Author: Griffin-Smith Ben
Date: August 2007
When it comes to Malaria, a disease that still kills over one million people every year, mosquitoes are usually our worst enemies. When the mosquitoes suck the blood of an infected host, plasmodium, a protozoan, passes into its blood. The insects act as a carrier of the disease - allowing bacteria to pass into their next victim when they go for their next meal. The malarial parasites use the mosquitoes not only as a vector for spreading infection, but also as a growth chamber, maturing inside the mosquitoes gut.
For years, humanity has been waging a biological war on two fronts. On the one hand, scientists have been developing anti-malarial drugs to combat the disease itself, giving us quinine, chloroquinine, and sulfadoxine-pyrimethamine, to name but a few. These drugs proved effective in treating the disease, but suffered from the same problem all antibiotics face, namely the creation of resistant strains. In addition, the distribution of these drugs is a costly logistical problem, even when the drugs themselves are cheap, many costing less than 20 US cents.
Computer generated image of plasmodium malariae destroying old red blood cells
A Continuing Struggle
The scale of the problem that malaria posed demanded a war that had to be waged against the mosquitoes, instead of directly on the disease. The battle was fought using aggressive and defensive methods. Insecticidal bed-nets greatly reduced the mortality rate in malaria afflicted countries, especially among young children. Targeting the habitats of mosquitoes, draining their breeding grounds or spraying them with insecticide, also proved somewhat effective if not always environmentally sound. But these small victories have never measured up to the true scale of the disease, and no solution has ever proved both complete and permanent.
The Mosquitoes' Weapon
Malaria is not only a terrible disease for us, but also for the mosquitoes. Mosquitoes are, "as unhappy about malaria as we are ... they try to get rid of it", according to Nobel laureate Johann Eisenhofer. In fact, some mosquitoes have managed to develop a natural resistance to the disease. Early in July of this year, a team of researchers at the University of Texas Southwestern Medical Center (UTSW) discovered how these mosquitoes tackle the parasites, giving us a new avenue for attacking the disease. As Dr. Baxter, another researcher at UTSW, puts it, "We have been trying to cure people of malaria for over a century ... Only recently have people started to think about curing mosquitoes of Malaria".
The research conducted at UTSW focused on TEP1, a protein in the mosquitoes' immune system. It was revealed that when malaria entered a mosquito, the protein was transformed into an active form that adhered to the parasite and acted as a marker for the insect's immune defense. Baxter explains, "TEP1 is a scout that finds the enemy, in this case malarial parasites, then plants a homing signal on the enemy and calls in the air strike".
The team of researchers were especially interested in a particular segment of the TEP1 protein dubbed the warhead'. This is the part of the protein that actually grabs the malarial parasite, similar in many ways to the active site of an enzyme. Eisenhofer, who won his Nobel prize for use of x-ray crystallography on proteins involved in photosynthesis, applied the same technique to the TEP1 protein. The analytical technique involves firing x rays at a crystalline sample and then looking at the image produced by the bending of the rays through the sample, or "diffraction pattern". This is a popular method used to determine protein structure.
French collaborators had determined in previous years that the TEP1 protein occurs in two genetic variations or alleles'. Describing the TEP1 protein showed the differences between the allele that is effective in combating malaria and the dormant version. Most of these differences are located in the warhead' segment of TEP1. This reinforces the suggestion that it is this segment which is instrumental in the protein's function.
Future research is likely to involve looking more closely at how the protein binds to the malarial parasite, as well as how the other parts of a mosquitoes immune system kick in once the parasite has been marked for termination. Although it may appear that this research doesn't directly help cure the disease, Dr. Baxter hopes that "Understanding how some mosquitoes can fend off malaria might someday lead to reducing or even eliminating the mosquito's capacity to transmit the devastating disease." This would possibly mean encouraging the growth of malaria resistant strains of mosquitoes. There is also the possibility of genetically engineering a new breed, although this would have serious ecological implications. Mosquitoes, which have always been an enemy in fighting malaria, might have given us a new weapon against it. If mosquitoes were wholly or even partially cured of the disease, ceasing to carry it from human to human, it would be our greatest victory in this ongoing biochemical war.
- By Ben-Griffin Smith.