Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
Dengue Fever. Malaria. Yellow Fever. West Nile Virus. These are some of the major mosquito-borne illnesses on Earth; that is, infectious diseases you can contract from a mosquito bite. And if you’ve been reading the news lately, you’ve likely seen Zika virus rapidly ascending the list. Zika is a Flavivirus just like most of the other mosquito-borne viruses, and despite its generally mild symptoms it has recently been implicated in serious birth defects. Several months ago, Brazil reported a spike in poor pregnancy outcomes in women who contracted Zika while they were pregnant. One such condition seen so far is microcephaly, in which a baby’s head is much smaller than it should be due to an improperly developing brain.
So what do we do to fight mosquito-borne illnesses? Scientists have been working on vaccines for years; recently, a new malaria vaccine called Mosquirix was approved by European regulators, and a couple of dengue vaccines are making their way through clinical trials. We all know about various mosquito repellents on the market, too, to ward these nuisance insects – try camping in the summer without fortifying your skin or clothing with some 25+ percent DEET. And in malaria-endemic nations, mosquito nets are highly recommended during the night. What about approaches that might be a little easier to impart on regions lacking robust enough infrastructure to provide their citizens with the proper precautions?
Recently, some researchers have been exploring a new approach to warding off mosquito-borne illnesses. Companies like UK-based Oxitec and labs around the United States such as UC Irvine and UC San Diego have turned to genetically engineered mosquitoes to eliminate the source of the problem. Oxitec has developed a “self-limiting gene”; that is, the company has developed a way to control mosquito populations by wiping them out. The genetically modified mosquitos are designed to be released into the wild, and when they reproduce they pass on the new gene to all their offspring. The resulting offspring then die before reaching reproductive maturity, and the mosquito population declines. By killing the mosquitoes in a given region, the diseases they carry die off as well.
So how are these mosquitoes made? As with most genetic manipulation, it all begins with the eggs: scientists use microscopic, specialized needles to inject DNA into one end of an egg. While most eggs won’t survive the penetration, the ones that do end up taking the DNA into the cells within them, incorporating the self-limiting gene into the developing insect’s genetic makeup. The insect’s genetic makeup includes its sex organs, meaning the new DNA can be passed on to future generations. Genetically modified eggs are incubated, hatched, and screened: in Oxitec’s case, the injected DNA contains both the lethal gene and a fluorescence gene in order to visualize successful DNA uptake. The success rate of this initial procedure is about one in several thousand, but all it takes is one viable genetically modified mosquito to then be bred countless times.
Another approach to genetic mosquito control involves modifying mosquitoes so that they kill pathogenic microbes living inside them and therefore cannot transmit deadly diseases to humans. At UC Irvine and UC San Diego, researchers have successfully done this to combat malaria. Scientists at UC Irvine discovered a set of genes in mice that confers a strong immune response to Plasmodium falciparum, the parasite responsible for malaria in humans. They inserted these genes into mosquito DNA, and the insects resisted parasitic infection. The issue was that these malaria-resistance genes were only passed on to offspring about 50% of the time; and in a region containing millions of mosquitoes, this isn’t good enough. Meanwhile, at UC San Diego, scientists developed a gene drive system using CRISPR/Cas9 and successfully engineered fruit flies to pass on an artificially inserted trait with a success rate closer to 97%. Couple this technology with UC Irvine’s genes, and you’ve got yourself a potential victory.
And victory it was. After months of trial and error to create a gene drive for mosquitoes that contained anti-malarial mouse genes (bet you don’t read that sentence every day), the tool was inserted into 680 mosquito larvae. About 37% of these larvae survived to adulthood and were mated with wild mosquitoes, and out of 25,712 offspring that were generated, 2 of them carried the mice genes. Those two mosquitoes were bred to produce 143 offspring, half of which carried the malaria-warding genes. The malaria resistant mosquitoes were once again bred with wild insects, and this time the malaria-resistance genes transferred to over 99% of the resulting offspring. This feat is just the beginning – more work needs to be done to produce a robust genetically-modified mosquito that is ready for release into the wild: fully reliable proliferation of the gene through generations is essential, and people living in regions where these insects could be released would need to okay the efforts.
Both genetic manipulations of mosquitoes are wonderfully innovative and show potential in the prevention of the diseases these insects can spread in human populations. Oxitec’s approach, which aims at wiping out mosquitoes altogether, sounds pretty good in theory – however, we don’t know the exact importance of mosquitoes in their ecosystems; what if the eradication of mosquitoes brings forth an even more dangerous pest? As a result, methods targeting insect immune responses to parasites might seem more attractive. This, too, could pose problems though – there are drug-resistant forms of malaria emerging in different parts of the world. What if mosquito-resistant malaria arises when challenged enough times with the immune-modified insects? Where else can the parasites learn to survive and circulate to complete their life cycles in humans or other hosts? Either way, it will be fascinating to see where both technologies, coupled with more traditional medical and environmental efforts, take us in the battle against mosquito-borne illnesses.
Read the UC Irvine and UC San Diego papers: