen tundra—what is the best potential use of our time and resources?
As the science and technology of gene editing continue to advance, and conversations about the corresponding regulatory frameworks and responsible deployment progress, perhaps now is an appropriate time to ask which areas should be prioritized in a geopolitical context to ensure we exploit powerful technologies for the most benefit to humankind. Is the promising National Institutes of Health Somatic Cell Genome Editing–fueled translational effort (in combination with clinical programs underway) sufficient or not? Is industry and/or academia best suited to breed next-generation crops and livestock on a global basis? Should governments or investors increase the sense of urgency of leading scientists to work on carbon capture, environmental stewardship, and climate remediation?
The questions don't end there. At a time when it is nearly impossible to keep up with the CRISPR literature, are we wise enough to plot where we should go next and define the future? To get the right answer, one must ask the right question. But is it “what should we do with CRISPR” or “where can genome editing have the biggest impact”?
We hope the diverse stories featured in this issue provide a glimpse of what may come next and will guide colorful discussions regarding where we should invest our limited resources to address these grand challenges. We are all, hopefully, up to the task.
