This important article by the evolutionary biologist Christophe Boete - a researcher at the Institute of Research for Development (IRD, Montpellier, France) - was translated into English for GM Watch by Claire Robinson.
The French original and references at
http://www.ircm.qc.ca/bioethique/obsgenetique/cadrages/cadr2007/c_no32_07/c_no32_07_02.html
NOTE: L'Observatoire de la Genetique is a periodical of IRCM's Centre de Bioethique (Centre for Bioethics). IRCM = Institut de recherches cliniques de Montreal [Clinical Research Institute of Montreal], affiliated with the Universite de Montreal.
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GM mosquitoes to fight malaria: at what price?
IRCM, L'Observatoire de la Genetique, No. 32 April/May 2007
The scientific media and reviews increasingly repeat the promise of the use of GM mosquitoes to fight malaria. However, as the author of this article explains, the success of such a use is only hypothetical and many questions remain unanswered. If research on GM mosquitoes can lead to useful and beneficial discoveries, it is however vital that it is not carried out at the expense of financing and access of the affected populations to prevention and treatments that exist right now. A plea in favour of the precautionary principle and the democratic orientation of science.
Christophe Boete*
In January 2006, a citizens' jury of cotton producers of the area of Sikasso (Mali) decided unanimously against the introduction of GMOs in their country. This exercise in participatory democracy, named "Citizens' Space of Democratic Interpellation [a procedure in some legislative bodies of asking a government official to explain an act or policy]" (ECID) was held at the request of the general assembly of Sikasso in order to obtain the opinion of cotton producers on the introduction of the GMOs into agriculture in Mali (1). What would be the result of such a step if the question did not relate to agricultural seeds, but to releasing GM mosquitoes, a hypothetical future means of fighting malaria?
There is a lot at stake, since the situation as regards malaria is far from improving: mortality has more than doubled during the last twenty years, because of biological factors (resistance to drugs, for example), but also because of political and socio-economic factors due in particular to measures of strict budgetary policy and reforms of public services dictated by structural adjustment plans of the IMF (2). Moreover, without effective intervention, it is estimated that the number of victims will double again in the next twenty years. It thus appears urgent to take all measurements likely to stop the propagation of this disease, which is mainly prevalent in developing countries.
Besides the tools of prevention and treatment we have right now (improvement of habitat, adequate treatment, impregnated mosquito nets, etc.), a number of researchers are exploring new paths. Among those, there is one that is being once again talked about in the press: GM mosquitoes.
Fighting malaria using GM mosquitoes
Researchers hope to create GM mosquitoes that are able to kill the malarial parasites and, in particular, Plasmodium falciparum, the species considered most dangerous of those able to infect man, in order to stop the transmission and the propagation of the disease. The objective is not to remove the mosquito vectors of malaria, but to replace all or part of the malaria-vector population with mosquitoes which, because of the genetic modification, should no longer transmit the parasite.
As for the method which would make it possible to achieve this goal, it was planned by a small group of molecular biologists at a meeting which took place at the beginning of the 1990s at Tucson, Arizona, USA(3). It is based on an ambitious programme which puts great emphasis on technology and does not seem to take account of any ecological, evolutionary and epidemiological aspects. The plan has three phases:
*to genetically modify in a stable way vector mosquitoes of the Anopheles type; *to genetically modify a mosquito so that it is resistant to the Plasmodium parasite and thus can no longer be the vector for it; *and finally, to understand how to provoke and control the propagation of this resistance to Plasmodium in natural populations.
To date, the first two stages have been achieved, but only to a certain extent. In effect, if a stable transformation were carried out and a mosquito resistant to Plasmodium were created, its resistance would be limited to the parasite Plasmodium berghei, a parasite of rodents which does not affect man.
As for the stage of propagation, a necessary condition, but insufficient to ensure the success of this method, it remains problematic today. Indeed, a recent study published by an American team showed that even under extremely favorable artificial conditions, it is difficult to introduce the genetic modification which is responsible for resistance to the parasite, into the whole target population of mosquitoes (4).
Lastly, as we shall further see, epidemiological and evolutionary aspects are often perplexing, when one takes into account the many pitfalls that must be avoided (5,6).
As yet unanswered questions ... and a dubious success
Thus, if the potential use of GM mosquitoes to combat malaria is considered by certain scientists, the effectiveness of this means of combat remains very dubious. It is therefore essential that the researchers involved in this type of research do not exploit hopes based on hypothetical solution that they present with an excessive, even delirious, optimism (7).
If they should avoid such optimistic flights in favour of technological progress, the researchers should also avoid exploiting certain fears in order to obtain more funds and in order to justify their research on GM mosquitoes. It is however the impression that they give when they put forward the possible risk of the appearance of parasitic stocks more virulent than those existing currently, or worse, of a hypothetical transmission of a virus hitherto not transmitted by mosquitoes. In effect, what is known about these significant points? Absolutely nothing. At the present time, it is not known, for example, if the introduction of genetic resistance to Plasmodium falciparum could provoke the selection of parasites more virulent for man (8). On the contrary, it is perfectly possible that the selection will work in favour of a more virulent stock against the mosquito itself, which actually would reinforce the effectiveness of a anti-malaria campaign based on GM mosquitoes.
