Blood Beyond Borders
SPOTLIGHT it would protect everyone living in the region regardless of their access to medical care .”
Genetically modifying one mosquito won ’ t change malaria prevalence , so scientists need to create a gene drive . While gene drives sometimes occur naturally , advances in gene editing have made it easier than ever to develop gene drives quickly and efficiently .
Researchers have identified two potentially powerful ways to use the gene drive to minimize the effects of malaria in sub-Saharan Africa , one that suppresses the population and one that modifies the population , Dr . Mbogo explained .
In the first approach , scientists insert a selfdestructive gene into the population that causes the malaria-transmitting species of mosquitoes to die out . The other idea is to use a gene drive that makes mosquitoes incapable of transmitting disease ; in one example , Italian researchers inserted a mutation that alters the organism ’ s mouth so it cannot bite humans . 3 By genetically modifying the mosquito population , the vector isn ’ t killed , but it becomes unable to transmit disease , Dr . Mbogo said .
“ [ Gene drive approaches ] would protect everyone living in the region regardless of their access to medical care .”
— Stephanie James , PhD
The gene-drive idea is about 70 years old , said Michael Santos , PhD , GeneConvene Director and Associate Vice President of Science at FNIH . “ The drive is a naturally occurring phenomenon but engineered gene drives have never been introduced into any wild population ,” he said .
These approaches are being explored entirely in the lab , Dr . Santos added . “ There ’ s laboratory work on both of these kinds of approaches that have demonstrated that , at least in principle and under laboratory conditions , it is possible to accomplish those goals at high enough rates that they could [ have an impact ] on controlling malaria rates in the field .”
Labs around the world have designed studies to at least partially mimic the environment in which the mosquitoes will eventually be released . For example , in the Italian experiment , researchers created a hot , humid lab and fed genetically modified mosquitoes warm cow ’ s blood to test a gene drive that caused mosquitoes to become sterile and unable to bite . The study showed that the gene was likely to disappear within 3 years of being introduced , meaning its impact on the overall environment might be temporary . 4
In experiments in a London lab , researchers were able to develop a gene drive that eliminated the population of mosquitoes in a cage after 11 generations by guaranteeing mostly male offspring ( only female insects transmit malaria ). 5
Risk Versus Reward
These scientific developments have been met with pushback about unforeseen effects on the environment . Typically , scientists try to prevent genetically engineered organisms from spreading their mutations ; with gene-drive approaches , wide spread of the mutation is the goal .
Environmental groups criticized a September 2019 project led by the research consortium Target Malaria , in which a group of 10,000 genetically modified sterile male mosquitoes were released into a small village in Burkina Faso . 6 Researchers tracked the insects for a year to understand how they would interact with the natural environment upon release , and in the end there weren ’ t enough mosquitoes to spread their genes to the entire population of mosquitoes in the area .
There are myriad concerns about genetically modifying an organism in such a way that the gene will permeate the species , and then releasing it into the wild . “ Those include risks to biodiversity , risks to ecosystem diversity and pollination , or even risks to human and livestock health – for example , changes in the fitness of the mosquitoes to be able to carry other diseases ,” said Dr . Santos .
To help minimize known and unknown risks of gene editing , scientists are also designing controls to keep the experiment from running amok . For instance , in the Italian experiment , investigators engineered the genes to lose potency over time .
“ The research community is very aware of those concerns and is working hard to address them ,” Dr . James added .
From the Lab to the Field
Drs . James and Mbogo were part of an international working group that described a pathway to safely test the gene-drive mosquitoes . 7 These recommendations include completing laboratory and cage experiments , identifying potential risks , mathematically modeling different outcomes and conducting limited releases in geographically isolated areas . The working group also emphasized the need for transparent testing strategies , plans to mitigate damage , and self-limiting gene drives .
“ It is important to recognize this is a proposed pathway ,” Dr . James said , but eventually , regulators will decide what scientists can and cannot do .
In the U . S ., gene drives would need oversight and involvement by biosafety and health authorities . For example , in the U . S ., since a gene drive acts on mosquitoes , it is most closely related to a pesticide , so it would likely fall under the Environmental Protection Agency ’ s purview . However , because its hopeful outcome is to improve health , the FDA would need to be involved , as well .
A gene drive presents the type of scientific scenario that can instill fear in the general public – the kind with the potential to lead to a cascade of unforeseen changes in the environment – so the FNIH ’ s GeneConvene Global Collaborative is working to ensure that any solutions are thoroughly vetted before being deployed into the world .
“ The collaborative is intended to help the community address some of these important issues and challenges and develop a set of best practices and guidance that will help to ensure that this research is pursued responsibly and safely ,” Dr . James stressed . — By Emma Yasinski
References 1 . World Health Organization . Fact Sheet : Malaria . Accessed October 14 , 2020 , from https :// www . who . int / news-room / fact-sheets / detail / malaria . 2 . Ferreira A , Marguti I , Bechmann I , et al . Sickle hemoglobin confers tolerance to
Plasmodium infection . Cell . 2011 ; 145:398-409 .
3 . Stein R . Scientists release controversial genetically modified mosquitoes in high-security lab . NPR , February 20 , 2019 . Accessed October 14 , 2020 , from https :// www . npr . org / sections / goatsandsoda / 2019 / 02 / 20 / 693735499 / scientists-release-controversial-genetically-modified-mosquitoes-in-highsecurit .
4 . Pollegioni P , North AR , Persampieri T , et al . Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes . J Applied Ecol . 2020:57:2086-2096 .
5 . Simoni A , Hammond AM , Beaghton AK , et al . A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae . Nat Biotech . 2020 ; 38:1054-1060 .
6 . Diabate A . Target Malaria . Target Malaria proceeded with a small-scale release of genetically modified sterile male mosquitoes in Bana , a village in Burkina Faso . July 1 , 2019 . Accessed October 14 , 2020 , from https :// targetmalaria . org / target-malaria-proceeded-with-a-small-scale-release-of-geneticallymodified-sterile-male-mosquitoes-in-bana-a-village-in-burkina-faso /.
7 . James S , Collins FH , Welkhoff PA , et al . Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in sub- Saharan Africa : recommendations of a scientific working group . Am J Trop Med Hyg . 2018 ; 98:1-49 .
40 ASH Clinical News November 2020