GMO Mosquitos - what say you?

This is my primary research area. Been working on GM mosquito and similar strategies for the last (almost) 17 years.

There are a number of GM and GM-like vector-borne disease control strategies currently being tested in the field. This is the Oxitech version, called “Release of Insects carrying a Dominant Lethal”, or RIDL. It was developed by my my colleague Dr. Luke Alphey at Oxford University way back in 2000(in fruit flies, took a few more years to get it to work in mosquitoes). Luke started a spin-of company (Oxitech) to commercialize the technology and has been at the forefront of this type of thing. They don’t just do mosquitoes - they have extended the RIDL approach to lots of pest insects. In fact, the first releases of GM insects into the wild wasn’t mosquitoes, but rather pink bollworm about 6 or 7 years ago.

The RIDL strategy is in in principle identical to the Sterile Insect Technique (SIT) that has been used for pest insect control for decades. In SIT, you mass rear millions of male insects, sterilize them by radiation, chemosterilants, or by creative classical genetic approaches. You release these sterile males into the environment, they mate with the wild females (who in most species where this works only mate once), and she doesn’t have offspring. You keep releasing sterile males every generation to suppress (or in theory eliminate) the population.

In RIDL, instead of sterilizing the mosquitoes by radiation etc…, they are genetically engineered using some very clever science. The genetic modification only affects females - its a dominant trait (meaning a single copy of the gene is enough to cause the effect) that ONLY kills the female - males who carry the trait are fine.

That’s actually a simplification - in the released mosquitoes, the trait they ended up using doesn’t kill the female, but renders her flightless. Flightless female mosquitoes can’t feed or mate and are easy pickings for predators, so they are functionally dead from an evolutionary standpoint.

The transgene is also tetracyline-repressive. In the lab, the mosquitoes are reared with tetracycline which suppresses transgene expression leading to normal females.This allows you to mass rear them normally. In the wild, mosquitoes are not exposed to tetracycline and females carrying the gene are killed.

Males homozygous for the gene are released, they mate with wild females. All of the females offspring are heterozygous for the gene. The female offspring die (because the gene is dominant and they are not exposed to tetracycline). The male offspring are fine and they go on to mate with normal females. Since they were heterozygous, they pass the gene on to 1/2 of their offspring. Again, male offspring with the gene are fine, females are killed. And so on and so forth.

The endpoint being, you get multiple generations of control (that dampens by 1/2 each generation) from a single release. Because of this (and due to the fact that the transgenic mosquitoes are MUCH more fit that irradiated mosquitoes), RIDL is much more efficient than traditional SIT.

The other upshot is that RIDL is not a self-sustaining process. There is a severe fitness load associated with being transgenic in this case, so the gene will rapidly be eliminated from the population. If something does go wrong, releases are stopped and within a couple generations everything is back to normal. Its very safe. Much more controllable that some other GM-like strategies that are currently being tested (such as Wolbachia, which I have worked on extensively).

RIDL has a much smaller environmental footprint than just about any other strategy out there (including traditional pesticide use). It is very specific, non-target effects are just about impossible, it is controllable and safe, and has been tested in a bunch of countries at this point. The main downside is that it is labor-intensive; releases have to be continuous to work. If you stop releasing, the situation rebounds very quickly. But this isn;t a weakness limited to RIDL, its common to most strategies that don’t go all the way to complete mosquito elimination (very hard to pull off).

In short, there is really only upside to this. It is a very cool example of very clever molecular biology in the lab being brought forth all the way to important field applications, and I’ve been able to watch it happen. I have a fun job.