A Microscopic Solution for a Microscopic Killer

Kalyan Sankar

Imagine that you lived 500 years ago...what would you say is the biggest threat to your life? You might guess war, or maybe injury, or maybe even an animal attack. The truth is, what is most likely to take your life at any given moment is too small to even see with your eye. Diseases like The Plague, malaria, COVID-19, and influenza have killed more humans than anything else in history, and they are often spread through vectors such as rats and mosquitoes. Mosquitoes, in particular, are especially deadly; some studies show they have indirectly killed over 10 million people in the past decade or so. To put this number in perspective, 10 million people is about the entirety of the Bay Area combined. These many deaths happen despite modern medicine. In the past, just malaria could have killed 50 billion people in total. That’s close to half of all the people who have ever lived.

Today, science has helped quell the spectre of disease into a shadow of its former self. That’s not to say, however, that disease doesn’t kill people even now. The chief offender of mosquito-related deaths, malaria, still kills almost half a million people a year, of which 2/3 are children under the age of 5. The issue with containing malaria is that animal-borne illnesses are notoriously hard to contain. Keeping track of these tiny insects is a hard enough feat in just your bedroom; now imagine that for an entire house, city, or even nation. Killing them is out of the question too, as things like bug zappers and insect killers often catch harmless or helpful insects in the crossfire. So, what can be done to control this issue?

One promising new treatment is using gene editing to selectively target malaria within mosquitoes, eliminating the disease and only the disease. This is done through the CRISPR-Cas9 method; originally found in a bacterial defense mechanism, scientists have repurposed it to give precise gene removal and replacement. This is done through the Cas9 nuclease, which is a molecule in bacteria that specializes in removing invading virus DNA from its own. If it’s loaded with a target DNA strand, it can find and replace it precisely, allowing for instant and accurate gene editing.

In 2018, researchers developed a gene modification that can spread to offspring, which would render females completely sterile. This modification also contains some CRISPR-Cas9, so that as soon as the offspring is conceived, it automatically copies itself from one copy to the other, causing almost 100% of all offspring to get two copies of the gene. In just a few generations, it would turn the mosquito from a persistent threat into a manageable nuisance.

This technology is revolutionary because it allows for widespread action. As the gene spreads within the population, every mosquito population (even those hidden away from past efforts) would be sufficiently controlled. The effects would also be long-lasting as the gene will stay present in the gene pool as a “check” for the population. Finally, there would be no additional casualties of helpful insects. Unlike chemicals or insect traps, this method would be restricted to only mosquitoes and only the specific species that carries malaria (or whatever disease you want to attack). This would limit additional damage to the ecosystem.

So why haven’t we used it yet? The truth is, we are still understanding the implications of what we have developed. For starters, gene drives are irreversible. Once the gene is released into the population, there is no going back. Gene drives are also immensely powerful: once introduced, they can affect almost all of the population in a matter of weeks. Additionally, mutations are a much more frightening risk. What if, during conception, the gene drive mutates to nullify its effects and make the mosquitoes more resilient, have better reproduction, or maybe even make them better carriers for the disease? This kind of mutation is a real possibility (since mosquitoes make thousands of larvae in one go), and it would spread like wildfire due to the CRISPR addition to the gene. To address these issues, researchers work tirelessly to find ways to cover these gaps, but nothing can stop pure chance. There will always be a risk, no matter how slight, of mutation. The debate lies in the question of “when will the benefits outweigh the risks?” Every day that we don’t use this technology, more people die from diseases that we could prevent. At the same time though, hasty decisions might cause more damage than we seek to prevent. 

I believe that, in its current state, gene drives are too volatile. A version of the gene drive that can be controlled, or that has a smaller scope or effect, might be more suitable to mitigate potential errors. For now, many other strategies, including a potential malaria vaccine or cure, could help lessen the impact of malaria. But for now, like Jurassic Park, we should focus more on whether we should instead of getting caught up in whether we could.