Are genetically engineered mosquitoes realistic solution to Zika?

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Earlier this week the Director of the World Health Organization Dr. Margaret Chan declared that the ongoing Zika outbreak was a ‘Public Health Emergency of International Concern.’ This was a significant move by the international body as it is the fourth time that the declaration has been made since such a designation was formally defined as a response to a public health crisis by the WHO in 2005, with the most recent one being for the Ebola outbreak.

As part of the declaration, the Director called for a “coordinated international response” a big part of which was to “to intensify the control of mosquito populations,” which are the primary way by which Zika is being spread.

Among the many options being reported on as a control measure is the use of modern biotechnology methods. The most notable is a genetically modified sterile male mosquito created by the British firm Oxitec which has been successfully conducting field trials in Brazil to reduce the population of Aedes aegypti mosquito — the species that carries the Zika virus along with other viruses known to cause epidemics such as the dengue and chikungunya virus. Similarly recently published research has shown that the use of gene drives, a genetic modification method that rapidly propagates a transgene through a population could be used to engineer an efficient decline of a mosquito population to cut the numbers by more than 99%. The gene editing technique CRISPR-Cas9 has made it much easier to create gene drives, renewing interest in the possibility of their use for vector control methods.

The use of genetically modified mosquitoes has also been a controversial issue, having been met with resistance from anti-GM activists who have denounced its benefits and claimed that it could pose a risk to human health. Some recent conspiracy theories have even falsely suggested that Oxitec’s mosquitoes may have caused the Zika outbreak, a claim that I wrote about recently for the GLP.

With several current epidemics — such as malaria, dengue, chikungunya and Zika — being the direct result of mosquito borne illnesses the question of whether we should completely eliminate, or at least attempt to eliminate mosquitoes with the use of genetic technologies has come up. However, it’s worth asking is it a realistic goal to try and eliminate certain species of mosquitoes?

The Genetic Expert News Service which provides reporters with access to scientific expertise reached out to scientists to get their reaction on such a possibility and received a wide range of reactions.  

Technical and Regulatory Challenges

Several experts were enthusiastic about Oxitec’s approach and the use of gene drives as methods to control mosquito populations, but noted that it there were several challenges that needed to be solved.

Thomas Scott, a professor of entomology at the University of California, Davis who had previously collaborated with Oxitec on a different vector control project than the one currently being tested, said,

Results from field trials in Brazil for Oxitec’s existing genetically engineered mosquitoes are encouraging. The big challenge for this approach is logistics. How do you scale this system up to the huge areas and cities that need to be treated? I have not seen a clear, convincing answer to this critical question. And there are other questions: is the cost-effectiveness of this approach within reach of governmental budgets? And how sustainable will it be over broad geographic areas and densely populated modern mega-cities?

Creating gene drive systems has been one of the key road blocks for genetic strategies of mosquito-borne disease control. New results using the CRISPR-Cas9 system are very encouraging, but they are currently lab based. It would be a gamble, and one I would not be comfortable taking, to start releasing CRISPR-modified mosquitoes into natural settings without a series of properly designed incremental studies that assess how well it performs in the field.

Thomas Scott even questioned the idea that a species could be completely eradicated saying,

Another big question is whether elimination of a mosquito species is feasible. There are probably a few species we could eliminate with huge budgets and teams of people, but for the species that constitute the biggest public health problems I’m doubtful that with current tools eradication is feasible. Hopefully genetic strategies will evolve in their design and impact so that they can be effectively deployed for disease prevention in the future.

Max Scott, a professor of entomology at North Carolina State University also noted that scaling up would be an issue, saying “Oxitec’s approach is promising but it will be a challenge to scale to larger areas.” He also noted that mosquitoes developing resistance to Oxitec’s technology could be a problem since it relied on a single transgene that wasn’t a hundred percent expressed in all the modified mosquitoes.

Bruce Hay, a professor of biology at California Institute of Technology said,

Oxitec’s technology can be scaled up. It is largely a question of money, will and a lack of fear about something new. I think of Oxitec’s technology as akin to the invention of the seatbelt. Seatbelts are a really simple, pretty much foolproof way of preventing death. They won’t prevent every death, but the mechanism of action is so well understood that there is simply no biologically plausible mechanism by which it could go wrong. In the same way, Oxitec mosquitoes won’t eradicate every mosquito but nor will there be any unpredictable side-effects.

Gene drives are still in their infancy, in several ways. First, genes that mosquitoes could carry to prevent infection are still being developed. Good progress is being made, but the ideal genes do not quite exist yet. Second, the gene drive technologies, while promising, are also still in early stages of development.

Maria Jacobs-Lorena, a professor at Johns Hopkins Bloomberg School of Public Health said,

[Oxitec’s] strategy has worked extremely well, but one limitation is that in order to be effective you have to release enormous numbers of mosquitoes, in vast excess of the existing population. That is perfectly feasible if enough political and economical will is available, and this strategy should be explored.

…From a scientific point of view, in 2-5 years gene drive technology could be ready for field introduction but the big ‘if’ is the regulatory aspect and there is quite a bit of public opposition to genetically engineered organisms in nature.

 

Ecological Impact

The other aspect of whether to eliminate a species using genetic modification is the ecological impact. Some experts raised the question of whether there would be an empty ecological niche left that could be filled in by other species. Thomas Scott, professor of entomology at the University of California, Davis said, “removing some species could open a niche for others to occupy, and the result of that change are hard to predict.”

Others however, believed that eliminating certain Aedes species would not have a major impact. Anthony James, a professor at the University of California, Irvine said,

Both Aedes aegypti and Aedes albopictus are not native to the Americas so eliminating them is a form of bioremediation. Gene drive technologies are the best and safest chance of getting elimination, with the fewest anticipated non-target effects and are a realistic solution for targeting specific problems; in this case, transmission of viruses (dengue, Chikungunya and Zika) by the major invasive Aedes species.”

Gregory Lanzaro, a professor at the University of California, Davis said

As far as eliminating species, as some have suggested for A. aegypti, I do not believe there would be a significant environmental impact. Firstly, A. aegypti was eradicated from large parts of South, Central America and the Caribbean in the 1960’s-70’s and there were no major issues with the environment noticed. Secondly, A. aegypti is not native to the New World and it seems the environment here did just fine before this mosquito was introduced by man from Africa. Finally, I think it is safe to say that we are doing more damage to the environment by using insecticide-based strategies to control these mosquitoes.

As most of the experts have pointed out, whether it is the approach using genetically modified mosquitoes designed by Oxitec or the potential use of gene drives, small scale applications may be possible in the near future, but large scale applications are likely to be many years away and several technical, regulatory and political challenges will have to be crossed. Importantly, people who live in the communities where modified mosquitoes will be deployed must also be convinced that the benefits significantly outweigh the risks. If these challenges are eventually crossed, the use of modern biotechnology could yet another useful tool in the fight against mosquito borne illnesses.

Arvind Suresh is a science media liaison at the Genetic Expert News Service. He is also a science communicator and a former laboratory biologist. Follow him @suresh_arvind.