Killing Disease with Bugs

A schematic of how Medea is passed on. If neither the father or the mother contributes the Medea element, the embryo dies (indicated by the Credit: Bruce Hay

Friday, March 30th, 2007--

One proposed method to fight malaria, a disease that infects half a billion people each year, is to modify the genes of the mosquitoes that carry the disease. Mosquitoes are the main vectors—no organisms, other than humans and mosquitoes transmit malaria—so eliminating malaria in mosquitoes could eliminate malaria in people, says Bruce Hay, a researcher at the California Institute of Technology in Pasadena, CA.

Scientists have already created genetically engineered mosquitoes that are immune to the disease and therefore can’t transmit it. And according to Hay, the changes “are quite modest—you can think of them really as simply boosting the mosquito’s immune system in a very specific way so that [the mosquito] will be resistant just to the parasites we’re interested in attacking.”

But researchers haven’t figured out how to get these malaria resistant bugs into the wild. The modified mosquitoes are less fit than wild mosquitoes: “It is generally observed that anything you do to stimulate the immune system of an organism, and in particular insects, has other costs,” Hay says. In this case, the immune boost leads to lower fertility and shorter life span. This cost means that even if billions of malaria-resistant mosquitoes were released into the wild, they and their malaria-resistant genes would disappear as the fitter, wild mosquitoes out-competed them.

But Hay and his colleagues reported a a potential way around the fitness cost, in a study published in the journal Science this week. They say the malaria-resistance can be linked to another gene element, called Medea. Named partly after the Medea of Greek mythology who killed her children after her lover ran away with another woman, Medea genes are also (evolutionarily-speaking) spiteful and selfish—propagating themselves at all costs.

If the Medea element is not passed on to the offspring, then the offspring die. This makes Medea a powerful tool for genetic modification, because Medea ensures that a trait will be passed on, even if that trait comes with a fitness cost. “Medea is like a pack animal,” Hay explains. “Medea can move through a population even if it carries a load—even if it carries a heavy load, like the disease resistance gene.”

The study showed that linking malaria resistance to Medea is possible in fruit flies (Drosophila)—the next task is to make it work in mosquitoes. But even if the genetic challenge is surmounted, who would approve the use of the bugs? “There has been no formally articulated pathway for these to be approved,” says Michael Fernandez, Executive Director of the Pew Initiative on Food and Biotechnology. “And that poses a challenge for researchers who might want to do this.”

Another challenge the researchers may confront--although Hay says he hasn't seen resistance so far--is convincing people that releasing millions of genetically modified organisms into the wild is a good idea. “I think there is no question that there is potential there, but I think there are a lot of questions still,” says Fernandez. For instance, our experience with genetically modified organisms relates mainly to crops, which are planted and harvested. In this case, “you’re talking about establishing a genetically modified organism in an ecosystem,” Fernandez says. These mosquitoes are intended to replace the wild population and they can’t be culled back like corn, if something goes awry.

On the other hand, Fernandez and Hay both point out, the risk-benefit analysis may be different when the benefit isn’t increasing a company’s bottom line, but instead potentially saving millions of human lives. Hay also argues that in comparison to the other malaria-eradication options—including the widespread use of pesticides and eliminating all standing water from an environment—this is a much more refined and ecologically-friendly solution. “I think the most likely worst-case scenario is simply that we would spend a lot of money and a lot of time putting these organisms into the environment and then that they would not work,” Hay says.

But the risk of failing is not negligible. “People are raising questions about whether this where we should be investing our money,” Fernandez says. “Are there lower-cost solutions?" Is mosquito netting a better place to start?

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--Flora Lichtman