In short, few things are known about the potential consequences of the use of GM mosquitoes and it is first a matter of putting relatively simple questions in order to know if this method can be valid: will resistance to the parasite be able to propagate in natural mosquito populations? Under what conditions? What will be the effect of this resistance on the epidemiology of the Plasmodium species mainly targeted (Plasmodium falciparum), but also on that of the minor species (9)? Will mechanisms of evolution select strains of parasites able to escape this resistance of the mosquito? If such a selection were to intervene, the situation could be similar to that caused during the 1950s and 1960s at the time of the malaria eradication programme involving the massive use of DDT. Indeed, that programme led to the selection of a resistance to DTT in the vector mosquitoes and has proved a failure. In spite of that, very few studies to date focus on the impact of ecology and evolution on such a campaign and the few results published in this respect prompt scepticism (5,6,10).
Need for adopting a responsible and democratic approach
Another point which raises a problem is that the development of this new technology seems unfortunately to follow the same road as that borrowed from a model dating from the 19th century and described in these terms by Tom Wakeford in a document for the Intermediate Technology Development Group (ITDG) (11): "Development, for the majority of new technologies, employs a model unchanged since the 19th century - initially, to optimize the technology, then to check acceptance by the users, and finally to examine all regulations governing its use. Given the investments made in the first stages, it becomes difficult to re-develop a technology when potentially harmful social effects are identified later. Consequently, once confronted with the opposition to a new technology, the decision makers are obliged to defend it, a technocratic management response in which potential effects on society or the environment identified outside the narrow process of design are regarded as problems of acceptance by the users."
Legal and ethical issues relating to the use of GM mosquitoes to fight malaria have received little attention. Moreover, civil society, communities concerned in the countries affected by endemic disease, associations working in the fields of development and public health, and NGOs were not consulted, while at the same time it seems vital to involve them in the process. It is now clear that the development of infrastructures and technologies relative to GM mosquitoes must involve those active in Africa (12). But, it is necessary also that this development is carried out so as to ensure the presence of democratic structures allowing informed and critical choices as to the orientation of sciences and technologies (13).
As for the decision makers, they should allow themselves to be guided by the precautionary principle which, in essence, recommends avoiding using a technology when the risks concerned are not rigorously evaluated and when they could exceed the anticipated benefits. It is this principle that should prevail when one plans to introduce GM mosquitoes into a natural environment for medical purposes.
Acting also and above all on the socio-economic level and with current means of combating malaria
Lastly, it is wise to recall that effective means to fight malaria exist already (drugs, impregnated mosquito nets, ...), but that very often, for the populations concerned, access is lacking. This is the sad corollary of an economic ruin largely caused by the ultra-liberal policies of the IMF (2,14). Indeed, how can one not connect this point to the study led by Paul Reiter on the cases of dengue fever (a viral infection, potentially fatal, transmitted by mosquitoes) on both sides of the border which separates Mexico from Texas (15). Between 1980 and 1999, in Texas, the number of cases of contracted dengue was 64, whereas it was 62,514 in the three adjacent Mexican states (Coahuila, Nuevo Leon and Tamaulipas). Such a contrast cannot be ascribed to global warming, but can well be ascribed to differences in the socio-economic conditions between the states of these two countries. It is necessary to work on economic levers, investing in social programmes rather than in emerging research, if one wants truly to place oneself in sight of an improvement in public health.
In addition, many false hopes have been raised in the fight against malaria during the last decades. The urgent need is to improve or facilitate access to, and use of, the current means of combating malaria: improvement of habitat, free distribution and use of impregnated mosquito nets, the access to quality care, the early diagnosis and adequate treatment by the derivatives of artemisinin (a natural substance [derived from wormwood, artemisia] contained in a new generation of drugs against malaria).
Without doubt, any research concerning the various aspects of malaria will bring unforeseen beneficial discoveries, but it is necessary to bear in mind that the financial dictates favoring research on GM mosquitoes could work to the detriment of financing and effective use of the current means of fighting malaria. Simultaneously with this risk, one might fear that science may lose its freedom if it is forced to be the bearer of concrete applications, as occurs when it is subject to geopolitical considerations or financial interests. Reduced to a medium of the technique, it would be no more than a technoscience, as Jacques Ellul said in his criticism of the technical society (16).
Whether one wonders what will become of science or one invests in the improvement of public health in developing countries, it is always necessary to entertain the results of scientific research and their possible effects on humanity with modesty and the greatest precaution.
Meanwhile, the situation of malaria does not improve and, without wanting to be cynical, the funds poured into research on GM mosquitoes, as into GM agriculture (17), remain a godsend for many research laboratories.
*Christophe Boete is a researcher at the Institute of Research for Development (IRD, Montpellier, France). He holds a doctorate in ecology from the Pierre and Marie Curie University of Paris and a post-doctoral qualification at the University of Wageningen (Netherlands) and in the Joint Malaria Programmes in Moshi, Tanzania...