Are Genetic Weapons the Best Tools to Fight Zika Virus? (Op-Ed)
David O'Brochta is a professor in the Department of Entomology at the Institute for Bioscience and Biotechnology Research at the University of Maryland - College Park. He studies genetic technologies for use in insects and the application of those technologies to explore the physiology and genetics that make some mosquitoes excellent vectors of human pathogens. David O'Brochta has no conflicts of interest regarding the content of this piece. He contributed this article to Live Science's Expert Voices: Op-Ed & Insights.
The unexpected risks unborn children appear to face from the Zika virus have drawn renewed attention to the importance of mosquito control in public health, but the Zika outbreak does not necessarily justify the immediate application of new — and relatively untested — mosquito controls.
Mosquito control today involves a combination of chemical insecticide applications to kill adults and larvae, natural insecticides produced by Bacillus bacteria and elimination of mosquito habitats such as standing water.
The standard approaches to controlling mosquitoes
Generally speaking, the relationship between the number of mosquitoes and the number of virus or parasite infections is not a direct one. Reducing the mosquito population by half, for example, may not reduce the infection rate by half, if at all. How many infected mosquitoes there are and how many bites it takes to acquire an infection determine how much a mosquito population needs to be reduced before it has an effect on public health. So just killing some mosquitoes is not necessarily going to be helpful, although it may feel like it is. All efforts need to be evaluated in light of public health outcomes. [5 Things to Know About Zika Virus ]
Furthermore, "low-tech" approaches can be effective — like removing sources of standing water around dwellings to reduce contact with Aedes aegypti, the vector of Zika in South America, or spraying insecticides to kill adults, or applying chemical or natural insecticides to standing water to kill developing mosquitoes.
There are no new silver bullets to deal with the current threats from Zika-infected Aedes aegypti. A faster and more effective response may come from better organization of existing local mosquito control programs and providing them with the resources they need to implement low-tech solutions such as insecticide applications and reducing the sources of mosquitoes. Although relatively low tech, these efforts require people, equipment and supplies to implement them, as well as strong community support.
Gene warfare against Zika
While low-tech strategies need to be considered, genetics-based "high-tech" strategies do have their benefits, and their research and development are fully justified.
The genetic technology developed by the British biotech company Oxitec and introduced into Aedes aegypti is a variation of a well-tested approach called the sterile-insect technique. The sterile-insect technique has been most often applied to agricultural insect pests such as the Mediterranean fruit fly (Ceratitis capitata) and the screwworm (Cochliomyia hominivorax).
This strategy involves large numbers of "smart bomb"-like male insects being released into the wild pest population where they deliver their lethal genetic load. In the case of the sterile insect technique, the sperm of males released into the wild carry a large number of genetic mutations induced by radiation that render the males sterile. Unwitting wild females mating with these sterile males will produce no offspring.
Oxitec's male mosquitoes that are released into the wild contain genes they inserted into the insect’s genome that will cause the progeny arising from wild females that mated with these males to die. The genes inserted by Oxitec into their mosquitoes are lethal to the developing mosquitoes — these insects carry a lethal genetic load. Both the sterile insect technique and Oxitec's approach require the capability of growing large numbers of these smart-bomb-like insects. Some sterile-insect control programs grow and release millions of insects per week.
These genetics-based strategies require constant input — the regular production and release of insects — but one thing genetics-based approaches are particularly good at is reducing populations that are already at low densities. The released insects, which are either sterile or carrying a lethal genetic load, actively seek out mates, finding them even when their numbers are low. Insecticides cannot do this, and the best efforts to remove sites where insects hatch, such as pools of standing water, can still leave residual populations.
Future controls
So-called gene-drive systems are genetics-based approaches that will not require large and continuous inputs and are "self-sustaining." Genetic drive refers generally to when genes or combinations of genes rapidly increase in frequency within a population because those genes preferentially are passed on to the next generation. These genetic-drive systems might be used to spread genes through mosquito populations, for example, that affect virus transmission or sex ratios or some other phenotype that makes the insects less of a threat to human health. But these systems are not going to be simple to develop, and while promising results showing rapid spread in laboratory populations have been reported, how these systems will perform in natural populations is currently unknown.
The insect research community's experiences with custom-designed gene-drive systems are still at the Model T stage of development, although the sex ratio distortion system based on a unique DNA-cutting enzyme called a meganuclease under testing by Austin Burt and colleagues as part of a Gates Foundation-funded project is close to being tested under field-like conditions in Africa and looks promising. This genetic-drive system causes males to produce only sperm with a male-determining Y chromosome and consequently any female mating with a drive-containing male will only produce male offspring and those males will have the same effect on females with which they mate. This situation is unsustainable and the mosquito population will crash. This is an exciting approach to controlling the very difficult to control African malaria mosquito, Anopheles gambiae.
Recently developed gene-editing technology based on CRISPR/Cas9 has been used to create gene drives in malaria mosquitoes that show similarities to what Burt and colleagues created with a meganuclease, except instead of distorting sex ratios, the gene drive in one case reduced female fertility and in another it carried a gene with the potential to reduce the mosquito's susceptibility to infection by malaria parasites. These cases were experimental demonstrations, and developing these strategies into something that can be tested in the field will likely take five to 10 years. [Does Zika Cause Microcephaly? CDC Seeks More Answers]
Time will tell if gene-drive systems become a new form of insecticide. Certainly, the idea of locally eradicating insect species is not a foreign or even controversial concept. After all, local eradication is the intention of insecticide applications by farmers in their fields, public health officials in cities and even homeowners in their own backyards.
Now we are talking about doing it in a very specific, nonchemical way — and in that context, gene-drive technologies for some situations look very attractive and certainly warrant increased attention from researchers. I am optimistic that they can be developed and used against species such Aedes aegypti, in Brazil or the United States, which is a non-native invasive species whose removal from these locations is not an act of ecological destruction but restoration. Gene-drive technology is too immature to assist with the current Zika crisis but within the next decade it is likely that there will be a number of new options on the table for controlling mosquito populations.
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