Malaria-Fighting Mosquitoes

Stephen DeAngelis

April 12, 2007

On several occasions I have written about efforts to eliminate malaria in developing countries. Malaria kills more than a million people annually, most of them African children under the age of five. The Bush administration launched a $1.2 malaria initiative in June 2005 with hopes of halving malaria-related deaths in more than a dozen African countries. Former president Jimmy Carter has set up African clinics to treat and help eliminate diseases (malaria among them). The World Bank, Unicef, and the Bill and Melinda Gates Foundation have contributed to efforts aimed at creating a malaria vaccine. Companies are now making and selling mosquito nets impregnated with insecticide. In villages where residents use mosquito (even unimpregnated nets) cases of malaria drop dramatically. When Billiton, one of the world’s biggest aluminum producers, found malaria affecting its bottom line, it entered into a partnership with the governments of three African countries and with other businesses to take on malaria systematically across a broad region. Six years later malaria is losing. This public/private partnership successfully used a combination of new medicines, better mosquito nets, and pesticides (aided by computer analysis) to clean up the most afflicted areas.

 

The Economist now reports that a new approach is about to be tried. This approach turns enemies — mosquitoes that spread malaria — into allies [“A shift of perspective,” 24 March 2007].

“Making an ally out of an enemy is often a good policy. And that is what Mauro Marrelli and Chaoyang Li of Johns Hopkins University are trying to do. Until recently, Anopheles, the mosquito that spreads malarial parasites, has been seen by those trying to eradicate the disease as a target. Now, a few far-sighted researchers see it as an opportunity. The idea put forward by these researchers, Dr Marrelli and Dr Li among them, is to break the chain of transmission by breeding mosquitoes that are themselves resistant to malarial parasites, and then to take the genes that confer this resistance and establish them in the wild. The first bit of this strategy is not too difficult; several resistance genes have already been found. It is the second part that seems ambitious for, in order to get these genes to spread through the Anopheles population of Africa and other infected areas, they will have to confer higher fitness on the insects that contain them than is found in the natural population.”

There are a number of reasons that this story attracted my attention. First, of course, was the humanitarian side of it. Drastically reducing malaria deaths would be a great thing. Second, it demonstrates the importance of thinking out of the box (i.e., looking at a challenge from a different perspective). Think of grandma sitting in the living room trying to knit but little Kristina keeps bothering her. The mother recommends that Kristina be put in the playpen. The father, on the other hand, suggests that they put grandma in the playpen. Either solution will work, but the father’s idea is more likely to make Kristina happy. Grandma, if her pride can handle the playpen, should also be happy. Finally, this story takes advantage of a natural process — survival of the fittest. Here is how that works:

“Dr Marrelli and Dr Li are part of a group which has already discovered a gene that protects mosquitoes from malaria. The gene in question, called SM1, encodes a small protein that stops malarial parasites from getting through a mosquito’s gut, thus preventing infection. The question is, at what cost? Other genes that protect against the parasite do so by stimulating the insect’s immune system. That works, but imposes a burden on the animal, since materials and energy have to be diverted to the boosted immune system. In practice, such insects are worse off than they would be without the gene. But because SM1 prevents infection rather than suppressing it, Dr Marrelli and Dr Li hoped that different rules might apply. And so, it seems, they do. The two researchers and their colleagues took a mixture of ‘wild type’ mosquitoes and those that had had SM1 added to their genomes and fed them on mice infected with malarial parasites. The genetically modified beasts did better. To make absolutely certain, the team used two different strains of parasite in different groups of mice. One strain was a type that, in any circumstances, only breeds in mammals, not insects. The other can breed in both. The upshot was that in mosquitoes fed on the mice carrying the mammalian parasite, the SM1 gene had no advantage. In mosquitoes fed on the other group, though, it spread rapidly. By the ninth generation, 70% of the insects were carrying it. So, not only is SM1 protective, it has a clear evolutionary advantage over the wild type, at least in the cosseted conditions of the laboratory.”

This all sounds great, but as with any new technology or scientific breakthrough, there are questions (both practical and ethical) that must be addressed. We are all aware, for example, of concerns expressed about genetically modified foods. People who fear “frankenfood” worry about the uncontrolled spread of modified species. The same concerns have been expressed about loosing genetically modified mosquitoes into the wild. There are unanswered scientific questions as well.

“There is first a question of principle—namely whether it can ever be sensible to release genetically modified organisms to achieve an end like this. But there are also practical questions. One is why SM1 did not sweep the population completely. This is probably because the gene helps when only one copy is present, but hinders when there are two, one from each parent. However, the details are unclear. Another practical point is that the type of malarial parasite used in this and many other experiments is not actually one that causes human disease. Just as researchers use mice to model human physiology, so they use this parasite, Plasmodium berghei, to model the lethal Plasmodium falciparum. Nevertheless, Dr Marrelli and Dr Li have produced a noteworthy result. The idea that helping mosquitoes, rather than destroying them, may be the way to eradicate malaria is pleasingly counterintuitive, even if it would mean more mosquito bites at night.”

I suspect that if experimental results continue to hold up a controlled release of genetically modified mosquitoes will take place. Even if such a trial proves effective, a combination of old and new strategies is likely to be used. Nobody likes being bitten by mosquitoes and I doubt that mosquito nets will disappear, even if mosquitoes no longer pose a significant threat. Using them would be a good idea anyway since even a genetically modified mosquito population poses some risk of passing on malaria.