Crisp Genes

Crisp Genes

Imagine we had the power to use genetic technologies to stop one of humanity’s most dangerous predators. What is that predator? Sharks? Crocodiles? Snakes? Think far, far smaller. It is in fact, the mosquito.

Mosquitos cause all sorts of nasty diseases like the Zika Virus, Dengue Fever, Yellow Fever, and malaria. While nobody really wants to contract any of those diseases, and they’ll all make you pretty miserable, they’re nothing compared to the frankly hellacious malaria being one of the single biggest killers of humans in history.

Well, plot twist, we actually do have the technology and it comes in the form of some genetic machinery discovered in bacteria: CRISPR-Cas9 (or CRISPR for short).

What is CRISPR-CAS9?

Basically, (and I apologise to any geneticists reading this for my oversimplification) there’s a protein that acts like pair of scissors able to cut DNA (the CAS9 part), and a length of RNA that directs the protein to any point in the genome that you want (the CRISPR part).

Once that cut is made, the DNA can either stitch itself back together with the cut section of the DNA now removed from the genome (called homologous end joining), or that break can be filled by a new sequence of DNA by providing the cell with a template or a recipe so it can make the new gene the scientists are interested in. Essentially, CRISPR is a mix of cutting and pasting that happens inside our cells instead of Microsoft word.

So, we just need to CRISPR some mosquitos and they won’t be able to carry the malaria-causing parasite (called plasmodium); problem solved. Well, obviously it’s not that simple, and that’s because of the way genes are inherited.

Thanks, meiosis.

Here comes a crash course in meiosis and gene inheritance (thanks for getting me through undergrad, Hank Green). Most genes have two copies (one inherited from each parent), so when those genes are passed down from one generation to another, it’s only a 50:50 chance that a given gene variant (called an allele) will be expressed by the offspring. In essence, if you CRISPR a mosquito (the white mosquito in the image) so it can’t carry plasmodium, statistically, half of its offspring will still be able to carry it, and half won’t. In just two generations, the plasmodium-immune mosquitos only represent 25% of the population. Back to the drawing board, scientists!

Well, it would be if they didn’t already have a solution to this problem: Insert gene drive.

Gene drive forces the new allele to become dominant over the other allele, thus making inheritance of the plasmodium-immunity allele 99.5% rather than 50% – Tada!

While CRISPR tech has only been around for roughly a decade, gene drive was actually proven to work with 100% efficacy in a 2018 study. So, I hear you asking… Why haven’t we done it yet? Why do we still have malaria?

Playing God

The COVID-19 pandemic has proven to the world how quickly science can move when given the proper funding and attention. However, the ethics and policy behind a lot of scientific discoveries and applications often lags far behind.

Also, humans have never edited the genome of another living organism on this scale before, and once we do it, there’s no going back. So, should we even do this? What are the implications of using CRISPR on mosquitos? Will plasmodium evolve into an even scarier, more deadly version of itself or just find another host? Well, scientists are optimistic as the change to the mosquito genome is very minor, and mosquitos breed so rapidly that plasmodium won’t have time to evolve (we hope…).

Scientific modelling can provide a lot of guesses on what could or is likely to happen, but we just won’t know until it’s done. Clearly, there’s still a lot of debate and uncertainty out there, and technology as powerful as gene drive needs to be handled with a lot of care and its ethical consderations heavily scrutinised. However, we also have to ask ourselves if it’s unethical to not use this technology while it’s available when 1,000 children die every day from the disease.

So, until the world can come up with a decision, for now, at least, scientists have their scissors locked away in the top drawer until they’re safe enough to use.