Primary Source: Rode, N. O., Estoup, A., Bourguet, D., Courtier-Orgogozo, V., & Débarre, F. (2019). Population management using gene drive: molecular design, models of spread dynamics and assessment of ecological risks. Conservation Genetics, 20(4), 671–690. https://doi.org/10.1007/s10592-019-01165-5
Featured Image: CRISPR complex, Source: Wikipedia.com
CRISPR and Gene Drives: What are they?
CRISPR, pronounced “crisper”, is the technology behind some of the most controversial topics we hear about in the media. A CRISPR-associated protein named “Cas-9” chops up DNA like a pair of scissors. In 2012, scientists found that Cas-9 could be directed to cut along specific parts of the DNA sequence, allowing us to edit genes more easily, cheaply, and quickly than before.
One potential use of CRISPR technology is gene drives. A parent’s traits are usually inherited among 50% of their offspring. A gene drive allows a trait to be inherited greater than 50% of the time. We can therefore manipulate DNA so that individuals and populations express traits that we desire.
Gene drives can be used for a variety of purposes with drastically different goals. They can be used to rescue an endangered population, or to either suppress or eradicate an undesirable population, such as a disease- carrying species, the disease itself, or an invasive species. These uses have significant implications for conservation biology and ecosystem management.
Rescuing at-risk populations
Rescue drives could help save endangered populations by promoting the spread of advantageous, adaptive traits. For example, amphibians around the world are under severe threat from chytrid fungus. A chytrid is a type of fungus, and a specific species, known as Bd, is a parasite spreading rapidly through frog and amphibian populations worldwide. Its spread was likely facilitated by the global trade of amphibians for food, scientific research, and pets, and conservationists have struggled to rein in the disease. Scientists have identified a version of a gene that is associated with higher survival rates among infected frogs. It’s possible that someday, with further research, gene drive technology could allow for the propagation of this resistant gene through frog populations.
Shrinking harmful populations
Eradication and suppression drives may eliminate or shrink populations of invasive species or pathogens by promoting the spread of negative traits. For example, invasive populations have established on many islands worldwide. Black rats in New Zealand have eradicated native plants and negatively affected several insect, snail, spider, reptile, and bird species. A government plan called Predator Free 2050 is working with universities and non-profits to develop research on gene drives in rodents which could propagate genetic traits associated with infertility in females, leading to population decline. This project is researching gene editing technology in addition to utilizing more traditional control measures.
A promising but imperfect tool
CRISPR may sound like magic, but it is a tool that requires a significant amount of knowledge and skills for safe and effective use. Scissors cut paper, but the user decides when, where, and how to use them- the scissors could be rusty or get stuck, or the user could make a mistake or get a papercut! Just like there are outside factors affecting how we use a tangible and simple tool like scissors, there are many factors that play into the effectiveness of a gene drive.
First, gene drives aren’t feasible with all species. They take a few dozen generations to take hold. This isn’t a big deal for insects, which reproduce quickly and in large numbers. However, for long-lived species, a gene drive may not be feasible because the threat (such as climate change) will occur more quickly than a gene can drive through a population. Additionally, many species produce asexually or via mixed mating systems, but gene drives are most effective in sexually reproducing taxa. Population dynamics and connectivity also influence how quickly a gene drive can spread through a population.
There is a risk that gene drives won’t always work as intended. CRISPR doesn’t work perfectly 100% of the time, as chromosomes are sometimes not recognized or cut by Cas-9 (the scissor protein). We also can’t perfectly predict how gene drives will manifest at the behavioral level. It is plausible that wild-type individuals could avoid mating with gene drive individuals, although this risk has yet to be investigated. Additionally, a population could evolve to become resistant to a gene drive over time.
Gene drives for conservation purposes are controversial because we are still researching potential risks, and regulatory bodies are still debating best practices.
Cas-9 may act as a mutagen, causing cutting and mutations to occur at non-targeted sites within the DNA, with unintended and unpredictable effects. More study is needed to better understand how often these unintended mutations occur, and how they could affect a gene drive-targeted population.
Gene drives may spread to non-target populations. Black rats are invasive and harmful in New Zealand, so eradicating them there would be considered beneficial. However, if a gene drive rat was intentionally or unintentionally transported to the native range, the effects would be severely detrimental. Some strains of bentgrass, often used for golf courses, have been genetically modified for herbicide resistance so that courses can be sprayed to kill weeds without killing the grass. Scientists have found that these modified populations were capable of “escaping” into the wild and mixing with wild populations up to 9 miles away. The species and circumstances under which gene drives can feasibly escape are still being investigated.
Gene drives may even spread to non-target species. This could occur when individuals from different species mate (like when a donkey and a horse produce a mule). It can also occur through horizontal gene transfer, when genetic material is transferred from one individual to another of the same generation, instead of through reproduction (this is common in bacteria). Artificial gene transfer (when test subjects escape from the lab and mate!) are also a risk factor for the unintentional spread of gene drives.
Removing invasive species may not always be positive. Invasive species may have replaced natives and taken over their ecological roles. For example, the invasive American brine shrimp has replaced native brine shrimp in southern France, and now serves as an important food source for native birds.
Gene drives may also lead to unstable population dynamics through overcompensation. If a rescue drive is “too” successful and an endangered population grows too much, too quickly, it could become invasive.
The persistence time of gene drives is still unknown, and researchers are investigating methods to brake or reverse gene drives if they do become harmful.
How can we make informed and ethical decisions?
There are a range of opinions on the use of gene drives for conservation, with some highly in favor and some strongly against. Much more research is needed before gene drives can feasibly be implemented, but it is imperative that we establish guidelines for their safe and ethical use in the meantime.
Several national regulatory agencies have made recommendations on using gene drives safely. The International Union for Conservation of Nature is in the process of developing a policy for regulating synthetic biology, including gene drives. There is a need for a strong and well-defined international regulatory framework.
Establishing effective regulation of this technology depends on making sure decision-makers can access and understand the necessary information. Gene drives don’t only cause changes at the molecular level: they could affect ecosystems, natural communities, and social communities. Scientists, therefore, have a social responsibility to communicate their research to lawmakers and the public so that regulators and potentially affected communities can make informed decisions.