CRISPR/Cas9

A new technique to tackle malaria?

This week brought news of a fascinating new approach to preventing malaria. Malaria is an illness caused by a parasite that is spread by mosquitos and causes 219 million illnesses per year, and 500,000 deaths.MosquitoThis statistic however, doesn’t convey the extent of a problem malaria poses. It is a disease that kills vulnerable people in countries least equipped to tackle it: 90% of those deaths occur in sub-Saharan Africa, and shockingly almost 80% occur in children under 5 years old (400,000 deaths).Furthermore, economically, it is thought to impact the GDP of some countries by up to 5 – 6% per year (Nigeria and the DRC for example). To put that into context, the same problem in the UK would cost the country around £120 billion; the entire annual budget of the NHS is £95.6 billion.It is easy to see how this disease is financially ruinous for sub-Saharan Africa, and how big an affect fewer cases of malaria could have.This is why it is big news that a strain of mosquito that is resistant to the parasite (and thus cannot spread the disease) has been created in the lab.The scientists introduced a gene into the DNA of the mosquitos, one that gives the insect an antibody against the malaria parasite. This antibody causes the insect’s immune system to kill the parasite. In tests, the researchers found no transmission of the disease by these mosquitos.This is an impressive feat in itself; however on its own it isn’t much use. This is because every individual has 2 copies of every gene, and only one copy is transmitted to the offspring. So normally the modified mosquito would pass its copy of the resistance gene to half its offspring (see figure, below). They in turn will pass it to half their offspring, and so on. Very soon the resistance gene would be naturally drowned out of the population.This is where a second bit of technology comes into play. The scientists took advantage of something called a Gene Drive, a system aimed at forcing the expansion of a gene in a population using Crispr/Cas9 technology, Crispr/Cas9 is a system with the ability to snip out and replace bits of genes, which Myriam has previously blogged about here. Using this approach, they resistant gene could actually snip out the “unresistant” second copy and replace it with a copy of itself.This way, when the modified mosquito passes the resistance gene to its offspring, the unresistant second gene from the other parent gets replaced by another copy of resistant one. As a result, ALL the offspring inherit the malarial resistance (see figure, below). This resistance would then become more and more common, theoretically reducing the incidence of malaria in humans.Gene driveAt present there are no plans to release the resistant mosquitos into the wild however. We are, in effect, forcing genetic changes on an entire species, driving its evolution in a particular direction. This could have very unpredictable ecological consequences, as was emphasised in a warning recently published in the journal Science.Additionally, the technology isn’t quite ready yet, but it is only a matter of time before it is. When it is actually ready, we will be presented with a difficult question: considering how devastating malaria is in sub-Saharan Africa, is it ethical to delay the release of this gene drive because of these ecological concerns?This question obviously doesn’t have a simple answer. It is something governments and the science community will have to thrash out in the coming years.