Malaria is a parasitic disease that affects 300 million people worldwide, and kills nearly 1 million people each year, according to the World Health Organization. Because it is transmitted by mosquitoes, it is prevalent in sub-tropical regions of the world, putting about 40% of the world’s population at risk and creating one of the most important and challenging health problems faced by our global society. This month, a research study published in Science magazine suggests an extremely creative and interesting idea for how science might battle this epidemic in the future.

While some malaria researchers are working to develop vaccines, others are taking a more unconventional approach to eradicate the disease – closer to its source. The strategy is to create genetically modified mosquitoes that cannot transmit malaria to humans and then to further modify their genes so that these resistant mosquitoes rapidly replace the disease-carrying population. Although it may sound like science fiction, two teams of researchers are working to prove that this could be a viable strategy. First, a group of scientists at Case Western University in Ohio found a way to alter the genes of mosquitoes to make them resistant to malaria infection. Then, a different research group from California Institute of Technology (CIT) demonstrated that it is theoretically possible to give these resistant mosquitoes a survival advantage relative to their wild, disease-transmitting, counterparts. They modeled the population replacement strategy in fruit flies, a species that is commonly used in research labs, identifying the right genes to tinker with and simulating a population take-over among fruit flies.

Making a resistant mosquito

The parasite, Plasmodium, resides in mosquitoes and is the culprit for causing the malaria disease. When mosquitoes bite humans the parasites enter the blood. There the parasites go through their lifecycle and reproduce, invading and destroying blood cells and remaining available to infect any future mosquitoes that bite the infected human. In this way, more mosquitoes become infected and then more humans are bitten by infected mosquitoes, continuing the dangerous cycle.

Just as scientists have developed technology to modify foods to have particular desirable characteristics (longer shelf life etc.) scientists can also insert foreign genes into insects. The researchers at Case Western inserted a gene into the mosquitoes that causes them to produce a toxin in their guts, where the parasite resides. The toxic gene is, curiously enough, a gene from bumble bees that produces the venom in bee stingers. Volia! –These mosquitoes now automatically kill the malaria-causing parasites in their guts with the poison of bumble bees.

Giving resistant mosquitoes a leg up in the environment

If bumble bee venom in mosquitoes doesn’t sound enough like science fiction, the researchers at California Institute of Technology also took a cue from Mother Nature’s creativity to show how such resistant mosquitoes might someday replace disease-carrying mosquitoes in the environment. They found inspiration in the unusual flour beetle. Normally, genes are inherited from both parents, allowing the offspring to have an equal mix of genetic material from both its mother and father. The flour beetle evades these rules of inheritance and has what scientists have described as “selfish genes”. Certain genes in the female beetle behave “selfishly” and are transmitted exclusively to each and every one of her offspring (without the father’s version of the gene having any impact). Researchers have proposed that the mysterious “selfish genetic element” is actually a type of toxin/antidote combination. The toxin acts to kill all the eggs as they develop in the mother, but the antidote acts inside the eggs that have inherited it and saves these eggs. This combination of selfish genes results in an important outcome: only the eggs with the antidote survive.

Using fruit flies to prove their point, the CIT researchers modified the flies to carry a test gene that isn’t normally found in flies. This gene is what the bee venom gene would be in mosquitoes— a gene that they would eventually want the entire population to have. Then they inserted a maternally-made-toxin gene linked to an egg-made antidote into the same flies. The mother flies produced a toxin that killed all of her eggs except those eggs that contained the antidote (which was tightly linked to the test gene). These modified flies can breed with wild flies and only the genes of the modified flies are passed on in the surviving offspring. Thus, when they introduced some of these modified flies into a normal fly population in the lab, they found that within several generations, all of the flies contained the test gene.

Selfish genes in practice: ethical obstacles

While intriguing and exciting as a creative way to rid the world of malaria, this research is definitely not without its caveats or reasons for caution. For starters, applying this “selfish gene”-driven population replacement model for mosquitoes in the real world is still technically prohibitive. Researchers know far less about the genes of mosquitoes than they do about the genes of fruit flies, so extensive research would need to be done to find the appropriate toxin/antidote combination in mosquitoes. In particular, researchers would need to learn how to introduce these genes into mosquitoes such that the toxin is produced by the mother, the antidote is present in her eggs, and both of these genes are packaged and transmitted with the bumble bee venom gene. Beyond that, there would be even more vital ethical considerations that accompany the suggestion of releasing a genetically engineered insect into our environment. Could we predict how these mosquitoes and their genes would behave in a real life situation with innumerable variables and complications? For now, these questions are answered only by the musings of science fiction writers. However, this research will hopefully open the door to conversations about the advantages and disadvantages of such potential science of the future in scientific, public, and political circles.

— Amy Vashlishan, Harvard Medical School

For More Information:

World Health Organization < >

Primary Literature:

“Selfish Genes Could Help Disease-Free Mosquitos Spread.” Science. 30 March 2007 315: 1777-1778

Chen, C.H. et al. “A synthetic Maternal-Effect Selfish Genetic Element Drives Population Replacement in Drosophila” 27 April 2007 316: 597-600 (published online 28 March 2007)

Moreira, L.A. et al. “Bee Venom Phospholipase Inhibits Malaria Parasite Development in Transgenic Mosquitoes” J. Biol. Chem., Vol. 277:43. p 40839. 2001

Ito, J. et al. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite” Nature 417. p 452. May 2002

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