CLEVELAND, Ohio, May 23, 2002 (ENS) - A genetically altered mosquito could help reduce the threat of malaria, a disease that kills about two million people each year - mostly African children under the age of five. The insect being developed in Cleveland, Ohio, would be less likely to carry the disease, offering an alternative to the use of toxic pesticides to combat malaria.

Conventional approaches to controlling malaria, including heavy spraying of dangerous pesticides such as DDT, have been ineffective, say the researchers at Case Western Reserve University (CWRU) School of Medicine in Cleveland. The team is now working on a transgenic, or genetically altered, version of a mosquito that would be unable to carry the parasite that causes malaria.

Some mosquito bites in tropical parts of the world may carry the parasite that causes malaria. (Photo courtesy Centers for Disease Control and Prevention)

When a mosquito ingests blood from an infected host, the parasite Plasmodium enters the mosquito's body and goes through several transformations before taking a form that the mosquito can pass on by biting another person.

In today's issue of the journal "Nature," CWRU genetics professor Dr. Marcelo Jacobs-Lorena explains that the genetically altered anopheles mosquito he is helping to develop would prevent the malaria parasite from developing into a transmissible form inside the insect.

When a mosquito feeds on an infected individual, the parasite reproduces in the mosquito's gut and takes a form called an ookinete. The ookinetes then move through the lining of the gut into the body of the mosquito and mature into oocysts.

After a period of 10 to 15 days, the cysts burst and thousands of sporozoites are released and invade the mosquito's salivary glands, where they stay until the insect bites the next person.

Plasmodium oocysts on a mosquito's gut will burst to release sporozoites, the version of the malaria parasite that can be transmitted through the mosquito's saliva. (Photo courtesy University of Minnesota)

The protein produced by the SM1 gene binds to the surface of the mosquito's gut, competing with the parasite and inhibiting its development by about 80 percent. The parasites that fail to cross the gut lining die.

The researchers are also pursuing another avenue: inhibiting the parasite's invasion of the mosquito's salivary glands. Jacobs-Lorena said it is important to find ways to block the parasite at a variety of points in its development, because no method is 100 percent effective.

"I think the value of this research is that it will provide an extra weapon," said Jacobs-Lorena. "Drugs and insecticides exist and help, but they are not very effective because of resistance. Vaccines are very hard to develop."

"What we need is a multipronged approach," he added. "The more weapons we have, the more effective it will be in our fight against malaria."

Transforming mosquitoes with multiple genes, each inhibiting parasite development in a different way, will also help researchers counter the development of resistant parasites. As biologists alter the mosquito to resist the malaria parasite, the parasite may evolve into a form that can overcome the new barriers to its development.

Already, the Plasmodium parasite has developed resistance to many malaria treatment medications, and the Anopheles mosquito is no longer affected by some commonly used pesticides.

Dr. Marcelo Jacobs-Lorena, author of the "Nature" report. (Photo courtesy CWRU Department of Genetics)

Critics like the Institute of Science in Society (ISIS, http://www.i-sis.org.uk/), a group which has opposed the release of engineered species without an assessment of their environmental effects, warn that no one knows how engineered insects could affect larger ecosystems.

"The impact of introduced transgenes on humans and the ecosystems must be carefully evaluated before the genes are widely spread around the globe," wrote Professor Joe Cummins in a piece for ISIS in November 2001.

"The impact of transgenic insects must be carefully evaluated, especially in the light of safer methods for controlling malaria already available," such as pesticide treated bed nets, Cummins added.

But supporters say any tactic that might replace the most common method of combating malaria - massive spraying with toxic pesticides - would be a boon for the environment.

Spraying the walls of homes with pesticides is the most common defense against malaria carrying mosquitos. (Photo courtesy University of Minnesota)

Another researcher has used a modified virus to infect a mosquito and stop the spread of the parasite, but that method had several drawbacks, including the fact that the virus could also infect people, and the virus could not be transmitted from one mosquito generation to the next. Once the mosquito died, so ended the virus' capabilities in fighting malaria.

Genetically altering mosquitoes with the SM1 gene does not the insects' lifespan or their ability to reproduce. This is important because one of the challenges to using pesticides against mosquitoes is that once the spraying stops, other mosquitoes can move into the area.

If genetically modified mosquitoes were released into an area where the local population has been destroyed, they would occupy that niche. Jacobs-Lorena said this type of population replacement could be tested in the future.

The Anopheles stephensi mosquitoes are known to transmit malaria on the Indian continent, but not in Africa. Jacobs-Lorena said technology to introduce genes into the mosquitoes that spread malaria through Africa has only recently been achieved, while the technique for introducing genes into Anopheles stephensi was created about two years ago.

Future studies are planned to test the SM1 gene on the African mosquitoes, but funding shortages may slow the research. The current study was supported by grants from the National Institutes of Health and the Special Program for Research and Training in Tropical Diseases, a joint venture of several international organizations.

The "Nature" paper is titled "Transgenic Anopheline Mosquitoes Impaired in Transmission of a Malaria Parasite."