The lesser evil

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The lesser evil
The lesser evil

The Lesser Evil

Mutant mosquitoes could one day become a powerful weapon in the fight against malaria. A research team has found a substance in mosquitoes that is necessary for the development cycle of the malaria pathogen. Mutant insects that lack this substance would pose a serious problem for the parasite. The scientists might not be able to kill two mosquitoes with one stone, but they could at least play them off against each other. The substance is xanthurenic acid (4,8-dihydroxyquinoline-2-carboxylic acid). It is a by-product of the production of eye pigment in Anopholes mosquitoes. It is quite possible that the parasitic Plasmodium cannot use mutant mosquitoes, which cannot produce eye pigment, as hosts. Because without the substance, the parasites are unable to reproduce.

Howard R. Morris of Imperial College, University of London and his colleagues have followed earlier evidence that pointed to an important chemical component in controlling the developmental cycle of Plasmodium. When mosquitoes alight on a human for a blood spree, they ingest human red blood cells that are infested with parasites at what is called the gametocyte phase of their complex life cycle. Within seconds, the parasites undergo a change called gametogenesis. In the course of this they become sex cells, which emerge from the red blood cells, unite and multiply. From these oocytes, the asexual sporozoites form in the salivary glands of the mosquito. It is these sporozoites that the bloodthirsty mosquito injects into the nearest human. There they continue to develop, invade red blood cells and become gametocytes, completing the cycle.

What causes gametogenesis to occur so suddenly? The sudden drop in temperature from the warm human to the relatively cool mosquito is an important factor. Experiments have also shown how a rapid drop in acidity can also stimulate gametogenesis-but this sudden drop doesn't usually happen inside a mosquito; therefore another factor must be at play. After a patient search, it has now been found that xanthurenic acid appears to be the key (Nature 19 March 1998).

Why Xanthurenic Acid? The answer to this question is not known. Presumably, the parasites require an insect-specific trait such that gametogenesis occurs in a mosquito but is suppressed in the human host. Xanthurenic acid occurs in the human bloodstream in much smaller amounts than in insects.

By researching fruit flies (distant relatives of mosquitoes), scientists discovered how xanthurenic acid is produced as a by-product of eye pigment synthesis. Flies with certain mutations do not make the substance. One day, researchers may be able to breed strains of mutant mosquitoes with a similar defect and release them into the wild. At the moment, however, this project is still a long way off.

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