Jason Delborne: The Gene Drive Conundrum

Although islands make up only a small percentage of land area globally, they contain an overwhelming percentage of endangered and threatened species. Invasive rodents - rats and mice - have played a significant role in the extinction of many island species. Groups like Island Conservation have developed mechanical and chemical methods to eradicate invasive rodents, but it’s expensive, ecologically-risky, and difficult to implement on larger land areas or islands with human inhabitants. The search for new tools has included genetic strategies that would be more specific to invasive rodents (not harming birds or other mammals with poison). The Genetic Biocontrol of Invasive Rodents (GBIRd) partnership is investigating whether gene drives could be used.

Gene drives are systems of biased inheritance - driving a trait through a sexually-reproducing population of organisms at higher than Medelian rates. Remember Mendel’s peas, which inherit 50% of their genes from each parent? Gene drives can change that percentage upwards toward 100%, almost ensuring that a given trait is passed on to the next generation, even if it doesn’t provide a fitness advantage. Gene drives occur naturally, but new techniques of gene editing have enabled scientists to consider engineering gene drives, which have already shown success in laboratory studies with yeast, mosquitoes, and fruit flies. The GBIRd strategy is to engineer mice with a gene drive attached to the genetic trait for maleness. Introducing a relatively small number of such mice on an island could turn that population to all-male within a few generations, leading to the collapse of the population.

But a lot is unknown about how gene drives will behave in the wild. They aren’t like typical GMOs (genetically modified organisms), which typically have lower fitness in the environment than wild relatives. Although there have been cases of genetically engineered crops crossing with wild relatives, we don’t have evidence of ecological harm, and over time we would expect such traits to be selected out of an unmanaged population. In contrast, gene drives are designed to spread. If a gene drive mouse escaped and found itself on the mainland, could it drive all mice - globally - to extinction?

Scientists are taking this possibility seriously. There are clever techniques under development that could localize a gene drive, making it work only in a certain sub-population of mice, or that could turn off the gene drive after a certain number of generations. Some scientists even propose that we could create “reversal drives” in advance of an environmental release to recall a gene drive that has negative consequences. These strategies show some promise, but their success and reliability remains as uncertain as gene drives themselves. In fact, some in the scientific community think the bigger problem is getting gene drives to work at all outside of the highly controlled laboratory environment with genetically homogenous test organisms.

All of this technical uncertainty is intertwined with social, ethical, and political uncertainty! How should we decide when a gene drive mouse is safe enough to test? Will residents of islands with invasive mice allow gene drive mice to be released in or near their communities? How do we balance the mix of risks and potential benefits? Are existing regulations sufficient to consider gene drive organisms? And who gets to decide?

GBIRd has adopted a set of guiding principles that help us navigate these difficulties. “Early and sustained consistent engagement with stakeholders and communities” is at the top of the list. As a social scientist in the partnership, it’s my role to help the scientific team interface with diverse stakeholders - and communities once possible release sites are identified. We’re doing this not to convince the public that gene drive mice are safe, but rather to get their input and understand their perspectives. Too often, experts remain blind to local or indigenous knowledge that could inform the design of their technologies, and we need to respect the values and autonomy of diverse peoples and communities.

We took a first step by organizing a workshop for diverse stakeholders in March 2019. At that workshop we explored the many decisions that are part of research, development, testing, and potential deployment of a gene drive mouse for biodiversity conservation. New perspectives were shared, and participants got a chance to see how people with different values and kinds of expertise evaluated the tradeoffs that are central to decisions about emerging technologies for conservation. In the future, I hope to continue this type of stakeholder engagement and eventually engage with communities who will have a say in the first field trials.

Jason Delborne is Associate Professor of Science, Policy and Society in the College of Natural Resources at North Carolina State University. His research interests include genetic engineering and politicized scientific controversies.