Prevention is Better than Cure

Scientists at Imperial College, London, point the way to stopping malaria at its source: the mosquito

Malaria remains one of the world's most intransigent diseases, causing suffering and posing serious threats to development in some of the world's poorest countries. Transmitted through the bite of a female mosquito (Anopheles stephensi), it affects more than 300 million people and causes more than one million deaths each year, 90 percent of which occur in Africa. According to the World Health Organisation (WHO), most of these deaths are among children under the age of five. Pregnant women are also especially vulnerable to this disease, which is increasingly resistant to the drugs used to treat it. Malaria is characterised by the WHO as 'both a disease of poverty and a cause of poverty'. As no effective vaccination been developed and none is on the horizon, the situation seems to hold little promise for those whose lives and livelihoods are threatened by the disease.

Now progress in the field of genetics has led scientists from Imperial College, London, to map the means by which it could be eradicated - not by treatment but by prevention. Genetically modified mosquitoes that do not transmit malaria were first bred under laboratory conditions three years ago. The hope has been that such a strain, if released into the wild, would become absorbed into the native population and spread the gene that stops the transmission of the malaria parasite, thus transforming the insects from 'disease carriers to disease fighters.'

Unfortunately this hope has so far been thwarted. It seems that the transgenic mosquitoes do not have the clout to dominate over their wild relatives. On the contrary, they quickly die out if they breed freely with their unmodified counterparts. The Imperial College Study, in which the transgenic mosquitoes were mated with unmodified insects showed that the beneficial gene was lost over the course of between 4 and 16 generations. Given the short life-cycle of the insects, this represents only a very slight time span. Infinite numbers of mosquitoes would therefore need to be released in a particular place to give them a hope of replacing the wild, parasite-riddled varieties - meaning that the scale and cost of such an activity would probably be prohibitive.

However, the scientists involved in the project, which is funded by the Wellcome Trust, are confident that what has been learnt points the way ahead. Now they have to carry out feasibility studies and look at the costs involved to see if they can find solutions to the problems they have encountered. Surmounting these difficulties would make possible not just a malaria-free future but would also allow similar techniques to be applied in fighting yellow fever and dengue.
The obstacle race
Professor Andrea Crisanti, who has recently jointly published a paper on these studies, acknowledges that further work is needed on the molecular genetics of the problem: 'an increasingly important challenge is to study the population biology of transformed mosquitoes and understand how a beneficial gene can be driven through a wild population,' he says.
He recognises too that public concern over genetic modification in general means that the environmental and bio-safety aspects of the work will play an important role. The population studies being undertaken by himself and his team will be essential to the regulatory processes associated with such issues.

Mathematical modelling, carried out by Professor Charles Godfray also at Imperial College is helping the scientists to understand more about how the GM mosquitoes react in mixed populations. Already it seems as if one problem has been identified. As the GM mosquitoes have been bred from a single ancestor, it may be that inbreeding is causing the introduced gene to become associated with detrimental mutations. While these do not actually kill the mosquito, they impair its competitiveness with unmodified insects. Fortunately such effects can be overcome by cross-breeding.

Hope for the future

While current weapons against malaria remain inadequate to protect the thousands of very young children who die each year from this cruel disease, the research being conducted by the Imperial College team holds real hope that the end is in sight.

References:
Catteruccia, F., Godfray, C. J. & Crisanti, A. Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes. Science, 299, 1225 - 1227, (2003).
Catteruccia, F. et al. Stable germline transformation of the malaria mosquito Anopheles stephensi. Nature, 405, 959 - 962, (2003).

For further information, please contact:
Judith Moore
Imperial College of Science, Technology and Medicine
j.h.moore@ic.ac.uk
+44 (0) 20 7594 6702