Here’s a clever (I think) observation in the efforts to eradicate malaria: the mosquitos that transmit malaria are also infected with the disease-causing parasite, so maybe if we cure malaria in mosquitos, it will end one intermediate step in the transmission chain. It sounds like a crazy idea, but recent experiments suggest that it might just work. It’s got the advantage of allowing the use of transgenic techniques on the mosquito population, where you don’t have to worry about patient’s rights or whether a few of your experimental subjects will die during the procedure, and you can just let the untreated population wither away and die, and no one can complain. There are a few other ethical concerns, however.

The experiment is summarized well enough in the abstract to the paper:

The introduction of genes that impair Plasmodium development
into mosquito populations is a strategy being considered for
malaria control. The effect of the transgene on mosquito fitness is
a crucial parameter influencing the success of this approach. We
have previously shown that anopheline mosquitoes expressing the
SM1 peptide in the midgut lumen are impaired for transmission of
Plasmodium berghei. Moreover, the transgenic mosquitoes had no
noticeable fitness load compared with nontransgenic mosquitoes
when fed on noninfected mice. Here we show that when fed on
mice infected with P. berghei, these transgenic mosquitoes are
more fit (higher fecundity and lower mortality) than sibling non-
transgenic mosquitoes. In cage experiments, transgenic mosqui-
toes gradually replaced nontransgenics when mosquitoes were
maintained on mice infected with gametocyte-producing parasites
(strain ANKA 2.34) but not when maintained on mice infected with
gametocyte-deficient parasites (strain ANKA 2.33). These findings
suggest that when feeding on Plasmodium-infected blood, trans-
genic malaria-resistant mosquitoes have a selective advantage
over nontransgenic mosquitoes. This fitness advantage has impor-
tant implications for devising malaria control strategies by means
of genetic modification of mosquitoes.

So, in even simpler terms: malaria is caused by an infection with the Plasmodium parasite. Transgenic mice modified to produce a small protein called SM1 do not transmit the parasite as effectively. The transgenic modification doesn’t seem to reduce the viability of the mosquitos—they don’t show any selective disadvantage in environments with no Plasmodium. However, they do show a selective advantage over non-transgenic mosquitos when there’s Plasmodium around. In other words, mosquitos are also affected by malaria, and curing them of the disease makes them healthier and better able to reproduce. Cool! Maybe we’ve been treating the wrong patients all along!

What this suggests is that all we have to do is make a bunch of transgenic, malaria-resistant mosquitos, release them into the wild, and they’ll gradually take over the natural populations and block the transmission of Plasmodium to people indirectly.

There are a few reservations. The SM1 modification isn’t perfect: the frequency of the transgenic mosquitos in lab populations steadily rises over time, but then plateaus at 70% after about 9 generations. The investigators speculate that this might be an example of overdominance: mosquitos heterozygous for the transgene have an advantage over the wildtype, but those homozygous for it have some deficit. This is analogous to the sickle-cell anemia allele in humans, which is a good thing when present in one copy, but disastrous when present in two. This means that population dynamics will not naturally allow the transgenic mosquitos to completely take over a population.

Even if it worked perfectly, though, there’s still this other major concern: do we really want to make a single species that feeds on us even healthier? One way to think of it is that Plasmodium acts as one check on the proliferation of mosquitos, and we’re proposing to remove it and shift the balance of species a little bit in one direction … and we have no idea what indirect effects this change might have. Also, while it may be a great idea to eradicate malaria, the transgenic trick still leaves a prolific general vector of disease thriving, and perhaps even more densely populated. What if some other disease rises to take the place of malaria, and is even more effective, thanks to increased numbers of transmitting agents?

This one is a hard problem. If we could make some small change to mosquitos that would prevent a disease but would give an advantage to one species, should we release it? It would be an irreversible action, and we don’t know ahead of time what all the consequences would be.

Also, as a resident of Minnesota where malaria isn’t an issue, but mosquitos are an ubiquitous pest, it rankles to help them out. Mosquitos don’t need to be bearing a load of Plasmodium to be a pain in the neck.

Marrelli MT, Li C, Rasgon JL, Jacobs-Lorena M (2007) Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood. Proc.Nat.Acad.Sci.USA Early Edition.