Millions of genetically modified mosquitoes were just released in the US for the first time, thanks to a biotech firm owned by Bill Gates
by
Chris Young and Robert Gorter, MD, PhD.
Apr 30th, 2021
The Bill Gates-backed biotech firm Oxitec is going ahead with plans to release hundreds of millions of gene-altered mosquitos in Florida, USA, in order to test an experimental new form of population control, the company confirmed in a press release. The initial batch of mosquitoes was released this week.
The controversial project, conducted as part of a partnership between the Florida Keys Mosquito Control District (FKMCD) and Oxitec, will see six locations in the region host Oxitec’s gene-hacked male Aedes aegypti mosquitos over the next few months.
Oxitec — which announced a collaboration with the Bill & Melinda Gates Foundation in 2018 — says the new tests could help to greatly reduce populations of the mosquito breed, which is responsible for spreading diseases such as dengue and malaria.
As Oxitec emphasizes in its press statement, the company’s mosquitos are all male and, therefore, do not bite.
There are significant concerns that the release of GMO mosquitos could also be part of Gain-of-Function research project as biological warfare through gene-manipulated insects that could spread new diseases by genetically-engineered viruses and parasites.
Instead, they are intended to reduce the number of potentially disease-transmitting female Aedes aegypti by introducing a self-limiting gene that sees offspring die before reaching adulthood.
Oxitec says the Aedes aegypti accounts for only 4 percent of the mosquito population in the Florida Keys, but is responsible for almost all disease transmission. The company also states that community support for the project is “high.”
Controversy amid global plans to gene-hack mosquitos
Still, the method is controversial due to the fact that a genetically altered species is being released into an ecosystem with potentially unknown consequences. Critics have also pointed to the fact that this may open doors for firms to use gene-altered invasive species for other uncontrolled projects (Gain-of-Function).
Oxitec faced a backlash in August 2020, when it originally released its Florida Keys plans. In a press statement at the time, Dana Perls, the food and technology Program Manager at Friends of the Earth, said that “the release of genetically engineered mosquitoes will needlessly put Floridians, the environment and endangered species at risk in the midst of a pandemic.”
The Oxitec technology has already been tested in São Paulo, Brazil, where after 13 weeks, it suppressed up to 95 percent of the mosquito species.
Oxitec’s isn’t the only method for gene-altering mosquitos to curb their populations — this month, it was announced that researchers from Imperial College London have successfully altered the gut genes of mosquitos to spread antimalarial genes to their offspring. The same team had previously used A genetically modified (GM) insect is an insect that has been genetically modified, either through mutagenesis, or more precise processes of transgenesis, or cisgenesis or CRISPR. Motivations for using GM insects include biological research purposes and genetic pest management. Genetic pest management capitalizes on recent advances in biotechnology and the growing repertoire of sequenced genomes in order to control pest populations, including insects. Insect genomes can be found in genetic databases such as NCBI,[1] and databases more specific to insects such as FlyBase,[2] VectorBase,[3] and BeetleBase.[4] There is an ongoing initiative started in 2011 to sequence the genomes of 5,000 insects and other arthropods called the i5k.[5] Some Lepidoptera (e.g. monarch butterflies and silkworms) have been genetically modified in nature by the wasp bracovirus.[6]to eradicate a population of Anopheles gambiae in a lab.
A genetically modified (GM) insect is an insect that has been genetically modified, either through mutagenesis, or more precise processes of transgenesis, or cisgenesis or by means of CRISPR.
Principle of CRISPR
The Challenge of Using CRISPR to Knock In Genes
Researchers are developing an array of techniques for accurately and efficiently inserting genes into DNA.
Almost always, building something is harder than tearing it down. Similarly, knocking in genes poses a greater challenge than knocking them out. It is a reality that researchers will have to overcome in order to get the most out of gene editing. Knocking in genes allows scientists to study the effects of specific gene variants, to use reporter genes like green fluorescent protein to track gene products in time and space, to probe genome regulation, and ultimately, to repair disease-causing genes. “It is a really effective way to interrogate every base of a gene,” says Greg Findlay, an MD/PhD candidate at the University of Washington.
CRISPR, a gene editing technology known for its user-friendliness, can knock genes in or out. Knocking out a gene involves inserting CRISPR into a cell using a guide RNA that targets the tool to the gene of interest. There, CRISPR cuts the gene, snipping through both strands of DNA, and the cell’s regular DNA repair mechanism fixes the cut using a process called non-homologous end joining (NHEJ). NHEJ is highly efficient but inaccurate. The process tends to introduce errors in the form of small insertions or deletions that are usually enough to knock out the gene.
