Fig 1. Image of an Aedes aegypti mosquito
The world's deadliest animal, the mosquito, is thought to kill between 750,000 and 1 million people annually. There may be 110 trillion mosquitoes on the earth, and these insects can spread deadly illnesses like West Nile virus, Zika virus, dengue fever, malaria, and dengue fever.
One such species of mosquito is Aedes aegypti. When fully mature these adults can lay over 200 eggs at a time, which are capable of hatching in about 2 to 3 days in optimal temperatures. Because of the incredibly high turnover rate, mosquito populations can quickly dominate temperate regions, and rapidly spread infectious diseases like malaria across countries.
Not only that, but generations can develop mutations exceptionally quickly, as is the case with the pyrethroid resistance in Florida as a result of rapid natural selection. Since mosquitoes with genes that make them more resistant to pesticides are able to live longer, hence have a higher likelihood of reproducing and spreading their genes over generations. This rapid response to preventative measures is why mosquito populations are incredibly difficult to control.
In an effort to drastically reduce the spread of mosquito-borne diseases in various different countries, the UK-based business Oxitec has released male Aedes aegypti mosquitoes dubbed "Friendly™" mosquitoes into the wild. These mosquitoes have a self-limiting gene that produces a protein known as Tetracycline-controlled trans activator (tTAV).
tTAV is special for two reasons, the first is its innate ability to overexpress itself during protein production. This is because tTAV is able to bind its own control region, tetO. Thus, the production of tTAV increases the expression of even more tTAV in a positive feedback loop, where an overabundance of tTAV is made instead of other essential proteins. Resulting in detrimental impacts on the health of a cell.
However, how could a self-limiting gene be able to be spread to a host in the first place? The other reason tTAV is special is that its destructive nature can be halted through tetracycline. Thus, the parent males are given anti-biotic tetracycline so that they are able to spread their gene and ensure the death of their female offspring and overall reduce the population.
Thus, in theory, there should be an enormous impact when these genetically modified male mosquitoes are released into the environment. The study reported a 100% mortality rate for female larvae. And additionally, because none of the Friendly™ offspring survived past full maturity, a resistance to the treatment could not be passed down and mutated over several generations, which means that the method’s use is sustainable and is not as prone to the issues of overexploitation, unlike current commonly used pesticides.
While this sounds like fantastic news, the actual results of genetic modification are much different than one would expect.
Oxitec’s mosquitoes are limited by the fact that their self-limiting gene only lasts for a single generation - the GM mosquitoes constantly need to be restocked if long-term effects to reduce the population over time are to be achieved. In the 10-year program mentioned before, an estimated total of 1,040,000,000 mosquitoes need to be meticulously bred, engineered then transported to specific areas to be released. It’s an extremely labour-intensive process for a theoretical 10% decrease in population.
However, the biggest issue is that, rather than reduce the population as a whole, evidence from Oxitec’s own 2009 Cayman Islands experiments, suggests that while the number of wild Aedes aegypti mosquito eggs in the release area decreased, there was a simultaneous increase in the neighbouring control area without genetically modified mosquitoes. Indicating that instead of a decrease in the population as expected, non-genetically modified mosquitoes instead chose to as biting females move towards areas with a greater number of Aedes aegypti mosquitoes.
Fig 2. Diagram showing the resulting relocation diffusion as a result of the release of GM mosquitoes
This is a great example of the potential pitfalls of genetic modification. Humans have never been able to manipulate the genome of an entire population, as such, there are bound to be unforeseen ecological complications that go beyond what can be learned in a laboratory.
Anon, (2022). Fighting the World’s Deadliest Animal. [online] Available at: https://www.cdc.gov/globalhealth/stories/2019/world-deadliest-animal.html [Accessed 7 Nov. 2022].
Oxitec’s Genetically Modified Mosquitoes: Ready to Roll Out? 2017. [Accessed 7 Nov. 2022].
Roser, Max, and Hannah Ritchie. “Malaria.” Our World in Data, 12 Nov. 2019, ourworldindata.org/malaria [Accessed 31 May 2022].
“World Malaria Report 2021.” Who. int, 2021, [online] Available at: www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021 [Accessed 31 May 2022].
Written by Samuel Lim