Superb article by the evolutionary biologist Christophe Boete on the limitations of GM mosquitoes.
More of Boete's papers available at http://cboete.free.fr/publications.html
The French original of this article available at
Genetically modified mosquitoes and malaria
Nets still protect best
By Christophe Boete
Translated by Donald Hounam Le Monde diplomatique, August 2006 http://mondediplo.com/2006/08/12malaria
Christophe Boete researches evolutionary ecology at the Institut de recherche pour le developpement-Centre national de la recherche scientifique, Montpellier, and is editor of 'Genetically Modified Mosquitoes and Malaria Control' (Eurekah/Landes Bioscience, Georgetown, Texas, 2006)
Scientists are researching the use of genetically modified mosquitoes to destroy the malaria parasite. Will this approach be more successful than previous chemical and technological campaigns against the disease? Simple solutions, properly carried out, work just as well.
By Christophe Boete
A new weapon may be deployed in the struggle against malaria over the next few years: genetically modified mosquitoes. The struggle matters, since malaria is one of the most serious threats to global public health, affects almost 10% of the world’s population and may kill between one and three million people annually. Africa, with 90% of the deaths (which are especially high among the under-fives), is most afflicted by the Plasmodium falciparum parasite.
The parasitic nature of malaria was discovered late in the 19th century and the parasite soon identified. A little later female mosquitoes of the Anopheles species were proved to be responsible for transmission. Yet over a century later, the disease still rages. There was a successful eradication programme during the 1950s and 1960s, particularly in India, Zanzibar and what was the Soviet Union. But the costs, the development of resistance to dichlorodiphenyl-trichloroethane (DDT) and the misgivings of communities about operations to eliminate mosquitoes finally halted the programme. Interest lapsed, particularly with the eradication of malaria from Europe and North America.
Now the disease is returning and mortality has more than doubled over the past 20 years. There are biological, socio-economic and political factors. The parasite's resistance to medicines, the mosquito's immunity to many insecticides, environmental changes and new agricultural practices have all made control more difficult.
In some parts of Swaziland, irrigation for export crops such as sugar cane has caused a resurgence. Thai rubber plantations provide a habitat that suits vector mosquitoes (1). The construction of dams in Ethiopia has led to an increase in transmission of the disease. Other factors include political instability in developing countries, wars, the flow of refugees into camps and the collapse of health systems, particularly after structural adjustment programmes imposed by the International Monetary Fund. As a symptom of underdevelopment and poverty, malaria is rising, start-lingly in some republics of the former Soviet Union (especially Tajikistan in the late 1990s) and in Nicaragua. It is estimated that without effective counter-strategies the number of victims will double again in the next 20 years.
Technology to the rescue
With current methods regarded as inadequate, the interruption of disease transmission is seen as the most promising of many new techniques being considered. Research is being funded to develop mosquitoes that have been genetically modified to kill the parasite. The Bill & Melinda Gates Foundation has donated almost $20m to a consortium led by Anthony James of the University of California, Irvine, to develop technological and transgenic approaches against vectorial diseases such as dengue and malaria.
The idea of creating these targeted GM organisms was inspired by recent molecular research into the control of malaria. In the early 1990s a small group of molecular biologists met at a conference convened in Tucson, Arizona, and agreed on a 20-year programme to develop a GM mosquito. Two of the project's three major stages would be technological; the third would concentrate on the ecology and biology of mosquito populations to discover how, once a GM mosquito had been created, it could successfully establish itself in the natural environment.
The idea is to prevent transmission by substituting non-vectorial for vectorial mosquito populations. Researchers set a series of goals. By 2000 they would achieve the stable transformation of Anopheles mosquitoes. By 2005 they would develop Anopheles mosquitoes that were not vectors for malaria. Finally they would conduct controlled experiments to determine how to make this genotype propagate among wild populations by 2010.
So far, a team from the United States has succeeded in creating a resistant transgenic mosquito; but its resistance is to Plasmodium berghei, which attacks rodents, not to Plasmodium falciparum.
The programme's use of molecular techniques to control malaria was ambitious and pioneering, which partly explains why attention has concentrated on its technological aspects at the expense of ecological and epidemiological considerations. But these are fundamental to predicting the success or failure of the propagation of resistance to the Plasmodium parasite among wild populations of mosquitoes and to estimating the real public health benefits.
Scientific ecologists and molecular biologists have called for more funding, to determine whether GM mosquitoes can be successfully deployed and because the creation of such an organism demands further expensive hi-tech research. But is such a technological, futuristic approach the way forward? The scientific consensus is that the most effective way to combat malaria is through a combination of methods. It is difficult to see how GM mosquitoes can be made to work alongside other vector control programmes. Current anti-vectorial campaigns will presumably have to be halted while GM mosquitoes are introduced, which may not be wise in countries afflicted by other insect-borne diseases or in areas where Anopheles is not the only species of vector mosquito.
Malaria transmission will continue and in many contexts the removal of one species will do little or nothing to improve the overall epidemiological situation. Perhaps we should also fear the natural selection of parasites capable of bypassing the new resistance. There are many examples of the selection of such a mechanism, among bacteria contending with antibiotics or among mosquitoes faced with insecticides.
No doubt scientists will rush to back the project, inspired by the sequencing in 2002 of one of the four types of human malaria (Plasmodium falciparum) and one of its many vectors (Anopheles gambiae). Results from optimistic mathematical models have allowed their authors to declare: "Once the ethical and economic implications of GM mosquito introduction have been settled, we may be able to rid the world of malaria in a short period of time" (2).