To knock a gene in, however, the cuts must be repaired very precisely, with no extra insertions or deletions. This requires harnessing a second DNA repair mechanism called homology-directed repair (HDR), which—in mammalian cells, at least—occurs less efficiently, so its frequency is dwarfed by that of NHEJ. Complicating the process further is the fact that some gene loci and cell types are inherently less hospitable to CRISPR editing.
In the past few years, researchers have developed many new strategies to boost the efficiency of knocking in genes both large and small using CRISPR, and along the way they’ve proposed and tested new applications for this type of gene editing. Here, The Scientist explores a few of the most promising approaches.
CRISPR technology is a major tool in Gain-for-Function research.
Motivations for using GM insects include biological research purposes and genetic pest management. Genetic pest management capitalizes on recent advances in biotechnology and the growing repertoire of sequenced genomes in order to control pest populations, including insects. Insect genomes can be found in genetic databases such as NCBI,[1] and databases more specific to insects such as FlyBase,[2] VectorBase,[3] and BeetleBase.[4] There is an ongoing initiative started in 2011 to sequence the genomes of 5,000 insects and other arthropods called the i5k.[5] Some Lepidoptera (e.g. monarch butterflies and silkworms) have been genetically modified in nature by the wasp bracovirus.[6]. Motivations for using GM insects include biological research purposes and genetic pest management. Genetic pest management capitalizes on recent advances in biotechnology and the growing repertoire of sequenced genomes in order to control pest populations, including insects. Insect genomes can be found in genetic databases such as NCBI,[1] and databases more specific to insects such as FlyBase,[2] VectorBase,[3] and BeetleBase.[4] There is an ongoing initiative started in 2011 to sequence the genomes of 5,000 insects and other arthropods called the i5k.[5] Some Lepidoptera (e.g. monarch butterflies and silkworms) have been genetically modified in nature by the wasp bracovirus.[6]
The fruit-fly Drosophila melanogaster,
often used in genetic modification studies
Release of insects carrying Dominant Lethals (RIDL) is a control strategy using genetically engineered insects that have (carry) a lethal gene(s) in their genome (an organism’s DNA). Lethal genes cause death in an organism. Similar to how inheritance of brown eyes is dominant to blue eyes, this lethal gene is dominant so that all offspring of the RIDL insect will also inherit the lethal gene. This lethal gene has a molecular on and off switch, allowing these RIDL insects to be reared. The lethal gene is turned off when the RIDL insects are mass reared in an insectary, and turned on when they are released into the environment. RIDL males and females are released to mate with wild males and their offspring die when they reach the larval or pupal stage because of the lethal gene. This causes the population of insects to crash. This technique is being developed for some insects and for other insects has been tested in the field. It has been used in the Grand Cayman Islands, Panama, and Brazil to control the mosquito vector of dengue, Ae. aegypti.[10][11][12] It is being developed for use in diamondback moth (Plutella xylostella),[13][14] medfly[15][16] and olive fly.[17]
But the same techniques are being developed as part of Gain-of-Function to develop weapons of mass destruction.
The scientific community and firms such as Oxitec, aim to tackle the problem of mosquito-borne diseases, which according to the World Mosquito Program, kill up to one million people per year as well as assisting in Gain-of-Function projects.
References
Notes and references
1 “National Center for Biotechnology Information”. www.ncbi.nlm.nih.gov. Retrieved 2016-04-08.
2 Group, FlyBase Web Development. “FlyBase Homepage”. flybase.org. Retrieved 2016-04-08.
3 “Welcome to VectorBase! | VectorBase”. www.vectorbase.org. Retrieved 2016-04-08.
4 “BeetleBase |”. beetlebase.org. Retrieved 2016-04-08.
5 “5,000 Insect Genome Project (i5k) Launched | Entomological Society of America”.
6 Gasmi, Laila; Boulain, Helene; Gauthier, Jeremy; Hua-Van, Aurelie; Musset, Karine; Jakubowska, Agata K.; Aury, Jean-Marc; Volkoff, Anne-Nathalie; Patrick, Susanne (2015-09-17). “Recurrent Domestication by Lepidoptera of Genes from Their Parasites Mediated by Bracoviruses”. PLOS Genet. 11 (9): e1005470. doi:10.1371/journal.pgen.1005470. ISSN 1553-7404. PMC 4574769. PMID 26379286.
