Carriersof the sickle cell hemoglobin (SCH) gene are protected to a certain degreeagainst malaria. The researchers have identified the mechanism by which thisprotection occurs and see it as a future point of treatment for malaria. Usinggenetically modified mice containing one faulty copy of the sickle cellhemoglobin gene, the researchers found that these mice were better protectedagainst malaria–the disease caused by the Plasmodiumparasite. It was previously thought that the SCH gene protected against theinfection of the Plasmodium parasite itself.However, the actual protection mechanism works by preventing the disease afterthe animal has already been infected. Highlevels of the prosthetic group heme–a component of hemoglobin–was present in freeform in the blood of the heterozygote mice, but absent to a great extent fromthe blood of the normal mice. This prosthetic group helps protect mice againstmalaria before infection from the parasite.
Nonetheless, high levels of heme inthe blood after infection with the Plasmodiumparasite seemed to increase the probability of contracting the disease. Lowlevels of free circulating heme prompt the production of the enzyme hemeoxygenase-1–HO-1–which in turn releases carbon monoxide–a gas that is verytoxic in large concentrations. When found in low concentrations in the blood ofthe mice, carbon monoxide actually seemed to help prevent accumulation of hemeafter the infection with the Plasmodium parasite.The free heme can therefore be both protective and dangerous at once.
Iwill use the researchers results to try and demonstrate that the SCH geneprovides a survival advantage against malaria which is a major reason whyevolution has not eliminated this gene completely, even though sickle cellanemia it is a disease itself. Similarly, the SCH gene induces the expressionof HO-1 which confers tolerance to Plasmodiuminfection. I will use this information to demonstrate that the HO-1 systemmight be used therapeutically to treat severe forms of malaria in the nearfuture, presenting the possibility of potential treatment for this parasiticdisease.