By Jacob Kang
The use of CRISPR-Cas9, a gene modification tool that uses enzymes to cut nucleotide chains, evokes an uncanny resemblance to childhood playtime. Like toddlers who tirelessly pull apart and connect blocks to perfect their LEGO creations, geneticists toss aside and join together the building blocks of all life on Earth to ensure that their model organisms exhibit traits desirable to the maker. These geneticists even take extra steps to ensure that every future creation is perfect in their eyes. After building their ideal creation, scientists use gene drive—copying manufactured genes onto inherited chromosomes or lowering the fertility of sex cells that lack the manufactured gene—as a guarantee that a majority of the population will possess the same traits as the starting organism. The capabilities of CRISPR-Cas9 and gene drive to orchestrate the destruction of any population raises the question of when it is appropriate to employ such drastic measures.
In fact, CRISPR-Cas9’s capabilities have led to its experimentation as a form of population control for pestilent species including the Aedes and Anopheles mosquito populations; this would theoretically help limit the transmittance of deadly diseases such as malaria, dengue, encephalitis, and yellow fever. One particular genetic modification is coined “doublesex” and causes the mouths of female offspring to transform into the pollen-specialized mouths possessed by males. In February 2019, an Italian laboratory successfully eradicated a captive mosquito population by utilizing CRISPR-Cas9 to implant doublesex into female genomes, and gene drive to rapidly propagate doublesex in offspring. Other control mechanisms created through gene editing have also experienced success in managing mosquito populations. For example, Oxitec, a biotechnology company specializing in insect control, reduced annual Brazilian Aedes aegypti populations by 95% after implanting a gene in mosquitoes that produces dying larvae. Although both studies are isolated to single test sites and subjected to extensive monitoring, the fact that we can choose to eliminate entire species right now is a revolutionary feat that confirms that CRISPR-Cas9 will be employed in the near future.
CRISPR-Cas9’s imminent use calls for a closer examination of the impact of unravelling millions of years’ worth of natural selection and destroying the survivability of entire populations. Joe Conlon, an entomologist in the American Mosquito Control Association who supports mosquito eradication, acknowledges the unknown ways in which ecosystems might respond to the removal of specific players: “Something better or worse would take over.” We’ve already seen the collateral impacts of eliminating specific species: for example, sea otter overhunting along the California coast led to the overpopulation of sea urchins and the destruction of kelp forests, which are needed to house biodiversity and buffer storms. Some experts project that removing mosquitoes could lead to the decline of flora and fauna ranging from mosquitofish, which are specialized to eat mosquitoes, to tropical plant species that rely on mosquitoes for pollination. Our decision to use CRISPR-Cas9 is humanity’s fork in the road. If we choose incorrectly, we can potentially inflict irreversible ecological damage that outweighs any medical benefit and permanently alters our ability to survive.
Interfering with the survivorship of wild mosquito populations raises the issue of ecological collapse via gene overselection, which is a risk inherent to genetic modification. We certainly have been able to customize gene pools to our advantage: the Green Revolution in the 1970’s introduced pest-resistant crops and saved millions of lives in impoverished countries. However, other human endeavors have resulted in genetic invariance and the subsequent destruction of a specie’s fitness. A prominent example involves the near-extinction of the Gros Michel banana variant by Fusarium oxysporum (Panama Disease-Tropical Race 1), a wilting disease that induces rotting in banana cultivars. Due to humans overbreeding the Gros Michel for more optimal traits, the species became unable to effectively ward off Panama disease, resulting in the destruction of Gros Michel as a marketable cultivar. Despite farmers’ transition to a hardier species of banana (Cavendish) as the primary banana crop, the same problems remain. Tropical Race 4, a variant of Panama Disease, has already destroyed banana farms in Taiwan and is projected to spread to major growing regions such as Latin America. Furthermore, it’s been estimated that nearly half of the current Cavendish yield has been derived from a single Cavendish’s genetic makeup. Ongoing issues with Panama Disease highlight limitations in our understanding of the relationship between selective genetics and a species’ ecological fitness, as well as of the ability to integrate desirable traits with evolutionarily optimized defensive genetic traits. If we’re unable to prevent a single disease from ravaging banana crops, we can’t expect to exert full control over the genetic makeup of entire ecological niches—even with the aid of powerful tools like CRISPR-Cas9.
The plight of the banana caused by human oversight underlines the biggest hurdle: even though scientists can and will probably alter species’ genetic pools, new issues can arise that will either have to be addressed through more gene editing or left unacknowledged. So, as we move forward in saving millions of lives using CRISPR-Cas9, let’s take a moment and ponder the potentially widespread ripple we’re creating by interfering with nature.