7 Hendrichs, J.; Franz, G.; Rendon, P. (1995-01-12). “Increased effectiveness and applicability of the sterile insect technique through male-only releases for control of Mediterranean fruit flies during fruiting seasons”. Journal of Applied Entomology. 119 (1–5): 371–377. doi:10.1111/j.1439-0418.1995.tb01303.x. ISSN 1439-0418.
8 Klassen, W.; Curtis, C. F. (2005-01-01). Dyck, V. A.; Hendrichs, J.; Robinson, A. S. (eds.). History of the Sterile Insect Technique. Springer Netherlands. pp. 3–36. doi:10.1007/1-4020-4051-2_1. ISBN 9781402040504.
9 Klassen, Waldemar (2004-01-01). “Sterile Insect Technique”. Encyclopedia of Entomology. Springer Netherlands. pp. 2099–2118. doi:10.1007/0-306-48380-7_4080. ISBN 9780792386704.
10 Harris, Angela F.; Nimmo, Derric; McKemey, Andrew R.; Kelly, Nick; Scaife, Sarah; Donnelly, Christl A.; Beech, Camilla; Petrie, William D.; Alphey, Luke (2011-11-01). “Field performance of engineered male mosquitoes”. Nature Biotechnology. 29 (11): 1034–1037. doi:10.1038/nbt.2019. ISSN 1087-0156. PMID 22037376.
11 Harris, Angela F.; McKemey, Andrew R.; Nimmo, Derric; Curtis, Zoe; Black, Isaac; Morgan, Siân A.; Oviedo, Marco Neira; Lacroix, Renaud; Naish, Neil (2012-09-01). “Successful suppression of a field mosquito population by sustained release of engineered male mosquitoes”. Nature Biotechnology. 30 (9): 828–830. doi:10.1038/nbt.2350. ISSN 1087-0156. PMID 22965050.
12 Carvalho, Danilo O.; McKemey, Andrew R.; Garziera, Luiza; Lacroix, Renaud; Donnelly, Christl A.; Alphey, Luke; Malavasi, Aldo; Capurro, Margareth L. (2015). “Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes”. PLOS Neglected Tropical Diseases. 9 (7): e0003864. doi:10.1371/journal.pntd.0003864. PMC 4489809. PMID 26135160.
13 Harvey-Samuel, Tim; Ant, Thomas; Gong, Hongfei; Morrison, Neil I; Alphey, Luke (2014-05-01). “Population-level effects of fitness costs associated with repressible female-lethal transgene insertions in two pest insects”. Evolutionary Applications. 7 (5): 597–606. doi:10.1111/eva.12159. ISSN 1752-4571. PMC 4055180. PMID 24944572.
14 Harvey-Samuel, Tim; Morrison, Neil I.; Walker, Adam S.; Marubbi, Thea; Yao, Ju; Collins, Hilda L.; Gorman, Kevin; Davies, T. G. Emyr; Alphey, Nina (2015-07-16). “Pest control and resistance management through release of insects carrying a male-selecting transgene”. BMC Biology. 13 (1): 49. doi:10.1186/s12915-015-0161-1. PMC 4504119. PMID 26179401.
15 Leftwich, Philip T.; Koukidou, Martha; Rempoulakis, Polychronis; Gong, Hong-Fei; Zacharopoulou, Antigoni; Fu, Guoliang; Chapman, Tracey; Economopoulos, Aris; Vontas, John (2014-10-07). “Genetic elimination of field-cage populations of Mediterranean fruit flies”. Proceedings of the Royal Society of London B: Biological Sciences. 281 (1792): 20141372. doi:10.1098/rspb.2014.1372. ISSN 0962-8452. PMC 4150327. PMID 25122230.
16 Gong, Peng; Epton, Matthew J.; Fu, Guoliang; Scaife, Sarah; Hiscox, Alexandra; Condon, Kirsty C.; Condon, George C.; Morrison, Neil I.; Kelly, David W. (2005-04-01). “A dominant lethal genetic system for autocidal control of the Mediterranean fruitfly”. Nature Biotechnology. 23 (4): 453–456. doi:10.1038/nbt1071. ISSN 1087-0156. PMID 15750586.
17 Ant, Thomas; Koukidou, Martha; Rempoulakis, Polychronis; Gong, Hong-Fei; Economopoulos, Aris; Vontas, John; Alphey, Luke (2012-06-19). “Control of the olive fruit fly using genetics-enhanced sterile insect technique”. BMC Biology. 10 (1): 51. doi:10.1186/1741-7007-10-51. PMC 3398856. PMID 22713628.
