Tuesday, March 20, 2007

A mosquito for fighting malaria

There’s been some buzz in the news recently, about genetically engineered mosquitoes that can no longer transmit the malaria causing plasmodium parasite to humans. The idea now is to now potentially introduce these mosquitoes among populations of normal mosquitoes. Over time, as the mosquitoes mate with each other, the normal mosquitoes would pick up the gene that would prevent infection by the plasmodium parasite, and so if the plasmodium can no longer infect mosquitoes, the mosquitoes would no longer be able to transmit the parasite to humans.

There are two angles to this story that interest me. First, there is the science itself, which is fascinating. Understanding the mechanisms of how the plasmodium parasite infects mosquitoes, and enters their gut and propagates is interesting in itself. There is also the other side, the “practical” side which proposes making these engineered mosquitoes as tools to control and prevent malaria, which at a first glance seems reasonable. So, I thought I’d post my thoughts on both these aspects.

I heard of the research itself some three years ago, when the research group published an interesting paper in Nature. Now, for those of you unfamiliar with malaria, the disease is caused by a parasitic protozoan called plasmodium. The disease is transmitted to humans by mosquitoes, which have simplistically described as the “insect vector” for the parasite. In reality, the plasmodium is a parasite of both humans and mosquitoes (and the mosquito is a parasite of humans), and needs both in order to go through its full developmental cycle. In mosquitoes, the parasite (in a specific life cycle stage) needs to go through two epithelial regions of the salivary gland and the midgut, and only then can it complete its development. Now, researchers had identified a small peptide, called SM1 that bound these two epithelial regions, and inhibited the crossing of this region by the malarial parasite. After doing some rather challenging experiments, they were able to now genetically engineer mosquitoes that expressed this SM1 peptide on their own. The big finding in this study was that when these mosquitoes ingested the malarial parasite, the parasite was not able to cross the epithelial region, and so could not complete its development. So, these mosquitoes would not pass on the parasite to mammals (and us).

The authors then suggest that it might be possible to use these mosquitoes, and introduce this gene in wild mosquitoes. This could be another way of disease control. However, those early studies did not show if these genetically engineered mosquitoes were really fit for breeding, and if they could be used to control infective mosquito populations. Contrastingly, it is also known that mosquitoes that are infected with the plasmodium parasite have decreased fertility. So, the authors carried out some follow-up studies (which are now in the news), where they hypothesized that if the genetically engineered mosquitoes (where the plasmodium could not complete its life-cycle) were fed with infected blood, they would be more fit and reproduce better than normal mosquitoes. If this were so, then if there were two equal starting populations (of normal or genetically engineered mosquitoes), the engineered mosquitoes should survive and proliferate better than the normal “wild-type” mosquitoes. They found exactly that.

The two groups of mosquitoes were allowed to feed on mice which were infected with the plasmodium parasite. Over time the mutant engineered mosquitoes began to rapidly outbreed the normal mosquitoes, and soon became the majority population. For a control, the researchers used normal, uninfected mice as food. In this control, the two groups of mosquitoes proliferated at the same rate, with no advantage for any group.

All this is nice from a scientific perspective. There’s no doubt that the researchers have proven their two main points. They’ve shown that you can engineer mosquitoes that won’t be fully infected with plasmodium and these mosquitoes can no longer transmit the parasite to mammals. They’ve also shown that these mosquitoes have a growth advantage over normal mosquitoes when infected with the parasite, so will outgrow normal, infected mosquitoes.

What I am far more skeptical about is the use of these mosquitoes in controlling and perhaps helping to eradicate malaria. The idea is that if these mosquitoes were released in the wild, they would soon become a dominant population. So, not only will they no longer be able to transmit malaria, but the plasmodium parasite itself will find itself without a host, and so over a long time will not be able to propagate.

Sure, it might work. But the thing about malaria (and a bunch of other infectious diseases) is that it isn’t impossible to control or diminish malaria. It’s just that in the places where malaria now still persists, there isn’t an infrastructure in place to really combat the disease. The disease goes along with breeding mosquitoes, poor sanitation and lots of stagnant water, poor hygiene, and poverty. Malaria was very common in the United States about 70 years ago. Systematic efforts on mosquito population control, dredging stagnant water pools and good sanitation pretty much wiped out malaria from the States (in less than 20 years). It’s possible to control the disease without releasing mutant mosquitoes (though I personally do not have too many ethical issues on starting trials with these engineered mosquitoes to see if they’ll help). And by just keeping it simple, it will actually improve the lives of many people along with controlling the disease.

But the world isn’t simple, is it?

(references: Nature 417, 452-455 (23 May 2002) | doi:10.1038/417452a, Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0609809104)


Shripriya said...

Fascinating post. One question - in the past, people have introduced foreign animal populations into countries to control pests. These have often backfired and the predator becomes a pest that's more dangerous.

Do you think there is any risk with that in the new strain of mosquito? Any chance of them mutating into something worse?

Btw, I love your posts - you explain science really well :) Thanks!

Sunil said...

shripriya.....you're absolutely right. I don't think there is one single instance of a foreign species that has been introduced anywhere without making a nuisance of itself, and causing havoc with local ecosystems. This is for plants, insects and animals.

Of course, here the mosquito would technically be the same "species", just a modified version of the same. But there will always remain doubts about it, and the possibility that something will go wrong. That's part of the reason why I don't really like the idea of introducing any foreign species. There will always remain too many unknowns (for example, even if it is less susceptible to plasmodium, could it be compensated for something else? Unlikely, but certainly possible. Would that be bad in the grand scheme of things?)

Kiran said...

I totally agree. Mosquitoes probably have as much right to live on earth as we do - we can just choose to ensure that they dont live with us - just like we dont allow "wild" or even stray animals into our houses and increasingly our cities and villages.

Moreover, elimination of the means for mosquitoes to breed and propagate in places of human habitation invariably means making the habitats "better" in most senses of the word.

BTW, as you mentioned in a previous post, chilli peppers are not native species on the subcontinent, and I dont think they are a nuisance yet. Well you could point out that chilli farmers in South India periodically go broke (and unfortunately some even commit suicide), but I dont think that is the crux of the message above.

Sunil said...

heh....kiran, I was mostly talking about introducing foreign species as a means of pest control or elimination. Those have largely been disasters, in almost every country in the world.

But actually, in most cases, introducing any foreign species has caused a lot of trouble for endemic species.

with agriculture and crops, in some ways the spread of potatoes, tomatoes and even say the chilli pepper have resulted in a large loss of endemic crop species, and a resulting move towards worldwide monoculture. So, in some ways, even this has hurt a lot of other species (though we're ok with it, and are eating "well").

Ashutosh said...

Sunil, you are absolutely right about this. In fact, a lot of the biodiversity in the world has been lost because supposedly "tame" species have been introduced into regions where they rapidly colonised ecosystems and decimated endemic species. Not to mention the foreign nature of the human beings themselves.
Both Edward O. Wilson in his 'The Future of Life' and Jared Diamond in his 'Guns, Germs, and Steel' talk lucidly about this.

Sunil said...

Ashutosh....I haven't yet read Wilson's "The future of life", but it's on my "to read" list. But "Guns, germs and Steel" was wonderful to read, and is now amongst my favorites.

Niket said...

In case you haven't read Pharyngula's take on this.

Sunil said...

yeah, I saw PZ's take on this yesterday. Thanks for the link here though......other readers might like to read it.

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