Akash Mehta

Core Biology
Beatrice Fineschi
April 19th, 2019
Citation Format: MLA
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Literature Review: Gene Drives Targeting Malaria
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1. POPULAR PRESS
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Matthews, Dylan. “A Genetically Modified Organism Could End Malaria and Save Millions of
Lives - If We Decide to Use It.” Vox, Vox Media, 26 Sept. 2018, www.vox.com/science-and-
health/2018/5/31/17344406/crispr-mosquito-malaria-gene-drive-editing-target-africa-regulation-
gmo.
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This article provides a broad overview of the history, science and ethics of gene drives aimed at
modifying specific mosquito species in order to reduce rates of malaria. It describes the historical
development of the concept of gene drives, which originated in 1960 but has become a much
more practically possible technology with this decade’s discovery of the CRISPR gene-editing
technology. It discusses the various potential kinds of malaria-targeted gene drives, broadly
classifiable into the “California school” approach of propagating resistance to malaria among
mosquito populations and the “London school” approach of reducing the number of malaria-
transmitting mosquitos. It describes the stakes of the issue: on the one hand, every year we delay
implementation of these gene drives comes at the opportunity cost of up to 720,000 deaths; on
the other hand, overhasty implementation could result in ecological ramifications and political
blowback. This article provides me with a fantastic overview of the history and stakes of the
field, although I will need to turn to other sources (e.g. source #3) for more detailed comparison
of the scientific methods behind the different approaches.
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2. PRIMARY SOURCE
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Gantz, Valentino M., et al. "Highly efficient Cas9-mediated gene drive for population
modification of the malaria vector mosquito Anopheles stephensi." Proceedings of the National
Academy of Sciences 112.49 (2015): E6736-E6743.
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In this groundbreaking 2015 study, researchers used the CRISPR-Cas9 genetic engineering
technology to develop a gene drive capable of introducing malaria resistance into the vast
majority of the Asian mosquito species Anopheles stephensi. This particular mosquito is
responsible for roughly 12% of malaria cases in India, and possibly several recent malaria
outbreaks in Africa as well. Using a previously developed gene that confers resistance to malaria
parasites, the researchers were able to use the CRISPR-CAS9 system to spread that gene into
over 99% of a A. stephensi population in a lab. Note that this study followed the “California
school” approach of attempting to propagate resistance among a mosquito species, rather than
trying to exterminate or reduce the numbers of that species. This study will help me understand
the technical details of gene drive development and implementation, and is also of historical
interest as the first laboratory demonstration of the efficacy of gene drives against malaria.
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3. SECONDARY SOURCE
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Burt, Austin, et al. "Gene drive to reduce malaria transmission in sub-Saharan Africa." Journal of
Responsible Innovation 5.sup1 (2018): S66-S80.
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This review article assesses the state of gene drives targeting malaria vectors, focusing on its
potential impacts and dangers if deployed in sub-Saharan Africa. It provides an overview of how
gene drives are able to increase gene transmission rates to greater than 50% of progeny and thus
(in a number of generations) to spread them throughout a population. It discusses the most
feasible gene drive systems under development, the difficulty of overcoming malaria resistance
to the gene drive, and several questions that would need to be asked before any gene drive could
be deployed outside of a laboratory. This review article provides me with a great walk-through of
the genetics behind gene drives, and also enables me to compare and assess some of the most
promising methods under development.
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4. EXTRA: SECONDARY SOURCE
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Callaway, Ewen. "Gene drives thwarted by emergence of resistant organisms." Nature News
542.7639 (2017): 15.
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This article discusses recent research indicating that mosquito populations may quickly evolve
resistance to the gene drive, inhibiting transmission of the modified genes. The article provides a
survey of the different kinds of resistance and the different approaches for overcoming it,
including potentially targeting multiple genes at once or multiple sites with a single gene, or
simply designing a drive capable of spreading a gene faster than resistance can develop. The
research the article discusses will be important for me to consider as one major challenge to the
effective use of gene drives to combat malaria.