Malaria: Genetic control (experimental)

Among the 400 species of Anopheles mosquitoes, only a limited number can be infected with plasmodia. The other mosquitoes are genetically resistant to this infection. If the natural mosquito population could be replaced by a genetically resistant population it would stop the transmission of malaria. There are a number of problems, however. First, the mosquito genes which make the parasite’s cycle in the mosquito impossible would have to be isolated and understood. It would then be necessary to find a way to bring those genes into a natural vector and to make them function properly. Thirdly and most difficult, the transgenic mosquito must have a competitive advantage over the natural vector in the Darwinian battle for survival. It is highly unlikely that a mosquito strain selected in a laboratory would be able to compete with wild-type mosquitoes. New, malaria-resistant mosquitoes would probably not be able to force out a natural population (so they would need to have a selective survival advantage). They should of course also not transmit other diseases. Fourthly, the Anopheles gambiae populations have various subpopulations which do not mix much. This partially sexual isolation of the natural mosquito populations would make the transgenic vector method extremely difficult.

One possible approach would be to spread a gene which codes for resistance in the mosquito in a wild population, e.g. if it can be coupled to transposons (these small DNA sequences are not inherited according to Mendel’s law, i.e. all the progeny contain the elements, cf. the transposon P in Drosophila). A reasonable amount of work has already been carried out on the transposon Minos which can penetrate the genome of Anopheles stephensi. Research into the use of Wolbachia, intracellular bacteria related to rickettsia, is a hot topic. They take their generic name from the microbiologist Wolbach of Harvard Medical School (1920). These non-pathogenic symbionts can quickly spread in a natural population. They cause a reproductive imbalance in mosquitoes (an infected population replaces a non-infected one). Thus, for example, Wolbachia pipientis infects gonadal tissue from both male and female mosquitoes. [Symbiont-free insects can be cultured in the laboratory by feeding them tetracyclines]. An infected female can pair successfully with both infected and non-infected males and her progeny are themselves fertile whereas a non-infected female can only pair productively with a non-infected male. Insemination of a non-infected female by an infected male leads to non-viable ova (cytoplasmic incompatibility). An infected female lays infected eggs. The general consequence is that infected females have a reproductive advantage. A mosquito population infected with these bacteria quickly replaces a virginal population. Transgenic Wolbachia which interfere with the maturation of malaria parasites in a natural vector, are a theoretical possibility which is being studied. In the genus Anopheles there are, however, no Wolbachia known which infect natural populations. The last word about such transgenic mosquitoes has not yet, however, been said. If the public outcry against genetically manipulated food is a guide, any method which uses transgenic malaria vectors will have to be able to convince public opinion that there is no better alternative.

Category: Medicine Notes