Figure 1: Research of genetically modifying mosquitoes to prevent the spread of malaria is in the process of developing. Although there are some issues with gene drives, scientists are trying their best to bring the idea to real life.
Source Credit: Flickr.com (LINK)
Every year, more than one million people die of malaria, most of them being children under the age of five. In fact, one child dies every 30 seconds due to this disease, making the daily death count approximately 3000 children. If this is such a big problem, why is nothing being done to stop it? In fact, scientists have found an antimalarial drug called Chloroquine back in 1934; treatments have improved over the years, and the disease is eliminated in most developed countries today. However, malaria still remains a deadly threat in many developing countries, especially in Sub-Saharan Africa. Why would this be if treatments for malaria already exist?
For one, developing countries lack the resources and governmental support to build a malaria prevention program. The low-cost drugs that most people are using for malaria treatments are becoming more and more ineffective, as about 70 percent of malaria cases are resistant to cheap drugs, and most effective treatments often cost ten times more than traditional antimalarials. However, the biggest problem lies in mosquitoes since they are able to transmit malaria very efficiently. Even worse, warm and humid environments allow the mosquitoes, such as Anopheles gambiae, and the malaria parasites to thrive. Thus, it is difficult to eliminate or even reduce the population of mosquitoes in many of these developing countries. However, a new ongoing research sparks a new possible way of preventing malaria.
Recently, researchers have begun a study on genetically modifying mosquitoes to carry antimalarial genes and breeding them. This method––called gene drives––uses a gene-editing technology called CRISPR-Cas9 to insert a gene that codes for antimalarial protein into the mosquito’s genes. The mosquitoes are then released to breed with other mosquitoes, limiting their ability to spread the parasite. Another approach of gene drive aims to modify the genes of mosquitoes to create offspring that are mostly male, thus reducing the population. However, scientists are hesitant to take this approach because of the possibility that they could cause irreversible damage to the ecosystem. On the other hand, some say that gene drives would actually prevent damaging the ecosystem because of its ability to target specific species. Other mosquito species that don’t transmit malaria will not be affected by this modification. Furthermore, gene drives are believed to be more cost-effective than previous methods. Alekos Simoni, a researcher at Imperial College London working in the development of gene drives, stated that there was significant progress in reducing malaria for the past 15 to 20 years, but recently, the decline was stalled. The halt, he said, was due to a lack of investment. However, researchers hope that gene drives would be able to solve this problem.
Unfortunately, gene drives are not perfect. It is impossible to predict the consequences of using gene drives on a wild population. In fact, more than 75 environmental organizations prompted the EU commission to impose a suspension on the use of gene drives since many believe that it would be more wise to discuss the issue in depth and run more tests indoors to ensure the safety of the experiment. To address the potential issue of gene drives causing long term harm on the ecosystem, Target Malaria, a non-profit research organization, is running a study in Ghana on the role of malaria-transmitting mosquitoes in the ecosystem. So far it seems that Anopheles mosquitoes do not play a major role in the ecosystem, although further research is being carried out.
An additional concern is the potential of gene drive spreading uncontrollably beyond country borders, leading to environmental and legal issues. In response to those concerns, the scientists at the University of California San Diego developed two genetic systems that would stop or eliminate the gene drive. The first system, called e-CHACR, mutates and inactivates the Cas9 gene by using the enzyme Cas9 in the gene drive. e-CHACR can be inherited like a normal gene until it encounters a gene drive, where it would then cause the gene drive’s inactivation. The second system, called ERACR, entirely eliminates the gene drive by cutting the either sides of CAS9 and removing it. The gap is then filled up with a copy of the ERACR gene.
Whether this method will actually be used is still unknown. The scientists are continuing to run tests in an attempt to address all the concerns because if this technology could be perfected, there is little doubt that it would be a breakthrough in not only epidemiology, but also in genetic engineering. Until then, the only thing we can do is spread awareness of this issue so that more people would be more willing to help.
Q&A Section
Jiwon: In your article, you mentioned how the legal and environmental concerns of the gene drive process had caused scientists to develop two new genetic systems, and briefly outlined how they work. However, how are these different from the traditional gene drive methods and why do they eliminate the debate over environmental and legal issues?
In the end all of these methods involve having to use enzymes and adding or removing a specific part of the gene. The difference is just that e-CHACR tries to inactivate Cas9 and ERACR would cut out the gene entirely. These systems can eliminate the debate over some environmental and legal issues because it allows scientists to always stop the gene drive when they want. If the environment is being harmed too much or if gene drive is spreading to other countries causing legal issues, these two systems can be released to the mosquitoes and attempt to control the problem.
Sally: Are gene drives used for other diseases or other purposes? Is this the first attempt to use this technology for diseases?
There are ongoing tests on other animals using gene drives. For example, scientists are trying to eliminate a certain rodent species on an island using gene drive. However, as this technology was introduced relatively recently, this test on mosquitoes is considered to be one of the first attempts of using gene drives for diseases.
Xavier: How effective are gene drives in diminishing the spread of malaria? Would you say the potential of this technology outweighs its risks?
The effectiveness of gene drives is still a question because scientists have not been able to test it in real life. I personally think that the potential of this technology outweighs the risks but we would need to see how further research turns out.
Eric: How do you think the bioethics of gene editing for animals like mosquitos differs from that of humans?
Bioethics oftentimes go ignored for animals like mosquitoes (and other insects) because they are so common and small. It’s hard for people to think of mosquito rights when most people smash these insects with a fly swatter as soon as they see one flying around in their room. On the contrary, bioethics of gene editing with humans is still a hotly debated topic today.
John: In what ways does reducing mosquito populations in areas with frequent malaria cases create problems for the ecosystem?
If the mosquito population was decreased, scientists fear that there will also be a decrease in the number of animals that have mosquitoes as food sources. Bats, birds, frogs, and fish are all animals that eat mosquitoes so it is possible that the absence of mosquitoes could topple down the ecosystem.
Wooseok: Are there more potential dangers of utilizing gene drives (other than uncontrollable spread)? If so, are there currently corresponding solutions to these problems?
Another potential danger is that some might build resistance even to gene drives. It is impossible to predict what kind of mutations would occur in mosquitoes and what may end up happening if the mosquitoes become resistant to gene drives. Currently there are no corresponding solutions to this problem that I know of.
Works Cited
Albert, Helen. “Gene Drives: A Controversial Tool in the Fight Against Malaria.” Labiotech.eu, 2 Nov. 2020, www.labiotech.eu/in-depth/gene-drives-controversy/#:~:text=Researchers are introducing gene drives,to pass on the parasite.&text=So they can target many,just mosquitoes,” emphasizes Simoni.
Biologists Create New Genetic Systems to Neutralize Gene Drives, 18 Sept. 2020, ucsdnews.ucsd.edu/pressrelease/biologists-create-new-genetic-systems-to-neutralize-gene-drives.
“CDC - Malaria - About Malaria - FAQs.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 26 Jan. 2021, www.cdc.gov/malaria/about/faqs.html#:~:text=eradicated years ago?-,No.,subtropical parts of the world.
Scudellari, Megan. “Self-Destructing Mosquitoes and Sterilized Rodents: the Promise of Gene Drives.” Nature News, Nature Publishing Group, 9 July 2019, www.nature.com/articles/d41586-019-02087-5.
UNICEF. “The Reality of Malaria.” UNICEF, www.unicef.org/media/files/MALARIAFACTSHEETAFRICA.pdf.
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