THE gene modifying technology that produces sterile male mosquitoes has distinct potential against all mosquito-borne diseases and against Zika, chikungunya and dengue in particular. As a result, programmes to suppress and potentially eliminate the Aedes aegypti mosquito vector have been proposed to some countries in the Caribbean by a company in the United Kingdom that specialises in breeding genetically modified (GM) mosquitoes.

However, there is a need to collect further data on the intervention, as there is no technical consensus on the benefits or risks of the widespread use of this technology.

GENE MODIFICATION OF MOSQUITOES

The idea behind modifying the reproductive ability of the male mosquito is simple.

Mosquito eggs are injected with a small amount of DNA to be incorporated into the mosquito cells in the lab. When this happens for the sperm cells of the male mosquito, the new DNA will be passed on to their offsprings. These genetically modified males are identified and released into the environment to compete with healthy males for female mosquitoes, but their union should produce non-viable offsprings that would or should soon die.

Consequently, the GM mosquitoes would be ‘self-extinguishing’, and the genes that have been altered would not be expected to survive among the mosquito population in the wild.

However, in 2010, a geneticist wrote to a biosafety regulator in Malaysia, which was considering a release of GM mosquitoes at the time, pointing to the 2007 finding by researchers that 3-4 per cent of the first-generation GM mosquitoes actually survived.

Their survival occurred as the genetic engineering method employed by the UK company allows the widely available antibiotic tetracycline to be used to reduce the lethality or death rate of the mosquito during breeding. However, as a side effect, the death rate is also reduced by the presence of any tetracycline in the environment.

So, in environments that use anti-microbials like tetracycline in its commercial farming sector, some of the genetically modified mosquitoes might be able to survive. Tetracycline may also be widely present in sewage, septic tanks, contaminated water sources, and the run-off from farms. Since even small amounts of tetracycline can repress the engineered lethality in the mosquito larvae, it was projected that up to 15 per cent of the GM mosquitoes may survive.

WHAT MAY HAPPEN?

An even graver possibility that has been suggested is that the ‘jumping’ sequence of DNA that is used in the gene-modifying process to introduce new genes into a target organism could result in a particular DNA sequence being introduced into new genes way beyond its intended target. So whilst genetic engineering may use the DNA sequence technique in insect vector control, there is a possibility that ‘trans-genes’ borne by the ‘jumping sequence of DNA’ technique could transfer horizontally to human cells or to the Zika virus, if present.

If the latter occurred, then certain mutated strains of the Zika virus could acquire a selective advantage, making them more virulent (powerful) and thereby giving them an enhanced ability to enter and disrupt human DNA. This possibility might explain, with GM mosquitoes present in the environment, how the development of a human embryo in the womb of a woman infected with Zika could result in microcephaly and other possible deformations.

This credible hypothesis has resulted in some people calling for a halt in the release of GM mosquitoes into the wild in countries like Brazil where a Zika virus epidemic is currently occurring, until more is known about this possibility. Certainly, there should be cautious studies of these phenomena within the ambit of clinical trials. Any calls for more release of GM mosquitoes to halt the transmission of the Zika virus therefore should be addressed in this way.

PHASE THREE CLINICAL TRIALS

As we do not know all the possible outcomes, use of genetically modified mosquitoes should occur through a research process of discovery that would include a monitoring and evaluation plan. More research is needed to identify the number of GM mosquitoes required and the time to suppress mosquito populations adequately per unit of environment, a risk mitigation plan to show how outbreaks of GM mosquitoes might be controlled given that transgenic mosquitoes are not susceptible to insecticides, and the effect of any total reduction of the mosquito vector where wild strains of the mosquito may be reintroduced into an area.

FAR-REACHING EFFECTS

Whilst the gene-modifying mosquito technology, when appropriately tested under specified research conditions, may make a significant positive impact on health within a country or region, there are still many unknowns in the process.

The reduction of mosquito vectors through genetic modification should therefore be regarded as being in the research stages, and should be advanced in a planned manner and driven through a process of independent monitoring and evaluation. Any beneficial outcome must be sustainable.

Derrick Aarons MD, PhD is a consultant bioethicist/family physician, a specialist in ethical issues in medicine, the life sciences and research, and is the ethicist at the Caribbean Public Health Agency — CARPHA. (The views expressed hereare not written on behalf of CARPHA)