I mention this article, because it is interesting for three reasons. For one, mosquito-borne illnesses are a major world health problem, and anything that holds promise for defeating them is a matter of interest. Second, it raises some knotty bioethical questions. Unlike the issue I discussed in my prior posts (1 2) on genetically-modified rice, the technology here would be a deliberate attempt to cause a major change in a complex ecosystem, and would have a higher potential for unanticipated consequences. It also would have a higher potential for great benefit. Third, it is a very good illustration of the importance of a good understanding of evolutionary theory in the field of medicine.
Genetic Strategies for Controlling Mosquito-Borne Diseases
Engineered genes that block the transmission of malaria and dengue can hitch a ride on selfish DNA and spread into wild populations
Fred Gould, Krisztian Magori, Yunxin Huang
American Scientist
Volume: 94 Number: 3 Page: 238
DOI: 10.1511/2006.3.238
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities. To combat malaria and dengue, health agencies try to get rid of mosquitoes, which transmit both diseases. But a scarcity of resources hampers most control programs, and the insects are increasingly resistant to pesticides after decades of patchwork spraying. The disease organisms are evolving, too: The single-celled microbes that cause malaria are becoming resistant to widely used, inexpensive anti-malarial drugs such as chloroquine, which have been the first-choice treatment for malaria. (Drug therapies for dengue virus have never been available.) Many research teams are trying to develop vaccines for these diseases, but the complex biology of the two parasites—malaria is caused by four species of the protist Plasmodium, and four different viruses, or serotypes, can cause dengue—makes it difficult to predict whether vaccination will eventually confer broad immunity. And although pesticide-treated bed nets offer a promising low-tech means of preventing bites from malarial mosquitoes at night, the mosquitoes that carry dengue bite during the day.
To oppose these grim realities, several research teams (including our group at North Carolina State University) are now exploring a different approach to controlling the spread of mosquito-borne diseases, one that would reduce an insect's ability to transmit disease or would induce a population crash among selected disease-carrying species. How could either of these goals be achieved? By creating genetic changes in wild mosquitoes. Biologists have already extinguished other insect pests with genetic methods and in the laboratory have blocked the transmission of dengue and malaria in mosquitoes with engineered fragments of DNA. If scientists could breed some of those same genes into the wild mosquito population, the insect's bite might still be a nuisance—but it would no longer be a threat...
The first point of interest, that mosquito-borne illnesses are a major health problem, hardly requires elaboration. Malaria alone kills about one million people per year, most of them being young children, and most of those being in Africa. Dengue infects about 50 million people per year, with a mortality rate of 2.5 to 5% (20%, if untreated). The economic impact of each of these illness is astronomical.
The second point of interest, that the techniques mentioned in the article raise bioethical questions, is illstruted by the following:
Too much success could also cause trouble in the future. For example, if all the mosquitoes in a certain region were dengue-free, then a growing fraction of the population would never have been exposed to the virus. If dengue then evolved so that it could hitch a ride even on a transgene-carrying mosquito, then the human population could be vulnerable to an epidemic...Given the evolutionary plasticity of microbes there is no room for complacency...The uncertainty, effort and expense have led some scientists on the front lines in the fight against mosquito-borne diseases to oppose this line of high-tech research.
The article goes into greater detail about the potential problems. It is not my intention to discuss all the potential problems in detail, but I do want to highlight the fact that there will be risks, and considerable political opposition, to the use of genetically-modified disease vectors.
One thing that the article does not mention, and that I hesitate to even mention, is the possibility that advances in this area could potentially be used to make mosquitoes more effective at transmitting diseases. It is hard to imagine that anyone would seriously be seriously interested in doing so, but warlike persons have been known to do some pretty crazy things.
The final point of interest, that the article illustrates how important evolutionary theory is to medicine, probably needs no explanation to anyone who has gotten this far in reading this post. The article contains an interesting discussion of some of the nitty-gritty details of evolution. They discuss how it might be possible to get the genetically-modified mosquitoes to become predominant in a population, even if the modifications cause a selective disadvantage:
The idea of designing a gene that actively spreads through a pest population without conveying some fitness advantage is not new. A Soviet geneticist, Alexander S. Serebrovskii of Moscow University, and a British biologist, Frederic L. Vanderplank of the Tanganyika (Tanzania) Research Department, sowedthe intellectual seeds for this approach in the 1940s. The two men realized independently that in certain circumstances, competition between two interbreeding insect strains doesn't favor the fitter group. This dynamic involves the genetic property that scientists call underdominance, which can actually cause the strain with greater fitness to die out...
This is a complex idea, from my point of view, not being an expert in population genetics. They explain it fairly well, although I expect that someone who is not familiar with evolutionary concepts would have a hard time following it. They mention in the article, that the Gates Foundation has devoted $35 million to the project. If it works out, it could be one of the greatest advances in world health in this century. Even if it does not, it should contribute to our understanding of evolutionary principles in general, and the evolution of mosquito-borne disease in particular. That alone would be worth the price. The main point, though, is that this novel approach to fighting disease simply would not be possible without a detailed understanding of evolution.
Comments
Great review of the issue.
The good thing is that this is done by an evolutionary biologist Fred Gould, who has left a question about mosquitoes on his blog to which I linked late last night, so if anyone knows anything about mosquito ecology/physiology/behavior, see if you can answer his question.
Posted by: coturnix | July 23, 2006 7:55 PM