Genes and dreams

Scientists are on the breakthrough of better malaria drugs

Published: Thursday 31 October 2002

-- with the recent genome decoding of both the malaria parasite Plasmodium falciparum and its vector Anopheles gambiae, scientists have got a vital framework for exploring new ways to block disease transmission at molecular and cellular levels. The feat is particularly significant as both the parasite and the vector are associated with the most severe form of the disease. The work was accomplished by an international team of 160 researchers from 10 different countries. They took nearly six years to map the 5,300 genes of the P falciparum, but just three months to map the 14,000 genes of the mosquito.

Though the immediate use of the new knowledge is uncertain, researchers feel that the gene cataloguing would help decide future research areas for developing better drugs. "The sequencing heralds a new era in the fight against malaria. When joined with information we have about the human genome, a much fuller understanding of the disease and its transmission would be possible," says Anthony S Fauci, director of the Bethesda-based National Institute of Allergy and Infectious Diseases.
In the pipeline One of the major hindrances in controlling the disease is the complex lifecycle of P falciparum. It has four stages in its lifecycle and each of them is vastly different from the other. It is essential to develop a single vaccine that is effective against all the four stages. Knowledge of the genome may make this possible. The genetic map would also help in utilising the existing knowledge in a better way. For instance, researchers at Justus Liebig University of Giessen, Germany, used the parasite's unfinished sequence to identify genes of a particular enzyme, secretion of which is known to be essential for P falciparum's functioning. By transferring the gene into a bacterium, the researchers were able to test several drugs. They found that the antibiotic fosmidomycin could block the enzymes' activity.

The genetic map of the vector would help in developing better insecticides and repellents. Mosquitoes produce enzymes to break down insecticides. The genome could help find ways of inactivating these enzymes. Furthermore, as the mosquito also tries to fight the pathogen, strengthening this response could help in controlling the parasite. The researchers have also found a set of genes, which are smell receptors and analysing these might explain the particular preference of the mosquito for human blood.

Genetically modifying mosquitoes to disable them is, however, not a viable proposition. Researchers worry that if the modified mosquitoes are transferred into the wild population, they might remain stable only for a short period of time: the mosquitoes could revert to their vector status. This could have adverse effects, as the temporary halt in disease transmission would lead to humans losing their natural immunity, as a result of which the disease would assume more overwhelming proportions once the parasite reverts.
Poor man's hope The genome would go a long way in helping developing countries such as India, where the disease kills more than 20,000 people every year. " P falciparum is prevalent in India and availability of its genetic map would be beneficial for research," says Sarala K Subbarao, director of the New Delhi-based Malaria Research Centre. Moreover, even though A gambiae is not found in India, Subbaroa feels that its similarity to Anopheles culicifacies -- the species prevalent in India -- would tremendously help. For example, A gambiae has developed resistance against synthetic pyrethroids that are used in Africa to control its spread. As the Indian species is also doing the same, we could utilise future research that would be carried out in this context.

However, there are some scientists who fear that the genome knowledge would divert scant funds available in developing countries from more orthodox malaria research to areas that might not be really helpful. There is also a fear that the drug development bandwagon based on the genome knowledge might further delay vaccine discovery in developed countries.

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