18 “Here’s how GM mosquitos with ‘self-destruct’ genes could save us from Zika virus”. The Washington Post. 2016.
19 “Press release: Oxitec mosquito works to control Aedes aegypti in dengue hotspot”. Oxitec. 2015. Archived from the original on 2016-02-03. Retrieved 2016-01-29.
20 Powell, Jeffrey R. (1997-01-01). Progress and Prospects in Evolutionary Biology: The Drosophila Model. Oxford University Press. ISBN 9780195076912.
21 Sokolowski, Marla B. (2001-11-01). “Drosophila: Genetics meets behaviour”. Nature Reviews Genetics. 2 (11): 879–890. doi:10.1038/35098592. ISSN 1471-0056. PMID 11715043.
22 Clyne, Peter J.; Warr, Coral G.; Freeman, Marc R.; Lessing, Derek; Kim, Junhyong; Carlson, John R. (1999-02-01). “A Novel Family of Divergent Seven-Transmembrane Proteins: Candidate Odorant Receptors in Drosophila”. Neuron. 22 (2): 327–338. doi:10.1016/S0896-6273(00)81093-4. PMID 10069338.
23 Reiter, Lawrence T.; Potocki, Lorraine; Chien, Sam; Gribskov, Michael; Bier, Ethan (2001-06-01). “A Systematic Analysis of Human Disease-Associated Gene Sequences In Drosophila melanogaster”. Genome Research. 11 (6): 1114–1125. doi:10.1101/gr.169101. ISSN 1088-9051. PMC 311089. PMID 11381037.
24 Chintapalli, Venkateswara R.; Wang, Jing; Dow, Julian A. T. (2007-06-01). “Using FlyAtlas to identify better Drosophila melanogaster models of human disease”. Nature Genetics. 39 (6): 715–720. doi:10.1038/ng2049. ISSN 1061-4036. PMID 17534367.
25 Hammond, Andrew; Galizi, Roberto; Kyrou, Kyros; Simoni, Alekos; Siniscalchi, Carla; Katsanos, Dimitris; Gribble, Matthew; Baker, Dean; Marois, Eric (2015-12-07). “A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae”. Nature Biotechnology. 34 (1): 78–83. doi:10.1038/nbt.3439. ISSN 1546-1696. PMC 4913862. PMID 26641531.
26 Roberts, Michelle (24 November 2015). “Mutant mosquitoes ‘resist malaria'”. BBC News Health. Retrieved 24 November 2015.
27 Gantz, Valentino M.; et al. (26 October 2015). “Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi”. Proceedings of the National Academy of Sciences of the United States of America. 112 (49): E6736–43. doi:10.1073/pnas.1521077112. PMC 4679060. PMID 26598698. Retrieved 24 November 2015.
28 You, Minsheng; Yue, Zhen; He, Weiyi; Yang, Xinhua; Yang, Guang; Xie, Miao; Zhan, Dongliang; Baxter, Simon W.; Vasseur, Liette (2013-02-01). “A heterozygous moth genome provides insights into herbivory and detoxification”. Nature Genetics. 45 (2): 220–225. doi:10.1038/ng.2524. ISSN 1061-4036. PMID 23313953.
29 Harvey-Samuel, Tim; Morrison, Neil I.; Walker, Adam S.; Marubbi, Thea; Yao, Ju; Collins, Hilda L.; Gorman, Kevin; Davies, T. Ge; Alphey, Nina (2015). “Pest control and resistance management through release of insects carrying a male-selecting transgene”. BMC Biology. 13 (1): 49. doi:10.1186/s12915-015-0161-1. ISSN 1741-7007. PMC 4504119. PMID 26179401.
30 Miyata, Tadashi; Saito, Tetsuo; Noppun, Virapong. “Studies on the mechanism resistance to insecticides of diamondback moth” (PDF). Laboratory of Applied Entomology and Nematology, Faculty of Agriculture, Nagoya University. Retrieved September 2015. Check date values in: |access-date= (help)
31 Powell, Devin (August 31, 2015). “Replacing pesticides with genetics”. New York Times. Retrieved September 2015. Check date values in: |access-date= (help)
32 Hogenboom, M. (August 14, 2015). “Genetically modified flies ‘could save crops'”. BBC. Retrieved September 12, 2015.
33 “Genetically modified insects subject of new Lords inquiry”. www.parliament.co.uk. July 20, 2015. Retrieved September 11, 2015.