Could Genetic Engineering Help Us Eliminate Malaria?
Student Summary by Olivia Liu
Original Source: Kyrou, K., Hammond, A., Crisanti, A. & others. Science Journal for Kids and Teens, March 2020.
https://www.sciencejournalforkids.org/wp-content/uploads/2020/03/dsx_article.pdf; https://www.nature.com/articles/nbt.4245
Cover Created by Olivia Liu
Abstract
Background: For every 2 minutes we live, one child dies due to a fatal disease called malaria. Malaria is transmitted from person to person by mosquitoes (mainly the Anopheles gambiae mosquitoes), the main carriers of malaria (only female mosquitoes bite). Currently, there are efforts to prevent malaria such as insecticides and sleeping nets. However, these efforts aren't enough to stop malaria. This is why Kyros Kyrou and his team believe that genetic engineering could be the possible solution to end malaria.
Objective: Kyrou and his team wanted to develop a way to genetically modify Anopheles mosquitoes in order to disrupt sexual development and cause the whole mosquito population to collapse.
Method: The sex of the mosquito is determined by the doublesex gene (dsx). Both male and female mosquitoes have this gene; however, females have another region of DNA called exon5, which is responsible for the female mosquito's body structure, her ability to be fertile, her ability to bite the host, and her ability to suck the host's blood. Using CRISPR/Cas9, Kyrou and his team modified this area so that the female mosquitoes would lose these traits, while the males were unaffected but still carried the altered gene. The team then developed a gene drive for the modified exon5 region. A gene drive is a technology that allows the mutated gene to copy itself and replace the normal copy inherited from the unmodified parent, so that all offspring carry the mutation and it spreads much faster than normal. Kyrou and his team also created a mathematical model which stated that an initial population that contained 25% of the heterozygous individuals (mosquitoes with 1 copy of the mutated gene) would cause the mutation to spread within 9–13 generations. In order to test this, the team caged two populations of 600 mosquitoes each (300 wild females, 150 wild males, and 150 males with one copy of the mutation). These were called Cage 1 and Cage 2. Every generation, the hatched larvae were counted and were genetically screened for any sign of the modified gene.
Results: After performing the procedures, several results were shown. 1.) Male mosquitoes weren't affected by the change in their doublesex gene. They continued to spread the modified gene until there were no longer any eggs. 2.) Females that had one copy of the mutation continued to act normally. They were noticed to have lower fertility levels, but continued to pass down the mutated gene to their offspring. 3.) Females that were born with two copies of the mutation had characteristics of both males and females, including male-type mouthparts, so they were unable to bite or transmit diseases. They were also infertile and could not lay eggs, causing the whole population to crash. 4.) In Cage 1, the population had reached 100% mutation in the 11th generation and had collapsed in the 12th generation. In Cage 2, the mosquitoes had mutated by the 7th generation and the females weren't able to lay eggs, causing the population to collapse in the 8th generation. These results supported the mathematical model, and it took around 6 months for both populations to crash.
Conclusion: If genetic engineering on mosquitoes was used in the wild, Anopheles mosquito numbers could be reduced. Malaria could even be eliminated across significant areas of Africa by releasing 200 mosquitoes with the gene drive in each village, over a couple of decades. However, releasing a gene drive into the wild would require agreement at local, national, and international levels, and once released it could not be kept in one country or easily disabled. Some people are also worried about the ecological consequences. Gene drives are a powerful tool against malaria and some other mosquito-borne diseases, but small-scale field trials and public approval are still needed.
