Mosquito vs Mosquito

Genetically modified mosquitoes are being prepared to tackle regular mosquitoes. But we need to proceed with caution.

Tata Trusts has recently invested $70 million for developing genetically modified  mosquitoes to fight Malaria in India. In Maharashtra, a British company Oxitec has been testing gene drive mosquitoes to reduce dengue and chikungunya vectors for the past few months. Sounds enticing? Who wouldn’t want to get rid of those pesky insects? Research into gene drive mosquitoes began in 2015 and has attracted considerable funding from the Bill and Melinda Gates Foundation and US Defense Advanced Research Projects Agency (DARPA). But what are gene drive mosquitoes?

Dr. Reety Arora, a Postdoctoral Fellow who has been using the gene editing technology CRISPR at the National Centre for Biological Sciences explains,

Gene Drive is designed to first externally introduce an RNA-guided enzyme that cuts a specific target sequence on one chromosome in the recipient cells. Following this, the cells own DNA repair machinery inserts a cassette expressing an identifiable gene, the Cas9 endonuclease and gRNA. Once inserted, the Cas9-gRNA can again target the cut-site in the other chromosome with the original/native allele during sexual reproduction. This ensures that gene-drive mediated insertion re-occurs in each offspring that carries at-least one copy of the modification. With each generation, the mutation will spread in the population. By releasing sufficient numbers of edited organisms in the population, it may take only 12-15 generations to be successfully found in all the individuals of the group.

In simple terms, they are genetically-modified mosquitoes (GMM) that can pass on their gene modification to their offspring at a rapid rate, converting the majority of the mosquito population into GMM. Scientists are designing GMMs that either have low fertility rates or are unable to host the disease-causing agent. Once these GMM are released in the environment, they will mate with the wild type mosquitoes and the offspring will either die or be unable to carry the disease. In the first scenario, mosquito population will eventually reduce, and in the second scenario, the disease carrying ability of the mosquito will go down.

The possible eradication of diseases like malaria or dengue has obviously caused a lot of excitement. However, as with any new technology, there will be risks associated with its use. Ecological effects, ethical questions and possibility of adverse events are risks associated with all genetically modified organisms. Certain risks of using gene drive are however, more worrying than with other GMOs.

Firstly, when deployed in the environment, there will be no way to recall these GMMs. Glitches can occur with any technology, but in most cases these can be resolved when discovered by identifying and fixing the problem, even in sold goods. Even GM crops and animals can be traced based on who has created and bought them. But there will be no way of identifying and recalling the GMMs. This means that the risk assessment and monitoring protocols for their deployment need to be more strenuous than other technologies.

Another differentiator for GMMs is that there is minimal chance for market forces to regulate the technology. Think of Bt cotton – even after governmental approval, farmers have a choice whether to buy the seed and customers have a choice of buying GM or non-GM foods. GMMs, once deployed, will leave citizens with little choice, apart from relocating if they don’t agree to the move. Hence, the deployment of GMMs can only follow an informed public dialogue regarding the its risks, benefits and liability. Clearly, if the GMMs work, the company/institution, the government and society benefits.

What happens if the GMMs don’t work? Or cause further problems? Oxitec for example, had released GMMs targeting dengue in Brazil in 2012. In the subsequent years, there was a big outbreak of Zika incidence in the country. There is no causal data linking the GMMs to the Zika outbreak. However, it raises the question of who bears the cost of monitoring and redressal if such an outbreak does occur? These questions need to be addressed before deploying any GMMs.

Prof Vijay Chandru, Executive Chairman and Managing Director of Strand Life Sciences, explains:

Biotechnology in the 21st century is an extraordinary gift to mankind that can at once address issues of health, food, environmental and energy security – the four greatest challenges we face. With such power comes great responsibility that requires societies to demand transparency, debate and regulation in governance. To even assess the pros and cons of GMMs we need a much higher fidelity of epidemiological models of vector densities and vector borne diseases. The national academies of the US have stated in the 2016 report that there is insufficient evidence available at this time to support the release of gene-drive modified organisms into the environment.

Mosquito-borne diseases result in many deaths and are a big economic burden in India. Given India’s huge land mass, population distribution and inefficient governance structures, conventional methods for preventing mosquito breeding have not worked effectively. It is therefore prudent to consider emerging technologies that may aid in stopping this menace. However, given the associated risks to GMMs an open dialogue, an exhaustive risk assessment and a comprehensive review of the project including improved disease monitoring and liability resolution should be a must before approving deployment of these mosquitoes.