Such announcements are about as realistic as predictions that GM plants will solve world hunger. In its pursuit of progress, science is in danger of being seduced by reductionist, mechanistic approaches like those offered by molecular biology (3). This encourages cuttingedge solutions at the expense of those that rely on simple techniques. Molecular biology has indeed made important discoveries and found solutions to major scientific problems, but it cannot replace other fundamental disciplines such as ecology and epidemiology. Meanwhile the technical nature of its analyses makes it impenetrable to the uninitiated.
Molecular biologists often regard ecological issues as mere formalities to be dealt with by cutting-edge solutions. Maybe this is optimism, utopianism or simple ignorance. Or maybe is it bad faith.
Ecologists have sought funding to research the ecology and biology of mosquito populations. Biological and evolutionary approaches should try to determine the main factors that may influence resistance to Plasmodium once transgenic mosquitoes are released into the wild.
They should also raise questions about long-term consequences: will there be a real fall in mortality and morbidity, or will natural evolution allow the parasite to circumvent this resistance? There must be proof of the validity of the technique, since there is more at stake than research grants and articles in scientific journals. Molecular biologists have already begun work on the required ecological studies and, although their conclusions are not very positive, they agree that technological solutions should work.
In Europe and North America, malaria was eradicated decades ago without genomic techniques, mostly because there was political will to carry through economic and social changes including the draining of stagnant water, improvements to living conditions and systematic treatment of the disease. Transgenic mosquitoes may be a scientific breakthrough, but they will be ineffective unless their introduction is followed by a long-term, large-scale, organised and adequately funded campaign.
That genomics is perceived as crucial in the struggle against malaria may unfairly skew the allocation of limited resources between research and control programmes. More worryingly, as work by two British researchers on the control of trypanosomiasis (sleeping sickness) in Africa has revealed, programmes involving cutting-edge technologies tend to depend on external expertise and technology that require a large preliminary investment. So any failure results in massive debt and less money for traditional control methods. The response is that established methods do not draw their funding from the same sources as those based on cutting-edge technologies. It is also pointed out that established methods face major problems of implementation: less than 2% of Africans at risk use impregnated mosquito nets, even though the Abuja declaration (4) called for 60% coverage by 2005. If such simple methods are ineffective, why should more complex methods succeed?
The debate about the legal and ethical implications of transgenic mosquitoes has been mostly futile. Little attention has been paid to the precautionary principle or to the possible negative consequences of introducing transgenic mosquitoes. There have been symposiums and workshops devoted to the new technology (London 2001, Atlanta 2001, Wageningen 2002, Nairobi 2004) but these have not always consulted those at risk from malaria. It is essential to involve communities and NGOs.
It has been claimed that the development of infrastructures and technologies associated with transgenic mosquitoes is of absolute importance in Africa (5). What use are these without the development of organisations capable of defining the direction that science and technology should take, in both developed countries and those where malaria is endemic? This is essential to the democratisation of science and technology.
According to a document published by the Intermediate Technology Development Group: "The development process for most new technologies still uses a model unchanged since the 19th century: first, optimise the technology, then check user acceptance, and finally examine any regulations governing its use. Given the investments made in the earlier stages, it becomes difficult to redesign a technology even when potentially harmful social effects have been subsequently identified. Hence, when faced with opposition to a new technology, policymakers are forced into defending the technology, a technocratic managerial response in which potential social and environmental impacts, identified outside the narrow design process, are regarded as problems of user acceptance" (6).
If scientists working on GM mosquitoes had to talk to the rest of society, they would have to devise an accessible, jargon-free way to describe what they were doing. They would benefit from allowing the potential beneficiaries of their research to evaluate its relevance and potential dangers.
There have been too many damaging failures in the history of the struggle against malaria, such as the irradiated sporozoite vaccine tried in the 1960s. There is nothing glamorous about the most effective tools in current use, including the free distribution and use of impregnated nets, artemisine-derived medicines and better housing. It is also necessary to provide finance and logistics to improve or facilitate access to high-quality local healthcare, often a casualty of collapsing states, structural adjustment programmes and neoliberal policies. None of this has much to do with powerful 21st-century biotechnology.
It is inevitable that malaria research, including that into vector mosquitoes, will lead to biological discoveries with unforeseen consequences. The danger is that the struggle against malaria will be blamed for those consequences and will have its funding cut.
There is a further cause for concern: science may be changing into pure technoscience (7). As pressure for applicable results threatens freedom of research, a science fixated on technological innovation could eclipse a science whose only function is to satisfy human curiosity. We should remember the words of the biochemist Erwin Chargaff, who dismissed as arrogant the belief that science could make the world a better place. Within today's scientific community there should be honesty and modesty about motives and about the results of research and their potential benefits for humanity.
(1) A vector is an organism that transmits a parasite between hosts; see http://sutteryubamvcd.org/glossary.htm
(2) Matthew Hahn and Sergey Nuzhdin, "The fixation of malaria refractoriness in mosquitoes", Current Biology, London, vol 14, 2004.
(3) Pierre-Henri Gouyon, "Pas de progres sans raison ni precaution", POUR (Revue du groupe de recherche pour l'education et la prospective), no 178, Paris, 2003.
(4) In 2000 African leaders meeting in Nigeria agreed on the need to take effective action against malaria.
(5) Hassan Mshinda, Gerry Killeen, ed, "The development of genetically modified mosquitoes in Africa", The Lancet Infectious Diseases, London, vol 4, 2004.
(6) Tom Wakeford, Democratising Technology: Reclaiming Science for Sustainable Development, ITDG-Practical Action, Rugby, Britain, 2004.
(7) Jacques Ellul, The Technological Society, Jonathan Cape, London, 1965.